cssi/SciSciGPT-SciSciNet huggingface dataset:
Alternative Mating Tactics in Socially Monogamous Prairie Voles, Microtus ochrogaster

ABSTRACT: Alternative mating tactics appear to evolve when sexual selection is strong. Because such conditions are usually observed in species with polygynous or polyandrous mating systems, alternative mating tactics in monogamous mating systems are seldom documented and are poorly understood. In prairie voles, Microtus ochrogaster, a species widely known for forming monogamous pair-bonds, the expression of territoriality within each sex is dimorphic, and includes non-territorial “wanderers” as well as territorial “residents.” To explore the variance in fitness, measured in offspring numbers, among breeding individuals expressing these alternative mating tactics, we compiled parentage data over three years for male and female prairie voles from natural populations in Indiana and Kansas, USA. We found that: (1) the average fitnesses of males and females within each population were identical when adjusted by the sex ratio; (2) the variance in fitness in male and female prairie voles was comparable to that of many highly polygynous species; (3) The average fitnesses of male tactics, and of female tactics, were equivalent within and among years within each location; (4) consistent with negative frequency-dependent selection acting on mating phenotypes, the between-tactic variance in fitness for male and female mating tactics decreased with increasing study duration; (5) consistent with negative assortative mating, resident males and wanderer females produced offspring primarily in monogamous partnerships, whereas wanderer males and resident females produced offspring primarily in polygamous partnerships. Our results show that the conditions necessary for the persistence of alternative mating tactics are indistinguishable from those for phenotypically less flexible alternative mating strategies, and that alternative mating tactics can evolve in both sexes in monogamous species when fitness variance within each sex is large.
Jacob Gallagher-Ross. Theaters of the Everyday: Aesthetic Democracy on the American Stage.

In four elegant case studies, Jacob Gallagher-Ross convincingly argues for a re-evaluation of the American concern for the quotidian as an avant-garde tradition that imagines the everyday as centra...
THE IMPACT OF TRANSCATHETER AORTIC VALVE IMPLANTATION ON LEFT VENTRICULAR REMODELING AT ONE YEAR POST INTERVENTION

The effect of Transcatheter Aortic Valve Implantation (TAVI) on left ventricular (LV) geometry is not well defined. We aimed to assess the LV mass regression and changes in LV dimensions in patients with normal and reduced ejection fraction (EF) at 1 year post-TAVI. We queried our institutional
Mild erythrocytosis as a presenting manifestation of PIEZO1 associated erythrocyte volume disorders

Piezo1, encoded by the gene PIEZO1, is an erythrocytic cellular membrane mechanoactivated cation channel. Mutations have been implicated in erythrocyte volume disorders (EVDs)—especially hereditary...
Laser Safety Management

An effective laser safety program can mean big savings in time, money, effort, and most importantly, human well-being. It can improve the quality of your research program, your organization's reputation, and ultimately, improve your bottom line. Based on the extensive experience of active Laser Safety Officer Kenneth Barat, Laser Safety Management provides practical tools for successfully implementing a laser safety program in any environment. The book defines the three elements of laser safety: users, the laser safety officer, and incidental personnel. It covers the types of laser injuries, standard operating procedures to ensure safety, tips and tools to avoid pitfalls, training, control measures, and personal protection equipment. The author explores the laser safety officer position and delineates the required elements of effective SOPs. He also discusses non-beam hazards, includes practical control examples and sample forms, and covers U.S. and European regulations and standards. Taking a pedagogical approach, the book covers not only how to avoid accidents, but how to investigate them if they do occur. It includes a sample safety program designed to evaluate your current safety plan and act as a roadmap for where you need to be and how to get there. Filled with common sense solutions for laser safety issues, the book makes setting up a safety program practically painless.
Research-Based Updates in Swallowing and Communication Dysfunction in Parkinson Disease: Implications for Evaluation and Management

Purpose Individuals with Parkinson disease (PD) present with complex and variable symptoms, with recent findings suggesting that the etiology of PD extends beyond the involvement of just the basal ...
Interleukin-33 Promotes Th2/Th17 Response in Eosinophilic and Non-Eosinophilic Nasal Polyps.

Background Interleukin-33 (IL-33) is reported to be involved in Th2-skewed eosinophilic inflammation. A recent study also found that IL-33 exerted opposite effects on Th17 response in different diseases. However, the role of IL-33 in chronic rhinosinusitis with nasal polyps (NPs) was not explored. Objectives The purpose of this study was to investigate the expression and function of IL-33 in chronic rhinosinusitis with NPs. Materials and methods NP tissues from 60 NP patients and normal tissues of the inferior turbinate from 20 controls were sampled in operation. Immunochemistry was performed to identify eosinophilic or non-eosinophilic NPs. The expressions of IL-33 and Th1/2/17 cytokines were compared between different subtypes of NPs. The effect of IL-33 on Th response was detected in dispersed nasal polyp cells (DNPCs), and the signaling pathways involved in the process were detected using Western blot. Results The concentration of IL-33 was signiﬁcantly elevated in both eosinophilic and non-eosinophilic NPs compared with controls. By in vitro study, we found that IL-33 can induce IL-4 and IL-5 production from eosinophilic DNPCs through the PI3K/AKT pathway, whereas IL-33 can induce IL-17 production from non-eosinophilic DNPCs through the ERK1/2 pathway. Conclusion IL-33 is involved in Th2/Th17 response in NPs. Our study suggests that different types of NPs need a different treatment target.
Clinical Outcome of Chronic Lymphocytic Leukemia Patients with Sole 13q FISH Detectable Defects: One Versus Two 13q Deletions.

![Figure][1] Figure Background: An isolated 13q deletion in patients with chronic lymphocytic leukemia (CLL) is the single most common cytogenetic abnormality and is a favorable prognostic parameter (Dohner et al., NEJM 3432:1910, 2000). Although 13q- can occur as either a heterozygous (13q-x1) or homozygous (13q-x2) deletion, it is unknown whether these two genetic types differ in their impact on clinical outcome. We previously postulated that 13q-x2 may be a more aggressive anomaly than 13q-x1 (Dewald et al., BJH 121:287, 2003) and have undertaken a long-term clinical follow-up of patients with an isolated FISH detectable 13q- to test this hypothesis. Methods: We identified patients diagnosed with CLL between October 1992 to May 2008 and who had 13q deletion as their sole FISH abnormality. FISH was performed within 2 years of diagnosis and prior to treatment in all patients. Patients were sorted into three groups: 13q-x1 only, 13q-x2 only, or mosaic with both 13q-x1 and 13q-x2 cells. We assessed differences in percentage of abnormal cells, demographic characteristics, and clinical outcome among the three groups. Results: We identified 259 patients with isolated 13q deletion. Age ranged from 38 to 90 years (median=61) and included 99 women and 160 men. With respect to Rai stage, 142 patients (60%) had low risk [Rai 0], 81 (34%) intermediate risk [Rai I-II], and 13 (6%) high risk [Rai III-IV] disease. After a median follow-up of 1.9 years, 40 patients (15%) have been treated and 17 (7%) have died. Median TFS and OS for all patients were 6.9 and 9.3 years, respectively. The mean percentage of abnormal nuclei in the three groups was 44%, 53%, and 47% for 13q-x1 only, mosaic 13q-x1/13q-x2, or 13q-x2 only, respectively (p=0.22). No significant difference in age or gender was observed based on whether 13q- occurred as a heterozygous or homozygous deletion, or was mosaic. Likewise, no significant difference in survival (p=0.313, see Table) or time to treatment (p=0.53) was found among the three groups. Five year OS rates for the 13q- x1 only, 13q- x2 only, and mosaic 13q- x1/13q- x2 are 85%, 95%, and 83%, respectively Median time to treatment for 13q-x1 was not reached, and for the mosaic13q-x1/13q-x2 and 13q-x2 groups median time to treatment was 6.9 and 4.9 years, respectively. Conclusions: The presence of deletion in one versus two 13q- chromosomes in CLL patients appears to have no significant impact on treatment free or overall survival. This observation supports the grouping of CLL patients with isolated 13q- of one or both alleles into a single risk category as originally proposed in the risk categorization by Dohner et al. Taking the present findings together with those of Dohner et al and Dewald et al, we propose a hierarchical risk model of FISH abnormalities in CLL as 17p- a 11q- a 6q- a +12 a normal a 13q-, from most to least aggressive. The 13q- group would now include 13q-x1, 13q-x2, and the mosaic subgroups. [1]: pending:yes
IMPACT OF OBESITY IN HEART FAILURE PATIENTS PARTICIPATING IN PHASE II CARDIAC REHABILITATION

The presence of obesity in patients with heart failure with reduced ejection fraction (HFrEF) has been paradoxically associated with improved prognosis compared with non-obese counterparts. We aimed to assess whether the “obesity paradox” impacts both exercise capacity (EC) and prognosis in
Endometrioid sarcoma ("stromal endometriosis"). Report of 15 cases including 5 with metastases.

Abstract “Endometrioid sarcoma” is the proposed designation of a rare neoplasm of the endometrial stroma commonly called “stromal endometriosis.” It occurs most frequently in the fifth decade of life but its onset may be earlier or later. The clinical features are not diagnostic; rather they suggest other commoner pelvic neoplasms. The lesion has a readily identifiable and diagnostic gross and histologic appearance, which, once seen and identified, can scarcely be confused with any other lesion of the pelvic organs. The initial treatment should be surgical, preferably total abdominal hysterectomy with bilateral salpingo-oophorectomy. Intravascular extensions should be sought and removed if found. The concept that this condition is benign is erroneous. This malignant neoplasm is directly responsible for death in perhaps 25 per cent of cases, usually after a protracted course.
Mixed Phospholipid Vesicles Catalytically Inhibit and Reverse Amyloid Fibril Formation.

While many approaches to reduce fibrillation of amyloid-β (Aβ) have been aimed at slowing fibril formation, the degradation of fibrils remains challenging. We provide insight into fibril degradatio...
Association of race and ethnicity to incident epilepsy, or epileptogenesis, after subdural hematoma.

Objective To determine whether race is associated with the development of epilepsy after subdural hematoma (SDH), we identified adult survivors of SDH in a statewide administrative dataset and followed them up for at least 1 year for revisits associated with epilepsy. Methods We performed a retrospective cohort study using claims data on all discharges from emergency departments (EDs) and hospitals in California. We identified adults (age ≥18 years) admitted from 2005 to 2011 with first-time traumatic and nontraumatic SDH. We used validated diagnosis codes to identify a primary outcome of ED or inpatient revisit for epilepsy. We used multivariable Cox regression for survival analysis to identify demographic and medical risk factors for epilepsy. Results We identified 29,342 survivors of SDH (mean age 71.2 [SD 16.4] years, female sex 11,954 [41.1%]). Three thousand two hundred thirty (11.0%) patients had revisits to EDs or hospitals with a diagnosis of epilepsy during the study period. Black patients (n = 1,684 [5.7%]) had significantly increased risk compared to White patients (n = 16,945 [57.7%]; hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.28–1.64, p Conclusions We found an association between Black race and ED and hospital revisits for epilepsy after SDH, establishing the presence of a racial subgroup that is particularly vulnerable to post-SDH epileptogenesis.
Design and Implementation of a Modular Multiplier for Public-Key Cryptosystems Based on Barrett Reduction

This paper refers to a hardware implementation for executing modular multiplication in public-key cryptosystems using the Barrett reduction, which is a method of reducing a number modulo another number without the use of any division. Considering the flexibility of hardware, the modular multiplier we proposed is able to work over 3 prime fields \( {\text{GF}}\left( p \right) \), standardized by NIST for use in Elliptic Curve Cryptography (ECC), where the size of primes \( p \) are 256, 384, and 521 bits. We designed two methods to optimize the modular multiplier: Firstly, the circuit departed \( 257 \times 257 \) multiplier into two \( 257 \times 129 \) multipliers and an adder, three parts to optimize for clock frequency. Secondly, we proposed a parallel computing architecture to improve the utilization of multiplier and achieve high throughput. This modular multiplier runs at the clock rate of 300 MHz on 40 nm CMOS and performs a 256-bit modular multiplication in 3 cycles, while 384-bit modular multiplication costs 10 cycles and 521-bit modular multiplication costs 25 cycles. The architecture is very suitable for situations requiring high computing speed, such as online ECC signature verification.
Modeling the impact of solar and ocean energy integration on the reliability and resiliency of the Eastern North Carolina power grid system

The research performed is focused on the impact of solar generation sites on the existing power grid. The area of focus for the study is the customers served by Tideland EMC in Beaufort County, NC. Beaufort County North Carolina has a population of 47,079 people with a household size averaging 2.5 people per household [1]. With the average household consuming 1072kWh a month, this means Beaufort county consumes around 17.1 GWh per month [2]. Tideland EMC is the Cooperative that provides electric energy in this area, and several other nearby counties: Washington, Dare, Hyde, Pamlico, Craven, Ocracoke island [3].
MYBL2-Driven Transcriptional Programs Link Replication Stress and Error-prone DNA Repair With Genomic Instability in Lung Adenocarcinoma

It has long been recognized that defects in cell cycle checkpoint and DNA repair pathways give rise to genomic instability, tumor heterogeneity, and metastasis. Despite this knowledge, the transcription factor-mediated gene expression programs that enable survival and proliferation in the face of enormous replication stress and DNA damage have remained elusive. Using robust omics data from two independent studies, we provide evidence that a large cohort of lung adenocarcinomas exhibit significant genome instability and overexpress the DNA damage responsive transcription factor MYB proto-oncogene like 2 (MYBL2). Across two studies, elevated MYBL2 expression was a robust marker of poor overall survival and disease-free survival outcomes, regardless of disease stage. Clinically, elevated MYBL2 expression identified patients with aggressive early onset disease, increased lymph node involvement, and increased incidence of distant metastases. Analysis of genomic sequencing data demonstrated that MYBL2 High lung adenocarcinomas had elevated somatic mutation burden, widespread chromosomal alterations, and alterations in single-strand DNA break repair pathways. In this study, we provide evidence that impaired single-strand break repair, combined with a loss of cell cycle regulators TP53 and RB1, give rise to MYBL2-mediated transcriptional programs. Omics data supports a model wherein tumors with significant genomic instability upregulate MYBL2 to drive genes that control replication stress responses, promote error-prone DNA repair, and antagonize faithful homologous recombination repair. Our study supports the use of checkpoint kinase 1 (CHK1) pharmacological inhibitors, in targeted MYBL2 High patient cohorts, as a future therapy to improve lung adenocarcinoma patient outcomes.
iTRAQ-Based proteomic dataset for bovine pre-ovulatory plasma and follicular fluid containing high and low Estradiol

Abstract This is isobaric tags for a relative and absolute quantification (iTRAQ)-Based Proteomic Data on bovine plasma (PL) and follicular fluid (FF) containing high and low pre-ovulatory circulating concentration of estradiol (E2). The PL and FF were collected from nine beef cows that were identified to initiate a new follicular wave on day -4 during synchronization. Follicular dynamics and ovulatory response were monitored using transrectal ultrasonography. Blood samples were collected at slaughter and FF was aspirated from dominant follicles (DF; >10 mm). Estradiol concentrations in PL and FF were measured by radioimmunoassays. Plasma and FF were labeled as containing high E2 (PL HE2 and FF HE2) or low E2 (PL LE2 and FF LE2). Abundant proteins (albumin, IgG, IgA, and alpha-1-antitrypsin) were depleted from the four PL and FF samples. Peptides were labeled with iTRAQ reagents and analyzed using 2-dimentional liquid chromatography ESI-based mass spectrometry. Proteins were identified and quantified using SEQUESTTM search engine embedded in Proteome Discoverer. The proteins matched with at least one unique peptide at minimum 95% confidence were considered positive identifications. Protein expression levels were determined by assigned fold change of >2.0 or https://doi.org/10.1016/j.domaniend.2021.106606
Design of a toolkit for real-time executive function assessment in custom-made virtual experiences and interventions

Abstract Virtual Reality (VR) and other game-like experiences are popular intervention platforms in neurocognitive rehabilitation research. Executive Functions (EF), the cognitive processes that regulate attention and goal-oriented action, are recognized as a domain of concern in several congenital and acquired neurocognitive conditions (e.g.: ADHD, autism, addiction, cognitive decline, traumatic brain injury, and stroke). VR-based simulations of real-world tasks have shown potential for rehabilitation in independent functioning. The custom nature of such projects makes cross-intervention analysis difficult and complicates development of best-practices. We have designed a toolkit for building virtual interactions that can consistently replicate traditional cognitive tests (such as the Wisconsin Card Sorting Task and Multitasking Task) as well as extend to more complex tasks in any virtual context. Analysis of participant performance data between traditional tasks and these VR replications may indicate the toolkit can successfully replicate traditional measures while also extending into more complex contexts.
An in vivo drug repurposing screen and transcriptional analyses reveals the serotonin pathway and GSK3 as major therapeutic targets for NGLY1 deficiency

NGLY1 deficiency, a rare disease with no effective treatment, is caused by autosomal recessive, loss-of-function mutations in the N-glycanase 1 (NGLY1) gene and is characterized by global developmental delay, hypotonia, alacrima, and seizures. We used an adult Drosophila model of NGLY1 deficiency to conduct an in vivo, unbiased, small molecule, repurposing screen of FDA-approved drugs to identify therapeutic compounds. Seventeen molecules rescued lethality in a patient-specific NGLY1 deficiency model, including multiple serotonin and dopamine modulators. Exclusive dNGLY1 expression in serotonin and dopamine neurons, in an otherwise dNGLY1-null fly, was sufficient to rescue lethality. Further, genetic modifier and transcriptomic data supports the importance of serotonin signaling in NGLY1 deficiency. Connectivity Map analysis identified glycogen synthase kinase 3 (GSK3) inhibition as a potential therapeutic mechanism for NGLY1 deficiency, which we experimentally validated with TWS119 and lithium. Strikingly, GSK3 inhibitors and a serotonin modulator rescued size defects in dNGLY1 deficient larvae upon proteasome inhibition, suggesting that these compounds act through NRF1, a transcription factor that regulates proteasome expression. This study reveals the importance of the serotonin pathway in NGLY1 deficiency, and serotonin modulators or GSK3 inhibitors may be effective therapeutics for this rare disease.
The Confluence of Law and Antebellum Black Literature

This article argues that the acculturation of black Bostonians to the rhetoric of the law during the Revolutionary era was constitutive and sustaining. This article examines how three pivotal Boston-based antebellum authorsPrince Hall, David Walker, and Maria Stewart appropriated the rhetoric of legal pleading used in Revolutionary-era government petitions and freedom suits (petitioning for redress of grievances, closely analyzing precedential texts, distilling ideas into reasoned arguments, adding factual proof, the pointed use of narrative and interrogative mode) to produce a literature of complaint and rights-assertion. The central premise of the article is that antebellum black texts used these lawyerly discursive practices ironically, as an empowering move, to draw attention to the disparity between the rhetoric of rights and actual practice. Because these "lawyers' words" called upon the authority and salience of the law as a source of rights in the process of claiming rights, lawyerly discourse served as a sustaining strategy of empowerment for black people, and captured the sense of irony in their experience.
Opella, Stanley J.: NMR Spectroscopy and Structural Biology

The sections in this article are 1 Personal Perspective 2 Research Perspective 3 The Development of Solid State NMR Spectroscopy of Proteins 4 The Application of NMR Spectroscopy to Proteins 5 Acknowledgements 6 Biographical Sketch
Electron beam induced effects on gas adsorption utilizing auger electron spectroscopy: Co and O2 on Si: I. Adsorption studies

Abstract The effect of electron beam monitored gas adsorption on the clean Si surface is studied using Auger electron spectroscopy. It is shown that the beam affects the AES adsorption signal of CO and O2 on Si by dissociating the adsorbed molecules on the surface and subsequently promoting diffusion of atomic oxygen into the bulk. A qualitative explanation of the adsorption data is presented and the initial sticking probability of O2 on Si (111) surface is estimated to be S0 = 0.21.
Redox signalling to nuclear regulatory proteins by reactive oxygen species contributes to oestrogen-induced growth of breast cancer cells

Historically, a majority of breast cancer research has focused on exploring conventional oestrogen receptor (ER) and growth factor pathways with limited investigations on alternative mechanisms of oestrogen action. Redox signalling as an alternative mechanism of oestrogen-dependent breast tumor growth is rapidly emerging with the promise of therapeutic potential. Physiologically achievable concentrations of oestrogen increase reactive oxygen species (ROS) formation in breast cancer cells (Felty et al, 2005a; Parkash et al, 2006). An increasing body of evidence supports the postulate that oxidative stress generated from exposure to oestrogen, either directly or by influencing the ER, may be an important driver in the development and evolution of human breast cancer (Okoh et al, 2011; Penny and Roy, 2013). The role of ROS in breast cancer is not new; however, a gap in knowledge currently exists with regard to how oestrogen-induced ROS signals nuclear regulatory proteins by way of redox-sensitive proteins. It is widely believed that an impaired redox signalling pathway leads to the dysregulated phosphorylation and/or dephosphorylation of proteins involved in the activation or deactivation of nuclear regulatory proteins (Okoh et al, 2011; Penny and Roy, 2013). We have previously shown that 17β-estradiol (E2)-induced DNA synthesis in MCF-7 breast cancer cells depends on mitochondrial oxidant signalling to AP-1, CREB, and NRF-1 (Felty et al, 2005a; Parkash et al, 2006). This study aims to extend our previous efforts in understanding how an increase in ROS from E2 exposure transduces a signal to nuclear regulatory proteins as well as to identify the key downstream nuclear proteins responsible for the growth of breast cancer cells. We demonstrate for the first time a molecular mechanism of E2-induced activation of NRF-1 leading to the upregulation of cell cycle genes; in addition, the impairment of p27 activity through the ROS-inducible PI3K→PDK1/2→AKT signal-transduction pathway may be necessary for E2-mediated growth of MCF-7 breast cancer cells.
On robustness and localization accuracy of optical flow computation from color imagery

Accurate and efficient optical flow estimation is a major step in many computational vision problems, including tracking and 2D/3D mapping applications. Processing of grayscale images has been the dominant approach, with only a few studies investigating selected aspects in the use of color imagery. In a physics-based analysis to study the impact of the spectral-dependent medium attenuation on the color channels, we have shown merit in the use of color cues in the computation of optical flow for underwater imagery- the primary motivation of the investigation [Negahdaripour, S. et al., (2002)]. Comparisons among various color representations and traditional intensity component on the optical flow computation are given, suggesting that the HSV representation could be the most suitable. For both underwater and terrestrial imagery, even where data in the 3 color channels are highly correlated, one expects multiple constraints from color channels to give increased robustness due to the independent channel noises. Results of experiments are given to demonstrate improved localization and accuracy.
Abstract 2059: In situ imaging of antibody drug conjugate (ADC) binding and pharmacodynamic biomarkers of response in models of human cancer

Antibody drug conjugates (ADCs) are clinically validated as a modality for targeted therapy of solid and hematological cancer due to advancements in target selection, conjugation chemistry and linker technology. However, much about mechanism of action (MoA) is yet to be fully understood. Our goal was to interrogate ADC pharmacokinetics and pharmacodynamics establishing proof of mechanism (PoM) of drug action with a diverse panel of ADCs. Herein, we describe the development of novel immunohistochemical (IHC) methods for in situ visualization of ADCs binding to target expressing cells and their cognate downstream biomarkers of response in formalin fixed paraffin embedded cells/tissues. We demonstrate specific binding of 4 different ADCs spanning 2 solid tumor targets and an endothelial cell target using IHC with anti-human IgG in human tumor xenograft models expressing the respective targets. ADC binding to target is observed as early as 20 minutes after a single dose of ADC at 3 mg/kg. Utilizing an anti-microtubule inhibitor (MTI) payload-specific antibody we additionally detect ADC binding to tumor cells by monitoring the cytotoxic payload. The cell type where the antibodies and payload localized was identified by double and triple IHC. Pharmacodynamic biomarkers of response for two payload classes (DNA damaging agents and MTIs) were detected with antibodies against phospho-Histone H2AX and phospho-Histone H3, respectively - confirming the expected ADC MoAs. Downstream apoptosis of target cells was detected with cleaved caspase 3 IHC. The kinetics of biomarker response and downstream cellular impact was quantified via image analysis with biomarkers evident as early as 24 hours after a single dose for both tumor cell and vascular targets. Furthermore, we observed a correlation between biomarkers of response and efficacy of the ADCs as measured by statistically significant tumor growth inhibition for the 4 ADCs we studied. These data suggest that IHC interrogations of drug action should be used to further the clinical development of ADCs via demonstration of pharmacodynamic activities at the cellular level, establishing PoM data, and enabling predictive preclinical oncology models in order to reduce clinical attrition of ADCs. Citation Format: Jonathon Golas, Andrea T. Hooper, Justin Lucas, Heather Jones, Timothy Nichols, Kiran Khandke, Manoj Charati, Roger Conant, Michael Cinque, Judy Lucas, Marc Damelin, Ken Geles, Caiazzo Teresa, Frank Loganzo, Puja Sapra, Hans-Peter Gerber, Chad May. In situ imaging of antibody drug conjugate (ADC) binding and pharmacodynamic biomarkers of response in models of human cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2059. doi:10.1158/1538-7445.AM2014-2059
The Tripotential Glial-Restricted Precursor (GRP) Cell and Glial Development in the Spinal Cord: Generation of Bipotential Oligodendrocyte-Type-2 Astrocyte Progenitor Cells and Dorsal–Ventral Differences in GRP Cell Function

We have found that the tripotential glial-restricted precursor (GRP) cell of the embryonic rat spinal cord can give rise in vitro to bipotential cells that express defining characteristics of oligodendrocyte-type-2 astrocyte progenitor cells (O2A/OPCs). Generation of O2A/OPCs is regulated by environmental signals and is promoted by platelet-derived growth factor (PDGF), thyroid hormone (TH) and astrocyte-conditioned medium. In contrast to multiple observations indicating that oligodendrocyte precursor cells in the embryonic day 14 (E14) spinal cord are ventrally restricted, GRP cells are already present in both the dorsal and ventral spinal cord at E13.5. Ventral-derived GRP cells, however, were more likely to generate O2A/OPCs and/or oligodendrocytes than were their dorsal counterparts when exposed to TH, PDGF, or even bone morphogenetic protein-4. The simplest explanation of our results is that oligodendrocyte generation occurs as a result of generation of GRP cells from totipotent neuroepithelial stem cells, of O2A/OPCs from GRP cells and, finally, of oligodendrocytes from O2A/OPCs. In this respect, the responsiveness of GRP cells to modulators of this process may represent a central control point in the initiation of this critical developmental sequence. Our findings provide an integration between the earliest known glial precursors and the well-studied O2A/OPCs while opening up new questions concerning the intricate spatial and temporal regulation of precursor cell differentiation in the CNS.
PlayMaker: An Application of Case-Based Reasoning to Air Traffic Control Plays

When events such as severe weather or congestion interfere with the normal flow of air traffic, air traffic controllers may implement plays that reroute one or more traffic flows. Currently, plays are assessed and selected based on controllers’ experience using the National Playbook, a collection of plays that have worked in the past. This paper introduces PlayMaker, a CBR prototype that replicates the Playbook and models how controllers select plays. This paper describes the PlayMaker design, a model validation, and discusses developments necessary for a full-scale CBR tool for this application.
A correlation of the relative rates of heteroarylmethyl cation formation by SCF molecular orbital theory

Abstract Recent experimental findings have made it possible to extend molecular orbital correlations for the generation of arylmethyl systems to heteroaromatic species. In the present paper an SCF pi electron approach has been used to correlate the relative rates of pyrolysis of 1-pyridyl-, 1-quinolyl and 1-isoquinolylethyl acetates. Although far from good, it was found that calculated total energy differences yielded a correlation superior to that obtained from charge densities. The latter parameter, however, may have utility within the framework of a four parameter equation.
Quinidine-related mortality in the short-to-medium-term treatment of ventricular arrhythmias. A meta-analysis.

BACKGROUNDThe interim results of the Cardiac Arrhythmia Suppression Trial requires physicians to use a higher threshold for employing antiarrhythmic agents in the treatment of benign or potentially lethal ventricular arrhythmias. Many have managed patients by switching to the traditional class I quinidine despite its known proarrhythmic tendency.METHODS AND RESULTSTo evaluate the relation between quinidine therapy and mortality in patients with benign or potentially lethal ventricular arrhythmias, we performed a meta-analysis on four randomized double-blind active controlled parallel trials evaluating 1,009 patients in which quinidine (n = 502) was compared to flecainide (n = 141), mexiletine (n = 246), tocainide (n = 67), and propafenone (n = 53). All four trials had similar patient selection, protocols, and methodology (e.g., placebo lead-in and Holter monitoring) but varying lengths of drug exposure. A total of 12 deaths were reported on quinidine and four deaths on the other drugs: two on mexiletine, ...
Fluoro-Substituted Polysiloxanes. II. Synthesis of Poly(Pentafluorophenylmethylsiloxane)

Abstract Pentafluorophenylmethyldiethoxysilane is an interesting new monomer for preparing fluoropolysiloxanes because of its unusually high fluorine content. It was synthesized using either a bromo- or iodo-Grignard reagent, and its structure was characterized by GC-MS, IR, andlH-NMR. It was polymerized by hydrolysis and condensation reactions to yield poly(pentafluorophenylmethylsiloxane) [-Si(C6F5)(CH3)O-]X, which was characterized by FTIR and 1H-NMR. Its relatively high number-molecular weight, 6.5 × 104 g mol−1, should encourage further characterization studies with regard to unusual properties such as permeability and surface activity.
Research on Parasitic Infections in Raw Seafood Industry

Seafood products has a long history and the teachings ‘Raw crabs and shrimp live’ spread among people. This study carrys out an investigation into parasitic infections of raw seafood of Qinhuangdao through sampling, smearing, UV examination and statistical methods. The experimental datas we get tell that there is various kinds of parasite lar-vae in body of shrimp frequently and metacercariae in crabs. The seafood likeoster and clam aren't without parasites also. Experiments show that the lung fl-uke metacercaria could live about 48 hours in Salt solution with concentration-f 10%, 43 hours in 15% liquor and 28 hours in 14 degrees of yellow wine. Itis obvious that these parasites could not killed through salt leaching and temul-entia. Due to domestic waters pollution is serious, so don't eat raw food.
Viscosity and stress relaxation in commercial glasses in the glass transition region

Abstract Two concepts: a) thermorheological simplicity and b) linear viscoelastic behavior are subjected to experimental verification for a variety of commercial glasses. While homogeneous glasses are thermorheologically simple, this concept is shown to be intrinsically inapplicable to phase-separated glasses when the viscosities of phases are markedly different. Differences in the viscosities of soda-lime-silica glass measured by different methods, i.e., creep and stress relaxation, may indicate non-linear behavior.
Patch-exploitation patterns in an egg parasite of elm leaf beetle

Eggs of elm beetle,Pyrrhalta luteola (Muller), normally occur in masses which can be viewed as discrete host patches in space and time. Analysis of>800 egg masses from 3 field sites in northern California revealed that the number of eggs/mass varied from 2 to>40 and that the imported egg parasiteTetrastichus gallerucae (Fonsc.) exploited a relatively large proported of the egg masses at certain times. The spatial relationship between parasitization and number of eggs/egg mass was assessed in 2 ways-i.e., for exploited masses only and for all masses combined (exploited+nonexploited). Percent parasitization was density independent in most cases for both data sets. It is suggested that both methods of analysis can provide patterns which are relevant to biological control of insect pests.
Inverted humanitarian service and learning: The CSI haitian pilot examined in doodles and parables

While engineers are eminently qualified as logical, mathematical, and precise problem-solvers who work creatively with energy, soil, water, metallurgy, and chemical elements, they often slam into illogical walls ... diverse cultural, political, linguistic, psychological stress, and economic contexts way beyond their professional training and practice. CSI's goal of working alongside Haitian, South Sudanese, Nigerian, and Cameroonian villagers through a franchisee model of off-grid SunBlazer charging stations does its best with the logical side, and is coming to appreciate the illogical attributes of applied humanitarian service and learning. Further refinement of its design for off-grid communities and its grasp of local supply and value chain economics is a basis for further incubation/design, scientific demonstration of engineering and economic models, and education that connects the weak ties - that is communities of learning to other communities of learning.
Healthcare utilization following mild traumatic brain injury in female veterans.

AbstractBackground: Mild traumatic brain injury (TBI) is a significant problem for Veterans. Gender differences in mild TBI outcomes such as return-to-work, resolution of symptoms and mental health diagnoses have been reported. The purpose of the study is to characterize gender differences in VA healthcare utilization in the year following mild TBI diagnosis.Methods: This was a retrospective database study of 12 144 Veterans diagnosed with mild TBI in fiscal year 2008 and their healthcare utilization in the following year.Results: The mean age was 43.6 ± 17 and the majority were men (94.1%). Overall, women had more outpatient utilization than men with mild TBI (mean: 48 vs. 37 visits; p ≤ 0.001). Adjusted analyses indicated that women had a rate of outpatient utilization 25% higher than men (IRR = 1.25, 95% CI = 1.17–1.33). It was found that 13.6% of the difference in outpatient utilization by gender could be explained by other factors such as race, age, marital status, geographic location and illness bur...
A Rational Reconstruction of the Domain of Feature Structures

Feature structures are employed in various forms in many areas of linguistics. Informally, one can picture a feature structure as a sort of tree decorated with information about constraints requiring that specific subtrees be identical (isomorphic). Here I show that this informal picture of feature structures can be used to characterize exactly the class of feature structures under their usual subsumption ordering. Furthermore, once a precise definition of tree is fixed, this characterization makes use only of standard domain-theoretic notions regarding the information borne by elements in a domain, thus removing (or better, explaining) all apparentlyad hoc choices in the original definition of feature structures. In addition, I show how this characterization can be parameterized in order to yield similar characterizations of various different notions of feature structure, including acyclic structures, structures with appropriateness conditions and structures with apartness conditions (used to model path inequations). The generalizations to other notions of feature structure also emphasize that the construction given here is in fact independent of the application to feature structures.
Kinetic mechanisms of human placental choline acetyltransferase.

Abstract Choline acetyltransferase (ChA) from human placenta was assayed by the formation of [acetyl- 14 C]choline (ACh) from choline (Ch) and [acetyl- 14 C]CoA (ACoA). The bisubstrate kinetics of this enzyme (0.15 nmoles ACh min mg protein; ACoA, 10 −5 M; Ch, 5 × 10 −4 ; pH 7.4, 37°) were studied by the following experiments: (1) variation of the initial velocity as a function of Ch concentration (6 × 10 −5 to 2.5 × 10 −4 M) at fixed ACoA concentrations (6 × 10 −6 to 2.5 × 10 −5 M); (2) variation of the initial velocity as a function of ACoA concentration (6 × 10 −6 to 2.5 × 10 −5 M) at fixed Ch concentrations (6 × 10 −5 to 2.5 × 10 −4 M); (3) enzyme inhibition by ACh (10 −2 M) and CoA (2.5 × 10 −5 , 10 −4 M) with Ch as the variable substrate and ACoA as the fixed substrate; and (4) enzyme inhibition by ACh and CoA with ACoA as the variable substrate and Ch as the fixed substrate. In experiments (1) and (2), double reciprocal plots intersecting in the third quadrant were obtained. In experiment (3), ACh is a competitive inhibitor and CoA is a noncompetitive inhibitor. In experiment (4), CoA is a competitive inhibitor and ACh a noncompetitive inhibitor. These results suggest that the steady state concentrations of ternary complexes (ACoA. ChA. Ch, CoA. ChA. ACh) are very low. CoA was about 100 times stronger as a product inhibitor than ACh. Therefore, an ordered Theorell-Chance mechanism was tentatively postulated with ACoA as the leading substrate and CoA as the obligatory product. A ping-pong mechanism has been proposed for the human placental ChA in the published literature which was based upon the parallel double reciprocal plots in experiments (1) and (2) at higher substrate concentrations for ACoA and choline than those used by us. At these high substrate concentrations, the experimental points fall within the region of mixed first-order and zero-order kinetics instead of first-order kinetics on the initial velocity-substrate concentration curves. Therefore, the intersecting double reciprocal plots in experiments (1) and (2) were altered into plots which appeared approximately parallel. At high substrate concentrations of ACoA, a significant degree of substrate inhibition and product inhibition due to CoA was observed.
Late Treatment With Ramipril Increases Survival in Old Spontaneously Hypertensive Rats

Abstract —Spontaneously hypertensive rats (SHR) begin to die from cardiovascular complications at ≈15 months of age. We tested whether chronic ACE-inhibitor treatment would extend the lifespan of such old animals. We also studied cardiac hypertrophy and function, endothelial function and expression, and activity of NO synthase (eNOS). One hundred 15-month-old SHR were randomized into 3 groups, control (n=10), placebo-treated (n=45), and ramipril-treated with an antihypertensive dose of 1 mg · kg −1 · d −1 in drinking water (n=45). Ex vivo experiments were performed after 15 months (control) and 21 months, when ≈80% of the placebo group had died. Late treatment with ramipril significantly extended lifespan of the animals from 21 to 30 months. Fully established cardiac hypertrophy, observed in placebo-treated animals and in controls, was significantly reversed by ramipril treatment. In isolated working hearts, a significantly improved function associated with increased cardiac eNOS expression was seen versus placebo and control hearts. Endothelial dysfunction in isolated aortic rings from control and placebo-treated SHR was significantly improved by ACE inhibition and associated with enhanced NO release. Late treatment of SHR with the ACE inhibitor ramipril extended lifespan from 21 to 30 months, which is comparable to the lifespan of untreated normotensive Wistar-Kyoto rats. This lifespan extension, probably due to blood pressure reduction, correlated with increased eNOS expression and activity followed by a regression of left ventricular hypertrophy and cardiac and vascular dysfunction.
Physical modulation based cell manipulation in microfluidic devices

Cell manipulation has important applications in biological research and clinical diagnostics. We integrate microfabrication with physical modulation to enable selective and flexible cell manipulation, such as isolation, trapping and recovery of cells. We use the strong temperature dependence of affinity binding between aptamers and cells to enable specific cell capture and temperature-mediated release of selected cells. We also exploit the large compliance of elastomers to create an array of cell-trapping microstructures, whose dimensions can be mechanically modulated to capture a predetermined number of cells. Thus, enhanced utility and flexibility for practical applications can be attained, as demonstrated by specific capture and temperature-mediated release of CCRF-CEM cells, as well as tunable trapping of MCF-7 cells.
Finite element displacement method for large amplitude free flexural vibrations of beams and plates

Abstract A finite element method to determine the nonlinear frequency of beams and plates for large amplitude free vibrations is presented. The equation of motion is characterized by the basic stiffness, mass, geometrical stiffness and the associated inplane force matrices. The procedures for solving the system equations of motion are discussed, and the explicit formulations of the geometrical stiffness and inplane force matrices of a rectangular plate element are given. Examples of large amplitude free oscillations for rectangular plates and beams with various boundary conditions are given. Characteristics of convergence are investigated. In all the cases where comparisons with previous investigations are made, good agreement has been obtained. It indicates that the present method will give results entirely adequate for engineering purposes.
Forever young: START and aftermath

Abstract The New Strategic arms reduction treaty nuclear arms control agreement signed by US President, Barack Obama, and Russian President, Dmitry Medvedev, in 2010 is likely to achieve ratification in both Washington and Moscow, but it is too early to break out the champagne or vodka. Even successful ratification of this agreement is, at best, an important but incremental part of the US–Russian policy ‘reset’ and the larger agenda for both states with respect to arms reduction and nonproliferation. Further reductions in both states’ inventories of strategic nuclear weapons are a necessary preface toward credible leadership in stopping the spread of nuclear arms – especially in the looming test cases of Iran and North Korea. In addition, both states have to decipher a policy-strategy nexus for emerging missile defense technologies: in particular, whether missile defenses should be seen as possible means of cooperative security, as between NATO and Russia, or whether they are firewalls in the way of furth...
Localization of a Gene Responsible for Familial Dilated Cardiomyopathy to Chromosome 1q32

Background Dilated cardiomyopathy, characterized by ventricular dilatation and decreased systolic contraction, is twofold to threefold more common as a cause of heart failure than hypertrophic cardiomyopathy and costs several billion dollars annually. The idiopathic form occurring early in life, with a 75% mortality in 5 years, is a common reason for transplantation. It is estimated that at least 20% of cases are familial. Methods and Results A family of 46 members spanning four generations underwent history and physical examinations, echocardiographic analysis, and blood sampling for genotyping. Diagnostic criteria, detected by echocardiography, consisted of ventricular dimension of ≥2.7 cm/m2 with an ejection fraction ≤50% in the absence of other potential causes. DNA from all members was analyzed by polymerase chain reaction for amplification of short tandem-repeat polymorphic markers located every 10 cM throughout the human genome. Assuming a penetrance of 90%, linkage analysis was performed to map th...