cssi/SciSciGPT-SciSciNet huggingface dataset:
TRACE LEVEL DETERMINATION AND QUANTIFICATION OF POTENTIAL GENOTOXIC IMPURITIES IN DASATINIB DRUG SUBSTANCE BY UHPLC/INFINITY LC

Objective: A simple, cost-effective and mass compatible ultra-high fast performance liquid chromatographic (Agilent-Infinity LC 1290) method has been developed and validated for the determination of potentially genotoxic impurities in dasatinib active pharmaceutical ingredients. Methods: This method comprises the determination of three possible genotoxic impurities in dasatinib. The mobile phase is trifluoroacetic acid, acetonitrile and water with linear gradient elution curve number 6. The column used for the development and validation is zorbax RRHD eclipse plus C18 with the length of 50 mm, the internal diameter of 2.1 mm and particle size of 1.8 microns. Results: The limit of detection of the potential genotoxic impurities are less than 0.1 µg/ml with respect to dasatinib test concentration of 1000 µg/ml. The limit of quantification of the potential genotoxic impurities is less than 0.3 µg/ml with respect to dasatinib test concentration of 1000 µg/ml. Conclusion: This method has been validated as per ICH guidelines Q2 (R1). These three potential mutagenic impurities are not degradant impurities of dasatinib and its only process related impurities. The method development has been approached using the QbD principle.
Feature-locked loop and its application to image databases

We present a new dynamical system called the "feature-locked loop". The inputs to this feedback neural network are a set of feature vectors and a one-parameter function that characterizes the data. We show that the feature-locked loop is locally stable for one example of the characteristic function and determines the value of its unknown parameter. We apply this property of the feature-locked loop to the problem of sorting textures by their similarity. We use the feature-locked loop and a priori information to quantify the degree of similarity between the input image and the reported set of image as a whole. The prior knowledge is encoded in the form of the one-parameter function and a general assumption about the number of perceptual outliers in the reported set. The unknown parameter, computed by the feature-locked loop, is then related to the entire set of image features produced by the retrieval.
An Application Development Platform for neuromorphic computing

Dynamic Adaptive Neural Network Arrays (DANNAs) are neuromorphic computing systems developed as a hardware based approach to the implementation of neural networks. They feature highly adaptive and programmable structural elements, which model artificial neural networks with spiking behavior. We design them to solve problems using evolutionary optimization. In this paper, we highlight the current hardware and software implementations of DANNA, including their features, functionalities and performance. We then describe the development of an Application Development Platform (ADP) to support efficient application implementation and testing of DANNA based solutions. We conclude with future directions.
Writing Process Products in Intermediate-Grade Children With and Without Language-Based Learning Disabilities.

Purpose Difficulties with written expression are an important consideration in the assessment and treatment of school-age children. This study evaluated how intermediate-grade children with and wit...
Analytical and Numerical Characterization of Autocorrelation and Perturbation-Correlation Moving-Window Methods

Moving-window (MW) approaches to two-dimensional correlation spectroscopy (2D-COS) make it possible to characterize spectral changes occurring in a narrow range of perturbation variable (e.g., time, temperature, and concentration). Despite the wide range of application, the physical meanings of MW correlation intensities have been only qualitatively associated with the direction and curvature of spectral intensity change with regard to a perturbation variable. Here are full and simplified analytical expressions of autocorrelation moving-window (ACMW) and synchronous and asynchronous perturbation-correlation moving-window ( s-PCMW and as-PCMW) intensities. When the window is set sufficiently narrower than the bandwidth of spectral change, the square root of ACMW intensity and s-PCMW intensity becomes proportional to the first order derivative, and as-PCMW intensity becomes proportional to the negative of the second order derivative. This paper demonstrates that both ACMW and PCMW profiles can be significantly altered by non-uniform perturbation spacing. It is also found that intensity noise can cause ACMW to display a false offset drift. This analytical and numerical characterization of the two MW correlation intensities elucidates their physical meanings and ascertains the analysis conditions for reliable interpretation.
Equidistributed icosahedral configurations on the sphere

Abstract We present and analyze a new sequence of equidistributed icosahedral configurations. These configurations are created by combining the ( m , n ) icosahedral nodes of Caspar and Klug and adapting the azimuthal projection method of Snyder to create a low deformation equal area mapping from the regular icosahedron to S 2 . We prove an upper bound on the mesh ratio of these configurations and analyze numerically the Riesz potential energies of the point sets of size N 50 , 000 .
State Probabilities and Fluxes in Terms of the Rate Constants of the Diagram

The basic principles of free energy transduction were introduced in Chapter 1. Steady-state probabilities and especially forces and fluxes played a prominent role in the discussion. One important topic was bypassed, however, which is covered in the present chapter: How are the state probabilities and the fluxes related to the firstorder rate constants of α ij of the kinetic diagram? This subject does not add much to the general concept of free energy transduction per se, but it is essential to an understanding of the steady-state kinetic activity of the cyclic system that carries out the free energy transduction. Section 6 deals with state probabilities (and fluxes in very simple systems) and Section 7 is concerned with fluxes and related kinetic topics. Section 8 is essentially an appendix on recent and more advanced topics related to cycles and diagrams.
Perception Updating Networks: On architectural constraints for interpretable video generative models

We investigate a neural network architecture and statistical framework that models frames in videos using principles inspired by computer graphics pipelines. The proposed model explicitly represents "sprites" or its percepts inferred from maximum likelihood of the scene and infers its movement independently of its content. We impose architectural constraints that forces resulting architecture to behave as a recurrent what-where prediction network.
Stress modeling to determine the through-going active fault geometry of the Western North Anatolian Fault, Turkey

The North Anatolian Fault (NAF) is a 1200 km long dextral strike-slip fault which is part of an east-west trending dextral shear zone (NAF system) between the Anatolian and Eurasian plates. The North Anatolian shear zone widens to the west, complicating potential earthquake rupture paths and highlighting the importance of understanding the geometry of active fault systems. In the central portion of the NAF system, just west of the town of Bolu, the NAF bifurcates into the northern and southern strands, which converge, then diverge to border the Marmara Sea. At their convergence east of the Marmara Sea, these two faults are linked through the Mudurnu Valley. The westward continuation of these two fault traces is marked by further complexities in potential active fault geometry, particularly in the Marmara Sea for the northern strand, and towards the Biga Peninsula for the southern strand. Potential active fault geometries for both strands of the NAF are evaluated by comparing stress models of various fault geometries in these regions to a record of focal mechanisms and inferred paleostress from a lineament analysis. For the Marmara region, the best-fit active fault geometry consists of the northern and southern bounding faults of the Marmara basin, as the model representing this geometry better replicated primary stress orientations seen in focal mechanism data and stress field interpretations. In the Biga Peninsula region, the active geometry of the southern strand has the southern fault merging with the northern fault through a linking fault in a narrow topographic valley. This geometry was selected over the other two as it best replicated the maximum horizontal stresses determined from focal mechanism data and a lineament analysis.
Small Cell Tumors of Bone

Bone tumors are fortunately rare, but small cell tumors of bone are a relatively common subset of these lesions. They comprise of a diverse group of primary and metastatic neoplasms in both children and adults. The most common small cell tumors of bone include Ewing sarcoma/primitive neuroectodermal tumor, small cell osteosarcoma, multiple myeloma, lymphoma, leukemia, neuroblastoma, rhabdomyosarcoma, and Langerhans cell histiocytosis. Although each entity has its distinctive features, the differential diagnosis of this group of tumors is still challenging because they are all "small, blue, and round cell tumors", histologically. The correct diagnosis of small cell tumors of bone depends on an evaluation of clinical, radiologic, pathologic, and genetic features. Patients' age and sex are very important, as are the signs and symptoms at presentation. Radiologically, which bone is involved, the specific portion of the bone (epiphysis, metaphysis, or diaphysis; cortex vs. medulla) involved, and the radiographic manifestations (lytic, blastic, or mixed lytic and blastic) are also often critical parameters for the diagnosis. In recent years, with a better understanding of the molecular and cytogenetic background of several small cell tumors, more accurate diagnoses have been supported by the clinicopathologic criteria and by a panel of immunohistochemical studies. In this review we will provide an overview of the clinical, radiologic, pathologic, and genetic characteristics of these tumors.
Interpersonal Psychotherapy and Mindfulness for Treatment of Major Depression With Anxious Distress

This single case study examined symptom change in the treatment of a 22-year-old Caucasian female college student presenting with anxious and depressive symptoms and maladaptive coping strategies i...
Factors associated with nurses' perceptions, self-confidence, and invitations of family presence during resuscitation in the intensive care unit: A cross-sectional survey.

Abstract Background Family presence during resuscitation is not widely implemented in clinical practice. Prior research about nurse factors that may influence their decision to invite family members to remain in the room during resuscitation is contradictory and inconclusive. Objectives To describe intensive care unit nurses’ perceptions, self-confidence, and invitations of family presence during resuscitation, and to evaluate differences according to nurse factors. Design A cross-sectional survey design was used for descriptive and correlational analyses. Setting Data collection occurred online. Participants A convenience sample of 395 nurses working in intensive care units across the United States was obtained. Methods Participants completed a survey to collect personal, professional, and workplace information. The Family Presence Risk-Benefit Scale and Family Presence Self-confidence Scale were administered, and frequency of inviting family members to be in the room during resuscitation was collected by self-report. Following descriptive analysis of univariate distributions, a series of hierarchical OLS regression analyses was used to identify which personal, professional, or workplace factors yielded the largest unique impact on nurse perceptions, self-confidence, and invitations of family presence during resuscitation. Results Despite high frequency of performing resuscitative care, one-third of participants had never invited family members to be in the room during resuscitation during their careers, and another 33% had invited family members to be present just 1–5 times. Having had clinical experience with family presence during resuscitation was the strongest predictor of positive perceptions, higher self-confidence, and increased invitations. In addition, having received education on family presence during resuscitation and a written facility policy were found to be key professional and workplace predictors of perceptions and invitations. Conclusions Nurses who work in a facility with a policy on family presence during resuscitation, are educated on it, and have experienced it in the clinical setting are more likely to have positive perceptions and higher self-confidence, and to invite family members to be in the room during resuscitation with increased frequency. Nurses in leadership roles should create policies for their units and provide education to nurses and other healthcare providers. Due to the apparent importance of clinical experience with family presence during resuscitation, it is recommended to initially provide this experience using simulation and role modeling.
Patients Undergoing Parastomal Hernia Repair Using the Americas Hernia Society Quality Collaborative: A Prospective Cohort Study.

Background Parastomal hernia is the most common complication after stoma creation. It can create significant morbidity and is associated with a lower quality of life. Current parastomal hernia repair techniques and outcomes are not well characterized. We aimed to describe patient characteristics, operative techniques, and outcomes of patients undergoing parastomal hernia repair. Study design Patients in the Americas Hernia Society Quality Collaborative (AHSQC) ≥18 years old, who underwent parastomal hernia repair were identified. Descriptive statistics were performed for patient demographics, preoperative characteristics, operative details, 30-day follow-up, and patient-reported outcomes. The surgical techniques used in parastomal hernia repair and postoperative outcomes were described, and predictors of open vs minimally invasive surgery (MIS) and type of mesh used were analyzed. Results We identified 672 patients in the AHSQC who underwent parastomal hernia repair between 2013 and Nov 2017. Almost all operations were elective, 22% of patents had their stoma reversed, and 94% of repairs used mesh. Elective status and surgeon practice type were associated with use of synthetic mesh. A surgeon's preference for MIS, defect size, and age were associated with use of an MIS approach. Quality of life scores improved for patients who completed a postoperative questionnaire. Conclusions This is the first multi-institutional report of parastomal hernia repair using prospective data complete with operative details. Parastomal hernia repair remains a difficult operation without a clear best practice. Multiple factors appear to influence operative approach. Surgical treatment may improve quality of life at 6 to 12 months postoperatively.
Breast Cancer Diagnosis in Digital Breast Tomosynthesis: Effects of Training Sample Size on Multi-Stage Transfer Learning Using Deep Neural Nets

In this paper, we developed a deep convolutional neural network (CNN) for the classification of malignant and benign masses in digital breast tomosynthesis (DBT) using a multi-stage transfer learning approach that utilized data from similar auxiliary domains for intermediate-stage fine-tuning. Breast imaging data from DBT, digitized screen-film mammography, and digital mammography totaling 4039 unique regions of interest (1797 malignant and 2242 benign) were collected. Using cross validation, we selected the best transfer network from six transfer networks by varying the level up to which the convolutional layers were frozen. In a single-stage transfer learning approach, knowledge from CNN trained on the ImageNet data was fine-tuned directly with the DBT data. In a multi-stage transfer learning approach, knowledge learned from ImageNet was first fine-tuned with the mammography data and then fine-tuned with the DBT data. Two transfer networks were compared for the second-stage transfer learning by freezing most of the CNN structures versus freezing only the first convolutional layer. We studied the dependence of the classification performance on training sample size for various transfer learning and fine-tuning schemes by varying the training data from 1% to 100% of the available sets. The area under the receiver operating characteristic curve (AUC) was used as a performance measure. The view-based AUC on the test set for single-stage transfer learning was 0.85 ± 0.05 and improved significantly ( ${p} ) to 0.91 ± 0.03 for multi-stage learning. This paper demonstrated that, when the training sample size from the target domain is limited, an additional stage of transfer learning using data from a similar auxiliary domain is advantageous.
Multi-Agent Planning with Cardinality: Towards Autonomous Enforcement of Spectrum Policies

The distributed nature of policy violations in spectrum sharing necessitate the use of mobile autonomous agents (e.g., UAVs, self-driving cars, crowdsourcing) to implement cost-effective enforcement systems. We define this problem as Multi-agent Planning with Cardinality (MPC), where Cardinality represents multiple, unique agents visiting each infraction location to collectively improve the accuracy of the enforcement tasks. Designed as a practical and deployable system, our solution leverages crowdsourced information to determine the optimum Cardinality and provide a routing schedule for the agents to achieve the desired level of accuracy of detection and localization at minimum possible cost. We show that by estimating spatial orientation of the agents with single antenna, the accuracy is improved by 96% over crowdsourcing only. Using geographical maps as the basis, we solve the scheduling problem with a 3-approximation ratio in polynomial time that exhibits statistically similar performance under variety of urban locale across multiple continents. The longest path traversed by an agent on average is 1.2km per unit diagonal length of a rectangular geographic area, even when there are twice as many infractions as agents.
Communicating social support online: The roles of emotional disclosures and gender cues in support provision

Abstract The anonymity of online support forums presents both benefits and challenges for online supportive communication. This study investigates how support seekers’ verbal disclosure of emotions and gender cues in their user profiles may affect viewers’ intended support provision. Participants were asked to view a mockup page containing a support seeker’s profile along with a support-seeking post. They were then instructed to complete a survey on their appraisal of the support seeker and their intentions to provide support to him/her. The study found that compared to support seekers who made limited emotional disclosures, those with high levels of emotional disclosures were perceived as more legitimate to seek support online, which, in turn, enhanced viewers’ intentions to provide that support. Further, gender-ambiguous support seekers were more likely to be attributed females if they made more rather than fewer emotional disclosures. However, support seekers’ gender cues did not moderate the impact of emotional disclosures on viewers’ intentions to provide emotional support. Implications of the findings are discussed.
Implications of genotypic and microenvironmental heterogeneity for the cure of solid tumors by neutron capture therapy.

There is increasing evidence for genotypic, phenotypic, and microenvironmental heterogeneity within solid tumors in experimental animals and in humans. This heterogeneity influences the response of the tumors to treatment with radiation, cytotoxic drugs, hyperthermia, and immunotherapy, and may also influence the efficacy of neutron capture therapy. This paper reviews the data on heterogeneity in solid tumors and considers the implications of these data for curative NCT.
Enhancement of the performance of a double layered microchannel heatsink using PCM slurry and nanofluid coolants

Advanced coolants such as nanofluids or PCM slurries are realized and reported as effective substitutions for conventional coolants in order to enhance the cooling performance of microchannel heatsinks. However, there are a number of disadvantages associated with using these advanced coolants that are always considered as their inevitable downsides including the increase of the needed pumping power of the system for both of the mentioned coolants and decrease of the fluid average thermal conductivity for PCM slurries. In this paper, a 3D conjugated heat transfer model of a double layer microchannel heatsink (MCHS) to investigate its thermal performance is presented and the effectiveness of simultaneous employing of both of these types of advanced coolants in a heatsink is assessed. Finite volume method (FVM) is used to solve the flow and heat governing equations simultaneously and the obtained results are validated with the experimental data. The assessed parameters in this study are: coolant type, coolant configurations, particle concentration, bottom surface temperature, and inlet fluid velocity. In order to investigate the flow and cooling efficiency of the heatsink, two dimensionless parameter, Nusselt and Euler numbers, are computed and compared between the considered configurations. The goal is to balance and optimize the desirable cooling enhancement that is obtained by using advanced coolants and is represented by associated Nusselt number from one side, and undesirable increase of the needed pumping power which is implied by relevant Euler number, from the other side. Results showed that using the proposed configurations, the cooling performance of the systems are enhanced and the disadvantages associated with advanced coolant are relieved, substantially.
Occupational Competitiveness Analysis of the U.S. Transportation and Logistics Cluster

This paper explores occupational or human capital attributes of transportation and logistics clusters in the U.S., by analyzing logistics clusters, such as Memphis and uncovers the differences in o...
Bayesian nonparametric modeling for predicting dynamic dependencies in multiple object tracking

Some challenging problems in tracking multiple objects include the time-dependent cardinality, unordered measurements and object parameter labeling. In this paper, we employ Bayesian Bayesian nonparametric methods to address these challenges. In particular, we propose modeling the multiple object parameter state prior using the dependent Dirichlet and Pitman-Yor processes. These nonparametric models have been shown to be more flexible and robust, when compared to existing methods, for estimating the time-varying number of objects, providing object labeling and identifying measurement to object associations. Monte Carlo sampling methods are then proposed to efficiently learn the trajectory of objects from noisy measurements. Using simulations, we demonstrate the estimation performance advantage of the new methods when compared to existing algorithms such as the generalized labeled multi-Bernoulli filter.
Combining Radiation with Immunotherapy: The University of Pennsylvania Experience

Immune checkpoint inhibitors have shown remarkable clinical benefit across a variety of cancer types. However, the majority of patients do not respond or develop relapse after therapy. Radiation can favorably modulate the immune system and enhance tumor antigen recognition and rejection. Thus, the combination of radiation and immune checkpoint blockade (ICB) has been recognized as a promising strategy to improve tumor response and broaden the clinical utility of immunotherapy. In this review, we highlight the preclinical and clinical experience at our institution aimed at understanding and promoting the immunostimulatory effect of radiation. We discuss the rationale, design, results, and lessons from our clinical trials in combining radiation with anti-CTLA4 and/or anti-PD-1 therapy. In parallel, our studies to understand the resistance mechanism to radiation and ICB have converged on interferon (IFN) signaling as a key regulatory pathway. Persistent IFN-γ signaling impairs anti-tumor immune responses which can be reversed by using JAK inhibitor to disrupt the IFN signaling. Lastly we discuss remaining challenges, ongoing studies, and future directions in combining radiation with immunotherapy.
Mechanism of brain dysfunction on children with nocturnal enuresis by the technique of fractional amplitude of low frequency fluctuation of functional magnetic resonance imaging

Objective To research the pathological mechanism of the performance of enuresis and the brain dysfunction of attention and memory deficit of nocturnal enuresis (NE) by fractional amplitude of low frequency fluctuation (fALFF) of resting-state functional magnetic resonance imaging (rs-fMRI). Methods The approach of fALFF was used to analyze on 18 NE children and normal children, both of whom had been examined by rs-fMRI scans. Then the differences of fALFF were compared by two sample t-test. Results The brain regions which had obvious differences of fALFF between two groups were cerebellum(MNI: -12, -57, -33), left frontal lobe(-21, 42, -9), right temporal lobe(45, -12, -12) and occipital lobe(-18, -90, 39). And the group of NE was lower than normal children on all the four regions. The decrease of the value of fALFF on cerebellum made the dysfunction of timing of controlling urinary. And the weaken of the activity of left frontal lobe made the inhibition of attentional perform. The decrease of the value of fALFF on right temporal lobe and occipital lobe was probably related to memory. Conclusion The performance of NE is associated with the impairment of cerebellum.The dysfunction of cerebellum and left frontal lobe makes attention decrease and the deficit of memory is probably related to the impairment of right temporal lobe and occipital lobe. Key words: Resting-state functional magnetic resonance imaging; Nocturnal enuresis; Fractional amplitude of low frequency fluctuation
Leadership & Diversity: Synergistic Cross-culturalism

As the harbinger of change, globalization has led to increased demand for leaders who exhibit a broad range of competencies. The required nature of cross-cultural interaction has emerged as an area of major importance for leaders within the private and public sectors. Leaders in distinct roles and sectors are likely to find themselves in situations where they must navigate a range of contrasting cultures while learning to cooperate with others from diverse backgrounds. To adequately equip leaders from divergent fields, it is quintessential to have a firm understanding of six key areas of cross-cultural synergism and leadership: approaches to conflict and conflict resolution, communication styles, decision-making, task completion, levels of disclosure, and epistemological approaches. This article describes each of these areas and explains the ways in which it is imperative for future leaders to succeed.
Molecular dynamics study of the influence of aggregation and percolation in Al 2 O 3 /polyethylene oxide nanofluids on the effective thermal conductivity

Nanocomposites and nanofluids have the potential to be used widely as effective coolant materials. The motivation for this study is a belief that aggregation and percolation of nanoparticles in coolants could help explain the considerable variability in the values of thermal conductivity observed in systems containing similar components. This paper reports the results of the molecular dynamics study of the impact of aggregation and percolation of nanoparticles on the thermal conductivity in nanofluids containing aluminum oxide (α-alumina) nanospheres surrounded by polymer, polyethylene oxide (PEG400). The Reverse Non-Equilibrium Molecular Dynamics (RNEMD) [1] approach implemented in the open source code Molecular Dynamics Simulator LAMMPS [2] was utilized for the simulations. The values of the effective thermal conductivities obtained from the RNEMD simulations increased with growing aggregation from 0.4 W/m•K to 0.8 W/m•K for the structures with no aggregation and with a percolation channel, respectively. Equilibrium Molecular Dynamics (EMD) simulations of these system were also performed as an alternative method to study the thermal conductivity. The existence of the elastic modes in the nanoparticles/matrix superstructure was confirmed. These non-propagating elastic modes do not influence directly the heat flow but their presence in nanocomposites and nanofluids affects the applicability of EMD as an adequate tool for determining the value of thermal conductivity in such systems.
Imprinting disorders in humans: a review.

Purpose of review Mammals have two complete sets of chromosomes, one from each parent with equal autosomal gene expression. Less than one percentage of human genes are imprinted or show expression from only one parent without changing gene structure, usually by DNA methylation, but reversible in gametogenesis. Many imprinted genes affect fetal growth and development accounting for several human disorders reviewed in this report. Recent findings Disorders include Prader-Willi and Angelman syndromes, the first examples of imprinting errors in humans, chromosome 15q11.2-q13.3 duplication, Silver-Russell syndrome, Beckwith-Weidemann syndrome, GNAS gene-related inactivation disorders (e.g. Albright hereditary osteodystrophy), uniparental chromosome 14 disomy, chromosome 6q24-related transient neonatal diabetes mellitus, parent of origin effects in 15q11.2 BP1-BP2 deletion (Burnside-Butler) syndrome and 15q11-q13 single gene imprinted disorders. Summary Periconceptional and intrauterine life can be influenced by environmental factors and nutrition impacting DNA methylation. This process not only alters development of the fetus, but pregnancy complications may result from large fetal size. Epigenetic processes control imprinted gene functions and regulation with susceptibility to diseases as described. A better understanding of these processes will impact on care and treatment of affected individuals.
Masking Attendance: How Education Policy Distracts from the Wicked Problem(s) of Chronic Absenteeism.

Traditionally, education policy focuses on reforms that address class size, teaching and learning within classrooms, school choice, and changes in leadership as ways to improve students’ educationa...
Impaired clock gene expression and abnormal diurnal regulation of hippocampal inhibitory transmission and spatial memory in a mouse model of Alzheimers disease

ABSTRACT Patients with Alzheimer’s disease (AD) often have fragmentation of sleep/wake cycles and disrupted 24-h (circadian) activity. Despite this, little work has investigated the potential underlying day/night disruptions in cognition and neuronal physiology in the hippocampus. The molecular clock, an intrinsic transcription-translation feedback loop that regulates circadian behavior, may also regulate hippocampal neurophysiological activity. We hypothesized that disrupted diurnal variation in clock gene expression in the hippocampus corresponds with loss of normal day/night differences in membrane excitability, synaptic physiology, and cognition. We previously reported that the Tg-SwDI mouse model of AD has disrupted circadian locomotor rhythms and neurophysiological output of the suprachiasmatic nucleus (the primary circadian clock). Here, we report that Tg-SwDI mice failed to show day-night differences in a spatial working memory task, unlike wild-type controls that exhibited enhanced spatial working memory at night. Moreover, Tg-SwDI mice had lower levels of Per2, one of the core components of the molecular clock, at both mRNA and protein levels when compared to age-matched controls. Interestingly, we discovered neurophysiological impairments in area CA1 of the Tg-SwDI hippocampus. In controls, spontaneous inhibitory post-synaptic currents (sIPSCs) in pyramidal cells showed greater amplitude and lower inter-event interval during the day than the night. However, the normal day/night differences in sIPSCs were absent (amplitude) or reversed (inter-event interval) in pyramidal cells from Tg-SwDI mice. In control mice, current injection into CA1 pyramidal cells produced more firing during the night than during the day, but no day/night difference in excitability was observed in Tg-SwDI mice. The normal day/night difference in excitability in controls was blocked by GABA receptor inhibition. Together, these results demonstrate that the normal diurnal regulation of inhibitory transmission in the hippocampus is diminished in a mouse model of AD, leading to decreased daytime inhibition onto hippocampal CA1 pyramidal cells. Uncovering disrupted day/night differences in circadian gene regulation, hippocampal physiology, and memory in AD mouse models may provide insight into possible chronotherapeutic strategies to ameliorate Alzheimer’s disease symptoms or delay pathological onset.
High-frequency hospital users: The tail that wags the readmissions dog.

OBJECTIVE To describe the characteristics of high-frequency hospital users (four or more hospitalizations in a year) and the consequences of including or excluding their data from a readmission-based measure. DATA SOURCES 2015 and 2016 Massachusetts Medicaid data. STUDY DESIGN We compare demographics, morbidity burden, and social risk factors for high- and low-frequency hospital users, and membership in 17 accountable care organizations. We evaluate how excluding hospitalizations of high-frequency users from a 30-day readmission measure (with or without risk adjustment) changes its rate and variability and affects performance rankings of accountable care organizations. The outcome is readmission within 30 days; each live discharge from a hospital contributes one observation. DATA COLLECTION/EXTRACTION METHODS We studied 74 706 hospitalizations of 42 794 MassHealth members, 18-64 years old, managed-care-eligible, and ever hospitalized in 2016. PRINCIPAL FINDINGS Among adult managed-care-eligible MassHealth members with at least one acute hospitalization, 8.7% were high-frequency hospital users; they contributed 30.2% of hospitalizations and 69.4% of readmissions. High-frequency users were more often male (77.1% vs. 50.0%; P < 0.001) and sicker (mean medical morbidity score was 3.3 vs. 1.9; P < 0.001) than others. They also had significant social risks: 33.1% with housing problems, 44.1% disabled, 83.2% with serious mental illness, and 77.1% with substance abuse disorder (vs. 22.0%, 27.3%, 60.2%, and 50.0%, respectively, for other hospital users [all P values <0.001]). Fully 50.7% of hospitalizations for high-frequency users led to 30-day readmissions (vs. 9.7%), contributing 72.0% of the variance in 30-day readmission, and substantially affecting judgments about the relative performance of accountable care organizations. CONCLUSIONS A small group of high-frequency hospital users have a disproportionate effect on 30-day readmission rates. This negatively affects some Medicaid ACOs, and more broadly is likely to adversely affect safety net hospitals. How these metrics are used should be reconsidered in this context.
Differentially Private Federated Learning: An Information-Theoretic Perspective

We propose a new technique for deriving the differential privacy parameters in federated learning (FL). We consider the setting where a machine learning model is iteratively trained using stochastic gradient descent (SGD) and only the last update is publicly released. In this approach, we interpret each training iteration as a Markov kernel. We then quantify the impact of the kernel on privacy parameters via the contraction coefficient of the $E_{\gamma}$ -divergence that underlies differential privacy. To do so, we generalize the well-known Dobrushin's ergodicity coefficient, originally defined in terms of total variation distance, to a family of $f$ -divergences. We then analyze the convergence rate of SGD under the proposed private FL framework.
The Inescapable Conclusion—A Large Glacier

Glacial action west of the Kennebec—Transformation of the slates into granitoid rocks—The lake states essentially those of great boulder denudations—The principle applied to other continents—Africa and Australia in their pre-glacial age—The true negro of those countries, the modern counterpart of the pre-historic races—Conclusions as to the cause of the general denudation of the surface rocks of the state—Truth as a revelation to man in physical things—Little by little it dawns upon the mind—Obtaining it second handed—Now the truth of the former presence of a great glacier in the country grew upon the mind.
Surgeons, ERCP, and laparoscopic common bile duct exploration: do we need a standard approach for common bile duct stones?

Variation exists in the management of choledocholithiasis (CDL). This study evaluated associations between demographic and practice-related characteristics and CDL management. A 22-item, web-based survey was administered to US general surgeons. Respondents were classified into metropolitan or nonmetropolitan groups by zip code. Univariate tests and multivariable logistic regression were used to determine factors associated with CDL management preferences. The survey was sent to 32,932 surgeons; 9902 performed laparoscopic cholecystectomy within the last year; 750 of 771 respondents had a valid US zip code and were included in the analysis. Mean practice time was 18 ± 10 years, 87 % were male, and 83 % practiced in a metropolitan area. For preoperatively known CDL, 86 % chose preoperative endoscopic retrograde cholangiopancreatography (ERCP). Those in metropolitan areas were more likely to select preoperative ERCP than those in nonmetropolitan areas (88 vs. 79 %, p < 0.001). For CDL discovered intraoperatively, 30 % selected laparoscopic common bile duct exploration (LCBDE) as their preferred method of management with no difference between metropolitan and nonmetropolitan areas (30 vs. 26 %, p = 0.335). The top reasons for not performing LCBDE were: having a reliable ERCP proceduralist available, lack of equipment, and lack of comfort performing LCBDE. Factors associated with preoperative ERCP were: metropolitan status, selective intraoperative cholangiography (IOC), and availability of a reliable ERCP proceduralist. Those who perform selective IOC were 70 % less likely to prefer LCBDE (OR 0.32, 95 % CI 0.18–0.57, p < 0.001). Those with a reliable ERCP proceduralist available were 90 % less likely to prefer LCBDE (OR 0.10, 95 % CI 0.04–0.26, p < 0.001). The majority of respondents preferred ERCP for the management of CDL. Having a reliable ERCP proceduralist available, use of selective IOC, and metropolitan status were independently associated with preoperative ERCP. Postoperative ERCP was preferred for managing intraoperatively discovered CDL. Many surgeons are uncomfortable performing LCBDE, and increased training may be needed.
BiCMOS Process Technology

For high performance LSI and VLSI digital circuit applications, BiCMOS technology has become predominantly driven from a CMOS processing base. The principle reason for this is that LSI and VLSI digital BiCMOS circuits tend to be CMOS-intensive because of power dissipation limitations (for example, high density ECL I/O SRAMs and gate arrays). The CMOS-intensive nature of these circuits requires a process technology that will result in the highest possible CMOS performance. Consequently, BiCMOS fabrication technology tends to be CMOSbased, and the process steps needed to realize a high performance bipolar device are usually merged with a core CMOS process flow [3.1, 3.2, 3.3]. In the case of analog BiCMOS, the increasing demand to have on-board digital logic integration has also resulted in these processes being CMOS-oriented.
Factors affecting fertilization: endometrial placental protein 14 reduces the capacity of human spermatozoa to bind to the human zona pellucida*†

Objective To examine whether placental protein 14 (PP14) may affect directly those sperm functions crucial to fertilization and early embryo development. Design In these prospective studies, we evaluated semen samples of fertile men incubated under capacitating conditions with and without PP14. Setting Academic tertiary institution. Interventions Biologically active PP14 was purified from human midtrimester amniotic fluid by anion exchange and immunoaffinity chromatography. After separation of the motile fraction, spermatozoa were incubated for 30 minutes with or without PP14 (concentration range of 0.01 to 100 µ g/mL), washed, and then aliquots were prepared for use in the different assays. Human sperm-zona pellucida (ZP) binding was assessed using the hemizona assay (HZA) in a 4-hour gametes coincubation period. Sperm motility parameters were evaluated using a computerized semen analyzer. The acrosome reaction (AR) was determined by fluorescein isothiocyanate-conjugated Pisum sativum agglutinin and indirect immunofluorescence. Main Outcome Measures Sperm-ZP binding, sperm motility patterns, and AR. Results Preincubation of sperm (and not the hemizonae) with PP14 produced a significant and dose-dependent inhibition of binding in the HZA. Monoclonal antibodies generated against PP14 showed no direct effect in the HZA and partially neutralized the inhibitory activity of PP14 in the HZA. Insulin-like growth factor binding protein-1 (IGFBP-1), an endometrial stromal cell product, showed no effect in the HZA. Neither PP14 nor IGFBP-1 interfered with sperm motility parameters or the AR. Conclusions Placental protein 14 produced a potent, fast, and dose-dependent inhibition of binding of human spermatozoa to the human ZP without affecting other prefertilization events (i.e., hyperactivated motility or AR). The detrimental effect on sperm-zona interaction seems to be specific for this endometrial epithelial protein (not observed with an endometrial stromal product) and may have fundamental bearance to the fertilization process thus providing a mechanism for endometriosis-related infertility.
Nitinol Heat Engines

Thermally-related shape memory properties of certain Nickel-Titanium alloys were first observed at the Naval Ordnance Laboratory in the early 1960’s, and their application to thermomechanical energy conversion systems recognized.(1) The first successful application of these materials to a continuously operating heat engine was demosrated at the Lawrence Berkeley Laboratory in August 1973.(2) Since that time parallel programs in materials study, thermodynamic analysis, prototype concepts and design of Ni-Ti heat engines have been initiated at LBL principally under a grant from the National Science Foundation/RANN. As the specific mechanisms of the Ni-Ti phase transformation and the thermodynamic analysis of its energy conversion effeciency will be presented in detail elsewhere, this paper will deal with practical aspects of the use of the shape-memory material in low-temperature heat engines, and their application to energy conversion.
Development of neural selectivity for birdsong during vocal learning

Juvenile white-crowned sparrows learn to sing by first memorizing an adult's song and then progressively matching their vocalizations to this model during plastic song. Previous studies have shown that neurons in the song-system nucleus HVC of adult sparrows respond preferentially to a bird's own song. In this study, the auditory selectivity of HVC neurons in subadult birds was examined. In young, nonsinging birds who had been song tutored, these cells responded to song stimuli, and at some recording sites had distinct preferences for one song or another. As a population, however, HVC neurons in these birds showed no preference for familiar song. They were no more likely to prefer normal tutor song to reversed tutor song or to the song of another white-crowned subspecies. By contrast, in birds producing plastic song, HVC neurons were selective for the bird's own songs, even in preference to their tutor song. Therefore, during song learning the response properties of HVC neurons appear to be dynamically modified, perhaps by auditory feedback from the bird's own vocalizations. The emergence of song selectivity during plastic song may be significant both for song learning and for song perception in adult birds.
Glucose uptake by the corn scutellum.

Abstract The rate of uptake of glucose into corn scutellum slices was dependent both on glucose concentration and the time the slices were incubated in water prior to the addition of glucose. As the length of the incubation period was increased, so was the rate of glucose uptake. This effect was nullified by high glucose concentrations (e.g. 4·9 × 10−2 M) during the uptake period. Incubation in the absence of glucose caused the total reducing sugars and glucose to decrease in the tissue during the first hour and increase slightly thereafter. The sucrose and glucose-6-phosphate contents decreased throughout the 4-hr period of measurement. During incubation in the presence of different concentrations of glucose, the contents of reducing sugars, glucose, sucrose and glucose-6-phosphate decreased more slowly than during incubation in water or were maintained at levels equal to or greater than initial levels. Mannose inhibited glucose uptake. During incubation with mannose the slices accumulated mannose and mannose-6-phosphate, and evidence is presented that both mannose and mannose-6-phosphate are responsible for the inhibition of glucose uptake. It is suggested that glucose-6-phosphate competitively inhibits an enzymatic step (hexokinase-catalyzed reaction ?) associated with net glucose uptake.
Coming Home Again: Returns to the Parental Home of Young Adults

The route to residential independence is not a one-way street; many young adults who leave their parents' homes subsequently return. Data from the (U.S.) National Longitudinal Study of the High School Class of 1972 are used to study young adults' returns to the parental home, to test hypotheses about the influences on these residential decisions and to examine the likely causes of the increases in returning home in recent years. Our conceptual framework considers returning home in terms of the costs and benefits of separate residence; it also considers the relative youth of those now living away from home, and the high density of ‘normal’ transitions in their lives, as well as their continued dependency in many ways on their parents. We find returns home not only to be associated with ‘failure’ transitions, such as losing a job or ending a marriage, but also to follow the completion of such transitional roles as student and military service. They occur as well in conjunction with the role changes, such as...