We explore the role of sex in judging by addressing two questions of long-standing interest to political scientists: whether and in what ways male and female judges decide cases ...distinctly—"individual effects"—and whether and in what ways serving with a female judge causes males to behave differently—"panel effects." While we attend to the dominant theoretical accounts of why we might expect to observe either or both effects, we do not use the predominant statistical tools to assess them. Instead, we deploy a more appropriate methodology: semiparametric matching, which follows from a formal framework for causal inference. Applying matching methods to 13 areas of law, we observe consistent gender effects in only one—sex discrimination. For these disputes, the probability of a judge deciding in favor of the party alleging discrimination decreases by about 10 percentage points when the judge is a male. Likewise, when a woman serves on a panel with men, the men are significantly more likely to rule in favor of the rights litigant. These results are consistent with an informational account of gendered judging and are inconsistent with several others.
Methods are reported for the efficient assembly of a series of phenol-derived propiolates, including the parent system 56, and their Au(I)-catalyzed cyclization (intramolecular hydroarylation) to ...give the corresponding coumarins (e.g., 1). Simple syntheses of natural products such as ayapin (144) and scoparone (145) have been realized by such means, and the first of these subject to single-crystal X-ray analysis. A related process is described for the conversion of propargyl ethers such as 156 into the isomeric 2H-chromene precocene I (159), a naturally occurring inhibitor of juvenile hormone biosynthesis.
The literature related to eosinophilic gastritis (EG), gastroenteritis (EGE), and colitis (EC) is limited. We aimed to characterize rates of diagnosis, clinical features, and initial treatments for ...patients with EG, EGE, and EC.
In this retrospective study, data were collected from 6 centers in the Consortium of Eosinophilic Gastrointestinal Researchers from 2005 to 2016. We analyzed demographics, time trends in diagnosis, medical history, presenting symptoms, disease overlap, and initial treatment patterns/responses.
Of 373 subjects (317 children and 56 adults), 38% had EG, 33% EGE, and 29% EC. Rates of diagnosis of all diseases increased over time. There was no male predominance, and the majority of subjects had atopy. Presenting symptoms were similar between diseases with nausea/vomiting and abdominal pain, the most common. One hundred fifty-four subjects (41%) had eosinophilic inflammation outside of their primary disease location with the esophagus the second most common gastrointestinal (GI) segment involved. Multisite inflammation was more common in children than in adults (68% vs 37%; P < 0.001). Initial treatment patterns varied highly between centers. One hundred-nine subjects (29%) had follow-up within 6 months, and the majority had clinical, endoscopic, and histologic improvements.
In this cohort, EG, EGE, and EC were diagnosed more frequently over time, and inflammation of GI segments outside the primary disease site co-occurrence of atopy was common with a lack of male predominance. Symptoms were similar between diseases, and initial treatment strategies were highly variable. Future investigation should assess the cause of the increased prevalence of eosinophilic GI disorders and prospectively assess outcomes to establish treatment algorithms.
Regulated secretion is critical for diverse biological processes ranging from immune and endocrine signaling to synaptic transmission. Botulinum and tetanus neurotoxins, which specifically proteolyze ...vesicle fusion proteins involved in regulated secretion, have been widely used as experimental tools to block these processes. Genetic expression of these toxins in the nervous system has been a powerful approach for disrupting neurotransmitter release within defined circuitry, but their current utility in the brain and elsewhere remains limited by lack of spatial and temporal control. Here we engineered botulinum neurotoxin B so that it can be activated with blue light. We demonstrate the utility of this approach for inducibly disrupting excitatory neurotransmission, providing a first-in-class optogenetic tool for persistent, light-triggered synaptic inhibition. In addition to blocking neurotransmitter release, this approach will have broad utility for conditionally disrupting regulated secretion of diverse bioactive molecules, including neuropeptides, neuromodulators, hormones, and immune molecules.
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•Few tools allow inhibition of neural activity for long time periods with light•We engineered botulinum neurotoxin B so that it can be activated with blue light•Photoactivated botulinum toxin efficiently cleaves the SNARE protein VAMP2•We demonstrate utility in diverse systems, from mammalian brain slices to worms
Few tools in neuroscience allow long-term synapse inhibition with light. We engineered botulinum neurotoxin B so that it can be switched on with blue light. Light activation results in robust proteolysis of VAMP2, a SNARE protein universally required for neurotransmitter release.
•First synthesis of estimates for strength of BCP in the North Atlantic.•Current understanding of the North Atlantic BCP is critically assessed.•Priorities for future research into the BCP are ...identified.
Mediated principally by the sinking of organic rich particles from the upper ocean, the Biological Carbon Pump (BCP) is a significant component of the global carbon cycle. It transfers roughly 11GtCyr−1 into the ocean’s interior and maintains atmospheric carbon dioxide at significantly lower levels than would be the case if it did not exist. More specifically, export by the BCP in the North Atlantic is ∼0.55–1.94GtCyr−1. A rich set of observations suggests that a complex set of processes drives this export. However, significant uncertainties exist regarding the BCP in the North Atlantic, including both the magnitude of the downward flux and the ecological, chemical and physical processes by which it is sustained and controlled. Our lack of detailed mechanistic understanding has also hindered modelling attempts to quantify and predict changes to the BCP. In this paper, we assess current knowledge concerning the BCP in the North Atlantic in order to identify priorities for future research, as well as suggesting how they might be addressed.
The title natural products (1 and 2, respectively) have been synthesized by Au(I)-catalyzed intramolecular hydroarylation (IMHA) of the relevant aryl propiolate esters (e.g., 13), which were ...themselves formed by reaction of the corresponding phenols with either 3-(trimethylsilyl)propiolic acid or propiolic acid and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride or dicyclohexylcarbodiimide. (±)-Purpurasol (3) was readily derived from fraxetin (2) by established procedures.
Using femtosecond time-resolved photoelectron spectroscopy we demonstrate that photoexcitation transforms monoclinic VO2 quasi-instantaneously into a metal. Thereby, we exclude an 80 fs structural ...bottleneck for the photoinduced electronic phase transition of VO2. First-principles many-body perturbation theory calculations reveal a high sensitivity of the VO2 band gap to variations of the dynamically screened Coulomb interaction, supporting a fully electronically driven isostructural insulator-to-metal transition. We thus conclude that the ultrafast band structure renormalization is caused by photoexcitation of carriers from localized V 3d valence states, strongly changing the screening before significant hot-carrier relaxation or ionic motion has occurred.
Smallpox, caused by
(VARV), was eradicated in 1980; however, VARV bioterrorist threats still exist, necessitating readily available therapeutics. Current preparedness activities recognize the ...importance of oral antivirals and recommend therapeutics with different mechanisms of action.
(MPXV) is closely related to VARV, causing a highly similar clinical human disease, and can be used as a surrogate for smallpox antiviral testing. The prairie dog MPXV model has been characterized and used to study the efficacy of antipoxvirus therapeutics, including recently approved TPOXX (tecovirimat). Brincidofovir (BCV; CMX001) has shown antiviral activity against double-stranded DNA viruses, including poxviruses. To determine the exposure of BCV following oral administration to prairie dogs, a pharmacokinetics (PK) study was performed. Analysis of BCV plasma concentrations indicated variability, conceivably due to the outbred nature of the animals. To determine BCV efficacy in the MPXV prairie dog model, groups of animals were intranasally challenged with 9 × 10
plaque-forming units (PFU; 90% lethal dose LD
) of MPXV on inoculation day 0 (ID0). Animals were divided into groups based on the first day of BCV treatment relative to inoculation day (ID-1, ID0, or ID1). A trend in efficacy was noted dependent upon treatment initiation (57% on ID-1, 43% on ID0, and 29% on ID1) but was lower than demonstrated in other animal models. Analysis of the PK data indicated that BCV plasma exposure (maximum concentration
) and the time of the last quantifiable concentration (AUC
) were lower than in other animal models administered the same doses, indicating that suboptimal BCV exposure may explain the lower protective effect on survival.
Preparedness activities against highly transmissible viruses with high mortality rates have been highlighted during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Smallpox, caused by variola virus (VARV) infection, is highly transmissible, with an estimated 30% mortality. Through an intensive vaccination campaign, smallpox was declared eradicated in 1980, and routine smallpox vaccination of individuals ceased. Today's current population has little/no immunity against VARV. If smallpox were to reemerge, the worldwide results would be devastating. Recent FDA approval of one smallpox antiviral (tecovirimat) was a successful step in biothreat preparedness; however, orthopoxviruses can become resistant to treatment, suggesting the need for multiple therapeutics. Our paper details the efficacy of the investigational smallpox drug brincidofovir in a monkeypox virus (MPXV) animal model. Since brincidofovir has not been tested
against smallpox, studies with the related virus MPXV are critical in understanding whether it would be protective in the event of a smallpox outbreak.
Monkeypox virus (MPXV) is a member of the genus Orthopoxvirus, endemic in Central and West Africa. This viral zoonosis was introduced into the United States in 2003 via African rodents imported for ...the pet trade and caused 37 human cases, all linked to exposure to MPXV-infected black-tailed prairie dogs (Cynomys ludovicianus). Prairie dogs have since become a useful model of MPXV disease, utilized for testing of potential medical countermeasures. In this study, we used recombinant MPXV containing the firefly luciferase gene (luc) and in vivo imaging technology to characterize MPXV pathogenesis in the black-tailed prairie dog in real time. West African (WA) MPXV could be visualized using in vivo imaging in the nose, lymph nodes, intestines, heart, lung, kidneys, and liver as early as day 6 post infection (p.i.). By day 9 p.i., lesions became visible on the skin and in some cases in the spleen. After day 9 p.i., luminescent signal representing MPXV replication either increased, indicating a progression to what would be a fatal infection, or decreased as infection was resolved. Use of recombinant luc+ MPXV allowed for a greater understanding of how MPXV disseminates throughout the body in prairie dogs during the course of infection. This technology will be used to reduce the number of animals required in future pathogenesis studies as well as aid in determining the effectiveness of potential medical countermeasures.
Coastal and shelf environments support high levels of biodiversity that are vital in mediating ecosystem processes, but they are also subject to noise associated with mounting levels of offshore ...human activity. This has the potential to alter the way in which species interact with their environment, compromising the mediation of important ecosystem properties. Here, we show that exposure to underwater broadband sound fields that resemble offshore shipping and construction activity can alter sediment-dwelling invertebrate contributions to fluid and particle transport--key processes in mediating benthic nutrient cycling. Despite high levels of intra-specific variability in physiological response, we find that changes in the behaviour of some functionally important species can be dependent on the class of broadband sound (continuous or impulsive). Our study provides evidence that exposing coastal environments to anthropogenic sound fields is likely to have much wider ecosystem consequences than are presently acknowledged.
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