cssi/SciSciGPT-SciSciNet huggingface dataset:
Incomplete block of NMDA receptors by intracellular MK-801.

NMDA receptors (NMDARs) are essential components in glutamatergic synaptic signaling. The NMDAR antagonist MK-801 has been a valuable pharmacological tool in evaluating NMDAR function because it binds with high affinity to the NMDAR ion channel pore and is non-competitive with ligand binding. MK-801 has also been used to selectively inhibit NMDAR current in only the cell being recorded by including the drug in the intracellular recording solution. Here, we report that intracellular MK-801 (iMK-801) only partially inhibits synaptic NMDAR currents at +40 mV at both cortical layer 4 to layer 2/3 and hippocampal Schaffer collateral to CA1 synapses. Furthermore, iMK-801 incompletely inhibits heterologously expressed NMDAR currents at -60 mV, consistent with a model of iMK-801 having a very slow binding rate and consequently ∼30,000 times lower affinity than MK-801 applied to the extracellular side of the receptor. While iMK-801 can be used as a qualitative tool to study reduced postsynaptic NMDAR function, it cannot be assumed to completely block NMDARs at concentrations typically used in experiments.
Early clinical progression in patients with gynecologic malignancies receiving immunomodulatory antibody therapy.

e17087Background: The success of immunomodulatory antibodies have led to their increasing investigation in GYN cancers. Many of these patients, however, discontinue the drugs early in treatment due...
Non-premixed axisymmetric flames driven by ion currents

Abstract Non-premixed flames under the influence of external electric fields can become complicated as ion winds change the transport/mixing dynamics of the flame environment. Burke and Schumman type flames are well studied non-premixed flames and provide a well-suited combustion environment for studying non-premixed flames in longitudinal electric fields. This work studies external electric field effects on a coflow burner stabilized flame. The flame’s spatial features and CH* chemiluminescence light emission are studied under various positive field strengths. The flame base modification was dependent on the geometry of the coflow burner. Despite this geometric dependence, CH* and chemi-ion production rates also increased in the flames that did not show modification to the flame base height indicating that the enhanced ion current is not due to partial premixing as previously suggested. Roper’s flame model for axially symmetric conical type flames was expanded upon to predict what type of electric field forcing is needed to create the observed changes in flame geometries, e.g. flame height and width. The core assumptions made from the classical model were all retained while introducing an ion wind acceleration term to the gas velocity. Ion current measurements from a long wire electrical probe positioned just below the downstream mesh electrode were deconvoluted to reveal the ion current density spatial distribution, and the electrical body force was derived. The calculated body force (200–400 N/m2) agreed well with the theoretical model. The probe measurements also revealed that for the coflow geometry the peak current density develops 2.5 mm from the center axis. This result shows that the plane-to-plane configuration produces a distinctly different current distribution from a point-to-plane configuration whose peak current density remains at the centerline.
Analysis of solar and battery requirements for hybrid DC/AC powered households in the USA

US households consume more electricity compared to other developed countries due to the fact that majority of the US household loads are inefficient. As a result, deployment of residential solar PV cost is increased given the high-power consumption and becomes less viable. Utilities are also increasingly applying surcharges to customers with solar PV installations because of direct impacts to the grid, making purely solar PV installations unattractive. This is especially in the case for low-income households, where they are seemingly shut out from participating in the energy economy given the penalties and the costs. This research primary focus is to make Installed Cost Benchmarks for Residential Solar Photovoltaic with Energy Storage costs more affordable for an average-income home owner in the USA; one approach is to reduce power consumption within the household by adapting DC appliances. So, a compelling means towards reducing household load is to convert a portion of household electrical loads such as LED lighting, air conditioning, ceiling fans, and electronic loads to DC. Secondly, optimizing size of solar panels and battery and without the need for energy export, it compensates for surcharges and recover return on solar investment. Data provided in this paper gives an insight into adapting suitable hybrid DC/AC architecture for three different types of households associated with five different geographical regions based of different climactic conditions spread across the USA. The systems are distinguished by the degree to which redundant AC to DC conversion stages are reduced, which will be inversely proportional to cost. This paper shows that deployment of DC distribution within the house will result in lower average cost and better returns on solar and battery investment than revealed by the NREL study. Also, outlines the costs and savings of different architecture that can be adaptable based on the type of the house, location, savings, and affordability. Only this paper shows the benefits occur due to the reduced number of solar panels and battery storage required when compared to conventional AC powered households. The end goal of this work is to increase the adoptability of solar PV across a more diverse population with a particular focus on low-income households.
MANAGING R&D IN VERTICAL RELATIONSHIPS

We study the optimal strategy for research and development (R&D) in a buyer‐supplier relationship. The buyer chooses whether to (1) insource a cost‐reducing R&D to its own research‐subunit or to (2) outsource it to its manufacturing supplier. The buyer cannot observe the R&D effort in either case, but can better observe the R&D result when the R&D is conducted internally. According to our analysis, the buyer prefers insourcing R&D to mitigate information asymmetry when the R&D cost is either small or large. When the R&D cost is intermediate, however, the buyer prefers outsourcing R&D, and can achieve the full information outcome (first‐best outcome) despite the information asymmetry associated with outsourcing R&D. Moreover, the buyer's preference for outsourcing high‐cost R&D increases when the R&D is more likely to succeed or to generate significant cost reductions, or the R&D result is more difficult to predict. Our analysis provides a theoretical explanation for the increasing trend of outsourcing innovation to manufacturing suppliers. (JEL D82, L22, L23)
Postprocedure Intravenous Patient-Controlled Analgesia Compared to Epidural Patient-Controlled Analgesia Use after Uterine Fibroid Embolization: A Clinical Audit.

Purpose: Postprocedure epidural analgesia has a proven benefit over intravenous (i.v.) analgesia for pain management, but has not yet been demonstrated for uterine fibroid embolization (UFE). The objectives of this clinical audit were to determine if epidural patient-controlled analgesia (PCA) was beneficial to patient outcome as compared to i.v. PCA in decreasing parenteral opioid requirements and its associated side effects and determine if there is a difference in required oral opioids after the PCA is stopped. Materials and Methods: This manuscript audited postprocedural pain management of 51 patients after UFE was performed. 20 patients received an i.v. PCA for post-UFE pain control and 31 received an epidural PCA for post-UFE pain control. Total hydromorphone dose, the frequency of anti-nausea medication use, the frequency of anti-pruritus medication use, and patient pain satisfaction data was collected. Results: Total hydromorphone dose administered to patients post-UFE using epidural PCA was significantly less than patients using an i.v. PCA (P = 0.001). However, the frequency of nausea and pruritus between the two groups did not achieve statistical significance with (P = 0.663) and (P = 0.639) respectively. Conclusion: Our clinical audit found that parenteral opioid requirements administered after UFE can be significantly reduced by using epidural PCA instead of i.v. PCA. However, we found no statistically significant difference in medication related side effects or oral opioid use thereafter.
In Vivo Evaluation of a Fully-Passive Wireless Neurosensing System

Neural implants are used to continuously record essential signals in studies of neurological disorders. Existing systems involve the use of invasive procedures and revision surgeries to maintain adequate system performance. Our previous work demonstrated a fully-passive wireless system, tested in vitro, and was demonstrated capable of sensing even minute neural signals. This recorder has a minimum detectable signal (MDS) below 15 µV in amplitude and a RF sensitivity down to about - 135 dBm. While results have been promising, this system is yet to be used to study neurological disorders, the final intended application of the system. In this paper, for the first time, we evaluate the wireless neurosensing system's ability to capture the characteristic components of epilepsy, namely interictal epileptiform discharges. The present validation of this technology has great future clinical implications in neuroscience, especially epilepsy studies.
Abstract LB-238: Characterization of circulating tumor cells and its PD-L1 expression with high-sensitivity liquid biopsy panel in non-small cell lung cancer patients

Early detection and intervention are crucial for long-term survival of either primary or recurrent lung cancer patients. Circulating tumor cells (CTCs) could be powerful biomarkers for the diagnosis, prognosis, and treatment planning of cancer. In this work we applied our FAST cytometer, a fiber-optic array scanning technology (FAST) to develop a sensitive diagnostic blood tests (“liquid biopsies”) for NSCLC. This technology is based on the ultra-rapid, sensitive and accurate detection of rare circulating cells expressing the biomarker(s) of interest. By applying the FAST cytometer with a unique NSCLC specific cocktail, we were able to detect CTC in NSCLC setting with higher sensitivity as compared with traditional cytokeratin-based detection. In a pilot cohort of 51 NSCLS patients, we have detected CTC in 74.2% using our unique panel for NSCLC CTC, this has raised our sensitivity from 48.8% using traditional cytokeratin-based detection. In addition, we have also interrogated circulating cancer associated fibroblasts (cCAF) as an additional liquid biopsy marker for NSCLC. We detected cCAF in 67% NSCLC patients. When combined with our enhanced CTC detection method, addition of cCAF further increased our sensitivity to 88.5%. Moreover, using clinically validated PD-L1 antibody (Ventana SP263) as reference, we have demonstrated our capacity to analyze PD-L1 expression on CTC at protein level, we have shown detection of PD-L1+ CTC in 80% of the patients. To summarize, we have developed an unique panel to detect CTC with higher sensitivity using combinational detection and we have demonstrated that by combining CTC detection with cCAF detection, liquid biopsy sensitivity for cancer detection can be further increased without significant increase in false positive rates. Lastly, we developed a method to analyze the PD-L1 expression on CTC using clinically validated Ventana PD-L1 (SP263) rabbit monoclonal antibody as reference which can potentially serve as a companion diagnostics tool for NSCLC immunotherapy Citation Format: Xiaohe Liu, Zheng Ao, Jordan S. Preiss, Joel Neal, Lisa Ya Zhou, Lidia Sambucetti, Heather A. Wakelee. Characterization of circulating tumor cells and its PD-L1 expression with high-sensitivity liquid biopsy panel in non-small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-238.
ON THE DEVELOPMENT OF UNUSUALLY HIGH FATIGUE CRACK PROPAGATION RESISTANCE IN STEELS: ROLE OF CRACK TIP SHIELDING IN DUPLEX MICROSTRUCTURES

ABSTRACT The role of crack tip shielding in retarding fatigue crack growth has been examined in duplex microstructures, with the objective of achieving maximum resistance to fatigue. Specifically, ferritic-martensitic structures have been developed in AISI 1008 steel, where shielding is generated from crack deflection and resultant crack closure. Such techniques yield fatigue thresholds which are 100% higher than in normalized structures, i.e., over 20 MPam, representing the highest thresholds reported for a metallic alloy to date. Effects of the dual-phase microstructures on crack initiation and small crack (10 to 1000 μm) growth are quite different. Structures which show the highest resistance to long crack growth show the lowest resistance to crack initiation and small crack growth, characteristic of behavior influenced by the mutual competition of intrinsic and extrinsic (shielding) “toughening” mechanisms.
Light Scattering Studies of Molecular Orientation Fluctuations in Two Dimensions

The static and dynamic behavior of the two dimensional orientation field of molecules in the plane of thin, freely-suspended smectic C liquid crystal films is effectively studied by light scattering. Films of 1 to 10 layers in thickness (30A per layer) have been studied. Thin smectic C (SC) films are a nearly ideal physical representation of the Classical Continuous XY Model. Light scattering with well-defined wave-vector has been used to study the dispersion relations for the two allowed orientation fluctuation modes in two dimensions (bend and splay). These exhibit Frank-like elastic behavior with, in ferroelectric SC films, an additional term in the bend mode dispersion relation due to polarization space charge interaction effects. Exploitation of this latter term allows the absolute measurement of the polarization, elastic constants, and viscosities. The Frank elastic constants decrease with increasing temperature to values comparable to those predicted for the Kosterlitz-Thouless transition at which point a phase transition to an isotropic (smectic A) film is found to occur. Measurements of the 2-d elastic constants vs. film thickness shows that, 3-d Frank elasticity is dispersive (nonlocal) at wave vectors q ~ 106cm−1. Light scattering studies which employ the collection of a broad distribution of wave vectors have also been carried out. These allow the direct visualization of the 2-d molecular orientational field, a feature unique to these systems. The static and dynamic behavior of spontaneous and field induced point and line defects has been investigated using this method. It has also been used to study directly the fluctuations in the average local orientation which show contributions of modes having inverse wavevectors ranging from the size of the averaging area to the size of the sample.
A Class II-Restricted CD8γ13 T-Cell Clone Protects During Chlamydia muridarum Genital Tract Infection.

Background The T-cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I restricted (referred to here as "unrestricted" or "atypical"). We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included interferon (IFN)-γ and interleukin (IL)-13. Methods In this study, we investigated the transcriptome of CD8γ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8γ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8γ13 T-cell clone to determine whether either influenced bacterial clearance or immunopathology during Chlamydia muridarum genital tract infections. Results To our surprise, an adoptively transferred CD8γ13 T-cell clone was remarkably proficient at preventing chlamydia immunopathology, whereas the multifunctional Tc1 clone did not enhance clearance or significantly alter immunopathology. Mapping studies with major histocompatibility complex (MHC) class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T-cell clones are MHC class II restricted. Conclusions The MHC class II-restricted CD8 T cells may play an important role in protection from intracellular pathogens that limit class I antigen presentation or diminish CD4 T-cell numbers or impair their function.
Trends in Regional Supply of Peritoneal Dialysis in an Era of Health Reform, 2006 to 2013.

Peritoneal dialysis (PD), a home-based treatment for kidney failure, is associated with similar mortality, higher quality of life, and lower costs compared with hemodialysis. Yet <10% of patients receive PD. Access to this alternative treatment, vis-a-vis providers' supply of PD services, may be an important factor but has been sparsely studied in the current era of national payment reform for dialysis care. We describe temporal and regional variation in PD supply among Medicare-certified dialysis facilities from 2006 to 2013. The average proportion of facilities offering PD per hospital referral region increased from 40% (2006) to 43% (2013). PD supply was highest in hospital referral regions with higher percentage of facilities in urban areas (p = .004), prevalence of PD use (p < .0001), percentage of White end-stage renal disease patients (p = .02), and per capita income (p = .02). Disparities in PD access persist in rural, non-White, and low-income regions. Policy efforts to further increase regional PD supply should focus on these underserved communities.
Human Regulatory T Cells From Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood.

The human T lymphocyte compartment is highly dynamic over the course of a lifetime. Of the many changes, perhaps most notable is the transition from a predominantly naive T cell state at birth to the acquisition of antigen-experienced memory and effector subsets following environmental exposures. These phenotypic changes, including the induction of T cell exhaustion and senescence, have the potential to negatively impact efficacy of adoptive T cell therapies (ACT). When considering ACT with CD4+CD25+CD127-/lo regulatory T cells (Tregs) for the induction of immune tolerance, we previously reported ex vivo expanded umbilical cord blood (CB) Tregs remained more naive, suppressed responder T cells equivalently, and exhibited a more diverse T cell receptor (TCR) repertoire compared to expanded adult peripheral blood (APB) Tregs. Herein, we hypothesized that upon further characterization, we would observe increased lineage heterogeneity and phenotypic diversity in APB Tregs that might negatively impact lineage stability, engraftment capacity, and the potential for Tregs to home to sites of tissue inflammation following ACT. We compared the phenotypic profiles of human Tregs isolated from CB versus the more traditional source, APB. We conducted analysis of fresh and ex vivo expanded Treg subsets at both the single cell (scRNA-seq and flow cytometry) and bulk (microarray and cytokine profiling) levels. Single cell transcriptional profiles of pre-expansion APB Tregs highlighted a cluster of cells that showed increased expression of genes associated with effector and pro-inflammatory phenotypes (CCL5, GZMK, CXCR3, LYAR, and NKG7) with low expression of Treg markers (FOXP3 and IKZF2). CB Tregs were more diverse in TCR repertoire and homogenous in phenotype, and contained fewer effector-like cells in contrast with APB Tregs. Interestingly, expression of canonical Treg markers, such as FOXP3, TIGIT, and IKZF2, were increased in CB CD4+CD127+ conventional T cells (Tconv) compared to APB Tconv, post-expansion, implying perinatal T cells may adopt a default regulatory program. Collectively, these data identify surface markers (namely CXCR3) that could be depleted to improve purity and stability of APB Tregs, and support the use of expanded CB Tregs as a potentially optimal ACT modality for the treatment of autoimmune and inflammatory diseases.
Quantization of Pseudoclassical Systems in the Schrodinger Realization

We examine the quantization of pseudoclassical dynamical systems, models that have classically anticommuting variables, in the Schrodinger picture. We quantize these systems, which can be viewed as classical models of particle spin, using the generalized Gupta–Bleuler method as well as the reduced phase space method in even dimensions. With minimal modifications, the standard constructions of Schrodinger quantum mechanics of constrained systems work for pseudoclassical systems. We generalize the standard Schrodinger norm and implement the correct adjointness properties of observables and constraints. We construct the state space corresponding to spinors as physical wave functions of anticommuting variables, finding that there are superselection sectors in both the physical and ghost subspaces. The physical states are isomorphic to those of the Dirac–Kahler formulation of fermions, though the inner product in Dirac–Kahler theory is not equivalent to ours.
Computational 4D-OCM for label-free imaging of collective cell invasion and force-mediated deformations in collagen

Traction force microscopy (TFM) is an important family of techniques used to measure and study the role of cellular traction forces (CTFs) associated with many biological processes. However, current standard TFM methods rely on imaging techniques that do not provide the experimental capabilities necessary to study CTFs within 3D collective and dynamic systems embedded within optically scattering media. Traction force optical coherence microscopy (TF-OCM) was developed to address these needs, but has only been demonstrated for the study of isolated cells embedded within optically clear media. Here, we present computational 4D-OCM methods that enable the study of dynamic invasion behavior of large tumor spheroids embedded in collagen. Our multi-day, time-lapse imaging data provided detailed visualizations of evolving spheroid morphology, collagen degradation, and collagen deformation, all using label-free scattering contrast. These capabilities, which provided insights into how stromal cells affect cancer progression, significantly expand access to critical data about biophysical interactions of cells with their environment, and lay the foundation for future efforts toward volumetric, time-lapse reconstructions of collective CTFs with TF-OCM.
Visible-Wavelength Beam Shaping using Two-Dimensional Meta-Grating Outcouplers

We design and fabricate large-scale meta-grating outcouplers at 461 nm. Our design employs subwavelength scattering elements to accurately reproduce Gaussian free-space beams with waists greater than 100 µm.
Determining validity, discriminant ability, responsiveness, and minimal clinically important differences for PROMIS in adult spinal deformity.

Objective The aim of this study was to determine the concurrent validity, discriminant ability, and responsiveness of the Patient-Reported Outcomes Measurement Information System (PROMIS) in adult spinal deformity (ASD) and to calculate minimal clinically important differences (MCIDs) for PROMIS scores. Methods The authors used data obtained in 186 surgical patients with ASD. Concurrent validity was determined through correlations between preoperative PROMIS scores and legacy measure scores. PROMIS discriminant ability between disease severity groups was determined using the preoperative Oswestry Disability Index (ODI) value as the anchor. Responsiveness was determined through distribution- and anchor-based methods, using preoperative to postoperative changes in PROMIS scores. MCIDs were estimated on the basis of the responsiveness analysis. Results The authors found strong correlations between PROMIS Pain Interference and ODI and the Scoliosis Research Society 22-item questionnaire Pain component; PROMIS Physical Function and ODI; PROMIS Anxiety and Depression domains and the 12-Item Short Form Health Survey version 2, Physical and Mental Components, Scoliosis Research Society 22-item questionnaire Mental Health component (anxiety only), 9-Item Patient Health Questionnaire (anxiety only), and 7-Item Generalized Anxiety Disorder questionnaire; PROMIS Fatigue and 9-Item Patient Health Questionnaire; and PROMIS Satisfaction with Participation in Social Roles (i.e., Social Satisfaction) and ODI. PROMIS discriminated between disease severity groups in all domains except between none/mild and moderate Anxiety, with mean differences ranging from 3.7 to 8.4 points. PROMIS showed strong responsiveness in Pain Interference; moderate responsiveness in Physical Function and Social Satisfaction; and low responsiveness in Anxiety, Depression, Fatigue, and Sleep Disturbance. Final PROMIS MCIDs were as follows: -6.3 for Anxiety, -4.4 for Depression, -4.6 for Fatigue, -5.0 for Pain Interference, 4.2 for Physical Function, 5.7 for Social Satisfaction, and -3.5 for Sleep Disturbance. Conclusions PROMIS is a valid assessment of patient health, can discriminate between disease severity levels, and shows responsiveness to changes after ASD surgery. The MCIDs provided herein may help clinicians interpret postoperative changes in PROMIS scores, taking into account the fact that they are pending external validation.
The role of RFamide-related peptide 3 (RFRP3) in regulation of the neuroendocrine reproductive and growth axes of the boar

RFamide-related peptide 3 (RFRP3) has been implicated in regulating reproduction and growth. This regulation appears to be dependent upon sex, species, physiological status, and developmental stage. The objective of the present study was to evaluate the effects of RFRP3 on circulating concentrations of luteinizing hormone (LH) and growth hormone (GH) in mature boars. The hypothesis was RFRP3 would reduce circulating concentrations of LH and increase concentrations of GH. Meishan boars (716.6±2.8 days of age; 125.0±12.4kg BW) were randomly assigned to treatment: saline (n=4) or RFRP3 (8.5mg; n=5). Plasma was collected at 15-min intervals during 3 periods: pre-treatment, treatment, and post-treatment. During the treatment period, saline or RFRP3 were administered at 15-min intervals. Treatment was administered as a loading dose of 5mg RFRP3, followed by seven repeated injections of 0.5mg RFRP3. Pulsatile secretion of LH and GH were not affected by saline treatment. Mean concentrations of LH in RFRP3-treated boars were greater (P<0.01) in the pre-treatment period than in the treatment and post-treatment periods; however, the individual response to RFRP3 challenge was varied. RFRP3 suppressed (P<0.05) mean concentrations of GH during the treatment period. It is concluded that RFRP3 can act to suppress LH secretion in some boars, but the minimal and varied response between animals does not strongly support the idea that RFRP3 is a potent hypohysiotropic hormone in the pig. Results indicate that RFRP3 may function in regulating the growth axis of swine.
Factors Affecting the Efficiency of EEG Laboratories of Varying Sizes

(1965). Factors Affecting the Efficiency of EEG Laboratories of Varying Sizes. American Journal of EEG Technology: Vol. 5, No. 2, pp. 26-29.
TU‐B‐213‐02: MBAs for Medical Physicists: DABR‐MBA Alumni Panel

A panel of board-certified medical physicists with MBA degrees will share their insights about business schools and career paths in a moderated discussion format. The panelists bring a broad range of experience in terms of medical physics specialties, MBA program types, current organizational roles, and business school alma maters. The discussion will include: 1) the process of deciding if, where, when, why, and how to pursue the MBA; 2) the MBA student experience, including workload, networking, and school-life-work balance; 3) post-MBA career impact, and 4) advice to medical physicists considering an MBA. The conversation will also include questions from the audience. This session is the second of two consecutive sessions exploring the professional impact of supplementing medical physics credentials with formal business education, and is also part of a larger block of sessions concentrating on the Management, Business and Supervision aspects of Medical Physics. Learning Objectives: 1. To learn about the pre-, intra-, and post-MBA experiences of several medical physicists. 2. To gain a sense of possible career outcomes that business credentials could catalyze.
424. Myd88/TLR Signaling Is Required for Immunotherapy-Mediated Glioblastoma Regression

5554 Glioblastoma multiforme (GBM) is the most common type of brain tumor and is a leading cause of mortality with mean patient survival 6–12 months following diagnosis. We have recently shown that combined treatment of glioma bearing rats with RAdFlt3L and RAdTK dramatically improved survival. RAdFlt3L encodes human soluble Flt3L and stimulates dendritic cell proliferation and improves antigen presentation. RAdTK expresses herpes simplex type I-thymidine kinase and selectively kills rapidly dividing cells when used in combination with the non-toxic prodrug ganciclovir. We now show that combined treatment with RAdTK and RAdFlt3L improves long-term survival in C57BL/6 mice bearing intracranial GL26 tumors when all individual therapies completely fail (p
Online Compensation of Detuning Effects in Vector Control Based on Adaptive Sensorless Rotor Thermal Model Identification

Temperature-related variations of the rotor resistance induce detuning effects in a vector control drive. This paper focuses on the development of an adaptive sensorless rotor thermal model identification algorithm to compensate for such detuning effects. The proposed rotor thermal model identification algorithm is divided into two parts: a sensorless rotor temperature estimator and an adaptive rotor thermal model identifier. First, the rotor temperature estimator utilizes a sensorless rotor speed detector and an online rotor resistance estimator to estimate the rotor temperature. This estimated rotor temperature serves as a reference signal to the subsequent adaptive identification of rotor thermal model parameters. Then, based on the analysis of the rotor thermal model, a digital antialiasing filter using a Kaiser window is designed to suppress the noise in the previously estimated rotor temperature in conjunction with a downsampling stage. After that, the rotor thermal model parameters are identified online to establish the relationship between the motor losses and the rotor temperature. Once these thermal parameters are successfully determined, the rotor temperature can be predicted from the motor losses alone, in an online fashion, and such predicted rotor temperature can be used to provide proper compensation to the detuning effects. The proposed algorithm is validated through experimental results.
Experimental chemotherapy of human medulloblastoma cell lines and transplantable xenografts with bifunctional alkylating agents.

A series of bifunctional alkylators were tested against the genotypically and phenotypically heterogeneous continuous human medulloblastoma cell lines, TE-671, Daoy, and D283 Med in vitro and against TE-671 and Daoy growing as s.c. and intracranial xenografts in athymic mice. Drugs tested included melphalan, cyclophosphamide, iphosphamide, phenylketocyclophosphamide, thiotepa, 1,3-bis(2-chloroethyl)-1-nitrosourea (in vivo), and busulfan (in vivo). Melphalan and phenylketocyclophosphamide were the most active agents in vitro with drug doses at which there is a 90% reduction in the number of colonies in comparison to controls of 2.13, 5.29, and 4.72 microM for melphalan and 4.60, 5.01, and 4.34 microM for phenylketocyclophosphamide against TE-671, D283 Med, and Daoy, respectively. Melphalan, cyclophosphamide, iphosphamide, phenylketocyclophosphamide, and thiotepa produced significant growth delays against s.c. TE-671 and Daoy xenografts, while no activity could be demonstrated for 1,3-bis(2-chloroethyl)-1-nitrosourea or busulfan. Melphalan, cyclophosphamide, iphosphamide, and thiotepa also produced significant increases in median survival in mice bearing intracranial TE-671 and Daoy xenografts. These results extend our previous studies demonstrating the antitumor activity of nitrogen and phosphoramide mustard-based bifunctional alkylating agents in the treatment of human medulloblastoma continuous cell lines and transplantable xenografts, and support the continued use of these agents in clinical trials.
Wireless Sensor Networks

This study introduces a new self-configuring, multirooted tree topology ad hoc network designed to offer robust and scalable sensor communication services. A generic sensor node is equipped with a short-range wireless transceiver, while border nodes acting as gateways between sensor clusters and cyberspace are equipped with an additional network interface. All traffic is assumed to originate from or terminate at the sensors. A new cost metric is proposed to partition a network of sensors into multiple trees each rooted from a gateway node. The novel cost function proposed here takes into account several metrics including link capacity, link reliability, number of hops to a gateway, and power constraints of a node. The contribution of each metric to the cost function is decided by weights assigned to each metric. A middleware offering services similar to Universal Plug and Play (UPnP) is developed. This middleware offers sensor discovery, sensor event notification, and sensor object access services for simple deployment and operation of sensor nodes. A network is modeled and simulated with Opnet Technologies’ Opnet Modeler prior to implementation on a low power baseband processor and a low-bit-rate radio frequency (RF) transceiver. Simulations have revealed that the proposed architecture adapts well to changes in the state of links/nodes, and always converged to a valid solution.
An Assessment of Infertility in a Rural Area

Objective: The incidence of infertility is increasing steadily and is not restricted to any geographic area. An assessment of infertility in rural areas was made to determine if there was a difference in infertility rates and related factors between urban and rural groups. Design: Survey research methodologies were used. Setting: Phone interviews were conducted to collect data in the homes of subjects who were 18 years or older. Results: Descriptive statistics were used to analyze data. There was a statistically significant difference in the number of urban and rural subjects who were infertile (p=.05) in this sample. Rural infertile subjects were less satisfied with their health care provider if they sought treatment for infertility. Additionally, the sample of total rural citizens had to travel longer to their health care provider. Conclusion: There are differences related to infertility for rural and urban groups. Implications for health care providers and policy makers include providing enhanced reproductive services to rural citizens.
“I Coulda Been a Contender”: Lost Profits After a Contract Breach

This article forewarns litigators and transactionalists of the potential pitfalls regarding lost profits where a seller breaches a contract it conveys property. Considerations cover the various stages of a purchase agreement from negotiating the deal, conducting litigation, and introducing evidence.
The use of serum creatine phosphokinase in genetic counseling for Duchenne muscular dystrophy. II. Review of methods of assay and factors which may be relevant in the interpretation of serum creatine phosphokinase activity.

Abstract Several methods of CPK assay are compared and some factors which may affect serum CPK activity and which may be relevant to genetic counseling for carriers of DMD are discussed. We conclude from the published material that, for practical purposes, normal daily activity, the stage of the menstrual cycle and the use of the contraceptive pill do not affect CPK activity. CPK activity is higher in males than females and higher in Blacks than Whites, and these factors should be considered in the choice of controls for studies on this subject. CPK activity may be lowered during pregnancy; it appears to rise as the day progresses; and the effect of advancing age is not yet clear. Although other methods of diagnosing carriers have been suggested, for the present the CPK will probably remain the principal corroborative test for this purpose, and the various factors which may affect CPK activity should be considered in its interpretation.
Comparative utilization of intravenous fructose and invert sugar.

Summary 1.Total 24-hour urinary losses of sugar were studied following inf usion of 10 per cent fructose and of 10 per cent invert sugar at rates of 1000 ml. per hour and 1000 ml. per 2.5 hours in normal subjects on alternate days, each patient thus serving as his own control. The average losses were 3.8 per cent to 7.1 per cent of the total amount infused, with a maximum of 11.4 per cent in any single patient. 2.The average amount of sugar excreted in the urine is less at the slowerrate of infusion with both sugars. 3.At each infusion rate, less sugar is excreted with fructose than with invertsugar, and the difference is largely due to the larger loss of glucose in the urine following infusion of invert sugar. Fructose given at a rate of 1000 ml. per 2.5 hours was most efficiently retained. 4.The results of this study suggest that 10 per cent invert sugar is notutilized as if the 5 per cent fructose and 5 per cent glucose components were treated independently by the body, but rather that the urinary sugar losses lie between those anticipated with 10 per cent fructose alone and 10 per cent glucose alone. There is certainly no suggestion of a favorable effect of one sugar on the other and retention of fructose is even less than would be expected had it been given alone. 5.Fructose and invert sugar infused into patients with widespread cancerbehave much as they do in normal subjects, although losses are somewhat greater, particularly at more rapid infusion rates. However, losses of glucose far in excess of those seen in normal patients after infusions of fructose were observed in 2 cases, suggesting abnormal conversion of fructose to glucose. 6.After major operations, infusions of both fructose and invert sugar areefficiently retained, just as in the case of normal patients. One patient excreted an unusual amount of glucose in the urine after infusions of fructose. 7.Postoperative urinary losses of sodium and potassium are of the ordernoted in previous studies with glucose infusion or with no infusion. Average losses of sodium were slightly higher with fructose than with invert, but in neither case is the loss exceptional (56.9 mEq. and 39.8 mEq.).
Asiatic acid induces endoplasmic reticulum stress and apoptotic death in glioblastoma multiforme cells both in vitro and in vivo.

Glioblastoma multiforme (GBM) is an untreatable malignancy. Existing therapeutic options are insufficient, and adversely affect functional and non-cancerous cells in the brain impairing different functions of the body. Therefore, there is an urgent need for additional preventive and therapeutic non-toxic drugs against GBM. Asiatic acid (AsA; 2,3,23-trihydroxy-12-ursen-28-oic acid, C30H48O5) is a natural small molecule widely used to treat various neurological disorders, and the present research investigates AsA's efficacy against GBM both in vitro and in vivo. Results showed that AsA treatment (10–100 µM) decreased the human GBM cell (LN18, U87MG, and U118MG) viability, with better efficacy than temozolomide at equimolar doses. Orally administered AsA (30 mg/kg/d) strongly decreased tumor volume in mice when administered immediately after ectopic U87MG xenograft implantation (54% decrease, P ≤ 0.05) or in mice with established xenografts (48% decrease, P ≤ 0.05) without any apparent toxicity. Importantly, AsA feeding (30 mg/kg/twice a day) also decreased the orthotopic U87MG xenografts growth in nude mice as measured by magnetic resonance imaging. Using LC/MS-MS methods, AsA was detected in mice plasma and brain tissue, confirming that AsA crosses blood-brain barrier. Mechanistic studies showed that AsA induces apoptotic death by modulating the protein expression of several apoptosis regulators (caspases, Bcl2 family members, and survivin) in GBM cells. Furthermore, AsA induced ER stress (increased GRP78 and Calpain, and decreased Calnexin and IRE1α expression), enhanced free intra-cellular calcium, and damaged cellular organization in GBM cells. These experimental results demonstrate that AsA is effective against GBM, and advocate further pre-clinical and clinical evaluations of AsA against GBM. © 2014 Wiley Periodicals, Inc.
Nitric oxide does not contribute to the hypotension of heatstroke.

The purpose of this study was to determine whether nitric oxide (NO) contributes to the hypotensive state induced by prolonged environmental heat (EH) stress. Ketamine-anesthetized rats were instru...
Monitoring system for infant movement, vocalization, and nurse interaction

An instrument which monitors and records certain behaviors of the neonate is described. By means of an air-inflated mattress and pressure transducer, the instrument measures whole-body movement. By means of a crib-located microphone, the device measures vocalizations. In addition, the presence and activity of nurse or observer are also monitored and recorded as part of the complete record. Except for the mattress and transducers, the monitor is completely self-contained, even including in its 8½-in.-high x 19-in.-wide size a 10-channel event recorder.
Biology Evolves to Fight Chemistry

A human enzyme variant, PON1-G3C9, accidentally catalyzes the hydrolysis of organophosphorus chemical weapons. In this issue of Chemistry & Biology, Goldsmith and coworkers describe a new PON1 variant with improved hydrolysis by several hundred fold; enough that it may protect animals from a toxic dose.
An alpha globin pseudogene is located within the mouse t complex

Restriction fragment length polymorphisms have been identified in the α-globin pseudogene carried on chromosome 17. Different inbred strains of mice carry one of two forms of the sequence, whereas all complete t haplotypes carry a third form. With the use of partial t haplotypes, the α-ψ44 sequence has been mapped to the distal end of the t complex. This sequence appears to be closely linked to the tufted locus in the t complex.
A Scaleable Synthesis of Methyl 3-Amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate

A scaleable synthesis of methyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate (1b), starting from 5-bromo-2-methoxypyridine (8) and 4-fluorobenzaldehyde (9), is described. Key steps in the process include lithium–bromine exchange of 8, addition of the resulting lithiate to aldehyde 9, regioselective nitration of pyridone 12, and Pd-catalyzed alkoxycarbonylation of bromopyridine 15b. Overall yield of the five-stage synthesis was 23%; intermediates 10, 12, 13, 15b, and final product 1b·HCl were isolated as filterable solids. Compounds 1a,b are important intermediates in the synthesis of 7-benzylnaphthyridinones (e.g., 2) and related HIV-1 integrase inhibitors.
Initial experience with soft-copy display of computed radiography images on three picture archive and communication systems

We recently installed picture archive and communication systems (PACS) from three different vendors on our campus for evaluation. A major part of this evaluation involved assessing the capabilities of these systems for displaying computed radiography (CR) images for primary interpretation. The three PACS provided different functionality for CR image display in terms of availability of the proprietary Fuji CR image processing algorithms, availability of user-specified contrast look-up tables, and application of the processing at the time of CR image capture or image display. We found that the Fuji processing algorithms were important for printing film, but were not necessary for acceptable soft-copy display. Non-linear contrast processing produced superior results compared to simple linear processing (via standard window width and level controls). Display processing was best applied immediately prior to the display operation, as opposed to at the image capture time. This allows the display to be adjusted to demonstrate the full 10-bit range of the CR image, and also allows raw CR data (i.e. not optimized for any particular display device) to be stored in the long-term archive.
Extraction of morphological features from biological models and cells by fourier analysis of static light scatter measurements

Models of biological cells of varying geometric complexity were used to generate data to test a method of extracting geometric features from light scatter distributions. Measurements of the dynamic range and angular distribution of intensity and light scatter from these models was compared to the distributions predicted by a complete theory of light scatter (Mie) and by diffraction theory (Fraunhofer). An approximation to the Fraunhofer theory provides a means of obtaining size and shape features from the data by a spectrum analysis. Experimental verification using nucleated erythrocytes as the biological material show the potential application of this method for the extraction of important size and shape parameters from light scatter data.
ATM Influences the Efficiency of TCRβ Rearrangement, Subsequent TCRβ-Dependent T Cell Development, and Generation of the Pre-Selection TCRβ CDR3 Repertoire

Generation and resolution of DNA double-strand breaks is required to assemble antigen-specific receptors from the genes encoding V, D, and J gene segments during recombination. The present report investigates the requirement for ataxia telangiectasia-mutated (ATM) kinase, a component of DNA double-strand break repair, during TCRβ recombination and in subsequent TCRβ-dependent repertoire generation and thymocyte development. CD4−CD8− double negative stage 2/3 thymocytes from ATM-deficient mice have both an increased frequency of cells with DNA break foci at TCRβ loci and reduced Vβ-DJβ rearrangement. Sequencing of TCRβ complementarity-determining region 3 demonstrates that ATM-deficient CD4+CD8+ double positive thymocytes and peripheral T cells have altered processing of coding ends for both in-frame and out-of-frame TCRβ rearrangements, providing the unique demonstration that ATM deficiency alters the expressed TCRβ repertoire by a selection-independent mechanism. ATMKO thymi exhibit a partial developmental block in DN cells as they negotiate the β-selection checkpoint to become double negative stage 4 and CD4+CD8+ thymocytes, resulting in reduced numbers of CD4+CD8+ cells. Importantly, expression of a rearranged TCRβ transgene substantially reverses this defect in CD4+CD8+ cells, directly linking a requirement for ATM during endogenous TCRβ rearrangement to subsequent TCRβ-dependent stages of development. These results demonstrate that ATM plays an important role in TCRβ rearrangement, generation of the TCRβ CDR3 repertoire, and efficient TCRβ-dependent T cell development.
Feeding and Drinking in Sheep Following Hyphothalamic Injections of Carbachol

Abstract Carbachol (carbamycholine chloride) (28 nmol) was injected on 77 occasions into 69 loci in the hypothalamus of 13 sheep. Of the injections, 31% elicited feeding, 14% elicited drinking, and 4% elicited both feeding and drinking responses. One carbachol feeding locus in each of eight sheep was injected with carbachol at doses from 1.75 to 112 nmol. Feeding was elicited by 3.5 nmol or more carbachol. At carbachol-bound feeding loci in eight sheep, the effect of carbachol was blocked by atropine, a cholinergic antagonist, but not by phe-noxybenzamine or LB-46, α and β -adrenoceptor antagonists, respectively; atropine alone had no effect. Increases in water intake accompanying carbachol-induced feeding may be due to increased dry matter intake. There were no significant effects on intraperitoneal temperature. Cholinergic pathways passing through the hypothalamus of sheep is proposed as an explanation for the feeding.