cssi/SciSciGPT-SciSciNet huggingface dataset:
MiR-980 Is a Memory Suppressor MicroRNA that Regulates the Autism-Susceptibility Gene A2bp1.

MicroRNAs have been associated with many different biological functions, but little is known about their roles in conditioned behavior. We demonstrate that Drosophila miR-980 is a memory suppressor gene functioning in multiple regions of the adult brain. Memory acquisition and stability were both increased by miR-980 inhibition. Whole cell recordings and functional imaging experiments indicated that miR-980 regulates neuronal excitability. We identified the autism susceptibility gene, A2bp1, as an mRNA target for miR-980. A2bp1 levels varied inversely with miR-980 expression; memory performance was directly related to A2bp1 levels. In addition, A2bp1 knockdown reversed the memory gains produced by miR-980 inhibition, consistent with A2bp1 being a downstream target of miR-980 responsible for the memory phenotypes. Our results indicate that miR-980 represses A2bp1 expression to tune the excitable state of neurons, and the overall state of excitability translates to memory impairment or improvement.
Collisional and intramolecular dynamics of low lying vibrational states of infrared multiphoton excited molecules

Current models of IR multiphoton excitation of a polyatomic molecule suggest that photon absorption proceeds initially through coherent stepwise excitation of low lying levels of an anharmonic vibrational ladder up to the threshold of the qua sicontinuum.1 The enormous density of states (typically 105/cm-1) and level mixing at this energy provides incoherent excitation and ultimately leads to energy redistribution in the molecule via intramolecular and collisional relaxation processes. Such redistribution creates a broad band of excited vibrational states in spontaneous and anti-Stokes coherent Raman spectra of molecules.2
Adenosine attenuates oxidant injury in human proximal tubular cells via A1 and A2a adenosine receptors

We have recently demonstrated protection against renal ischemic-reperfusion injury in vivo by A1- and A2a-adenosine receptor (AR) modulations. To further elucidate the signaling cascades of AR-indu...
Cocaine self-administration disrupted by the N-methyl-D-aspartate receptor antagonist ketamine: a randomized, crossover trial

Repeated drug consumption may progress to problematic use by triggering neuroplastic adaptations that attenuate sensitivity to natural rewards while increasing reactivity to craving and drug cues. Converging evidence suggests a single sub-anesthetic dose of the N-methyl-D-aspartate receptor antagonist ketamine may work to correct these neuroadaptations and restore motivation for non-drug rewards. Using an established laboratory model aimed at evaluating behavioral shifts in the salience of cocaine now vs money later, we found that ketamine, as compared to the control, significantly decreased cocaine self-administration by 67% relative to baseline at greater than 24 h post-infusion, the most robust reduction observed to date in human cocaine users and the first to involve mechanisms other than stimulant or dopamine agonist effects. These findings signal new directions in medication development for substance use disorders.
Simultaneous Analysis of Five Kinds of Synthetic Colorants in Meat Products by SPE-UPLC

Objective To develop a method for the simultaneous determination of five kinds of synthetic colorants, including tartrazine, amaranth, carmine, sunset yellow and allura red in meat products by solid phase extractionultra performance liquid chromatography(SPE-UPLC). Methods After ultrasonic-assisted extraction using ethanol-ammonia(75:25, v/v) solution, the extract of meat products was purified on an OASIS WAX SPE column; chromatographic separation was performed on a ACQUITY UPLC BEH C18 analytical column(2.1 mm×50 mm, 1.7 μm) by gradient elution, using methanol-0.02 mol/L ammonium acetate solution as mobile phase, with the flow rate of 0.3 m L/min and column temperature of 30 ℃. The injection volume was 3 μL, the detection wavelength was 200-500 nm. Results The linear concentration range of five colorants was 0.5-25.0 mg/L(r20.9999). The limits of detection(LOD) were in the range of 0.05-0.20 mg/kg and the limits of quantification(LOQ) were in the range of 0.15-0.60 mg/kg. The relative standard deviations(RSD) were in the range of 1.2 %-3.3 %. The recoveries were 89.7 %-96.0 % when the standard addition level was three times of LOD, and 91.3 %-97.5 % when the standard addition level was six times of LOD, respectively. Conclusion The method is sensitive, accurate and reproducible, and is suitable for determination of five kinds of synthetic colorants in meat products.
Socioeconomic Factors Impact Inpatient Mortality in Pediatric Lymphoma Patients

Purpose: Our objective was to determine the risk factors for inpatient mortality of pediatric patients diagnosed with lymphoma through the utilization of a large national pediatric database. Methods: This cross-sectional study uses data from the Healthcare Cost and Utilization Project Kids' Inpatient Database (HCUP KID) for the year of 2012 to estimate the risk factors for inpatient mortality for pediatric patients diagnosed with lymphoma. All patients diagnosed with lymphoma between the ages of one and 18 years were included. Chi-square test was used to analyze categorical variables. Independent t-test was used to analyze continuous variables. Results: A total of 2,908 study subjects with lymphoma were analyzed. Of those, 56.1% were male and the average age was three years old. Total inpatient mortality was 1.2% or 34 patients. We found that patients with four or more chronic conditions were much more likely to die while hospitalized (p < 0.0001). In addition, we also saw that patients with median household incomes below $47,999 dollars (p = 0.05) having a need for a major procedure (p = 0.008) were associated with inpatient mortality. Congestive heart failure, renal failure, coagulopathy, metastatic disease, and electrolyte abnormalities were all found to be associated with inpatient mortality. Conclusions: Pediatric lymphoma mortality in children is not only influenced by their medical condition but also by their socioeconomic condition as well.
Regulating the Product Distribution of CO Reduction by the Atomic-Level Structural Modification of the Cu Electrode Surface

Cu catalyzes the electrochemical reduction of CO_2 or CO to an assortment of products, a behavior that is a detriment when only one reduced compound is desired. The present article provides an example in which, through the atomic-level control of the structure of the Cu electrode surface, the yield distribution is regulated to generate only one product. The reaction investigated was the preferential reduction of CO to C_2H_5OH on Cu at a low overpotential in alkaline solution. Experimental measurements combined electrochemical scanning tunneling microscopy (ECSTM) and differential electrochemical mass spectrometry (DEMS). An atomically ordered Cu(100) surface, prepared from either a single crystal or by Cu(pc)-to-Cu(100) reconstruction, did not produce ethanol. When the surfaces were subjected to monolayer-limited Cu↔Cu_2O cycles, only the reconstructed surface underwent an additional structural transformation that spawned the selective production of ethanol at a potential 645 mV lower than that which generates multiple products. Quasi-operando ECSTM indicated transformation to an ordered stepped surface, Cu(S) − [3(100) × (111)], or Cu(511). The non-selective, multiple-product Cu-catalyzed reduction of CO had thus been regulated to yield only one liquid fuel by an atomic-level structural modification of the electrode surface.
Trends in infective endocarditis hospitalisations at United States children's hospitals from 2003 to 2014: impact of the 2007 American Heart Association antibiotic prophylaxis guidelines.

Objective National organisations in several countries have recently released more restrictive guidelines for infective endocarditis prophylaxis, including the American Heart Association 2007 guidelines. Initial studies demonstrated no change in infective endocarditis rates over time; however, a recent United Kingdom study suggested an increase; current paediatric trends are unknown. Methods Children ( 5 years of age. Interrupted time series analysis was used to evaluate rates over time indexed to total hospitalisations. Results A total of 841 cases were identified. The median age was 13 years (interquartile range 9–15 years). In the pre-guideline period, there was a slight increase in the rate of infective endocarditis by 0.13 cases/10,000 hospitalisations per semi-annual period. In the post-guideline period, the rate of infective endocarditis increased by 0.12 cases/10,000 hospitalisations per semi-annual period. There was no significant difference in the rate of change in the pre- versus post-guidelines period (p=0.895). Secondary analyses in children >5 years of age with CHD and in children hospitalised with any type of infective endocarditis at any age revealed similar results. Conclusions We found no significant change in infective endocarditis hospitalisation rates associated with revised prophylaxis guidelines over 11 years across 29 United States children’s hospitals.
Enter the Maronites and the Druzes

History knew little about Lebanon and the Lebanese in the first centuries of Islam. Not until the beginning of the Crusades, late eleventh century, did they begin to figure prominently. Sidon, Beirut, Jubayl, Tripoli and other coastal towns must have lost some of their Byzantine or pro-Byzantine inhabitants as a result of the conquest, necessitating transplanting by Muawiyah (ca. 663) of Persians to replace them as a measure of protection against possible naval incursions by the enemy. A few Arabians, no doubt, also settled there. The same possibility influenced this caliph in his choice of an inland seat of government, Damascus. But the mountain offered no attraction to desert people. Agriculture was considered below their dignity. They knew little about industry and less about maritime trade. The caliphs in distant Medina could not have realized the strategic importance of Lebanon. They left it to itself. The preponderant number of village names of Canaanite or Aramaic origin attest the Arabian failure to settle in the area. The Arabic vocabulary used today in agriculture and farming is likewise rich in pre-Arabic terms.
E-Collaboration at Celadon Trucking Services

Technology has influenced industries around the world. Not only is the use of technology essential to the success of a business, but the continuous improvement of technology is a determinant factor in obtaining a competitive advantage. Electronic collaboration e-collaboration has made a presence in the supply chain of international trade. The logistics industry, in particular the area of trucking, has to continuously improve their technology and use e-collaboration in order to continue having a profitable advantage in a highly regulated and competitive arena. Some methods of e-collaboration used by a particular trucking company along the U.S.-Mexico border will be discussed.
Joint Attention and Early Social Developmental Cascades in Neurogenetic Disorders.

Abstract This review examines what is known about joint attention and early social development in three neurogenetic syndromes: Down syndrome, Williams syndrome, and fragile X syndrome. In addition, the potential cascading effects of joint attention on subsequent social development, especially social interaction and social cognition, are proposed. The potential issues and complexities associated with conducting prospective, longitudinal studies of infant social development in neurogenetic disorders are discussed.
Memory support strategies and bundles: A pathway to improving cognitive therapy for depression?

Objective Therapist use of memory support (MS) alongside treatment-as-usual, with the goal of enhancing patient recall of treatment contents, has been of recent interest as a novel pathway to improve treatment outcome. The memory support intervention (MSI) involves treatment providers' using 8 specific MS strategies to promote patient memory for treatment. The present study examines to what extent therapist use of MS strategies and bundles improves patient recall of treatment contents and treatment outcome. Method The data were drawn from a pilot RCT reported elsewhere. Participants were 48 adults (mean age = 44.27 years, 29 females) with major depressive disorder (MDD), randomized to receive 14 sessions of either CT + Memory Support (n = 25) or CT-as-usual (n = 23). Therapist use of MS was coded using the Memory Support Rating Scale. Patient memory and treatment outcomes were assessed at baseline, midtreatment (patient recall only), posttreatment, and 6-month follow-up. Results Participants in CT + Memory Support received significantly higher amount of MS relative to CT-as-usual. Although not reaching statistical significance, small-to-medium effects were observed between MS strategies and patient recall in the expected direction. Although MS variables were not significantly associated with changes in continuous depressive symptoms, MS was associated with better global functioning. MS also exhibited small to medium effects on treatment response and recurrence in the expected direction but not on remission, though these effects did not reach statistical significance. Conclusions These results provide initial empirical evidence supporting an active method for therapists to implement MS strategies. (PsycINFO Database Record
Abstract B47: Drug-induced EMT is fundamentally distinct from pathologic EMT

Abstracts: AACR Special Conference on Tumor Metastasis; November 30-December 3, 2015; Austin, TX Background: Receptor tyrosine kinase ErbB2 (Her2) is overexpressed in an estimated 25% of the breast cancer patients. A therapeutic regime of Her2 targeted therapies, consists of Trastuzumab followed by the dual EGFR/Her2 tyrosine kinase inhibitor, Lapatinib. These therapies continue to show success in blocking the progression of this breast cancer subtype. Of clinical concern, however, cancer cells eventually develop pathways to evade Lapatinib-mediated tumor inhibition and acquire drug resistance. In this study, we sought to understand the molecular mechanism of resistance towards Lapatinib. Methods: We used Her2 overexpressing human mammary epithelial cells to generate Lapatinib resistant cell lines (LapR) in vitro. The LapR cells acquired growth persistence within the continued presence of Lapatinib for four weeks. We analyzed the resultant cell populations via cell viability assays, immunoblotting, flow cytometry, 3D cell culture and Nano-string gene expression analysis. Results: Generated LapR cell lines showed robust epithelial-mesenchymal transition (EMT) phenotypes that included upregulated FGFR1 and preservation of their Her2 expression. We tested the viability of LapR cells using dose response assays with Afatinib, a second-generation covalent ErbB kinase inhibitor, and Trastuzumab emtansine (T-DM1), an anti-Her2 antibody drug conjugate. We also utilized recently developed covalent inhibitors of FGFR. LapR cells were highly resistant to Afatinib but did show sensitivity to T-DM1 and FGFR kinase inhibition. Importantly, resistance to ErbB inhibition was maintained in the LapR cells for several weeks following removal of Lapatinib. This stable phenotype was consistent with a maintained yet distinct regulation of the cancer stem cell markers (CD44/CD24) compared to a transient EMT induced by transforming growth factor β (TGF-β). Strikingly, we observed that unlike their parental counterparts LapR cells were unable to grow in a compliant 3D matrix. Furthermore, unlike TGF-β-treated cells, LapR cells were unable to metastasize in vivo. By using Nano-string pan cancer progression panel analysis, we characterized key differences in the LapR EMT phenotype as compared to a TGF-β induced EMT. Future Directions: Currently, we are analyzing the expression data of LapR and TGF-β-induced EMT to identify key targets required for EMT-induced tumor progression. Overall, our studies seek to define what aspects of EMT are involved in cellular persistence in response to anti-cancer drugs versus those utilized by cells during metastatic progression. Citation Format: Saeed Salehin Akhand, Michael Wendt. Drug-induced EMT is fundamentally distinct from pathologic EMT. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B47.
Congregational Composition and Explanations for Racial Inequality Among Black Religious Affiliates.

Prior research suggests that congregational characteristics are associated with the racial attitudes of Black churchgoers. This study examines the relationship between congregational diversity and beliefs about the Black/White socioeconomic gap among Black religious adherents. Drawing upon pooled data from the General Social Survey and the National Congregations Study, we fit binary logistic regression models to estimate the association between congregational diversity and the explanations of Black/White economic inequality among Black religious adherents. Findings from our study reveal that congregational diversity is one factor that accounts for intragroup differences in racial attitudes among Black religious affiliates. Relative to Blacks that attend religious services in overwhelmingly Black congregations, Blacks that attend religious services in congregations that are overwhelmingly White are significantly less likely to attribute Black/White socioeconomic gaps to a lack of educational opportunities. Our study demonstrates that congregational diversity is a source of intragroup variation in racial attitudes among Black religious affiliates, which may attenuate the ability of such congregations to bridge racial divisions.
CONDUCTION ABNORMALITIES FOLLOWING ORTHOTOPIC HEART TRANSPLANTATION

Conduction abnormalities following orthotopic heart transplantation (OHT) are unique in that there is loss of autonomic nervous system modulation, occurring in the background of immunosuppressive therapy, in addition to the risk of allograft rejection and vasculopathy. They can happen at any time
Quantifying changes in lens biomechanical properties due to cold cataract with optical coherence elastography

Cataract is the most prevalent cause of visual impairment worldwide. Cataracts can be formed due to trauma, radiation, drug abuse, or low temperatures. Thus, early detection of cataract can be immensely helpful for preserving visual acuity by ensuring that the appropriate therapeutic procedures are performed at earlier stages of disease onset and progression. In this work, we utilized a phase-sensitive optical coherence elastography (OCE) system to quantify changes in biomechanical properties of porcine lenses in vitro with induced cold cataracts. The results show significant increase in lens Young’s modulus due to formation of the cold cataract (from ~ 35 kPa to ~60 kPa). These results show that OCE can assess lenticular biomechanical properties and may be useful for detecting and, potentially, characterizing cataracts.
Does the LDP Want to Build a Wall Too? Immigration and the 2017 Election in Japan

Given the results of the 2017 Japanese general election, how likely are we to see a rapid increase in immigration in the near future? Will we see the rise of an anti-immigrant populist political force in Japan? This chapter addresses these questions with reference to candidate positions and public opinion from the last several Japanese elections. One of this chapter’s most surprising findings is that, although a plurality of Diet members (DMs) consistently do not take a position on foreign labor, in 2017 there was a strong correlation between the percentage of DMs in a prefecture who took a position on foreign labor and the percentage of DMs in that prefecture who support increasing foreign labor. This suggests that many DMs not taking a position on foreign labor might actually support foreign labor but do not want to be one of only a few candidates in their prefecture taking that position.
Novel approaches to the prevention and therapy of neonatal bacterial sepsis

A variety of adjunctive treatments have been shown to offer potential benefits for neonates with sepsis. Most are not available clinically, and those that are available should be considered experimental or limited in their use; however, these efforts are far from complete and should continue to evolve in the coming years. Efforts toward the rapid diagnosis of bacterial infections are a necessary component in the eventual implementation of these potential novel strategies. As a better understanding of the intricate mechanisms of neonatal sepsis is developed, it will be possible to provide patients with an increasingly effective array of treatment and prevention strategies.
Palliative Care and Chronic Obstructive Lung Disease

99 Chronic Obstructive Pulmonary Disease (COPD) is a major public health problem in the United States and throughout the world with a global prevalence estimated at 9.3 per 1000 males and 7.3 per 1000 females (all ages). (Vital and Health Statistics, 1996; Murray and Lopez, 1997). COPD was ranked as the sixth most common cause of death worldwide in 1990, and the Global Burden of Disease Study predicted that it would become the third most common cause by 2020 (Lopez and Murray, 1998). In 2003, an estimated 10.7 million adults in the U.S. were reported as having physician diagnosed COPD. However data from the NHANES III (National Health and Nutrition Evaluation Survey) estimated that approximately 24 million adults in the U.S. have evidence of impaired lung function, indicating an underdiagnosis of COPD especially in its milder forms which are most amenable to treatment. It is estimated that there may be 16 million people in the U.S. currently diagnosed with COPD (Hilleman et al., 2000; NCHS, 2002). Mortality and morbidity is significant in patients who have severe COPD, are elderly and have acute exacerbations of COPD requiring hospitalization or ICU admission. According to estimates by the National Heart Lung and Blood Instiute, in 2004 the total annual expenditure for COPD in the U.S. was $37.2 billion, including $20.9 billion for hospital costs and treatment of the disease and $1,613 billion in indirect costs such as work loss. (National Institutes of Health. National Heart, Lung and Blood Institute, 2002). Despite the relatively high prevalence, morbidity, and mortality, end-of-life care such as hospice placement occurs in only a small percentage of patients with COPD.
The International Regulatory Environment

It is a widely held premise that a sustainable future for nuclear power depends upon world-wide compliance with consistent regulatory safety standards. Competent, objective national regulatory authorities are needed to establish those standards and to assure that compliance. But another widely held premise is that, since competitive markets result in major economies to the consumer, price regulation of electricity, including nuclear power generation, should give way to competitive pricing.
Anatomy and Histology of the Digestive Tract

This chapter presents a brief overview of the gross anatomy and histology of the digestive tract. Each of the four major organs, esophagus, stomach, small intestine and large intestine, are described in terms of anatomical relationships, architecture and cytology of the organ wall, as well as blood supply and innervation.
Laparoskopische Behandlung der adhäsionsbedingten Dünndarmobstruktion

Ziel dieses Reviews ist die Darstellung der aktuellen Datenlage bezuglich der Behandlung der Dunndarmobstruktion. Das Thema ist auf die durch postoperative Adhasionen (Verwachsungen) bedingte Obstruktion des Dunndarms begrenzt. Andere Ursachen einer Obstruktion beim Dunndarm werden nicht angesprochen. Hier wird versucht, den Lesern einen kurz gefassten Einblick in die in der englischsprachigen Literatur verfugbaren Ergebnisse zu geben. Dieser Artikel bietet keine umfassende Darstellung des Themas; stattdessen werden einige relevante Themen herausgegriffen und dann skizziert, welche Rolle, wenn uberhaupt, die laparoskopische Operation bei der Behandlung der Dunndarmobstruktion durch Verwachsungen spielen sollte.
Electric Forces and Fields

By imagining a gas to be a collection of tiny spheres, we were able to explain many features of the behavior of gases and estimate the number and size of molecules. The results gave further credibility to the idea that atoms exist, but the numbers were imprecise, yielding estimates of Avogadro’s number and atomic sizes accurate only to within an order of magnitude, i.e., only to within a factor of ten.
Paying Low-Income Smokers to Quit? The Cost-Effectiveness of Incentivizing Tobacco Quit Line Engagement for Medicaid Recipients Who Smoke

Abstract Objectives To determine the cost-effectiveness of an incentive-based stop-smoking intervention that paid Medicaid recipients who smoke to take calls from a tobacco quit line. Methods A cost-effectiveness analysis was conducted alongside a randomized controlled trial. The analysis was conducted from a health care systems perspective on the basis of costs and effectiveness over a 6-month follow-up. Participants (n = 1900) were recruited from May 2013 to June 2015 through quit line (n = 980), clinic-based (n = 444), or community-based (n = 476) referrals. Incentive group participants (n = 948) received $30 a call for taking up to five tobacco quit line calls and $40 for biochemically verified tobacco abstinence at 6 months. Control group participants (n = 952) did not receive financial incentives for taking quit line calls. Intervention resource costs included incentive payments to participants, counselor and administrative staff time, and smoking cessation medications. Smoking status at baseline and 6 months was determined for all study participants via carbon monoxide (CO) breath tests (abstinence: CO Results Incentive treatment produced higher 6-month CO-confirmed 7-day point-prevalence abstinence than did the control treatment (21.6 vs. 13.8%; P Conclusions Use of financial incentives to engage with tobacco quit line treatment is a cost-effective option to enhance smoking cessation rates for low-income smokers.
Spatially variable warming of the Laurentian Great Lakes: an interaction of bathymetry and climate

Previous research has identified significant and highly variable summertime (July–August–September) warming trends across the Great Lakes, with critical implications for aquatic ecosystems. However, these analyses of long-term warming trends have generally been constrained by the short duration or coarse spatial resolution of available observational datasets. Here, we integrate two existing datasets of Great Lakes surface temperature (LSWT) to evaluate long-term warming trends during 1982–2012 at fine spatial scales and understand the roles of lake bathymetry and climatic factors in regulating the spatially heterogeneous warming rates with the aid of regional climate modeling. Our results show amplified warming in Lake Superior, central-northern Lake Michigan, and central Lake Huron, and muted lake warming elsewhere. This spatial heterogeneity in summertime lake warming is primarily ascribed to the interplay of lake bathymetry and climatological springtime (April–May–June) air temperature. The climatological air temperature strongly influences the relationship between lake warming rates and bathymetry, as the summertime warming rates increase markedly with greater lake depth in the relatively cold environment of Lake Superior but change little in the warmer environment of Lake Ontario. This conditional dependence on background temperature has important implications for understanding and predicting global lake temperature trends.
The long-run impact of zoning: Institutional hysteresis and durable capital in Seattle, 1920–2015

Abstract This paper examines the coevolution of land use and zoning in Seattle from 1920 to 2015. Multiple waves of zoning and land use conversion data at the parcel level allow for a decomposition of the long-run effects of zoning and an exploration of the mechanisms through which zoning influenced future land use. In particular, I disentangle short-run impacts on land use from long-term institutional hysteresis, showing that the latter played a sizable role in shaping future land use. Additionally, data on variances allows me to examine early compliance levels, an underexplored topic with implications for long-run impacts. While much has been written about persistence in urban form due to purely economic forces, relatively little research has explored how institutional forces can entrench or alter this trajectory, and I find that such institutional constraints can have substantial influence.
Fat-regulating phosphatidic acid phosphatase: a review of its roles and regulation in lipid homeostasis

Phosphatidic acid (PA) phosphatase is an evolutionarily conserved enzyme that plays a major role in lipid homeostasis by controlling the cellular levels of its substrate, PA, and its product, diacylglycerol. These lipids are essential intermediates for the synthesis of triacylglycerol and membrane phospholipids; they also function in lipid signaling, vesicular trafficking, lipid droplet formation, and phospholipid synthesis gene expression. The importance of PA phosphatase to lipid homeostasis and cell physiology is exemplified in yeast, mice, and humans by a host of cellular defects and lipid-based diseases associated with loss or overexpression of the enzyme activity. In this review, we focus on the mode of action and regulation of PA phosphatase in the yeast Saccharomyces cerevisiae The enzyme Pah1 translocates from the cytosol to the nuclear/endoplasmic reticulum membrane through phosphorylation and dephosphorylation. Pah1 phosphorylation is mediated in the cytosol by multiple protein kinases, whereas dephosphorylation is catalyzed on the membrane surface by an integral membrane protein phosphatase. Posttranslational modifications of Pah1 also affect its catalytic activity and susceptibility to degradation by the proteasome. Additional mechanistic understanding of Pah1 regulation should be instrumental for the identification of small-molecule inhibitors or activators that can fine-tune PA phosphatase function and thereby restore lipid homeostasis.
Salt restriction lowers blood pressure at rest and during exercise without altering peripheral hemodynamics in hypertensive individuals

This is the first study to examine the potential blood pressure lowering benefit of a salt-restrictive diet in individuals with hypertension without any deleterious effects of exercising blood flow...
DP Pareto optimal balanced orthogonal subplot designs

This paper considers the problem of identifying optimal Split-Plot Designs (SPDs) using traditional design criteria along with pure error degrees of freedom. An optimal SPD is of little use if it d...
Theoretical Probe to the Mechanism of Pt-Catalyzed C–H Acylation Reaction: Possible Pathways for the Acylation Reaction of a Platinacycle

Density functional theory (DFT) and nudged elastic band (NEB) theory have been used to study the possible pathways for the acylation of cycloplatinated complex A derived from 2-phenoxypyridine, which is conceived as the key step in the platinum-catalyzed acylation of 2-aryloxypyridines. Geometry optimization indicates that the previously proposed intermediate, an arenium ion species as a result of analogous aromatic substitution, is not an energy minimum, but rather cationic Pt-arene η2-complex E is obtained as a stable intermediate. NEB simulations suggest that the minimum energy pathway for the acylation reaction has energy barrier of 33.6 kcal/mol and consists of the following steps: (1) Nucleophilic substitution at acetyl chloride by the platinum of the reactant A forms five-coordinate Pt(IV) acylplatinum complex B with an energy barrier of 21.7 kcal/mol. (2) B undergoes 1,2-acyl migration from the platinum to the cyclometalated carbon through a three-membered platinacycle transition state to give Pt-arene η2-complex E with an energy barrier of 14.0 kcal/mol. (3) E undergoes ligand exchange with chloride to form neutral Pt-arene η2-complex F. (4) F undergoes ligand substitution with acetonitrile to give the product and the energy barrier is small (10.6 kcal/mol). The rate-determining step is the 1,2-acyl migration step. It is interesting to note that intermediate F was not included in the proposed mechanism but was identified by the NEB simulations. Five-coordinate Pt(IV) acylplatinum complex B undergoes barrierless ligand coordination with chloride to form neutral formal oxidative addition acylplatinum complex D; however, D is less stable than reactant A by 2.9 kcal/mol, which also implies that the isolation of an oxidative addition product Pt(IV) complex may be very challenging. The direct reductive elimination of D to form product P has a higher energy barrier (36.6 kcal/mol).
Transcriptome Profiling of Immune Response to Dendritic/AML Fusion Vaccine

Introduction In a clinical trial of patients vaccinated after chemotherapy-induced remission with patient-derived AML cells fused with autologous dendritic cells (DC/AML fusions) we demonstrated durable AML-specific immunity. 71% of patients sustained long-term remission from AML at 55-91 months (responders) while those who experienced relapse had recurrence at 2-26 months (non-responders). Objectives We performed genomic analysis of the marrow microenvironment to identify factors associated with durable remission after vaccination. Methods RNA sequencing was done using banked formalin-fixed paraffin embedded (FFPE) marrow at serial time points. Ingenuity Pathways IPA 9.0 was used to define pathways and upstream regulators. To characterize the cellular components, single cell RNA-seq was performed on fresh frozen aspirates with cell cluster annotation performed by Single Cell Wizard software and peripheral blood was used for TCR clonal diversity by NGS. Results Heatmaps depict significant (p-value ≤0.01 and fold change ≥2) differential gene expression both pre- and post-vaccination in responders compared to non-responders. Prior to vaccination there was inhibition of TGF-β in responders. Notable upregulated pathways in responders after vaccination (p value Conclusion In a cohort of AML patients treated with DC/AML fusions, we found distinct gene signatures amongst patients with long term remisison vs those with early relapse. The transcriptomes indicate a microenvironment in which TGF-β-mediated immunosuppression is inhibited after chemotherapy and in which interleukins, B cell and macrophage signaling are activated are associated with vaccine response, and have potential for combinatorial therapeutic strategies. T cell costimulation and activation are key components of response with NK cells and DC activation playing a supporting role. A durable oligoclonal T cell expansion suggests vaccine is capable of enhancing the T cell repertroie which could provide a unique opportunity to identify target antigens by TCR-epitope pairing.
Analytics and Operations Research Increases Win Rates for IBM’s Information Technology Service Deals

IBM Research in partnership with IBM Services developed an innovative set of tools that automatically and cognitively reads a request for proposal, extracts client requirements, and maps them to IB...
The Cost of Doing Business: Corporate Crime and Punishment Post-Crisis

For many years, law and economics scholars, as well as politicians and regulators, have debated whether corporate criminal enforcement overdeters beneficial corporate activity or in the alternative, lets corporate criminals off too easily. This debate has recently expanded in its polarization: On the one hand, academics, judges, and politicians have excoriated enforcement agencies for failing to send guilty bankers to jail in the wake of the 2008 financial crisis; on the other, the U.S. Department of Justice has since relaxed policies that encouraged individual prosecutions and reduced the size of fines and number of prosecutions. A crucial and yet understudied piece of evidence in this debate is to understand how corporate crime rates have responded to changes in enforcement practices. And yet, unlike most other types of crime, the government does not provide data about corporate crime levels. Therefore, we cannot easily determine whether these policy changes are effectively deterring future incidents of crime. In this paper, we take important first steps in determining whether corporate crime, and financial institution crime in particular, is on the rise. Specifically, we proxy for corporate crime using three novel sources: the Financial Crimes Enforcement Network (FinCEN) Suspicious Activity Reports (SARs), consumer complaints made to the Consumer Financial Protection Bureau (CFPB), and whistleblower complaints made to the Securities and Exchange Commission (SEC). Each source reveals an increase in complaints or reports indicative of corporate misconduct in the wake of the 2008 financial crisis. We also examine levels of public company recidivism and find that they are also on the rise. And we document a potential explanation: recidivist companies are much larger than non-recidivist companies, but they receive smaller fines than non-recidivist companies (measured as a percentage of market capitalization and revenue). Put simply, for large companies, criminal penalties may be just another cost of doing business—and quite a low cost at that. We conclude by offering recommendations for enforcement agencies and policymakers. In particular, our results suggest that enforcers are unlikely to achieve optimal deterrence using fines alone. Enforcement agencies should therefore consider other ways of securing deterrence, such as by seeking penalties against guilty individuals and the top executives who facilitate their crimes.
Adjoint invariants of second Frobenius kernels of GL(2)

In this article, we apply general results about adjoint invariants of Frobenius kernels for the general linear group GL(m) established by Marko (Adjoint invariants of Frobenius kernels of GL(m) and...
Getting to Complete and Accurate Medication Lists During the Transition to Home Health Care.

Abstract Objectives Characterize the work that home health care (HHC) admission nurses complete as part of the medication reconciliation tasks, explore the impact of shared electronic medication data (interoperability) from the referral source on medication reconciliation, and highlight opportunities to enhance medication reconciliation with respect to transition in care to HHC agencies. Design Observational field study. Settings and Participants Three diverse Pennsylvania HHC agencies; each used different electronic health record systems with different interoperability characteristics. Six nurses per site admitted 2 patients each (36 patients total). Methods Researchers observed the admission process in the patient home and at the HHC agency. The nurses’ tasks related to medication reconciliation were characterized by (1) number and change types (ie, medications dropped or added; changes to dose, frequency/administration time, or tablet types) made to the referrer medication list during and after the home visit, and (2) reasons that the nurse called the health provider (doctor, pharmacy) to resolve medication-related issues. Differences between interoperable and non-interoperable observations were explored. Results Polypharmacy (on average, study patients were taking more than 12 medications) and high-risk medications (on average, more than 8 per patient) were pervasive. For 91% of patients, the number of medications decreased between pre- and post-reconciliation medication lists; 41% of the medications required changes. Nurses using interoperable systems needed to make fewer changes than nurses using non-interoperable systems. In two-thirds of observations, the nurse called a provider. Conclusions and Implications Changes to the referrer medication list and calls to providers highlighted the nurses’ effort to complete the medication reconciliation. Interoperability appeared to reduce the number of changes required, but did not eliminate changes or calls to providers. We highlight opportunities to enhance medication reconciliation with respect to transition in care to HHC agencies.
Interlude on $$(\infty ,1)$$-Categories

If the reader does not care for this chapter, they may soon find out, and they may just as soon skip to the next section. Here we introduce various models of \((\infty ,1)\)-categories. When discussing the model of quasi-categories (otherwise known as weak Kan complexes, or \((\infty ,1)\)-categories), we emphasize the importance of either not having a notion of composition inside a category, or of a functor not “respecting” on the nose some notion of composition between a domain and codomain \((\infty ,1)\)-category.
Cost-Effectiveness of Venous Thromboembolism Prophylaxis During Neoadjuvant Chemotherapy for Ovarian Cancer.

PURPOSE:Two recent clinical trials have demonstrated that direct oral anticoagulants (DOACs) are effective as venous thromboembolism (VTE) prophylaxis in patients with moderate-to-high risk ambulat...
Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries.

Background Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joints at the time of ACL and meniscal surgeries.
Human Beta Cell Mass Expansion In Vivo With A Harmine and Exendin-4 Combination: Quantification and Visualization By iDISCO+ 3D Imaging

Abstract 463 million people globally suffer from diabetes. The majority are deficient in insulin-producing pancreatic beta cells, although beta cells remain in most people with diabetes. Unfortunately, although many diabetes drugs exist, none is able to increase adult human beta cell numbers. Recently, small molecules that inhibit the kinase, DYRK1A, have been suggested to induce human beta cell replication in vitro and in vivo as assessed using proliferation markers, and this is enhanced by drugs that stimulate the GLP1 receptor (GLP1R) on beta cells. DYRK1A inhibitors also enhance human beta cell differentiation and function. However, it is unknown whether any drug can actually increase human beta cell mass in vivo, reflecting: 1) the intrinsic resistance of human beta cells to regeneration; and, 2) the current technical inability to accurately assess human beta cell mass in vivo. Here, we demonstrate for the first time that combining a DYRK1A inhibitor with a GLP1R agonist increases actual human beta cell numbers and overall mass in vivo by 400-700% in diabetic and non-diabetic mice over three months. We further describe a novel application of tissue-clearing and 3D imaging for quantification of human beta cell mass. These findings should be transformative for diabetes treatment.
A cost-effective mobility modelling in nested network mobility

A mobile network is an entire network, moving as a unit, which dynamically change its point of attachment to the Internet and its reach-ability in the topology. Network Mobility is thus the opportunity to realize the Ubiquitous Internet, i.e. permanent access anywhere at anytime, in fixed locations and while on the move, provided that any available access network can be accommodated. In this paper, we propose a cost-effective mobility modelling in nested Network Mobility which is based on binding update multi-cast by various mobility patterns of mobile nodes in nested Network Mobility. This proposed scheme is combined Hierarchical Mobile IPv6 with Network Mobility because a mobile networks and mobile nodes move in tandem and create a hierarchy in the wireless network to management of micro-mobility and seamless handoff. These issues are focuses on the area of mobility modelling in nested Network Mobility. We address the key function for our proposed scheme and simulate the usefulness of our proposed method using mathematically analyze. We then testify that the proposal has best performance compared with Network Mobility protocol.
If Violence Is Domestic, Does It Really Count?

Estimates of the prevalence of marital violence have been found to vary dramatically from survey to survey. This paper addresses one potential explanation for this difference which involves the focus and format of different surveys. We examine the extent to which survey respondents are willing to report marital violence in a context which focuses on criminal behaviors as opposed to a family violence context. In a very basic way, this answers a question as to whether individuals are willing to define acts of marital violence as criminal. Methodologically, it is a measurement issue which seriously affects the ability to compare findings across samples. National Youth Survey data are used to compare rates of generalized spousal assault and victimization reported in a crime context with rates of marital assault and victimization reported in a family violence context. Results indicate that 40 to 83% of all marital assaults and victimizations reported in the marital violence section are not reported in a format which focuses on criminal assault and victimization.
The Persistence and Predictability of Closed-End Fund Discounts

It is well-known that the level of closed-end fund discounts appears to predict the corresponding fund's future returns. We further document that such predictability decays slowly. The popular explanations, including the tax effect, investor sentiment risk, and the funds's dividend yield, do not fully account for the observed predictability. At the same time, discounts are very persistent especially on an aggregate level. Using an AR(1) model for discounts, we demonstrate that such predictability is largely due to persistence in discounts. Our calibration exercise can produce most characteristics of an aggregate equity close-end fund index over the ten year period from 1993 to 2001. A cross-sectional study links discount persistence to rational factors such as dividend yield, unrealized capital gains, and turnover. In addition, we document a second independent source for predicting fund returns from large stock portfolio returns. This suggests that the well-known lead lag relationship between large stocks and small stocks also exists between NAV returns and fund returns. Finally, we find no evidence for "excess volatility" on the aggregate level both for conditional and unconditional volatility.
Influence of Ochratoxin A and Deoxynivalenol on Growing Broiler Chicks

Abstract The effects of feeding diets containing ochratoxin A (OA) (2.0 mg/kg) and deoxynivalenol (DON) (16 mg/kg) singly and in combination were characterized in male broiler chicks from 1 to 3 wk of age. Body weight gains and efficiency of feed utilization were significantly reduced by feeding OA singly, DON singly, and the OA/DON combination. Increased relative liver, kidney, and proventriculus weights were observed in the OA and OA-DON groups and blood urea nitrogen (BUN) was increased in the DON group. Serum uric acid, creatinine, and triglycerides were significantly elevated, and total protein, albumin, cholesterol, and aspartate amino transferase (AST) activity were decreased in the OA group. Histopathological examination of the liver, kidney, spleen, proventriculus, gizzard, and bursa revealed that lesions were confined primarily to mild hepatocellular degeneration, with milk diffuse lipidosis of the liver and mild swelling of the renal tubular epithelium of the OA and OA/DON combination groups. For a few parameters such as efficiency of utilization and relative liver, gizzard, and spleen weights, OA and DON appear to interact additively. However, many of the parameters such as body weights, body weight gains, BUN, total protein, and AST show significant interactions that can best be described as less than additive or in some cases antagonistic.