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Section 1202 of the Internal Revenue Code provides a way for taxpayers to exclude much, if not all, of the gain on the sale of stock in certain small businesses. [...]

While recent years have seen great progress in determining the three-dimensional structure of isolated proteins, monitoring protein structure inside live cells remains extremely difficult. Here, we examine the utility of Fourier transform infrared (FTIR) spectroscopy as a probe of protein structure in live bacterial cells. Selective isotope enrichment is used both to distinguish recombinantly expressed NuG2b protein from the cellular background and to examine the conformation of specific residues in the protein. To maximize labeling flexibility and to improve spectral resolution between label and main-band peaks, we carry out isotope-labeling experiments in “reverse-labeling” mode: cells are initially grown in 13C-enriched media, with specific 12C-labeled amino acids added when protein expression is induced. 1Because FTIR measurements require only around 20 μL of sample and each measurement takes only a few minutes to complete, isotope-labeling costs are minimal, allowing us to label multiple different residues in parallel in simultaneously grown cultures. For the stable NuG2b protein, isotope difference spectra from live bacterial cultures are nearly identical to spectra from isolated proteins, confirming that the structure of the protein is unperturbed by the cellular environment. By combining such measurements with site-directed mutagenesis, we further demonstrate that the local conformation of individual amino acids can be monitored, allowing us to determine, for example, whether a specific site in the protein contributes to α-helix or β-sheet structures.

The developing placenta, which in mice originates through the extraembryonic ectoderm (ExE), is essential for mammalian embryonic development. Yet unbiased characterization of the differentiation dynamics of the ExE and its interactions with the embryo proper remains incomplete. Here we develop a temporal single-cell model of mouse gastrulation that maps continuous and parallel differentiation in embryonic and extraembryonic lineages. This is matched with a three-way perturbation approach to target signalling from the embryo proper, the ExE alone, or both. We show that ExE specification involves early spatial and transcriptional bifurcation of uncommitted ectoplacental cone cells and chorion progenitors. Early BMP4 signalling from chorion progenitors is required for proper differentiation of uncommitted ectoplacental cone cells and later for their specification towards trophoblast giant cells. We also find biphasic regulation by BMP4 in the embryo. The early ExE-originating BMP4 signal is necessary for proper mesoendoderm bifurcation and for allantois and primordial germ cell specification. However, commencing at embryonic day 7.5, embryo-derived BMP4 restricts the primordial germ cell pool size by favouring differentiation of their extraembryonic mesoderm precursors towards an allantois fate. ExE and embryonic tissues are therefore entangled in time, space and signalling axes, highlighting the importance of their integrated understanding and modelling in vivo and in vitro.

Pluripotent stem cells are being used to generate models of early embryogenesisthat are promising for discovery and translational research. To be useful, these models require critical consideration of their level of efficiency and fidelityto natural embryos. Here we propose criteria with which to raise the standards of stem-cell-based embryo models of human embryogenesis.

Biocatalytic oxidations have the potential to address many synthetic challenges, enabling the selective synthesis of chiral intermediates, such as carbonyl compounds, alcohols, or amines. The use of oxygen-dependent enzymes can dramatically reduce the environmental footprint of redox transformations at the manufacturing scale. Here, as part of the biocatalytic cascade to the anti-HIV investigational drug islatravir (1), we describe the development of an aerobic oxidation process delivering (R)-ethynylglyceraldehyde-3-phosphate (3) using an evolved galactose oxidase enzyme. Integrated enzyme and reaction engineering were critical for achieving a robust, high-yielding oxidation performed at pilot-plant scale (>20 kg, 90% yield).

Decarboxylation reactions are frequently found in the biosynthesis of primary and secondary metabolites. Decarboxylase enzymes responsible for these transformations operate via diverse mechanisms and act on a large variety of substrates, making them appealing in terms of biotechnological applications. This Perspective focuses on the occurrence of decarboxylation reactions in natural product biosynthesis and provides a perspective on their applications in biocatalysis for fine chemicals and pharmaceuticals.

The nursery industry produces and sells plants for landscape and environmental purposes and represents a major sector within the US agricultural industry. In recent years, the nursery industry has undergone rapid growth as a result of various factors, including increased demand from housing development and pandemic-fueled interest in home horticulture. As with any industry, the nursery industry must adapt to changes in societal trends to sustain growth. In the wake of unprecedented societal and supply chain issues stemming from the global coronavirus disease 2019 pandemic, the American Society for Horticultural Science Nursery Crops Professional Interest Group gathered experts in various disciplines to provide their opinions and insights into the future of the nursery industry, focusing specifically on the changes and challenges the nursery industry will face in the coming decade. Nursery crop specialists spanning the United States identified three primary areas that will steer the future momentum of the nursery industry: consumer trends, natural resources, and labor. Six experts were selected to represent these areas in a workshop held Jul 2022 at the American Society for Horticultural Science Annual Conference in Chicago, IL, USA. This article was developed to disseminate to the greater scientific community the discussions held and insight shared during that workshop. [ABSTRACT FROM AUTHOR]

Stacking van der Waals crystals allows for the on-demand creation of a periodic potential landscape to tailor the transport of quasiparticle excitations. We investigate the diffusion of photoexcited electron–hole pairs, or excitons, at the interface of WS2/WSe2van der Waals heterostructure over a wide range of temperatures. We observe the appearance of distinct interlayer excitons for parallel and antiparallel stacking and track their diffusion through spatially and temporally resolved photoluminescence spectroscopy from 30 to 250 K. While the measured exciton diffusivity decreases with temperature, it surprisingly plateaus below 90 K. Our observations cannot be explained by classical models like hopping in the moiré potential. A combination of ab initio theory and molecular dynamics simulations suggests that low-energy phonons arising from the mismatched lattices of moiré heterostructures, also known as phasons, play a key role in describing and understanding this anomalous behavior of exciton diffusion. Our observations indicate that the moiré potential landscape is dynamic down to very low temperatures and that the phason modes can enable efficient transport of energy in the form of excitons.

Video Abstract1_cd6u7v58Kaltura

Semiconductor nanocrystals (NCs) offer prospective use as active optical elements in photovoltaics, light-emitting diodes, lasers, and photocatalysts due to their tunable optical absorption and emission properties, high stability, and scalable solution processing, as well as compatibility with additive manufacturing routes. Over the course of experiments, during device fabrication, or while in use commercially, these materials are often subjected to intense or prolonged electronic excitation and high carrier densities. The influence of such conditions on ligand integrity and binding remains underexplored. Here, we expose CdSe NCs to laser excitation and monitor changes in oleate that is covalently attached to the NC surface using nuclear magnetic resonance as a function of time and laser intensity. Higher photon doses cause increased rates of ligand loss from the particles, with upward of 50% total ligand desorption measured for the longest, most intense excitation. Surprisingly, for a range of excitation intensities, fragmentation of the oleate is detected and occurs concomitantly with formation of aldehydes, terminal alkenes, H2, and water. After illumination, NC size, shape, and bandgap remain constant although low-energy absorption features (Urbach tails) develop in some samples, indicating formation of substantial trap states. The observed reaction chemistry, which here occurs with low photon to chemical conversion efficiency, suggests that ligand reactivity may require examination for improved NC dispersion stability but can also be manipulated to yield desired photocatalytically accessed chemical species.

Here, we report the synthesis of multinary, heterostructured, and octahedral nanoshells with tunable structures. The synthesis leverages a unique combination of widely used post-synthetic modifications, including galvanic replacement, facet selective growth and etching, as well as cation exchange (CE) reactions. We start by using octahedral Au nanoparticles, converting these to PtAu nanoframes, and then depositing Se windows onto that framework. The subsequent reaction of Se with Cu+/2+ions yields a hollow, metal–semiconductor hybrid PtAu@Cu2–xSe structure with observable plasmonic features from the Cu2–xSe component. We then show that these Cu2–xSe domains can undergo CE and metal deposition reactions using Ag and Pd to yield both quinary and senary nanoshells with control over the identity, composition, and spatial arrangement of the domains. Taken together, these experiments yield a new class of complex, hollow, metal–semiconductor hybrid particles. More broadly, these results demonstrate remarkable modularity of the constituent reactions and indicate that these structures, as well as even more diverse and complex structures, are likely accessible by retrosynthetic design.

Innate lymphoid cells (ILCs) can quickly switch from a quiescent state to an active state and rapidly produce effector molecules that provide critical early immune protection. How the post-transcriptional machinery processes different stimuli and initiates robust gene expression in ILCs is poorly understood. Here, we show that deletion of the N6-methyladenosine (m6A) writer protein METTL3 has little impact on ILC homeostasis or cytokine-induced ILC1 or ILC3 responses but significantly diminishes ILC2 proliferation, migration and effector cytokine production and results in impaired antihelminth immunity. m6A RNA modification supports an increase in cell size and transcriptional activity in activated ILC2s but not in ILC1s or ILC3s. Among other transcripts, the gene encoding the transcription factor GATA3 is highly m6A methylated in ILC2s. Targeted m6A demethylation destabilizes nascent Gata3mRNA and abolishes the upregulation of GATA3 and ILC2 activation. Our study suggests a lineage-specific requirement of m6A for ILC2 responses.

This paper describes the formation and ongoing efforts of a collaborative partnership between students, faculty, and staff within the Chemistry department at Amherst College. Formation of the group was inspired by calls for structural, inclusive, change from students, faculty, and alumni. There are many benefits to collaborating across traditional academic hierarchies, and this report aims to show that these partnerships can help identify avenues for the implementation of inclusive change in STEM departments. The Amherst College Chemistry community agrees that graduates of the Chemistry department should leave the College with a critical understanding of the implications of systemic discrimination as they pertain to chemical research and education; this paper shares organizational methods and strengths, as well as limitations and holistic reflections, of creating spaces for student, staff, and faculty partnership to shape a STEM educational community. A specific outcome of this committee was the creation of a diversity-equity-inclusion (DEI) requirement in the major. We share how CARAC helped the department arrive at this decision and discuss the departmental course, Chemistry in Society, that was developed in response.

When the Volcker Rule was enacted, and its proposed regulations were released, a shockwave of fear and uncertainty reverberated through the international community. The Volcker Rule, as proposed, had unprecedented [...]

Small-molecule mitochondrial uncouplers are gaining recognition as potential therapeutics for metabolic diseases such as obesity, diabetes, and nonalcoholic steatohepatitis (NASH). Specifically, heterocycles derived from BAM15, a potent and mitochondria-selective uncoupler, have yielded promising preclinical candidates that are efficacious in animal models of obesity and NASH. In this study, we report the structure–activity relationship studies of 6-amino-[1,2,5]oxadiazolo[3,4-b]pyridin-5-ol derivatives. Using oxygen consumption rate as a readout of mitochondrial uncoupling, we established 5-hydroxyoxadiazolopyridines as mild uncouplers. In particular, SHM115, which contains a pentafluoro aniline, had an EC50value of 17 μM and exhibited 75% oral bioavailability. SHM115treatment increased the energy expenditure and lowered the body fat mass in two diet-induced obesity mouse models, including an obesity prevention model and an obesity reversal model. Taken together, our findings demonstrate the therapeutic potential of mild mitochondrial uncouplers for the prevention of diet-induced obesity.

I. INTRODUCTION This past June, the New York Court of Appeals struck down as exceeding the scope of permissible regulation the proposed "soda ban" in New York City, a public [...]

III. A STUDY OF COLLEGE AND UNIVERSITY OWNERSHIP OF TRADEMARKS In the fall of 2012, (1) undertook a study to collect comprehensive trademark registration data for colleges and universities within [...]

Ultra-wide band gap semiconductor devices based on β-phase gallium oxide (Ga2O3) offer the potential to achieve higher switching performance and efficiency and lower manufacturing cost than that of today’s wide band gap power electronics. However, the most critical challenge to the commercialization of Ga2O3electronics is overheating, which impacts the device performance and reliability. We fabricated a Ga2O3/4H–SiC composite wafer using a fusion-bonding method. A low-temperature (≤600 °C) epitaxy and device processing scheme was developed to fabricate MOSFETs on the composite wafer. The low-temperature-grown epitaxial Ga2O3devices deliver high thermal performance (56% reduction in channel temperature) and a power figure of merit of (∼300 MW/cm2), which is the highest among heterogeneously integrated Ga2O3devices reported to date. Simulations calibrated based on thermal characterization results of the Ga2O3-on-SiC MOSFET reveal that a Ga2O3/diamond composite wafer with a reduced Ga2O3thickness (∼1 μm) and a thinner bonding interlayer (<10 nm) can reduce the device thermal impedance to a level lower than that of today’s GaN-on-SiC power switches.

The ability to study human post-implantation development remains limited owing to ethical and technical challenges associated with intrauterine development after implantation1. Embryo-like models with spatially organized morphogenesis and structure of all defining embryonic and extra-embryonic tissues of the post-implantation human conceptus (that is, the embryonic disc, the bilaminar disc, the yolk sac, the chorionic sac and the surrounding trophoblast layer) remain lacking1,2. Mouse naive embryonic stem cells have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation structured stem-cell-based embryo models with spatially organized morphogenesis (called SEMs)3. Here we extend those findings to humans using only genetically unmodified human naive embryonic stem cells (cultured in human enhanced naive stem cell medium conditions)4. Such human fully integrated and complete SEMs recapitulate the organization of nearly all known lineages and compartments of post-implantation human embryos, including the epiblast, the hypoblast, the extra-embryonic mesoderm and the trophoblast layer surrounding the latter compartments. These human complete SEMs demonstrated developmental growth dynamics that resemble key hallmarks of post-implantation stage embryogenesis up to 13–14 days after fertilization (Carnegie stage 6a). These include embryonic disc and bilaminar disc formation, epiblast lumenogenesis, polarized amniogenesis, anterior–posterior symmetry breaking, primordial germ-cell specification, polarized yolk sac with visceral and parietal endoderm formation, extra-embryonic mesoderm expansion that defines a chorionic cavity and a connecting stalk, and a trophoblast-surrounding compartment demonstrating syncytium and lacunae formation. This SEM platform will probably enable the experimental investigation of previously inaccessible windows of human early post implantation up to peri-gastrulation development.

Background The furosemide stress test (FST) is a safe and easy assessment of renal tubular function. Other factors, such as mean arterial pressure (MAP), which may influence the success rates of the FST, have not been well defined.Objective To evaluate the relationship between MAP and success rates of the FST in critically ill patients.Methods Retrospective, single-center, institutional review board (IRB)-approved cohort study. Critically ill adult patients given at least one dose of intravenous (IV) furosemide (≥1-1.5 mg/kg) were included. Primary outcome was whether a MAP ≥ 75 mm Hg would equate to a higher FST success rate. Secondary outcome was the success rates of patient on one or more vasopressors.Results Of 225 patients, 88 (39.1%) had a successful FST. In patients with a MAP ≥ 75 mm Hg, 60 out of 104 (57.7%) had a successful FST compared to 28 out of 121 (23.1%) of patients who had a MAP < 75 mm Hg (odds ratio [OR], 4.53, 95% CI, 2.55-8.74, P< 0.001). Patients on vasopressors at the time of the furosemide dose had lower rates of success compared to those not on vasoactive agents (30.4% versus 68.2%, p= 0.026). Limitations of this study include its retrospective design and reliance on documented urine output.Conclusion and Relevance Patients with a MAP ≥ 75 mm Hg were significantly more likely to have a successful FST compared to those with a MAP < 75 mm Hg. This represents the first report of factors that may influence FST success rates.

The ocean–atmosphere exchange of CO2largely depends on the balance between marine microbial photosynthesis and respiration. Despite vast taxonomic and metabolic diversity among marine planktonic bacteria and archaea (prokaryoplankton)1–3, their respiration usually is measured in bulk and treated as a ‘black box’ in global biogeochemical models4; this limits the mechanistic understanding of the global carbon cycle. Here, using a technology for integrated phenotype analyses and genomic sequencing of individual microbial cells, we show that cell-specific respiration rates differ by more than 1,000× among prokaryoplankton genera. The majority of respiration was found to be performed by minority members of prokaryoplankton (including the Roseobactercluster), whereas cells of the most prevalent lineages (including Pelagibacterand SAR86) had extremely low respiration rates. The decoupling of respiration rates from abundance among lineages, elevated counts of proteorhodopsin transcripts in Pelagibacterand SAR86 cells and elevated respiration of SAR86 at night indicate that proteorhodopsin-based phototrophy3,5–7probably constitutes an important source of energy to prokaryoplankton and may increase growth efficiency. These findings suggest that the dependence of prokaryoplankton on respiration and remineralization of phytoplankton-derived organic carbon into CO2for its energy demands and growth may be lower than commonly assumed and variable among lineages.

Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro1–5, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem (TS) cells, extraembryonic endoderm stem (XEN) cells and inducible XEN (iXEN) cells6–11. Here we assembled stem cell-derived embryos in vitro from mouse ES cells, TS cells and iXEN cells and showed that they recapitulate the development of whole natural mouse embryo in utero up to day 8.5 post-fertilization. Our embryo model displays headfolds with defined forebrain and midbrain regions and develops a beating heart-like structure, a trunk comprising a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and primordial germ cells. This complete embryo model develops within an extraembryonic yolk sac that initiates blood island development. Notably, we demonstrate that the neurulating embryo model assembled from Pax6-knockout ES cells aggregated with wild-type TS cells and iXEN cells recapitulates the ventral domain expansion of the neural tube that occurs in natural, ubiquitous Pax6-knockout embryos. Thus, these complete embryoids are a powerful in vitro model for dissecting the roles of diverse cell lineages and genes in development. Our results demonstrate the self-organization ability of ES cells and two types of extraembryonic stem cells to reconstitute mammalian development through and beyond gastrulation to neurulation and early organogenesis.

The amount of phosphorus (P) conventionally recommended and applied to container nursery crops commonly exceeds plant requirements, resulting in unused P leaching from containers and potentially contributing to surface water impairment. An experiment was replicated in the Middle Atlantic Coastal Plain (MACP) and Ridge and Valley ecoregions of Virginia to compare the effect of a low-P controlled-release fertilizer (CRF, 0.9% or 1.4% P depending on species) vs. a conventional CRF formulation (control, 1.7% P) on plant shoot growth, crop quality, and substrate nutrient concentrations of four species: 'Natchez' crape myrtle (Lagerstroemia indica × Lagerstroemia fauriei), 'Roblec' Encore azalea (Rhododendron hybrid), 'Radrazz' Knock Out rose (Rosa hybrid), and 'Green Giant' arborvitae (Thuja plicata × Thuja standishii). In both ecoregions, the low-P CRF resulted in 9% to 26% lower shoot dry weight in all four species compared with those given the conventional formulation, but quality ratings for two economically important species, 'Radrazz' Knock Out rose and 'Green Giant' arborvitae, were similar between treatments. When fertilized with the low-P CRF, 'Roblec' Encore azalea and 'Natchez' crape myrtle in both ecoregions, and 'Green Giant' arborvitae in the MACP ecoregion had ~56% to 75% lower substrate pore-water P concentrations than those that received the control CRF. Nitrate-nitrogen (N) concentrations in substrate pore water at week 5 were more than six times greater in control-fertilized plants than in those that received a low-P CRF, which may have been a result of the greater urea-N content or the heterogeneous nature of the low-P CRFs. Lower water-extractable pore-water P and N indicate less environmental risk and potentially increased crop efficiency. Our results suggest low-P CRFs can be used to produce certain economically important ornamental nursery crops successfully without sacrificing quality; however, early adopters will need to evaluate the effect of low-P CRFs on crop quality of specific species before implementing on a large scale. [ABSTRACT FROM AUTHOR]

A simple and efficient process to prepare Uprifosbuvir intermediate, 2′-deoxy-α-2′-chloro-β-2′-methyluridine (1), from bis-pivaloyl tertiary alcohol 5ais described. The key discoveries are a novel BSA-promoted anhydrouridine formation catalyzed by HCl as an additive and a milder safe Me2SiCl2-promoted chlorination of anhydrouridine. These discoveries collectively enabled the establishment of a robust process toward compound 1, which was demonstrated successfully at the plant scale.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and the leading cause of liver-related morbidity and mortality. We aimed to predict the burden of NAFLD by examining and estimating the temporal trends of its worldwide prevalence and incidence.

The article discusses the importance of Aviation Ground Support (AGS) in the Marine Corps and its role in enabling expeditionary aviation operations. AGS provides tailored engineering and logistics capabilities for sustained air operations in austere environments. The Marine Corps' focus on expeditionary advanced base operations in the Pacific Theater has highlighted the need for AGS to establish and maintain aviation bases and support small, agile, and lethal forces. However, the Marine Corps currently lacks sufficient AGS structure and efforts are underway to restore it to meet the requirements of distributed aviation operations. AGS is considered a critical supporting capability that enables maximum sortie generation for Marine Corps, naval, joint, and coalition aviation forces. [Extracted from the article]

Historically, Rio Grande wild turkey (Meleagris gallopavo intermedia) density in south‐central Texas has been lower than other regions within the species' Texas range. Within the Oak‐Prairie Wildlife District of Texas, Rio Grande wild turkey harvest regulations are more restrictive for counties in the eastern portion of the district. Due to a perceived increase in turkey density in the eastern portion of the district, Texas Parks and Wildlife Department (TPWD) has considered increasing the spring hunting season harvest bag limit. Because estimates of sex‐specific abundance and male harvest rates are not available, estimates of female driven population parameters such and nest success and female survival can be used to support regulatory decision‐making. Therefore, before a regulation change we evaluated survival of radio‐marked female Rio Grande wild turkeys during the breeding season in 4 counties in the Special 1‐Male zone (hereafter 1‐bird zone) and 2 counties in the South zone (hereafter 4‐bird zone). We captured and monitored breeding season survival for 138 females during 2016–2018, of which 51 were in the 4‐bird zone and 87 were in the 1‐bird zone. Breeding season (1 Mar–14 Aug) naive mortality rate was 23% (19/81) of tagged females in the 1‐bird zone and 32% (14/43) in the 4‐bird zone. The best approximating candidate model for breeding season survival indicated variation in daily survival (Sˆ $\hat{S}$) was primarily related to daily distance of individual movements (Sˆ $\hat{S}$ = 0.998 at average daily distance of 2,471 m). Estimated breeding season survival at the mean daily movement distance was 81% for the 167‐day period. Breeding season survival was similar between the 1‐bird and 4‐bird regulatory zone. Based on our results, female breeding season survival does not seem to be a limiting factor within the Oak‐Prairie Wildlife District of Texas for Rio Grande wild turkeys. We suggest that TPWD focus efforts on supporting landowners to enhance conditions more conducive for reproductive success and suggest future efforts focus on collection of harvest and harvest rate data to estimate population size in lieu of continued monitoring of female reproductive or survival parameters for decision processes. [ABSTRACT FROM AUTHOR]

Poor performance is common in the delivery of large-scale transport infrastructure. Despite previous studies examining the management of transport megaprojects, there is a lack of systematic reviews on performance Controls and Accountability in Megaprojects (CAMP). We analyze research on CAMP in Africa. Out of the 947 records retrieved, 35 articles published between 1980 and 2022 meet our inclusion criteria. We identify four main research themes: “project governance,” “performance management,” “project conceptual management,” and “complexity management.” Our findings indicate significant weaknesses in project governance and a lack of proper project conception. Practical implications involve restructuring project governance policies and implementing a multi-level project governance model. The research supports recognizing corruption as a characteristic of megaprojects, implementing project governance as a standard management practice, and improving governance in public-private partnerships. Additionally, future research should prioritize integrating and developing policies, strengthening institutions, implementing participatory governance mechanisms, and building capacity for project management.

An investigation on whether levels of annexin A5(AnxA5)-related parameters, including plasma levels of AnxA5, AnxA5 anticoagulant activity and AnxA5 binding activity, and anti-AnxA5 antibodies are altered in pregnant women with a history of recurrent spontaneous pregnancy losses (RSPL). No significant differences were observed during pregnancy in women with RSPL and controls, with the state of pregnancy itself associated with altered levels of AnxA5 parameters.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2005.11.005 Byline: Peter Van Eerden (a), Xiao-Xuan Wu (b), Cynthia Chazotte (a), Jacob H. Rand (b) Abstract: The purpose of this study was to determine whether amniotic fluid levels of annexin A5 (AF-AnxA5) may be associated with intrauterine growth restriction (IUGR). Author Affiliation: (a) Departments of Obstetrics & Gynecology and Women's Health (b) Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY Article History: Received 9 June 2005; Revised 6 September 2005; Accepted 4 November 2005 Article Note: (footnote) Supported in part by the National Institutes of Health/National Heart Lung and Blood Institute, grant #HL-61331.

A study is carried out to investigate whether levels of annexin A5, evidence for resistance to annexin A5 activity and levels anti-annexin A5 antibodies might be altered in women with a history of recurrent spontaneous pregnancy losses. It is found that reduction of annexin A5 and interference with its anticoagulant and biding activities are associated significantly with a history of recurrent spontaneous pregnancy losses and these data support the concept of a significant role for annexin A5 in the maintenance of pregnancy.

In July 1800, Toussaint Louverture, one of the founding fathers of Haitian independence, had marched and conquered the Spanish port of the island. Then, with all of his enemies presumably [...]

On New Year's Day, Haiti will celebrate 200 years of independence, the second black nation in the Western hemisphere to achieve independence (the first was Palmares established around 1595 in [...]

Ultrahigh‐temperature (UHT; >900°C) metamorphism drives crustal differentiation and is widely recognized in the rock record, but its geodynamic causes are debated. Previous work on granulite‐facies metapelite xenoliths from San Luis Potosí, Mexico suggests the lower crust experienced a protracted UHT metamorphic event that coincided with the onset of regional extension. To determine the duration, conditions, and heat sources of UHT metamorphism recorded by these xenoliths, this study characterizes the major‐element, trace‐element, and U‐Pb isotopic systematics of quartz, rutile, feldspar, garnet, and zircon by in situ electron microprobe (EPMA) and laser‐ablation inductively coupled‐plasma mass spectrometry (LA‐ICP‐MS), and augments these data with detailed petrography, thermobarometry, phase equilibria modeling, and diffusion modeling. Thermobarometry and phase equilibria modeling suggest peak metamorphic conditions exceeded 0.7 GPa and 900°C. Zircon petrochronology confirms >15 Myr of UHT conditions since its onset at ∼30 Ma. A small population of zircon record elevated temperatures following transition from backarc compression to extension during the waning stages of orogenesis (60–37 Ma). Garnet preserves trace‐element zoning and mineral inclusions consistent with suprasolidus garnet growth and subsequent compositional modification by intracrystalline rare‐earth element diffusion during protracted heating, with diffusion chronometry timescales in agreement with zircon data, followed by fluid‐driven remobilization of trace elements along now‐healed fractures within ∼1 Myr of eruption. In sum, these data are most compatible with lithospheric mantle attenuation or removal as the dominant heat transport mechanism driving synextensional UHT metamorphism and crustal melting, which has bearing on models for crustal differentiation and formation of modern and ancient granulite terranes globally. The production of melt in the deep crust has important implications for how continents are physically and chemically modified, which in turn controls the distribution of critical mineral resources and the expression of plate tectonics at Earth's surface. One setting where significant partial melting can occur is in a high‐temperature granulite terrane, such as the lower crust beneath the Basin and Range province of southwestern North America. The Basin and Range province is a region where the continent is actively experiencing tectonic extension and, in several places, has been interpreted to have lower crust that was (or is currently) heated to above 900°C. To understand the causality between continental extension in North America and these extreme metamorphic conditions, we study exotic rock fragments of the deep crust beneath San Luis Potosí, Mexico that were brought up by a geologically recent volcanic eruption. These rocks record chemical information that tracks the temperature of the geologically modern lower crust prior to eruption and the duration of extreme temperatures and melting in this crust over the last 60 million years. Using this chemical information, we further our understanding of how tectonic extension is actively driving deep crustal melting beneath southwestern North America. Lower crustal metapelite xenoliths from San Luis Potosi, Mexico record ultrahigh (>900°C) temperature (UHT) metamorphismZircon petrochronology suggests protracted (>15 Myr) UHT conditions since the onset of regional extensionGarnet preserves complex trace‐element zoning despite extreme temperatures; garnet diffusion chronometry timescales agree with zircon data Lower crustal metapelite xenoliths from San Luis Potosi, Mexico record ultrahigh (>900°C) temperature (UHT) metamorphism Zircon petrochronology suggests protracted (>15 Myr) UHT conditions since the onset of regional extension Garnet preserves complex trace‐element zoning despite extreme temperatures; garnet diffusion chronometry timescales agree with zircon data

In the two years following the bursting of the high-technology and telecommunications stock 'bubble,' various legal proceedings and regulatory actions have brought Wall Street to the brink of creating a [...]

Here we report the fluorination–dynamic kinetic resolution (DKR) process for the commercial supply of belzutifan (MK-6482). Key process safety and robustness issues in the Selectfluor fluorination reaction were identified and addressed on the basis of increased mechanistic understanding. Aggressive process optimization enabled a single-pot direct isolation process that allowed delivery of the fluorodiol product with low process mass intensity.

The introduction of molecular complexity in an atom- and step-efficient manner remains an outstanding goal in modern synthetic chemistry. Artificial biosynthetic pathways are uniquely able to address this challenge by using enzymes to carry out multiple synthetic steps simultaneously or in a one-pot sequence1–3. Conducting biosynthesis ex vivo further broadens its applicability by avoiding cross-talk with cellular metabolism and enabling the redesign of key biosynthetic pathways through the use of non-natural cofactors and synthetic reagents4,5. Here we describe the discovery and construction of an enzymatic cascade to MK-1454, a highly potent stimulator of interferon genes (STING) activator under study as an immuno-oncology therapeutic6,7(ClinicalTrials.gov study NCT04220866). From two non-natural nucleotide monothiophosphates, MK-1454 is assembled diastereoselectively in a one-pot cascade, in which two thiotriphosphate nucleotides are simultaneously generated biocatalytically, followed by coupling and cyclization catalysed by an engineered animal cyclic guanosine-adenosine synthase (cGAS). For the thiotriphosphate synthesis, three kinase enzymes were engineered to develop a non-natural cofactor recycling system in which one thiotriphosphate serves as a cofactor in its own synthesis. This study demonstrates the substantial capacity that currently exists to use biosynthetic approaches to discover and manufacture complex, non-natural molecules.

Background: Nephrolithiasis is a well-known complication of indinavir treatment and may result in urological symptoms ranging from renal colic to renal insufficiency. Objective: To obtain further knowledge regarding the incidence and risk factors of urological symptoms associated with indinavir sulfate use. Methods: This study was performed in the ATHENA (AIDS Therapy Evaluation National AIDS Therapy Evaluation Centre) cohort of patients infected with human immunodeficiency virus (HIV) receiving antiretroviral therapy in the Netherlands. The incidence rate of urological symptoms was assessed in a subcohort of 1219 patients starting HIV protease inhibitor treatment after 1996. Urological symptoms were defined as an initial report of nephrolithiasis, renal colic, flank pain, hematuria, renal insufficiency, or nephropathy. Using multivariate Cox regression analysis, risk factors for urological symptoms during indinavir treatment were subsequently studied among the subset of 644 patients who started indinavir treatment after 1996. Results: The incidence of urological symptoms was 8.3 per 100 treatment-years for indinavir vs 0.8 per 100 treatment-years for other HIV protease inhibitors. Risk factors for urological symptoms during indinavir treatment were low weight (relative risk [RR], 2.1; 95% confidence interval [CI], 1.1-3.9), low lean body mass (RR, 1.7; 95% CI, 1.0-2.9), undetectable HIV-1 RNA when starting indinavir treatment (RR, 3.2; 95% CI, 1.5-6.0), prior treatment change because of intolerance (RR, 2.4; 95% CI, 1.2-5.1), indinavir regimens of 1000 mg or more twice daily (RR, 3.1; 95% CI, 1.3-8.2), and warm environmental temperatures (RR, 3.9; 95% CI, 1.7-8.8). Risk estimates were highest among patients with a low lean body mass. Conclusion: Increased alertness for urological symptoms is warranted for patients starting indinavir treatment, particularly among those with a low lean body mass, during indinavir regimens of 1000 mg or more twice daily, and in warm weather environments. Arch Intern Med. 2002; 162:1493-1501

Blood platelets may effectively seal punctures in fetal membranes. Premature rupture of fetal membranes rapidly leads to delivery and, therefore, a premature infant. A technique to patch ruptured fetal membranes may permit a pregnancy to continue, improving the outcome for the baby. Researchers experimented with fresh fetal membranes, amniotic fluid, and platelets obtained from a blood bank. Fetal membrane connective tissue, as would be exposed in a rupture, caused platelet activation and the formation of a platelet plug. This may form the basis of a membrane repair.

Two recent studies provide mechanistic insights into how LIN28A controls changes in cell fate identity, focusing on either a let-7-independent or let-7-dependent pathway of action involving LIN28A.

Immunoglobulin G (IgG) in patients with the antiphospholipid syndrome appears to inhibit the activity of a powerful anti-blood-clotting protein called annexin V. This could account for the increased incidence of miscarriage among pregnant women with this syndrome. Annexin V levels were lower in placental tissue from a patient with the antiphospholipid syndrome than in a healthy mother. Annexin V production decreased in normal placental tissue treated with IgG from patients with the antiphospholipid syndrome.

β-phase gallium oxide (Ga2O3) is an emerging ultrawide bandgap (UWBG) semiconductor (EG∼ 4.8 eV), which promises generational improvements in the performance and manufacturing cost over today’s commercial wide bandgap power electronics based on GaN and SiC. However, overheating has been identified as a major bottleneck to the performance and commercialization of Ga2O3device technologies. In this work, a novel Ga2O3/4H-SiC composite wafer with high heat transfer performance and an epi-ready surface finish has been developed using a fusion-bonding method. By taking advantage of low-temperature metalorganic vapor phase epitaxy, a Ga2O3epitaxial layer was successfully grown on the composite wafer while maintaining the structural integrity of the composite wafer without causing interface damage. An atomically smooth homoepitaxial film with a room-temperature Hall mobility of ∼94 cm2/Vs and a volume charge of ∼3 × 1017cm–3was achieved at a growth temperature of 600 °C. Phonon transport across the Ga2O3/4H-SiC interface has been studied using frequency-domain thermoreflectance and a differential steady-state thermoreflectance approach. Scanning transmission electron microscopy analysis suggests that phonon transport across the Ga2O3/4H-SiC interface is dominated by the thickness of the SiNxbonding layer and an unintentionally formed SiOxinterlayer. Extrinsic effects that impact the thermal conductivity of the 6.5 μm thick Ga2O3layer were studied via time-domain thermoreflectance. Thermal simulation was performed to estimate the improvement of the thermal performance of a hypothetical single-finger Ga2O3metal–semiconductor field-effect transistor fabricated on the composite substrate. This novel power transistor topology resulted in a ∼4.3× reduction in the junction-to-package device thermal resistance. Furthermore, an even more pronounced cooling effect is demonstrated when the composite wafer is implemented into the device design of practical multifinger devices. These innovations in device-level thermal management give promise to the full exploitation of the promising benefits of the UWBG material, which will lead to significant improvements in the power density and efficiency of power electronics over current state-of-the-art commercial devices.

Reduction of annexin-V in the placental villi appears a likely mechanism for recurrent miscarriage caused by the formation of placental clots among women with antiphospholipid antibodies (APA). Annexin-V is an anticoagulant produced in the placental villi that bonds to phospholipid proteins in the tips of the placental villi. It is believed to keep the blood in the maternal capillary sinuses fluid. The amount and location of annexin-V were evaluated in placental samples taken from eight placentas each from the following groups: healthy term births, women with APA and recurrent miscarriage, women with miscarriage from other causes, and women undergoing elective abortion. Normal placental villi were also cultured with APA. Placentas from women with APA had much less annexin-V in the villi tips compared with the other groups. It remained present deeper in the villous cells. The same results were seen in normal villi cultured in the presence of APA.

Progressive advances in perfusion technology and perioperative supportive management have made it possible for members of the Jehovah's Witnesses religious group to undergo open cardiac operations with remarkable safety. However, [...]

Although certain brain disorders are associated with impairment of the ability to drive motor vehicles, the effects of dementia (impairment of cognitive, emotional, and behavioral functions) on driving have not been studied. To learn more about this issue, a survey was carried out of 487 patients evaluated consecutively at an Alzheimer's disease center (Alzheimer's disease, or AD, is a progressive disorder involving loss of cognitive function). Based on their performance on standard neuropsychological tests, patients were classified as having probable AD (ADprob), possible AD (ADposs, in cases where other medical or neurologic disorders besides AD could not be ruled out), or other disorders. Patients' caregivers completed questionnaires about patients' driving status, licensure, and (if appropriate) driving safety records for the six previous months. Consumption of alcohol and medication was also investigated. Results showed that 154 patients were not driving when their disease developed, 240 patients had stopped driving, and 93 still drove. On average, patients who continued to drive after disease onset (DAO) drove for 24 more months. The length of time that patients continued to drive was associated with their diagnoses: those with ADprob and ADposs had longer DAO than those with vascular disease. One-third of the patients who still drove had had at least one unsafe experience operating a motor vehicle in the preceding six months. These experiences included single- or multiple-car accidents, in which 21 patients were involved (average of 1.7 accidents per patient); none involved personal injuries. No patient had a history of drug abuse; however, the 24 patients who took prescribed drugs known to impair cognition (sedatives) had a higher frequency of accidents than the patients who did not take such drugs. The results suggest that patients with dementia are at significantly increased risk for motor vehicle accidents and other unsafe driving experiences. Factors that could reduce that risk should be investigated. (Consumer Summary produced by Reliance Medical Information, Inc.)