Laser-induced projectile impact testing (LIPIT) based on synchrotron imaging is proposed and validated. This emerging high-velocity, high-strain microscale dynamic loading technique offers a unique perspective on the strain and energy dissipation behavior of materials subjected to high-speed microscale single-particle impacts. When combined with synchrotron radiation imaging techniques, LIPIT allows for in situ observation of particle infiltration. Two validation experiments were carried out, demonstrating the potential of LIPIT in the roentgenoscopy of the dynamic properties of various materials. With a spatial resolution of 10 µm and a temporal resolution of 33.4 µs, the system was successfully realized at the Beijing Synchrotron Radiation Facility 3W1 beamline. This innovative approach opens up new avenues for studying the dynamic properties of materials in situ.

Errors in variable subscripts, equations and Fig. 8 in Section 3.2 of the article by Lotze et al. [(2024). J. Synchrotron Rad. 31, 42–52] are corrected.

Full-field transmission X-ray microscopy has been recently implemented at the hard X-ray ROCK–SOLEIL quick-EXAFS beamline, adding micrometre spatial resolution to the second time resolution characterizing the beamline. Benefiting from a beam size versatility due to the beamline focusing optics, full-field hyperspectral XANES imaging has been successfully used at the Fe K-edge for monitoring the pressure-induced spin transition of a 150 µm × 150 µm Fe(o-phen)2(NCS)2 single crystal and the charge of millimetre-sized LiFePO4 battery electrodes. Hyperspectral imaging over 2000 eV has been reported for the simultaneous monitoring of Fe and Cu speciation changes during activation of a FeCu bimetallic catalyst along a millimetre-sized catalyst bed. Strategies of data acquisition and post-data analysis using Jupyter notebooks and multivariate data analysis are presented, and the gain obtained using full-field hyperspectral quick-EXAFS imaging for studies of functional materials under process conditions in comparison with macroscopic information obtained by non-spatially resolved quick-EXAFS techniques is discussed.

In the paper by Oliveira et al. [IUCrData (2023), 8, x230971], there was an error in the name of the first author.

In the title compound, {(C6H8N)[Zn2(HPO3)2(H2PO3)]}n, the constituent ZnO4, HPO3 and H2PO3 polyhedra of the inorganic component are linked into (010) sheets by Zn—O—P bonds (mean angle = 134.4°) and the layers are reinforced by O—H⋯O hydrogen bonds. The protonated templates are anchored to the inorganic sheets via bifurcated N—H⋯(O,O) hydrogen bonds.

The well-known copper car­box­yl­ate dimer, with four car­box­yl­ate ligands ex­ten­ding outwards towards the corners of a square, has been employed to generate a series of crystalline com­pounds. In particular, this work centres on the use of the 4-hy­droxy­benzoate anion (Hhba−) and its deprotonated phe­nol­ate form 4-oxidobenzoate (hba2−) to obtain complexes with the general formula [Cu2(Hhba)4–x(hba)xL2–y]x−, where L is an axial coligand (including solvent mol­ecules), x = 0, 1 or 2, and y = 0 or 1. In some cases, short hy­dro­gen bonds result in complexes which may be represented as [Cu2(Hhba)2(H0.5hba)2L2]−. The main focus of the investigation is on the formation of a variety of extended networks through hy­dro­gen bonding and, in some crystals, coordinate bonds when bridging coligands (L) are employed. Crystals of [Cu2(Hhba)4(di­ox­ane)2]·4(di­ox­ane) consist of the expected Cu dimer with the Hhba− anions forming hy­dro­gen bonds to 1,4-di­ox­ane mol­ecules which block network formation. In the case of crystals of com­position [Et4N][Cu2(Hhba)2(H0.5hba)2(CH3OH)(H2O)]·2(di­ox­ane), Li[Cu2(Hhba)2(H0.5hba)2(H2O)2]·3(di­ox­ane)·4H2O and [Cu2(Hhba)2(H0.5hba)2(H0.5DABCO)2]·3CH3OH (DABCO is 1,4-di­aza­bicyclo­[2.2.2]octa­ne), square-grid hy­dro­gen-bonded networks are generated in which the complex serves as one type of 4-con­necting node, whilst a second 4-con­necting node is a hy­dro­gen-bonding motif assembled from four phenol/phenolate groups. Another two-dimensional (2D) network based upon a related square-grid structure is formed in the case of [Et4N]2[Cu2(Hhba)2(hba)2(di­ox­ane)2][Cu2(Hhba)4(di­ox­ane)(H2O)]·CH3OH. In [Cu2(Hhba)4(H2O)2]·2(Et4NNO3), a square-grid structure is again apparent, but, in this case, a pair of nitrate anions, along with four phenolic groups and a pair of water mol­ecules, combine to form a second type of 4-con­necting node. When 1,8-bis­(di­methyl­amino)­naphthalene (bdn, `proton sponge') is used as a base, another square-grid network is generated, i.e. [Hbdn]2[Cu2(Hhba)2(hba)2(H2O)2]·3(di­ox­ane)·H2O, but with only the copper dimer complex serving as a 4-con­necting node. Complex three-dimensional networks are formed in [Cu2(Hhba)4(O-bipy)]·H2O and [Cu2(Hhba)4(O-bipy)2]·2(di­ox­ane), where the potentially bridging 4,4'-bi­pyridine N,N'-dioxide (O-bipy) ligand is employed. Rare cases of mixed car­box­yl­ate copper dimer complexes were obtained in the cases of [Cu2(Hhba)3(OAc)(di­ox­ane)]·3.5(di­ox­ane) and [Cu2(Hhba)2(OAc)2(DABCO)2]·10(di­ox­ane), with each structure possessing a 2D network structure. The final com­pound re­por­ted is a simple hy­dro­gen-bonded chain of com­position (H0.5DABCO)(H1.5hba), formed from the reaction of H2hba and DABCO.

The synthesis and structural characterization of four novel supra­molecular hy­dro­gen-bonded arrangements based on self-assembly from mol­ecular `[Cu(2,2'-bi­imid­az­ole)]' modules and malonate anions are pre­sent­ed, namely, tetra­kis­(2,2'-bi­imid­az­ole)di-μ-chlorido-dimal­on­atotricopper(II) penta­hydrate, [Cu3(C3H2O4)2Cl2(C6H6N4)4]·5H2O or [Cu(H2biim)2(μ-Cl)Cu0.5(mal)]2·5H2O, aqua­(2,2'-bi­imid­az­ole)­mal­on­atocopper(II) dihydrate, [Cu(C3H2O4)(C6H6N4)(H2O)]·2H2O or [Cu(H2biim)(mal)(H2O)]·2H2O, bis­[aqua­bis­(2,2'-bi­imid­az­ole)­cop­per(II)] di­mal­on­atodi­perchloratocopper(II) 2.2-hydrate, [Cu(C6H6N4)2(H2O)]2[Cu(C3H2O4)(ClO4)2]·2.2H2O or [Cu(H2biim)2(H2O)]2[Cu(mal)2(ClO4)2]·2.2H2O, and bis­(2,2'-bi­imid­az­ole)­copper(II) bis­[bis­(2,2'-bi­imid­az­ole)(2-carb­oxy­acetato)mal­on­atocopper(II)] tridecahydrate, [Cu(C6H6N4)2][Cu(C3H2O4)(C3H3O4)(C6H6N4)2]·13H2O or [Cu(H2biim)2][Cu(H2biim)2(Hmal)(mal)]2·13H2O. These as­sem­blies are characterized by self-com­plementary donor–acceptor mol­ecular inter­actions, demonstrating a recurrent and distinctive pattern of hy­dro­gen-bonding preferences among the carboxyl­ate, carb­oxy­lic acid and N—H groups of the coordinated 2,2'-bi­imid­az­ole and malonate ligands. Additionally, co­or­din­ation of the carboxyl­ate group with the metallic centre helps sustain re­mark­able supra­molecular assemblies, such as layers, helices, double helix columns or 3D channeled architectures, including mixed-metal com­plexes, into a single structure.

The detection of specific biological macromolecules in cryogenic electron tomography data is frequently approached by applying cross-correlation-based 3D template matching. To reduce computational cost and noise, high binning is used to aggregate voxels before template matching. This remains a prevalent practice in both practical applications and methods development. Here, the relation between template size, shape and angular sampling is systematically evaluated to identify ribosomes in a ground-truth annotated data set. It is shown that at the commonly used binning, a detailed subtomogram average, a sphere and a heart emoji result in near-identical performance. These findings indicate that with current template-matching practices macromolecules can only be detected with high precision if their shape and size are sufficiently different from the background. Using theoretical considerations, the experimental results are rationalized and it is discussed why primarily low-frequency information remains at high binning and that template matching fails to be accurate because similarly shaped and sized macromolecules have similar low-frequency spectra. These challenges are discussed and potential enhancements for future template-matching methodologies are proposed.

Fragment-based drug design using X-ray crystallography is a powerful technique to enable the development of new lead compounds, or probe molecules, against biological targets. This study addresses the need to determine fragment binding orientations for low-occupancy fragments with incomplete electron density, an essential step before further development of the molecule. Halogen atoms play multiple roles in drug discovery due to their unique combination of electronegativity, steric effects and hydrophobic properties. Fragments incorporating halogen atoms serve as promising starting points in hit-to-lead development as they often establish halogen bonds with target proteins, potentially enhancing binding affinity and selectivity, as well as counteracting drug resistance. Here, the aim was to unambiguously identify the binding orientations of fragment hits for SARS-CoV-2 nonstructural protein 1 (nsp1) which contain a combination of sulfur and/or chlorine, bromine and iodine substituents. The binding orientations of carefully selected nsp1 analogue hits were focused on by employing their anomalous scattering combined with Pan-Dataset Density Analysis (PanDDA). Anomalous difference Fourier maps derived from the diffraction data collected at both standard and long-wavelength X-rays were compared. The discrepancies observed in the maps of iodine-containing fragments collected at different energies were attributed to site-specific radiation-damage stemming from the strong X-ray absorption of I atoms, which is likely to cause cleavage of the C—I bond. A reliable and effective data-collection strategy to unambiguously determine the binding orientations of low-occupancy fragments containing sulfur and/or halogen atoms while mitigating radiation damage is presented.

Tryptophan is the most prominent amino acid found in proteins, with multiple functional roles. Its side chain is made up of the hydrophobic indole moiety, with two groups that act as donors in hydrogen bonds: the Nɛ—H group, which is a potent donor in canonical hydrogen bonds, and a polarized Cδ1—H group, which is capable of forming weaker, noncanonical hydrogen bonds. Due to adjacent electron-withdrawing moieties, C—H⋯O hydrogen bonds are ubiquitous in macromolecules, albeit contingent on the polarization of the donor C—H group. Consequently, Cα—H groups (adjacent to the carbonyl and amino groups of flanking peptide bonds), as well as the Cɛ1—H and Cδ2—H groups of histidines (adjacent to imidazole N atoms), are known to serve as donors in hydrogen bonds, for example stabilizing parallel and antiparallel β-sheets. However, the nature and the functional role of interactions involving the Cδ1—H group of the indole ring of tryptophan are not well characterized. Here, data mining of high-resolution (r ≤ 1.5 Å) crystal structures from the Protein Data Bank was performed and ubiquitous close contacts between the Cδ1—H groups of tryptophan and a range of electronegative acceptors were identified, specifically main-chain carbonyl O atoms immediately upstream and downstream in the polypeptide chain. The stereochemical analysis shows that most of the interactions bear all of the hallmarks of proper hydrogen bonds. At the same time, their cohesive nature is confirmed by quantum-chemical calculations, which reveal interaction energies of 1.5–3.0 kcal mol−1, depending on the specific stereochemistry.

A key prerequisite for the successful application of protein crystallography in drug discovery is to establish a robust crystallization system for a new drug-target protein fast enough to deliver crystal structures when the first inhibitors have been identified in the hit-finding campaign or, at the latest, in the subsequent hit-to-lead process. The first crucial step towards generating well folded proteins with a high likelihood of crystallizing is the identification of suitable truncation variants of the target protein. In some cases an optimal length variant alone is not sufficient to support crystallization and additional surface mutations need to be introduced to obtain suitable crystals. In this contribution, four case studies are presented in which rationally designed surface modifications were key to establishing crystallization conditions for the target proteins (the protein kinases Aurora-C, IRAK4 and BUB1, and the KRAS–SOS1 complex). The design process which led to well diffracting crystals is described and the crystal packing is analysed to understand retrospectively how the specific surface mutations promoted successful crystallization. The presented design approaches are routinely used in our team to support the establishment of robust crystallization systems which enable structure-guided inhibitor optimization for hit-to-lead and lead-optimization projects in pharmaceutical research.

Bacterial ABC toxin complexes (Tcs) comprise three core proteins: TcA, TcB and TcC. The TcA protein forms a pentameric assembly that attaches to the surface of target cells and penetrates the cell membrane. The TcB and TcC proteins assemble as a heterodimeric TcB–TcC subcomplex that makes a hollow shell. This TcB–TcC subcomplex self-cleaves and encapsulates within the shell a cytotoxic `cargo' encoded by the C-terminal region of the TcC protein. Here, we describe the structure of a previously uncharacterized TcC protein from Yersinia entomophaga, encoded by a gene at a distant genomic location from the genes encoding the rest of the toxin complex, in complex with the TcB protein. When encapsulated within the TcB–TcC shell, the C-terminal toxin adopts an unfolded and disordered state, with limited areas of local order stabilized by the chaperone-like inner surface of the shell. We also determined the structure of the toxin cargo alone and show that when not encapsulated within the shell, it adopts an ADP-ribosyltransferase fold most similar to the catalytic domain of the SpvB toxin from Salmonella typhimurium. Our structural analysis points to a likely mechanism whereby the toxin acts directly on actin, modifying it in a way that prevents normal polymerization.

This work focuses on molecules that are encoded by the major histocompatibility complex (MHC) and that bind self-, foreign- or tumor-derived peptides and display these at the cell surface for recognition by receptors on T lymphocytes (T cell receptors, TCR) and natural killer (NK) cells. The past few decades have accumulated a vast knowledge base of the structures of MHC molecules and the complexes of MHC/TCR with specificity for many different peptides. In recent years, the structures of MHC-I molecules complexed with chaperones that assist in peptide loading have been revealed by X-ray crystallography and cryogenic electron microscopy. These structures have been further studied using mutagenesis, molecular dynamics and NMR approaches. This review summarizes the current structures and dynamic principles that govern peptide exchange as these relate to the process of antigen presentation.

In this work, regenerated cellulose textile fibers, Ioncell-F, dry-wet spun with different draw ratios, have been investigated by scanning wide-angle X-ray scattering (WAXS) using a mesoscopic X-ray beam. The fibers were found to be homogeneous on the 500 nm length scale. Analysis of the azimuthal angular dependence of a crystalline Bragg spot intensity revealed a radial dependence of the degree of orientation of crystallites that was found to increase with the distance from the center of the fiber. We attribute this to radial velocity gradients during the extrusion of the spin dope and the early stage of drawing. On the other hand, the fiber crystallinity was found to be essentially homogeneous over the fiber cross section.

Conformational heterogeneity of biological macromolecules is a challenge in single-particle averaging (SPA). Current standard practice is to employ classification and filtering methods that may allow a discrete number of conformational states to be reconstructed. However, the conformation space accessible to these molecules is continuous and, therefore, explored incompletely by a small number of discrete classes. Recently developed heterogeneous reconstruction algorithms (HRAs) to analyse continuous heterogeneity rely on machine-learning methods that employ low-dimensional latent space representations. The non-linear nature of many of these methods poses a challenge to their validation and interpretation and to identifying functionally relevant conformational trajectories. These methods would benefit from in-depth benchmarking using high-quality synthetic data and concomitant ground truth information. We present a framework for the simulation and subsequent analysis with respect to the ground truth of cryo-EM micrographs containing particles whose conformational heterogeneity is sourced from molecular dynamics simulations. These synthetic data can be processed as if they were experimental data, allowing aspects of standard SPA workflows as well as heterogeneous reconstruction methods to be compared with known ground truth using available utilities. The simulation and analysis of several such datasets are demonstrated and an initial investigation into HRAs is presented.

Thio­phosgene is one of the principal C=S building blocks in synthetic chemistry. At room temperature, thio­phosgene is a red liquid. While its properties in the liquid and gaseous states are well known, a comprehensive characterization of thio­phosgene in its solid state is presented here. Differential scanning calorimetry shows that thio­phosgene forms a supercooled melt before rapidly crystallizing. Its melting point is 231.85 K (−41.3 °C). At 80 K, thio­phosgene crystallizes in space group P63/m [No. 174, a = b = 5.9645 (2), c = 6.2835 (3) Å, V = 193.59 (2) Å3]. The molecule shows a distinct rotational disorder: all S and Cl positions are of mixed occupancy and the disorder does not resolve at temperatures as low as 10 K, as was shown by neutron powder diffraction. Infrared, Raman and inelastic neutron scattering spectra were collected and assigned with the aid of quantum chemical calculations. A larger ordered structural model allowed for better agreement between the measured and calculated spectra, further indicating that disorder is an inherent feature of solid-state thio­phosgene.

The ternary magnesium/lithium boride, MgxLi3 − xB48 − y (x = 1.11, y = 0.40, idealized formula MgLi2B48), crystallizes as its own structure type in P43212, which is closely related to the structural family comprising α-AlB12, Be0.7Al1.1B22 and tetra­gonal β-boron. The asymmetric unit of title structure contains two statistical mixtures Mg/Li in Wyckoff sites 8b with relative occupancies Mg:Li = 0.495 (9):0.505 (9) and 4a with Mg:Li = 0.097 (8):0.903 (8). The boron atoms occupy 23 8b sites and two 4a sites. One of the latter sites has a partial occupancy factor of 0.61 (2). Both unique Mg/Li atoms adopt a twelvefold coordination environment in the form of truncated tetra­hedra (Laves polyhedra). These polyhedra are connected by triangular faces to four [B12] icosa­hedra. The boron atoms exhibit four kinds of polyhedra, namely penta­gonal pyramid (coordination number CN = 6), distorted tetra­gonal pyramid (CN = 5), bicapped hexa­gon (CN = 8) and gyrobifastigium (CN = 8). At the gas hydrogenation of MgLi2B48 alloy, formation of the eutectic composite hydride LiBH4+Mg(BH4)2 and amorphous boron is observed. In the temperature range 543–623 K, the hydride eutectics decompose, forming MgH2, LiH, MgB4, B and H2.

The structures of 16 phosphane chalcogenide complexes of gold(I) halides, with the general formula R13-nR2nPEAuX (R1 = t-butyl; R2 = isopropyl; n = 0 to 3; E = S or Se; X = Cl, Br or I), are presented. The eight possible chlorido derivatives are: 1a, n = 3, E = S; 2a, n = 2, E = S; 3a, n = 1, E = S; 4a, n = 0, E = S; 5a, n = 3, E = Se; 6a, n = 2, E = Se; 7a, n = 1, E = Se; and 8a, n = 0, E = Se, and the corresponding bromido derivatives are 1b–8b in the same order. However, 2a and 2b were badly disordered and 8a was not obtained. The iodido derivatives are 2c, 6c and 7c (numbered as for the series a and b). All structures are solvent-free and all have Z' = 1 except for 6b and 6c (Z' = 2). All mol­ecules show the expected linear geometry at gold and approximately tetra­hedral angles P—E—Au. The presence of bulky ligands forces some short intra­molecular contacts, in particular H⋯Au and H⋯E. The Au—E bond lengths have a slight but consistent tendency to be longer when trans to a softer X ligand, and vice versa. The five compounds 1a, 5a, 6a, 1b and 5b form an isotypic set, despite the different alkyl groups in 6a. Compounds 3a/3b, 4b/8b and 6b/6c form isotypic pairs. The crystal packing can be analysed in terms of various types of secondary inter­actions, of which the most frequent are `weak' hydrogen bonds from methine hydrogen atoms to the halogenido ligands. For the structure type 1a, H⋯X and H⋯E contacts combine to form a layer structure. For 3a/3b, the packing is almost featureless, but can be described in terms of a double-layer structure involving borderline H⋯Cl/Br and H⋯S contacts. In 4a and 4b/8b, which lack methine groups, Cmeth­yl—H⋯X contacts combine to form layer structures. In 7a/7b, short C—H⋯X inter­actions form chains of mol­ecules that are further linked by association of short Au⋯Se contacts to form a layer structure. The packing of compound 6b/6c can conveniently be analysed for each independent mol­ecule separately, because they occupy different regions of the cell. Mol­ecule 1 forms chains in which the mol­ecules are linked by a Cmethine⋯Au contact. The mol­ecules 2 associate via a short Se⋯Se contact and a short H⋯X contact to form a layer structure. The packing of compound 2c can be described in terms of two short Cmethine—H⋯I contacts, which combine to form a corrugated ribbon structure. Compound 7c is the only compound in this paper to feature Au⋯Au contacts, which lead to twofold-symmetric dimers. Apart from this, the packing is almost featureless, consisting of layers with only translation symmetry except for two very borderline Au⋯H contacts.

The structures of ten phosphane chalcogenide complexes of gold(III) halides, with general formula R13–nR2nPEAuX3 (R1 = t-butyl; R2 = i-propyl; n = 0 to 3; E = S or Se; X = Cl or Br) are presented. The eight possible chlorido derivatives are: 9a, n = 3, E = S; 10a, n = 2, E = S; 11a, n = 1, E = S; 12a, n = 0, E = S; 13a, n = 3, E = Se; 14a, n = 2, E = Se; 15a, n = 1, E = Se; and 16a, n = 0, E = Se, and the corresponding bromido derivatives are 9b–16b in the same order. Structures were obtained for 9a, 10a (and a second polymorph 10aa), 11a (and its deutero­chloro­form monosolvate 11aa), 12a (as its di­chloro­methane monosolvate), 14a, 15a (as its deutero­chloro­form monosolvate 15aa, in which the solvent mol­ecule is disordered over two positions), 9b, 11b, 13b and 15b. The structures of 11a, 15a, 11b and 15b form an isotypic set, and those of compounds 10aa and 14a form an isotypic pair. All structures have Z' = 1. The gold(III) centres show square-planar coordination geometry and the chalcogenide atoms show approximately tetra­hedral angles (except for the very wide angle in 12a, probably associated with the bulky t-butyl groups). The bond lengths at the gold atoms are lengthened with respect to the known gold(I) derivatives, and demonstrate a considerable trans influence of S and Se donor atoms on a trans Au—Cl bond. Each compound with an isopropyl group shows a short intra­molecular contact of the type C—Hmethine⋯Xcis; these may be regarded as intra­molecular ‘weak’ hydrogen bonds, and they determine the orientation of the AuX3 groups. The mol­ecular packing is analysed in terms of various short contacts such as weak hydrogen bonds C—H⋯X and contacts between the heavier atoms, such as X⋯X (9a, 10aa, 11aa, 15aa and 9b), S⋯S (10aa, 11a and 12a) and S⋯Cl (10a). The packing of the polymorphs 10a and 10aa is thus quite different. The solvent mol­ecules take part in C—H⋯Cl hydrogen bonds; for 15aa, a disordered solvent region at z ≃ 0 is observed. Structure 13b involves unusual inversion-symmetric dimers with Se⋯Au and Se⋯Br contacts, further connected by Br⋯Br contacts.

The structures of fourteen halochalcogenyl­phospho­nium tetra­halogen­ido­aurates(III), phosphane chalcogenide derivatives with general formula [R13–nR2nPEX][AuX4] (R1 = t-butyl; R2 = isopropyl; n = 0 to 3; E = S or Se; X = Cl or Br) are presented. The eight possible chlorido derivatives are: 17a, n = 3, E = S; 18a, n = 2, E = S; 19a, n = 1, E = S; 20a, n = 0, E = S; 21a, n = 3, E = Se; 22a, n = 2, E = Se; 23a, n = 1, E = Se; and 24a, n = 0, E = Se, and the corresponding bromido derivatives are 17b–24b in the same order. Structures were obtained for all compounds except for the tri-t-butyl derivatives 24a and 24b. Isotypy is observed for 18a/18b/22a/22b, 19a/23a, 17b/21b and 19b/23b. In eleven of the compounds, X⋯X contacts (mostly very short) are observed between the cation and anion, whereby the E—X⋯X groups are approximately linear and the X⋯X—Au angles approximately 90°. The exceptions are 17a, 19a and 23a, which instead display short E⋯X contacts. Bond lengths in the cations correspond to single bonds P—E and E—X. For each group with constant E and X, the P—E—X bond-angle values increase monotonically with the steric bulk of the alkyl groups. The packing is analysed in terms of E⋯X, X⋯X (some between anions alone), H⋯X and H⋯Au contacts. Even for isotypic compounds, some significant differences can be discerned.

The crystal structure of the title 2:1 mol­ecular complex between 2-(allyl­thio)­pyridine and 1,2,4,5-tetra­fluoro-3,6-di­iodo­benzene, C6F4I2·2C8H9NS, at 100 K has been determined in the monoclinic space group P21/c. The most noteworthy characteristic of the complex is the halogen bond between iodine and the pyridine ring with a short N⋯I contact [2.8628 (12) Å]. The Hirshfeld surface analysis shows that the hydrogen⋯hydrogen contacts dominate the crystal packing with a contribution of 32.1%.

In the title compound, C10H8N2·2C6H5NO3, 4-nitro­phenol and 4,4'-bi­pyridine crystallized together in a 2:1 ratio in the space group P21/n. There is a hydrogen-bonding inter­action between the nitro­gen atoms on the 4,4'-bi­pyridine mol­ecule and the hydrogen atom on the hydroxyl group on the 4-nitro­phenol, resulting in trimolecular units. This structure is a polymorph of a previously reported structure [Nayak & Pedireddi (2016). Cryst. Growth Des. 16, 5966–5975], which differs mainly due to a twist in the 4,4'-bi­pyridine mol­ecule.

In the title salt, C6H16N22+ ·H2P2O72−, the complete dication is generated by a crystallographic centre of symmetry with the methyl groups in equatorial orientations. The complete dianion is generated by a crystallographic twofold axis with the central O atom lying on the axis: the P—O—P bond angle is 135.50 (12)°. In the crystal, the di­hydrogen diphosphate anions are linked by O—H⋯O hydrogen bonds, generating (001) layers. The organic cations bond to the inorganic layers by way of N—H⋯O and C—H⋯O hydrogen bonds. A Hirshfeld surface analysis shows that the most important contributions for the crystal packing are from O⋯H/H⋯O (60.5%) and H⋯H (39.4%) contacts.

In this work, we showed that the use of ethanol to increase image contrast when imaging cardiac tissue with synchrotron X-ray phase-contrast imaging (X-PCI) leads to heterogeneous tissue shrinkage, which has an impact on the 3D organization of the myocardium.

Hendrickson & Lattman [Acta Cryst. (1970), B26, 136–143] introduced a method for representing crystallographic phase probabilities defined on the unit circle. Their approach could model the bimodal phase probability distributions that can result from experimental phase determination procedures. It also provided simple and highly effective means to combine independent sources of phase information. The present work discusses the equivalence of the Hendrickson–Lattman distribution and the generalized von Mises distribution of order two, which has been studied in the statistical literature. Recognizing this connection allows the Hendrickson–Lattman distribution to be expressed in an alternative form which is easier to interpret, as it involves the location and concentration parameters of the component von Mises distributions. It also allows clarification of the conditions for bimodality and access to a simplified analytical method for evaluating the trigonometric moments of the distribution, the first of which is required for computing the best Fourier synthesis in the presence of phase, but not amplitude, uncertainty.

NdGa hydride and deuteride phases were prepared from high-quality NdGa samples and their structures characterized by powder and single-crystal X-ray diffraction and neutron powder diffraction. NdGa with the orthorhombic CrB-type structure absorbs hydrogen at hydrogen pressures ≤ 1 bar until reaching the composition NdGaH(D)1.1, which maintains a CrB-type structure. At elevated hydrogen pressure additional hydrogen is absorbed and the maximum composition recovered under standard temperature and pressure conditions is NdGaH(D)1.6 with the Cmcm LaGaH1.66-type structure. This structure is a threefold superstructure with respect to the CrB-type structure. The hydrogen atoms are ordered and distributed on three fully occupied Wyckoff positions corresponding to tetrahedral (4c, 8g) and trigonal–bipyramidal (8g) voids in the parent structure. The threefold superstructure is maintained in the H-deficient phases NaGaH(D)x until 1.6 ≥ x ≥ 1.2. At lower H concentrations, coinciding with the composition of the hydride obtained from hydrogenation at atmospheric pressure, the unit cell of the CrB-type structure is resumed. This phase can also display H deficiency, NdGaH(D)y (1.1 ≥ y ≥ 0.9), with H(D) exclusively situated in partially empty tetrahedral voids. The phase boundary between the threefold superstructure (LaGaH1.66 type) and the onefold structure (NdGaH1.1 type) is estimated on the basis of phase–composition isotherms and neutron powder diffraction to be x = 1.15.

This work presents observations of symmetry breakages in the intensity distributions of near-zone-axis convergent-beam electron diffraction (CBED) patterns that can only be explained by the symmetry of the specimen and not the symmetry of the unit cell describing the atomic structure of the material. The specimen is an aluminium–copper–tin alloy containing voids many tens of nanometres in size within continuous single crystals of the aluminium host matrix. Several CBED patterns where the incident beam enters and exits parallel void facets without the incident beam being perpendicular to these facets are examined. The symmetries in their intensity distributions are explained by the specimen morphology alone using a geometric argument based on the multislice theory. This work shows that it is possible to deduce nanoscale morphological information about the specimen in the direction of the electron beam – the elusive third dimension in transmission electron microscopy – from the inspection of CBED patterns.

Here, it is investigated how optical properties of single scatterers in interacting multi-particle systems influence measurable structure factors. Both particles with linear gradients of their scattering length density and core–shell structures evoke characteristic deviations between the weighted sum 〈S(Q)〉 of partial structure factors in a multi-component system and experimentally accessible measurable structure factors SM(Q). While 〈S(Q)〉 contains only the structural information of self-organizing systems, SM(Q) is additionally influenced by the optical properties of their constituents, resulting in features such as changing amplitudes, additional peaks in the low-wavevector region or splitting of higher-order maxima, which are not related to structural reasons. It is shown that these effects can be systematically categorized according to the qualitative behaviour of the form factor in the Guinier region, which enables assessing the suitability of experimentally obtained structure factors to genuinely represent the microstructure of complex systems free from any particular model assumption. Hence, a careful data analysis regarding size distribution and optical properties of single scatterers is mandatory to avoid a misinterpretation of measurable structure factors.

The upgrade of the Swiss Light Source, called SLS 2.0, necessitates comprehensive updates to all 18 user front ends. This upgrade is driven by the increased power of the synchrotron beam, reduced floor space, changing source points, new safety regulations and enhanced beam properties, including a brightness increase by up to a factor of 40. While some existing front-end components are being thoroughly refurbished and upgraded for safety reasons, other components, especially those designed to tailor the new synchrotron beam, are being completely rebuilt. These new designs feature innovative and enhanced cooling systems to manage the high-power load and meet new requirements such as mechanical stability and compact footprints.

Autonomous methods to align beamlines can decrease the amount of time spent on diagnostics, and also uncover better global optima leading to better beam quality. The alignment of these beamlines is a high-dimensional expensive-to-sample optimization problem involving the simultaneous treatment of many optical elements with correlated and nonlinear dynamics. Bayesian optimization is a strategy of efficient global optimization that has proved successful in similar regimes in a wide variety of beamline alignment applications, though it has typically been implemented for particular beamlines and optimization tasks. In this paper, we present a basic formulation of Bayesian inference and Gaussian process models as they relate to multi-objective Bayesian optimization, as well as the practical challenges presented by beamline alignment. We show that the same general implementation of Bayesian optimization with special consideration for beamline alignment can quickly learn the dynamics of particular beamlines in an online fashion through hyperparameter fitting with no prior information. We present the implementation of a concise software framework for beamline alignment and test it on four different optimization problems for experiments on X-ray beamlines at the National Synchrotron Light Source II and the Advanced Light Source, and an electron beam at the Accelerator Test Facility, along with benchmarking on a simulated digital twin. We discuss new applications of the framework, and the potential for a unified approach to beamline alignment at synchrotron facilities.

The Next-Gen Technologies to Detect Fraud and Financial Crime Report 2024 highlights how banks, fintechs, and PSPs leverage AI and emerging tech to detect and combat advanced fraud.

Archival still from the documentary "Street Gang: How We Got to Sesame Street"; Credit: HBO

This content is from Southern California Public Radio. View the original story at SCPR.org.

Lithuania-based Genome has launched SEPA Instant Transfers,...

Source: Rob Goff 11/11/2024

Volatus Aerospace Inc. (TSXV:FLT; OTCQX:TAKOF:ABBA.F) secured CA$2.8 million (CA$2.8M) through a private placement after having recently completed a financing package for CA$15M, reported Ventum Capital Markets analyst Rob Goff in a Nov. 6 research note. Volatus provides aerial intelligence solutions using drones and other aircraft systems, including inspections, surveillance, design, and sales.

"We believe the two financing rounds should be positively rewarded by investors for the financial flexibility they bring to Volatus, while the commitment of the two debt partners represents a strong validation," Goff wrote.

192% Return Implied

Goff reiterated Ventum's target price on the Canadian aircraft solutions provider of CA$0.38 per share. In comparison, it was trading at the time of the report at CA$0.13 per share. From this price, the return to target is 192%.

Volatus is a Buy.

Plans for Using the Funds

Goff discussed the private placement and Volatus' intended uses of it. For the offering, a total of 19,766,000 units was sold at CA$0.14 apiece. Each unit consists of one common Volatus voting share and one common Volatus voting share purchase warrant. With each warrant, the holder may purchase one Volatus common share for CA$0.20 per warrant share during the 24 months after the close of the raise.

"We believe the equity and debt financing will allow Volatus to invest in working capital to support higher equipment sales," an advantage its smaller peers do not have, Goff wrote.

The company expects to fund about CA$9–12M in unmet equipment sales demand, so Goff forecasts it will designate CA$3–4M to this purpose, to purchase working capital. Other uses of the proceeds are for research and development, capital expenditures and inventory.

Goff reported that Volatus wants to leverage every incremental CA$1M of invested working capital into about CA$3–4M of incremental equipment sales annually, aiming for gross profit margins of about 25% and modest incremental operating costs.

Volatus plans to use proceeds from the debt raise to back pay the outstanding CA$6M senior loan it has with a major Canadian bank. The company also intends to open a new secured line of credit to support anticipated growth. Current debt related to its fleet financing is about CA$5M.

Opportunities for Growth

With more balance sheet flexibility, Goff wrote, Volatus may pursue longer-term contracts with utilities and pipelines for inspection services using unmanned and manned fleets. This would position the company to become a leader in this specific market.

Volatus can monetize its portfolio of drones and landing stations. The U.S.' initiatives and intention to reduce use of Chinese-manufactured products could help drive this expansion. The company has third-party manufacturing capabilities to significantly boost its equipment sales.

"We anticipate that Volatus will leverage its unique software, network, and equipment capabilities, stewarded by an experienced and commercially focused leadership team," Goff wrote.

Future Financial Expectations

Goff discussed forecasts for merger synergies, EBITDA, and revenue. As for initial efficiencies achieved from Volatus' merger with Drone Delivery Canada, they should be seen in Volatus' Q4/24 and Q1/25 financial results, Goff wrote. Already, the company has exceeded CA$2.6M in cost synergies and expects to surpass CA$3M in the near term. By 2026, the company estimates revenue synergies will be about CA$5M-plus and will include initial traction gained from business-to-business cargo delivery.

Looking to 2025, Ventum expects Volatus to turn EBITDA break even in Q2/25 and produce CA$5.7M in positive EBITDA in 2025 versus Volatus' estimate of CA$10M-plus, Goff reported. Ventum estimates that Volatus will generate CA$60.3M in revenue in full-year 2025, less than Volatus' guidance of CA$70M+.

"We anticipate that Volatus will leverage its unique software, network, and equipment capabilities, stewarded by an experienced and commercially focused leadership team," wrote Goff.

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1. Doresa Banning wrote this article for Streetwise Reports LLC and provides services to Streetwise Reports as an independent contractor.
2. This article does not constitute investment advice and is not a solicitation for any investment. Streetwise Reports does not render general or specific investment advice and the information on Streetwise Reports should not be considered a recommendation to buy or sell any security. Each reader is encouraged to consult with his or her personal financial adviser and perform their own comprehensive investment research. By opening this page, each reader accepts and agrees to Streetwise Reports' terms of use and full legal disclaimer. Streetwise Reports does not endorse or recommend the business, products, services or securities of any company.

For additional disclosures, please click here.

Disclosures for Ventum Capital Markets, Volatus Aerospace Inc., November 6, 2024

Analyst Certification I, Rob Goff, hereby certify that all of the views expressed in this report accurately reflect my personal views about the subject securities or issuers. I also certify that no part of my compensation was, is, or will be, directly or indirectly related to the specific recommendations or views expressed in this report. I am the research analyst primarily responsible for preparing this report.

Research Disclosures

1. Ventum Financial Corp. and its affiliates’ holdings in the subject company’s securities, in aggregate exceeds 1% of each company’s issued and outstanding securities.
2. Ventum Financial Corp. and/or its affiliates have received compensation for investment banking services for the subject company over the preceding 12- month period.
3. Ventum Financial Corp. and/or its affiliates expect to receive or intend to seek compensation for investment banking services from the subject company.
4. Ventum Financial Corp. and/or its affiliates have managed or co-managed a public offering of securities for the subject company in the past 12 months.

General Disclosure The affiliates of Ventum Financial Corp. are Ventum Financial (US) Corp., Ventum Financial Services Corp., and Ventum Capital Corp. Analysts are compensated through a combined base salary and bonus payout system. The bonus payout is amongst other factors determined by revenue generated directly or indirectly from various departments including Investment Banking. Evaluation is largely on an activity-based system that includes some of the following criteria: reports generated, timeliness, performance of recommendations, knowledge of industry, quality of research and investment guidance, and client feedback. Analysts and all other Research staff are not directly compensated for specific Investment Banking transactions. None of the material, nor its content, nor any copy of it, may be altered in any way, transmitted to, copied or distributed to any other party, without the prior express written permission of Ventum Financial Corp. Ventum Financial Corp.’s policies and procedures regarding dissemination of research, stock rating and target price changes can be reviewed on our corporate website at www.ventumfinancial.com (Research: Research and Conflict Disclosure).

Participants of all Canadian Marketplaces. Members: Canadian Investment Regulatory Organization, Canadian Investor Protection Fund and AdvantageBC International Business Centre - Vancouver. Estimates and projections contained herein are our own and are based on assumptions which we believe to be reasonable. Information presented herein, while obtained from sources we believe to be reliable, is not guaranteed either as to accuracy or completeness, nor in providing it does Ventum Financial Corp. assume any responsibility or liability. This information is given as of the date appearing on this report, and Ventum Financial Corp. assumes no obligation to update the information or advise on further developments relating to securities. Ventum Financial Corp. and its aೀiliates, as well as their respective partners, directors, shareholders, and employees may have a position in the securities mentioned herein and may make purchases and/or sales from time to time. Ventum Financial Corp. may act, or may have acted in the past, as a ೃnancial advisor, ೃscal agent or underwriter for certain of the companies mentioned herein and may receive, or may have received, a remuneration for their services from those companies. This report is not to be construed as an oೀer to sell, or the solicitation of an oೀer to buy, securities and is intended for distribution only in those jurisdictions where Ventum Financial Corp. is registered as an advisor or a dealer in securities. Any distribution or dissemination of this report in any other jurisdiction is strictly prohibited. Ventum Financial Corp. is a Canadian broker-dealer and is not subject to the standards or requirements of MiFID II. Readers of Ventum Financial Corp. research in the applicable jurisdictions should make their own eೀorts to ensure MiFID II compliance. For further disclosure information, reader is referred to the disclosure section of our website

( Companies Mentioned: TSXV:FLT;OTCQX:TAKOF:ABBA.F), )

The general equation of the δ direct methods is established and applied in its difference form to the definition of one of the two residuals that constitute the SMAR phasing algorithm. These two residuals use the absolute value of ρ and/or the zero conversion of negative Fourier ripples (≥50% of the unit-cell volume). Alternatively, when solved for ρ, the general equation provides a simple derivation of the already known δM tangent formula.

Source: Streetwise Reports 11/07/2024

Jericho Energy Ventures Inc. (JEV:TSX.V; JROOF:OTC; JLM:FRA) has announced a strategic move to spin off its hydrogen solutions platform into a separate entity. The new entity, to be named Hydrogen Technologies Corp. (HTC), was approved by the company's board of directors. The intention is to create two specialized companies focusing on hydrogen technology and traditional energy assets, respectively. Each Jericho Energy shareholder will retain their Jericho shares while receiving shares of the new HTC entity on a pro-rata basis in consideration of the transfer of Jericho's hydrogen assets.

The planned transaction, still subject to regulatory and shareholder approvals, aims to allow both companies to focus on their distinct markets and strategies. Jericho Energy expects this restructuring to enable each company to operate with tailored capital structures and investment plans, positioning them for growth within their specific sectors. The final terms of the spinout will be detailed in a management information circular to be shared with shareholders before they vote on the proposal.

Approval processes for the spinout include a review by the TSX Venture Exchange, shareholder consent, and possibly court approval in British Columbia if the plan proceeds via a formal arrangement. Jericho's CEO, Brian Williamson, noted in the news release, "By separating our hydrogen platform, we can create two agile, focused companies . . . positioning them for long-term growth and success."

Jericho Energy, which will continue trading on the TSX Venture Exchange under the symbol JEV, will retain its traditional oil and gas assets following the separation. The company's annual general meeting on January 15, 2025, may serve as a venue for shareholder approval, or a separate meeting may be scheduled.

Hydrogen Energy and Clean Tech

Energy Storage, in its November 5 report, underscored the growth potential for green hydrogen in the U.S. Supported by the government's US$7 billion Regional Clean Hydrogen Hubs program, this program aimed to boost clean hydrogen production and reduce costs. The report noted that the Mid-Atlantic Hydrogen Hub (MACH2) anticipated large-scale green hydrogen projects, generating over 20,000 jobs and incorporating hydrogen applications across sectors like steel, aviation, and maritime.

On November 6, Reuters reported that despite political shifts, U.S. clean energy momentum continues to be driven by federal tax credits and technology advancements. Renewable energy sources, including hydrogen, were identified as the fastest-growing segments on the power grid, benefiting from initiatives like the Inflation Reduction Act (IRA) and state mandates. Carl Fleming, a partner at McDermott Will & Emery, highlighted that "the jobs and the economic benefits have been so heavy in red states, it's hard to see an administration come in that says we don't like this." Although political challenges might impact renewable sectors like offshore wind, the trajectory of clean energy, including hydrogen, remained strong due to market demand and state-level support.

The International Energy Agency's (IEA) 2024 Global Hydrogen Review reported that global hydrogen demand reached 97 Mt (metric tons) in 2023. This demand was projected to approach 100 Mt in 2024. The IEA highlighted a rising focus on low-emissions hydrogen, particularly for refining and heavy industries. Although new applications in transport and energy storage accounted for less than 1% of global demand, industry interest grew, with chemical, refining, and shipping sectors making strides in contracting low-emissions hydrogen. The IEA also noted substantial investments in electrolyzer projects worldwide, with installed capacity expected to grow significantly.

Jericho's Catalysts

According to Jericho Energy's April 2024 investor presentation, the spinout of Hydrogen Technologies Corp. aligns with a broader strategy to drive advancements in hydrogen technology. Currently, an area experiencing significant momentum due to global energy transition efforts, the investor presentation highlights key growth drivers, including Jericho’s patented hydrogen-based boiler technology and emerging partnerships with institutions and companies across the hydrogen sector. [OWNERSHIP_CHART-7025]

The decision to separate hydrogen assets positions HTC to capture opportunities within the rapidly expanding hydrogen ecosystem, benefiting from policy support and rising market demand for green energy solutions. As part of its strategy, Jericho intends to leverage its expertise in traditional energy systems while directing resources to support innovation in hydrogen applications.

Ownership and Share Structure

Around 35% of Jericho's shares are held by management, insiders, and insider institutional investors, the company said. They include CEO Brian Williamson, who owns 1.19% or about 3.1 million shares; founder Allen Wilson, who owns 0.76% or about 1.97 million shares; and board member Nicholas Baxter, who owns 0.44%, or about 1.14 million shares, according to Refinitiv' latest research.

Around 10% of shares are held by non-insider institutions, and approximately 55% are in retail, the company said.

On March 6, 2023, JEV completed an insider-led private placement financing, above the current share price, for gross proceeds of CA$2.23 million.

JEV's market cap is CA$25.19 million, and it trades in a 52-week range of CA$0.07 and CA$0.18. It has 259.75 million shares outstanding, approx.. 189.99 million floating.

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Important Disclosures:

1. As of the date of this article, officers and/or employees of Streetwise Reports LLC (including members of their household) own securities of Jericho Energy Ventures Inc.
2. James Guttman wrote this article for Streetwise Reports LLC and provides services to Streetwise Reports as an employee.
3. This article does not constitute investment advice and is not a solicitation for any investment. Streetwise Reports does not render general or specific investment advice and the information on Streetwise Reports should not be considered a recommendation to buy or sell any security. Each reader is encouraged to consult with his or her personal financial adviser and perform their own comprehensive investment research. By opening this page, each reader accepts and agrees to Streetwise Reports' terms of use and full legal disclaimer. Streetwise Reports does not endorse or recommend the business, products, services or securities of any company.

For additional disclosures, please click here.

( Companies Mentioned: JEV:TSX.V; JROOF:OTC; JLM:FRA, )

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The molecular mechanism used by many bacteria to kill neighboring cells has redundancy built into its genetic makeup, which could allow for the mechanism to be expressed in different environments, say researchers at Penn State and the University of Wisconsin-Madison. Their new study provides insights into the molecular mechanisms of competition among bacteria. "Many organisms, including humans, acquire bacteria from their environment," said Tim Miyashiro, a biochemist and molecular biologist at Penn State and the leader of the research team. "These bacteria can contribute to functions within the host organism, like how our gut bacteria help us digest food. We're interested in the interactions among bacteria cells, and between bacteria and their hosts, to better understand these mutually beneficial symbiotic relationships." Cells of the bioluminescent bacteria Vibrio fisheri take up residence in the light organ of newly hatched bobtail squid. At night, the bacteria produce a blue glow that researchers believe obscures a squid's silhouette and helps protect it from predators. The light organ has pockets, or crypts, in the squid's skin that provide nutrients and a safe environment for the bacteria. "When the squid hatches, it doesn't yet have any bacteria in its light organ," said Miyashiro. "But bacteria in the environment quickly colonize the squid's light organ." Some of these different bacteria strains can coexist, but others can't. "Microbial symbioses are essentially universal in animals, and are crucial to the health and development of both partners," says Irwin Forseth, a program director in the National Science Foundation's Division of Integrative Organismal Systems, which funded the research. "The results from this study highlight the role small genetic changes can play in microbe interactions. Increased understanding will allow us to better predict organisms' performance in changing environments."

Image credit: Andrew Cecere

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Scientists have recovered the first genetic data from an extinct bird in the Caribbean, thanks to the remarkably preserved bones of a Creighton's caracara in a flooded sinkhole on Great Abaco Island in the Bahamas. Studies of ancient DNA from tropical birds have faced two formidable obstacles. Organic material quickly degrades when exposed to heat, light and oxygen. And birds' lightweight, hollow bones break easily, accelerating the decay of the DNA within. But the dark, oxygen-free depths of a 100-foot blue hole known as Sawmill Sink provided ideal preservation conditions for the bones of Caracara creightoni, a species of large carrion-eating falcon that disappeared soon after humans arrived in the Bahamas about 1,000 years ago. Florida Museum of Natural History researcher Jessica Oswald and her colleagues extracted and sequenced genetic material from the 2,500-year-old C. creightoni femur. Because ancient DNA is often fragmented or missing, the team had modest expectations for what they would find –- maybe one or two genes. But instead, the bone yielded 98.7% of the bird's mitochondrial genome, the DNA most living things inherit from their mothers. The mitochondrial genome showed that C. creightoni is closely related to the two remaining caracara species alive today: the crested caracara and the southern caracara. The three species last shared a common ancestor between 1.2 and 0.4 million years ago. "This project enhanced our understanding of the ecological and evolutionary implications of extinction, forged strong international partnerships, and trained the next generation of researchers," says Jessica Robin, a program director in National Science Foundation's Office of International Science and Engineering, which funded the study.

Image credit: Florida Museum photo by Kristen Grace

A friend is investigating the use of generative AI in his classes. I asked two different popular chatbots to write MATLAB programs for a mathematically nontrivial problem. Both chatbots understood my query and both wrote plausible MATLAB programs, but one of the programs was not correct. My recommendation for coursework: carefully read and test programs produced by generative AI and repair any incorrect ones.... read more >>

Patrick Doherty volunteered for a new medical intervention of gene-editor infusions for the treatment of genetically-based diseases.; Credit: /Patrick Doherty

Patrick Doherty had always been very active. He trekked the Himalayas and hiked trails in Spain.

But about a year and a half ago, he noticed pins and needles in his fingers and toes. His feet got cold. And then he started getting out of breath any time he walked his dog up the hills of County Donegal in Ireland where he lives.

"I noticed on some of the larger hill climbs I was getting a bit breathless," says Doherty, 65. "So I realized something was wrong."

Doherty found out he had a rare, but devastating inherited disease — known as transthyretin amyloidosis — that had killed his father. A misshapen protein was building up in his body, destroying important tissues, such as nerves in his hands and feet and his heart.

Doherty had watched others get crippled and die difficult deaths from amyloidosis.

"It's terrible prognosis," Doherty says. "This is a condition that deteriorates very rapidly. It's just dreadful."

So Doherty was thrilled when he found out that doctors were testing a new way to try to treat amyloidosis. The approach used a revolutionary gene-editing technique called CRISPR, which allows scientists to make very precise changes in DNA.

"I thought: Fantastic. I jumped at the opportunity," Doherty says.

On Saturday, researchers reported the first data indicating that the experimental treatment worked, causing levels of the destructive protein to plummet in Doherty's body and the bodies of five other patients treated with the approach.

"I feel fantastic," Doherty says. "It's just phenomenal."

The advance is being hailed not just for amyloidosis patients but also as a proof-of-concept that CRISPR could be used to treat many other, much more common diseases. It's a new way of using the innovative technology.

"This is a major milestone for patients," says Jennifer Doudna of the University of California, Berkeley, who shared a Nobel Prize for her work helping develop CRISPR.

"While these are early data, they show us that we can overcome one of the biggest challenges with applying CRISPR clinically so far, which is being able to deliver it systemically and get it to the right place," Doudna says.

CRISPR has already been shown to help patients suffering from the devastating blood disorders sickle cell disease and beta thalassemia. And doctors are trying to use it to treat cancer and to restore vision to people blinded by a rare genetic disorder.

But those experiments involve taking cells out of the body, editing them in the lab, and infusing them back in or injecting CRISPR directly into cells that need fixing.

The study Doherty volunteered for is the first in which doctors are simply infusing the gene-editor directly into patients and letting it find its own way to the right gene in the right cells. In this case, it's cells in the liver making the destructive protein.

"This is the first example in which CRISPR-Cas9 is injected directly into the bloodstream — in other words systemic administration — where we use it as a way to reach a tissue that's far away from the site of injection and very specifically use it to edit disease-causing genes," says John Leonard, the CEO of Intellia Therapeutics, which is sponsoring the study.

Doctors infused billions of microscopic structures known as nanoparticles carrying genetic instructions for the CRISPR gene-editor into four patients in London and two in New Zealand. The nanoparticles were absorbed by their livers, where they unleashed armies of CRISPR gene-editors. The CRISPR editor honed in on the target gene in the liver and sliced it, disabling production of the destructive protein.

Within weeks, the levels of protein causing the disease plummeted. Researchers reported at the Peripheral Nerve Society Annual Meeting and in a paper published in The New England Journal of Medicine.

"It really is exciting," says Dr. Julian Gillmore, who is leading the study at the University College London, Royal Free Hospital.

"This has the potential to completely revolutionize the outcome for these patients who have lived with this disease in their family for many generations. It's decimated some families that I've been looking after. So this is amazing," Gillmore says.

The patients will have to be followed longer, and more patients will have to be treated, to make sure the treatment's safe, and determine how much it's helping, Gillmore stresses. But the approach could help those struck by amyloidosis that isn't inherited, which is a far more common version of the disease, he says.

Moreover, the promising results potentially open the door for using the same approach to treatment of many other, more common diseases for which taking cells out of the body or directly injecting CRISPR isn't realistic, including heart disease, muscular dystrophy and brain diseases such as Alzheimer's.

"This is really opening a new era as we think about gene-editing where we can begin to think about accessing all kinds of different tissue in the body via systemic administration," Leonard says.

Other scientists who are not involved in the research agree.

"This is a wonderful day for the future of gene-editing as a medicine,"
agree Fyodor Urnov, a professor of genetics at the University of California, Berkeley. "We as a species are watching this remarkable new show called: our gene-edited future."

Doherty says he started feeling better within weeks of the treatment and has continued to improve in the weeks since then.

"I definitely feel better," he told NPR. "I'm speaking to you from upstairs in our house. I climbed stairs to get up here. I would have been feeling breathless. I'm thrilled."

This content is from Southern California Public Radio. View the original story at SCPR.org.

NASA released a workshop report on the UNBOUND-FEW workshop series, which was facilitated in part by Tribal Resilience Learning Network staff from the Alaska CASC. The workshop report reveals key recommendations for making data tools more useful for climate adaptation planning.

USGS Western Fisheries Research Center (WFRC) biological science technician, Genevieve Kent, is the winner of this issue’s photo contest. 

This Buy-rated Canadian explorer-developer is working to achieve first mover status in this emerging clean energy space. Find out what all it has done and is doing.

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A National Science Foundation-funded study found that Charles Darwin's famous finches defy what has long been considered a key to evolutionary success: genetic diversity. The research on finches of the Galapagos Islands could change the way conservation biologists think about a species' potential for extinction in naturally fragmented populations. Researchers examined 212 tissue samples from museum specimens and living birds. Some of the museum specimens in the study were collected by Darwin himself in 1835. Only one of the extinct populations, a species called the vegetarian finch, had lower genetic diversity compared to modern survivors. Specifically, researchers believe a biological phenomenon called sink-source dynamics is at play in which larger populations of birds from other islands act as a "source" of immigrants to the island population that is naturally shrinking, the "sink." Without these immigrant individuals, the natural population on the island likely would continue to dwindle to local extinction. The immigrants have diverse genetics because they are coming from a variety of healthier islands, giving this struggling "sink" population inflated genetic diversity.

Image credit: Jose Barreiro

Source: Streetwise Reports 10/28/2024

Sernova Corp. (SVA:TSX.V; SEOVF:OTCQB; PSH:XERTA) and its Cell Pouch technology could be the solution to existing challenges involving the delivery of medical treatments to patients, such as the ones described here.

Diabetic patients in resource-limited settings are having to revert back to one of the less favored, alternative ways to take insulin, via syringes or glass vials, because Danish pharmaceutical company, Novo Nordisk A/S (NVO:NYSE), will stop making its insulin pens, The Guardian reported. Patients generally prefer this method for dosing themselves with insulin, as shown in a 2024 survey, because it is more convenient and more accurate.

Type 1 diabetic patients already are being impacted as Novo stopped supplying its insulin pens to certain regions, South Africa for instance. Patients there have switched back to using glass vials.

In a second situation, Novo Nordisk is working to bring stem cell-based therapies to patients more efficiently and, in seeking a solution, formed a partnership with Evotec SE (EVO:NASDAQ) to develop technologies that will achieve this, noted Evotec is a Germany-based global biotech firm with its own cell therapy and partnered cell types all in preclinical development for various indications, including diabetes, oncology, cardiology, and ophthalmology.

Per the agreement, Novo Nordisk is to provide research and development funding and potentially monetary incentives to Evotec, and Evotec is to develop the desired new technologies. Novo has the option to obtain exclusive rights to use, in a predefined medical indication, the product(s) born out of this collaboration agreement. Novo's areas of focus, along with diabetes, are cardiovascular diseases, rare diseases, growth hormone-related diseases, hemophilia, nonalcoholic steatohepatitis, and weight management.

Safe, Effective Therapeutic Cell Delivery

Sernova Corp.'s Cell Pouch is a vehicle for delivering various types of therapeutic cells to patients, such as donor islet cells to insulin-dependent diabetics.

When used, the Cell Pouch's containment channels are filled with the appropriate therapeutic cells, and then the device is implanted in the patient. In situ, the cells release therapeutic proteins or hormones the patient's body completely or partially lacks. The device creates a vascularized, organ-like environment that protects the therapeutic cells from immune system attacks, keeping them alive and functioning.

"The Cell Pouch is the most advanced encapsulation device in development," Ventum Capital Markets Analyst Stefan Quenneville wrote in a Sept. 12 research report.

Sernova is testing its Cell Pouch in the clinic, specifically in Type 1 diabetes. In its ongoing Phase 1/2 study, the Canadian company is evaluating the treatment of insulin-dependent diabetes with donor islets implanted via the Cell Pouch, with added immunosuppression therapy. Study data so far have shown the Cell Pouch to be safe and well tolerated and the treatment, effective, reported Dr. Joseph Pantginis, analyst at H.C. Wainwright & Co., in a Sept. 12 research report.

Seven patients, all six of Cohort A and one in Cohort B, achieved sustained insulin independence, between 5.5 and 50 months in duration, free of hypoglycemic episodes. Their blood sugar levels were controlled in the nondiabetic range (i.e.,) HbA1c less than 6.5%.

"The Cell Pouch is the most advanced encapsulation device in development," Ventum Capital Markets Analyst Stefan Quenneville wrote.

A Cell Pouch removed from one of the study patients showed it still contained functioning insulin, glucagon, and somatostatin-producing cells. No evidence was seen of detrimental fibrotic tissue, too many T-cells, material degradation, or changes in the device architecture.

"We believe the impressive response rates and observed durability support Sernova's strategy and justify further investigation while positioning the technology for potential commercial success," noted Pantginis.

The results add to an expanding collection of evidence that the Cell Pouch is functioning as it should. The data also support the "impressive" results already reported from this study and help derisk future related trials.

"If Sernova is successful in bringing its functional cure for insulin-dependent diabetes to the stage where it can go into commercial production, the global market for it will be massive," wrote Technical Analyst Clive Maund in a Sept. 16 note.

In another of its programs, Sernova, in collaboration with Evotec, is developing an implantable off-the-shelf, induced pluripotent stem cell (iPSC)-based islet replacement therapy, Maund reported.

"This partnership provides Sernova a potentially unlimited supply of insulin-producing cells to treat millions of patients with insulin-dependent diabetes (Type 1 and Type 2)," he added.

This partnership was announced on May 17, 2022. You can read more about it in the press release here.

Market Growth Predicted to 2030

The global live cell encapsulation market, encompassing drug delivery, regenerative medicine and cell transplantation, is expected to continue growing through at least 2030, according to Grand View Research. The market's value, US$210.7 million in 2022, is forecasted to increase at a 3.97% compound annual growth rate between that year and 2030.

"If Sernova is successful in bringing its functional cure for insulin-dependent diabetes to the stage where it can go into commercial production, the global market for it will be massive," wrote Technical Analyst Clive Maund.

Along with diabetes, live cell encapsulation is being used to treat neurological disorders like Parkinson's disease, The market research firm noted. Further, it has been proven to be a suitable way to deliver treatment for other types of diseases, including cancer, anemia, heart failure and more.

Several factors are expected to keep driving market growth during the forecast period, Grand View noted. A significant one is the increasing use of live cell encapsulation in regenerative medicine to replace disease or damaged tissues. A related contributor is rising public and private funding and investments in cell and gene therapies.

The advantages of live cell encapsulation in controlled drug delivery are boosting the market, too. They include enhanced therapeutic effects, lowered drug dose, reduced cytotoxicity, improved patient convenience and better patient compliance.

Novel new products and technological advancements are expected to add value to the market as well.

The Catalysts: Progress With Programs

Various potential stock-moving events are slated for Sernova, according to its September 2024 Corporate Presentation.

Two catalysts are expected by Sernova in 2025, related to the company's ongoing Phase 1/2 clinical trial in Type 1 diabetes. One is results for the remaining Cohort B patients. The other is commencement of Cohort C, who will receive, along with the islet cells, an optimized immune suppression regimen.

Several analysts are bullish on Sernova. One of them is Loe, who rates it as a Speculative Buy. His price target on the life sciences firm implies a 455% return from its current share price.

Next year, Sernova plans to start a Phase 1/2 trial of the regeneratively produced islet cells to result from its partnership with Evotec, delivered via the Cell Pouch to Type 1 diabetes patients.

Other catalysts are expected to come as a result of Sernova advancing its preclinical programs. One is a personalized treatment with patient corrected cells via Cell Pouch for hypothyroidism. Another is a Cell Pouch-delivered, ex vivo lentiviral factor VIII gene therapy for hemophilia, being developed in partnership with the European Haemacure Consortium.

Also, through partnerships, Sernova is developing technologies that would eliminate the need for concurrent immunosuppression during Cell Pouch-delivered cell treatment, a "blue sky objective," Douglas Loe, a Leede Financial Inc. analyst, noted in a Sept. 12 research report.

"Any advances in this regard could be incorporated into future Cell Pouch studies," he wrote. "We do not consider the need for such therapy to be relevant to Cell Pouch function itself."

Analyst: Company is "Very Undervalued"

Several analysts are bullish on Sernova. One of them is Loe, who rates it as a Speculative Buy. His price target on the life sciences firm implies a 455% return from its current share price.

According to H.C. Wainwright's Pantginis, the deepening responses of Type 1 diabetes patients in its Phase 1/2 trial continue to "crystallize Sernova stock's possible upside." The upside reflected in Pantginis' price target is 2,122%. The analyst recommends the company as a Buy.

Ventum's Quenneville also has a Buy on Sernova, and his target price reflects an 826% return on investment. In his report, the analyst highlighted the impressive efficacy and tolerability of the Cell Pouch up to five years post-implantation, as shown in the Phase 1/2 clinical trial data.

"This represents the longest-lasting implanted encapsulation device containing functioning islets without fibrosis," Quenneville wrote.

According to Technical Analyst Maund, Sernova is "very undervalued here given its huge potential" in the Type 1 diabetes market, as indicated on the stock charts. The fundamental outlook for the company is improving, and evidence is strong that a reversal to the upside may be happening. SVA may appreciate significantly soon. [OWNERSHIP_CHART-4790]

"Sernova is therefore viewed as a good stock to accumulate in this area, between the current price and recent lows," Maund wrote on Sept. 16. At that time, Sernova's share price was about the same as it is now.

Ownership and Share Structure

According to Refinitiv, about 12.96% of the company is held by insiders and management, and 0.05% by institutions. The rest is retail.

Top shareholders include Tomas Angel with 4.91%, Director Steven Sangha with 4.27%, Betty Anne Millar with 1.32%, Brett Alexander Whalen with 0.87%, and Garry Deol with 0.77%.

Its market cap is CA$83 M. Its 52-week range is CA$0.20−0.82 per share.

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Important Disclosures:

1. Sernova Corp. has a consulting relationship with Street Smart an affiliate of Streetwise Reports. Street Smart Clients pay a monthly consulting fee between US$8,000 and US$20,000.
2. As of the date of this article, officers and/or employees of Streetwise Reports LLC (including members of their household) own securities of Sernova Corp.
3. Doresa Banning wrote this article for Streetwise Reports LLC and provides services to Streetwise Reports as an independent contractor.
4. Streetwise Reports does not render general or specific investment advice and the information on Streetwise Reports should not be considered a recommendation to buy or sell any security. Each reader is encouraged to consult with his or her personal financial adviser and perform their own comprehensive investment research. By opening this page, each reader accepts and agrees to Streetwise Reports' terms of use and full legal disclaimer. Streetwise Reports does not endorse or recommend the business, products, services or securities of any company.
5. This article does not constitute medical advice. Officers, employees and contributors to Streetwise Reports are not licensed medical professionals. Readers should always contact their healthcare professionals for medical advice.

For additional disclosures, please click here.

( Companies Mentioned: SVA:TSX.V;SEOVF:OTCQB;PSH:XERTA, )

Source: Dr. Jonathan Aschoff 11/07/2024

BioRestorative Therapies Inc. (BRTX:OTCBB) received a provisional license from the New York State Department of Health (NYSDOH) to process allogeneic donor tissue for various cells, like stem, to be isolated, expanded, and cryopreserved for medical research, reported MKM analyst Dr. Jonathan Aschoff in a Nov. 5 research note.

The biotech develops therapeutic products using cell and tissue protocols, primarily involving adult stem cells.

1,100% Upside Implied

Aschoff reiterated Roth's US$18 per share target price on the biotech, trading at the time of the report at about US$1.50 per share, the analyst noted. These figures reflect a potential return for investors of 1,100%.

BioRestorative Therapeutics remains a Buy.

Sources of Revenue

Aschoff discussed how BioRestorative can generate revenue. This new license is the second from NYSDOH that the biotech holds. The previous one allows it to process autologous mesenchymal stem cells, in other words, act as a tissue bank.

The U.S.-based biotech now may capitalize on its Current Good Manufacturing Practices capabilities and process, bank and distribute clinical-grade allogeneic biologics. This revenue generation would better position the biotech financially, "allowing it to reduce cash burn and dependence on equity markets," wrote Aschoff.

Another source of revenue for BioTherapeutics is from its supply agreement with Cartessa Aesthetics LLC signed earlier in 2024. Per the five-year agreement, BioTherapeutics will supply Cartessa with a preset minimum quantity of finished vials of the aesthetic company's initial cell-based biologic commercial product each year. This product, intended to reduce the appearance of fine lines and wrinkles, will be sold under the Chronos ExoCR mark. Cartessa, on the other hand, will give BioTherapeutics access to its marketing and distribution capabilities to get its technologies to aesthetic providers.

The biotech may expand the Cartessa agreement into a broader offering of biocosmeceuticals and therapeutics if future clinical trials support their approval by the U.S. Food and Drug Administration. This expansion would transform the partnership into "a vertically integrated biocosmeceutical platform," Aschoff wrote.

Clinical Trial Catalyst

Meanwhile, Aschoff reported, BioRestorative will continue its Phase 2 clinical evaluation of its novel back pain treatment, BRTX-100, in patients with chronic lumbar disc degeneration.

Preliminary results from this clinical trial are expected in late Q4/24 or early Q1/25.

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Important Disclosures:

1. Doresa Banning wrote this article for Streetwise Reports LLC and provides services to Streetwise Reports as an independent contractor.
2. This article does not constitute investment advice and is not a solicitation for any investment. Streetwise Reports does not render general or specific investment advice and the information on Streetwise Reports should not be considered a recommendation to buy or sell any security. Each reader is encouraged to consult with his or her personal financial adviser and perform their own comprehensive investment research. By opening this page, each reader accepts and agrees to Streetwise Reports' terms of use and full legal disclaimer. Streetwise Reports does not endorse or recommend the business, products, services or securities of any company.
3. This article does not constitute medical advice. Officers, employees and contributors to Streetwise Reports are not licensed medical professionals. Readers should always contact their healthcare professionals for medical advice.

For additional disclosures, please click here.

Disclosures for Roth MKM, BioRestorative Therapies Inc., November 5, 2024

Regulation Analyst Certification ("Reg AC"): The research analyst primarily responsible for the content of this report certifies the following under Reg AC: I hereby certify that all views expressed in this report accurately reflect my personal views about the subject company or companies and its or their securities. I also certify that no part of my compensation was, is or will be, directly or indirectly, related to the specific recommendations or views expressed in this report.

Disclosures: Within the last twelve months, ROTH Capital Partners, or an affiliate to ROTH Capital Partners, has received compensation for investment banking services from BioRestorative Therapies, Inc.. ROTH makes a market in shares of BioRestorative Therapies, Inc. and as such, buys and sells from customers on a principal basis. Shares of BioRestorative Therapies, Inc. may be subject to the Securities and Exchange Commission's Penny Stock Rules, which may set forth sales practice requirements for certain low-priced securities.

ROTH Capital Partners, LLC expects to receive or intends to seek compensation for investment banking or other business relationships with the covered companies mentioned in this report in the next three months. The material, information and facts discussed in this report other than the information regarding ROTH Capital Partners, LLC and its affiliates, are from sources believed to be reliable, but are in no way guaranteed to be complete or accurate. This report should not be used as a complete analysis of the company, industry or security discussed in the report. Additional information is available upon request. This is not, however, an offer or solicitation of the securities discussed. Any opinions or estimates in this report are subject to change without notice. An investment in the stock may involve risks and uncertainties that could cause actual results to differ materially from the forward-looking statements. Additionally, an investment in the stock may involve a high degree of risk and may not be suitable for all investors. No part of this report may be reproduced in any form without the express written permission of ROTH. Copyright 2024. Member: FINRA/SIPC.

( Companies Mentioned: BRTX:OTCBB, )

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