cssi/SciSciGPT-SciSciNet huggingface dataset:
(343) Localized Sympathectomy Drives Macrophage Polarization to Reduce Chemotherapy-Induced Neuropathic Pain

Chemotherapy-induced neuropathic pain (CINP) is a disabling condition affecting up to 80% of patients during treatment with antineoplastic drugs, including the frontline chemotherapeutic agent paclitaxel. There are no FDA-approved drugs to treat CIPN and many drugs that are used for the treatment of other neuropathic pain states have shown poor or no analgesic effect on CINP, which suggests unique mechanisms underlie CINP. Paclitaxel is a common drug for various solid cancers. However, it is often associated with neuropathic pain, which is generally localized in the distal extremities of the body and can persist for months or years after the end of the treatment. Although the exact mechanisms underlying paclitaxel CINP remain incompletely known, there are several line of evidence indicating that immune cells in dorsal root ganglia (DRGs) play critical roles in the development and progression of CINP. Interestingly, our recent study has shown that sympathetic innervation not only drives immune responses in organs such as the thymus, spleen and lymph nodes, but also orchestrates localized immune responses in DRGs maintaining inflammatory pain. Here, we report that localized “microsympathectomy” (mSYMPX) significantly reverses mechanical allodynia in male and female mice after paclitaxel. Mechanistically, the mSYMPX analgesic effect is driven by an anti-inflammatory polarization of macrophages and TGF-β1 signaling in DRGs. Thus, localized sympathetic blockade may offer a novel therapeutic approach for the clinical relief of CIPN.
Preparing for Discharge From the Neonatal Intensive Care Unit

BACKGROUND: Discharge readiness is a key determinant of outcomes for families in the NICU. Since 2003, using a broad set of outcome and process measures, we have conducted an ongoing quality improvement initiative to improve the discharge preparation process in our NICU and readiness of families being discharged from the NICU. METHODS: Iterative improvements to the discharge preparation process were made by a multidisciplinary committee. Discharge readiness was measured by using a parental and nurse survey for all families discharged from our NICU. Primary outcome measures included parental self-assessment of discharge readiness and nurse assessment of the family’s emotional and technical discharge readiness. Secondary outcome measures included assessment of specific technical skills and emotional factors. Process measures included nursing familiarity with family at discharge. Improvement over time was analyzed by using statistical process control charts. RESULTS: Significant improvement was seen in all primary outcome measures. Family self-assessment of discharge readiness increased from 85.1% to 89.1%; nurse assessment of the family’s emotional discharge readiness increased from 81.2% to 90.5%, and technical discharge readiness increased from 81.4% to 87.7%. Several secondary outcome measures revealed significant improvement, whereas most remained stable. Nurse familiarity with the family at discharge increased over time. CONCLUSIONS: Quality improvement methodology can be used to measure and improve discharge readiness of families with an infant in the NICU. This model can provide the necessary framework for a structured approach to systematically evaluating and improving the discharge preparation process in a NICU.
Classical and nonclassical effects in surface hopping methodology for simulating coupled electronic-nuclear dynamics

In this paper, we analyze the detailed quantum-classical behavior of two alternative approaches to simulating molecular dynamics with electronic transitions: the popular fewest switches surface hopping (FSSH) method, introduced by Tully in 1990 [Tully, J. Chem. Phys., 1990, 93, 1061] and our recently developed quantum trajectory surface hopping (QTSH) method [Martens, J. Phys. Chem. A, 2019, 123, 1110]. Both approaches employ an independent ensemble of trajectories that undergo stochastic transitions between electronic surfaces. The methods differ in their treatment of energy conservation, with FSSH imposing conservation of the classical kinetic plus potential energy by rescaling the classical momentum when a surface hop occurs while QTSH incorporates a quantum force throughout the dynamics which leads naturally to the conservation of the full quantum-classical energy. We investigate the population transfer and energy budget of the surface hopping methods for several simple model systems and compare with exact quantum results. In addition, the detailed dynamics of the trajectory ensembles in phase space are compared with the quantum evolution in the Wigner representation. Conclusions are drawn.
The Habenular Receptor GPR151 Regulates Addiction Vulnerability Across Drug Classes

The habenula controls the addictive properties of nicotine but also densely expresses opioid and cannabinoid receptors. As such, identification of strategies to manipulate habenular activity may yield new approaches to treat substance use disorders. Here we show that GPR151, an orphan G protein-coupled receptor (GPCR) highly enriched in the habenula of humans and rodents plays a critical role in regulating habenular function and behavioral responses to addictive drugs. We show that GPR151 is expressed on axonal and presynaptic membranes and synaptic vesicles, and regulates synaptic fidelity and plasticity. We find that GPR151 associates with synaptic components controlling vesicle release and ion transport and couples to the G-alpha inhibitory protein Gαo1 to reduce cAMP levels. Stable cell lines expressing GPR151 confirm that it signals via Gi/o and are amenable to ligand screens. Gpr151 null mice show diminished behavioral responses to nicotine, and self-administer greater quantities of the drug, phenotypes rescued by viral re-expression of Gpr151 in the habenula. Gpr151 null mice are also insensitive to the behavioral actions of morphine and cannabinoids. These data identify GPR151 as a critical modulator of habenular function that controls addiction vulnerability across different drug classes.
Killing on the Ground and in the Mind: The Spatialities of Genocide in Belarus

In the late summer and fall of 1941, a Holocaust was taking place across the Soviet Union.¹ This was not the Holocaust of popular memory. There were no gas chambers, no train journeys, no barbed This was a “holocaust by bullets,” an intimate iteration of the Nazi genocidal project in which Jews were murdered at home, by killers who found themselves acting in the closest proximity to the victims.² If Auschwitz has come to symbolize the industrial, assembly-line face of the Holocaust, the murder of approximately one and a half to two million by the Einsatzgruppen (EG) mobile killing squads...
Language style matching as a measure of librarian/patron engagement in email reference transactions

Abstract In both virtual and in-person reference transactions, creating a supportive environment for patrons is the crucial first step. Evaluating librarians success in creating a supportive environment, however, is challenging. Language style matching (LSM) is a text analysis technique that measures the level of engagement between people. A high level of LSM has been shown to contribute to a sense of perceived support and other positive social outcomes. In this exploratory study, LSM is used to evaluate >1200 email threads from two virtual reference services to determine the level of engagement between patrons and librarians. Results show that email reference provided through the LibAnswers general reference service demonstrated a moderate to high level of LSM 67% of the time and email reference provided by a liaison librarian demonstrated a moderate to high level of LSM 84% of the time. By measuring how well librarians are meeting patrons' affective needs, LSM has the potential to provide a more holistic assessment of virtual reference services.
Taking Down Nonconsensual Pornographers: An Argument that 'Takedown' is the Only Meaningful Legal Remedy Against Perpetrators of Revenge Porn

The advent of social media and websites that feature user-generated content, in conjunction with the ease of taking and sharing digital photographs and video, has spawned the phenomenon of nonconsensual pornography. Nonconsensual pornography, known colloquially as “revenge porn” involves a perpetrator (whether an ex-romantic partner or not) who distributes or shares sexually explicit depictions or depictions of a person in a state of nudity to third persons without consent and with no legitimate purpose. This Article explores the issues associated with combatting revenge porn and reviews the current regulatory environment. Based on this analysis, the authors conclude that any effective remedy must involve revenge porn legislation that provides a take-down requirement and brings Internet Service Providers and host sites within the scope of the regulatory scheme.
Provider networks and health plan premium variation.

Objective To examine how plan premiums are associated with physician network breadth, hospital network breadth, and hospital network quality on the Affordable Care Act's Health Insurance Marketplaces in all 50 states and the DC in 2016. Data sources Data on plan premiums and characteristics came from 2016 Robert Wood Johnson Foundation Health Insurance Exchange (HIX) Compare. Provider network information was obtained from Vericred. Hospital characteristics were obtained from CMS Hospital Compare and the American Hospital Association (AHA) survey. Study design We analyzed how plan premiums were associated with variations in physician network breadth, hospital network breadth, and hospital network quality using ordinary least square regressions with state-rating area fixed effects and carrier fixed effects. Principal findings Plan premiums were positively associated with physician network breadth and hospital network breadth. We find the following statistically significant results: a one standard deviation increase in physician network breadth was linked to a premium increase of 2.8 percent or $101 per year; a one standard deviation increase in hospital network breadth was linked to a premium increase of 2.4 percent or $86 per year. There was no significant association between premiums and hospital network quality, as measured by hospital star ratings and the inclusion of teaching hospitals or the top-20 hospitals nationwide. Conclusions Physician network breadth and hospital network breadth contributed positively to plan premiums. The roles of the two types of provider network breadth are quantitatively similar. Premiums appear to be insensitive to hospital network quality.
ENAMORARSE ANTES DE JUBILARSE: LAS CUATRO SOMBRAS DE MARTÍN SANTOMÉ

This article analyzes La tregua of Mario Benedetti. The study examines the different phases or rather the shades for which Martin Santome, main character of the novel, happened after an unexpected change upset his life: the death of his beloved Laura Avellaneda. The text is divided in four parts. The first one alludes to the topic of the retirement and how Martin Santome faces this moment with a certain degree of obsession. The second one is focused on the importance that the character of Laura Avellaneda has in Martin's life. The third one studies the elements that make their affective relationship something significant for both of them. Finally, the fourth one examines the motif of desolation that emerges as a result of Avellaneda’s death.
The Failed Promise of User Fees: Empirical Evidence from the U.S. Patent and Trademark Office

In an attempt to shed light on the impact of user-fee financing structures on the behavior of administrative agencies, we explore the relationship between the funding structure of the Patent and Trademark Office (PTO) and its examination practices. We suggest that the PTO's reliance on prior grantees to subsidize current applicants exposes the PTO to a risk that its obligatory costs will surpass incoming fee collections. When such risks materialize, we hypothesize, and thereafter document, that the PTO will restore financial balance by extending preferential examination treatment—that is, higher granting propensities and/or shorter wait times—to some technologies over others.
The Myogenesis Program Drives Clonal Selection and Drug Resistance in Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a pediatric cancer with features of skeletal muscle; patients with unresectable or metastatic RMS fare poorly due to high rates of disease recurrence. Here, we use single cell and single nucleus RNA-sequencing to show that RMS tumors recapitulate the spectrum of embryonal myogenesis. Using matched patient samples from a clinical trial and orthotopic patient-derived xenografts (O-PDXs), we show chemotherapy eliminates the most proliferative component with features of myoblasts; after treatment, the quiescent immature population with features of paraxial mesoderm expands to reconstitute the developmental hierarchy of the original tumor. We discovered that this paraxial mesoderm population is dependent on EGFR signaling and is sensitive to EGFR inhibitors. Taken together, this data serves as a proof-of-concept that targeting each developmental state in RMS is an effective strategy for improving outcomes by preventing disease recurrence.
Study Abroad as a Means of Unpacking Pedagogical Complexity in Context

While teacher education programs are increasingly creating short-term study abroad programs to support developing teacher interculturality, programs often focus on schools typical of the host country. Few programs target a specific philosophical approach and its enactment in classrooms. This case study focuses on a two-week trip to the city of Reggio Emilia and other cities in northern Italy. The program was intended to support students in deeper understandings of the Reggio Emilia approach as well as the ways in which the approach is culturally embedded within northern Italy with the goal of students recognizing more profoundly how the approach adapts to international contexts (e.g., the United States). Students studied the Reggio Emilia approach (an approach previously encountered in university courses) and its practical application in the municipal infant/toddler centers and preschools in the city. Students demonstrated understandings of the approach and the enactment of the Reggio Emilia approach in the local context. This led to deep reflections of themselves as teachers and learners.
Focus on Pharmacotherapy for Irritable Bowel Syndrome with Constipation

Irritable bowel syndrome with constipation is a common disorder that significantly impairs quality of life. There are now multiple classes of therapeutics that have been shown via rigorous clinical testing to improve the abdominal and bowel symptoms attributed to irritable bowel syndrome with constipation. These include the secretagogues (lubiprostone, linaclotide, plecanatide, tenapenor) and the prokinetic agent tegaserod. This article highlights the pivotal evidence for these agents and most recent treatment guidance from the major North American gastroenterological societies. When pharmaceuticals are used, a patient-specific approach based on efficacy, safety, tolerability, access, and affordability is recommended.
Altered Ocular Fibrillin Microfibril Composition in Mice With a Glaucoma-Causing Mutation of Adamts10.

Purpose Previously, we identified a G661R mutation of ADAMTS10 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 10) as being disease causative in a colony of Beagles with inherited primary open-angle glaucoma (POAG). Mutations in ADAMTS10 are known to cause Weill-Marchesani syndrome (WMS), which is also caused by mutations in the fibrillin-1 gene (FBN1), suggesting functional linkage between ADAMTS10 and fibrillin-1, the principal component of microfibrils. Here, we established a mouse line with the G661R mutation of Adamts10 (Adamts10G661R/G661R) to determine if they develop features of WMS and alterations of ocular fibrillin microfibrils. Methods Intraocular pressure (IOP) was measured using a TonoLab rebound tonometer. Central cornea thickness (CCT), anterior chamber depth (ACD) and axial length (AL) of the eye were examined by spectral-domain optical coherence tomography. Sagittal eye sections from mice at postnatal day 10 (P10) and at 3 and 24 months of age were stained with antibodies against fibrillin-1, fibrillin-2, and ADAMTS10. Results IOP was not elevated in Adamts10G661R/G661R mice. Adamts10G661R/G661R mice had smaller bodies, thicker CCT, and shallower ACD compared to wild-type mice but normal AL. Adamts10G661R/G661R mice displayed persistent fibrillin-2 and enhanced fibrillin-1 immunofluorescence in the lens zonules and in the hyaloid vasculature and its remnants in the vitreous. Conclusions Adamts10G661R/G661R mice recapitulate the short stature and ocular phenotypes of WMS. The altered fibrillin-1 and fibrillin-2 immunoactivity in Adamts10G661R/G661R mice suggests that the G661R mutation of Adamts10 perturbs regulation of the fibrillin isotype composition of microfibrils in the mouse eye.
Compact 2x2 and 4x4 MIMO Antenna Systems for 5G Automotive Applications

In this paper, three Vehicular multiple-input multiple-output (MIMO) 5G antenna systems have been constructed from using a newly developed 5G cellular branched Monopole element are presented. The MIMO systems operates in the 5G frequency bands (617MHz- 5GHz) with a compact structure that allows for up to four elements to be integrated in the same Sharkfin. The 3 configurations of MIMO systems have been simulated using HFSS, measured on a 1-meter ground plane (GND), then measured on a vehicle roof and the individual antenna parameters in terms of reflection coefficient and efficiency have captured. The MIMO antenna systems performance in terms of passive isolation, combined radiation pattern, envelope correlation coefficient (ECC), and diversity gain (DG) have been reported and discussed.
The clinical course and role of surgery in pediatric malignant peripheral nerve sheath tumors: a database study.

OBJECTIVE Malignant peripheral nerve sheath tumors (MPNSTs) are rare tumors found throughout the body, with their clinical course in children still not completely understood. Correspondingly, this study aimed to determine survival outcomes and specific clinical predictors of survival in this population from a large national database. METHODS All patients with MPNSTs aged ≤ 18 years in the US National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Data were summarized, and overall survival was modeled using Kaplan-Meier and Cox regression analyses. RESULTS A total of 251 pediatric patients with MPNSTs (132 [53%] females and 119 [47%] males) were identified; the mean age at diagnosis was 13.1 years (range 1-18 years). There were 84 (33%) MPNSTs located in the extremities, 127 (51%) were smaller than 1 cm, and 22 (9%) had metastasis at the time of diagnosis. In terms of treatment, surgery was pursued in 187 patients (74%), chemotherapy in 116 patients (46%), and radiation therapy in 129 patients (61%). The 5-year overall survival rate was estimated at 52% (95% CI 45%-59%), with a median survival of 64 months (range 36-136 months). Multivariate regression revealed that older age (HR 1.10, p < 0.01), metastases at the time of diagnosis (HR 2.14, p = 0.01), and undergoing biopsy only (HR 2.98, p < 0.01) significantly and independently predicted a shorter overall survival. Chemotherapy and radiation therapy were not statistically significant. CONCLUSIONS In this study, the authors found that older patient age, tumor metastases at the time of diagnosis, and undergoing only biopsy significantly and independently predicted poorer outcomes. Only approximately half of patients survived to 5 years. These results have shown a clear survival benefit in pursuing maximal safe resection in pediatric patients with MPNSTs. As such, judicious workup with meticulous resection by an expert team should be considered the standard of care for these tumors in children.
Plasma for Crewed Transit and Planetary Habitation

As human exploration moves beyond low Earth orbit, innovative life support and resource production systems become forerunners for human colonization. Plasma systems allow for complex chemical processes while mitigating consumable needs. Plasma technology and applications can redefine the space environment. With this, scientists at NASA are looking to close known space technology gaps and create a paradigm shift in space-based applications. NASA’s Kennedy Space Center is exploring the use of low-temperature plasma for applications in agriculture, sanitation, regolith reduction, waste gasification, water activation, and nutrient recovery techniques. Using low temperature plasmas, we report on the success criteria and experimental results for plasma applications for crewed transit and planetary habitation.
REGULATORY MECHANISMS IN THE BIOSYNTHESIS OF ISOLEUCINE AND VALINE. I. GENETIC DEREPRESSION OF ENZYME FORMATION.

Ramakrishnan, T. (Yale University, New Haven, Conn.), and Edward A. Adelberg. Regulatory mechanisms in the biosynthesis of isoleucine and valine. I. Genetic derepression of enzyme formation. J. Bacteriol. 87:566–573. 1964.—A total of 60 mutants of Escherichia coli K-12 resistant to 10−2m valine were isolated from the valine-sensitive F′ strain AB1206. Conjugation experiments showed that in five of these mutants the valine-resistance locus is closely linked to the structural genes governing isoleucine-valine biosynthesis. In these five valine-resistant mutants, three enzymes of the isoleucine-valine pathway were found to be coordinately derepressed: l-threonine deaminase, dihydroxy acid dehydrase, and transaminase B. Two other enzymes of this pathway, the condensing enzyme and the reductoisomerase, were unaffected. The mutation from valine-sensitivity to valine-resistance appears to have altered an operator locus, because the derepressed state is dominant over the repressed state in diploids heterozygous for the valine-resistance locus. The valine-resistant mutants excrete isoleucine into the medium. The significance of these findings with respect to the valine-sensitivity of E. coli K-12 and the regulation of the biosynthesis of isoleucine and valine by this organism are discussed.
Structural Analysis of the Light Subunit of the Entamoeba histolytica Galactose-specific Adherence Lectin*

Adherence of Entamoeba histolytica trophozoites to colonic mucins and resistance to lysis by the membrane attack complex of complement are mediated by a galactose- and N-acetyl-D-galactosamine-specific cell-surface lectin. This lectin is a heterodimeric glycoprotein of heavy (170 kDa) and light (35/31 kDa) subunits. In this work, the amino acid sequence and membrane anchor of the light subunit were analyzed. The light subunit cDNA encoded a protein with a calculated molecular mass of 32 kDa containing two potential sites for N-linked glycosylation and putative amino- and carboxyl-terminal signal sequences characteristic of glycosylphosphatidylinositol (GPI)-anchored proteins. No classical carbohydrate-binding domains common to C- or S-type eukaryotic lectins were detected by sequence analysis of either the heavy or light subunits, leaving the location of the ligand-binding site of the lectin unknown. Analysis of restriction enzyme-digested E. histolytica DNA by Southern blotting was consistent with the presence of more than one light subunit gene. Two light subunit isoforms of 31 and 35 kDa were identified by SDS-polyacrylamide gel electrophoresis analysis of affinity-purified lectin, and the isoforms were shown on two-dimensional gel analysis to form distinct 170/35- and 170/31-kDa heterodimers. The amino acid compositions and cyanogen bromide peptide patterns of the two light subunit isoforms were nearly identical. The 35-kDa isoform labeled more efficiently than the 31-kDa isoform with [3H]glucosamine, while only the 31-kDa isoform labeled with [3H]myristate and [3H]palmitate. Nitrous acid deamination released lipid from the 31-kDa isoform, which co-migrated on thin layer chromatography with acylphosphatidylinositol, a component of some GPI anchors. Gas chromatography and mass spectrometry of the deamination product from the 31-kDa subunit identified both myo- and chiro-inositols, supporting the presence of a GPI membrane anchor. The covalent association of a transmembrane protein with a GPI-anchored protein, as suggested by the cDNA sequences of the lectin heavy and light subunits, is novel and suggests unique roles for the two subunits in the pathogenesis of amebiasis.
A single dominant gene for downy mildew resistance in broccoli

Downy mildew, incited by Peronospora parasitica (Pers.: Fr.) Fr., is a destructive disease of broccoli (Brassica oleraceaL., Italica Group). Resistant cultivars represent a desirable control method to provide a practical, environmentally benign, and long-term means of limiting damage from this disease. Doubled-haploid (DH) lines developed by us exhibit a high level of downy mildew resistance at the cotyledon stage. To determine the mode of inheritance for this resistance, a resistant DH line was crossed to a susceptible DH line to make an F1, from which F2 and backcross (BC) populations were developed. All populations were evaluated for response to artificial inoculation with P. parasitica at the cotyledon stage. All F1 plants (including reciprocals) were as resistant as the resistant parent, indicating no maternal effect for this trait. F2 populations segregated approximately 3resistant to 1 susceptible, BC populations using the resistant parent as the recurrent parent contained all resistant plants, and the BC to the susceptible parent segregated 1 resistant to 1 susceptible. These results indicate that resistance is controlled by a single dominant gene. This gene should be easily incorporated into F1 hybrids and used commercially to prevent downy mildew at the cotyledon stage.
Supraventricular tachycardia in the newborn with onset in utero

Abstract A report of congenital supraventricular tachycardia discovered in utero is presented. This is the fourth such case reported in the literature bringing to 13 the total number of infants found with congenital paroxysmal tachycardia. The markedly elevated fetal heart rate may be found early in the third trimester but usually is discovered in the last month of gestation. Cyanosis and dyspnea are often present, cardiac enlargement may be observed, and the electrocardiographic tracings are diagnostic. Cardiac failure has been seen as a sequela. However, digitalis has been effective in all but one of the cases where it has been used, both for the initial attacks and the recurrences. Follow-up studies have demonstrated no abnormal findings in all but one case.
Drug abuse in the hospitality industry.

Drug and alcohol abuse in the hospitality industry is an ongoing problem, reflective of business as a whole. A series of surveys were conducted at national drug rehabilitation centers seeking information from patients currently or formerly employed in the hotel and restaurant industry. The author identifies a number of problem indicators and makes recommendations relevant to resolutions. This article is available in Hospitality Review: http://digitalcommons.fiu.edu/hospitalityreview/vol11/iss2/9 Drug Abuse in the Hospitality Industry
The Rainmaker in Today's Professional Service Organizations

ABSTRACT Professional service firms have relied heavily in the past on a small number of rainmakers-people who have influence and bring business into their firms. In today's competitive marketplace, everyone in the organization must be involved in the practice development process. This paper, based on a series of interviews with accounting professionals, identifies the roles and responsibilities for practice development inherent at every stage of the professional accountant's career path. Additionally, the roles and responsibilities of marketing professionals in professional service firms are also considered.
Impact breaching of Europa's ice: Constraints from numerical modeling

Numerical simulations show that impactors can penetrate Europa's ice, creating conduits to the underlying ocean. Breaching becomes inevitable when transient cavity depth exceeds 90% of ice thickness. Results indicate that a 0.5 km comet would penetrate 5 km ice, and a 5 km comet could breach 40 km ice. Thinner ice would be breached more frequently, thicker ice less so, but even the 40 km upper estimates for ice thickness would be penetrated by comets with recurrence intervals less than 250 Ma. If actual ice thickness is 8–13 km (indicated by comparing Europan and simulated crater geometries), the ocean could be exposed by impactors in the range 0.7–1.5 km, which have recurrence intervals ≈3 to 7 Ma. Thus, it seems that Europa's ice has been penetrated often in the past and possibly in geologically recent time. The largest known impact sites, Callanish and Tyre, probably represent transition from craters to penetrating impacts. The geomorphic expression of full penetration must exist on the surface; chaos terrain is a candidate. Astrobiological materials could be transported to the ocean via these impact-created conduits.
Gonadotropin-releasing hormone axons target the median eminence: in vitro evidence for diffusible chemoattractive signals from the mediobasal hypothalamus.

The projection of GnRH neurons to the median eminence of the medial basal hypothalamus (MBH) is established early in development and is also seen when preoptic area-derived GnRH cell-containing grafts are placed in the third ventricle of hypogonadal mice. To further study the factors directing GnRH axonal targeting, we cultivated embryonic or postnatal day 1 preoptic area with a coexplant on collagen- and laminin-coated membranes in insert chambers. After 7 days of culture, GnRH-immunoreactive fibers extended significantly farther and in greater number onto the sector of membrane facing a MBH coexplant than in the opposite sector, but not toward coexplants of control tissue. Moreover, such effects were specific, as outgrowth of a general axonal population, immunoreactive for growth-associated protein 43 was not influenced by the presence of the MBH. Preferential GnRH outgrowth toward the MBH was established early and was maintained during 10 days of culture. The importance of substrate-derived guidance wa...
Stereoselectivity of cyclopropylchlorocarbene

Abstract Cyclopropylchlorocarbene adds to cis -butene (25°) with a 4.6:1 preference for the syn Cl— anti -cyclopropyl mode of addition, more than twice the stereoselectivity of phenylchlorocarbene in the analogous reaction.
The use of Neutral Red as an intracellular pH indicator in rat brain cortex in vivo

Abstract Intracellular pH in the intact, normally perfused rat brain cortex was determined by rapid scanning reflectance spectrophotometry of Neutral Red. Neutral Red, a pH indicator dye, was administered intraperitoneally to rats. Reflectance spectra recorded from the exposed dural surface of 11 anesthetized rats were used to calculate an intracellular pH of 7.04 ± 0.01. Detailed studies on the interactions of the dye with brain tissue were carried out in vitro to define the in vivo calibration curves. In addition, the physiological effect of dye administration on systemic blood pressure was determined, as well as uptake curves for Neutral Red into plasma and brain. It is concluded that Neutral Red can be used as an in vivo brain intracellular pH indicator and compares favorably with other methods of brain intracellular pH measurement with respect to accuracy, sensitivity, noninvasiveness, and stability and has the potential to exceed any existing method in time resolution.
Critical appraisal of efficacy and safety of abatacept in the treatment of refractory rheumatoid arthritis

Rheumatoid arthritis is a chronic, progressive, autoimmune disease that leads to significant disability and premature mortality. Various treatment options are available, but the foundation of treatment includes nonbiologic and biologic disease-modifying antirheumatic drugs. The incidence of patients with rheumatoid arthritis refractory to first-line agents is estimated to be at least 20%. Abatacept, a T cell costimulation modulator, is the first agent to interfere with full T cell activation by competing with CD28 for binding of CD80 and CD86, which results in decreased secretion of proinflammatory cytokines and autoantibody production. Current American College of Rheumatology treatment guidelines recommend abatacept for patients with at least moderate disease activity and a poor prognosis demonstrating an inadequate response to other agents. Several key Phase III trials have been conducted to evaluate the efficacy and safety of abatacept in patients with an inadequate response to methotrexate or anti-tumor necrosis factor alpha therapy. Response rates in all trials showed statistically significant improvements compared with placebo according to American College of Rheumatology criteria for disease improvement. The most common adverse event report in patients receiving abatacept was infection; however, the frequency of adverse events was similar to placebo. Abatacept is a safe and effective rheumatoid arthritis treatment for patients with an inadequate response to methotrexate or anti-tumor necrosis factor alpha therapy.
The Nature of the “Rate Base” in the Regulation of Public Utilities

I. An impasse in analysis of the "rate base" derives from inadequate examination of the theoretical case for appraisal methods of construction, 299.— II. The economic desiderata of utility rates cannot be attained by administrative determination of service charges from a "rate base," however constructed, 303.— III. The assumption that the "rate base" has a rate-determining function is therefore erroneous, 311.— IV. Recognition that the "rate base" is an earning base only is essential to intelligent appraisal of accounting methods of construction, and of the problems of public utility regulation, 314.
Real-Time Driving Simulation of Magneto-Rheological Active Damper Stryker Suspension

Abstract : Real-time driving simulations are an important tool for verifying vehicle and vehicle component designs with a driver in the loop. They not only provide a cost effective solution but also an ability to verify designs in a safe and controlled operating environment. A real-time driving experiment has been developed for Stryker to compare the ride and handling performance of a baseline passive suspension to that of a Magneto-Rheological (MR) semi-active damper suspension. The Tank Automotive Research Development and Engineering Center (TARDEC) has integrated this new suspension into a real time vehicle dynamics model of the Stryker using the MR suspension model developed by the Original Equipment Manufacturer (OEM). Using this real-time model and the TARDEC Ride Motion Simulator (RMS), TARDEC associates, along with associates from the Stryker Program Management office and the suspension OEM were able to drive and compare the passive and MR Stryker in a virtual environment. This paper describes the simulation model, motion simulator integration, operating scenarios, terrain modeling, model validation, and subjective as well as objective results from this study.
RECURRENT UROLITHIASIS AFTER AUGMENTATION GASTROCYSTOPLASTY

Urolithiasis has become an increasingly reported longterm complication following enterocystoplasty in children.' In contrast, the absence of stone formation after gastrocystoplasty has been a major benefit of using stomach for bladder augmentation. To date, only 1 case of stone formation after gastrocystoplasty has been reported in the urological literature.' We report on a child with recurrent stone formation following gastrocystoplasty.
The Impact of Juvenile Curfew Laws on Arrests of Youth and Adults

Youth curfew ordinances are a widely touted, yet little studied, policy tool available to local police departments. This paper evaluates the effectiveness of curfew ordinances by comparing the arrest behavior of various age groups within a city before and after curfew enactment. The evidence suggests that curfews are effective at reducing both violent and property crimes committed by juveniles below the statutory curfew age. Arrests of adults and youth above the curfew age also appear to decrease in the wake of curfew enactment; however, these effects are smaller and statistically insignificant. Copyright 2011, Oxford University Press.
Tensile Testing of MEMS Materials at High Temperatures

This paper presents three kinds of high-temperature test methods for three different materials along with the results. Resistively heated polysilicon film 3.5 micron thick shows ductile behavior at 500°C. Resistively heated nickel 200 microns thick shows decreasing strength at 400°C. Furnace heated silicon carbide 200 microns thick maintains its strength at 1000°C. Strain is measured by laser-based interferometry in the first two cases to obtain complete stress-strain curves, while force-displacement is measured in the third case.
Stalemate and Stagnation in Turkish Democratization: The Role of Civil Society and Political Parties

Both civil society organizations (CSOs) and political parties are expected to be vital actors in democratic societies, yet the ideal relationship between the two types of groups has not been fully explored. This article analyses how the interaction between CSOs and political parties has affected democratic consolidation in contemporary Turkey. Through personal interviews with leaders of both types of groups, the study finds that traditional power relations have shifted to include a greater number of political actors. Islamists, who were previously peripheral in politics, have joined the traditionally dominant secular nationalists at the ‘centre’ of political power. However, instead of increased pluralism, the study finds Turkish society now polarized along secularist/Islamist lines, both in political parties and among CSOs. While restrictions against non-governmental organizations have been lifted in recent years and the number of groups has grown, most are still viewed as ‘arms’ of political parties, lac...
Age-Related Reductions in the Activation of Mitogen-Activated Protein Kinases p44mapk/ERK1 and p42mapk/ERK2 in Human T Cells Stimulated via Ligation of the T Cell Receptor Complex

Age-related changes in the functional properties of human T cells are well described, but less is known about possible changes in T cell signaling pathways. The signaling pathways mediated by mitogen-activated protein kinases (MAPK) are considered essential for normal cellular growth and function. Several stimuli trigger MAPK activation in human T cells and MEK (MAPK or ERK kinases) are immediate upstream inducers of MAPK activation. The current study investigated if aging might influence the activation and expression of MAPK and MEK in human T cells. Exposure of peripheral blood T cells from young subjects to PHA or cross-linked anti-CD3 monoclonal antibodies stimulated rapid increases in MAPK and MEK enzymatic activity. By contrast, significant reductions of MAPK and MEK activation were observed in stimulated T cells from 7 of 13 elderly subjects. Kinetic studies showed that the age-related impairments represented reduction in both the levels and duration of MAPK activation. In addition, Western immunoblot analysis did not reveal significant age-related differences in T cell expression of p42mapk/ERK2, p44mapk/ERK1, or MEK, suggesting impairments in upstream inducers of MEK/MAPK activation. Other experiments determined if agents that directly stimulate upstream Ras or Raf kinase components of the early MAPK cascade might reverse the age-related impairments of MAPK activation. Treatment of elderly T cells with fluoroaluminate (AlF(-)4), phorbol esters/Ca2+ ionophores, or okadaic acid stimulated increased MAPK activation compared to anti-CD3. However, these agents failed to restore MAPK activation in elderly T cells to the levels seen in young T cells. These results suggest that aberrancies in the MAPK activation cascade may underlie the age-related reductions of MAPK activation in human T cells stimulated via the TCR/CD3 complex.
Reducing cluster size for computing remedial adjustments for voltage and loading violations on the power system

A technique was earlier proposed by the authors [1], [2] for solving sectional outbreaks of voltage and overload violations on large electric power transmission systems by finding relatively small size clusters of controls and violated as well as nonviolated network elements to which they react sensitively. Since the clusters are as much as two orders of magnitude smaller than the entire system, immense savings of computation are possible. Unfortunately the size of the clusters can not be well regulated a priori so that there is a possibility for oversize clusters. This paper introduces an effective algorithm for splitting up such undesirably large clusters by inactivating a few well chosen controls. It was necessary to develop some new results in graph theory to develop the new algorithm.
Novel electron impact-induced hydrogen rearrangements in the mass spectra of organorhenium hydrides and alkyls

Abstract The electron impact-induced hydrogen rearrangement of an organorhenium hydride is described, in which the remote hydrogen is identified to be the hydride hydrogen by deuterium-labelling experiments. Rearrangement accompanies intra-ligand cleavage of the triphenylphosphine ligand, an unusual event in itself, resulting in neutral loss of benzene from the molecular ion. Closer examination of the electron impact mass spectra of a series of organorhenium alkyl compounds indicates that another rearrangement of a beta hydrogen from the alkyl ligand onto the metal center produces the rhenium hydride, which then undergoes rearrangement and neutral loss. These two rearrangements serve to explain the heretofore anomalous fragment peaks in the spectra of the organorhenium alkyl compounds.
A FAMILY OF UNCONVENTIONAL MYOSINS FROM THE NEMATODE CAENORHABDITIS ELEGANS

The unconventional myosins are a superfamily of actin-based motor proteins that are expressed in a wide range of cell types and organisms. Thirteen classes of unconventional myosin have been defined, and current efforts are focused on elucidating their individual functions in vivo. Here, we report the identification of a family of unconventional myosin genes in Caenorhabditis elegans. The hum-1, hum-2, hum-3 and hum-6 (heavy chain of an unconventional myosin) genes encode members of myosin classes I, V, VI and VII, respectively. The hum-4 gene encodes a high molecular mass myosin (ca 307 kDa) that is one of the most highly divergent myosins, and is the founding and only known member of class XII. The physical position of each hum gene has been determined. The hum-1, hum-2 and hum-3 genes have been mapped by extrapolation near previously uncharacterized mutations, several of which are lethal, identifying potentially essential unconventional myosin genes in C. elegans.
Moving on in Schizophrenia Research to the next decade.

Research on the biology of schizophrenia has been ongoing for several decades. As editors of this journal and researchers as well, both Dr. Nasrallah and I have participated in over 30 years of progress in this field. A comprehensive array of current ongoing research in this field can be found by attending the annual schizophrenic congresses and keeping up with their corresponding reports (e.g. Baharnoori et al., 2010). Much of the accumulation of new “facts” has been driven over the years by the application of new technology, such as in brain imaging (CT and MRI) and in genetics (mapping the genome). On the other hand, hypotheses about origins of schizophrenia have advanced at a slower rate, although there is a growing recognition that not only can one conceptual model not account for all of schizophrenia, but several models may account for pathology that crosses clinical diagnostic boundaries. Clearly, there is a renewed focus on examining biological deviances from normal that may put one at greater risk for mental illness, but not necessarily be pathognomonic of one specific clinical entity. In a series of papers (Tandon et al., 2008a, 2008b, 2009, 2010; Keshavan et al., 2008, 2011, in this issue), Drs. Keshavan, Nasrallah and Tandon began by reviewing the facts about schizophrenia and whether they have changed since they were outlined in the inaugural issue of Schizophrenia Research (Wyatt et al., 1988). They have meticulously reviewed all aspects of the biology of the disorder called schizophrenia that have been supported by strong findings in the literature to date, from its biochemistry and brain pathology to its newest treatments available. In this last paper, they bring together all these data and try to “connect the dots” that draw seemingly disparate results together toward a unified understanding of what schizophrenia really is. They conclude by providing several key directions for the next generation of schizophrenia research. Many senior leaders in this field have also attempted in their own ways to rise to this challenge (e.g. Insel, 2010) and each individual who has studied schizophrenia and treated patients with this illness over these decades has developed his/her own framework for how to interpret the deluge of data that continues to accumulate, some inconsistent and others non replicable. However, this field can no longer be one of whether you believe in one speculative hypotheses or an alternative one, but rather a formulation of a picture that is now clearly evidence based, although complex. Furthermore, it is imperative as Keshavan and colleagues emphasize, that the isolated pieces be integrated together into a more formative view of the “elephant” as a whole.
Application of fluorescent in situ hybridization in the mouse xenograft model of human fat grafting.

Background Determining the optimal technique for autologous fat grafting requires elucidation of the engraftment process at the cellular level. The nude mouse xenograft model for autologous human fat grafting is an excellent tool to evaluate the incorporation of grafted fat into the recipient. Objectives The authors present a murine xenograft model that uses fluorescent in situ hybridization (FISH) to differentiate between murine (host) cells and human (grafted) cells. Methods Fat grafts were harvested from human abdominoplasty specimens, fixed, embedded in paraffin blocks, and cut into 5 µm sections. The sections were stained and used for in situ hybridization with fluorescently labeled murine and human nucleic acid reagents. A fluorescence microscope was used for photographic analysis of the grafts, allowing identification of murine and human cell populations based on the wavelength at which they stained. DAPI (4,'6-diamidino-2-phenylindole) counterstaining was also applied to confirm that the images obtained represented cell nuclei. Results At 20× magnification, strong species-specific staining of cells was seen within the tissue sections, which allowed the authors to easily discriminate between graft-derived and host-derived cells. Using this approach, human fat xenografts were revealed to comprise a complex matrix of closely interacting graft- and host-derived structures. Conclusions FISH has the potential to be a powerful technique for distinguishing between murine and human cells in the nude mouse xenograft model of human fat grafting. By applying this technique, it may be possible to evaluate the engraftment process at a cellular level, which may ultimately allow clinicians to obtain more predictable results with grafted fat.