The results of the seventh blind test of crystal structure prediction are presented, focusing on structure generation methods.

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern. The use of CSP in the prediction of likely cocrystal stoichiometry was also explored, demonstrating multiple possible approaches. Crystallographic disorder emerged as an important theme throughout the test as both a challenge for analysis and a major achievement where two groups blindly predicted the existence of disorder for the first time. Additionally, large-scale comparisons of the sets of predicted crystal structures also showed that some methods yield sets that largely contain the same crystal structures.

Algebraic expressions for averaging linear and nonlinear stiffness tensors from general anisotropy to different effective symmetries (11 Laue classes elastically representing all 32 crystal classes, and two non-crystalline symmetries: isotropic and cylindrical) have been derived by automatic symbolic computations of the arithmetic mean over the set of rotational transforms determining a given symmetry. This approach generalizes the Voigt average to nonlinear constants and desired approximate symmetries other than isotropic, which can be useful for a description of textured polycrystals and rocks preserving some symmetry aspects. Low-symmetry averages have been used to derive averages of higher symmetry to speed up computations. Relationships between the elastic constants of each symmetry have been deduced from their corresponding averages by resolving the rank-deficient system of linear equations. Isotropy has also been considered in terms of generalized Lamé constants. The results are published in the form of appendices in the supporting information for this article and have been deposited in the Mendeley database.

Large-bandwidth pulses produced by cutting-edge X-ray free-electron lasers (FELs) are of great importance in research fields like material science and biology. In this paper, a new method to generate high-power ultrashort FEL pulses with tunable spectral bandwidth with spectral coherence using a dielectric-lined waveguide without interfering operation of linacs is proposed. By exploiting the passive and dephasingless wakefield at terahertz frequency excited by the beam, stable energy modulation can be achieved in the electron beam and large-bandwidth high-intensity soft X-ray radiation can be generated. Three-dimensional start-to-end simulations have been carried out and the results show that coherent radiation pulses with duration of a few femtoseconds and bandwidths ranging from 1.01% to 2.16% can be achieved by changing the undulator taper profile.

A new experimental setup combining X-ray photon correlation spectroscopy (XPCS) in the hard X-ray regime and a high-pressure sample environment has been developed to monitor the pressure dependence of the internal motion of complex systems down to the atomic scale in the multi-gigapascal range, from room temperature to 600 K. The high flux of coherent high-energy X-rays at fourth-generation synchrotron sources solves the problems caused by the absorption of diamond anvil cells used to generate high pressure, enabling the measurement of the intermediate scattering function over six orders of magnitude in time, from 10−3 s to 103 s. The constraints posed by the high-pressure generation such as the preservation of X-ray coherence, as well as the sample, pressure and temperature stability, are discussed, and the feasibility of high-pressure XPCS is demonstrated through results obtained on metallic glasses.

Fourth-generation synchrotron storage rings represent a significant milestone in synchrotron technology, offering outstandingly bright and tightly focused X-ray beams for a wide range of scientific applications. However, due to their inherently tight magnetic lattices, these storage rings have posed critical challenges for accessing lower-energy radiation, such as infrared (IR) and THz. Here the first-ever IR beamline to be installed and to operate at a fourth-generation synchrotron storage ring is introduced. This work encompasses several notable advancements, including a thorough examination of the new IR source at Sirius, a detailed description of the radiation extraction scheme, and the successful validation of our optical concept through both measurements and simulations. This optimal optical setup has enabled us to achieve an exceptionally wide frequency range for our nanospectroscopy experiments. Through the utilization of synchrotron IR nanospectroscopy on biological and hard matter samples, the practicality and effectiveness of this beamline has been successfully demonstrated. The advantages of fourth-generation synchrotron IR sources, which can now operate with unparalleled stability as a result of the stringent requirements for producing low-emittance X-rays, are emphasized.

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.

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.

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.

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.

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 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.

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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.

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

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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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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.
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( 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.

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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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Many business users have approached generative AI technology more cautiously because it can make up untrue facts and be tricked into saying unsettling things. Oracle's human resources software is used by big businesses for hiring new employees and providing performance evaluations, among other things. Oracle will put a button on many of the fields in the software that will automatically generate draft text for things like job listings or performance goals.

Microsoft-owned OpenAI has announced the general availability of its latest text-generating model GPT-4, through its API.

D.C. Attorney General Karl Racine, pictured in 2019, is hoping to change how the justice system handles cases involving 16- and 17-year-olds who are charged as adults.; Credit: Claire Harbage/NPR

A new proposal from D.C. Attorney General Karl Racine could overhaul the way juveniles are charged as adults and offer greater opportunities for rehabilitation than a federal prison.

If passed, the proposal would impact people like Charlie Curtis, who was charged with armed robbery and sent to adult court at the age of 16 — a decision that he said left him confused and adrift.

Curtis said he had problems reading and writing back then, let alone asking the court to appoint him a lawyer. After his conviction, he spent years in a federal prison in New Jersey.

"It's a little bit of everything," Curtis said. "A little scary, a little nervous, you got to grow up real fast. You're not in the high school gym no more."

Curtis returned home when he was 22. It would be a while before he stabilized, got a good job driving a truck and started a family that grew to include three children. He now volunteers to help other young people leaving jail and prison — trying to offer the support he got too late.

What the legislation would change

NPR has learned Racine will introduce legislation in the D.C. Council Wednesday to ensure that 16- and 17-year-olds accused of certain crimes start in the family court system.

"Children should be treated like children, including 16- and 17-year-olds, notwithstanding the seriousness of their alleged offense," Racine said.

The proposed legislation would apply to teens charged with murder, first-degree sexual abuse, and armed robbery, among other crimes. Currently, the lead federal prosecutor in D.C. can file those kinds of cases directly in adult court — without any say from a judge — even if those defendants ultimately plead guilty to lesser charges.

D.C. has no federal prisons of its own, so young people convicted as adults can spend years in other states, at great distances from their families. The D.C. attorney general said the majority of underaged defendants charged as adults return home to the District before they are 21, but without the benefit of access to educational programs, vocational training and mentoring they could have received if their cases had been handled in the family courts.

"The adult system doesn't work that way," Racine said. "Federal Bureau of Prisons people will tell you the adult system is not made for kids."

Eduardo Ferrer, the policy director at the Georgetown Juvenile Justice Initiative, said research demonstrates charging young people in the adult system decreases public safety by making it more likely they'll break the law in the future. Most charging decisions in these cases in D.C. are made within a half a day, without the benefit of a longer review of the facts of the case and the background of the teenager, he said.

"The process in D.C. right now, because the U.S. Attorney's Office does not exercise discretion often in terms of keeping kids down in juvenile court, is more of a sledgehammer," Ferrer said. "What we really need is a scalpel."

The U.S. Attorney's Office in Washington and the Metropolitan Police Department did not return calls for comment about the proposal. But its supporters expect some resistance when it's ultimately considered by the City Council.

Ferrer pointed out that the legislation still leaves room for a judge to transfer a young person in D.C. into adult court if the judge has concerns about the ability for rehabilitation and worries about public safety. "The reality is that a young person still can be transferred to adult court," he said. "The difference is we're taking the time to get it right."

The potential impact

The vast majority — 93% — of the 16- and 17-year-olds who are charged as adults in D.C. are Black. One of them is the son of Keela Hailes. In 2008, he was charged with armed robbery. Hailes said she wasn't consulted about decisions about what was best for her son.

"It's like my son went from a 16-year-old to a 30-year-old overnight," Hailes said.

Her son was convicted and sent to federal prison in North Dakota, too far for her to visit regularly as she had done in the D.C. area. Her son, now 30 years old, is incarcerated again. Hailes said she wishes he would have had more options years ago — a chance for an education, and time spent in a juvenile facility instead of around adults in prison.

She said science suggests young people have less judgment and maturity because their brains are still developing. She thinks the new proposal will make a "huge difference" for juveniles in the legal system in the District.

The proposal is the latest in a series of steps Racine has taken to overhaul juvenile justice in D.C. He pushed the courts to stop shackling young defendants; started a restorative justice program for juveniles to meet with and make amends to victims; and worked to limit the ability of police to put handcuffs on most people under age 12.

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

Many U.S. farmers who grow genetically engineered (GE) crops are realizing substantial economic and environmental benefits -- such as lower production costs, fewer pest problems, reduced use of pesticides, and better yields -- compared with conventional crops, says a new report from the National Research Council.

The National Academy of Sciences and the National Academy of Medicine are launching a major initiative to guide decision making about controversial new research involving human gene editing.

The analysis used by federal agencies to set standards for fuel economy and greenhouse gas emissions for new U.S. light-duty vehicles -- passenger cars and light trucks -- from 2017 to 2025 was thorough and of high caliber overall, says a new report from the National Research Council.

Scientific advances in molecular biology over the past 50 years have produced remarkable progress in medicine. Some of these advances have also raised important ethical and societal issues – for example, about the use of recombinant DNA technologies or embryonic stem cells.

We thank the organizers of our International Summit on Human Gene Editing for their thoughtful concluding statement and welcome their call for us to continue to lead a global discussion on issues related to human gene editing.

The increase in the number of children from low-income families who are receiving federal disability benefits for speech and language disorders over the past decade parallels the rise in the prevalence of these disorders among all U.S. children, says a new report by the National Academies of Sciences, Engineering, and Medicine.

An extensive study by the National Academies of Sciences, Engineering, and Medicine has found that new technologies in genetic engineering and conventional breeding are blurring the once clear distinctions between these two crop-improvement approaches.

The emerging science of gene drives has the potential to address environmental and public health challenges, but gene-drive modified organisms are not ready to be released into the environment and require more research in laboratories and highly controlled field trials, says a new report from the National Academies of Sciences, Engineering, and Medicine.

U.S. adults perform comparably to adults in other economically developed countries on most measures of science knowledge and support science in general, says a new report from the National Academies of Sciences, Engineering, and Medicine.

The National Academies Committee on Genetically Engineered Crops - Past Experiences and Future Prospects authored an almost 600-page landmark report, released in May 2016. It was perhaps the most comprehensive analysis of genetically engineered crops to date.

Joint statements from the national science academies of the G7 nations were delivered today to the Italian government in advance of the G7 Summit to be held in Taormina, Italy, at the end of May.

A new report from the National Academies of Sciences, Engineering, and Medicine calls for a series of substantial reforms to strengthen the U.S. biomedical research system for the next generation of scientists.

The National Academies of Sciences, Engineering, and Medicine are launching the “New Voices in Sciences, Engineering, and Medicine” initiative to identify outstanding early-career science, engineering, and medicine (SEM) leaders.

A video created as part of the Transportation Research Board’s centennial celebration has been named the winner of three 2020 Telly Awards, which annually showcase the best work created within television and across all types of video production.

Categorizing workers with generational labels like “baby boomer” or “millennial” to define their needs and behaviors is not supported by research, and cannot adequately inform workforce management decisions, according to a new report from the National Academies of Sciences, Engineering, and Medicine.

Human embryos whose genomes have been edited should not be used to create a pregnancy until it is established that precise genomic changes can be made reliably without introducing undesired changes — a criterion that has not yet been met by any genome editing technology, says a new report by an international commission of the U.S. National Academy of Medicine, U.S. National Academy of Sciences, and the U.K.’s Royal Society.

The U.S. surgeon general has released a public advisory calling misinformation a “serious threat to public health.” The National Academies have been addressing misinformation in health and science on multiple fronts and are taking steps to help cultivate a fact- and evidence-based information environment.

To explore the complex interactions between the natural world and society and enhance our understanding of Earth’s systems, the National Science Foundation should create a next-generation Earth systems science initiative.

Race, ethnicity, and ancestry labels are often used in genomics and genetics research to describe human genetic differences, which is misleading and inaccurate. Researchers and scientists who utilize genetic and genomic data should rethink and justify how and why they use these descriptors in their work.

The country's leading search engine company is among tech firms shifting their focus to the commercialisation of large language model (LLM) applications after nearly two years of heavy investment in research and development in models that they tout as alternatives to OpenAI's GPT.