cssi/SciSciGPT-SciSciNet huggingface dataset:
Factors Affecting Performance and Disposition of “Heavy” Purebred Boars

Abstract Performance data were collected from 543 purebred boars that were grown to an average body weight of 144 kg. Animal weight (WT), daily gain (ADG), and backfat (BF) measures were collected individually, whereas feed conversion (FC) was recorded on a pen basis. Duroc and Yorkshire boars grew at a faster rate (P There were significant (P
Variable imprinting of the heterotrimeric G protein Gsα-subunit within different segments of the nephron

The heterotrimeric G protein Gs is required for hormone-stimulated intracellular cAMP generation because it couples hormone receptors to the enzyme adenylyl cyclase. Hormones that activate Gs in th...
On the Radiation Efficiency of Quasi-Homogeneous Sources of Different Degrees of Spatial Coherence

Recent researches on the foundation of radiometry [1,2] have made it possible to provide answers to a number of puzzling questions relating to radiation from sources of different states of coherence. In particular, a relationship between the coherence properties of a source and the directionality of the light that the source generates has been established [3,4] at least for a wide class of sources of practical interest, and the coherence properties of Lambertian sources have been clarified [5] to a large extent.
Exploring computer science students' learning of sensor-driven mobile app design: a case study

Sensor-driven applications, implemented using modern mobile or gaming devices, have great potential in motivating computer science students. Recent industry trends toward including more sensors on devices such as mobile phones, which enable new applications in health monitoring, smart homes, and human safety, among others, indicate that the number of such sensor-driven applications will continue to rise. Via a study to learn the difficulties that a group of students face in designing such sensor-driven applications, we uncover a set of instructional principles for instructors to follow in using sensor-driven applications in classrooms. Our findings include that: 1) exposing students to sensor data earlier helps improve self-efficacy; 2) focusing on extracting overall patterns from sensor data rather than understanding specifics of physical quantities is beneficial; 3) good sensor data visualisation is beneficial to design, but bad visualisation can confuse students.
Modulation of Dendritic Cell Chemotaxis by HIV-gp120.

Dendritic cells are essential antigen-presenting cells involved in the induction of T cell immunity against pathogens, such as Human Immunodeficiency Virus (HIV)-1. During the early stages of HIV infection, immature dendritic cells (iDCs) are the first cellular targets of HIV-1. These HIV-infected iDCs cross mucosal surfaces and facilitate transmission of the virus to nearby CD4+ T cells. To date, the effect of HIV envelope proteins such as gp120 on dendritic cell chemotaxis has not been well characterized. Thus, we studied the effect of recombinant gp120 on the chemotaxis of mature DCs (mDCs) and immature DCs. Immature DCs have been shown to express the CC chemokine receptor, CCR5. In contrast, mature DCs down-regulate CCR5 but upregulate CXCR4 as well as exhibit enhanced chemotaxis towards CXCL12. In our study, we analyzed the effect of soluble gp120 on the chemotaxis of DCs. We have shown that pre-treatment of DCs with M-tropic gp120 significantly inhibited the CCR5-induced chemotaxis of iDCs, whereas pre-treatment of DCs with T-tropic gp120 inhibited the CXCL12-induced chemotaxis of mDCs. In addition, we found that M-tropic gp120 itself induced the chemotaxis of iDCs in a dose-dependent manner, while T-tropic gp120 did not show any effect on iDC chemotaxis. We next analyzed the signaling mechanisms involved in the modulation of iDC chemotaxis by M-tropic gp120 and found that M-tropic gp120 increased the phosphorylation of Src kinase, paxillin, Erk, and Akt in these cells. Moreover, M-tropic gp120 induced an increased expression of Lymphocyte Specific Protein-1 (LSP1), which has been reported to regulate the chemotaxis of various immune cells. Taken together, these results suggest that HIV-gp120 plays an important role in modulating the chemotaxis of mDCs and iDCs. This study may help to elucidate the mechanisms of immune response and contribute to the development of vaccines against HIV.
Ketamine and MK-801 decrease acetylcholine release in the pontine reticular formation, slow breathing, and disrupt sleep.

Study objectives Ketamine induces a dissociated state of consciousness by binding to the phencyclidine binding site within the ion channel gated by the N-methyl-D-aspartate (NMDA) receptor. The brain regions and neurotransmitter systems mediating ketamine-induced alterations in arousal remain incompletely understood. This study used in vivo microdialysis to test the hypothesis that ketamine alters acetylcholine (ACh) release in the medial pontine reticular formation (mPRF). Design Acetylcholine (ACh) release, sleep, and breathing were quantified following systemic ketamine administration. Microdialysis was used to deliver the NMDA-channel blocker dizocilpine maleate (MK-801) and the R(-)-isomer of ketamine into the mPRF while measuring ACh release. Setting N/A. Participants N/A. Interventions N/A. Measurements and results Systemically administered ketamine disrupted normal sleep-cycle organization, reduced mPRF ACh release, and significantly slowed rate of breathing. Dialysis delivery of MK-801 to the mPRF significantly decreased respiratory rate and mPRF ACh release. Dialysis delivery to the mPRF of the R(-)-ketamine isomer significantly decreased mPRF ACh release. Conclusions Decreased mPRF ACh release caused by systemically administered ketamine was mimicked by mPRF dialysis delivery of MK-801 and the R(-)-ketamine isomer. These data are consistent with the conclusion that systemically administered ketamine may alter arousal and breathing, in part, by altering cholinergic neurotransmission in the mPRF.
Stability of Permanent Rotations and Long-Time Behavior of Inertial Motions of a Rigid Body with an Interior Liquid-Filled Cavity

A rigid body, with an interior cavity entirely filled with a Navier-Stokes liquid, moves in absence of external torques relative to the center of mass of the coupled system body-liquid (inertial motions). The only steady-state motions allowed are then those where the system, as a whole rigid body, rotates uniformly around one of the central axes of inertia (permanent rotations). Objective of this article is twofold. On the one hand, we provide sufficient conditions for the asymptotic, exponential stability of permanent rotations, as well as for their instability. On the other hand, we study the asymptotic behavior of the generic motion in the class of weak solutions and show that there exists a time t0 after that all such solutions must decay exponentially fast to a permanent rotation. This result provides a full and rigorous explanation of Zhukovsky’s conjecture, and explains, likewise, other interesting phenomena that are observed in both lab and numerical experiments.
Methods for classifying obesity in spinal cord injury: a review

Narrative review. Review methods used to measure and classify obesity in individuals with spinal cord injuries (SCI). Outline the strengths and weaknesses of each method used to measure obesity in individuals with SCI. International. PubMed was used to identify articles before 2016. Search terms (‘obesity’ or ‘weight status’ and ‘spinal cord injury’). Filters: adults, English and human. Studies were retained that (1) included participants, 18 years or older, with SCI; (2) took place in inpatient, outpatient or community-based settings and (3) measured obesity status. Unique methods for classifying individuals with SCI as obese were identified and examples are presented. Methods identified for classifying obesity were as follows: World Health Organization body mass index (BMI) cutoff⩾30 kg m−2, BMI cutoff ⩾25-29 kg m−2, and SCI-specific BMI cutoff ⩾22 kg m−2, waist circumference cutoff (women >102 cm, men >88 cm), percent body fat cutoffs ⩾25% using bioelectrical impedance analysis and dual-energy X-ray absorptiometry, computerized tomography scan visceral fat area ⩾100 cm2 and percentage of ideal body weight. BMI is the most widely used measure of obesity in the SCI literature. Although some studies identified alternative cutoffs or other metrics, there is no standardized obesity classification in SCI. However, research is needed to determine and validate obesity classification specific to SCI due to physiological changes that occur following injury. We recommend that researchers and clinicians proceed with caution and use methodology based on the purpose of measurement.
Mesenchymal stromal cells protect human cardiomyocytes from amyloid fibril damage

Abstract Background aims Light chain (AL) amyloidosis is a protein misfolding disease characterized by extracellular deposition of immunoglobulin light chains (LC) as amyloid fibrils. Patients with LC amyloid involvement of the heart have the worst morbidity and mortality. Current treatments target the plasma cells to reduce further production of amyloid proteins. There is dire need to understand the mechanisms of cardiac tissue damage from amyloid to develop novel therapies. We recently reported that LC soluble and fibrillar species cause apoptosis and inhibit cell growth in human cardiomyocytes. Mesenchymal stromal cells (MSCs) can promote wound healing and tissue remodeling. The objective of this study was to evaluate MSCs to protect cardiomyocytes affected by AL amyloid fibrils. Methods We used live cell imaging and proteomics to analyze the effect of MSCs in the growth arrest caused by AL amyloid fibrils. Results We evaluated the growth of human cardiomyocytes (RFP-AC16 cells) in the presence of cytotoxic LC amyloid fibrils. MSCs reversed the cell growth arrest caused by LC fibrils. We also demonstrated that this effect requires cell contact and may be mediated through paracrine factors modulating cell adhesion and extracellular matrix remodeling. To our knowledge, this is the first report of MSC protection of human cardiomyocytes in amyloid disease. Conclusions This important proof of concept study will inform future rational development of MSC therapy in cardiac LC amyloid.
Validation of Visual Objective Biomarkers for Acute Concussion.

Objective Despite an increase in the awareness and diagnosis of mild traumatic brain injury (mTBI), there remains a paucity of data examining the comparative efficacy of available assessments. This study aims to validate visual functions as potential biomarkers for mTBI. Methods This case-control correlational design utilizes military personnel diagnosed with acute (≤72 h post-injury) mTBI (n = 100) and age-matched controls (n = 100) to examine the relative effectiveness of the pupillary light reflex (PLR), near point of convergence (NPC) break, King-Devick (KD) test time, and Convergence Insufficiency Symptom Survey (CISS) score to discriminate between participants with mTBI. Results Three of the eight PLR parameters (i.e., average constriction velocity (ACV), average dilation velocity (ADV), and 75% re-dilation time; all p < 0.001) were affected in mTBI participants. Similarly, NPC break, KD test time, and CISS scores showed a statistically significant difference between groups (all p < 0.001). Area under the curve showed that ADV (0.82) and NPC (0.74) have the higher predictive values of all objective parameters. Conclusions ADV, ACV, and NPC break are objective visual functions markedly affected in the acute mTBI group compared with controls; therefore, we proposed that they could be used as biomarkers for acute mTBI.
Comparing Near Eastern Neolithic Megasites and Southwestern Pueblos: Population Size, Exceptionalism and Historical Trajectories

Catalhoyuk and other Near Eastern Neolithic ‘megasites’ are commonly interpreted as exceptional because of their large size and early dates. In this paper, we question exceptional claims about the size and social organization of megasites like Catalhoyuk by comparing them to pueblos in the American Southwest. We argue that Catalhoyuk and other Near Eastern Neolithic megasites are better understood as large villages whose size, layout and social organization compare readily to many of the late prehispanic and historic-period pueblos in the American Southwest. We suggest that four factors contribute to disparate interpretations of structurally similar sites in the Near East and American Southwest: 1) surface architectural visibility; 2) different regional intellectual traditions that emphasize ‘micro’ versus ‘macro’ scale social organization; 3) a tendency toward overestimation in archaeological population estimates, especially when the ‘biggest’ or the ‘earliest’ sites are involved; and 4) perceptions of continuity with later time periods.
Thermoelastic analysis of GaAs in lec growth configuration. II. Temporal evolution of the stress field

Abstract The temperature distribution in the growth system and the elastic thermal stress field in the growing crystal are calculated at three stages of the solidification process. Results indicate that at the early stages of growth excessive stresses are generated as the cone emerges from the encapsulant, and at later times the maximum stresses occur close to the solidification interface and the region where the crystal emerges from the encapsulant. Adjustment of heater power for reduction of stresses associated with excessive cooling of the crystal is found to be inadequate and result in enhanced convexity of the growth interface and generation of large stresses in that region.
Adaptive Agents in Coalition Formation Games

Coalition formation games form an important subclass of mixed-motive strategic situations, in which players must negotiate competitively to secure contracts. This paper compares the performance of two learning mechanisms, reinforcement learning and counterfactual reasoning, for modeling play in such games. Previous work [CK04] found that while the former type of agent converged to theoretical solutions, they did so much more slowly than human subjects. The present work addresses this issue by allowing agents to update extensively based on counterfactual reasoning.
Psychological Factors and Survivorship: A Focus on Post-treatment Cancer Survivors

Over the past decade, the number of people alive in the United States with a personal history of cancer has surpassed the 12 million mark. As the number of survivors has grown, accordingly, the field of psycho-oncology research and practice has increasingly focused on the post-treatment phase of the cancer trajectory. Post-treatment cancer survivors may experience numerous physical, emotional, and practical challenges that are distinct from the experiences people have earlier in the cancer trajectory near time of diagnosis or during treatment. Though post-treatment survivorship is an evolving field of inquiry and clinical care, there is evidence that psychological concerns are under-addressed in the post-treatment period, with estimates indicating that as many as half of post-treatment cancer survivors do not receive the help they need for emotional or psychological concerns. In this chapter, we review psychological factors in post-treatment cancer survivors and examine a unique data source, the 2010 LIVESTRONG Survey for People Affected by Cancer, to better understand the psychological experiences of post-treatment cancer survivors. The results of the survey suggest that emotional concerns among post-treatment cancer survivors are exceedingly common, and identify a gap between reports of emotional concerns and receipt of care for those concerns. We overview strategies for closing this gap using new innovations in survivorship care, such as survivorship care plans.
Budgets für verschiedene betriebliche Teilbereiche

In allen Bereichen des taglichen Lebens wird bewust oder unbewust budgetiert. Ob jemand uber die Deckung seines eigenen zukunftigen Bedarfs und desjenigen seiner Familie Uberlegungen anstellt oder ob er als Unternehmer die zur Kostendeckung und Gewinnerzielung notwendigen Erlose plant, immer wird ihm die Aufstellung eines Budgets seine Bemuhungen erleichtern.
Flow Network Formulations of Polymatroid Optimization Problems

In the ‘polymatroidal’ network flow model, capacity constraints are imposed by polymatroid rank functions on the sets of arcs directed into and out of each node. It is shown that a variety of matroid optimization problems can be easily formulated and solved in terms of this model. Among these problems are (poly)matroid intersection, matroid partitioning, problems of gammoids and linking systems, and problems formulated by Iri, Krogdahl, and Fujishige. It is shown that simple proofs of known min-max theorems for these problems are easily obtained as corollaries of the max-flow min-cut theorem for polymatroidal network flows, previously proved by the authors.
X-linked Juvenile Retinoschisis

X-linked juvenile retinoschisis (XLRS) occurs exclusively in males and is characterized by visual loss that begins in early childhood; patients are usually school-age and are experiencing visual disturbances, especially in reading. The prevalence is estimated to be 1 in 5000–25,000 men, worldwide. XLRS has complete penetrance but variable expressivity. Carrier females generally remain asymptomatic.
Novel agents may positively impact chemotherapy and transplantation in subsets of diffuse large B-cell lymphoma

Introduction: Molecular and biologic heterogeneity in diffuse large B-cell lymphoma (DLBCL) has resulted in a broad range of clinical outcomes. While standard frontline chemoimmunotherapy cures majority of patients with DLBCL, treatment failure in certain DLBCL subsets remains high. Prognosis in these patients is dismal. Therefore, optimization of front-line therapy, as well as development of more effective salvage treatments, is an unmet medical need. Areas covered: This article reviews the treatment advances in DLBCL with novel and targeted agents that are aimed to improve efficacy especially in those with high-risk features. Expert opinion: Incorporation of novel therapies such as immunomodulatory agents and Bruton tyrosine kinase (BTK) inhibitors in the treatment of higher-risk DLBCL subgroups have shown to be effective; however, confirmatory data are required to change the standard of care. While autologous chimeric antigen receptor (CAR) T-cell therapy targeting CD19-positive B-cells have revolutionized the outcomes of refractory DLBCL, the complexity of its production, post-infusion care, and the associated cost, currently has limited its use to select academic centers in the US. A multitude of other targeted agents and combinations as well as cellular and immunotherapeutic agents are under investigation.
Targeted Therapy for Malignant Gliomas

Malignant gliomas, including anaplastic astrocytomas, anaplastic oligodendrogliomas and glioblastomas are aggressive primary brain tumors and are associated with dismal prognosis. The standard treatment for glioblastomas consists of temozolomide and radiotherapy, but virtually all patients recur, with a fatal disease outcome. Molecular targeted therapy has been the focus of attention in the development of new treatments for malignant gliomas. Many signaling pathways that could potentially be targeted have been described, including P13k/Akt/mTOR, Ras/MAPK, and others. Unfortunately, the first generation of targeted therapy trials for malignant gliomas have been disappointing. While strategies targeting angiogenesis through VEFGR pathway inhibition have shown promising activity, results of single agent trials of several other drugs have been largely negative. Current research is focusing on the development of combination of different targeted agents and multi-targeted single agent treatments, as well as patient selection based on pre-existing molecular characteristics. In this chapter we review the development of targeted agents in malignant gliomas, with a focus on issues encountered in trials previously conducted, as well as future research venues.
FAMILY HISTORY OF DIABETES IS ASSOCIATED WITH INCREASED RISK OF RECURRENT DIABETIC KETOACIDOSIS IN PEDIATRIC PATIENTS.

Objective: To determine the relationship between family history of diabetes mellitus (DM) and diabetic ketoacidosis (DKA) recurrence in youth with established type 1 diabetes mellitus (T1DM). Methods: We performed a retrospective chart review of patients with DKA admitted to a pediatric hospital between January, 2009, and December, 2014. We compared patients with recurrent (≥2 admissions) and nonrecurrent DKA (1 admission) and investigated patient level factors, including family history, that may be associated with DKA recurrence in pediatric patients with established T1DM. Results: Of the 131 subjects in the study, 51 (39%) subjects were in the recurrence group. Age ≥15 years old, public health insurance, and family history of T1DM or type 2 diabetes mellitus were associated with recurrent DKA admissions in both univariable and multivariable analyses. Family history was associated with DKA recurrence, with an incidence rate ratio of 1.5 (95% confidence interval = 1.0 to 2.3; P = .03). The association was not explained by type of familial diabetes, first degree relative status, or whether the family member lived in the household. Conclusion: Recognition that a positive family history of DM may be associated with a higher risk for DKA recurrence in patients with established T1DM may allow for targeted education and focus on a previously unidentified population at increased risk for DKA. Understanding the mechanism underlying the effect of family history of diabetes on the rates of DKA in patients with established T1DM may allow for improved identification and education of patients who may be at risk for DKA recurrence. Abbreviations: CI = confidence interval; DKA = diabetic ketoacidosis; EHR = electronic health record; IBD = inflammatory bowel disease; IRR = incidence rate ratio; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.
Neuroergonomics and Its Relation to Psychophysiology

Psychophysiology measures physiological activities originating from the autonomic nervous system, including eye movement, heart rate, electromyography, and skin conductance resistance, while operators conduct behavioral tasks. Researchers have distinguished psychophysiology from neuroergonomics, the latter of which focuses on neural activities in brain functions using brain imaging techniques. Psychophysiology has served as a supplementary measure for representing indicators of the neural activity levels involved in physical and cognitive work. In affective ergonomics, however, the brain’s subcortical pathways play a key role, making it difficult to depend solely on the brain imaging techniques used in industrial task settings to quantify and predict human performance. In this chapter, the authors review and compare the strengths and weaknesses of psychophysiology metrics and their applications to cognitive/affective engineering.
The effectiveness of treatment supporter interventions in antiretroviral treatment adherence in sub-Saharan Africa: a systematic review and meta-Analysis.

This systematic review and meta-analysis evaluated the effectiveness of treatment supporter interventions (TSI) in improving ART adherence and viral suppression among adults living with HIV (PLWH) ...
Chapter 8 – Separation of Cells from the Rat Anterior Pituitary Gland

Publisher Summary This chapter discusses the separation of cells from rat anterior pituitary gland. In tissues containing mixed populations of cells, activity of one type can specifically modulate activity of another. The secretory patterns within a given hormone-containing cell type appeared to be dependent upon regional localization within the gland. Velocity sedimentation is a simple method for preparing enriched populations of the various types of hormone-producing cells contained in the rat anterior pituitary glandSpecific cell–cell interactions in the intact pituitary gland were completely destroyed by the procedures required for cell separation. Once enriched populations of different cell types became available, it was only natural to test their functional capabilities in various culture systems. From numerous studies, it is now quite clear that functional activity within a population of pituitary cells producing a given hormone may be heterogeneous. Extrapolation of the functional significance of data derived from separated cells back to the in vivo situation can be hazardous indeed.
Mitigating the Adverse Effects of 12-Hour Shifts: Nursing Leaders' Perspectives.

Objective The purpose of this study was to explore perspectives of nurse leaders regarding strategies to mitigate the job demands of 12-hour shift work and learn their views regarding the role of breaks in offsetting the cognitive and physical demands of acute care nurses working 12-hour shifts. Background The strain of long shifts can result in adverse outcomes for nurses, organizations, and patients. Methods A modified, 3-round, e-Delphi solicited input from nurse leaders. First, qualitative information about support and resources to mitigate the adverse effects of 12-hour shifts was collected, and then 2 subsequent rounds used consensus identification and item ranking to develop recommendations. Results Findings reinforce that job demands of 12-hour shifts can be mitigated via staffing practices, quiet break spaces, and the opportunity to work with familiar patients. Conclusions Recommendations from this work may enhance patient safety, positive organizational outcomes, and a resilient and sustainable nursing workforce.
The role of breast MRI in newly diagnosed breast cancer: An evidence-based review.

The utility of pre-operative MRI in patients with newly diagnosed invasive breast cancer remains a topic of debate. Those who advocate for pre-treatment imaging contend that MRI may detect additional disease not otherwise appreciated on conventional imaging and may provide more accurate staging information to guide treatment. Additionally, it has been proposed that MRI can be utilized to assess extent of residual disease in patients undergoing neoadjuvant chemotherapy. Conversely, those in opposition maintain that routine pre-operative MRI subjects patients to unnecessary ipsilateral mastectomies and prophylactic contralateral mastectomies with no difference in oncologic outcome. When stratified based on tumor biology and patient characteristics, the data suggests that pre-treatment MRI may be advantageous in certain subsets when compared to the general cohort of breast cancer patients. This review recapitulates the current literature on the impact of breast MRI on the surgical management and outcomes of newly diagnosed breast cancer.
Frequent Premature Atrial Contractions Are Associated With Poorer Cognitive Function in the Atherosclerosis Risk in Communities (ARIC) Study

Abstract Objective To evaluate the association of premature atrial contraction (PAC) frequency with cognitive test scores and prevalence of dementia or mild cognitive impairment (MCI). Materials and Methods We conducted a cross-sectional analysis using Atherosclerosis Risk in Communities study visit 6 (January 1, 2016, through December 31, 2017) data. We included 2163 participants without atrial fibrillation (AF) (age mean ± SD, 79±4 years; 1273 (58.9%) female; and 604 (27.97.0% Black) who underwent cognitive testing and wore a leadless, ambulatory electrocardiogram monitor for 14 days. We categorized PAC frequency based on the percent of beats: less than 1%, minimal; 1% to Results During a mean analyzable time of 12.6±2.6 days, 339 (15.7%) had occasional PACs and 107 (4.9%) had frequent PACs. Individuals with frequent PACs (vs minimal) had lower executive function factor scores by 0.30 (95% CI, -0.46 to -0.14) and lower global factor scores by 0.20 (95% CI, -0.33 to -0.07) after multivariable adjustment. Individuals with frequent PACs (vs minimal) had higher odds of prevalent dementia or MCI after multivariable adjustment (odds ratio, 1.74; 95% CI, 1.09 to 2.79). These associations were unchanged with additional adjustment for stroke. Conclusion In community-dwelling older adults without AF, frequent PACs were cross-sectionally associated with lower executive and global cognitive function and greater prevalence of dementia or MCI, independently of stroke. Our findings lend support to the notion that atrial cardiomyopathy may be a driver of AF-related outcomes. Further research to confirm these associations prospectively and to elucidate underlying mechanisms is warranted.
Abstract 2432: Somatic mutations in the STAT3 activation pathway are associated with improved survival in gynecologic malignancies and provide a molecular rationale for therapeutic targeting

Background: Signal transducer and activator of transcription 3 (STAT3) activation promotes tumor cell survival, immune evasion, metastasis, and drug resistance in PARP inhibitors and platinum-based chemotherapy. Objective: Based on our in-vitro findings of the tumoricidal potential of STAT3 inhibition in BRCAwild-type and PARP inhibitor-resistant tumor cells, we sought to evaluate whether ovarian and uterine cancer patients with somatic mutations in the STAT3 activation pathway had improved overall survival (OS) compared to those with intact STAT3 activation pathway-related genes. Method: We induced Olaparib resistance in BRCAwild-type ovarian cancer cell lines (OVCAR8 and A2780) and treated both parental and PARP inhibitor-resistant cell lines with various STAT3 inhibitors. We then attempted to establish clinical correlations of our in-vitro studies and queried the Cancer Genome Atlas (TCGA) Pan-Cancer Atlas for uterine and ovarian cancers. OS in patients with somatic mutations in the STAT3 gene and/or associated STAT3 activation genes (IL6ST, GNAS, JAK1, JAK2) was compared to OS in patients with intact STAT3 pathway-related genes. Kaplan-Meier survival curves were compared using the log-rank test. Results: In-vitro, STAT3 inhibition demonstrated potent, tumoricidal propensity in all cell lines (EC50: 0.34uM-0.46uM) including A2780parental, A2780parpi-resistant, OVCAR8parental, and OVCAR8parpi-resistant. Clinically, 1,154 total patients were identified in TCGA, including 571 high-grade serous ovarian carcinoma, 397 uterine endometrioid adenocarcinomas, 109 uterine serous carcinoma/uterine papillary serous carcinomas, 56 uterine carcinosarcomas/uterine malignant mixed Mullerian tumors, and 21 uterine mixed endometrial carcinomas. When pooling all uterine and ovarian cancer patients, median survival (MS) was 52 months (0-185) in patients with intact STAT3 (n=1,007) compared to not reached (NR, 0-225) in the STAT3 mutated group (n=147) with a Hazard Ratio (HR) of 0.25 and Confidence Interval (CI) 0.20-0.32 (p Conclusion: Pharmacologic and genetic (siRNA) inhibition of the STAT3 activation pathway killed PARP inhibitor-resistant ovarian cancer cells in-vitro. Clinically, somatic mutations in the STAT3 activation pathway were associated with improved OS in both ovarian and uterine cancer. These findings provide a rationale for the therapeutic targeting of this pathway in gynecologic malignancies. Citation Format: Adrian Kohut, Antons Martincuks, Thanh Dellinger, Hua Yu, Lorna Rodriguez-Rodriguez. Somatic mutations in the STAT3 activation pathway are associated with improved survival in gynecologic malignancies and provide a molecular rationale for therapeutic targeting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2432.
An experimental evaluation of the efficacy of imaging flow cytometry (FlowCam) for detecting invasive Dreissened and Corbiculid bivalve veligers

Hassett W, Zimmerman J, Rollwagen-Bollens G, Bollens SM, Counihan TD. 2021. An experimental evaluation of the efficacy of imaging flow cytometry (FlowCam) for detecting invasive Dreissened and Corb...
Complications with Christmas Factor (Factor IX) Concentrates

Excerpt To the editor: Several reports of thromboembolic complications after the use of factor IX concentrates have recently appeared (1-3). These reports have prompted us to survey our experience ...
BEITI Project: The Teaching of Entrepreneurship at Grade Schools

This paper proposes the teaching of entrepreneurship at grade schools for improvement in the economy of countries, strong empowerment of the critical age group youth and young adults for competitiveness in all aspects of creative pursuits for several years to come. The outlined program is entitled Business, Entrepreneurship, and Innovation Teaching Interface (BEITI), and it aims to teach the basic didactics in entrepreneurship and build on it the possible business and economic implications of the didactics; in addition teach it early as well as deliver the concepts using fun and creative technology applications most individuals are already comfortable with. The Proposal framework is built on Schumpeter’s 1934 advocate that entrepreneurship plays a great role in economic development. This is because entrepreneurs are able to innovate in order to transform commercial products through processes that add economic value. According to Acs et al (2004), that transformation is only made possible when entrepreneurship plays the role of "knowledge filter". Particularly where it is made an integral component of the curricula in schools, it tends to produce leaders in societies that have business knowledge (Nelson & Johnson, 1997). Keywords : Entrepreneurship Teaching, Creativity, Innovation, BEITI Project, Economic Growth.
Walker, J. R. (2010). British Nuclear Weapons and the Test Ban 1954–1973: Britain, the United States, Weapons Policies and Nuclear Testing: Tensions and Contradictions. B. Chakma (Ed.). (2011). The Politics of Nuclear Weapons in South Asia

The current debate surrounding the proliferation of nuclear weapons has increasingly focused on the “second nuclear age” typified by the nuclear states of the post-Cold War system. The first nuclea...
Effect of the transcription start region of the herpes simplex virus type 1 latency-associated transcript promoter on expression of productively infected neurons in vivo.

It has been previously reported that the latency-associated transcript (LAT) promoter contains a DNA sequence at the LAT transcription start site which resembles the ICP4 consensus DNA binding site and that this site allows ICP4-mediated downregulation of the LAT promoter in transient assays (A. H. Batchelor and P. O'Hare, J. Virol. 64:3269-3279, 1990). We have confirmed these data by showing that an ICP4-expressing plasmid will downregulate lacZ expression from a plasmid containing the LAT promoter and transcription start site (pJA1) and does not downregulate lacZ expression from a plasmid in which the start site has been mutagenized (pWAG15). To determine the role of the LAT transcription start site in regulating LAT promoter activity in the context of the virus, two recombinant viruses, KOS-1 and KOS-15, were studied. KOS-1 contains an 863-bp portion of the LAT promoter, including the LAT cap site, fused to the lacZ gene and inserted into the gC locus (T.P. Margolis, F. Sedarati, A.T. Dobson, L.T. Feldman, and J.G. Stevens, Virology 189:150-160, 1992). The second virus (KOS-15) was constructed in identical fashion, using plasmid pWAG-15, which is not downregulated by ICP4. Vero cells productively infected with KOS-15 produce 10-fold more beta-galactosidase than do those infected with KOS-1. In murine dorsal root ganglia acutely infected with KOS-1, only 1.2% of dorsal root ganglion neurons that expressed viral antigen also expressed beta-galactosidase. In contrast, in KOS-15-infected mice, beta-galactosidase was detected in 18% of viral antigen-positive neurons. Similar findings were observed in trigeminal ganglia acutely infected with KOS-1 and KOS-15. Thus, the region encompassing the LAT transcription start site appears to play an important role in repression of the LAT promoter activity not only in vitro but also in acutely infected neurons in vivo. These results suggest that during productive infection with HSV-1, LAT expression is tightly regulated.
Common Factors in Couple and Family Therapy: The Overlooked Foundation for Effective Practice

What Is Responsible for Therapeutic Change?: Two Paradigms. A Brief History of Common Factors. Common Factors Unique to Couple and Family Therapy. The Big-picture View of Common Factors. A Moderate View of Common Factors. Getting Clients Fired Up for a Change: Matching Therapist Behavior with Client Motivation. A Strong Therapeutic Alliance. Models: All Roads Lead to Rome. A Meta-model of Change in Couple Therapy. The Case Against Common Factors. Common-Factors Training and Supervision. Implications for Clinicians and Researchers. Appendix A: Moderate Common-Factors Supervision Checklist. Appendix B: Instruments from Other Authors Related to Common Factors.
Thermal Conductivity of Solid HD Containing Isotopic Impurities

The thermal conductivity of a sample of solid HD containing fixed H2 and D2 isotopic impurities has been measured over a period of 271 hr in the temperature range 4–0.2°K. During this time a substantial number of o-H2 impurities convert to p-H2, enabling one to determine in the same crystal the o-H2 dependence of the thermal conductivity. The o-H2 dependence is compared to the theory of Ebner and Sung1 and found to give reasonable agreement for temperatures above 0.6°K. Isotopic scattering was found to dominate the high-temperature data. The low-temperature results were characteristic of boundary scattering, from which it was inferred that the sample was polycrystalline.
On finding locally optimal solutions

The problem of finding locally optimal solutions to combinatorial problems in the framework of polynomial-time local search as defined by D.S. Johnson et al. (J. Comput. Syst. Sci., vol.37, no.1, p.79-100, Aug. 1988) is considered. A PLS-complete problem such that the problem of verifying local optimality can be solved in LOGSPACE is exhibited. For all previously known PLS-complete problems, verifying local optimality was P-complete, and it was conjectured in Johnson et al. that this was necessary. >
Role of the FcγR subclasses FcγRII and FcγRIII in the activation of human neutrophils by low and high valency immune complexes

Two Fc gamma receptor (Fc gamma R) subclasses on human neutrophils, Fc gamma RII and Fc gamma RIII, activate different cellular functions. To examine the involvement of each receptor subtype in polymorphonuclear leukocyte activation, Fab and F(ab')2 fragments of subclass-specific monoclonal antibodies ([mAbs] mAb IV.3 against Fc gamma RII and mAb 3G8 against Fc gamma RIII, respectively) were used to block the binding of low valency immune complexes (LICs) and high valency immune complexes (HICs). Flow cytometry then permitted the simultaneous quantitation of antibody and ligand binding, the elicited intracellular Ca2+ concentration (delta[Ca2+]int), initiation of the oxidative burst, and/or the phospholipase A activation in the same cell. We have previously demonstrated that subsaturating dosages of HIC bind uniformly to all the cells but elicit an "all-or-none" (i.e., dose independent) maximal delta[Ca2+]int in a dose-dependent subpopulation of the cells. In contrast, both the proportion of cells responding and the magnitude of the delta[Ca2+]int transient depend on the subsaturating dose of LIC, even though it too binds uniformly to all the cells, nonresponding as well as responding. These earlier findings have here been extended by single cell flow cytometric analysis to demonstrate that F(ab')2 Fc gamma RIII is the major Fc gamma R involved in HIC binding (and [Ca2+]int mobilization), as well as in oxidative burst and phospholipase A activation. In contrast, both receptor subclasses must be available for LIC-elicited delta[Ca2+]int, as blockage by either of the mAb Fab or F(ab')2 fragments abrogates this response, even though LIC binding to the receptors is not decreased. Furthermore, LIC elicited little oxidative burst activity and failed to activate phospholipase A but cross-linking to achieve multivalency, previously shown to induce [Ca2+]int and oxidative burst responses, elicited phospholipase A activity via Fc gamma RIII. Fc gamma RII's role appears to be modulation of the small, late Ca2+ influx observed at > 1 min, whereas Fc gamma RIII modulates all the earlier larger events. Thus, simultaneous observation of receptor identity, receptor occupancy, and consequent activation parameters in the same cell by flow cytometry permits use to demonstrate that Fc gamma RII is necessary for the small signal transduction elicited by LIC; it plays a relatively small role in polymorphonuclear leukocyte stimulation by HIC. Fc gamma RIII is the main receptor responsible for immune complex-elicited polymorphonuclear leukocyte responses; its efficacy is greatly enhanced when the receptors are cross-linked, either by preequilibrated multivalent complexes or by in situ cross-linking of bound LIC with excess antibody.
A "realistic" approach for educating systems programmers

Educating systems programmers to handle real world problems can be very difficult. Each step in the translation process from perception to production has the potential of inducing errors into the production system as a result of the complexity and abstractness of the "real world" system. The task involves developing a system of personnel, procedures, equipment, and computer programs which together emulate the "real world" system.
Evaluating the mean frequency of responding cells in limiting dilution assays

The validity of limiting dilution assays can be compromised or negated by the use of statistical methodology which does not consider all issues surrounding the biological process. This study critically evaluates statistical methods for estimating the mean frequency of responding cells in multiple sample limiting dilution assays. We show that methods that pool limiting dilution assay data, or samples, are unable to estimate the variance appropriately. In addition, we use Monte Carlo simulations to evaluate an unweighted mean of the maximum likelihood estimator, an unweighted mean based on the jackknife estimator, and a log transform of the maximum likelihood estimator. For small culture replicate size, the log transform outperforms both unweighted mean procedures. For moderate culture replicate size, the unweighted mean based on the jackknife produces the most acceptable results. This study also addresses the important issue of experimental design in multiple sample limiting dilution assays. In particular, we demonstrate that optimization of multiple sample limiting dilution assays is achieved by increasing the number of biological samples at the expense of repeat cultures.
Children with gender nonconformity.

Journal of the American Academy of Child & Adolescent Psychiatry - Vol. 42 - N° 3 - p. 266
Modern introductory computer science

There have been numerous testimonies to the inadequacies of our educational system [83]. For undergraduate computer science educators, major concerns regarding student preparation include poor problem solving and critical thinking skills, weak mathematics background, an inability to convey thoughts and concepts, and a lack of motivation. These problems can be addressed in the introductory computer science course by developing an integrated approach to effectively teaching discrete mathematical foundations, fundamental computer science concepts, and problem-solving skills. This paper is conceptual in nature and introduces some specific examples of possible approaches to overcoming these deficiencies and problems.
Image Charge Solvation Model (ICSM) with Improved Boundary Conditions

In previous work the Image Charge Solvation Model (ICSM) [1] was introduced as an alternative way to simulate bulk properties of solutions. The ICSM consists of a spherical cavity of explicit solvent embedded in a continuum dielectric medium, and solves the electrostatic interactions accurately and more efficiently than the Particle Mesh Ewald (PME) method on large scales. In spite of the success of the model in simulating a pure water system, and extremely dilute ionic solutions [2], periodic boundary conditions create unphysical charge-charge correlations at finite ion concentrations. Although expanding the system size can reduce these extraneous correlations to negligible levels in principle, the PME method remains more efficient on large scales. In this work we re-evaluate the applied boundary conditions at the cavity wall to correct the problem at its origin, which is related to torques on water molecules due to the electrostatic reaction field [3]. Here, we apply a mean field force representing bulk media outside the cavity, and a self-correcting torque field is introduced to enforce translational symmetry. Our modified ICSM maintains accuracy, performs more efficiently than previously and removes the primary cause of spatial correlations between ions.[1] Y. Lin, A. Baumketner, S. Deng, Z. Xu, D. Jacobs, W. Cai, An image-based reaction field method for electrostatic interactions in molecular dynamics simulations of aqueous solutions. J. Chem. Phys. 131, (2009).[2] Y. Lin, A. Baumketner, W. Song, S. Deng, D. Jacobs, and W. Cai, Ionic solvation studied by image-charge reaction field method. J. Chem. Phys. 134, (2011).[3] W. Song, Y. Lin, A. Baumketner, S. Deng, W. Cai and D. Jacobs, Effect of the reaction field on molecular forces and torques revealed by an Image-Charge Solvation Model, Comm. Comp. Phys. 13:129-149 (2013).
Downstream Effects of ROCK Signaling in Cultured Human Corneal Stromal Cells: Microarray Analysis of Gene Expression

PURPOSE Rho-associated coiled-coil-containing protein kinase (ROCK) is a downstream target of Rho GTPase signaling and regulates the assembly of stress fibers. Previous reports indicate that Rho/ROCK signaling is involved in the regulation of several cellular processes, some of which may be cell-type specific and are probably critical to corneal stromal cell activation. The present study identified ROCK-regulated gene expression in corneal stromal cells. METHODS Corneal stromal cells derived from eyes of three different donors were cultured to yield the following designated phenotypes: baseline fibroblasts (DMEM with 10% serum), activated fibroblasts (10% serum+bFGF+heparin), and myofibroblasts (1% serum+TGF-beta 1). Cells were exposed to the ROCK inhibitor Y-27632 or vehicle for 12 hours, and transcript levels altered by ROCK inhibition were identified with oligonucleotide microarrays (GeneChips; Affymetrix, Santa Clara, CA). RESULTS In these phenotypes, Y-27632 caused marked (twofold or more) increases or decreases in 14/4, 12/3, and 15/10 transcripts. In both fibroblast groups Y-27632-treatment increased expression of endothelin receptors and of parathyroid hormone-like hormone. The upregulation of alpha-smooth muscle actin in myofibroblasts was attenuated by Y-27632. Combining data from all groups identified ROCK-supported (Y-27632 inhibitable) expression of 10 transcripts, including ribonucleotide reductase M2, the cyclin B1-CDC2-CKS2 system, and four mitotic spindle-associated proteins. CONCLUSIONS ROCK inhibition causes broad inhibition of DNA synthesis and mitosis and causes changes that are different between (bFGF-activated) fibroblasts and (TGF-beta 1-induced) myofibroblasts. Thus, Rho/ROCK signaling regulates both common and distinct downstream events in corneal stromal cells activated (differentiated) to fibroblast or myofibroblast phenotype.