cssi/SciSciGPT-SciSciNet huggingface dataset:
The timing of hamster sperm nuclear decondensation and male pronucleus formation is related to sperm nuclear disulfide bond content.

The relationship between the timing of both sperm nuclear decondensation and male pronucleus formation in the oocyte and the relative level of disulfide bonds within the sperm nucleus was evaluated. Since reduction of sperm nuclear disulfide (S-S) bonds is a prerequisite for sperm nuclear decondensation in vitro and in vivo, we hypothesized that sperm nuclei with relatively few S-S bonds would require less time to decondense in the oocyte than sperm nuclei with higher numbers of S-S bonds, and that male pronucleus formation would occur more rapidly as well. Four types of hamster sperm nuclei, in which the extent of S-S bonding differed, were microinjected into hamster oocytes, and the time course of sperm nuclear decondensation and male pronucleus formation was charted. Cauda epididymal sperm nuclei, which are rich in S-S bonds, required 45-60 mm to deco ndense. In contrast, nuclei containing few S-S bonds (namely sonication-resistant spermatid nuclei and cauda epididymal sperm nuclei treated in vitro with the S-S bond-reducing agent dithiothreitol) decondensed within 5-10 mm of microinjection. Caput epididymal sperm nuclei, with intermediate S-S bond content, decondensed in 10-20 mm. Regardless of when decondensation occurred, formation of the male pronucleus never preceded that of the female pronucleus, which occurred 1.25-1.5 h after microinjection. However, sperm nuclei with few S-S bonds were more likely than S-S rich nuclei to transform into male pronuclei in synchrony with the formation of the female pronucleus. We conclude that the timing of sperm nuclear decondensation and pronucleus formation depends in part upon the S-S bond content of the sperm nucleus.
Territory-Based Regional Development Policy and Planning in a Learning Economy: The Case of ‘Real Service Centers’ in Industrial Districts

In addressing the intersections between territory-based regional industrial development programs and the challenges faced by firms in the emerging information-based economy, a prerequisite for a more holistic approach to region-wide economic policy development and planning is a public-sector strategic outlook that itself is informed about economic, sectoral and strategic trends and which is built around an understanding of organizational learning. The requirement for public sector ‘know-how’ and ‘know-why’ deviates substantially from past practice wherein the knowledge of sectoral change and economic trends was embedded in separate programs created to provide services to firms. Absent from this model is a feedback loop which builds this understanding into policy making and program design.The most common approach to sectoral programming, which involves linking sectoral problems with programmatic interventions, relies on investigations of markets, products, and production processes that form bottlenecks and...
Coffee Anyone? - Part 2: Additional Business Opportunity Statements For Unstructured Capital Budgeting Projects

This paper builds on an earlier paper that presented an unstructured, semester-long team-based capital budgeting project for senior level undergraduate accounting students. Successfully completing this project required accounting students to step outside of their narrow accounting transactions framework and to apply extensive organizational, analytical, information gathering, and critical thinking skills. This extension paper provides two additional Business Opportunity Statements that can be assigned to student groups for semester projects. Utilizing these additional Statements will allow faculty to challenge consecutive semesters of students.
Antispermatozoal immunoglobulin G in the sera of subfertile men.

Sera were obtained from seven men who had not fathered a child and whose semen showed self-agglutination of spermatozoa. These samples of sera produced considerably more immobilization and agglutination of spermatozoa and positive passive hemagglutination tests than did sera from men whose semen showed less than 10% self-agglutination of spermatozoa. Immunoglobulin G fractionated from the sera of the subfertile men by diethylaminoethylcellulose (DEAE) chromatography produced significantly greater amounts of spermatozoal immobilization and agglutination and passive hemagglutination than did immunoglobulin G obtained from the control group. Elutions of the DEAE columns following fractionation of the IgG from sera of the subfertile men had no antisemen effects.
Effects of Natural and Artificial Herbivory on Endophyte-Infected Tall Fescue, Festuca Arundinacea and Response by the Aphid, Rhopalosiphum Padi

Many endophytic fungi are asymptomatic, showing no external signs of infection. The majority, however, produce alkaloids (West, 1994). Alkaloids are the proposed toxic agents to vertebrate herbivores (Lyons et al., 1986; Read and Camp. 1986) and are also attributed to reducing insect herbivory (Siegel et a/., 1990; Breen, 1994)
2016 Young Investigator Award of the American Physiological Society Renal Section

Minolfa Prieto, M.D., PhD, Associate Professor at Tulane University ([Fig. 1][1]), is the recipient of the Young Investigator Award of the American Physiological Society (APS) Renal Section for 2016. Dr. Prieto is an exceptionally talented scientist in renal physiology working in the Department of
Reactivity of electrophilic Cp∗Ru(NO) complex towards alcohols

Abstract Treatment of the complex 1 Cp*Ru(NO)(OTf)2 (OTf = OSO2CF3, Cp* = η5-C(CH3)5) with neat 2-propanol results in the rapid quantitative formation of the Ru(0) complex [Cp*Ru(μ-NO)]2 and (CH3)2C O. Formation of H2 and CHDCl2 is detected when the reaction between 1 and 2-propanol occurs in CDCl3, indicating possible formation of a short-lived metal hydride species. Similar results are observed upon treatment of 1 with ethanol and methanol, with formation of acetaldehyde and formaldehyde, respectively. The kinetics of the oxidation of 2-propanol by complex 1 is studied by 1H NMR spectroscopy in CH2Cl2 at variable temperatures and the reaction is found to be first-order in complex 1 and in 2-propanol. The kinetic isotope effect for the reaction of 1 with (CD3)2CD-OD at −11 °C is determined to be kH/kD = 2.0 (3). A mechanism for alcohol oxidation by electrophilic ruthenium (II) complexes via a β-hydrogen elimination step is proposed. The pre-equilibrium exchange step between complex Cp*Ru(NO)(OTf)2 (1) and alcohol-coordinated species is examined by 19F and 1H NMR spectroscopy in CH2Cl2 solution, where triflate substitution is found to be exothermic and entropically unfavorable. The synthesis and solid state structure of the chelate-stabilized complex diol salt [Cp*Ru(NO)(HO–CH2CH2–OH)][2OTf] are discussed.
Displacement data assimilation

We show that modifying a Bayesian data assimilation scheme by incorporating kinematically-consistent displacement corrections produces a scheme that is demonstrably better at estimating partially observed state vectors in a setting where feature information is important. While the displacement transformation is generic, here we implement it within an ensemble Kalman Filter framework and demonstrate its effectiveness in tracking stochastically perturbed vortices.
Coarse Grained Simulation and Turbulent Material Mixing

Accurate predictions with quantifiable uncertainty are essential to many practical turbulent flow applications in engineering, geophysics, and astrophysics exhibiting extreme geometrical complexity and broad ranges of length and time scales. In contexts of interest, such as inertial confinement fusion and supernova implosions, mixing of materials by the small scales of turbulent motion is a critical element, and we are interested in detailed understanding of the consequences of material interpenetration, flow instabilities, and mixing arising from perturbations at the material interfaces. Simulation modeling and predictability issues are revisited for under-resolved material mixing driven by under-resolved velocity fields, and then also in conjunction with under-resolved initial conditions. Implications for turbulent mixing big data generation, reduction, and organization are discussed in this context.
INDUCTION OF SURFACE RECEPTORS ON GRANULOCYTE, T, AND B CELL PRECURSORS IN HUMAN BONE MARROW BY THYMIC AND NON-THYMIC AGENTS

Publisher Summary Human hemopoietic cells can be characterized by the presence of an array of unique and shared receptors on their surface. These surface receptors can be used as differentiation markers because they have been shown to be present on cells only at specific stages of development. Thymocytes and peripheral T lymphocytes have receptors for sheep erythrocytes and thus form E rosettes. B lymphocytes, monocytes, and mature granulocytes have complement receptors and form EAC rosettes. B lymphocytes alone have receptors for mouse erythrocytes and form M rosettes. The expression of all of these markers has been evaluated on all cell fractions after incubation with or without inducers. This chapter reviews some experiments to discuss the induction of surface receptors on granulocyte, T, and B-cell precursors in human bone marrow by thymic and non-thymic agents. It provides an overview of the methods used in the experiments and the results of the experiments. These experiments suggest that the cell separation procedures provide sufficiently homogeneous cell populations to allow identification of the cells responsive to the polypeptide hormones and cyclic nucleotide studied. These agents induce the expression of the receptor for sheep erythrocytes by a direct action on lymphocytes, and the complement receptor by a direct action on immature granulocytes. Some induction of a B-cell marker was observed in the experiments, but it is not clear whether this is due to a direct effect of thymopoietin on B cells or an indirect effect via thymopoietin influence on T cells. The chapter further presents several examples of the hormonal induction of hematopoietic differentiation.
A new peri-Amazonian species of Protium . Studies in neotropical Burseraceae XXI

Protium decorum is described and illustrated. The distribution of this new taxon exemplifies a rather common pattern around the southern periphery of the Amazon.
The reasons older immigrants in the United States of America report for returning to Mexico

Mexicans are the largest immigrant group in the United States and are ageing rapidly. Data support that many return to Mexico due to economic factors such as employment. Few studies have investigated if older immigrants return to Mexico for different reasons than younger immigrants. Using the Mexican Health and Aging Study (N=952), we examine whether Mexican immigrants in the United States who returned to Mexico at age 50 and older report different reasons for returning than those who returned at younger ages. Few immigrants (regardless of age) returned to Mexico for economic reasons. The most commonly reported reason for returning to Mexico for both groups was missing family. However, the odds of listing illness over missing family as their main reason for returning were higher for older immigrants than younger immigrants after controlling for duration in the United States and other sociodemographic factors (OR=0.27; 95% CI=0.11, 0.68). These results challenge existing theories of international migration which focus on employment considerations.
Analysis of very-high-resolution Galileo images and implications for resurfacing mechanisms on Europa

Abstract The young ( Greeley et al., 2000 )—during the E12 flyby of Europa in Dec. 1997. This dataset is now two decades old, but it has not been analyzed in detail until this work. Despite the largely different viewing and lighting conditions, we mosaic these high-resolution frames into the 220 m/pixel regional context frame. We then perform geomorphologic mapping of the high-resolution image mosaic and the regional image frame, for comparison, and we also create a structural map of the high-resolution image mosaic. The units in the geomorphologic map are defined by surface texture, landform shape (morphology), dimension, and relative albedo. The structural map units include interpretations from the geomorphologic map units and their interpretation implies potential kinematic processes for the formation of particular structures. Our primary mapping observations include the regular spacing and gentle slopes of the ridge-and-trough terrain, the sharp boundaries and preserved structures of the chaos terrain, and the symmetry but irregular size of double ridges. We then evaluate proposed formation mechanisms for these and other mapped features. The high-resolution images also reveal an abundance of small (
Insulin resistance is associated with depression risk in polycystic ovary syndrome.

Objective To test the hypothesis that insulin resistance is associated with depression risk in polycystic ovary syndrome (PCOS). Design Secondary analysis of data from a multicenter randomized trial. Setting Multicenter university-based clinical practices. Patient(s) Seven hundred thirty-eight women with PCOS by modified Rotterdam criteria seeking pregnancy enrolled in a randomized clinical trial comparing clomiphene citrate versus letrozole. Intervention(s) The Primary Care Evaluation of Mental Disorders Patient Health Questionnaire was self-administered to identify depression using a validated algorithm at enrollment. Demographic and anthropometric data were collected, and serum assays were performed. Insulin resistance was estimated using the homeostatic model of insulin resistance (HOMA-IR), with a cutoff of >2.2 considered abnormal. Main Outcome Measure(s) Demographic, endocrine, and metabolic parameters associated with depression. Result(s) In a univariate logistic regression analysis, elevated HOMA-IR was associated with 2.3-fold increased odds of depression (odds ratio [OR] = 2.32; 95% confidence interval [CI], 1.28–4.21). This association remained significant after controlling for age and body mass index (adjusted OR [aOR] = 2.23; 95% CI, 1.11–4.46) and in a model including additional potential confounders (aOR = 2.03; 95% CI, 1.00–4.16). Conclusion(s) Insulin resistance has a strong and independent association with depression in PCOS and may serve as a physiologic mediator. Our findings corroborate a growing body of evidence linking insulin resistance to depressed mood. The association between insulin resistance and depressed mood warrants further investigation to elucidate mechanisms and identify potential therapeutic targets.
A field-based rhetorical critique of ethical accountability

ABSTRACTThis essay suggests that the concept of interdependence provides a rhetorical telos for research ethics. Current field-based rhetoric work advocates for a postcolonial research ethic. However, this is often articulated with a discourse of ethical accountability. Although it has advantages, accountability limits us by excluding ethical pursuit and reifying people as autonomous individuals. In contrast, interdependence helps complete the liberatory trajectory of postcolonial research ethics. Drawing on work in a recent field site, I argue that interdependence encourages scholars to see dilemmas as an opportunity for rhetorical response and ethical lament, helps scholars take creative action to be shaped by participants directly, and helps scholars explain to others why they pursue ethical actions beyond what is socially required.
12 Chronometric Analysis of Human Information Processing

The covariation of P300 latency and reaction time was assessed in two sets of experiments designed to test the hypothesis that P300 latency reflects a subset of the information processes whose durations are reflected in RT. In the first experiments, P300 latency and RT were shown to covary as a function of the time required to categorize a stimulus. However, this relationship could be dissociated by requiring subjects to make highly speeded responses which also resulted in increased error rates. In the second experiments two factors, stimulus discriminability and stimulus-response compatibility, were shown to have additive and independent effects upon RT. The latency of P300 was strongly affected by stimulus discriminability but only minimally affected by S-R compatibility. These results are interpreted to support the hypothesis that P300 latency reflects primarily the durations of processes concerned with stimulus evaluation and is relatively unaffected by processes concerned with response selection and execution.
Analysis of Nucleocytoplasmic Shuttling of NFκB Proteins in Human Leukocytes

Controlled nucleocytoplasmic localization regulates activity of NF kappa B as well as other transcription factors. Analysis of the nucleocytoplasmic protein shuttling has been greatly facilitated by the use of leptomycin B (LMB), an inhibitor of CRM1-dependent nuclear export. The authors have previously shown that LMB inhibits NF kappa B activity in human neutrophils by increasing the nuclear accumulation of NF kappa B inhibitor, I kappa B alpha. In this chapter, the authors describe a protocol that uses LMB to study the nucleocytoplasmic shuttling of I kappa B alpha in human macrophage-like U937 cells, thus inhibiting NF kappa B activity. This protocol should be readily adaptable to analyze the nucleocytoplasmic shuttling of other proteins in human leukocytes.
STUDIES ON THE RELEASE OF PROPRANOLOL FROM ADRENERGIC NEURONS

ABSTRACT In dogs pretreated with propranolol, nerve stimulation or tyramine produced a simultaneous release of propranolol and norepinephrine from the heart. Direct myocardial stimulation with isoproterenol, however, did not release propranolol. Propranolol release was also observed in vitro with cultured sympathetic ganglia exposed to tyramine or veratridine. The results suggest that nerve endings may provide a presynaptic depot for the storage and release of antagonists as well as transmitter.
Differences in Functional Expression of Connexin43 and NaV1.5 by Pan- and Class-Selective Histone Deacetylase Inhibition in Heart

Class-selective histone deacetylase (HDAC) inhibitors were designed to improve safety profiles and therapeutic effectiveness in the treatment of multiple cancers relative to pan-HDAC inhibitors. However, the underlying mechanisms for their therapeutic and cardiotoxic potentials remain poorly understood. Cardiac sodium currents (INa) and gap junction conductance (gj) were measured by whole cell patch clamp techniques on primary cultures of neonatal cardiomyocytes. Cardiac NaV1.5 sodium channel and connexin43 (Cx43) gap junction protein levels were assessed by Western blot analyses. Panobinostat produced concentration-dependent reductions in ventricular gj, peak INa density, and NaV1.5 protein expression levels. Membrane voltage (Vm)-dependent activation of INa was shifted by +3 to 6 mV with no effect on inactivation. Entinostat (1 μM) did not affect ventricular gj, peak INa density, or INa activation. However, the INa half-inactivation voltage (V½) was shifted by −3.5 mV. Ricolinostat had only minor effects on ventricular gj and INa properties, though INa activation was shifted by −4 mV. Cx43 and NaV1.5 protein expression levels were not altered by class-selective HDAC inhibitors. The lack of effects of class-selective HDAC inhibitors on ventricular gj and INa may help explain the improved cardiac safety profile of entinostat and ricolinostat.
KeyBin2: Distributed Clustering for Scalable and In-Situ Analysis

We present KeyBin2, a key-based clustering method that is able to learn from distributed data in parallel. KeyBin2 uses random projections and discrete optimizations to efficiently clustering very high dimensional data. Because it is based on keys computed independently per dimension and per data point, KeyBin2 scales linearly. We perform accuracy and scalability tests to evaluate our algorithm's performance using synthetic and real datasets. The experiments show that KeyBin2 outperforms other parallel clustering methods for problems with increased complexity. Finally, we present an application of KeyBin2 for in-situ clustering of protein folding trajectories.
Self-stigma of antidepressant users through secondary analysis of PhotoVoice data.

Abstract Introduction: Aspects of self-stigma and medication-related stigma among individuals with depressive disorders remain largely unexplored. The primary objective of this study is to highlight and characterize self-stigma and medication-related stigma experiences of antidepressant users. Methods: This is a secondary analysis of data obtained from PhotoVoice studies examining psychotropic medication experiences. Transcripts of reflections from 12 individuals self-reporting a depressive disorder diagnosis and receipt of a prescription for an antidepressant were included. A directed content analysis approach based on expansion of the Self-Stigma of Depression Scale and an iterative process of identification of medication-stigma and stigma-resistance were used. Total mentions of self-stigma, stigma resistance, medication stigma, and underlying themes were tallied and evaluated. Results: Self-stigma was mentioned a total of 100 times with at least 2 mentions per participant. Self-blame was the most promi...
Effect of Surface Hydrophobicity of Pd/Al2O3 on Vanillin Hydrodeoxygenation in a Water/Oil System

Pickering emulsions stabilized by solid catalysts have received an increasing amount of attention as a reaction platform because of potential applications in the chemical industry. Here, we report a surface modification strategy for controlling the catalytic performance of Pd/Al2O3 during vanillin hydrodeoxygenation (HDO) in a water/decalin emulsion environment. A series of organophosphonic acids (PAs) were applied as modifiers to control the surface hydrophobicity, thereby determining the continuous and dispersed emulsion phases. The PAs also introduced Bronsted acid sites that promoted vanillin HDO. Reaction studies showed that the yield of the HDO product p-creosol was improved from 20% to as high as 90% upon PA modification after a reaction duration of 1 h at 50 °C. This improvement greatly depended on the surface hydrophobicity, which influenced the selectivity to different reaction pathways as well as the emulsion structures. Statistical analysis of the kinetic data confirmed the hydrophobic/hydroph...
Manufacture of Clinical-Grade Universal Antigen Presenting Cells (UAPC) for the Ex Vivo Expansion and Activation of Natural Killer (NK) Cells

NK cells are potent cellular immunotherapeutic agents against a wide array of human malignancies. Ex vivo expansion of NK cells to achieve clinically relevant numbers must overcome poor in vitro growth kinetics, low starting percentages within the mononuclear cell fraction (especially from autologous donors with active disease), and limited in vivo life span. We targeted three universally critical NK signaling pathways, namely IL-21, 4-1BB, and SLAM family member 4 (SLAMF4), to increase NK cell proliferation and enhance survival. We genetically-engineered HLA-A-ve and -B-ve K562 cells to enforce expression of membrane-bound IL-21 (mbIL21), 4-1BB-L, and CD48, forming a universal antigen presenting cell (UAPC) to generate highly potent clinical-grade umbilical cord blood (CB-NK) or peripheral blood NK cells (PB-NK). While the mbIL21 and 4-1BB signaling nexuses have been utilized previously, we highlight here SLAMF-mediated immunological sculpting of NK cells for clinical applications. SLAMF triggering of co-receptors modulate NK cell activation, in particular through high-avidity interactions between SLAMF4 (2B4/CD244) and its heterophilic, robust affinity, and physiological ligand CD48, a glycosyl-phosphatidyl-inositol (GPI)-anchored cell surface protein. Upon ligand binding and receptor phosphorylation, SLAMF4 recruits PTPN11/SHP-2 and SH2D1A/SAP for downstream signaling, including significant increases in NK cell-mediated cytotoxicity, granule exocytosis, and production of IFN-γ and IL-2. Other than a subset of low surface density expressers from aging subjects consistently associated with inefficient and impaired activating signal transduction, the majority of NK cells express SLAMF4. The functional prominence of SLAMF4, presently recognized as an activating co-receptor, is also evidenced by loss-of-function mutations associated with X-linked lymphoproliferative (XLP) disease. We achieved log-scale expansion of NK cells with UAPC (>1000 fold in 2 weeks), with excellent purity (>99% CD56+ve/CD3−ve and Disclosures Champlin:Sanofi: Research Funding; Otsuka: Research Funding. Shpall:Affirmed GmbH: Research Funding. Rezvani:Affirmed GmbH: Research Funding.
Informed consent for genetic research.

Genetic research often utilizes or generates information that is potentially sensitive to individuals, families, or communities. For these reasons, genetic research may warrant additional scrutiny from investigators and governmental regulators, compared to other types of biomedical research. The informed consent process should address the range of social and psychological issues that may arise in genetic research. This paper addresses a number of these issues, including recruitment of participants, disclosure of results, psychological impact of results, insurance and employment discrimination, community engagement, consent for tissue banking, and intellectual property issues. Points of consideration are offered to assist in the development of protocols and consent processes in light of contemporary debates on a number of these issues. Curr. Protoc. Hum. Genet. 66:1.16.1-1.16.13 © 2010 by John Wiley & Sons, Inc. Keywords: consent; regulatory; disclosure; ethics; genetic testing
Use of PCSK9 Inhibitor Therapy in a Small Cohort of Heart Transplant Recipients with Statin Intolerance or Refractory Hyperlipidemia

Purpose Use of statin therapy in heart transplant (HT) recipients offers the dual benefits of lipid control and as an anti-rejection agent. It is unknown whether PCSK9 inhibitors are safe and effective in transplant recipients and whether there might be similar anti-rejection or anti-inflammatory benefits in this patient population. Methods We identified eight patients in our outpatient HT clinic who were either statin intolerant (defined by myositis or transaminitis) or with refractory hyperlipidemia (defined as LDL > 80 in patients with cardiac allograft vasculopathy [CAV] or LDL > 120 in patients without prior CAV). Baseline demographics including lipid parameters and presence or absence of CAV were collected. Descriptive statistical analysis were performed in Excel. Results The mean age was 54 years. The average time after HT to PCSK9 initiation ranged from one month to 28 years. Two patients were treated for refractory hyperlipidemia, while the remaining were statin intolerant. All patients tolerated evolocumab 140 mg subcutaneously every two weeks, with no reported side effects. The average time on PCSK9 inhibitor therapy was 14 months. Six patients have follow up LDL values at 3 months after starting therapy. In this group the LDL decreased from a mean of 146.2 mg/ dL prior to therapy to 78.1 mg/ dL after 1-3 months of treatment (p = 0.016). One patient was intolerant to both statin therapy and everolimus. In this patient we saw an improvement in CAV at 1 year angiographic follow up. Conclusion Use of PCSK9 inhibitors in this small single-center cohort appears to be safe and effective. While this therapy has known benefit for atherosclerosis, additional research is needed to understand whether there are anti-inflammatory properties that may stabilize or improve CAV in a larger cohort of HT recipients.
Label-free absolute protein quantification with data-independent acquisition

Despite data-independent acquisition (DIA) has been increasingly used for relative protein quantification, DIA-based label-free absolute quantification method has not been fully established. Here we present a novel DIA method using the TPA algorithm (DIA-TPA) for the absolute quantification of protein expressions in human liver microsomal and S9 samples. To validate this method, both data-dependent acquisition (DDA) and DIA experiments were conducted on 36 individual human liver microsome and S9 samples. The MS2-based DIA-TPA was able to quantify approximately twice as many proteins as the MS1-based DDA-TPA method, whereas protein concentrations determined by the two approaches were comparable. To evaluate the accuracy of the DIA-TPA method, we absolutely quantified carboxylesterase 1 concentrations in human liver S9 fractions using an established SILAC internal standard-based proteomic assay; the SILAC results were consistent with those obtained from DIA-TPA analysis. Finally, we employed a unique algorithm in DIA-TPA to distribute the MS signals from shared peptides to individual proteins or isoforms and successfully applied the method to the absolute quantification of several drug-metabolizing enzymes in human liver microsomes. In sum, the DIA-TPA method not only can absolutely quantify entire proteomes and specific proteins, but also has the capability quantifying proteins with shared peptides. SIGNIFICANCE: Data independent acquisition (DIA) has emerged as a powerful approach for relative protein quantification at the whole proteome level. However, DIA-based label-free absolute protein quantification (APQ) method has not been fully established. In the present study, we present a novel DIA-based label-free APQ approach, named DIA-TPA, with the capability absolutely quantifying proteins with shared peptides. The method was validated by comparing the quantification results of DIA-TPA with that obtained from stable isotope-labeled internal standard-based proteomic assays.
Dextran coated superparamagnetic iron oxide nanoparticles produced by microfluidic process

Abstract Dextran coated biocompatible water-based magnetite (Fe3O4) nanostructured media was produced via microfluidic process at various flow rates. The influences of dextran molecular weight on the magnetite particle size and magnetic property of nano fluid were investigated. Magnetite produced at flow rate of 0.04 mL/s showed uniform particle size distribution with average size 10 nm and saturation magnetization (Ms) up to 60 emu/g. The X-ray diffraction pattern indicates pure phase of Fe3O4 as-synthesized nanoparticles with high crystallinity. Zero Field Cooled and Field Cooled measurements indicated a superparamagnetic nature of as synthesized particles with a low blocking temperature that varies by the amount of dextran introduced in the mixture. The Specific Power Absorption (SPA) value obtained of up to 130 W/g shows that the magnetite–dextran nanostructured fluid appears to be a promising active media for the local magnetic hyperthermia for cancer therapy.
Abstract 5103: The dark cancer kinome - untapped opportunities for the development of novel drugs

Kinases are firmly established drug targets in cancer. There are currently 44 FDA approved kinase drug and hundreds of compounds are in clinical development. However, less than 10% of the Kinome is currently targeted and a large proportion is considered understudied by the NIH Illuminating the Druggable Genome Program (https://druggablegenome.net/). No small molecule inhibitors are known for these “dark” proteins, yet many may be opportune novel cancer targets.We developed a computational pipeline to identify and prioritize understudied kinases as cancer drug targets. We analyzed the complete set of tumors in The Cancer Genome Atlas (TCGA). For 33 different cancers we performed differential expression analysis and identified 39 dark kinases that exhibit significant upregulation in at least four types. Using co-expression analysis we built functional networks prioritizing drug targets. To identify small molecules that reverse their expression levels, we leveraged transcriptional response signatures obtained from dozens of human cancer cell lines exposed to tens of thousands of small molecules from the Library of Integrated Network-based Cellular Signatures (LINCS). To identify small molecules that directly bind to and inhibit dark kinases, we have have combined an advanced AI (artificial intelligence) model trained on activity data from across the Kinome with structure-based simulations.Using the computational pipeline, we identified the dark Ca2+/Calmodulin dependent kinase PNCK as the most differentially overexpressed kinase in kidney cancer patients. Our analyses have demonstrated statistically significant correlation between PNCK mRNA levels and various clinical and pathological outcomes, including histologic grade, clinical staging and overall survival. We have confirmed high levels of PNCK expression in 5 renal cell carcinoma cell lines (Caki-1, ACHN, 786-O, A704 and A498). Knockdown and overexpression studies have suggested PNCK and the CaMK pathway may contribute to cellular proliferation and cell cycle progression. We have applied our AI-based screening pipeline to a library of >20 million commercially available compounds and confirmed three PNCK inhibiting chemotypes. In summary, using a novel computational pipeline, we have identified and experimentally validated PNCK as a prospective novel drug target in an understudied pathway that is highly upregulated in kidney cancer. We identified first in class small molecules that target this previously dark kinase as prospective starting points for optimization into a clinical candidate. Citation Format: Derek J. Essegian, Rimpi Khurana, Vasileios Stathias, Valery Chavez, Jaime R. Merchan, Stephan Schurer. The dark cancer kinome - untapped opportunities for the development of novel drugs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5103.
Vanishing of second cohomology for tensor products of type II1 von Neumann algebras

We show that the second cohomology group H2(M⊗¯N,M⊗¯N) is always zero for arbitrary type II1 von Neumann algebras M and N.
Swallowing Characteristics in Zenker's-like Diverticulum After Anterior Cervical Spine Surgery

OBJECTIVES A Zenker's diverticulum (ZD) is a hypopharyngeal pulsion diverticula caused by dysfunction of the cricopharyngeus muscle with herniation of hypopharyngeal mucosa through Killian's dehiscence. Anterior cervical spine surgery (ACSS) can cause a Zenker's-like traction diverticulum (ZTD) with a similar presentation but different pathophysiology. The purpose of this investigation was to compare the fluoroscopic parameters and surgical outcomes of ZTD after ACSS to those of typical ZD. STUDY DESIGN Case-control study. METHODS The charts of patients undergoing a videofluoroscopic swallow study after ACSS between January 1, 2014, and January 1, 2018, were evaluated for evidence of ZTD. Patients with ZTD were age and gender matched to persons with ZD. Fluoroscopic parameters and patient-reported outcomes were compared between groups. RESULTS Eleven patients with ZTD were identified. The mean pharyngeal constriction ratio (PCR) was significantly higher for persons with ZTD (0.87 [±0.07] vs. 0.17 [±0.08]; P < 0.05). Mean hyolaryngeal elevation was significantly less (2.5 [±0.9] cm vs. 3.5 [±0.7] cm) and mean diverticulum size significantly smaller (1.3 [±1.0] cm vs. 2.3 [±2.0] cm) for persons with ZTD (P < 0.05). Five ZTD patients had exposed hardware necessitating open approach for removal. CONCLUSION We report the largest cohort of ZTD after ACSS. ZTD are smaller than traditional Zenker's and associated with more pharyngeal weakness, poorer laryngeal elevation, and worse treatment outcomes. Although these diverticula can be managed endoscopically, the high percentage of exposed cervical hardware necessitates a thorough preoperative assessment and frequent need for open management and pharyngeal repair. LEVEL OF EVIDENCE 3b Laryngoscope, 130:1383-1387, 2020.
STATE TAXES AND LEGISLATIVE TURNOVER IN THE UNITED STATES

Mounting empirical evidence suggests that term limits and, by extension, higher legislative turnover increase the overall size of government and change its spending composition. However, less is known about the turnover's impact on the composition of tax revenues. This study fills this void by exploiting exogenous variation in term limits and redistricting as instruments for legislative turnover, which is found to be positively associated with most state taxes except for the corporate income tax. We hypothesize that the negative association between legislative turnover and corporate income taxes might be influenced by a higher propensity of business owners to enter term‐limited state legislatures.
Using Guilt and Shame Appeals from an Eastern Perspective to Promote Bystander Intervention: A Study of Mitigating Domestic Violence in India

Domestic violence is an ongoing health issue affecting women around the world. Bystander intervention is one way to help minimize occurrences of domestic violence in the future. However, bystanders...
Food insecurity, health care utilization, and health care expenditures

OBJECTIVE To disentangle the relationships among food insecurity, health care utilization, and health care expenditures. DATA SOURCES/STUDY SETTING We use national data on 13 465 adults (age ≥ 18) from the 2016 Medical Expenditure Panel Survey (MEPS), the first year of the food insecurity measures. STUDY DESIGN We employ two-stage empirical models (probit for any health care use/expenditure, ordinary least squares, and generalized linear models for amount of utilization/expenditure), controlling for demographics, health insurance, poverty status, chronic conditions, and other predictors. PRINCIPAL FINDINGS Our results show that the likelihood of any health care expenditure (total, inpatient, emergency department, outpatient, and pharmaceutical) is higher for marginal, low, and very low food secure individuals. Relative to food secure households, very low food secure households are 5.1 percentage points (P < .001) more likely to have any health care expenditure, and have total health care expenditures that are 24.8 percent higher (P = .011). However, once we include chronic conditions in the models (ie, high blood pressure, heart disease, stroke, emphysema, high cholesterol, cancer, diabetes, arthritis, and asthma), these underlying health conditions mitigate the differences in expenditures by food insecurity status (only the likelihood of any having any health care expenditure for very low food secure households remains statistically significant). CONCLUSIONS Policy makers and government agencies are focused on addressing deficiencies in social determinants of health and the resulting impacts on health status and health care utilization. Our results indicate that chronic conditions are strongly associated with food insecurity and higher health care spending. Efforts to alleviate food insecurity should consider the dual burden of chronic conditions. Finally, future research can address specific mechanisms underlying the relationships between food security, health, and health care.
Child Abuse, Spanking and Adult Dating Violence: A Replication Study of Temple et al., 2018

The issue of whether spanking does or does not contribute to later aggression remains controversial despite public policy statements by the American Academy of Pediatrics and other groups opposing spanking. Studies have remained inconsistent regarding whether spanking does or does not contribute to later aggression. One study, Temple et al., 2018, released results from an adult retrospective study suggesting that spanking and related corporal punishment could predict adult dating violence, but that actual physical child abuse exposure did not. This current study attempted to replicate this unusual finding using similar methodologies. Current results did not replicate the findings of Temple et al., 2018. Exposure to child physical abuse predicted adult dating violence, but exposure to spanking and related corporal punishment did not. These results suggest it may be premature to link spanking to aggression in adulthood.
Medicate to Graduate: Academic Strain and Nonmedical Prescription Stimulant Use Among Graduate and Undergraduate Students:

The nonmedical use of prescription stimulants has been prevalent on college campuses in recent years. Previously, nonmedical prescription stimulant use (NMPSU) has been associated with increased us...
The first digit of the discriminant of Eisenstein polynomials as an invariant of totally ramified extensions of p-adic fields

Let K be an extension of the p-adic numbers with uniformizer π. Let φ and ψ be Eisenstein polynomials over K of degree n that generate isomorphic extensions. We show that if the cardinality of the residue class field of K divides n(n−1), then v(disc(φ)− disc(ψ))>v(disc(φ)). This makes the first (nonzero) digit of the π-adic expansion of disc(φ) an invariant of the extension generated by φ. Furthermore we find that noncyclic extensions of degree p of the field of p-adic numbers are uniquely determined by this invariant.
Toward net-zero sustainable aviation fuel with wet waste–derived volatile fatty acids

With the increasing demand for net-zero sustainable aviation fuels (SAF), new conversion technologies are needed to process waste feedstocks and meet carbon reduction and cost targets. Wet waste is a low-cost, prevalent feedstock with the energy potential to displace over 20% of US jet fuel consumption; however, its complexity and high moisture typically relegates its use to methane production from anaerobic digestion. To overcome this, methanogenesis can be arrested during fermentation to instead produce C2 to C8 volatile fatty acids (VFA) for catalytic upgrading to SAF. Here, we evaluate the catalytic conversion of food waste-derived VFAs to produce n-paraffin SAF for near-term use as a 10 vol% blend for ASTM "Fast Track" qualification and produce a highly branched, isoparaffin VFA-SAF to increase the renewable blend limit. VFA ketonization models assessed the carbon chain length distributions suitable for each VFA-SAF conversion pathway, and food waste-derived VFA ketonization was demonstrated for >100 h of time on stream at approximately theoretical yield. Fuel property blending models and experimental testing determined normal paraffin VFA-SAF meets 10 vol% fuel specifications for "Fast Track." Synergistic blending with isoparaffin VFA-SAF increased the blend limit to 70 vol% by addressing flashpoint and viscosity constraints, with sooting 34% lower than fossil jet. Techno-economic analysis evaluated the major catalytic process cost-drivers, determining the minimum fuel selling price as a function of VFA production costs. Life cycle analysis determined that if food waste is diverted from landfills to avoid methane emissions, VFA-SAF could enable up to 165% reduction in greenhouse gas emissions relative to fossil jet.
The Calcium Signaling Mechanisms in Arterial Smooth Muscle and Endothelial Cells

The contractile state of resistance arteries and arterioles is a crucial determinant of blood pressure and blood flow. Physiological regulation of arterial contractility requires constant communication between endothelial and smooth muscle cells. Various Ca2+ signals and Ca2+ -sensitive targets ensure dynamic control of intercellular communications in the vascular wall. The functional effect of a Ca2+ signal on arterial contractility depends on the type of Ca2+ -sensitive target engaged by that signal. Recent studies using advanced imaging methods have identified the spatiotemporal signatures of individual Ca2+ signals that control arterial and arteriolar contractility. Broadly speaking, intracellular Ca2+ is increased by ion channels and transporters on the plasma membrane and endoplasmic reticular membrane. Physiological roles for many vascular Ca2+ signals have already been confirmed, while further investigation is needed for other Ca2+ signals. This article focuses on endothelial and smooth muscle Ca2+ signaling mechanisms in resistance arteries and arterioles. We discuss the Ca2+ entry pathways at the plasma membrane, Ca2+ release signals from the intracellular stores, the functional and physiological relevance of Ca2+ signals, and their regulatory mechanisms. Finally, we describe the contribution of abnormal endothelial and smooth muscle Ca2+ signals to the pathogenesis of vascular disorders. © 2021 American Physiological Society. Compr Physiol 11:1831-1869, 2021.
A Transdiagnostic Application of the Contrast-Avoidance Model: The Effects of Worry and Rumination in a Personal-Failure Paradigm:

The contrast-avoidance model (CAM) originally described emotion-regulation patterns in generalized anxiety disorder (GAD), proposing that chronic worry maintains negative emotionality, thus attenua...
A Case of Neuromyelitis Optica Spectrum Disorder Who Relapsed Under Oral Corticosteroid Treatment with Multiple Cerebrospinal Lesions and Severe Neurological Deficits

We present a case of a 59-year-old female who had been treated for optic neuritis 2 years before being transferred to our hospital. She had been positive for anti-AQP4 antibodies. No cerebrospinal lesions were observed, and based on the diagnosis of neuromyelitis optica spectrum disorder (NMOSD), 5 mg/day oral prednisolone was continued for 2 years. Acute lower back pain and urinary retention appeared on day X. On day X + 1, consciousness disturbance (JCS level II) and paraplegia appeared, and she was transferred to our hospital. Neck stiffness, paraplegia, and urinary retention were present. A cerebrospinal fluid examination revealed mononucleosis-dominant pleocytosis (1,232 cells/μl). Brain magnetic resonance imaging (MRI) showed multiple lesions around the ventricles and corpus callosum, and spinal MRI revealed a longitudinally extensive transverse myelitis lesion (C2-Th5). A relapse of NMOSD was diagnosed and steroid pulse therapy was started, but the symptoms progressed and quadriplegia and coma occurred. Head MRI showed new deep white matter lesions around the ventricles. Plasma exchange was added after the second steroid pulse. The patient's consciousness gradually improved, and spontaneous movement of the left upper limb eventually appeared. We experienced a case of NMOSD that relapsed with multiple cerebrospinal lesions despite corticosteroid therapy, but plasmapheresis therapy was effective.
Risk Patterns and Mortality in Postmenopausal Women Using Latent Class Analysis.

Introduction Although risk factors often co-occur, previous studies examining lifestyle or psychosocial factors often treat these factors as individual predictors of health. This study aims to identify the underlying subgroups of women characterized by distinct lifestyle and psychosocial risk patterns and to investigate the prospective associations between risk patterns and mortality among postmenopausal women. Methods A total of 64,812 postmenopausal women aged 50–79 years without prevalent diabetes, cardiovascular disease, and cancer at baseline (1993–1998) were followed until 2019 with a mean follow-up duration of 14.6 (SD=6.4) years. Latent class analysis was used to identify the latent classes of women with homogeneous combinations of lifestyle and psychosocial variables and to test whether the classes were prospectively associated with mortality. Analyses were stratified by race/ethnicity and were performed in 2020. Results A total of 4 latent classes (Healthy Lifestyle and Psychosocial, Risky Psychosocial, Risky Lifestyle, and Risky Lifestyle and Risky Psychosocial) were identified for Hispanic, Black, and White women, and 2 classes (High Risk or Low Risk) were identified for American Indian and Asian women. Women in the Risky Lifestyle and Risky Psychosocial group had the highest hazard ratios for all outcomes studied for all race/ethnicity groups than those in the Healthy Lifestyle and Psychosocial group, followed by those in the Risky Lifestyle group. Risky Psychosocial class was significantly associated with an elevated risk of overall and cardiovascular disease mortality only in Black women. Conclusions The class with concurrent risky lifestyle and psychosocial factors conveyed the greatest risk of all types of mortality than a low-risk ref group. Health promotion should address both behavioral and psychosocial risks concurrently.