[Culture] :
Two South Korean films, "Exhuma" and "Handsome Guys," won prizes at the 57th Sitges International Fantastic Film Festival of Catalonia, Spain. According to the South Korean film distributor Showbox on Tuesday, director Jang Jae-hyun's occult thriller "Exhuma," which was invited to the official competition ...

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The crystal structure of the intracellular domain of transforming growth factor β type I receptor (TβR1) in complex with the competitive inhibitor SB505124 is presented. The study provides insights into the structure and function of TβR1 in complex with SB505124, and as such offers molecular-level understanding of the inhibition of this critical signalling pathway. The potential of SB505124 as an avenue for therapy in cancer treatment is discussed on basis of the results.

X-ray and electron diffraction methods independently identify the S-enanti­omer of Berkecoumarin [systematic name: (S)-8-hy­droxy-3-(2-hy­droxy­prop­yl)-6-meth­oxy-2H-chromen-2-one]. Isolated from Berkeley Pit Lake Penicillium sp., Berkecoumarin is a natural product with a light-atom com­position (C13H14O5) that challenges in-house absolute structure determination by anomalous scattering. This study further demonstrates the utility of dynamical refinement of electron-diffraction data for absolute structure determination.

Leishmaniasis is a neglected parasitic tropical disease with numerous clinical manifestations. One of the causative agents of cutaneous leishmaniasis (CL) is Leishmania tropica (L. tropica) known for causing ulcerative lesions on the skin. The adverse effects of the recommended available drugs, such as amphotericin B and pentavalent antimonial, and the emergence of drug resistance in parasites, mean the search for new safe and effective anti-leishmanial agents is crucial. Miltefosine (MIL) was the first recommended oral medication, but its use is now limited because of the rapid emergence of resistance. Pharmaceutical cocrystallization is an effective method to improve the physicochemical and biological properties of active pharmaceutical ingredients (APIs). Herein, we describe the cocrystallization of coumarin-3-carb­oxy­lic acid (CU, 1a; 2-oxobenzo­pyrane-3-carb­oxy­lic acid, C10H6O4) with five coformers [2-amino-3-bromo­pyridine (1b), 2-amino-5-(tri­fluoro­methyl)-pyridine (1c), 2-amino-6-methyl­pyridine (1d), p-amino­benzoic acid (1e) and amitrole (1f)] in a 1:1 stoichiometric ratio via the neat grinding method. The cocrystals 2–6 obtained were characterized via single-crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis, as well as Fourier transform infrared spectroscopy. Non-covalent interactions, such as van der Waals, hydrogen bonding, C—H⋯π and π⋯π interactions contribute significantly towards the packing of a crystal structure and alter the physicochemical and biological activity of CU. In this research, newly synthesized cocrystals were evaluated for their anti-leishmanial activity against the MIL-resistant L. tropica and cytotoxicity against the 3T3 (normal fibroblast) cell line. Among the non-cytotoxic cocrystals synthesized (2–6), CU:1b (2, IC50 = 61.83 ± 0.59 µM), CU:1c (3, 125.7 ± 1.15 µM) and CU:1d (4, 48.71 ± 0.75 µM) appeared to be potent anti-leishmanial agents and showed several-fold more anti-leishmanial potential than the tested standard drug (MIL, IC50 = 169.55 ± 0.078 µM). The results indicate that cocrystals 2–4 are promising anti-leishmanial agents which require further exploration.

Human peptidylarginine deiminase isoform VI (PAD6), which is predominantly limited to cytoplasmic lattices in the mammalian oocytes in ovarian tissue, is essential for female fertility. It belongs to the peptidylarginine deiminase (PAD) enzyme family that catalyzes the conversion of arginine residues to citrulline in proteins. In contrast to other members of the family, recombinant PAD6 was previously found to be catalytically inactive. We sought to provide structural insight into the human homologue to shed light on this observation. We report here the first crystal structure of PAD6, determined at 1.7 Å resolution. PAD6 follows the same domain organization as other structurally known PAD isoenzymes. Further structural analysis and size-exclusion chromatography show that PAD6 behaves as a homodimer similar to PAD4. Differential scanning fluorimetry suggests that PAD6 does not coordinate Ca2+ which agrees with acidic residues found to coordinate Ca2+ in other PAD homologs not being conserved in PAD6. The crystal structure of PAD6 shows similarities with the inactive state of apo PAD2, in which the active site conformation is unsuitable for catalytic citrullination. The putative active site of PAD6 adopts a non-productive conformation that would not allow protein–substrate binding due to steric hindrance with rigid secondary structure elements. This observation is further supported by the lack of activity on the histone H3 and cytokeratin 5 substrates. These findings suggest a different mechanism for enzymatic activation compared with other PADs; alternatively, PAD6 may exert a non-enzymatic function in the cytoplasmic lattice of oocytes and early embryos.

Single-particle cryo-electron microscopy (cryo-EM) has become an essential structural determination technique with recent hardware developments making it possible to reach atomic resolution, at which individual atoms, including hydrogen atoms, can be resolved. In this study, we used the enzyme involved in the penultimate step of riboflavin biosynthesis as a test specimen to benchmark a recently installed microscope and determine if other protein complexes could reach a resolution of 1.5 Å or better, which so far has only been achieved for the iron carrier ferritin. Using state-of-the-art microscope and detector hardware as well as the latest software techniques to overcome microscope and sample limitations, a 1.42 Å map of Aquifex aeolicus lumazine synthase (AaLS) was obtained from a 48 h microscope session. In addition to water molecules and ligands involved in the function of AaLS, we can observe positive density for ∼50% of the hydrogen atoms. A small improvement in the resolution was achieved by Ewald sphere correction which was expected to limit the resolution to ∼1.5 Å for a molecule of this diameter. Our study confirms that other protein complexes can be solved to near-atomic resolution. Future improvements in specimen preparation and protein complex stabilization may allow more flexible macromolecules to reach this level of resolution and should become a priority of study in the field.

Two different multi-component crystals consisting of papaverine [1-(3,4-di­meth­oxy­benz­yl)-6,7-di­meth­oxy­iso­quinoline, C20H21NO4] and fumaric acid [C4H4O4] were obtained. Single-crystal X-ray structure analysis revealed that one, C20H21NO4·1.5C4H4O4 (I), is a salt co-crystal composed of salt-forming and non-salt-forming mol­ecules, and the other, C20H21NO4·0.5C4H4O4 (II), is a salt–co-crystal inter­mediate (i.e., in an inter­mediate state between a salt and a co-crystal). In this study, one state (crystal structure at 100 K) within the salt–co-crystal continuum is defined as the ‘inter­mediate’.

Recently, we introduced the liquid application method for time-resolved analyses (LAMA). The time-consuming cleaning cycles required for the substrate solution exchange and storage of the sensitive droplet-dispenser nozzles present practical challenges. In this work, a dispenser cleaning system for the semi-automated cleaning of the piezo-actuator-driven picolitre-droplet dispensers required for LAMA is introduced to streamline typical workflows.

Energy-dispersive Laue diffraction (EDLD) is a powerful method to obtain position-resolved texture information in inhomogeneous biological samples without the need for sample rotation. This study employs EDLD texture scanning to investigate the impact of two salivary peptides, statherin (STN) and histatin-1 (HTN) 21 N-terminal peptides (STN21 and HTN21), on the crystallographic structure of dental enamel. These proteins are known to play crucial roles in dental caries progression. Three healthy incisors were randomly assigned to three groups: artificially demineralized, demineralized after HTN21 peptide pre-treatment and demineralized after STN21 peptide pre-treatment. To understand the micro-scale structure of the enamel, each specimen was scanned from the enamel surface to a depth of 250 µm using microbeam EDLD. Via the use of a white beam and a pixelated detector, where each pixel functions as a spectrometer, pole figures were obtained in a single exposure at each measurement point. The results revealed distinct orientations of hydroxyapatite crystallites and notable texture variation in the peptide-treated demineralized samples compared with the demineralized control. Specifically, the peptide-treated demineralized samples exhibited up to three orientation populations, in contrast to the demineralized control which displayed only a single orientation population. The texture index of the demineralized control (2.00 ± 0.21) was found to be lower than that of either the STN21 (2.32 ± 0.20) or the HTN21 (2.90 ± 0.46) treated samples. Hence, texture scanning with EDLD gives new insights into dental enamel crystallite orientation and links the present understanding of enamel demineralization to the underlying crystalline texture. For the first time, the feasibility of EDLD texture measurements for quantitative texture evaluation in demineralized dental enamel samples is demonstrated.

Using a 5 µm-diameter X-ray beam, we collected scanning X-ray microdiffraction in both the small-angle (SAXS) and the wide-angle (WAXS) regimes from thin sections of fixed human brain tissue from Alzheimer's subjects. The intensity of scattering in the SAXS regime of these patterns exhibits essentially no correlation with the observed intensity in the WAXS regime, indicating that the structures responsible for these two portions of the diffraction patterns, which reflect different length scales, are distinct. SAXS scattering exhibits a power-law behavior in which the log of intensity decreases linearly with the log of the scattering angle. The slope of the log–log curve is roughly proportional to the intensity in the SAXS regime and, surprisingly, inversely proportional to the intensity in the WAXS regime. We interpret these observations as being due to the presence of sub-micrometre-sized voids formed during dehydration of the fixed tissue. The SAXS intensity is due largely to scattering from these voids, while the WAXS intensity derives from the secondary structures of macromolecular material surrounding the voids. The ability to detect and map the presence of voids within thin sections of fixed tissue has the potential to provide novel information on the degradation of human brain tissue in neurodegenerative diseases.

The closely-watched New York City mayoral primary election tumbled into chaos this week as the NYC Board of Elections announced it had released incorrect preliminary results on Tuesday.

City officials admitted they failed to remove 135,000 test ballots from the election management system before starting to count the real votes from Election Day and early voting, skewing the results.

"The Board apologizes for the error and has taken immediate measures to ensure the most accurate up to date results are reported," the agency tweeted.

The error is complicated by the fact that New York City is using ranked-choice voting, in which each round of vote counting hinges on the results from the previous round.

Some of the top candidates vying to lead the country's largest city blasted the board's mistake as they — and about 8.5 million other New Yorkers — awaited the results of a revised tally expected to be released on Wednesday.

Ranked-choice voting, explained

Instead of choosing just one candidate to vote for, New York City voters in last week's election were able to rank their top five candidates in order of preference.

It was the first time in decades New York used ranked-choice voting, which city voters overwhelmingly approved in a 2019 ballot measure.

NPR's Domenico Montanaro explained how the process works:

1. "If someone gets 50% plus one after all the first-choice votes are counted, then the election is over and that candidate wins. 
2. "But if no one gets 50% plus one, it's on to Round 2.
3. "The person with the lowest number of first-place votes is eliminated, and that candidate's voters' second choices get redistributed as votes for other candidates.
4. "This reallocation of votes goes on until someone reaches 50% plus one."

If just two candidates remain at the end, the candidate with the most votes wins.

What happened this week

On Tuesday, the city Board of Elections released the first ranked-choice voting reports from the election.

With only first-preference votes counted as of election night, Brooklyn Borough President Eric Adams boasted a nine-point lead over attorney Maya Wiley. Those first reported ranked-choice results shrank Adam's lead to just two points ahead of former Sanitation Commissioner Kathryn Garcia, Gothamist reported.

But just hours later, the board tweeted that it had become aware of a "discrepancy" in the ranked-choice voting results and pulled them from its website.

In a follow-up apology, the board acknowledged that it had erroneously left 135,000 test votes in its election system, producing "additional records" that likely impacted an accurate tally.

"At this point it really seems like an issue of human error," WNYC reporter Brigid Bergin told NPR's Morning Edition.

"The board does conduct a lot of pre-election testing to make sure their systems are working and, obviously, that was even more important this time, because it was the first time they were using this new ranked-choice voting system," she added.

Bergin said the board is expected to release a corrected ranked-choice voting report Wednesday, but it will still be preliminary and it won't include 124,000 absentee ballots.

How the candidates are reacting

All of the mayoral contenders expressed frustration with the board's blunder.

"Today's mistake by the Board of Elections was unfortunate," Adams tweeted Tuesday. "It is critical that New Yorkers are confident in their electoral system, especially as we rank votes in a citywide election for the first time."

Garcia, who was fleetingly thrust into second place by the incorrect ranked-choice voting report, called for a more thorough accounting of what went wrong.

"The Board of Elections' release of incorrect ranked choice votes is deeply troubling and requires a much more transparent and complete explanation. Every ranked choice and absentee vote must be counted accurately so that all New Yorkers have faith in our democracy and our government," she tweeted.

Progressive candidate Maya Wiley said this week's misstep was just the latest in a string of mistakes by the board.

"This error by the Board of Elections is not just failure to count votes properly today, it is the result of generations of failures that have gone unaddressed," Wiley said. "Today, we have once again seen the mismanagement that has resulted in a lack of confidence in results, not because there is a flaw in our election laws, but because those who implement it have failed too many times."

WNYC's Bergin said she thought the misstep would not cause voters to question the election results but that it may diminish the board's reputation in the eyes of the public.

"This agency is really the last bastion of true patronage politics in New York," she said. "There's been a push to overhaul the agency, to give the staff more authority over political appointees. But ultimately that's all up to state lawmakers to do."

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

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Machine learning algorithms can sometimes do a great job with a little help from human expertise, at least in the field of materials science. In many specialized areas of science, engineering and medicine, researchers are turning to machine learning algorithms to analyze data sets that have grown too large for humans to understand. In materials science, success with this effort could accelerate the design of next-generation advanced functional materials, where development now usually depends on old-fashioned trial and error. By themselves, however, data analytics techniques borrowed from other research areas often fail to provide the insights needed to help materials scientists and engineers choose which of many variables to adjust -- and the techniques can't account for dramatic changes such as the introduction of a new chemical compound into the process. In a new study, researchers explain a technique known as dimensional stacking, which shows that human experience still has a role to play in the age of machine intelligence. The machines gain an edge at solving a challenge when the data to be analyzed are intelligently organized based on human knowledge of what factors are likely to be important and related. "When your machine accepts strings of data, it really does matter how you are putting those strings together," said Nazanin Bassiri-Gharb, the paper's corresponding author and a scientist at the Georgia Institute of Technology. "We must be mindful that the organization of data before it goes to the algorithm makes a difference. If you don't plug the information in correctly, you will get a result that isn't necessarily correlated with the reality of the physics and chemistry that govern the materials."

Image credit: Rob Felt/Georgia Tech

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.

Cynthia Eades, a long-time resident of Catawba County who is currently serving as Human Resources Director in Iredell County and has ten years of experience in local government human resources, has been named Catawba County�s new Human Resources Director. She will begin her new duties with Catawba County on July 1, 2010.

Cancer-causing chemicals that occur naturally in foods are far more numerous in the human diet than synthetic carcinogens, yet both types are consumed at levels so low that they currently appear to pose little threat to human health, a committee of the National Research Council said in a report released today.

The United States should ban human reproductive cloning aimed at creating a child.

As part of the $4 billion settlement announced today between the federal government and BP concerning the 2010 Deepwater Horizon disaster, the National Academy of Sciences has been asked to establish a new $350 million, 30-year program on human health and environmental protection in the Gulf of Mexico.

A new report from the National Research Council has upheld the listing of styrene as “reasonably anticipated to be a human carcinogen” in the National Toxicology Program’s 12th Report on Carcinogens (RoC).

A new report from the National Research Council has upheld the listing of formaldehyde as “known to be a human carcinogen” in the National Toxicology Program 12th Report on Carcinogens (RoC).

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.

During the National Academy of Medicine (NAM) Annual Meeting, Leonard Rubenstein, Director of the Program on Human Rights, Health and Conflict (Center for Public Health and Human Rights) at Johns Hopkins Bloomberg School of Public Health, and Dr. Denis Mukwege, founder and medical director of Panzi Hospital in the DRC, spoke to NAM members about attacks against healthcare professionals globally and the importance of supporting the work of medical professionals in conflict zones.

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.

Infectious disease outbreaks that turn into epidemics or pandemics can kill millions of people and cause trillions of dollars of damage to economic activity, says a new report from the international, independent Commission on a Global Health Risk Framework for the Future.

Across the current military and civilian trauma care systems, the quality of trauma care varies greatly depending on when and where an individual is injured, placing lives unnecessarily at risk, says a new report from the National Academies of Sciences, Engineering, and Medicine.

A new report from the National Academies of Sciences, Engineering, and Medicine that examines the regulations governing federally funded research recommends that Congress authorize and the president appoint an independent national commission to examine and update the ethical, legal, and institutional frameworks governing research involving human subjects.

Rising levels of noise in the ocean have been identified as a growing concern for the well-being of marine mammals, but other threats such as pollution, climate change, and prey depletion by fisheries may also harm marine mammals and influence their response to additional noise.

Clinical trials for genome editing of the human germline – adding, removing, or replacing DNA base pairs in gametes or early embryos – could be permitted in the future, but only for serious conditions under stringent oversight, says a new report from the National Academy of Sciences and the National Academy of Medicine.

The U.S. Environmental Protection Agency (EPA) carries out experiments in which volunteer participants agree to be intentionally exposed by inhalation to specific pollutants at restricted concentrations over short periods to obtain important information about the effects of outdoor air pollution on human health.

At the spring 2017 meeting of the CHR, Professor José Torero—the John L. Bryan Chair in Fire Protection Engineering and Director of the Center for Disaster Resilience at the University of Maryland—spoke to members about his efforts to help protect human rights through the investigation of several high-profile fires.

During the National Academy of Sciences Annual Meeting, the CHR held a breakfast briefing to highlight issues surrounding digital security and human rights. The meeting featured John Scott-Railton of The Citizen Lab, who spoke about the use of digital surveillance and technologies to target members of civil society worldwide.

A new report by the National Academies of Sciences, Engineering, and Medicine proposes a strategy that the U.S. Environmental Protection Agency (EPA) should use to evaluate the evidence of adverse human health effects from low doses of exposure to chemicals that can disrupt the endocrine system.

New Report Outlines Research Agenda to Better Understand the Relationship Among Microbiomes, Indoor Environments, and Human Health

An emerging body of evidence suggests that integrating STEMM fields (science, technology, engineering, mathematics, and medicine) with the humanities and arts in higher education is associated with positive learning outcomes that may help students enter the workforce, live enriched lives, and become active and informed citizens, says a new report from the National Academies of Sciences, Engineering, and Medicine

An international, multidisciplinary organizing committee has been appointed to plan the Second International Summit on Human Genome Editing, which will take place Nov. 27-29 in Hong Kong.

Improved understanding of the coupled natural-human coastal system will help promote resilience of coastal communities and ecosystems under rapidly changing environmental conditions and support informed decision-making, says a new report from the National Academies of Sciences, Engineering, and Medicine.

On the eve of the Second International Summit on Human Genome Editing, we were informed of the birth of twins in China whose embryonic genomes had been edited.

Carrie Lam, Hong Kong’s chief executive, welcomed hundreds of participants from around the world to the Second International Summit on Human Genome Editing, which began today.

In December 2015, the U.S. National Academy of Sciences and U.S. National Academy of Medicine, the Royal Society of the United Kingdom, and the Chinese Academy of Sciences hosted an international summit in Washington, D.C., to discuss scientific, ethical, and governance issues associated with human genome editing.

We thank the organizing committee of the Second International Summit on Human Genome Editing, held this week in Hong Kong, for planning an important and timely conference on a rapidly advancing area of science and medicine.

To assess the effects of Venezuelas ongoing health crisis, CHR member Dr. Chris Beyrer organized and supported a team of public health and medical professionals from Johns Hopkins University that joined researchers from Human Rights Watch on a trip to Venezuelas borders.

A new publication from the U.S. National Academies of Sciences, Engineering, and Medicine, provides a brief summary of presentations and discussions at the Second International Summit on Human Genome Editing, held in Hong Kong on Nov. 27-29, 2018.

International Day for the Right to Truth concerning Gross Human Rights Violations and for the Dignity of Victims Today, on the International Day for the Right to the Truth concerning Gross Human Rights Violations and for the Dignity of Victims, we are sharing our interview with forensic anthropologist Mercedes Doretti, the Director of North and Central American Programs and Board Member of the Argentine Forensic Anthropology Team (EAAF), which she also co-founded. Doretti and her colleagues collect and analyze physical evidence of human rights abuses (which often includes identifying the remains of victims of grave human rights abuses and returning them to their families), and they regularly present their findings to tribunals and legal mechanisms around the world to secure justice for those whose rights to life and personal security have been violated.

The Gulf Research Program (GRP) of the National Academies of Sciences, Engineering, and Medicine today announced a new funding opportunity under its Healthy Ecosystems Initiative.

The U.S. Department of Veterans Affairs (VA) should expand the requirement in its disability compensation process regarding who can diagnose traumatic brain injury (TBI) to include any health care professional with pertinent and ongoing brain injury training and experience, says a new congressionally mandated report from the National Academies of Sciences, Engineering, and Medicine.

An international commission has been convened by the U.S. National Academy of Medicine, the U.S. National Academy of Sciences, and the Royal Society of the U.K., with the participation of science and medical academies around the world, to develop a framework for scientists, clinicians, and regulatory authorities to consider when assessing potential clinical applications of human germline genome editing.

In celebration of World Humanitarian Day, we are highlighting efforts by volunteers with Engineers Without Borders USA to help create and sustain job opportunities in refugee communities. Through such efforts, the organization helps individuals from these communities exercise their right to work.

The International Commission on the Clinical Use of Human Germline Genome Editing is tasked with identifying the scientific, medical, and ethical requirements to consider when assessing potential clinical applications of human germline genome editing — if society concludes that heritable human genome editing applications are acceptable.

In just a few years, digital technologies have allowed faster mobilization in response to humanitarian crises, better documentation of war crimes in conflict zones like Syria and Yemen, and more accessible platforms for organizing peaceful demonstrations around the world.

A Conversation with the Sudanese American Physicians Association & Physicians for Human Rights