cssi/SciSciGPT-SciSciNet huggingface dataset:
Running in reverse: the structural basis for translocation polarity in hexameric helicases

Hexameric helicases couple ATP hydrolysis to processive separation of nucleic acid duplexes, a process critical for gene expression, DNA replication, and repair. All hexameric helicases fall into two families with opposing translocation polarities: the 3'-->5' AAA+ and 5'-->3' RecA-like enzymes. To understand how a RecA-like hexameric helicase engages and translocates along substrate, we determined the structure of the E. coli Rho transcription termination factor bound to RNA and nucleotide. Interior nucleic acid-binding elements spiral around six bases of RNA in a manner unexpectedly reminiscent of an AAA+ helicase, the papillomavirus E1 protein. Four distinct ATP-binding states, representing potential catalytic intermediates, are coupled to RNA positioning through a complex allosteric network. Comparative studies with E1 suggest that RecA and AAA+ hexameric helicases use different portions of their chemomechanical cycle for translocating nucleic acid and track in opposite directions by reversing the firing order of ATPase sites around the hexameric ring. For a video summary of this article, see the PaperFlick file with the Supplemental Data available online.
Particle size distribution from a heavy-duty diesel engine: Steady-state and transient emission measurement using two dilution systems and two fuels

Particle size distribution and number concentration were measured in the dilute exhaust of a heavy-duty diesel engine for steady-state and transient engine operation using two different dilution systems that included a full flow CVS that was coupled to an ejector pump (CVS-EP), and a double-ejector micro-dilution tunnel (DEMDT) that was connected to engine exhaust close to turbocharger outlet. Measurements were performed using a scanning mobility particle sizer (SMPS), an electrical low pressure impactor (ELPI), and a parallel flow diffusion battery (PFDB). Fuels with sulfur content of about 385 ppm and 1 ppm were used for this work. The PFDB performed well in measuring nanoparticles in the size range below 56 nm when compared with the SMPS. This was especially valid when a distinct log-normal size distribution in the size range below 56 nm in diameter, the upper size limit of the PFDB, was present. The dilution method and the sulfur content in the fuel influenced the characteristics of the size distributions significantly under both steady-state and the FTP hot-start transient cycle. The CVS-EP resulted in more particle growth and higher number of nanoparticles compared to the DEMDT. Harmonizing the measurement method of total particle number and size emissions from engines by providing a reference condition to variables such as dilution temperature, dilution rate, dilution ratio, relative humidity, dilution and transfer line residence time, will be a key next step in developing a protocol and a standard operating procedure for such measurement. Until then, different researchers will continue to produce different results in measuring total particle size and number, depending on the sampling and dilution system selected.
BEDLOAD TRANSPORT DUE TO ASYMMETRIC AND SKEWED WAVES PLUS A CURRENT

Prediction of nearshore sediment transport is a fundamental, open problem in coastal engineering. In this paper, we extend an existing model to predict bedload due to pure asymmetric and skewed waves to the case of combined waves and currents. The choice of the appropriate bed roughness to compute bedload is discussed. Predictions based on different choices of roughness are compared with available experimental data. Depending on whether a current is present or absent, agreement between predictions and measurements is obtained for a different choice of the roughness. Rather than using a different roughness parameterization for the two cases, these results suggest the necessity of revising the model that predicts the bed shear stress used in the calculation of bedload transport.
Descriptive Indicators of Future Teachers' Technology Integration in the PK-12 Classroom: Trends from a Laptop-Infused Teacher Education Program

This research examined preservice teacher graduates' positioning toward integrating technology in future teaching. Participants included 115 preservice teachers across three cohorts in 2008–2009 wh...
Life stress versus traumatic stress: The impact of life events on psychological functioning in children with and without serious illness.

OBJECTIVE To determine the differential impact of potentially traumatic events (PTEs) and other stressful life events on psychological functioning in 2 groups of children: those with cancer and those without history of serious illness. METHOD Children with cancer age 8-17 (n = 254) and age-, sex-, and race/ethnicity-matched controls (n = 142) completed self-report measures of stressful life events and psychological functioning. Stressful life events included those that may meet Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 2000) A1 criteria (PTEs; 9 events) and others that would likely not (other events; 21 events). RESULTS Children with cancer endorsed significantly more PTEs than control children. There were no differences between groups in number of other events experienced. Hierarchical regression analyses revealed that number of other events accounted for significant variance in psychological functioning, above and beyond group status, demographic factors (age and socioeconomic status), and number of PTEs. DISCUSSION The number of cumulative other events experienced is a significant predictor of psychological functioning in both youth with serious illness and controls. In contrast, cumulative PTEs appear to have a minor (albeit significant) impact on children's psychological functioning. Assessment of psychological functioning would benefit from a thorough history of stressful life events, regardless of their potential traumatic impact.
Statistical and information-theoretic optimization and performance bounds of video steganography

This paper presents a novel approach to the optimization and performance bounds of video steganography. Hypothesis testing is used to derive the probability of detection and false alarm for a cooperator with a priori knowledge of a carrier signal and an attacker for whom the carrier signal is unknown. The result is then used to optimize the statistical performance of a well-known video steganography method (i.e., secure spread spectrum watermarking) while ensuring limits on the statistical performance of video steganalysis. In addition, the channel capacity for video steganography and steganalsyis are ascertained under the proposed statistical model. It is then used to characterize an optimal information-theoretic criterion for video steganography subject to performance bounds on statistical steganalysis. Theoretical and numerical results demonstrate the consistency of both the statistical and information-theoretic approaches to the optimization of video steganography.
Surveying the Landscape of Ovarian Cancer Research and Care

On 2 March 2016, the National Academies of Science, Engineering, and Medicine released a congressionally mandated report on the state of research on ovarian cancer and its subtypes. This commentary...
Immunoreactive endothelin-1 concentrations in follicular fluid of women with and without endometriosis undergoing in vitro fertilization-embryo transfer *

Objective To determine the concentrations of immunoreactive (IR) endothelin-1 in human follicular fluid (FF) and whether IR-endothelin-1 levels are different in women with endometriosis-associated infertility. Design Follicular fluid and plasma samples, obtained from women with and without endometriosis undergoing IVF-ET, were collected at the time of oocyte aspiration and analyzed for IR-en dothelin-1 levels. Setting Infertility clinic in an academic research environment. Results Overall, 90% of FF samples and 60% of plasma samples contained IR-endothelin-1 detectable above the threshold of assay sensitivity. Immunoreactive endothelin-1 levels (mean±SEM) in FF samples from women with and without endometriosis-associated infertility were 74±12 and 37±6pg/mL, respectively. There was no difference in IR-endothelin-1 levels in FF samples between controlled ovarian hyper stimulation cycles with or without leuprolide acetate. No significant differences were detected in plasma IR-endothelin-1 levels in women with endometriosis-associated infertility when compared with those without. Conclusions These results demonstrate the presence of IR-endothelin-1 in human FF obtained at the time of oocyte aspiration for IVF-ET and higher levels of IR-endothelin-1 in FF of women with endometriosis-associated infertility.
Optimal placement and sizing of distributed generation-based wind energy considering optimal self VAR control

The impact of distributed generation (DG) units on the voltage stability has become a challenging issue especially when squirrel cage induction generator (SCIG)-based wind DGs are utilised. Optimisation methods are tools which can be used to place and size the DG units in the distribution system, so as to utilise these units optimally within certain constraints. This study aims to optimally size and allocate advanced wind energy based DG technology with innovative reactive power capability, reduced capital cost, and improved energy capture capability to improve voltage stability. Therefore, a new combination of SCIG and doubly-fed induction generator (DFIG) based DG configuration is proposed. In this configuration, the reactive power absorbed by SCIG is supplied by DFIG, and therefore, the combined system operates at unity power factor, which makes it feasible to comply with the IEEE 1547 standard. A methodology is proposed to optimally size and allocate the DG system with an objective function to improve the voltage profile considering numerous technical and economic constraints. The performance of the proposed DG configuration is compared with DGs that utilise SCIG with a parallel reactive power compensation. IEEE 30-bus test system is used to demonstrate the effectiveness of the proposed methodology.
Review: A Japanese Constellation: Toyo Ito, SANAA, and Beyond

A Japanese Constellation: Toyo Ito, SANAA, and Beyond Museum of Modern Art, New York 13 March–31 July 2016 The most significant artifact in the MoMA exhibition A Japanese Constellation: Toyo Ito, SANAA, and Beyond was not one of the sumptuous architectural models, or any of the precise orthographic drawings, but a small, hand-drawn sketch. The sketch—labeled “Toyo Ito and Surroundings,” signed by Ito himself and dated 9 September 2012—depicts a series of interesting circles, each containing the name of an architect or engineer (Figure 1). Ito places his own name in the largest circle, at the center. Around him orbit smaller circles with the names of figures who worked for or with him. Figure 1 Toyo Ito, “Toyo Ito and Surroundings,” 2012, ink on paper, 8¼ × 1111/16 inches (21 × 29.7 cm) (© Toyo Ito & Associates, Architects). Placed prominently at the entrance of the exhibition, the sketch served as both a conceptual and a practical diagram of the show. Its overlapping circles suggest relationships and connections between the architects and engineers (the names of the latter appear in circles drawn with dashed lines), de-emphasizing individuals in favor of their adjacencies and commonalities. As the exhibition's curators, Pedro Gadanho and Phoebe Springstubb, wrote in their introductory wall text, the show “maps a network of architects who gravitate around Toyo Ito (born 1941) and SANAA, the office founded in 1995 by Kazuyo Sejima and Ryue Nishizawa.” These architects include Sou Fujimoto, Akihisa Hirata, and Junya Ishigami. The text stressed the “themes that link the architects’ careers,” their shared location in and around Tokyo, and, above all, “Ito's influence as a mentor.” The constellation is …
Tribological Studies of Microelectromechanical Systems

Understanding and controlling friction in micromachine interfaces is critical to the reliability and operational efficiency of microelectromechanical systems (MEMS). The relatively high adhesion forces and friction forces encountered in these devices often present major obstacles to the design of reliable MEMS devices. Using surface micromachining, arrays of microstructures are being designed and tested to examine the adhesion characteristics, static friction behavior, and dynamic friction response. Emphasis is also being given to the control and actuation of the test structures and the modeling of the dynamic response and contact mechanics at the interface. Specifically, the purpose of the research is to fabricate and test MEMS devices in order to obtain insight into the effect of surface topography, material properties, surface chemical state, environmental conditions, and contact load on the static and dynamic characteristics of the contact interface.
Analysis of anticoagulation strategies for venous thromboembolism during severe thrombocytopenia in patients with hematologic malignancies: a retrospective cohort.

The safety and efficacy of anticoagulation for venous thromboembolism (VTE) at times of severe thrombocytopenia is unclear. In this retrospective study, we evaluated patients with hematologic malig...
STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM V. SIMULTANEOUS SERIAL PASSAGE OF THE AGENTS OF INFLUENZA A AND B IN RELATION TO VARIATIONS IN THE GROWTH CYCLE OF INFLUENZA B VIRUS

The combined passage of influenza A and B viruses in series, as reported by Sugg and Magill, has been confirmed. When the mixed passage materials were not too highly diluted both agents could be traced through 10 transfers. Growth curve experiments revealed that both agents developed independently, as measured by hemagglutination-inhibition tests in the presence of specific immune sera against one or the other type. However, the hemagglutinin titers of the 2 viruses in the mixed series were always substantially lower than those recorded when the strains were used individually as seed in the same concentrations as were employed in the mixed series. Assay of the infectivity titers of the individual strains in the presence of appropriate immune sera led to the demonstration that the time required for the growth cycle of influenza B virus varied with the dose of seed virus. With undiluted infected allantoic fluid as seed only 4 to 5 hours elapsed before new generations of virus were liberated. With increasing 10-fold dilution of the seed the constant period became increasingly longer until it stabilized at 8 to 10 hours. This finding offers an explanation for the seeming discrepancy between the observations on interference between the 2 viruses and the difference reported previously in the extent of their growth periods, on the one hand, and the fact that the 2 agents could be carried simultaneously in series through numerous passages in the chick embryo.
Supramolecular Construction of an Aldehyde–Cyclobutane via the Solid State: Combining Reversible Imine Formation and Metal–Organic Self-Assembly

A combination of metal–organic self-assembly and reversible imine formation is used to achieve an organic synthesis via the solid state. Imine bond formation is employed to install a pyridyl to the alkene trans-cinnamaldehyde while Ag(I) ions are used in a second step to assemble the pyridyl-functionalized alkene into a geometry in the solid state for an intermolecular [2 + 2] photodimerization. The alkene undergoes the cycloaddition reaction via a 1D coordination polymer to generate a pyridyl-functionalized cyclobutane stereoselectively and in quantitative yield. Removal of the pyridyl group affords the aldehyde-functionalized cyclobutane α-truxilaldehyde.
Cooperative search versus random search using UAV swarms

Abstract We analyze and compare the performance of two rival search strategies for agents searching for moving, evasive targets. One strategy is a cooperative search plan that integrates the multiple agents—unmanned aerial vehicles (UAVs) with sensors—into an advantageous formation that enhances thedetection probability while minimizing the transmission of control information for maintenance of the team topology. The second strategy employs cheaper UAVs that search independently. The performance of the two strategies is compared interms of the probability of detection and time to first detection.
Nativity, Race-Ethnicity, and Dual Diagnosis among US Adults.

Abstract This study investigated disparities in dual diagnosis (comorbid substance use and depressive/anxiety disorders) among US adults by nativity and racial–ethnic origin and socioeconomic, cultural, and psychosocial factors that may account for the observed disparities. The study drew on data from two waves of the National Epidemiological Survey on Alcohol and Related Conditions. Racial–ethnic categories included African, Asian/Pacific Islander, European, Mexican, Puerto Rican, and other Hispanic/Latino. Substance use and depressive/anxiety disorders were assessed per DSM-IV. A four-category measure of comorbidity was constructed: no substance use or psychiatric disorder; substance use disorder only; depressive/anxiety disorder only; and dual diagnosis. The data were analyzed using multinomial logistic regression. The prevalence of dual diagnosis was low but varied by nativity, with the highest rates among Europeans and Puerto Ricans born in US states, and the lowest among Mexicans and Asians/Pacific Islanders. The nativity and racial–ethnic effects on likelihood of having dual diagnosis remained significant after all adjustments. The limitations included measures of immigrant status, race–ethnicity, and stress and potential misdiagnosis of mental disorder among ethnic minorities. This new knowledge will help to guide public health and health care interventions addressing immigrant mental and behavioral health gaps. This study addressed the research gap in regard to the prevalence and correlates of dual diagnosis among immigrants and racial–ethnic minorities. The study used the most current and comprehensive data addressing psychiatric conditions among US adults and examined factors rarely captured in epidemiologic surveys (e.g., acculturation).
Computer Aided Control System Design for Time Delay Systems using MATLAB

Computer Aided Control System Design (CACSD) allows to analyze complex interconnected systems and design controllers achieving challenging control requirements. We extend CACSD to systems with time delays and illustrate the functionality of Control System Toolbox in MATLAB for such systems. We easily define systems in time and frequency domain system representations and build the overall complex system by interconnecting subsystems. We analyze the overall system in time and frequency domains and design PID controllers satisfying design requirements. Various visualization tools are used for analysis and design verification. Our goal is to introduce these functionalities to researchers and engineers and to discuss the open directions in computer algorithms for control system design.
Association of body size metrics with left atrial phasic volumes and reservoir function in the elderly

Aims General obesity, defined by increased body mass index (BMI), is associated with left atrial (LA) enlargement, a marker of cardiovascular risk in the general population. The association between abdominal adiposity, defined by increased waist circumference (WC) or waist-to-hip ratio (WHR), and LA phasic volumes and reservoir function is not well known. The aim of this study was to evaluate the association between different body size metrics and LA phasic volumes and reservoir function in the elderly. Methods and results Participants from the CABL (Cardiovascular Abnormalities and Brain Lesions) study underwent measurement of BMI, WC, and WHR. The LA maximum (LAVmax) and minimum (LAVmin) volumes, and LA reservoir function, measured as total emptying volume index (LAEVI), total emptying fraction (LAEF), and expansion index (LAEI), were assessed by real-time 3D echocardiography. The study population included 629 participants (mean age 71 ± 9 years, 61% women). Mean BMI was 27.9 ± 4.6 kg/m2, WC was 95.0 ± 11.7 cm, WHR was 0.91 ± 0.08. After adjusting for multiple potential confounders (demographics, cardiovascular risk factors, left ventricular mass index, and diastolic function), higher WC was significantly associated with higher LA phasic volumes (LAVmax, β = 0.10, P = 0.007 and LAVmin, β = 0.12, P = 0.002) and reduced reservoir function (LAEVI, β = -0.15, P = 0.001 and LAEI, β = -0.09, P = 0.027). WHR was significantly associated only with reduced reservoir function (LAEVI, β = -0.11, P = 0.012), whereas BMI was not associated with either LA phasic volumes or reservoir function. Conclusion In the elderly, WC may have more impact on LA phasic volumes and reservoir function, and therefore risk for cardiovascular events, than WHR and BMI.
Abstract P244: MicroRNAs Implicated in Angiogenesis Are Upregulated in Lower Extremity Peripheral Artery Disease (PAD): the San Diego Population Study (SDPS)

Introduction: Lower extremity PAD affects approximately 9 million people in the US. However, the genetic factors underlying PAD remain elusive. MicroRNAs are short non-coding RNA segments that regu...
A WBG based three phase 12.5 kW 500 kHz CLLC resonant converter with integrated PCB winding transformer

The three phase resonant converter gains its popularity in high power areas like off-board charger due to its ability to reduce the current stress on devices and achieve higher efficiency. However, very few takes this advantage for the transformer integration to reduce the size of the magnetic components. In addition, by using wide-band-gap devices, the switching frequency of power electronics converters can be pushed to a much higher level, making it possible to implement Printed Circuit Board (PCB) transformer. In this paper, a novel 6-layer only PCB winding transformer is proposed for a three phase CLLC resonant converter. Not only all the resonant inductors are integrated into the transformer, but also the three phase transformers are integrated together so that the size of the magnetic component is significantly reduced. A 12.5 kW 500 kHz hardware prototype with over 97.3% efficiency and 155 W/in3 power density is built to verify the feasibility of the proposed structure.
STATIC AND KINETIC SITE-SPECIFIC PROTEIN-DNA PHOTOCROSSLINKING: ANALYSIS OF BACTERIAL TRANSCRIPTION INITIATION COMPLEXES

Static site-specific protein-DNA photocrosslinking permits identification of protein-DNA interactions within multiprotein-DNA complexes. Kinetic site-specific protein-DNA photocrosslinking--involving rapid-quench-flow mixing and pulsed-laser irradiation--permits elucidation of pathways and kinetics of formation of protein-DNA interactions within multiprotein-DNA complexes. We present detailed protocols for application of static and kinetic site-specific protein-DNA photocrosslinking to bacterial transcription initiation complexes.
Immunosuppression by Human and Feline Retroviruses

Among retroviruses which infect several species including humans, to date two groups have been firmly linked with immunodeficiency in addition to leukemia: feline leukemia viruses and human T-cell leukemia viruses. A mutant strain of HLTV is suspected to play a key etiological role in the development of the acquired immune deficiency syndrome (AIDS).
Thermal, mixing, and oxygen regimes of the Salton Sea, California, 1997–1999

The Salton Sea is a shallow (mean depth = 8 m; maximum depth = 15 m), saline (41–45 g 1−1), intermittently mixing, 57 km long, 980 km2 lake located in the arid southwestern United States. The Sea is a wind driven system, with predominant winds paralleling the long axis of the lake, being strongest in spring and weakest in summer and fall. The Sea mixed daily or nearly daily between September and January. During this cooling period, moderate to high levels of dissolved oxygen (3–11 mg 1−1) were found throughout the water column. Mean water column temperature ranged from a minimum of 13–14 °C in early January to a maximum of 30–34 °C in July—September. During most of this warming period, the Sea was thermally stratified but subject to periodic wind driven mixing events. Winds were stronger in spring 1998 than in 1997 or 1999, causing more rapid heating of the lake that year and also delaying onset of anoxic conditions in bottom waters. During summer months, mid-lake surface waters were sometimes supersatured with oxygen, and bottom waters were hypoxic or anoxic with sulfide concentrations > 5 mg 1−1. Oxic conditions (> 1 mg O2 1−1) often extended a few meters deeper nearshore than they did well offshore as a consequence of greater mixing nearshore. Mixing events in late summer deoxygenated the entire water column for a period of days. Consumption of oxygen by sulfide oxidation likely was the principal mechanism for these deoxygenation events. Sulfide concentrations in surface waters were 0.5–1 mg 1−1 approximately 3 days after one mixing event in mid-August 1999. These mixing events were associated with population crashes of phytoplankters and zooplankters and with large fish kills. In the southern basin, freshwater inflows tended to move out over the surface of the Sea mixing with saline lake water as a function of wind conditions. Salinity gradients often contributed more to water column stability than did thermal gradients in the southeasternmost portion of the lake.
Strongly positive representations of GSpin_{2n+1} and the Jacquet module method

We explicitly construct the structure of Jacquet modules of parabolically induced representations of \(GSpin_{2n+1}\) over a \(p\)-adic field \(F\) of any characteristic. Using this construction of the Jacquet module, we obtain a classification of strongly positive representations of \(GSpin_{2n+1}\) over \(F\) and describe the general discrete series representations of \(GSpin_{2n+1}\) over \(F\), assuming the half-integer conjecture. One application of this paper is the proof of the equality of \(L\)-functions from the Langlands–Shahidi method and Artin \(L\)-functions through the local Langlands correspondence (Kim in Langlands–Shahidi \(L\)-functions for \(GSpin\) groups and the generic Arthur packet conjecture, preprint).
Outcome of mismatch repair deficient metastatic colorectal cancer (CRC): The Mayo Clinic Experience.

e15030Background: Deficiencies in the DNA mismatch repair (dMMR) system cause errors during DNA replication, which in turn give rise to microsatellite instability (MSI-H). MSI-H in mCRC is rare and...
Characterization of Graphene Conductance Using a Microwave Cavity

Surface conductance of graphene films is investigated in a non-contact microwave cavity operating at 7.4543 GHz. This cavity technique characterizes specimens with high accuracy, without disruption of morphological integrity and without the processing required for definition and application of electrical contacts. The thickness of the conducting 2D material does not need to be explicitly known. Measurement results are illustrated for epitaxial mono-layer graphene formed on 4H-SiC(OOOl) wafers by annealing the substrate via high fidelity Si sublimation. We show that the resonant microwave cavity is sensitive to the surface conductance of atomically thin nano-carbon films. The method is applied to characterize diffusion of water through a thin film moisture barrier coated over epitaxial monolayer graphene. The monolayer graphene is lightly n-type doped and therefore the resulting surface resistance value becomes sensitive to complexation with p-type molecular dopants such as water in moisturized air. Our results suggest that coating graphene surface with 100 nm thick Parylene-C film serves as effective moisture barrier. The observed change in conductance of Parylene-C specimens after environmental stress is within 6% of the pre-test value and would satisfy the typical reliability requirements.
Type VI Secretion Systems and the Gut Microbiota

The human colonic microbiota is a dense ecosystem comprised of numerous microbes, including bacteria, phage, fungi, archaea, and protozoa, that compete for nutrients and space. Studies are beginning to reveal the antagonistic mechanisms that gut bacteria use to compete with other members of this ecosystem. In the healthy human colon, the majority of the Gram-negative bacteria are of the order Bacteroidales. Proteobacteria, such as Escherichia coli, are numerically fewer but confer important properties to the host, such as colonization resistance. Several enteric pathogens use type VI secretion systems (T6SSs) to antagonize symbiotic gut E. coli, facilitating colonization and disease progression. T6SS loci are also widely distributed in human gut Bacteroidales, which includes three predominant genera: Bacteroides, Parabacteroides, and Prevotella. There are three distinct genetic architectures of T6SS loci among the gut Bacteroidales, termed GA1, GA2, and GA3. GA1 and GA2 T6SS loci are contained on integrative and conjugative elements and are the first T6SS loci shown to be readily transferred in the human gut between numerous species and families of Bacteroidales. In contrast, the GA3 T6SSs are present exclusively in Bacteroides fragilis. There are divergent regions in all three T6SS GAs that contain genes encoding effector and immunity proteins, many of which function by unknown mechanisms. To date, only the GA3 T6SSs have been shown to antagonize bacteria, and they target nearly all gut Bacteroidales species analyzed. This review delves more deeply into properties of the T6SSs of these human gut bacteria and the ecological outcomes of their synthesis in vivo.
The Chd1 chromatin remodeler forms long-lived complexes with nucleosomes in the presence of ADP·BeF3- and transition state analogs.

Chromatin remodelers use helicase-like ATPase domains to reorganize histone–DNA contacts within the nucleosome. Like other remodelers, the chromodomain helicase DNA-binding protein 1 (Chd1) remodeler repositions nucleosomes by altering DNA topology at its internal binding site on the nucleosome, coupling different degrees of DNA twist and DNA movement to distinct nucleotide-bound states of the ATPase motor. In this work, we used a competition assay to study how variations in the bound nucleotide, Chd1, and the nucleosome substrate affect stability of Chd1–nucleosome complexes. We found that Chd1–nucleosome complexes formed in nucleotide-free or ADP conditions were relatively unstable and dissociated within 30 s, whereas those with the nonhydrolyzable ATP analog AMP-PNP had a mean lifetime of 4.8 ± 0.7 min. Chd1–nucleosome complexes were remarkably stable with ADP·BeF3− and the transition state analogs ADP·AlFX and ADP·MgFX, being resistant to competitor nucleosome over a 24-h period. For the tight ADP·BeF3−–stabilized complex, Mg2+ was a critical component that did not freely exchange, and formation of these long-lived complexes had a slow, concentration-dependent step. The ADP·BeF3−–stabilized complex did not require the Chd1 DNA-binding domain nor the histone H4 tail and appeared relatively insensitive to sequence differences on either side of the Widom 601 sequence. Interestingly, the complex remained stable in ADP·BeF3− even when nucleosomes contained single-stranded gaps that disrupted most DNA contacts with the guide strand. This finding suggests that binding via the tracking strand alone is sufficient for stabilizing the complex in a hydrolysis-competent state.
Cellular heterogeneity in brown adipose tissue

Brown adipose tissue (BAT) contains mitochondria-enriched thermogenic fat cells (brown adipocytes) that play a crucial role in the regulation of energy metabolism and systemic glucose homeostasis. It was presumed that brown adipocytes are composed of a homogeneous cell population. In this issue of the JCI, however, Song and colleagues report a previously uncharacterized subpopulation of brown adipocytes that display distinct characteristics from the conventional brown adipocytes in their molecular signature, regulation, and fuel utilization. The present study provides novel insight into our understanding of cellular heterogeneity in adipose tissues.
Outpatient surgery is the solution at hand for reducing costs and hospital stays for pediatric surgery too: a hospital trial.

BACKGROUND Outpatient management has proven to be the most useful method of treatment for various minimally complex surgical specialties compared to day-hospital management or ordinary inpatient processes, a fact confirmed by numerous technical documents and works in the literature. METHODS We analyzed 27,713 surgical interventions carried out in our hospital between 2005 and 2017. This analysis included all interventions for which the indication of the level of care has moved, over the years, to an outpatient setting. We evaluated the direct costs of these services, comparing them by year and by treatment setting. RESULTS From the analysis of costs in general, for the same number of services, a reduction of 56.6% can be seen in the comparison between 2005 and 2017. In addition, the analysis of the length of stay shows an average reduction in the number of days of hospitalization from 2.9 to 1.2 between 2005 and 2017. On the basis of a large quantity of data, our study confirms that outpatient surgery can have a significant impact in reducing costs and days of hospitalization, even in a pediatric setting, demonstrating that it is the best choice in terms of saving resources and, above all, clinical and organizational appropriateness. CONCLUSIONS Outpatient surgery is in fact a valuable solution that provides an advantage for both the patient and his/her family, especially in the pediatric field, for the hospital and more generally for the health system as a whole.
Segmentation of stem cell colonies in fluorescence microscopy images with transfer learning

We evaluate the use of TernausNet V2, a pre-trained VGG-16 U-net for segmentation of Green Fluorescent Protein (GFP) stained stem cells from giga pixel fluorescence microscopy images. Fluorescence microscopy is a difficult modality for automated stem cell segmentation algorithms due to high noise and low contrast. As such segmentation algorithms for cell counting and tracking typically yield more consistent results in other imaging modalities such as Phase Contrast (PC) microscopy due to greater ability to distinguish between foreground and background. Recent methods have shown that U-net based models can achieve state-of-the-art segmentation performance of GFP microscopy, although all available methods continue to overly segment the protein features and have difficulty capturing the entirety the cell. We investigate the use of TernausNet, a VGG-16 based U-Net architecture that was pre-trained from ImageNet and show that it is able to improve the accuracy of GFP stem cell segmentation on gigascale NIST fluorescence microscopy images in comparison to a baseline U-net model. Quantitative results show that the proposed TernausNet V2 architecture model is able to better distinguish the entire region of the cell and reduce overly segmenting proteins as compared to U-net. TernausNet achieved greater accuracy with ROC AUC of 0.956 and F1-Score of 0.810 as compared to the baseline U-net with AUC 0.936 and F1-Score 0.775. Therefore, we suggest that the TernausNet V2 architecture with transfer learning improves the performance of stem-cell segmentation is able to outperform U-net models for the segmentation of giga pixel GFP stained fluorescence microscopy images.
Instability in the Setting of Distal Radius Fractures: Diagnosis, Evaluation, and Treatment

Distal radius fractures with severe displacement or concomitant triangular fibrocartilage complex tears may be accompanied by distal radioulnar joint instability. Clinicians should examine the distal radioulnar joint closely when managing wrist fractures and treat coexisting instability appropriately. Chronic instability from distal radius malunion may require osteotomy or radioulnar ligament reconstruction. With proper management, most patients recover forearm stability and rotational motion after distal radius fracture.
Holographic particle localization using beam propagation method

We present a novel method for large-scale 3D particle localization from single-shot in-line holography using a multiple-scattering based multi-slice beam propagation model.
Surgical Management of Sialorrhea: A Systematic Review and Meta-analysis:

ObjectiveChronic sialorrhea commonly occurs in patients with neurodevelopmental disorders. While conservative management can provide sufficient symptom control, surgical intervention is often requi...
Psychological Interventions and Pharmacology

There exists a clear link between depression and pain and use of anti-depressants has resulted in an understanding of the pain-relieving effects of these medications. Further, non-pharmacologic psychological interventions remain a mainstay in treating psychological conditions in the pain patient. Consisting of drugs from multiple categories including serotonin-selective reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs) among others, anti-depressants have variable amount of relief from pain that must be balanced with adverse effects with these medications and various drug-drug interactions. Knowledge of this area is key not only for the board exam but for clinical practice. Questions regarding medications will be present throughout the text, not limited to this chapter alone which focuses more on non-pharmacologic treatments.
Ecology: Fungal Mimics Dupe Animals by Transforming Plants.

Summary Many fungi transform host tissues to benefit their own reproduction. A recent study investigates a fungus that converts its plant host’s reproductive tissues into ornate flower mimics. These ‘pseudoflowers’ present complex cues that may enlist insects to facilitate fungal dispersal.
Relationships between type 2 diabetes, cell dysfunction, and redox signaling: A meta-analysis of single-cell gene expression of human pancreatic α-and β-cells.

Background Type 2 diabetes (T2D) is a chronic disease characterized by insulin resistance and failure of β-cells to meet the metabolic demand for insulin. Recent advances in single-cell RNA sequencing (sc-RNA-Seq) have allowed for in depth studies to further understand the underlying cellular mechanisms of T2D. In β-cells, redox signaling is critical for insulin production. A meta-analysis of human pancreas islet sc-RNA-Seq data was conducted to evaluate how T2D may modify the transcriptomes of α-and β-cells. Methods Annotated sc-RNA-Seq data from 6 studies of human pancreatic islets from metabolically healthy and donors with T2D were collected. α- and β-cells, subpopulations of proliferating α-cells, immature, and senescent β-cells were identified based on expression levels of key marker genes. Each dataset was analyzed individually, before combining using weighted comparisons. Pathways of significant genes and individual redox-related gene expression was then evaluated to further understand the role that redox signaling may play in T2D-induced β-cell dysfunction. Results α- and β-cells from T2D donors modified genes involved in energy metabolism, immune response, autophagy, and cellular stress. α- and β-cells also had an increased nuclear factor-erythroid factor 2-related factor 2 (NFE2L2)-mediated antioxidant response in T2D donors. The proportion of immature and senescent β-cells increased in T2D donors, and in immature and senescent β-cells, genes regulated by NFE2L2 were further upregulated. Conclusions These findings suggest that NFE2L2 plays a role in β-cell maturation and dysfunction. Redox singling maybe a key pathway for β-cell restoration and T2D therapeutics. This article is protected by copyright. All rights reserved.
ACTH/ß-ENDORPHIN IN EXTRAPITUITARY TISSUES

Reports of hormonal polypeptides in various tissues of vertebrate species have burgeoned in recent years. These substances have been found not only in their classical locations, e.g. ACTH in the pituitary gland, but also in other endocrine and non-endocrine tissues, principally in the nervous system and the gastrointestinal tract. The evidence for the presence of these substances in non-classical sites has rested primarily on radioimmunoassay of tissue extracts or immunocytochemistry, but recent information supports the conclusion that in many cases the hormone (or related peptide) is synthesized in the tissue rather than deposited there. Table 1 lists some types of experimental data that can be brought to bear on the question of production of polypeptides in non-pituitary tissues. With respect to the question of ACTH/β-endorphin and related peptides in the nervous system nearly all of the listed studies have been reported. While final proof of the existence of ACTH (i.e. confirmation of chemical structure) has not yet been forthcoming, the cumulative evidence for synthesis in the nervous system is now quite compelling. On the other hand, it is much less clear that ACTH and related peptides are synthesized in the gastrointestinal tract. In this report we summarize presently available evidence for ACTH/β-endorphin existence and synthesis in nervous system and gastrointestinal tract.
Lumbar Herniated Nucleus Pulposus

This chapter will discuss the pathophysiology, exam, diagnosis, and management of lumbar disc herniation (LDH). In brief, LDH is a common pathology that will affect a significant portion of the population. The natural history of LDH is favorable, and excellent results have been obtained with conservative management. Both physical therapy and epidural steroid injections play a role in nonoperative treatment. Recent data, notably the large-scale SPORT trials, suggest that patients managed with discectomy may have a more favorable outcome when compared to conservative treatment. A “mini-open” technique is the most common modality of discectomy performed; however, minimally invasive approaches are gaining popularity. Percutaneous discectomies should be avoided as they have less favorable outcomes. Use of a tubular retractor system typifies the modern minimally invasive approach. A number of randomized controlled trials comparing open discectomy to minimally invasive microdiscectomy have been performed. A pooled analysis of these trials demonstrates that both techniques seem to be equally effective at relieving pain and have comparable reherniation rates. Overall complication rates are similar between open and minimally invasive approaches; however, there number of incidental durotomies is higher with minimally invasive approaches. Minimally invasive approaches offer the potential benefit of less soft tissue trauma and faster recovery; however, they are technically demanding. Excellent results can be obtained with either a minimally invasive or open approach.
Effects of Stroke on the Autonomic Nervous System

Stroke is the fourth leading cause of death in the United States and the second most common cause of death worldwide; stroke is also the leading cause of long-term disability worldwide. It is clear that the consequences of cerebral ischemia reach beyond the brain into the periphery, and a significant number of stroke related deaths are the result of conditions that develop poststroke in the periphery. The two leading causes of non-neurogenic death poststroke are cardiac abnormalities and infections. Changes in autonomic nervous system function that favor increased sympathetic nervous system activity and reduced parasympathetic nervous system activity appear to be causative factors in both conditions. Here, we review the evidence that sympathetic nervous system activity increases and parasympathetic nervous system activity declines poststroke. We discuss effects of autonomic dysfunction on cardiac arrhythmias and heart rate variability. Finally, we discuss the evidence supporting a role for autonomic dysfunction in the increased incidence of infection poststroke. Although the death rate from stroke is declining in the United States, the incidence of stroke is not. With more patients surviving the initial ischemic event it is important that we broaden our understanding of the chronic effects of stroke on the human condition.
Activation of the leu-500 promoter by adjacent transcription.

Abstract The leu-500 mutation is an A-to-G point mutation in the -10 region of the promoter controlling the leuABCD operon of Salmonella typhimurium. Suppression of the leu-500 mutation in an S. typhimurium topA mutant has demonstrated the functional dependency of this mutated promoter on negative supercoiling. A plasmid bearing a minimal leu-500 promoter region (positions -80 to +87) failed to restore its expression in the S. typhimurium topA mutant. We showed that transcription-mediated local negative supercoiling can activate the leu-500 promoter on a plasmid. The coupled transcription and translation process is required for this activation, but peptide-mediated membrane anchorage may not be involved in this activation. Although the effect of negative supercoiling generated during transcription away from the promoter is limited to a short distance of 250 bp, it can activate the negative-supercoiling-dependent leu-500 promoter from positions either 5' or 3' of the leu-500 promoter. In the presence of a parallel-oriented lac promoter which transcribed away from the 3' end of the leu-500 promoter, transcriptional activation of the leu-500 promoter is a strong indication of cooperativity during the transcriptional initiation process.
Correlation of ultrastructural aberrations with dysplasia and flow cytometric abnormalities in Barrett's epithelium.

Barrett's esophagus develops as a complication of chronic gastroesophageal reflux and predisposes patients to the development of dysplasia and adenocarcinoma of the esophagus. Because light microscopy of dysplasia in Barrett's esophagus shows diminished or absent mucus, we used transmission electron microscopy to compare cytoplasmic organelles required for mucus production in dysplastic and nondysplastic esophageal columnar epithelium. These observations of the rough endoplasmic reticulum, Golgi apparatus, and secretory granules were correlated with histologic interpretations and flow cytometric measurements of abnormalities of DNA content. Ultrastructural abnormalities included depletion and alteration of organelles required for mucus biosynthesis. These abnormalities often were accompanied by cells with markedly distended rough endoplasmic reticulum and massive accumulation of cytoplasmic glycogen aggregates. All 9 patients who had Barrett's dysplasia with or without early adenocarcinoma had ultrastructural abnormalities, as did 3 of 8 patients whose biopsy histology was indefinite for dysplasia. Abnormalities measured by flow cytometry correlated well with the presence of these ultrastructural aberrations. All 9 patients with Barrett's dysplasia with or without early adenocarcinoma had abnormalities observed by electron microscopy and aneuploidy or increased G2ltetraploid fractions measured by flow cytometry. Two of the 3 patients whose biopsies were indefinite for dysplasia and who had ultrastructural abnormalities also had aneuploidy or increased G 2 /tetraploid fractions. Neither ultrastructural nor flow cytometric abnormalities were found in the remaining 5 patients whose biopsies were indefinite for dysplasia, in 19 of 22 patients with Barrett's specialized metaplasia, or in any of the 7 patients with gastroesophageal reflux disease without Barrett's specialized meta plasia. Two of the 22 patients with Barrett's specialized metaplasia had distended rough endoplasmic reticulum in rare cells, and one other had an aneuploid cell population. We conclude that neoplastic progression in Barrett's esophagus is associated with abnormalities of cytoplasmic organelles required for mucus production. With few exceptions, these ultrastructural aberrations correspond to the presence of dysplasia or of aneuploidy or increased G 2 /tetraploid fractions. Electron microscopy and flow cytometry detect abnormalities associated with the development of dysplasia and cancer in Barrett's esophagus that may be biologically significant.