cssi/SciSciGPT-SciSciNet huggingface dataset:
Next Wave of Technology

AbstractA balanced electro-mechanical system must have the openness now represented by the electricals (computer chips, power boards, standardized interfaces, domain-relevant operational software) and the reconfigurability to not only meet the needs of ever-changing tasks, but also enable rapid assembly, repair, and refreshment on demand by means of highly-certified components made available by means of a competitive supply chain. This, then, requires a command/response in milli-sec for multi-input/multi-output (MIMO) systems that are normally perceived as highly non-linear and highly coupled (i.e., unsolvable by standard analytic tools).Criteria-based decisions in milli-sec essentially linearize these systems to make strictly algebraic processes viable with little or no uncertainty so long as the operational criteria have clear physical meanings. The human command (trains, surgery, aircraft, automobiles, etc.) in concert with semi-autonomous processes can be put into balance where each plays its relevant...
Neuronal networks in mental diseases and neuropathic pain: Beyond brain derived neurotrophic factor and collapsin response mediator proteins

The brain is a complex network system that has the capacity to support emotion, thought, action, learning and memory, and is characterized by constant activity, constant structural remodeling, and constant attempt to compensate for this remodeling. The basic insight that emerges from complex network organization is that substantively different networks can share common key organizational principles. Moreover, the interdependence of network organization and behavior has been successfully demonstrated for several specific tasks. From this viewpoint, increasing experimental/clinical observations suggest that mental disorders are neural network disorders. On one hand, single psychiatric disorders arise from multiple, multifactorial molecular and cellular structural/functional alterations spreading throughout local/global circuits leading to multifaceted and heterogeneous clinical symptoms. On the other hand, various mental diseases may share functional deficits across the same neural circuit as reflected in the overlap of symptoms throughout clinical diagnoses. An integrated framework including experimental measures and clinical observations will be necessary to formulate a coherent and comprehensive understanding of how neural connectivity mediates and constraints the phenotypic expression of psychiatric disorders.
Glucocorticoid Regulation of Vasopressin Messenger RNA

The vertebrate central nervous system responds to alterations in its humoral milieu. This is not surprising considering its constant exposure to changing hormonal states which are continually generated by a complex endocrine system. One aspect of this responsiveness is the homeostatic control of hormone synthesis and release. Many hormones released into the circulation by the pituitary, and other endocrine tissues, enter the CNS and exert feedback control on hypothalamic neurons that project to the median eminence. However, the roles of hormones may be quite complex, and are not restricted to the regulation of their own release. Certain hormones, in particular steroids, participate in the development of many complex behaviors that require coordinated actions at many levels in the CNS (1). Moreover, the ability of many classes of steroids to alter gene expression, even in a mature differentiated nervous system, suggests that neuronal phenotypes are continually influenced by the humoral environment.
The diagnostic challenge of salivary gland malignancies

The attainment of a precise preoperative diagnosis to guide patient discussion and development of a treatment plan, when evaluating a major salivary gland tumor suspicious for malignancy, remains a...
Extramedullary Relapse of Acute Myelogenous Leukemia Presenting as a Large Serous Retinal Detachment.

Background/Aims: To describe the rare presentation of a large, unilateral, serous retinal detachment as an extramedullary manifestation of acute myelogenous leukemia (AML) recurrence without bone marrow or central nervous system involvement after more than 1 year of follow-up. Methods: Case report. Results: A teenage patient with AML, previously treated with multiple courses of systemic chemotherapy, radiation, and bone marrow transplant, presented with acute vision loss. Ophthalmic workup revealed a large, unilateral, bullous, serous retinal detachment. Ultimately, he underwent subretinal fluid biopsy, which was found to be positive for leukemic blast cells. Cytologic markers matched his initial bone marrow biopsy, and therefore were diagnostic of extramedullary AML relapse. Conclusions: Leukemia can cause various ophthalmic manifestations. Autopsy studies suggest that choroidal infiltration is relatively common, but clinical progression to serous retinal detachment is quite uncommon. Furthermore, serous retinal detachment is generally shallow, posterior, and much more often reported in acute lymphocytic leukemia. The ophthalmologist plays a critical role in identifying leukemic ocular involvement. This case demonstrates the potential for ocular biopsy to secure the diagnosis of extramedullary relapse in order to initiate prompt treatment and systemic workup.
Mechanisms of Purine Overproduction in Man

Several elegant studies conducted first during the 1950s showed that a segment of the gouty population exhibited hyperuricemia as a result of an increased production of uric acid (1,2). Further investigation of this subgroup revealed that these patients also exhibited an accelerated rate of purine biosynthesis de novo. In other clinical situation, an increased production of uric acid was noted to result from an accelerated catabolism of purine nucleotides; examples of the latter included the acute leukemias and hemolytic anemias (3–5) where an accelerated turnover of cells leads to an increased degradation of purine nucleotides, thus enhancing uric acid formation. The recognition that the overproduction of uric acid was an important element in the pathophysiology of several clinical conditions provided an incentive to better define mechanisms by which purine biosynthesis was regulated in man. Indeed, the nature of this regulation is now well established and has been reviewed in an earlier paper in this volume (6). In effect, the rate of purine biosynthesis de novo (i.e., the pathway leading to the synthesis of inosinic acid from PRPP, glutamine, and other precursors) is tightly controlled by the intracellular concentration of 5-phosphoribosyl-l-pyrophosphate (PRPP) and purine nucleotides (Figure 1). For example, an elevation of the intracellular concentration of PRPP will increase the rate of purine biosynthesis de novo while a decrease of the intracellular level of PRPP will decrease the rate of purine biosynthesis de novo (7). An increase in the level of the purine nucleoside monophosphates, AMP or GMP, will decrease the rate of purine biosynthesis de novo while a decrease in the concentration of these compounds will result in a compensatory increase in purine biosynthesis de novo (2). In addition, the level of the purine nucleoside diphosphate, ADP, also appears to play an important role in that increased levels of ADP inhibit PRPP synthetase (8) (Figure 1, reaction 3) and thus reduce levels of PRPP in the cell, hence, reducing the rate of purine biosynthesis de novo. On the other hand, decreased levels of ADP in the cell lead to activation of PRPP synthetase and, thus, increased levels of PRPP in the cell and an accelerated rate of purine synthesis de novo. The molecular alterations of the enzyme PRPP amidotransferase (Figure 1, reaction 1), which nicely account for these observed changes induced by PRPP and purine nucleotides, have been published previously (9) and have been summarized in the paper by Dr. Wyngaarden in this volume (6).
Correlation Between Chiral Modifier Adsorption and Enantioselectivity in Hydrogenation Catalysis

Infrared absorption spectroscopy performed in situ at the solid–liquid interface revealed that the adsorption on platinum supported catalysts of 1-(1-naphthyl)-ethylamine, which is used as a chiral modifier in hydrogenation catalysis, occurs through the amine group, not the aromatic ring as is widely believed. Comparisons were performed against a set of related modifier compounds with targeted substitutions to help identify the key moiety involved in the adsorption. It was determined that neither naphthalene-based modifiers without amine groups nor those with tertiary amine moieties are capable of adsorbing on the metal surface to any significant extent. A direct correlation was also found between the ability of the amines to adsorb on the platinum surface and their performance as chiral modifiers that impart enantioselectivity to the hydrogenation of α-keto esters such as ethyl pyruvate.
Plasmonic Interference in Superstructured Metal Photonic Crystals

Surface plasma waves (SPWs) excited by illumination of 2-dimensional superstructured metal photonic crystals (SMPCs) are investigated with extraordinary optical transmission (EOT). An m × m lattice of holes (m = 3 with the period p of 3 μm) fabricated in an Au film atop a GaAs substrate (refractive index nd), referred to as a basis plasmonic antenna (BPA), forms an SMPC that consists of 24 × 24 BPAs with varying spacing between BPAs, d. Two categories of d are examined: κ = d/p = i (i an integer), where SPWs generated at each BPA interfere constructively and κ ≠ i (<1), where the interference leads to drastic changes in the EOT. In the first category, the EOT associated with the fundamental SPW wavelength, T1, decreases with increasing κ, but has an almost invariant peak wavelength, λ1, at ∼10.1 μm (≅ndp), as expected. In the second category, however, the λ1 for the dominant EOT peak clearly shows a red-shift to ∼12 μm with T1 reduced to ∼0 at κ = 0.5, and T1 has a damped oscillatory dependence on κ. The ...
Distributed state estimation for a stochastic linear hybrid system over a sensor network

In this study, the authors consider the distributed state estimation problem of a stochastic linear hybrid system (SLHS) observed over a sensor network. The SLHS is a dynamical system with interacting continuous state dynamics described by stochastic linear difference equations and discrete state (or mode) transitions governed by a Markovian process with a constant transition matrix. Most existing hybrid estimation algorithms are based on a centralised architecture which is not suitable for distributed sensor network applications. Further, the existing distributed hybrid estimation algorithms are restrictive in sensor network topology, or approximate the consensus process among connected sensor agents. This study proposes a distributed hybrid state estimation algorithm based on the multiple model based approach augmented with the optimal consensus estimation algorithm which can locally process the state estimation and share the estimation information with the neighbourhood of each sensor agent. This shared information comprises local mode-conditioned state estimates and edge-error covariances, and is used to bring about an agreement or a consensus across the network. The proposed distributed hybrid state estimation algorithm is demonstrated with an illustrative aircraft tracking example.
Efficient Shared Memory Orchestration towards Demand Driven Memory Slicing

Memory is increasingly becoming a bottleneck for big data and latency-sensitive applications in virtualized systems. Memory efficiency is critical for high-performance execution of virtual machines (VMs). Mechanisms proposed for improving memory utilization often rely on an accurate estimation of VM working set size at runtime, which is difficult under changing workloads. This paper explores opportunities for improving memory efficiency and their impacts on the performance of VM executions. First, we show that if each VM is initialized with an application-specified lower bound memory, then by maintaining a shared memory region across VMs in the presence of temporal memory usage variations on the host, those VMs under high memory pressure can minimize their performance loss by opportunistically and transparently harvesting idle memory on other VMs. Second, we show that by enabling on-demand VM memory allocation and deallocation in the presence of changing workloads, VM performance degradation due to memory swapping can be reduced effectively, compared to the conventional VM configuration scenario, in which all VMs are allocated with the upper-bound of memory requested by their applications. Third, we show that by providing shared memory pipes between co-located VMs, the inter-VM communication can speed up by avoiding unnecessary overhead of communication via the network. We develop MemLego, a lightweight shared memory based system, to achieve all these benefits without requiring any modification to user applications and the OSes. We demonstrate the effectiveness of these opportunities through extensive experiments on unmodified Redis and MemCached. Using MemLego, the throughput of Redis and Memcached improves by up to 4x over the native system without MemLego, up to 2 orders of magnitude when the applications working set size does not fit in memory.
Linear extrapolation distances for centrally and eccentrically located control rods

Using one-group diffusion theory, linear extrapolation distances for centrally and eccentrically located black control rods in cylindrical geometries have been determined by the pulsed neutron meth...
Family Environment and Psychological Distress in Persons Who Are Visually Impaired.

This study investigated the relationship between perceived family environment and psychological distress in 76 persons who are visually impaired, aged 18 to 94, who had undergone at least four mont...
Abstract 2343: Comprehensive evaluation of antibody-drug conjugate targets for drug development across tumor types: Analysis from TCGA

Introduction: Cancer cells over-express proteins on their cell surface that can be exploited as drug targets and has led to development of two successful Anti-body Drug Conjugates (ADCs), Brentuximab and Trastuzumab Emtansine. Because a strong correlation exists between mRNA levels and protein expression we analyzed RNAseq data from TCGA to look at known ADC targets as a proof-of-concept to discovering new therapeutic targets. Methods: We used mRNA expressions (transcripts per million, TPM) from publicly available RNA sequencing data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project to analyze the expression of ADC targets in tumor and normal tissues. We chose thirty-seven targets with known ADCs in clinical development. Graphs were generated to show distribution of each gene9s expression across all tumor and normal tissue types in TCGA and GTEx. Potential targets were determined based on tumor expression of at least two times the highest expression in any normal tissue. Proteins known to be secreted in the blood stream at high levels were excluded as they are unlikely to make a good ADC target (eg. AFP, FOLH1). Results: Using ERBB2 as the prototype gene, we were able to detect over-expression in all tumors that have HER-2 ove-rexpression in the literature including breast, bladder, NSCLC, Gastroesophageal, endometrial, HNSCC, ovarian, and colon cancer. Other genes with overexpression in select tumors including BSG (RCC, Melanoma, ACC), CD70 (RCC, DLBCL, mesothelioma, cervical), ENPP3 (RCC, endometrial, breast, lung adeno), FGFR2 (breast, gastric), FOLR1 (ovarian, lung adeno), GPNMB (lung, melanoma, HNSCC, renal), MSLN (lung adeno, mesothelioma, ovarian), SLC39A6 (breast), TDGF1 (thymoma, testicular, adrenocortical) were discovered as well. Tumors exhibited a significantly higher expression compared to normal tissue for ERBB2: breast cancer vs normal breast: p Conclusion: Overall, this large-scale analysis from TCGA reveals that RNA-seq can be used as an initial screen to identify novel targets for ADCs. Further analysis will identify previously unappreciated targets that can be exploited for drug development across diverse cancers. Further confirmation with protein expression is warranted. Citation Format: Roman Groisberg, Jason Rosznik, Funda Meric-Bernstam, Vivek Subbiah. Comprehensive evaluation of antibody-drug conjugate targets for drug development across tumor types: Analysis from TCGA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2343.
Step away from stepwise

Stepwise regression is a popular data-mining tool that uses statistical significance to select the explanatory variables to be used in a multiple-regression model. A fundamental problem with stepwise regression is that some real explanatory variables that have causal effects on the dependent variable may happen to not be statistically significant, while nuisance variables may be coincidentally significant. As a result, the model may fit the data well in-sample, but do poorly out-of-sample. Many Big-Data researchers believe that, the larger the number of possible explanatory variables, the more useful is stepwise regression for selecting explanatory variables. The reality is that stepwise regression is less effective the larger the number of potential explanatory variables. Stepwise regression does not solve the Big-Data problem of too many explanatory variables. Big Data exacerbates the failings of stepwise regression.
Understanding impulsivity scientifically: Some of the variables that affect the steepness of delay discounting and may affect suicide

Summary An important aspect of what is called impulsivity is making choices quickly. Often, when individuals choose an outcome that occurs earlier in time, they may at the same time be excluding a more valuable outcome that occurs somewhat later. Individuals who are overly impulsive often end up making choices that harm them in a variety of ways. This paper will first contrast two different ways of measuring impulsivity, one based on a model of impulsivity as a trait and the second based on a set of measures used in studies of what is called delay discounting. The study reviews research on delay discounting, summarizing evidence on how outcomes such as problematic substance use, gambling, and others are significantly related the tendency of individuals to choose an earlier but less valuable outcome. Because delay-discounting measures are more directly related to current behaviors, they may be better predictors than trait-based models. Implications of including such models in predictions of suicidal thoughts and behavior, and a few examples of research on that are discussed. While such research is still in its infancy, the few studies that exist suggest that this may be a productive addition to this area of research.
Understanding CancelRx: Results of End-to-End Functional Testing, Proactive Risk Assessment, and Pilot Implementation.

Background CancelRx allows prescribers to send electronic cancellation messages to pharmacies when medications are discontinued. Little is known about its functionality and impact on clinical workflows. Objectives To understand CancelRx functionality, its potential impact on workflows and medication safety risks, and to develop mitigating strategies for risks introduced by implementation. Methods We conducted direct observations and semi-structured interviews to develop CancelRx use cases and assessed CancelRx in an end-to-end test environment, proactive risk assessment, and pilot implementation from April 16 to July 15, 2018. Results E-cancellations were sent upon discontinuation of e-prescriptions written within the electronic health record (EHR), but not other medications (e.g., printed prescriptions) and could be initiated by nonprescribers. In our proactive risk assessment, CancelRx implementation eliminated five of seven failure modes in outpatient prescribing to Johns Hopkins pharmacies, but introduced new risks, including (1) failure to act if an e-cancellation was not sent or was unsuccessful; (2) failure to cancel all prescriptions for a medication; (3) errors in manual matching; and (4) erroneous medication cancellations. We identified potential mitigation strategies for these risks. During pilot implementation, 92.4% (428/463) of e-cancellations had confirmed approval by the receiving pharmacy, while 4.5% (21/463) were denied, and 3.0% (14/463) had no e-cancellation response. Among e-cancellations received by the pilot pharmacy, 1.7% (7/408) required manual matching by pharmacy staff. Based on performance in testing, 73.4% (340/463) of completed e-cancellations would be expected to generate an in-basket message, including 21 (6.2%) denials and 319/340 (93.8%) approvals with a note from the pharmacy. Conclusion CancelRx is an important functionality with the potential to decrease adverse events due to medication errors. However, changes in implementation in our EHR and pharmacy software and enhancements in the CancelRx standard are needed to maximize safety and usability. Further studies are needed to evaluate the impact of e-cancellation on medication safety.
Management of Pneumoperitoneum: Role and Limits of Nonoperative Treatment.

Objectives The aim of this study was to compare morbidity and mortality between nonoperative and operative treatment of pneumoperitoneum. Background Pneumoperitoneum is a potentially life-threatening condition that has been traditionally treated with surgical intervention. Adequately powered studies comparing treatment outcomes are lacking. Methods Chart review and computer-assisted abstraction were used to identify patients with pneumoperitoneum at 5 hospitals from 2010 to 2015. Patients with recent abdominal procedures or contained perforation were excluded. Patients were grouped by treatment modality: comfort measures only (CMO), nonoperative treatment, or operative intervention. CMO included only symptom-palliation, whereas nonoperative therapy included all interventions (antibiotics, peritoneal drains, resuscitation) excluding surgery. Outcomes were mortality, discharge disposition, and 30-day complications. Covariates included demographics, comorbidities, and acuity at presentation. Results Forty patients received CMO, 202 underwent nonoperative treatment, and 199 underwent operative intervention. CMO patients had 98% 30-day mortality. There was no difference in 30-day (P = 0.64) or 2-year mortality (P = 0.53) between patients treated nonoperatively and operatively. Compared with patients treated operatively, patients treated nonoperatively were more likely to have a colorectal source of pneumoperitoneum (37% vs 31%; P = 0.03). Using logistic regression, operative treatment was associated with increased dependence on enteral tube feeding or total parenteral nutrition [odds ratio (OR) 4.30, 95% confidence interval (CI), 1.99-9.29] and nonhome discharge (OR 3.61, 95% CI, 1.81-7.17). Among patients with clinical peritonitis, operative treatment was associated with reduced mortality (OR 0.17, 95% CI, 0.04-0.80). Conclusions Operative intervention is associated with reduced mortality in patients with pneumoperitoneum and peritonitis. In the absence of peritonitis, operative treatment is associated with increased morbidity and nonhome discharge.
Live-feed use in the classroom as an engagement tool

Abstract Background and purpose Recent studies suggest that social media use in the classroom leads to improved engagement and participation. However, student attitudes regarding classroom engagement, academic performance, and overall teaching effectiveness toward this tool have been mixed. The aim of this study was to determine the effectiveness of live-feed on students' classroom engagement. Educational activity and setting This study included the use of live-feed in a research and statistics course for first-year pharmacy students. At the end of the course, students were invited to participate in a post-survey to assess impressions on classroom engagement after the usage of live-feed in the classroom. Findings Fifty out of 62 students (81%) responded to the survey. Seventy percent reported that live-feed application promoted collaborative learning and discussion, and 68% stated that it increased their understanding of the topic. Sixty-six percent reported that live-feed application created a supportive anonymous environment, and 64% felt it encouraged them to ask questions. Sixty percent of the students reported that live-feed did not increase their engagement in the classroom but agreed that it lowered their anxiety toward class participation. Sixty-four percent of the students were positive about live-feed boosting their willingness to participate in topic discussions and 72% believed that live-feed made learning a fun activity. Summary Live-feed can be a useful tool in academic settings to provide a supportive environment and promote students' willingness to participate in classroom discussions.
Genome-scale CRISPR activation screen uncovers tumor-intrinsic modulators of CD3 bispecific antibody efficacy

Bispecific antibodies (bsAb) that bridge tumor cells and CD3-positive effector T cells are being developed against many tumor cell targets. While tumor cell factors other than target expression level appear to play a role in determining the efficacy of CD3 bsAb, the identity of such factors remains largely unknown. Using a co-culture system of primary human T cells and B lymphoma cell lines, we demonstrate a range of sensitivities to CD20xCD3 bsAb that is independent of CD20 surface expression. To identify genes that modulate tumor cell sensitivity to CD3 bsAb, we employed a genome-scale CRISPR activation screen in a CD20xCD3-sensitive human B lymphoma cell line. Among the most highly enriched sgRNAs were those targeting genes with predicted effects on cell-cell adhesion, including sialophorin (SPN). Increased expression of SPN impeded tumor cell clustering with T cells, thereby limiting CD3 bsAb-mediated tumor cell lysis. This inhibitory effect of SPN appeared to be dependent on sialylated core 2 O-glycosylation of the protein. While SPN is not endogenously expressed in the majority of B cell lymphomas, it is highly expressed in acute myeloid leukemia. CRISPR-mediated SPN knockout in AML cell lines facilitated T cell-tumor cell clustering and enhanced CD3 bsAb-mediated AML cell lysis. In sum, our data establish that the cell cross-linking mechanism of CD3 bsAb is susceptible to subversion by anti-adhesive molecules expressed on the tumor cell surface. Further evaluation of anti-adhesive pathways may provide novel biomarkers of clinical response and enable the development of effective combination regimens for this promising therapeutic class.
Relationships between reading profiles and narrative writing abilities in school-age children with autism spectrum disorder

Reading and writing are distinct skill areas that influence each other across development. Children with autism spectrum disorder (ASD) are noted to exhibit challenges in both skill areas, though relatively few studies have examined relationships between reading and writing skills. This study adopted a reading-to-writing framework to examine if school-age children differ in their narrative writing performance based on their categorically heterogeneous, empirically derived latent reading profiles. Sixty-four school-age (10–18 years old) children with ASD without co-occurring intellectual or severe communication difficulties completed a battery of reading and writing assessments, and reading profiles were examined using latent profile analysis with narrative writing skills, ASD symptom severity, and age included as auxiliary outcome variables. Average readers demonstrated significantly higher narrative writing performance compared to Below Average/Intact Receptive Vocabulary, Comprehension Disturbance, and Global Disturbance readers. Subgroups of readers with reading difficulties did not significantly differ on writing outcomes. While findings support that stronger readers appeared to be also stronger writers, questions remain about differences in the writing skills of individuals with ASD with specific or broad reading difficulties. Implications for researchers and practitioners are discussed regarding the need for continued examination into the reading and writing abilities of children with ASD.
Standard-setting in auditing: Insights from PCAOB inspections

Abstract We explore whether the Public Company Accounting Oversight Board (PCAOB) consistently follows its own standard-setting policies. We do this using a methodology that combines the reports of audit partners, the timing of enacted auditing standards, and the issuance of PCAOB inspection findings. Rules governing standard-setting are critical to ensure that auditing standards are appropriate, efficient, and are therefore likely to be generally accepted. Our results suggest that in some instances auditors were penalized for omitting evidence from their working papers which is not specified in the standards, in effect, changing or removing auditor judgment in the amount and nature of audit evidence to be gathered in corroboration of management’s assertions and creating new auditing standards outside of the formal standard-setting process. Beyond the societal benefits of standard-setters adhering to their own policy-making rules, changes in auditing procedures impact the behavior of both auditors’ and managers and is costly. Although subject to limitations, we believe our results are informative to policy makers and other participants in PCAOB standard-setting.
A Bayesian robust chi-squared test for testing simple hypotheses

Abstract In this paper, we introduce a new Bayesian chi-squared test based on an adjusted quadratic loss function for testing a simple null hypothesis. We show that the asymptotic null distribution of our suggested test is a central chi-squared distribution under some assumptions required for the Bayesian large sample theory. We refer to our test as the Bayesian robust chi-squared test, since it is robust to parametric misspecification in the alternative model. That is, the limiting null distribution of our test is a central chi-squared distribution irrespective of parametric misspecification in the alternative model. In addition to being robust to parametric misspecification, our test also shares properties of the test suggested by Li et al. (2015) based on a quadratic loss function. We provide four examples to illustrate the implementation of our suggested Bayesian test statistic.
Activation of Oxytocin Receptors Excites Subicular Neurons by Multiple Signaling and Ionic Mechanisms.

Oxytocin (OXT) is a nonapeptide that serves as a neuromodulator in the brain and a hormone participating in parturition and lactation in the periphery. The subiculum is the major output region of the hippocampus and an integral component in the networks that process sensory and motor cues to form a cognitive map encoding spatial, contextual, and emotional information. Whilst the subiculum expresses the highest OXT-binding sites and is the first brain region to be activated by peripheral application of OXT, the precise actions of OXT in the subiculum have not been determined. Our results demonstrate that application of the selective OXT receptor (OXTR) agonist, [Thr4,Gly7]-oxytocin (TGOT), excited subicular neurons via activation of TRPV1 channels, and depression of K+ channels. The OXTR-mediated excitation of subicular neurons required the functions of phospholipase Cβ, protein kinase C, and degradation of phosphatidylinositol 4,5-bisphosphate (PIP2). OXTR-elicited excitation of subicular neurons enhanced long-term potentiation via activation of TRPV1 channels. Our results provide a cellular and molecular mechanism to explain the physiological functions of OXT in the brain.
Efferent unmasking of speech-in-noise encoding?

The medial olivocochlear (MOC) reflex provides efferent feedback from the brainstem to cochlear outer hair cells. Physiologic studies have demonstrated that the MOC reflex is involved in “unmasking...
Centrality dependence of electroweak boson production in PbPb collisions at the LHC

Recent data on the nuclear modification of W and Z boson production measured by the ATLAS collaboration in PbPb collisions at $\sqrt{s_{\rm nn}}=5.02$ TeV show an enhancement in peripheral collisions, seemingly contradicting predictions of the Glauber model. The data were previously explained by arguing that the nucleon-nucleon cross section may be shadowed in nucleus-nucleus collisions, and hence suppressed compared to the proton-proton cross section at the same collision energy. This interpretation has quite significant consequences for the understanding of heavy-ion data, in particular in the context of the Glauber model. Instead, we provide an alternative explanation of the data by assuming that there is a mild bias present in the centrality determination of the measurement; on the size of the related systematic uncertainty. Using this assumption, we show that the data is in agreement with theoretical calculations using nuclear parton distribution functions. Finally, we speculate that the centrality dependence of the W$^-$/W$^{+}$ ratio may point to the relevance of a larger skin thickness of the Pb nucleus, which, if present, would result in a few percent larger PbPb cross section than currently accounted for in the Glauber model and may hence be the root of the centrality bias.
Factors Affecting Outcomes in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization: A Retrospective Analysis

Background: Hepatocellular carcinoma (HCC) patient’s outcomes after transarterial chemoembolization (TACE) are highly variable. Aims: The goal of this study is to find out what factors influence the outcome of TACE for HCC. Methods: We performed a retrospective analysis of HCC patients treated with TACE at the VA Medical Center in Gainesville, Florida, from January 2001 to December 2010, using Fisher's exact test and Mann Whitney U test for univariate analysis and the Kaplan-Meier method and Cox proportional hazard models to compare survival. Results: The study included 82 patients, 45 of whom received doxorubicin drug eluting beads (DEB TACE) and 37 of whom received conventional (CON) TACE. The two TACE groups had similar characteristics, with the exception of the CON TACE having a higher MELD score. Univariate analysis showed survival to be associated with type of TACE (p= 0.022), Child-Pugh (CP) class (p= 0.038), MELD score (p= 0.028), AFPmax (p=0.0002) and response after first TACE (p= 0.006). Kaplan Meier analysis showed significant survival benefit (p=0.014) in the DEB TACE group over the CON TACE group -26.4 months VS 15.8 months respectively and in patients with lower MELD scores (p=0.005). A multivariable analysis revealed a statistically significant interaction between TACE type and MELD score( p=0.395), with DEB TACE patients experiencing a better survival than CON TACE patients but the effect diminishing as MELD scores increased. Furthermore, the risk of death increased significantly with AFPmax (Hazard ratio 1.15, 95%CI= [1.06, 1.26], p=0.0001). Conclusions: Survival after TACE for HCC is better after DEB TACE, in CP class A, with lower MELD score and lower AFPmax.
THE ECONOMICS OF POSTED PRICES IN A CONCENTRATED MARKET WHERE DEMAND IS UNCERTAIN

Abstract This paper analyses the theory of the optimal output decision for a firm whose policy is to post a non-negotiable price for a good or service in a concentrated market where the demand facing the firm is determined, in part, by a random variable. The theoretical findings are the opposite of those in competitive markets; Proposition 1 states that the optimal output of a risk-averse firm is expected to be larger than that of a risk-neutral firm if the expected payoff of its marginal profit is less than or equal to 1. Proposition 2 states that the optimal output of a risk-seeking firm is expected to be smaller than that of a risk-neutral firm if the expected payoff of its marginal profit is greater than 1.
EFFECTS OF CERIUM OXIDE NANOPARTICLES ON GLUTAMATE-INDUCED OXIDATIVE STRESS IN AN IMMORTALIZED MOUSE HIPPOCAMPAL CELL LINE

Cerium oxide (CeO2) nanoparticles (nanoceria or CeNPs) are potent antioxidants that are being explored as a potential therapeutic for oxidative stress diseases. Nanoceria are small, they catalytically neutralize multiple types of reactive oxygen species and, due to cycling between the Ce3+ and Ce4+ oxidation states, they can regenerate depending on the redox conditions. However, both therapeutic and toxic effects of CeNPs have been reported1-3. We hypothesize that these disparate reports are due to small chemical differences in each type of particle arising from the synthetic process4. HT22 is an immortalized mouse hippocampal neuronal cell line that has been selected for its susceptibility to glutamate-induced oxidative stress. We utilized this property of HT22 cells to assess the ability of nanoceria generated via different synthetic methods to protect against oxidative stress induced cell death. Using the CyQuant cell proliferation assay to assess viability we found that larger, commercially available nanoparticles had no significant effects on cell viability. However, smaller, custom-synthesized CeNPs significantly decreased viability. These findings were surprising but support the literature that points to the potential therapeutic value of nanoceria as an anti-cancer treatment5. Future studies will be conducted to elucidate the mechanism of nanoceria toxicity in immortalized cells lines.
Extended-FOV magnetic resonance imaging with table translation and frequency cycling

A new method for MR imaging of an extended field-of-view (FOV) has been developed and validated. The method employs concurrent MR data acquisition and continuous table motion. Interference of motion to image formation is removed by sweeping the center frequency of the receiver at a rate matching the table's speed. Multiple regional images are collected and combined to reconstruct the full FOV. The imaging parameters and table speed are chosen to ensure that each regional image of the subject is collected while the corresponding anatomy is in the usable imaging volume of the scanner. The method is robust and can be easily incorporated into most multi-slice 2D and volumetric 3D imaging pulse sequences. A variety of uses are anticipated that include, for example, whole-body screening, angiographic runoffs, and short magnet imaging applications.
Dietary Strategies for Weight Management

In an 'obesogenic' environment, getting people to eat appropriate amounts is challenging. Several food-based strategies have the potential to promote satiety and moderate energy intake. Components of foods such as macronutrients and functional ingredients can affect satiety; however, for weight management a more comprehensive approach is needed that emphasizes behavioral strategies to improve the overall diet. Research shows that large portions of energy-dense foods facilitate overconsumption and that reductions in portion size and energy density are associated with reduced energy intake. While this suggests that people should eat smaller portions, recent data show that if people lower the energy density of their diet, they can continue to eat their usual amount of food while limiting calories. Furthermore, serving larger portions of low-energy-dense foods can be used strategically to encourage their consumption and reduce dietary energy density, and this has been shown to be associated with decreased energy intake while maintaining satiety. This new understanding of how portion size can be used positively to manage energy intake has the potential to help people achieve sustainable improvements in their energy intake and bodyweight. Science-based strategies that increase the availability of affordable nutrient-rich, lower energy-dense foods are urgently needed.
Pediatric Gastrointestinal Stromal Tumors and Leiomyosarcoma The St. Jude Children's Research Hospital Experience and a Review of the Literature

BACKGROUND With the introduction of molecularly targeted therapy for gastrointestinal stromal tumors (GISTs), it became important to distinguish GISTs from leiomyosarcomas (LMSs). The authors sought to characterize the clinicopathologic features of these tumors in pediatric patients. METHODS The authors reviewed the medical records of 11 patients for whom GIST or LMS was diagnosed between March 1962 and July 2002 at St. Jude Children's Research Hospital and reclassified the tumors according to current histologic and immunophenotypic criteria. The authors also reviewed the literature pertaining to pediatric GISTs and LMSs. RESULTS Seven patients had GISTs, and four had LMS. The median age of the patients at diagnosis was 11.5 years. At diagnosis, metastases were present in one patient with GISTs and in another with LMS. Unlike the focal distribution of CD117 (KIT) in LMS, diffuse and strong immunostaining was observed in GISTs. Only GISTs expressed CD34. Six patients underwent complete resection (four with GISTs and two with LMS), four patients underwent incomplete resection (three with GISTs and one with LMS), and one patient (with LMS) underwent a biopsy only. Radiotherapy or chemotherapy was used to treat one patient with GISTs and three patients with LMS. One patient with a high-risk GIST (largest dimension of 32 cm and high mitotic count) was treated with adjuvant imatinib mesylate outside the preferred setting of a clinical trial, due to concerns regarding the high risk of tumor recurrence. Four patients with GISTs and two with LMS survived median disease-free a median of 10.4 years and 4.3 years after diagnosis, respectively. Tumors in all but one survivor were completely resected. CONCLUSIONS KIT staining helped to distinguish GISTs from LMSs. Surgery was the treatment of choice for both entities, and tumor resectability was a key prognostic factor. Cancer 2004. © 2004 American Cancer Society.
Caucho, explotación y guerra: configuración de las fronteras nacionales y expoliación indígena en Amazonía

The border shared by the countries of the Amazon was reset in the republican period not without some difficulty due to its remoteness. Such reconfiguration was motivated by the private interests of farmers, exporters and businessmen, of which the most important one in the common border between Peru, Colombia and Brazil was the Casa Arana. The author reviews the case of the pillaging of indigenous groups in that geographical axis carried out by such company in places like La Pedrera, El Encanto and La Chorrera, and describes the related experiences of a uitoto woman. The war between Colombia and Peru is thus analysed from the perspective of this reconfiguration and the geopolitical context at the time. The final section highlights the need for an agenda for the justice and reparation of the indigenous groups that were victims of this genocide.
Amino Acid Neurotransmission

Publisher Summary This chapter discusses the participation of three representative amino acids: (1) the excitatory amino-acid glutamate, (2) inhibitory amino acids γ-aminobutyric acid (GABA), and (3) glycine in transmitting signals that modulate sympathetic output of one well-deﬁned cardiovascular reﬂex: the baroreceptor reflex. Each of the three putative transmitters is present in the nodose ganglion, but neurochemical evidence suggests that of the three, only GABA and glutamate may be released from baroreceptor afferent fibers in the nucleus tractus solitarii (NTS), the primary site of termination of those and other visceral afferent fibers of the vagus and glossopharyngeal nerves. At this important site, each amino acid potentially may modulate cardiovascular activity. Although none of the three amino acids has been implicated in mechanoreceptor or chemoreceptor transduction at the level of the peripheral receptor, some evidence suggests that glutamate transmission may be involved in the periphery. Glutamate binding sites are present on nodose ganglion neurons and are transported from the nodose ganglion toward the aortic arch. Thus, both receptors that bind glutamate and aortic baroreceptors may be found in close proximity.
Chemorepulsion from the Quorum Signal Autoinducer-2 Promotes Helicobacter pylori Biofilm Dispersal

ABSTRACT The gastric pathogen Helicobacter pylori forms biofilms on abiotic and biotic surfaces. We have shown previously that H. pylori perceives the quorum signal autoinducer-2 (AI-2) as a chemorepellent. We report here that H. pylori chemorepulsion from endogenous AI-2 influences the proportions and spatial organization of cells within biofilms. Strains that fail to produce AI-2 ( ∆luxS strains) or are defective for chemotaxis ( ∆cheA strains) formed more spatially homogenous biofilms with a greater proportion of adherent versus planktonic cells than wild-type biofilms. Reciprocally, a strain that overproduced AI-2 ( luxS OP ) formed biofilms with proportionally fewer adherent cells. Along with the known AI-2 chemoreceptor, TlpB, we identified AibA and AibB, two novel periplasmic binding proteins that are required for the AI-2 chemorepulsion response. Disruptions in any of the proteins required for AI-2 chemotaxis recapitulated the biofilm adherence and spatial organization phenotype of the ∆luxS mutant. Furthermore, exogenous administration of AI-2 was sufficient to decrease the proportion of adherent cells in biofilms and promote dispersal of cells from biofilms in a chemotaxis-dependent manner. Finally, we found that disruption of AI-2 production or AI-2 chemotaxis resulted in increased clustering of cells in microcolonies on cultured epithelial cells. We conclude that chemotaxis from AI-2 is a determinant of H. pylori biofilm spatial organization and dispersal. IMPORTANCE Bacterial biofilms are ubiquitous in nature, but the mechanisms governing their assembly and spatial organization are not fully understood. Bacterial communication through quorum sensing has been shown to influence biofilm growth through the regulation of biofilm genes. Our study revealed a new role for quorum sensing in biofilms through rapid chemotactic responses to quorum signals. Specifically, we studied how chemorepulsion of Helicobacter pylori from the universal quorum signal autoinducer-2 (AI-2) shapes the spatial organization of its biofilms. We demonstrate that the chemorepulsive response of H. pylori to AI-2 is necessary to promote its dispersal from biofilms grown on both abiotic and biotic surfaces and is sufficient to promote dispersal in a chemotaxis-dependent manner. This work has broad implications for understanding the mechanisms by which endogenously produced microbial compounds shape the assembly and spatial organization of microbial communities in their environments.
Female Competition over Core Areas in Pan Troglodytes Schweinfurthii, Kibale National Park, Uganda

Aggression is rare among wild female chimpanzees. However, in the Kanyawara chimpanzee community in Kibale National Park, Uganda, stable use of food-rich core areas is linked to increased reproductive success, suggesting that contest competition might occur over access to the highest-quality ranges. To examine this hypothesis, we studied aggression and dominance relationships among Kanyawara females during a 10-yr period that included the immigration of 5 females into the community. We tested 2 predictions: 1) that female-female aggression should intensify when immigrants enter the community because this is when core area access is determined and 2) that the quality of core areas should reflect relative female dominance relationships. In support of the first prediction, female-female aggression increased 4-fold when new immigrants were in the community, with rates peaking when there were multiple immigrants. This pattern was due primarily to aggression by resident mothers toward immigrants and featured coalitionary aggression, a rare behavior among female chimpanzees. In support of the second prediction, females occupying core areas high in foraging quality ranked high overall and higher than expected for their ages, whereas females occupying low-quality core areas were lower-ranking and ranked lower than expected for their ages. Together, the data indicate that though female aggression does not regularly occur in chimpanzees, contest competition continues to play an important role in determining long-term access to resources, an important correlate of reproductive success.