cssi/SciSciGPT-SciSciNet huggingface dataset:
Cell-type specific organization of glycine receptor clusters in the mammalian spinal cord

Glycinergic synapses play a major role in shaping the activity of spinal cord neurons. The spatial organization of postsynaptic receptors is likely to determine many functional parameters at these synapses and is probably related to the integrative capabilities of different neurons. In the present study, we have investigated the organization of gephyrin expression along the dendritic membranes of α- and γ-motoneurons, Ia inhibitory interneurons, and Renshaw cells. Gephyrin is a protein responsible for the postsynaptic clustering of glycine receptors, and the features of gephyrin and glycine receptor α1-subunit immunofluorescent clusters displayed similar characteristics on ventral horn spinal neurons. However, the density of clusters and their topographical organization and architecture varied widely in different neurons and in different dendritic regions. For motoneurons and Ia inhibitory interneurons, cluster size and complexity increased with distance from the soma, perhaps as a mechanism to enhance the influence of distal synapses. Renshaw cells were special in that they displayed an abundant complement of large and morphologically complex clusters concentrated in their somas and proximal dendrites. Serial electron microscopy confirmed that the various immunoreactivity patterns observed with immunofluorescence accurately parallel the variable organization of pre- and postsynaptic active zones of glycinergic synapses. Finally, synaptic boutons from single-labeled axons of glycinergic neurons (Ia inhibitory interneurons) were also associated with postsynaptic receptor clusters of variable shapes and configurations. Our results indicate that mechanisms regulating receptor clustering do so primarily in the context of the postsynaptic neuron identity and localization in the dendritic arbor. J. Comp. Neurol. 379:150-170, 1997. © 1997 Wiley-Liss, Inc.
Characteristics of a photonic bandgap single defect microcavity electroluminescent device

A microcavity surface-emitting coherent electroluminescent device operating at room temperature under pulsed current injection is described. The microcavity is formed by a single defect in the center of a 2-D photonic crystal consisting of a GaAs-based heterostructure. The gain region consists of two 70-/spl Aring/ compressively strained In/sub 0.15/Ga/sub 0.85/As quantum wells, which exhibit a spontaneous emission peak at 940 nm. The maximum measured output power from a single device is 14.4 /spl mu/W. The near-field image of the output resembles the calculated TE mode distribution in a single defect microcavity. The measured far-field pattern indicates the predicted directionality of a microcavity light source. The light-current characteristics of the device exhibit a gradual turn-on, or a soft threshold, typical of single- or few-mode microcavity devices. Analysis of the characteristics with the carrier and photon rate equations yields a spontaneous emission factor /spl beta//spl ap/0.06.
The fast Fourier transform for experimentalists. Part VI. Chirp of a bat

Two assumptions underlie the Fourier transform process: stationarity and linearity. When signals deviate from these conditions, the transform outcomes are suspect. A chirp, which by definition has a frequency that varies with time, doesn't satisfy these requirements, and its fast Fourier transform (FFT) doesn't adequately express the changing nature of the signal's frequency content. In this analysis of a bat chirp, I first examine how the FFT handles a chirp and then how we can use a sequence of windows that individually span only a portion of the total time-domain signal to generate a frequency versus time description of the signal. The trade-off in this kind of windowing is between dynamic response and resolution: we obtain improved dynamics if we use shorter windows, whereas we get better resolution with longer windows. This article and this series concludes with a brief look at the Hilbert-Huang transform, which isn't constrained by the same assumptions as the FFT. This transform process consists of two independent sets of operations. The first, called empirical mode decomposition, generates a set of intrinsic mode functions (IMFs), from the data. The second step extracts phase information from each IMF and its Hilbert transform. The derivative of the phase with respect to time yields the instantaneous frequency. The net effect of these operations is to transform the time-domain data to frequency versus time data instead of the amplitude versus frequency the FFT obtains
Intelligent control of an exercise machine

The control of a one degree of freedom exercise machine is considered. The control objective is to cause the human user to exercise at a rate which optimizes a prescribed weighted power criterion. The optimality condition is determined by the muscle mechanics which is assumed to satisfy a force-velocity relationship. In general, the parameters of this relationship are unknown and vary with the configuration of the exercise machine. As a consequence, the control scheme must simultaneously (i) identify the parameters, (ii) optimize the controller, and (iii) stabilize the system to the estimated optimal states. In this paper we derive a controller which is in the form of a nonlinear dynamic damper and makes the controlled system interact passively with the user. Assuming that the human's force-velocity muscular biomechanics relationship is known, this controller allows the user to exercise in an optimal manner.
Broad, but Not Universal, Transcriptional Requirement for yTAFII17, a Histone H3–like TAFII Present in TFIID and SAGA

Abstract The RNA polymerase II general transcription factor TFIID is a multisubunit complex comprising TATA box–binding protein (TBP) and associated factors (TAF II s). Experiments in yeast have shown that although most TAF II s are required for viability, many genes are transcribed normally upon inactivation of individual and even multiple yTAF II s. Here we analyze yTAF II 17, recently found to be present in both the SAGA HAT complex as well as TFIID. Functional inactivation of yTAF II 17 by temperature-sensitive mutation or depletion results in loss of transcription of many, but not all, genes. The upstream activating sequence (UAS), which contains the activator binding sites, is the region that renders a gene yTAF II 17 dependent. In conjunction with previous studies, our results reveal that different TAF II s have remarkably distinct properties.
Is the liquid water surface basic or acidic? Macroscopic vs. molecular-scale investigations

Abstract Many physical phenomena are affected by the intrinsic acidity/basicity of the free liquid water surface, yet it remains an active and controversial subject. Macroscopic bubble and droplet experiments have been interpreted to indicate an air–water interface covered with hydroxide, whereas recent molecular-scale studies produce the opposite conclusion, viz. that hydroxide is repelled from the interface while hydronium is strongly adsorbed. Here we report results from resonant UV second harmonic generation (SHG) experiments that are best modeled by surface depletion of hydroxide and establish at most a weak surface adsorption. This finding is consistent with our earlier SHG measurements indicating surface enhancement of hydrated protons, as well as with other molecular-scale experiments and simulations, but stands in stark contrast to the results from macroscopic studies. The acidity, or basicity, of aqueous surfaces could strongly influence heterogeneous atmospheric chemical processes, such as aerosol reactions and gas uptake.
Early Eocene Brontotheriidae (Perissodactyla) from the Eureka Sound Group, Ellesmere Island, Canadian High Arctic—implications for brontothere origins and high-latitude dispersal

Abstract The northernmost records of early Eocene brontotheres, fossils of cf. Eotitanops and Brontotheriidae gen. et sp. indet., are described here from late Wasatchian-aged strata of upper parts of the Eureka Sound Group on central Ellesmere Island (∼79°N). Although the fossils were initially tentatively identified on faunal lists as Lambdotherium, their larger size and dental morphology ally them more closely to mid-latitude Eotitanops and Palaeosyops. The Ellesmere Island specimens are dentally most similar to mid-latitude Eotitanops, but can be distinguished from the latter by derived characters on their premolars that are shared with the younger (i.e., Bridgerian) Palaeosyops. The presence of brontotheres in early Eocene strata on Ellesmere Island implies that the group's evolution was well underway early in its history at northern high latitudes, and is consistent with either an Asian or North American origin and trans-Beringian dispersal. While cf. Eotitanops from Ellesmere Island appears dentally...
Social Networks and Organizational Interventions: Insights from an Area-Wide Labor-Management Committee

In this article, the author discusses a study to determine the effects of interorganizational network structure on the adoption of intervention strategies. The author examined the social network structure of key actors in an area-wide labor-management committee in an industrial city in the northeastern U.S., seeking to determine why some community leaders supported organization development/quality-of-work-life interventions whereas others did not. Using a mail survey of leaders in labor, management, and local government, the author obtained data as to whether respondents had established professional ties only, informal ties only, or both professional and informal ties with members of the community elite. From this analysis, the author concludes that people and organizations with "weak" ties (i.e., professional only) or no ties to the community elite are more likely to support ODI Q WL interventions than are those with "strong" informal and/or professional ties, who will prefer programs that do not threate...
Characterizing hydraulic fractures in shale gas reservoirs using transient pressure tests

Abstract Hydraulic fracturing combined with horizontal drilling has been the technology that makes it possible to economically produce natural gas from unconventional shale gas or tight gas reservoirs. Hydraulic fracturing operations, in particular, multistage fracturing treatments along with horizontal wells in unconventional formations create complex fracture geometries or networks, which are difficult to characterize. The traditional analysis using a single vertical or horizontal fracture concept may be no longer applicable. Knowledge of these created fracture properties, such as their spatial distribution, extension and fracture areas, is essential information to evaluate stimulation results. However, there are currently few effective approaches available for quantifying hydraulic fractures in unconventional reservoirs. This work presents an unconventional gas reservoir simulator and its application to quantify hydraulic fractures in shale gas reservoirs using transient pressure data. The numerical model incorporates most known physical processes for gas production from unconventional reservoirs, including two-phase flow of liquid and gas, Klinkenberg effect, non-Darcy flow, and nonlinear adsorption. In addition, the model is able to handle various types and scales of fractures or heterogeneity using continuum, discrete or hybrid modeling approaches under different well production conditions of varying rate or pressure. Our modeling studies indicate that the most sensitive parameter of hydraulic fractures to early transient gas flow through extremely low permeability rock is actually the fracture-matrix contacting area, generated by fracturing stimulation. Based on this observation, it is possible to use transient pressure testing data to estimate the area of fractures generated from fracturing operations. We will conduct a series of modeling studies and present a methodology using typical transient pressure responses, simulated by the numerical model, to estimate fracture areas created or to quantity hydraulic fractures with traditional well testing technology. The type curves of pressure transients from this study can be used to quantify hydraulic fractures in field application.
Price Negotiations and Bargaining Costs

We study the role of consumers’ bargaining costs in a retail setting. First, we use a simple model to show how a retailer’s optimal pricing strategy (xed pricing vs. bargaining) varies with consumers’ bargaining costs and the retailer’s marginal costs. We then prove how bargaining costs can be non-parametrically identied separately from bargaining power and marginal utility of income. Using individual-level data on refrigerator transactions, we estimate an average bargaining cost of $28, i.e. on average consumers will negotiate prices if they get a discount of more than $28. While there exists substantial heterogeneity in bargaining costs, these costs are relatively low as compared to the retailer’s markup; thus, making a hybrid strategy (where retailers post prices but allow consumers to bargain) more protable than xed pricing. Finally, we provide evidence that ignoring bargaining costs may lead to biased counterfactual pricing analysis.
Assessing impact of formulation and process variables on in-vitro performance of directly compressed abuse deterrent formulations

Prescription drug products abuse/misuse is epidemic in United States. Opioids drug forms major portion of prescription drug product abuse. Abuse deterrence formulation (ADF) is one of the many approaches taken by sponsors to tackle this problem. It involves formulating opioids into dosage forms that will be difficult to abuse/misuse. Current investigation focused on evaluating the abuse deterrent properties (ADP) of ADF manufactured by direct compression method. Effect of process and formulation variables on ADP was investigated by statistical design of experiment (fractional factorial design). Independent factors studied were molecular weight of polyethylene oxide (Polyox™), curing time, temperature and method, and antioxidant type. Sotalol hydrochloride was selected as a model drug. ADP investigated were hardness/crush resistance, syringeability and injectability, physical manipulation (reduction into powder) and drug extraction in water and alcohol. Hardness and syringeability are evaluated by newly developed quantitative procedure. Other properties were also investigated such as morphology, crystallinity, assay and dissolution. The hardness and drug extraction was significantly (p<0.05) affected by curing temperature. Formulations could be powdered in 3 min irrespective of their hardness. Syringeability and injectability were intrinsic properties of the polymer used in the formulation, and were not affected by the investigated factors. Crystallinity of the polymer and drug changed, and was dependent upon curing temperature and time. The dissolution and assay were independent of formulation and process parameters studied. In conclusion, the study indicated some advantages of ADF product compared to non-ADF prepared by direct compression. However, the ADF should not be viewed as abuse proof product rather as incrementally improved product.
Midazolam Metabolism by Modified Caco-2 Monolayers: Effects of Extracellular Protein Binding

It has been suggested that the binding of a drug to plasma proteins will influence the intestinal extraction efficiency when drug is delivered to the mucosal epithelium via either the gut lumen or vasculature. We evaluated this hypothesis using cytochrome P-450 (CYP)3A4-expressing Caco-2 monolayers as a model for the intestinal epithelial barrier and midazolam as a CYP3A-specific enzyme probe. The rate of 1'-hydroxylation was measured following apical or basolateral midazolam administration to monolayers incubated in the presence or absence of 4 g/dl of human serum albumin (HSA) in the basolateral compartment medium. The midazolam-free fraction in culture medium containing HSA was 3.3%. Inclusion of HSA in the basolateral medium decreased peak intracellular midazolam accumulation after an apical midazolam dose (3 microM) by 35% and reduced the 1'-hydroxymidazolam formation rate by approximately 20%. Because of the accelerated diffusion of midazolam through the cell monolayer and into the basolateral compartment, there was a 61% reduction in the first-pass metabolic extraction ratio: 13.3 +/- 0. 12% for control versus 5.2 +/- 1% with HSA. Compared with control, addition of HSA resulted in a 91% decrease in the peak intracellular midazolam level and a 86% decrease in the rate of 1'-hydroxylation after the administration of midazolam into basolateral medium. These findings suggest that, in vivo, binding of a drug to plasma proteins will impact both first-pass and systemic intestinal midazolam extraction efficiency. Furthermore, the effect will be more pronounced for a drug that is delivered to mucosal enterocytes by way of arterial blood, compared with oral drug delivery.
Rapid catalyst-free hydrazone ligation: protein-pyridoxal phosphoramides.

Pyridoxal-5′-phosphate (PLP) represents an active form of Vitamin B6 that shows relatively fast imine formation with hydrazines under physiological conditions without the need of a catalyst. A convenient phosphate/amine conjugation protocol was developed to covalently link PLP to proteins, affording proteins capable of hydrazone formation with bioorthogonal hydrazinyl functional groups. Thus, the lectin Concanavalin A (Con A) was labeled with PLP. Pretreatment with fluorescein hydrazide gave dye-labeled Con A that labeled cell surfaces efficiently. Alternatively, pretargeting was achieved by labeling cells with Con A-PLP, then treatment in vitro with Alexa Fluor 488 hydrazide.
Design of Digital PID Controller Based on FPGA

The reliability and real time of PID controller is very important to realize the precise orientation of a motion control system. In the paper,based on the PID control algorithm,the increment-style PID controller is designed and simulated by using field programmable gate array (FPGA),the whole program is written by Verilog HDL language. The results proved that the method is available.
Dissimilarity Kernels for Paraphrase Identification

We present in this paper a novel solution to the problem of paraphrase identification based on lexical dissimilarity kernels. Lexical kernels in conjunction with Support Vector Machines are preferred over other learning methods, e.g. decision trees, due to their ability to handle a high number of features. Dissimilarity-based kernels emphasize dissimilarities among text fragments and therefore are appropriate for text similarity tasks characterized by high lexical overlap. We conducted experiments with our kernels on the Microsoft Research (MSR) Paraphrase Corpus, a standardized data set used for assessing approaches to paraphrase identification. Our reported accuracy results are competitive and robust when compared to state-of-the-art single-model approaches. The results were obtained using 10-fold cross-validation over the entire corpus. We also report competitive results on the test portion of the MSR Paraphrase Corpus, which is the standard way to report results on this corpus.
Computer Aided Detection of Spinal Degenerative Osteophytes on Sodium Fluoride PET/CT

Osteophytes, a common degenerative change in the spine, are found in 90 % of the population over 60 years of age. We have developed an automated system to detect and assess spinal osteophytes on \(^{18}\)F-sodium fluoride (\(^{18}\)F-NaF) PET/CT studies. We first segment the cortical shell of the vertebral body and unwrap it to a 2D map. Multiple characteristic features derived from PET/CT images are then projected onto the map. Finally, we adopt a three-tier learning based scheme to compute a confidence map and detect osteophyte sites and clusters. The system was tested on 20 studies (10 training and 10 testing) and achieved 84 % sensitivity at 3.8 false positives per case for the training set, and 82 % sensitivity at a 4.7 false positive rate for the testing set.
Preliminary Assessment and Analysis of Co2 Cleaning for an Inertial Fusion Device

The mechanisms of cleaning with carbon dioxide ice (CO2) for the National Ignition Facility (NIF) application are discussed and analyzed. The compatibility between this cleaning process and the mat...
Evaluating the Necessity of Antibiotics in the Treatment of Acute Epididymitis in Pediatric Patients: A Literature Review of Retrospective Studies and Data Analysis.

Objectives This literature review and data analysis aims to evaluate the percentage of pediatric patients with acute epididymitis found to have bacterial etiology and the percentage of patients in these studies that were treated with antibiotic therapy versus conservative therapy. Methods A search of EBSCO through January 13, 2016, using the key words epididymitis or epididymo-orchitis and child, children, or pediatric, identified 542 potential studies.Twenty-seven retrospective studies met the inclusion criteria, containing patients aged 21 years or younger with acute epididymitis or epididymo-orchitis. The number and age of patients, urine cultures and urinalysis results, number of patients treated with antibiotics, and incidence were extracted. Results A total of 1496 patients with acute epididymitis were identified. A urinalysis was obtained for 1124 patients, and 190 (16.9%) were positive. A urine culture was obtained for 670 patients, and 100 (14.9%) were positive. Fourteen studies addressed antibiotic administration wherein 652 patients were with acute epididymitis and 554 (85%) received antibiotics.Of 502 patients with urinalysis results, urine culture results, and antibiotic treatment rates, 54 (10.8%) were positive for a bacterial source. Antibiotics were administered to 410 (81.7%) of these 502 patients. Conclusions Practitioners should consider only prescribing antibiotics to patients with acute epididymitis if there is an abnormal urinalysis or urine culture.
Comment on the new Ds(∗)+π0 resonances

Abstract We propose an explanation of the new resonances observed in D s (∗)+ π 0 decays. We suggest that the data can be explained by the mixing of conventional p-wave excited Ds+ mesons with 4-quark states. The narrow states observed in Ds+π0 and D s ∗+ π 0 are primarily p-wave D sJ ∗ states, while the predominantly 4-quark states are shifted above D (∗) K threshold and should be broad. Ranges for the mixing parameter and mass of the 4-quark state in this scenario are given. Other experimental consequences are discussed.
Risk-Reducing Surgery for BRCA1/2 Genetic Mutation Carriers

Patients with a BRCA1 or BRCA2 (BRCA) are at high risk for developing breast cancer which may be mitigated through risk-reducing surgery. Risk-reducing mastectomy has been shown to reduce the risk of breast cancer by 90% or more among high-risk women including BRCA mutation carriers. The decision to undergo prophylactic surgery is a choice that patients make, in conjunction with their multidisciplinary healthcare team which often includes genetic counselors, surgeons, and additional professionals they can access to provide psychosocial support to assist women determine if they want surgery and, if so, the timing. Surgical options for mastectomy include a simple mastectomy without reconstruction or either a skin-sparing mastectomy or a nipple-sparing mastectomy with reconstruction. Clinical surveillance must continue at least annually for women after risk-reducing mastectomy because there remains a small, albeit greatly reduced, lifetime risk of breast cancer (<5%) after mastectomy.
Spatiotemporal Variation of Stress Drop During the 2008 Mogul, Nevada, Earthquake Swarm

We estimate stress drops for 148 shallow (<6 km) earthquakes in the complex 2008 Mogul, Nevada, swarm using empirical Green's function-derived spectral ratios. Near-source, temporary broadband seismometers deployed before the Mw4.9 main shock provide high-quality records of many foreshocks and aftershocks, and an ideal opportunity to investigate uncertainties in corner frequency measurement as well as stress drop (Δσ) variation related to space, time, depth, mechanism, and magnitude. We explore uncertainties related to source model, measurement approach, cross-correlation limit, and frequency bandwidth. P (S) wave Δσ results range from 0.2 ± 0.15 (0.3 ± 0.15) to 36±20 (58±7) MPa, a variation greater than the error range of each individual estimate. Although this variation is not explained simply by any one parameter, spatiotemporal variation along the main shock fault plane is distinct: coherent clusters of high and low Δσ earthquakes are seen, and high-Δσ foreshocks correlate with an area of reduced aftershock productivity. These observations are best explained by a difference in rheology along the fault plane. Average Δσs of 3.9±1.1 (4.0±1.1) MPa using P (S) are similar to those found for earthquakes in a variety of settings, implying that these shallow, potentially fluid-driven earthquakes do not have systematically lower Δσ than average tectonic earthquakes (~4 MPa) and, therefore, have similar (or higher, due to proximity to the surface) expected ground motions compared to typical earthquakes. The unprecedented detail achieved for these shallow, small-magnitude earthquakes confirms that Δσ, when measured precisely, is a valuable observation of physically meaningful fault zone properties and earthquake behavior.
Delocalization Drives Free Charge Generation in Conjugated Polymer Films

We demonstrate that the product of photoinduced electron transfer between a conjugated polymer host and a dilute molecular sensitizer is controlled by the structural state of the polymer. Ordered s...
Publishing papers that matter

Daniel G. Morrow introduces himself as the fifth editor of the Journal of Experimental Psychology: Applied (JEPA). The journal is the premier outlet for "use-inspired basic research" (Stokes, 2011) in the psychological sciences. (PsycINFO Database Record
Revisiting the “Informal Settlement” Phenomenon

This chapter provides a broad theoretical overview of informality by outlining some popular misconceptions on informality: that informal settlements are solely a developing countries’ problem; that those myths are essentially long-gone; and, that the distinction between formality and informality still holds. This chapter briefly touches on each of these myths and offers a fairly broad conceptual framework arguing that as the backbone of any physical upgrading policy, enabling or enablement of informal settlements should reflect the juxtaposition of two simultaneous undercurrents, namely, the “formalization of the informal” and the “informalization of the formal.” As part of this debate, the chapter takes a hard look at a series of government policies that have been in vogue in response to slum or informal settlement upgrading including benign neglect, forced relocation or evacuation, self-help, public housing, redevelopment and eventually, enabling since the 1950s and 1960s. Showcasing the legality–illegality discourse as a hotly debated component of informal settlements, this conceptual framework revisits the formal–informal nexus by distinguishing between regularization vs. regularizing aspects of each policy.
Chronic Stress in Children and Adolescents: A Review of Biomarkers for Use in Pediatric Research:

Problem:Incorporating biomarkers of chronic stress into pediatric research studies may help to explicate the links between exposure to adversity and lifelong health, but there are currently very fe...
BPIFB3 facilitates flavivirus infection by controlling RETREG1-dependent reticulophagy

The flavivirus genus, which includes dengue virus (DENV) and Zika virus (ZIKV), are significant human pathogens and the prevalence of infected vectors continues to geographically expand. Both DENV and ZIKV rely on expansion of the endoplasmic reticulum (ER) and the induction of autophagy to establish a productive viral infection. However, little is known regarding the interplay between the requirements for autophagy initiation during infection and the mechanisms used by these viruses to avoid clearance through the autophagic pathway. We recently showed that DENV and ZIKV inhibit reticulophagy (specific degradation of the ER through autophagy) by cleaving reticulophagy regulator 1 (RETREG1), an autophagy receptor responsible for targeted ER sheet degradation. These data suggest that DENV and ZIKV require specific autophagic pathways for their replication, while other autophagic pathways are antiviral. We previously identified BPI Fold Containing Family B Member 3 (BPIFB3) as a regulator of autophagy that negatively controls enterovirus replication. Here, we show that in contrast to enteroviruses, BPIFB3 functions as a positive regulator of DENV and ZIKV infection and that its RNAi-mediated silencing drastically inhibits the formation of viral replication organelles. We show that BPIFB3 depletion enhances ER fragmentation, while its overexpression protects against autophagy-induced ER degradation, demonstrating that BPIFB3 serves as a specific regulator of ER turnover. We further show that the antiviral effects of BPIFB3 depletion on flavivirus infection are reversed in RETREG1-depleted cells, and that BPIFB3 associates with RETREG1 within the ER, suggesting that BPIFB3 regulates a RETREG1-specific reticulophagy pathway. Collectively, these studies identify BPIFB3 as a regulator of the reticulophagy pathway and define the requirements for a novel host regulator of flavivirus infection.
Saving On-Line Privacy

With the increasing use of electronic media for our daily transactions, we widely distribute our personal information. Once released, controlling the dispersal of these information is virtually impossible. Privacy-enhancing technologies can help to minimize the amount of information that needs to be revealed in transactions, on the one hand, and to limit the dispersal, on the other hand. Unfortunately, these technologies are hardly used today. In this paper we aim to foster the adoption by providing a summary of what such technologies can achieve. We hope that by this, policy makers, system architects, and security practitioners will be able to employ privacy-enhancing technologies.
PTH and Acid-Base Regulation

PTH exerts effects on both the renal and extrarenal regulation of acidbase homeostasis. This brief revue will highlight the effects of the hormone on urinary acidification and on the whole body buffering of acid loads. Several balance studies will be cited to illustrate the integration of the renal and extrarenal effects of the peptide in the whole animal. Finally, I will discuss the modulating effect of metabolic acidosis on the anticalciuric action of PTH.
Evolution and Human Sexual Behavior

Few things come more naturally to us than sex--or so it would seem. Yet to a chimpanzee, the sexual practices and customs we take for granted would appear odd indeed. He or she might wonder why we bother with inconveniences like clothes, why we prefer to make love on a bed, and why we fuss so needlessly over privacy. Evolution and Human Sexual Behavior invites us into the thought-experiment of imagining human sex from the vantage point of our primate cousins, in order to underscore the role of evolution in shaping all that happens, biologically and behaviorally, when romantic passions are aroused. Peter Gray and Justin Garcia provide an interdisciplinary synthesis that draws on the latest discoveries in evolutionary theory, genetics, neuroscience, comparative primate research, and cross-cultural sexuality studies. They are our guides through an exploration of the patterns and variations that exist in human sexuality, in chapters covering topics ranging from the evolution of sex differences and reproductive physiology to the origins of sexual play, monogamous unions, and the facts and fictions surrounding orgasm. Intended for generally curious readers of all stripes, this up-to-date, one-volume survey of the evolutionary science of human sexual behavior explains why sexuality has remained a core fascination of human beings throughout time and across cultures.
Preoperative risk evaluation for pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND Pancreatic fistula remains common, with limited ability to risk stratify patients preoperatively. The objective of this study was to identify risk factors for clinically-relevant postoperative pancreatic fistula (CR-POPF) that are routinely available in the preoperative setting. METHODS Preoperatively available variables for all pancreaticoduodenectomies from 2014-2017 were examined using a national clinical registry. The cohort was separated into risk factor identification and internal validation subgroups. RESULTS Among 15 033 pancreaticoduodenectomies, the CR-POPF rate was 16.7%. CR-POPF was more likely in patients that were male (odds ratio [OR], 1.51), obese (body mass index [BMI] > 30, OR, 1.97), had minimal preoperative weight loss (OR, 1.25), had a nondilated pancreatic duct (OR, 1.81), did not have diabetes, (OR, 1.80), did not receive neoadjuvant therapy (OR, 1.78), had no evidence of biliary obstruction (OR, 1.18), or had nonadenocarcinoma pathology (OR, 1.96; all P < 0.01). Patients with three or fewer risk factors had a CR-POPF rate of 7.1%, while those with six or more risk factors had a CR-POPF rate of 26.3% (P < 0.001). CONCLUSION Preoperative CR-POPF risk evaluation could be a useful tool in patient counseling and surgical planning, and risk may allow for more well-informed decisions regarding perioperative management, including enhanced recovery protocols and use of somatostatin analogs.
Radioactive World: An Outreach Activity for Nuclear Chemistry

Nuclear chemistry is a topic of great societal importance with applications in the realms of medicine, energy, and national security. Despite its significance, this area receives little attention i...
Taste Modulator Influences Rare Case of Color-Gustatory Synesthesia

We investigated the effect of a sweetness blocker on the synesthetic taste experience of a rare color-gustatory synesthete, E.C., for whom specific colors elicit unique tastes. Blocking E.C.’s sweetness receptors while the tongue was otherwise unstimulated left other taste components of the synesthesia unaltered but initially reduced her synesthetic sweetness, which suggests a peripheral modulation of the synesthetic illusion.
Movement Disorders in Women with X-Linked Adrenoleukodystrophy (1608)

Objective: To describe the movement disorders seen among women with X-linked Adrenoleukodystrophy Background: X-linked Adrenoleukodystrophy (ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene which codes for the transporter of very long chain fatty acids. The clinical spectrum in males with ALD ranges from isolated adrenal insufficiency and slowly progressive myelopathy to devastating cerebral demyelination. As ALD is an X-linked disease, women were previously thought to be asymptomatic carriers. More recently it has been recognized that up to 80% of women with ALD experience some degree of myelopathy. These symptoms, while progressive in nature, are thought to a milder form of the myelopathy seen in men with ALD. Design/Methods: We did a systematic survey of X-ALD clinic patients seen from 2013–2018 at Massachusetts General Hospital. An estimate of 15% in retrospective review has myelopathy and concurrent movement disorders. Detailed medical and family history were obtained. Blood samples were collected for X-inactivation studies. Standardized videotaped neurological examination was performed and subsequently reviewed by two different movement disorder specialists. Results: Careful evaluation showed a combination of different movements such as cervical dystonia (4), spasmodic adductor dysphonia (3), action and postural tremor (6), bradykinesia (1) and ataxia (8). All patients exhibited gait difficulties and symptoms of myelopathy. Conclusions: Movement disorders may be a feature of many hereditary neurodegenerative and metabolic disorders especially among women affected by X-linked disorders. In most of these cases, dystonia and tremor usually occur in the setting of a broader clinical phenotype. Interestingly, movement disorders are not known to be associated with the slowly progressive myelopathy in men with ALD. Hence this finding represents a first distinct phenotype in women with ALD. The notion that ALD may be an underdiagnosed cause of movement disorder among women with ALD warrants further investigation. Disclosure: Dr. Supnet has nothing to disclose. Dr. Stephen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Xenon pharmaceuticals - scientific advisory board. Dr. Stephen has received research support from Sanofi-Genzyme.Dr. Andonian has nothing to disclose. Dr. Sharma has received personal compensation in an editorial capacity for received honoraria for serving as associate editor of Brain and Behavior, a journal published by John Wiley a Sons. Dr. Eichler has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Vertex Pharmaceuticals, Minoryx Therapeutics, and Orpheris. Dr. Eichler holds stock and/or stock options in Johnson & Johnson, and SwanBio. Dr. Eichler has received research support from Alexion, Retrophin, Neurovia, Applied Genetic Technologies Corp, Bluebird Bio, and Minoryx Therapeutics.
Prevalence of Persistent Corneal Epithelial Defects in Chronic Ocular Graft-Versus-Host Disease.

Purpose To establish the prevalence, clinical characteristics, and risk factors for persistent corneal epithelial defects (PED) in patients with chronic ocular graft-versus-host disease (oGVHD) and to determine visual outcomes after healing. Design Retrospective cohort study. Methods A chart review was conducted of patients in whom chronic oGVHD was diagnosed between January 2011 and December 2018 and their demographic and clinical characteristics were collected. Data were analyzed to determine prevalence of PED, and multivariate logistic regression was performed to determine the risk factors associated with it. Results A total of 405 patients at a mean age of 60 ± 13 years in whom chronic oGVHD was diagnosed; 58% were men. The prevalence of PED was 8.1%. The median time for PED development after hematopoietic stem cell transplantation was approximately 24 months. Median time to PED resolution was 4.5 weeks after starting therapy. The mean best-corrected visual acuity declined by 2 lines post-PED resolution. The prevalence rates of corneal ulcer and perforation were 6.2% and 4.0%, respectively, over 8 years. Logistic regression analysis, used to determine factors associated with PED, showed diabetes (P = .006), limbal stem cell deficiency (LSCD) (P = .02), filamentary keratitis (P = .02), subconjunctival fibrosis (P = .02), and a higher National Institutes of Health (NIH) oGVHD score (P = .01) were significant risk factors for PED development. Conclusions The study found the prevalence rate of PED, corneal ulceration, and corneal perforation in chronic oGVHD to be 8.1%, 6.2%, and 4%, respectively. Analysis showed that oGVHD patients with diabetes, LSCD, filamentary keratitis, subconjunctival fibrosis, and a high NIH score were at higher risk of developing severe corneal disease.
Regulated assembly of the ER membrane protein complex

The assembly of nascent proteins into multi-subunit complexes is tightly regulated to maintain cellular homeostasis. The ER membrane protein complex (EMC) is an essential insertase that requires seven membrane-spanning and two soluble subunits for function. Here we show that the kinase With no lysine 1 (WNK1), known for its role in hypertension and neuropathy, is required for assembly of the human EMC. WNK1 uses a conserved amphipathic helix to stabilize the soluble subunit, EMC2, by binding to the EMC2-8 interface. Shielding this hydrophobic surface prevents promiscuous interactions of unassembled EMC2 and precludes binding of ubiquitin ligases, permitting assembly. Using biochemical reconstitution, we show that after EMC2 reaches the membrane, its interaction partners within the EMC displace WNK1, and similarly shield its exposed hydrophobic surfaces. This work describes an unexpected role for WNK1 in protein biogenesis, and defines the general requirements of an assembly factor that will apply across the proteome.
EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer.

Background:EGFR/c-Met activation/amplification and co-expression, mTOR upregulation/activation, and Akt/Wnt signaling upregulation have been individually associated with more aggressive disease and...
Using process- and product-oriented measures to evaluate changes in motor skills across an intervention.

The purpose of this study was to: (1) determine if process- and product-oriented measures similarly evaluate changes in motor skills across an intervention and (2) examine the relationship between ...
Problems of delimitation of the Sea of Azov and the Kerch Strait

The article gradually considers the negotiation process between Ukraine and the Russian Federation on the delimitation of theSea of Azov and the Kerch Strait from 1991 to the present. It was established that according to the map of the inter-republican borderbetween the Ukrainian SSR and the Russian SSR, and according to the division of maritime waters on the basis of international law,Russia should get a smaller part of the Sea of Azov. That is why Russia was not interested in the rapid establishment of a state borderon water. It was advantageous for Russia to delay the negotiation process on this issue and use the Sea of Azov on the same terms asbefore the collapse of the USSR.The article also focuses on numerous attempts of Ukrainian diplomats to achieve legal certainty in the delimitation of the Sea ofAzov and the Kerch Strait. A total of 36 rounds of border talks about the Sea of Azov and the Kerch Strait, held from 1996 to 2012under the leadership of the Ministry of Foreign Affairs of Ukraine, showed that Russia was ready to delimit the Sea of Azov only onits own terms but not on the basis of international maritime law.After the annexation of Crimea, a new round of relations begins regarding the division of the Black Sea. Russia acted quicklyand in March 2014 announced a tender for a construction project of a bridge that would connect mainland Russia and the CrimeanPeninsula, which at that time had already been illegally incorporated into the Russian Federation. Moscow has stated that the KerchStrait should be fully controlled by them, as both shores are Russian.In 2016, Ukraine filed a lawsuit against Russia in the Hague Arbitration Court for breaking the UN Convention on the Law ofthe Sea in the Black and Azov Seas and in the Kerch Strait. For today we don’t know what decision will be made by the Hague tribunal,but there is reason to believe that the chances for winning of Ukraine are high.The problem of the Sea of Azov and the Kerch Strait has no simple solution. For today the only option is to wait for a decisionof the Arbitration Tribunal. Only on its basis Ukraine will be able to achieve the best strategy of the relations with Russia on the delimitationthe Sea of Azov and the Kerch Strait.
Physician, Protect Thyself: Why Psychiatrists Should Be Aware of Their Internet Presence and How to Protect Themselves.

ABSTRACT Modern psychiatric practice requires the use of the Internet, and the current pandemic has accelerated the adoption of technology in clinics. Psychiatrists receive significant education on protecting patient privacy and medical information when using these tools. However, they receive little training regarding protecting their own personal privacy in the Internet era. Private information, often without one's knowledge, is frequently available online and accessible by patients. The work of physicians and psychiatrists creates additional unique vulnerabilities to privacy. Given the essential nature of the Internet in modern clinical practice, physicians should understand how to monitor and protect personal privacy and safety online. We provide advice to minimize vulnerability to a privacy breach, with a focus on areas unique to psychiatrists and psychiatric practice. We review the literature on physician safety online and offer guidance to get started.
Caregiver Health-Related Quality of Life, Burden, and Patient Outcomes in Ambulatory Advanced Heart Failure: A Report From REVIVAL.

Background Heart failure (HF) imposes significant burden on patients and caregivers. Longitudinal data on caregiver health‐related quality of life (HRQOL) and burden in ambulatory advanced HF are l...
Does Regional Variation in Pathogen Prevalence Predict the Moralization of Language in COVID-19 News?

While there is substantial research on COVID-19’s general framing in the news, little is known about the antecedents and moderators of using moral language in communicating the disease to audiences...
Propeller Strain Measurements and Vibration Measurements on the SS Michigan

The paper is intended to acquaint the reader with the nature of the test program and to discuss the results of some of the preliminary analyses. The tests performed on the strain measurements indicate that the data are reliable provided that zero shifts and other factors are taken into account. The data, with the propeller shape, indicate that a pitching torque exists on the propeller in operation and that the peak tensile stresses occur near the 0.5 chord. The analyses of the vibration measurements are reported under the headings: General Hull Criticals; Local Vibrations in the Stern; Vibrations of the Super-structure; Vibrations in the Machinery Space; Longitudinal Vibration of the Shafting; Vibrations During Maneuvering; and Hull Motion Patterns at Resonances. Various graphs are provided to show pertinent relationships.
Are Global City Regions Governable

This paper summarizes findings from a soon to be published manuscript entitled Global City Regions in Transition: The Struggle for Governability in London, New York, Paris and Tokyo by Paul Kantor, Christian Lefevre, Asato Saito, H. V. Savitch and Andy Thornley. Our survey demonstrates that economic success in London, New York, Paris and Tokyo is contingent upon their governments helping to bring this about. This reality raises an obvious question: Are they governable? Have their governments effectively managed the problems and opportunities of the global metropolis well? Our analysis describes alternative concepts of governability against which these global city regions can be evaluated. Although some notions of governability suggest failure, the idea of “effective” governability highlights how the interplay of local, regional and national governmental agencies can have important and stable influences on the policies, development and governance in all four of the city regions. From this perspective, governance in global city regions is not as weak as some claim.
Functional analysis of human RPS14 null alleles

Previously we described a large collection of cloned human DNAs that encode chemically defined missense mutations within the ribosomal protein S14 sequence. We determined that biologically inactive (i.e. null) alleles resulted primarily from point mutations targeted to two internal segments of the S14-coding sequence and designated these functionally critical regions as domains B and D. Further, we inferred that structural determinants within domains B and D are required for proper incorporation of the S14 protein into nascent 40 S ribosomal particles and/or for the normal function of mature cytoplasmic ribosomes. In this study we have used immunofluorescence to monitor the intracellular trafficking of epitopically labeled human S14 protein isoforms transiently expressed by cultured Chinese hamster cells. Data obtained distinguish null alleles of RPS14 which encode proteins that are not incorporated into pre-ribosomal subunit particles from null alleles whose products are compatible with normal ribosome assembly processes but result in functionally inactive cytoplasmic 40 S ribosomal subunits. Mutations assigned to the first allele class involve amino acid replacements located within S14 domains B and D; whereas mutations assigned to the second class are distributed throughout the S14 protein-coding sequence.