cssi/SciSciGPT-SciSciNet huggingface dataset:
Management of fetal teratomas

Fetal teratomas are the most common tumors diagnosed prenatally. The majority of these tumors are benign and cured by complete resection of the mass during the neonatal period. Prenatal diagnosis has improved the perinatal management of these lesions and especially for the teratomas that might benefit from fetal intervention. A comprehensive prenatal evaluation including conventional ultrasounds, Doppler, echocardiography and fetal MRI, is essential for an effective counseling and perinatal management. Antenatal counseling helps the parents to better understand the natural history, fetal intervention, and perinatal management of these tumors, which differ dramatically depending on their size and location. Fetal surgical debulking improves survival in cases of sacrococcygeal teratoma with cardiac decompensation. Additionally, the use of an EXIT procedure reduces the morbidity and mortality if a complicated delivery in cases of cervical and mediastinal teratomas. Here, we offer an overview of all fetal teratomas and their recommended management, with emphasis on in utero treatment options.
Requirement of voltage-gated calcium (Cav) channels in T cell receptor-mediated calcium response and effector functions of T lymphocytes (99.13)

Calcium signals are required for the activation, differentiation and effector functions of T lymphocytes. However, the molecular machinery required for calcium influx upon TCR stimulation of T cells is not yet clear. Previously, we have shown that members of the Cav1 family of voltage-gated calcium channels are expressed in T lymphocytes and regulate calcium influx into these cells. Recently, we have demonstrated an essential role for the beta3 regulatory subunit of Cav channels in the maintenance of naive CD8 T cells since deficiency in beta3 resulted in a profound survival defect of naive CD8 T cells. Here, we investigated the expression and function of Cav1 channels in differentiated CD4 T lymphocyte populations and discovered a novel role of Cav1 channels in effector helper T cell population. We found a selective expression of Cav1.3 in effector Th2 cells but not naive CD4 T cells or effector Th1 cells. Both TCR-mediated calcium response and NFATs nuclear localization were severely impaired in Cav1.3-deficient Th2 cells. A profound and selective impairment of Th2 effector cytokine production was observed in vitro and in vivo after immunization of mice. Our data demonstrate a novel and essential role of Cav1 channels in different T cell functions. Therefore, Cav1 channels represent a specific and new therapeutic target for T cell-mediated inflammatory diseases.
Evaluation of Candidate Anti-HIV Agents in vitro

Significant progress has been made in the development of anti-HIV therapies for patients with AIDS and other HIV-related illnesses [1-4]. Because of major advances in our understanding of the HIV-1 replicative cycle and identification of potential targets for anti-retroviral therapy, many newer agents are now undergoing preclinical and clinical drug development [1-4]. Of particular interest are compounds with novel mechanisms of anti-HIV action and/or improved therapeutic indices when compared to drugs currently available. Ideally, these agents should have high potency, low toxicity, activity in multiple cell types (e.g., CD4-positive lymphocytes and monocyte/macrophages), penetration into target sites (e.g., the central nervous system), stability in body fluids, easy administration, and low production cost. Several promising compounds that attack different sites in the HIV-1 replicative cycle are undergoing clinical evaluation currently (Figure 13–1).
Excessive Isolated Erythrocytosis Linked to Induction of SCL/Tal1 and Erythropoietin Receptor Expression.

The JAK2 V617F mutation has been detected in more than 90% polycythemia vera patients and is associated with increased erythropoietin (EPO) sensitivity or EPO independence of erythroid progenitor cells during early erythropoiesis. To determine if other molecular lesions give rise to increased erythrocytosis and realizing that the JAK2 V617F mutation may not be the initiating event in polycythemia vera, we identified an individual with isolated, excessive erythrocytosis who showed erythroid precursor hypersensitivity to EPO; no mutations on sequencing genes for erythropoietin receptor (EPO-R), VHL, or HIF-1 IRE; normal serum EPO level; normal hemoglobin function and p50; normal cardiac, hepatic and pulmonary function; no JAK2 V617F mutation and no EPO independent BFU-E. While it was not certain that this individual’s erythrocytosis was lifelong, other relatives had increased hemoglobin levels. The cause of this individual’s increased erythropoiesis was investigated using EPO-stimulated cultures of hematopoietic progenitor cells isolated from peripheral blood. As with normal controls, cell numbers were not increased after 12 days of incubation with low levels of EPO ( JAK2 V617F positive erythroid progenitor cells. Analyses of transcription factor expression revealed that induction of GATA-1 and down regulation of GATA-2 were similar to control. However, SCL/Tal1 and EKLF markedly increased beginning at day 8 to 10 and continued to rise during late erythropoiesis in contrast to control and JAK2 V617F positive cultures in which SCL/Tal1 and EKLF peaked at day 10 and decreased with late erythroid differentiation. Since increased beta-globin expression is concomitant with induction of EKLF, the rise in EKLF may account for the marked increase in benzidine positive cells from our subject. Moreover, expression of EPO-R followed the continuing rise in SCL/Tal1, increasing by 3.5 fold at day 12 compared with control cultures. This high EPO-R expression is consistent with the dramatic increase in cell proliferation during late erythropoiesis. Using forced expression of SCL/Tal1, reporter gene assay and gel mobility shift analysis in erythroid cells, we determined that SCL/Tal1 is able to bind to E-boxes located 3′ of the EPO-R proximal promoter and to activate transcription. Although EPO stimulation of erythroid progenitor cells activates EPO-R, we found that forced expression of EPO-R in primary erythroid progenitor cells in the presence of EPO increases expression of GATA-1 as well as SCL/Tal1 and EKLF, providing further evidence that specific increase in SCL/Tal1 but not GATA-1 must precede induction of EPO-R in this case of excessive erythrocytosis. These data demonstrate a link between high level induction of SCL/Tal1 expression and increased erythrocytosis and suggest a mechanism that contributes to increased erythropoietin sensitivity during late erythropoiesis.
What’s new about truth

Governments always lie, but it feels like there’s something new and weird about Trump’s lies. It’s not that they’re more dangerous than other lies in my lifetime. Lies about the Gulf of Tonkin inci...
Structural elucidation of transmembrane domain zero (TMD0) of EcdL: A multidrug resistance-associated protein (MRP) family of ATP-binding cassette transporter protein revealed by atomistic simulation.

ATP-Binding cassette (ABC) transporters play an extensive role in the translocation of diverse sets of biologically important molecules across membrane. EchnocandinB (antifungal) and EcdL protein o...
The Role of Recreation and Recreational Therapists in Developing a Recovery-Oriented Identity for People with Substance Use Disorders

This conceptual article highlights pathways of identity transition through substance use disorders (SUD) and considers the role that recreation can play in the development of a recovery identity in...
Impacts of broth chemistry on silver ion release, surface chemistry composition, and bacterial cytotoxicity of silver nanoparticles

Here, we determine the impact of bacterial growth media on silver nanoparticle (diameter = 24.0 ± 3.2 nm) surface chemistry, the relationship of this surface chemistry to silver ion release from these nanoparticles, and ultimately the antimicrobial implications of those parameters. Importantly, we investigate the effects of multiple broths, as well as the isolated influence of individual broth components and their bicombinations. Our findings indicate that, in combination, broth components may exhibit additive, synergistic, and/or antagonistic effects on silver ion release. In addition, we find that the silver ion release does not always inversely correlate with ligand density, and interestingly, that the type of correlation (negative or positive) is dependent on the broth media. Finally, the impact of these media-dependent silver ion release profiles on bacterial cytotoxicity is studied using the model organism Escherichia coli. Overall, we establish the specific impacts of silver nanoparticle environment on silver nanoparticle surface chemistry, as well as the influence of those outcomes on bacteria growth in the presence of silver nanoparticles.
Trypanosomes have divergent kinesin-2 proteins that function differentially in IFT, cell division, and motility

Trypanosoma brucei, the causative agent of African sleeping sickness, has a flagellum that is crucial for motility, pathogenicity, and viability. In most eukaryotes, the intraflagellar transport (IFT) machinery drives flagellum biogenesis, and anterograde IFT requires kinesin-2 motor proteins. In this study, we investigated the function of the two T. brucei kinesin-2 proteins, TbKin2a and TbKin2b, in bloodstream form trypanosomes. We found that compared to other kinesin-2 proteins, TbKin2a and TbKin2b show greater variation in neck, stalk, and tail domain sequences. Both kinesins contributed additively to flagellar lengthening. Surprisingly, silencing TbKin2a inhibited cell proliferation, cytokinesis and motility, whereas silencing TbKin2b did not. TbKin2a was localized on the flagellum and colocalized with IFT components near the basal body, consistent with it performing a role in IFT. TbKin2a was also detected on the flagellar attachment zone, a specialized structure in trypanosome cells that connects the flagellum to the cell body. Our results indicate that kinesin-2 proteins in trypanosomes play conserved roles in IFT and exhibit a specialized localization, emphasizing the evolutionary flexibility of motor protein function in an organism with a large complement of kinesins.
Coverage and workload cost balancing in spatial crowdsourcing

This paper addresses the coverage and workload-balancing requirements of worker recruiting in spatial crowdsourcing. That is, the recruited workers should be able to visit all the crowdsourcing locations to satisfy a certain quality, e.g., traffic monitoring or climate forecast. In addition, each crowdsourcing operation has a cost, e.g., data traffic or energy consumption, and each crowdsourcing location might have a crowdsourcing budget for the visited workers. The objective of this paper is to find a worker recruiting algorithm, which ensures the coverage requirement and minimizes the maximal crowdsourcing cost for any crowdsourcing location. We gradually discuss the problem from the 1-D scenario to the general 2-D scenario. In the 1-D scenario, we propose a bounded directional greedy algorithm first. Then, we propose a PTAS extension. A dynamic programming solution is further proposed with a higher computation complexity. In the 2-D scenario, we propose a randomized rounding algorithm with an O(log n/log log n) approximation ratio in a high probability. Extensive experiments on realistic traces demonstrate the effectiveness of the proposed algorithms.
OpenCourseWare: open sharing of course content and design

The OpenCourseWare movement has generated excitement in many circles through its potential contributions to both lifetime learning and ubiquitous learning. These courses are certainly beneficial to such groups, but OpenCourseWare can also make valuable contributions to traditional educational environments. Referencing established courses at some of the most prestigious universities in the world provides educational institutions of all types a means through which they can expose their students to the very highest levels of course design and subject matter. This paper will introduce the OpenCourseWare movement, its scope, and also how the materials may be applied to traditional educational environments.
Stellate lesions of the breast.

A variety of risk factors for breast cancer have been identified, including genetic, hormonal, morphologic, radiation-linked, nutritional, and others. In particular, they include a personal history of breast cancer, a history of premenopausal breast cancer in the patient’s mother and/or sisters, and a previous biopsy finding of proliferative breast disease with atypia (Dupont and Page 1985). However, in over 75% of women with breast cancer, none of these factors are present; the only clearly identifiable risks are gender and aging (Berg 1984).
Migration and queer mobilisations: how migration facilitates cross-border LGBTQ activism

This article explores the relationship between migration and networks of transnational queer activism in Europe, arguing that migrant inflows increase the propensity for queer social movement organ...
Sustainable supplier selection and order allocation: A novel multi-objective programming model with a hybrid solution approach

Abstract Sustainable supplier selection is the process of identifying the appropriate supply partners of an organization with the most beneficial monetary value, while diminishing the various effects of its operations on society and environment. Therefore, it plays a significant role in moving an organization toward sustainable development. Alongside sustainable supplier selection, assigning proper quantity of orders to suppliers satisfying sustainability criteria is another activity that should be simultaneously carried out in order to develop a comprehensive tool in sustainable supplier management. Meanwhile, the issue of sustainable supplier selection and order allocation has attracted limited attention in the literature. The present paper aims at developing an inclusive multi-objective mixed integer linear programming model, which accounts for multiple periods, multiple products and multimodal transportation, to evaluate suppliers and allocate order quantities. Furthermore, the developed model that includes all sustainability aspects also takes both shortage and discount conditions into account. A hybrid three-step solution methodology is then presented, using which the original multi-objective problem is firstly converted to a single objective model by e -constraint method. In the second step, the current single objective programming model is solved using the Benders decomposition algorithm that in turn is accelerated by a variety of algorithmic enhancements. Finally, among all the Pareto optimal solutions of the original multi-objective programming problem, the preferable solution is intelligently selected based on the DEA super efficiency score of all purchasing firms as a decision support tool. The applicability of the proposed approach is illustrated by a real-world case study in automotive industry.
Detection of Epstein-Barr virus genome in Ki-1 (CD30)-positive, large-cell anaplastic lymphomas using the polymerase chain reaction.

Abstract Ki-1 (CD30)-positive, large-cell anaplastic lymphoma (LCAL) is a distinctive subset of non-Hodgkin's lymphoma; morphologically, the neoplastic cells of LCAL may closely resemble Reed-Sternberg cell variants of Hodgkin's disease. The neoplastic cells in Hodgkin's disease are often CD30-positive, as are some of the transformed lymphocytes in infectious mononucleosis. Recent evidence suggests an etiologic role for the Epstein-Barr virus (EBV) in Hodgkin's disease. Because of the phenotypic similarities between Hodgkin's disease and LCAL, we used the polymerase chain reaction (PCR) to analyze eight specimens of LCAL for EBV genome. Diagnoses were established by paraffin section morphology and immunohistochemistry. For comparison, we also analyzed nine non-Hodgkin's lymphomas other than the LCAL type, three Hodgkin's disease specimens, and nine non-neoplastic lymph nodes. PCR was performed using DNA extracted from frozen tissue; DNA was amplified using two sets of oligonucleotide primers corresponding to the BamH1 W-fragment of the EBV genome. Amplified EBV genome was obtained from all specimens except for one mantle zone lymphoma, one diffuse mixed-cell lymphoma, and six non-neoplastic lymph nodes. EBV terminus region probing and in situ hybridization techniques, each less sensitive than PCR, were performed in selected cases in an attempt to corroborate our PCR results. Only 2 of 13 specimens contained EBV detectable by these other techniques, and neither specimen was a LCAL. In view of the high incidence of latent EBV infections in humans, the biologic significance of our PCR results is uncertain. Despite the detection of EBV genome by PCR in a high percentage of lymphomas, we were unable to substantiate an etiologic role for EBV in LCAL. The PCR technique may be too sensitive to provide meaningful data on the possible role of EBV in lymphomagenesis.
Body measurements of crossbred calves sired by Simmental bulls divergently selected for progeny first-calf calving ease in relation to birth weight.

Simmental bulls (n = 27) were divergently selected on linear model first-calf calving ease expected progeny difference (CEPD) relative to birth weight expected progeny difference (BEPD) so that body measures of calves from sires whose progeny tended to be born either with more or less dystocia than expected from BEPD could be obtained. At birth, calf weight, head circumference, shoulder width, hip width, heart girth, cannon bone circumference and length, and body length were recorded for 204 calves. These measures had also been obtained from the Polled Hereford X Angus dams of the calves at their births. Sire differences (P less than .05) existed for calf cannon bone circumference and length before and after adjustment for gestation length and birth weight of the calf. Sire BEPD was positively associated with cannon and head circumferences independent of phenotypic birth weight and gestation length. No relationship existed between CEPD or threshold model first-calf calving ease expected progeny difference and any calf measure, either before or after adjustment for birth weight. Multivariate factor analysis was used to describe independent components of skeletal width, frame, and thickness after removal of birth weight effects; factors were not related to genetic merit for calving ease or observed calving performance. Independent of weight, newborn calf measures were not highly related to body measures at weaning or to dam birth measures. Body shape differences at constant weight existed in crossbred calves, but they were not related to sire genetic merit for calving ease or measured dystocia. Selection for calf body shape, independent of birth weight, would not reduce dystocia.
Magnon drag effect in Fe-Co alloys

We report here a systematic study of the magnon-drag induced thermoelectric properties of Fe-rich, Fe-Co body-centered-cubic alloys. The sign of the low temperature behavior of thermopower is explained well by the hydrodynamic theory for magnon-drag, informed by density functional theory calculations of the ground state of Fe-Co alloys. The high-temperature thermopower of some of the alloys, and indeed that of elemental iron, changes the sign, as previously observed. We propose a mechanism to elucidate this hitherto unexplained observation. Further, the power factor of Fe72Co28 peaks around 35 μV/cm K2 at 500 K, comparable to the standard thermoelectric material Bi2Te3. Because of their high thermoelectric power factor, Fe-Co alloys are potential candidate thermoelectric metals for active cooling of electronic devices.
Obsessive-Compulsive and Related Disorders

Obsessive-compulsive disorder (OCD) is a common and chronic neuropsychiatric disorder with a lifetime prevalence rate ranging from 1.9% to 3.3%. Although OCD symptomatology and heterogeneity are well established in the literature, the role of culture and its impact on the clinical manifestation of OCD has been largely understudied. This chapter reviews the forces by which culture influences OCD presentation across multiple groups. We discuss how cultural factors can shape the type of symptoms that individuals experience, the severity of symptoms, how people make sense of their experience, and how their treatment-seeking behaviors are impacted. We highlight practical implications for culturally informed assessment of OCD and examine how religion, culturally defined superstitions, and race influence OCD phenomenology. We also briefly touch on the role of culture in three common obsessive-compulsive related disorders, including body dysmorphic disorder, excoriation disorder, and hair-pulling disorder. The goal of this chapter is to review what is known about the extent and the mechanisms through which cultural forces shape OCD and related disorders in an effort to provide culturally informed care.
Negotiating dominance on Facebook: Positioning of self and others in pro- and anti-Trump comments on immigration:

The article examines the use of the modal auxiliaries MUST and HAVE (GOT) TO in politically charged online communication. Comments from D. Trump’s official Facebook page were categorized according ...
Abstract A42: Potassium channel activity unveils ovarian cancer vulnerability: From signaling to precision medicine

Decades of studies on ion channels have vastly demonstrated the critical functions of these proteins in many physiologic and pathologic conditions. Also, studies on ion channels have provided for an extraordinary pharmacopeia of useful compounds, often with selective actions and minimal side effects. Nevertheless, the function of ion channels in controlling cancer biology is still unknown and underexplored. Our research demonstrates that the Kir6.2/SUR2 potassium ion channel can be a prognostic factor in gynecologic cancers. Here we present data showing that the Kir6.2/SUR2 channel activity control biochemical pathways underlying proliferation and metabolism in gynecologic cancers, including endometrioid and high-grade serous ovarian cancer. Use of activators of the Kir6.2/SUR2 produced an arrest of the cell cycle, a significant mitochondrial dysfunction that is associated with alteration of the oxidative cellular state and DNA damage in cisplatin-resistant ovarian cancer. Also, our in vivo experiments show the antigrowth effects of pharmacologically targeting Kir6.2/SUR2 on ovarian cancer with FDA-approved molecules. This study offers the opportunity to consider the therapeutic benefits of repurposing drugs targeting the Kir6.2/SUR2 channel for a treatment of gynecologic cancers that is efficient and safe. Citation Format: Daniela Fukushiro Lopes, Alexandra Hegel, Vitaly Senyuk, Angela Russo, Margaret Liotta, Ronald Potkul, Craig Beeson, Joanna Brurgette, Saverio Gentile. Potassium channel activity unveils ovarian cancer vulnerability: From signaling to precision medicine [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A42.
Is one the loneliest number? A within-person examination of the adaptive and maladaptive consequences of leader loneliness at work.

Although leaders' daily work is inherently relational, it is possible that leaders can feel lonely and isolated from followers. Integrating theoretical ideas from regulatory loop models of loneliness with evolutionary perspectives of loneliness, we posit that daily leader loneliness (i.e., feelings of isolation stemming from one's followers) may prompt harmful self-perpetuating as well as beneficial self-correcting cycles of loneliness at work via different rumination processes. We expect that leader loneliness will relate to 2 forms of rumination after work-maladaptive affect-focused rumination and adaptive problem-solving pondering. We expect that each form of rumination will hinder or facilitate next-day work engagement and helping, which will then matter for subsequent leader loneliness. In a 10-day experience sampling investigation of 86 leaders, we found that daily leader loneliness exhibits a self-perpetuating pattern via affect-focused rumination because this type of rumination reduces next-day work engagement and helping. At the same time, daily leader loneliness exhibits a self-correcting pattern via problem-solving pondering, as this type of forward-thinking rumination facilitates work engagement and helping the next day. Furthermore, leader self-efficacy enhances the extent to which problem-solving pondering occurs when leaders feel lonely. In a supplemental experience sampling study with leaders and followers, we further show that daily leader loneliness is negatively related to followers' perceptions of leader effectiveness above and beyond more generalized loneliness. In summary, our work sheds theoretical and empirical light on the complex nature of leader loneliness. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Complete Genome Sequence Resource for the Endophytic Burkholderia sp. Strain MS389 Isolated from a Healthy Soybean Growing Adjacent to Charcoal Rot Disease Patch.

Burkholderia sp. strain MS389, an endophytic bacterium, was isolated from a healthy soybean plant growing adjacent to a patch of plants affected by charcoal rot disease, caused by the fungal pathog...
Decisions and Consequences: Validation of High-Stakes Simulation-Based Assessments in Gynecologic Surgery.

Abstract Study Objective Simulation-based assessment is poised for application in educational promotion and credentialing in gynecologic surgery. With high-stakes assessment, validation necessitates evidence, not just about the trustworthiness of decisions, but of beneficial consequences to education and healthcare as well. In this paper, we unpack the modern conceptualization of validity as it pertains to surgical simulation and high-stakes competency assessment. Design N/A Setting N/A Patients N/A Interventions N/A Measurements and Main Results N/A Conclusion Validity in high-stakes simulation-based assessment necessitates evidence, not just about the trustworthiness of score-based decisions, but of beneficial consequences to education and healthcare as well.
The Structure and Mechanism of Drug Transporters

Drug transporters are integral membrane proteins that play a critical role in drug disposition by affecting absorption, distribution, and excretion. They translocate drugs, as well as endogenous molecules and toxins, across membranes using ATP hydrolysis, or ion/concentration gradients. In general, drug transporters are expressed ubiquitously, but they function in drug disposition by being concentrated in tissues such as the intestine, the kidneys, the liver, and the brain. Based on their primary sequence and their mechanism, transporters can be divided into the ATP-binding cassette (ABC), solute-linked carrier (SLC), and the solute carrier organic anion (SLCO) superfamilies. Many X-ray crystallography and cryo-electron microscopy (cryo-EM) structures have been solved in the ABC and SLC transporter superfamilies or of their bacterial homologs. The structures have provided valuable insight into the structural basis of transport. This chapter will provide particular focus on the promiscuous drug transporters because of their effect on drug disposition and the challenges associated with them.
Is prediction nothing more than multi-scale pattern completion of the future?

Abstract While the notion of the brain as a prediction machine has been extremely influential and productive in cognitive science, there are competing accounts of how best to model and understand the predictive capabilities of brains. One prominent framework is of a “Bayesian brain” that explicitly generates predictions and uses resultant errors to guide adaptation. We suggest that the prediction-generation component of this framework may involve little more than a pattern completion process. We first describe pattern completion in the domain of visual perception, highlighting its temporal extension, and show how this can entail a form of prediction in time. Next, we describe the forward momentum of entrained dynamical systems as a model for the emergence of predictive processing in non-predictive systems. Then, we apply this reasoning to the domain of language, where explicitly predictive models are perhaps most popular. Here, we demonstrate how a connectionist model, TRACE, exhibits hallmarks of predictive processing without any representations of predictions or errors. Finally, we present a novel neural network model, inspired by reservoir computing models, that is entirely unsupervised and memoryless, but nonetheless exhibits prediction-like behavior in its pursuit of homeostasis. These explorations demonstrate that brain-like systems can get prediction “for free,” without the need to posit formal logical representations with Bayesian probabilities or an inference machine that holds them in working memory.
Tunneling nanotube formation promotes survival against 5-fluorouracil in MCF-7 breast cancer cells.

Tunneling nanotubes (TNTs) are F-actin-based open-ended tubular extensions that form following stresses, such as nutritional deprivation and oxidative stress. The chemotherapy agent 5-fluorouracil (5-FU) represents a significant stressor to cancer cells and induces thymidine deficiency, a state similar to nutritional deprivation. However, the ability of 5-FU to induce TNT formation in cancer cells and potentially enhance survival has not been explored. In this study, we examined whether 5-FU can induce TNT formation in MCF-7 breast cancer cells. Cytotoxic doses of 5-FU (150 - 350 μM) were observed to significantly induce TNT formation beginning at 24 hours after exposure. TNTs formed following 5-FU treatment probably originated as extensions of gap junctions as MCF-7 cells detach from cell clusters. TNTs act as conduits for exchange of cellular components and we observed mitochondrial exchange through TNTs following 5-FU treatment. 5-FU-induced TNT formation was inhibited by over 80% following treatment with the F-actin-depolymerizing agent, cytochalasin B (cytoB). The inhibition of TNTs by cytoB corresponded with increased 5-FU-induced cytotoxicity by 30-62% starting at 48 hours, suggesting TNT formation aides in MCF-7 cell survival against 5-FU. Two other widely used chemotherapy agents, docetaxel and doxorubicin induced TNT formation at much lower levels than 5-FU. Our work suggests that the therapeutic targeting of TNTs may increase 5-FU chemotherapy efficacy and decrease drug resistance in cancer cells, and these findings merits further investigation.
Design and Development of a Multi-Port Converter for Marine Microgrid Applications

In this work, a multi-port converter (MPC) design is presented that works as the key building block of a marine microgrid. An emulated wave energy converter (WEC) serves as the renewable energy resource of this microgrid system. The proposed MPC is comprised of a WEC interfacing port, energy storage port, and a split-phase AC load/grid port. Stable power exchange among these dissimilar energy resources are facilitated through a 400V internal DC bus. The full MPC design along with its control and thermal model is developed and implemented in PLECS. Commercially available SiC power modules have been used to leverage its high switching frequency capability that to achieve compact system design with reduced passive component sizes. Individual controller for each energy resource interfacing converter is analyzed, developed and implemented initially. A state-machine is developed utilizing these discrete controllers for MPC operation where all three ports are active simultaneously. These discretized controllers along with voltage/current sensor models with limited bandwidth and response delay in the feedback path are implemented in PLECS to emulate practical controller deployment. Simulation results are provided to validate both the power stage and the discrete controller design. Furthermore, iterative thermal analysis is carried out to have a realistic estimation of the device junction temperature during rated condition to evaluate the efficacy of the thermal management system. Finally, a virtual prototype design of the MPC is presented.
Metabolic stress induces GD2+ cancer stem cell-like phenotype in triple-negative breast cancer.

BACKGROUND Metabolic stress resulting from nutrient deficiency is one of the hallmarks of a growing tumour. Here, we tested the hypothesis that metabolic stress induces breast cancer stem-like cell (BCSC) phenotype in triple-negative breast cancer (TNBC). METHODS Flow cytometry for GD2 expression, mass spectrometry and Ingenuity Pathway Analysis for metabolomics, bioinformatics, in vitro tumorigenesis and in vivo models were used. RESULTS Serum/glucose deprivation not only increased stress markers but also enhanced GD2+ BCSC phenotype and function in TNBC cells. Global metabolomics profiling identified upregulation of glutathione biosynthesis in GD2high cells, suggesting a role of glutamine in the BCSC phenotype. Cueing from the upregulation of the glutamine transporters in primary breast tumours, inhibition of glutamine uptake using small-molecule inhibitor V9302 reduced GD2+ cells by 70-80% and BCSC characteristics in TNBC cells. Mechanistic studies revealed inhibition of the mTOR pathway and induction of ferroptosis by V9302 in TNBC cells. Finally, inhibition of glutamine uptake significantly reduced in vivo tumour growth in a TNBC patient-derived xenograft model using NSG (non-obese diabetic/severe combined immunodeficiency with a complete null allele of the IL-2 receptor common gamma chain) mice. CONCLUSION Here, we show metabolic stress results in GD2+ BCSC phenotype in TNBC and glutamine contributes to GD2+ phenotype, and targeting the glutamine transporters could complement conventional chemotherapy in TNBC.
Peeling away the layers of ubiquitin signaling complexities with synthetic ubiquitin–protein conjugates

Covalent attachment of ubiquitin, a process termed ubiquitination, affects the location, function, and stability of modified proteins. Significant advances have been made in building synthetic ubiquitin-protein conjugates that can be used to investigate how ubiquitin regulates diverse biological processes. Herein we describe recent advances and discuss how chemical methods have been implemented to address the molecular underpinnings of ubiquitin-dependent cellular signaling.
Alpha-Decay Systematics for Elements with 50 < Z < 83

From observing the slope of the mass-defect curve, one notes that most isotopes whose mass numbers are ≳ 140 are unstable toward a-emission. However, with the exception of naturally occurring 147Sm, α-decay was not observed for elements below bismuth until 30 years ago. This was due to the fact that the rate for a-decay is a very sensitive exponential function of the decay energy. The energy available for decay increases rapidly with mass, so that in the region above lead α-decay becomes a dominant decay mode. It was also known that, if one could produce nuclides sufficiently far to the neutron-deficient side of the β-stability line, then with nuclei Z < 83 would undergo α-particle emission. This was shown to be true experimentally in 1949 when Thompson, Ghiorso, Rasmussen and Seaborg1 reported the discovery of α-radioactivity in proton-rich isotopes of gold, mercury and the rare earths. Since that time, with the availability of new accelerators, the number of known α-active nuclides below bismuth has steadily increased.
A Pilot for a Robotic Vehicle System

The role of an automatic pilot in an autonomous land vehicle system is to guide the vehicle along its mission path, while at the same time avoiding unexpected obstacles. We demonstrate an algorithm that accomplishes this task in real-time with the capability to generate vehicle guidance commands every 60 milliseconds. Many aspects of obstacle avoidance and path following can be shown to depend only on the current snapshots of the local work space with only a few global parameters needed. The algorithm works by finding conical-shaped usable subsets of the local work space and is motivated by the heuristic requirement of staying in sensor view of the subgoal. Our approach allows for vehicle dynamics which is often neglected in other approaches and yields smooth paths. The problem of traps inherent in potential field approaches is avoided by introducing a winding angle principle. Before field testing, the performance of the pilot was evaluated by the computer simulation of a 10-ton tracked vehicle. During recent field tests, the pilot was successful in guiding an M113 armored personnel carrier around obstacles while staying inside the path corridor.
Lingering Questions: The Fairness Doctrine and the 2008 Presidential Campaign Coverage in Western Pennsylvania

The purpose of this study was to examine whether or not the demise of the Fairness Doctrine caused measurable bias in the news coverage of the 2008 Presidential Campaign between Senator John McCain (R) and then Senator Barak Obama (D). The demographic area involved Western Pennsylvania and included the markets of Altoona and Johnstown as well as the Pittsburgh television stations; both their local as well as affiliated national network coverage. A group of ten recorders were assigned to time and evaluate news stories on specific channels shown during the evening news shows on Tuesday, Thursday and Friday evenings from October 1, 2008 through Election Day, November 4, 2008 (The evenings were chosen randomly and were based on the availability of the recorders.) The results indicate that while the McCain Campaign received more news coverage than the Obama Campaign, that there were more negative news stories about McCain. In addition, and not surprisingly, there was less coverage of the Campaigns on the smaller stations called “Local-Local” for the purposes of the study. In the final analysis, it was shown that although there was more coverage of the McCain Campaign there were also more stories that were shown which could be construed as negative. Also included was a sub-analysis of selected Campaign Advertisements broadcast. No definitive conclusions were reached as to whether or not the Fairness Doctrine and related Election Laws should be reinstated or broadened. However, several additional studies are suggested including a replication of this study for the 2012 and 2016 elections as well as the possibility of conducting this methodology in a different but demographically similar market.
Traditional Cardiovascular Risk Factors in Relation to Left Ventricular Mass, Volume, and Systolic Function by Cardiac Magnetic Resonance Imaging: The Multiethnic Study of Atherosclerosis

OBJECTIVES The goal of this study was to examine the cross-sectional associations of cardiovascular risk factors with left ventricular (LV) geometry and systolic function measured by cardiac magnetic resonance imaging (MRI) in the Multiethnic Study of Atherosclerosis (MESA). BACKGROUND Cardiovascular risk factors including hypertension, smoking, and obesity are known to be associated with increased LV mass, but less is known about the association of risk factors with LV systolic function, particularly in populations without clinical cardiovascular disease. METHODS Participants were from 4 racial/ethnic groups and were free of clinical cardiovascular disease. Blood pressure, health habits, body mass index, lipid levels, and glucose abnormalities were assessed and MRI exams performed at baseline (n = 4,869). Multivariable linear regression was used to model the association of risk factors with LV mass, end-diastolic volume, stroke volume, ejection fraction, and cardiac output. RESULTS The mean age was 62 years, and 52% of the participants were women. After adjustment for sociodemographic variables and height, higher systolic blood pressure and body mass index were associated with larger LV mass and volumes. Current smoking and diabetes were associated with greater LV mass (+7.7 g, 95% confidence interval [CI] +5.5 to +9.9 and +3.5 g, 95% CI +1.2 to +5.8, respectively), and with lower stroke volume (-1.9 ml, 95% CI -3.3 to -0.5 and -4.5 ml, 95% CI -6.0 to -3.0, respectively) and lower ejection fraction (-1.6%, 95% CI -2.1 to -1.0 and -0.8%, 95% CI -1.5 to -0.2, respectively). CONCLUSIONS In this cohort free of clinical cardiovascular disease, modifiable risk factors were associated with subclinical alterations in LV size and systolic function as detected by cardiac MRI.
Family, Friends, and Romantic Partners of Eating Disorder Sufferers: The Use of Spiritual/Religious Coping Strategies

Individuals who reported having a friend, family member, or romantic partner with current eating disorder symptoms (n = 82) participated in this study. Participants documented the types of spiritual/religious coping strategies they used when coping with the stress of being close to an eating disorder sufferer. Following correlation analyses, we found a significant association between two types of negative spiritual/religious coping (spiritual discontent religious coping and punishing God/Higher Power reappraisal religious coping) and increased depression. In a regression analysis, only spiritual discontent religious coping remained significantly linked with depression. Clinicians who work with clients who are close to eating disorder sufferers can draw on these findings to inform therapeutic interventions.
Xanthogranulomatous pyelonephritis in childhood: pre-operative diagnosis is possible.

Objective To diagnose xanthogranulomatous pyelonephritis (XGP) in childhood pre-operatively. Patients and methods Eleven cases of XGP presenting to Birmingham Children's Hospital over a 10-year-period are reported. Nine (82%) were diagnosed pre-operatively on the clinical and radiological findings. Results The characteristic clinical findings were urinary tract infection (9 cases), palpable renal mass (8 cases) and anaemia (8 cases). The most common radiological findings were enlarged kidney (9 cases), renal calculi (7 cases) and non-functioning kidney (6 cases). Renal ultrasound typically demonstrated a central echoic area (6 cases) and multiple hypoechoic areas in the parenchyma (7 cases). A computed tomography (CT) scan was performed in three cases. This showed characteristic multiple, low attenuation, unenhanced areas within the parenchyma with extension of the inflammatory process into peri-nephric fat (two cases). Ten cases (91%) were of the diffuse type. There was extension into the peri-nephric fat in eight cases (73%). Three cases (27%) were associated with congenital urological abnormalities. Nephrectomy was performed in 10 cases and a partial nephrectomy in one. Conclusion XGP is uncommon in childhood but should always be considered in the differential diagnosis of renal masses, especially in the presence of anaemia. Nephrectomy usually results in a permanent cure.
Dying scenarios improve recall as much as survival scenarios

Merely contemplating one's death improves retention for entirely unrelated material learned subsequently. This "dying to remember" effect seems conceptually related to the survival processing effect, whereby processing items for their relevance to being stranded in the grasslands leads to recall superior to that of other deep processing control conditions. The present experiments directly compared survival processing scenarios with "death processing" scenarios. Results showed that when the survival and dying scenarios are closely matched on key dimensions, and possible congruency effects are controlled, the dying and survival scenarios produced equivalently high recall levels. We conclude that the available evidence (cf. Bell, Roer, & Buchner, 2013; Klein, 2012), while not definitive, is consistent with the possibility of overlapping mechanisms.
COMPARISON OF SHORT TERM VS. LONG TERM RITODRINE EXPOSURE

Ritodrine hydrochloride as a tocolytic agent is gaining widespread acceptance in the USA after over a decade of use in Europe. Records were reviewed during the initial year of ritodrine use at Pennsylvania Hosp.(7/81 - 6/82). The protocol for administration was IV ritodrine followed by oral maintenance (usually 40-80 mg daily) until delivery. 55 of 68 women (81%) were treated to 35 weeks or greater with the following results: Neonatal side effects (hyperbilirubinemia, hypoglycemia, or respiratory distress) were not significantly increased in either group as compared to previous European reports, although our mean length of exposure is almost 4 times longer. This suggests that the current ritodrine regimen does not increase neonatal side effects and is effective in prolonging pregnancy. However, this may change as maintenance therapy is increased (up to 120 mg daily) in attempts to improve ritodrine's success.
The role of targeted agents in preoperative chemoradiation for rectal cancer

In the United States, randomized trials have established preoperative chemoradiation as the standard of care for patients with locally advanced rectal cancer. Pathologic complete response (pCR) rates occur in 10% to 16% of patients and have been shown to be correlated with both disease-free and overall survival. Therefore, recent efforts incorporating newer cytotoxic and molecularly targeted agents into chemoradiotherapy regimens have reported the pCR rate to be a surrogate marker of clinical outcomes. Substitution of oral fluoropyrimidines, including capecitabine, for infusional 5-fluorouracil reportedly generated pCR rates of up to 32% in phase 2 studies, but definitive evaluation awaits results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 trial. Similarly, regimens incorporating irinotecan generated pCR rates as high as 38%, but to the authors' knowledge have not been evaluated in randomized trials. In contrast, 2 large randomized trials reported that the addition of weekly oxaliplatin to fluoropyrimidine-based chemoradiation led to an increase in grade 3/4 toxicity but no difference in pCR rates. Early phase trials evaluating the anti-epidermal growth factor receptor (EGFR) antibody cetuximab in combination with chemoradiation reported modest pCR rates of 5% to 12%, and efforts have focused on identifying biomarkers of response including EGFR copy number, k-ras mutational status, and both serum and tumor-specific expression of EGFR ligands. Finally, incorporation of the anti-vascular endothelial growth factor antibody bevacizumab into chemoradiation appears to be safe and feasible, with initial studies reporting a beneficial effect on vascular normalization and correlations between circulating biomarkers of angiogenesis and pathologic response. Future efforts should include prospective studies of these agents in biomarker-defined subpopulations, as well as studies of novel agents that target angiogenesis, tumor-stromal interaction, and the cell signaling pathways implicated in colorectal cancer.
Hydroxylations of Biphenyl by Fungi

Sixty-six species of fungi were screened for their ability to hydroxylate biphenyl. Thin-layer and gas chromatographic analyses indicated that seven organisms actively hydroxylated this substrate. Of particular interest were Cunninghamella echinulata ATCC 9244 which produced 4-hydroxybiphenyl as the major metabolite, Helicostylum piriforme QM 6945 which produced exclusively 2-hydroxybiphehyl, and Aspergillus parasiticus ATCC 15517 which produced a good yield of 4, 4′-dihydroxybiphenyl. These results were confirmed by isolation of the phenolic metabolites following preparative-scale conversions and comparisons of the isolated phenols with authentic reference materials.