Somalia is currently in the midst of a dire humanitarian crisis that threatens to destabilize the nation’s security. This crisis is a result of the Somali Civil War, which began in 1991. Altercations between clan-based operations have caused a host of issues over the years, including over 596 civilian casualties, according to the United Nations […]

The United States stressed at the United Nations that “there must be no forcible displacement, nor policy of starvation in Gaza” by Israel, warning such policies would have grave implications under U.S. and international law. The remarks by U.S. Ambassador to the U.N. Linda Thomas-Greenfield came just hours after Washington said its ally Israel was […]

Title: Taking a Shot at Pain Relief After Knee Replacement
Category: Health News
Created: 8/18/2022 12:00:00 AM
Last Editorial Review: 8/19/2022 12:00:00 AM

BACKGROUND AND PURPOSE:

Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI.

BACKGROUND AND PURPOSE:

Vertebrobasilar artery stent placement (VBS) is potentially effective in preventing recurrent posterior circulation strokes; however, the incidences of in-stent restenosis and stented-territory ischemic events based on the location of stent placement have rarely been investigated. We aimed to investigate the characteristics and prognosis of VBS between intracranial and extracranial.

Express Sport writers have decided who should replace Gary Lineker

It's no secret that most technology nowadays isn't exactly built to last forever, with new product models regularly on sale on replace malfunctioning items. However, Apple, which famously announces new products each September, is taking new steps to let people repair their own devices. Apple has launched parts and tools for the iPhone 16, including the Plus, Pro and Pro Max. 

Now, if you have an iPhone 16 model that's acting up, you can go to Apple's self service repair store and — possibly — get what you need to fix it. Choose the product type and model then pick from the iPhone 16's choices of back glass, battery, camera, top speaker, TrueDepth camera, SIM tray and more. Apple's iPhone 16 should be easier to fix than its predecessor, receiving a 7/10 on the iFixit repairability scale, compared to a 4/10 for the iPhone 15. 

You can either get kits or just the necessary part with prices varying based on your phone model. For example, a battery and screw kit for the iPhone 16 Pro Max is $119, but its $99 for the regular iPhone 16. You can get quite a lot of money back on the kit prices if you return the replaced piece afterward. The iPhone 16 Pro Max, for instance, goes down to $61.88 after you send back the old battery. 

Apple created its self-service program in 2022, giving its customers access to actual Apple parts when something in their device failed. However, Apple states that the service "is intended for individuals with the knowledge and experience to repair electronic devices. If you are experienced with the complexities of repairing electronic devices." So, repairs might not be as accessible if you or someone you know isn't savvy in making the swaps. 

UNITED NATIONS — The United States stressed at the United Nations (UN) on Tuesday (Nov 12) that "there must be no forcible displacement, nor policy of starvation in Gaza" by Israel, warning such policies would have grave implications under US and international law. The remarks by US Ambassador to the UN Linda Thomas-Greenfield came just hours after Washington said its ally Israel was doing enough to address the humanitarian crisis in Israel to avoid facing potential restrictions on US military aid. "Still, Israel must ensure its actions are fully implemented - and its improvements sustained over time," Thomas-Greenfield told the UN Security Council. It was also urgently important that Israel pause implementation of a law banning the operation of the UN Palestinian relief agency UNRWA, she added.

Welcome back to Cover Snark! From Mabry: This guy is suffering from sliding bicep syndrome, plus his forearm seems to be stolen from a 7 foot tall basketball player. And then there’s the nipple that’s trying to leave the scene altogether. He also looks like one of the Property Brothers. Sarah: Ok the proportions and perspective here are really weird to the point I feel like I should give everyone a warning. Like, uncanny valley … Continue reading Cover Snark: Yet Another Terrible Wolf Placement →

While disaster-induced migration tends to be short-term, slow-onset climate-induced migration may be more permanent and on a larger scale.

The post The hidden crisis of disaster displacement and host community struggles in rural areas of Pakistan first appeared on International Water Management Institute (IWMI).

IWMI research will support evidence-based design and the implementation of the Jordanian climate adaptation policy.

The post The multiple challenges from climate change, urbanization and forced displacement in Irbid Governorate, northwest Jordan first appeared on International Water Management Institute (IWMI).

Cambridge, MA. : National Bureau of Economic Research, 2023

The switch to renewable energy requires technology upgradation, funding and a collective push from public and private stakeholders

Refugee women, especially those with disabilities are guaranteed certain rights but are seldom able to realise them given the multitude of barriers they face

National Bureau of Economic Research

Total mobilisation six per cent higher than previous financial year

According to the institute, students received offers across diverse domains, including consulting, finance, product management, FMCG, retail, construction, energy, e-commerce, conglomerates, healthcare

‘Our students received offers from reputed companies despite a slowdown in the market,’ says Professor Debolina Dutta, chairperson, career development services, IIMB

In addition to IT firms, the service sector, marketing, finance, and banking industries have emerged as leading recruiters this year

The aspiration to own a good device without paying much is making the used smartphones a very attractive choice for consumers wanting to upgrade or even with first-time smartphone users

Antonelli took over for George Russell in the opening practice session for Sunday's Italian Grand Prix at Monza

Spotting a rapid surge in the Pre-Placement Offers (PPO) this year, students of IITs are also anticipating a growth in placements.

The Hero Duet could be replaced by something that was showcased at the Auto Expo 2016 but could still be undergoing development.

The Ducati Panigale V2 draws power from a 955cc, V-twin Superquadro engine which is now BS6/Euro5 compliant and pumps out 151 horses.

The total corporate bond issuance in FY19 was Rs 6.1 lakh crore, just slightly higher than `6 lakh crore mopped up in FY18.

There are no plans for new coal plants to be built in the United States. This opens doors for the geothermal industry possibly more than ever before in U.S. history. In an Energy Information Administration (EIA) forecast to 2018, coal was one of the top-cost commissioning technology options; geothermal was one of the lowest.

Introduction The long-awaited regulations on the Administration of Commercial Franchise Operations (the 'New Regulations') were promulgated by the State Council of the PRC on 6 February 2007, and will take effect on 1 May 2007. They apply equally t...

Calibration of area detectors from powder diffraction standards is widely used at synchrotron beamlines. From a single diffraction image, it is not possible to determine both the sample-to-detector distance and the wavelength, but, with images taken from multiple positions along the beam direction and where the relative displacement is known, the sample-to-detector distance and wavelength can both be determined with good precision. An example calibration using the GSAS-II software package is presented.

Molecular replacement (MR) is the predominant route to solution of the phase problem in macromolecular crystallography. Where the lack of a suitable homologue precludes conventional MR, one option is to predict the target structure using bioinformatics. Such modelling, in the absence of homologous templates, is called ab initio or de novo modelling. Recently, the accuracy of such models has improved significantly as a result of the availability, in many cases, of residue-contact predictions derived from evolutionary covariance analysis. Covariance-assisted ab initio models representing structurally uncharacterized Pfam families are now available on a large scale in databases, potentially representing a valuable and easily accessible supplement to the PDB as a source of search models. Here, the unconventional MR pipeline AMPLE is employed to explore the value of structure predictions in the GREMLIN and PconsFam databases. It was tested whether these deposited predictions, processed in various ways, could solve the structures of PDB entries that were subsequently deposited. The results were encouraging: nine of 27 GREMLIN cases were solved, covering target lengths of 109–355 residues and a resolution range of 1.4–2.9 Å, and with target–model shared sequence identity as low as 20%. The cluster-and-truncate approach in AMPLE proved to be essential for most successes. For the overall lower quality structure predictions in the PconsFam database, remodelling with Rosetta within the AMPLE pipeline proved to be the best approach, generating ensemble search models from single-structure deposits. Finally, it is shown that the AMPLE-obtained search models deriving from GREMLIN deposits are of sufficiently high quality to be selected by the sequence-independent MR pipeline SIMBAD. Overall, the results help to point the way towards the optimal use of the expanding databases of ab initio structure predictions.

Although the success of molecular-replacement techniques requires the solution of a six-dimensional problem, this is often subdivided into two three-dimensional problems. REMO09 is one of the programs which have adopted this approach. It has been revisited in the light of a new probabilistic approach which is able to directly derive conditional distribution functions without passing through a previous calculation of the joint probability distributions. The conditional distributions take into account various types of prior information: in the rotation step the prior information may concern a non-oriented model molecule alone or together with one or more located model molecules. The formulae thus obtained are used to derive figures of merit for recognizing the correct orientation in the rotation step and the correct location in the translation step. The phases obtained by this new version of REMO09 are used as a starting point for a pipeline which in its first step extends and refines the molecular-replacement phases, and in its second step creates the final electron-density map which is automatically interpreted by CAB, an automatic model-building program for proteins and DNA/RNA structures.

Good prior estimates of the effective root-mean-square deviation (r.m.s.d.) between the atomic coordinates of the model and the target optimize the signal in molecular replacement, thereby increasing the success rate in difficult cases. Previous studies using protein structures solved by X-ray crystallography as models showed that optimal error estimates (refined after structure solution) were correlated with the sequence identity between the model and target, and with the number of residues in the model. Here, this work has been extended to find additional correlations between parameters of the model and the target and hence improved prior estimates of the coordinate error. Using a graph database, a curated set of 6030 molecular-replacement calculations using models that had been solved by X-ray crystallography was analysed to consider about 120 model and target parameters. Improved estimates were achieved by replacing the sequence identity with the Gonnet score for sequence similarity, as well as by considering the resolution of the target structure and the MolProbity score of the model. This approach was extended by analysing 12 610 additional molecular-replacement calculations where the model was determined by NMR. The median r.m.s.d. between pairs of models in an ensemble was found to be correlated with the estimated r.m.s.d. to the target. For models solved by NMR, the overall coordinate error estimates were larger than for structures determined by X-ray crystallography, and were more highly correlated with the number of residues.

Many biologists are now routinely seeking to determine the three-dimensional structures of their proteins of choice, illustrating the importance of this knowledge, but also of the simplification and streamlining of structure-determination processes. Despite the fact that most software packages offer simple pipelines, for the non-expert navigating the outputs and understanding the key aspects can be daunting. Here, the structure determination of the type IV pili (TFP) protein PilA1 from Clostridioides difficile is used to illustrate the different steps involved, the key decision criteria and important considerations when using the most common pipelines and software. Molecular-replacement pipelines within CCP4i2 are presented to illustrate the more commonly used processes. Previous knowledge of the biology and structure of TFP pilins, particularly the presence of a long, N-terminal α-helix required for pilus formation, allowed informed decisions to be made during the structure-determination strategy. The PilA1 structure was finally successfully determined using ARCIMBOLDO and the ab initio MR strategy used is described.

The performance of automated protein model building usually decreases with resolution, mainly owing to the lower information content of the experimental data. This calls for a more elaborate use of the available structural information about macromolecules. Here, a new method is presented that uses structural homologues to improve the quality of protein models automatically constructed using ARP/wARP. The method uses local structural similarity between deposited models and the model being built, and results in longer main-chain fragments that in turn can be more reliably docked to the protein sequence. The application of the homology-based model extension method to the example of a CFA synthase at 2.7 Å resolution resulted in a more complete model with almost all of the residues correctly built and docked to the sequence. The method was also evaluated on 1493 molecular-replacement solutions at a resolution of 4.0 Å and better that were submitted to the ARP/wARP web service for model building. A significant improvement in the completeness and sequence coverage of the built models has been observed.

Fragment-based molecular replacement exploits the use of very accurate yet incomplete search models. In the case of the ARCIMBOLDO programs, consistent phase sets produced from the placement and refinement of fragments with Phaser can be combined in order to increase their signal before proceeding to the step of density modification and autotracing with SHELXE. The program ALIXE compares multiple phase sets, evaluating mean phase differences to determine their common origin, and subsequently produces sets of combined phases that group consistent solutions. In this work, its use on different scenarios of very partial molecular-replacement solutions and its performance after the development of a much-optimized set of algorithms are described. The program is available both standalone and integrated within the ARCIMBOLDO programs. ALIXE has been analysed to identify its rate-limiting steps while exploring the best parameterization to improve its performance and make this software efficient enough to work on modest hardware. The algorithm has been parallelized and redesigned to meet the typical landscape of solutions. Analysis of pairwise correlation between the phase sets has also been explored to test whether this would provide additional insight. ALIXE can be used to exhaustively analyse all partial solutions produced or to complement those already selected for expansion, and also to reduce the number of redundant solutions, which is particularly relevant to the case of coiled coils, or to combine partial solutions from different programs. In each case parallelization and optimization to provide speedup makes its use amenable to typical hardware found in crystallography. ARCIMBOLDO_BORGES and ARCIMBOLDO_SHREDDER now call on ALIXE by default.

Model quality assessment programs estimate the quality of protein models and can be used to estimate local error in protein models. ProQ3D is the most recent and most accurate version of our software. Here, it is demonstrated that it is possible to use local error estimates to substantially increase the quality of the models for molecular replacement (MR). Adjusting the B factors using ProQ3D improved the log-likelihood gain (LLG) score by over 50% on average, resulting in significantly more successful models in MR compared with not using error estimates. On a data set of 431 homology models to address difficult MR targets, models with error estimates from ProQ3D received an LLG of >50 for almost half of the models 209/431 (48.5%), compared with 175/431 (40.6%) for the previous version, ProQ2, and only 74/431 (17.2%) for models with no error estimates, clearly demonstrating the added value of using error estimates to enable MR for more targets. ProQ3D is available from http://proq3.bioinfo.se/ both as a server and as a standalone download.

There is no substitute for dramatic reductions in greenhouse gas emissions to mitigate the negative consequences of climate change, a National Research Council committee concluded in a two-volume evaluation of proposed climate-intervention techniques.

Conducting clinical investigations of mitochondrial replacement techniques (MRT) in humans is ethically permissible as long as significant conditions and principles are met, says a new report from the National Academies of Sciences, Engineering, and Medicine.