cssi/SciSciGPT-SciSciNet huggingface dataset:
Insights into the ClC-4 Transport Mechanism from Studies of Zn2+ Inhibition

The CLC family of chloride channels and transporters is a functionally diverse group of proteins important in a wide range of physiological processes. ClC-4 and ClC-5 are localized to endosomes and seem to play roles in the acidification of these compartments. These proteins were recently shown to function as Cl−/H+ antiporters. However, relatively little is known about the detailed mechanism of CLC-mediated Cl−/H+ antiport, especially for mammalian isoforms. We attempted to identify molecular tools that might be useful in probing structure-function relationships in these proteins. Here, we record currents from human ClC-4 (hClC-4) expressed in Xenopus oocytes, and find that Zn2+ inhibits these currents, with an apparent affinity of ∼50 μM. Although Cd2+ has a similar effect, Co2+ and Mn2+ do not inhibit hClC-4 currents. In contrast, the effect of Zn2+ on the ClC-0 channel, Zn2+-mediated inhibition of hClC-4 is minimally voltage-dependent, suggesting an extracellular binding site for the ion. Nine candidate external residues were tested; only mutations of three consecutive histidine residues, located in a single extracellular loop, significantly reduced the effect of Zn2+, with one of these making a larger contribution than the other two. An analogous tri-His sequence is absent from ClC-0, suggesting a fundamentally different inhibitory mechanism for the ion on hClC-4. Manipulations that alter transport properties of hClC-4, varying permeant ions as well as mutating the “gating glutamate”, dramatically affect Zn2+ inhibition, suggesting the involvement of a heretofore unexplored part of the protein in the transport process.
Tyrosine kinase inhibitors for epidermal growth factor receptor gene mutation–positive non-small cell lung cancers: an update for recent advances in therapeutics

The presence of activating gene mutations in the epidermal growth factor receptor of non-small cell lung cancer patients is predictive (improved progression-free survival and improved response rate) when treated with small molecule tyrosine kinase inhibitors such as gefitinib, erlotinib and afatinib. The two most common mutations that account for greater than 85% of all EGFR gene mutations are in-frame deletions in exon 19 (LREA deletions) and substitution in exon 21 (L858R). Exon 18 mutations occur much less frequently at about 4% of all EGFR gene mutations. Together, exon 19 deletion and exon 21 L858R gene substitution are present in about 10% of Caucasian patients and 20-40% of Asian patients with non-small cell lung cancer. T790M gene mutation at exon 20 is associated with acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. Early studies showed that activating EGFR gene mutations are most common in patients with adenocarcinoma histology, women, never smokers and those of Asian ethnicity. A recent multi-center phase III trial suggested that frontline epidermal growth factor receptor tyrosine kinase inhibitor therapy with afatinib is associated with improved progression-free survival compared to chemotherapy regardless of race. Moreover, guidelines now suggest EGFR gene mutation testing should be conducted in all patients with lung adenocarcinoma or mixed lung cancers with an adenocarcinoma component, regardless of characteristics such as smoking status, gender or race. The success of targeted therapies in non-small cell lung cancer patients has changed the treatment paradigm in metastatic non-small cell lung cancer. However, despite a durable response of greater than a year, resistance to epidermal growth factor receptor tyrosine kinase inhibitors inevitably occurs. This mini-review describes the clinically relevant EGFR gene mutations and the efficacy/toxicity of small molecule epidermal growth factor receptor tyrosine kinase inhibitors as targeted therapies for these gene mutations. Therapeutic strategies to overcome resistance, including emerging and novel therapies, are discussed.
Cisplatin and irinotecan in squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group.

Abstract Objective . To evaluate the combination of cisplatin and irinotecan as first-line treatment of patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix. Methods . Patients with no prior treatment for metastatic disease, presence of measurable tumors, performance status of 0 or 1, and adequate bone marrow, renal, and hepatic functions were potentially eligible for this trial. Cisplatin and irinotecan were given weekly at starting doses of 25 and 65 mg/m 2 , respectively, for three consecutive weeks. Cycles were to be repeated every 28 days with dose adjustments as required. Patient accrual was based on a two-stage design with at least seven responses out of 28 patients in the first stage required to proceed to a second stage of accrual seeking a response rate of 40% or better. Results . Of 34 patients entered onto the study, 31 were eligible and 27 were evaluable for response. Ten had received prior chemoradiation containing cisplatin. Among the five (two complete and three partial) observed responses, two were in the subset of patients who had received prior chemoradiation. This level of activity was deemed insufficient to warrant a second stage of accrual. Predominant toxicities were myelosuppression and gastrointestinal symptoms, although six patients experienced none of these adverse effects. Conclusion . At these doses, weekly cisplatin and irinotecan failed to demonstrate sufficient activity to undertake a phase III study. Although not apparent in this study, prior chemoradiation may affect response to platinum-based combinations and its impact should be considered in the design of future trials.
Hypomania in a Four-Year-Old

This case report of a 4-year-old boy has a particularly clear clinical history and pattern of hypomania. Besides hyperactivity and emotional lability, which has previously been described in the offspring of a bipolar parent, the boy displayed pathologically prolonged states of emotional arousal to minimal stimulus, as well as euphoria, overtalkativeness, irritability, episodic states of frenzied activity, and minor depressive feelings. Because the clinical picture was so clear, the identification of possible hypomanic behavior in other young children may be aided.
Women’s Movements in Latin America

This chapter explores several broad stages of women’s mobilization in contemporary Latin America. It first examines women’s mobilization in the 1970s and 1980s against authoritarian regimes and in favor of nationalist, class-based causes. This section focuses in particular on how women’s experiences of political opportunity structures, movement recruitment, framing, and identity-linked grievances have differed from those of male-dominated movements. I next analyze factors that shifted women toward greater feminist consciousness in the 1990s, and how women’s movements have grappled with autonomy from leftist political parties and the state. Finally, this chapter identifies several ongoing issues for women’s movements, implementation and enforcement of gender equity laws and policies, diversity among women, and the gendered implications of new regional social policies.
Committee on Physical Limnology, 1939-40

The members of this Committee are: Carl B. Brown, Soil Conservation Service, Washington, D.C.; C. S. Howard, United States Geological Survey, Washington, D.C.; Tom C. Mead, United States Bureau of Reclamation, Boulder City, Nevada; M. R. Miller, Agricultural Experiment Station, University of Nevada, Reno, Nevada; Dr. A. H. Wiebe, Tennessee Valley Authority, Norris, Tennessee; Professor Joseph Kittredge, Jr., University of California, Berkeley, California; Dr. Thomas C. Adams (Chairman), University of Utah, Salt Lake City, Utah. Appointments to the Committee were made February 16, 1940. It was directed to handle non-biological problems of limnology. Although much work has been done along this line, work which has very substantial scientific as well as immediately applicable value, the field of physical limnology has not been generally recognized as a separate one. Therefore, the Committee has been obliged to give more than usual consideration to its field of activity, and in the month intervening since its organization, has conducted correspondence between members with this in view.
Conceptual metaphor and embodied structures of meaning: A reply to Kennedy and Vervaeke

Abstract J. M. Kennedy and J. Vervaeke argue that my view of the bodily and imaginative basis of meaning commits me to a mistaken reductionism and to the erroneous view that metaphors actually impose structure on the target domain. I explain the sense in which image schemas are central to the bodily grounding of meaning, although in a way that is not reductionistic. I then show how conceptual metaphors can involve pre‐existing image‐schematic structure and yet can also be partially constitutive of the conceptual structure of the target domain. In this way human conceptual systems can be both rooted in patterns of our bodily interactions and at the same time can be subject to various kinds of imaginative development and extension.
Impact of Asian Dust Aerosol and Surface Albedo on Photosynthetically Active Radiation and Surface Radiative Balance in Dryland Ecosystems

We investigated the extent to which Asian dust can affect vegetation in dryland ecosystems through altering photosynthetically active radiation (PAR) and shortwave and longwave radiation components of the surface energy balance. Results show that dust decreases the surface radiative balance and total PAR. The diffuse component of PAR, however, increases with increasing dust load but then decreases after reaching a maximum at a certain optimum condition. The forcing efficiency ranges from −67.7 to −82.2 Wm−2 in total PAR and from −68.8 to −122.1 Wm−2 in surface radiative balance. The ratio of total PAR to downwelling shortwave flux remains nearly constant (%) similar to other aerosol types, while the ratio for the diffuse faction of PAR exhibits significant variations. The impact of dust on the gross photosynthetic rate varies among different types of crops. C4 plants such as corn tend to be less sensitive to the dust optical properties compared to C3 plants such as soybean and wheat.
T cell reactivity to MHC molecules: immunity versus tolerance

The specificity of mature CD8+ and CD4+ T lymphocytes is controlled by major histocompatibility complex (MHC) class I and class II molecules, respectively. The MHC class specificity of T cells is stringent in many assays, but is less evident when cells are supplemented with exogenous lymphokines. The repertoire of T cells is shaped through contact with MHC molecules in the thymus and involves a complex process of positive selection and negative selection (tolerance). Tolerance of immature T cells to MHC molecules can reflect either clonal deletion or anergy and results from intrathymic contact with several cell types, including epithelial cells and cells with antigen-presenting function. Unlike immature T cells, mature T cells are relatively resistant to tolerance induction. In certain situations partial unresponsiveness of mature T cells can be achieved by exposing T cells to foreign MHC molecules expressed on atypical antigen-presenting cells. Tolerance is rarely complete, however, and the precise requirements for tolerizing mature T cells are still unclear.
Technique and preliminary results of interstitial irradiation for recurrent glial tumors

We have conducted a phase-I clinical trial of CT-guided stereotactic implantation of Ir192 in the treatment of malignant astrocytomas. During the past year, 16 patients have been implanted with two to four catheters in the residual enchancing portion of their tumor. These patients represent 50% of our total experience with the CT compatible Leksell frame. Each catheter contains three to six high intensity (2.0 to 2.5 mg Ra equivalent) seeds with 0.5 cm separation between the sources. The total activity of Ir192 per implant has been 30–65 mg radium equivalent. In the 16 patients, 49 catheters have been placed, an average of three targets calculated per patient and no targets have been missed. The radiation exposure to personnel has been surveyed in detail and drops off to less than 2mr/hr six feet from the patient when our custom-built radiation shield is employed. We have reserved permanent implantation of I125 for patients with tumors in unusual locations (e.g., pineal) or for individuals with slowly growing nongliomatous lesions (i.e., meningioma). The tumor volumes have ranged from 12–120 cm3. Unique aspects of our implant procedure include the use of a Leksell frame already adapted to the GE-8800 scanner, the use of pre- and post-implant computerized treatment planning programs to determine the dose distribution profiles and the use of adjustable metal collars crimped to the outer catheters to provide ease of insertion, uniform pre-implant catheter length, and protection against source migration. Two of our patients have suffered from subacute radiation reactions, primarily due to delayed cerebral edema and both of these cases have largely resolved. We believe that it is technologically feasible to deliver 5000 rads to the tumor periphery in 50 hours without undue patient toxicity or environmental radiation hazard. The system we have been studying is fully compatible with the simultaneous use of mechanical cytoreduction, chemotherapy and interstitial hyperthermia.
Osteogenic sarcoma in 2 guinea pigs.

Summary A large tumour nodule arising from the 4th lumbar vertebra of a strain 2/N guineapig was observed: no metastases were detected. The other guineapig (strain 13IN) had multiple tumour masses, with lesions of osteogenic sarcoma in the lumbar vertebrae, pancreas, liver, stomach, lungs, kidneys and testis. The original site of the tumour was thought to be the upper lumbar vertebrae. Histologically these tumours consisted of a similar mixture of carcinoma with osteoid formation.
Pavement Management for Large Highway Networks

This paper presents the results of a special study which was conducted to determine how a heavily industrialized state, with a large highway network such as Pennsylvania, can develop a Pavement Management System (PMS). The study consisted of an evaluation of what other states have done to implement a PMS and how their work can be expanded for Pennsylvania’s purpose. The study also evaluated the various in-house PMS techniques which are currently being used by the Department, such as: Mays Meter roughness, Road Rater deflections, and distress surveys. A Pavement Management System was suggested for Pennsylvania and other large states that consisted of a modular implementation scheme. It was suggested that a PMS Development Group oversee the implementation of the system. The first module would consist of a complete inventory of the serviceability of the pavement network by Present Serviceability Index. The second module would be the development of a distress survey for prioritizing projects. Future modules would consist of prediction equations, life cycle costing, and optimization.
Clinical characteristics of angiotensinconverting enzyme inhibitor-induced angioedema

We present the cases of two patients with angiotensin-converting enzyme (ACE) inhibitor-induced angioedema that required intubation for life-threatening airway compromise. This side effect has been previously reported with all ACE inhibitors, but its incidence and potential for a fatal outcome may not be fully appreciated. A review of the literature reveals 227 reports of this reaction with an overall incidence of approximately 0.1% to 0.2%. The etiology is nonimmunogenic and thought to be related to accentuated bradykinin activity. There is no clinical profile that identifies patients at increased risk for this side effect. There are unique clinical characteristics to this idiosyncratic reaction: angioedema may suddenly occur even though the drug has been well tolerated for months or years; symptoms may regress spontaneously while the patient continues the medication, erroneously prompting an alternative diagnosis; the pathology has a special predilection for the tongue, a circumstance that renders orotracheal and nasotracheal intubation difficult; symptoms may progress rapidly despite aggressive medical therapy, necessitating emergency airway procedures; and a rebound phenomenon following successful medical therapy has been described. We recommend intensive medical treatment before angioedema is severe enough to thwart standard methods to ensure a protected airway. Once even minor angioedema is attributed to an ACE inhibitor, an alternative class of antihypertensive medication should be chosen. Individuals with a history of idiopathic angioedema probably should not be given ACE inhibitors.
Modulatory Effects of Plasma and Serum on T Lymphocyte Activation: Distinctive Patterns for Different Mitogens

Published reports have shown that fresh plasma, but not cryoprecipitate-depleted plasma or fresh serum, inhibits T cell activation by phytohemagglutinin (PHA). We sought to determine if this pattern of inhibition also characterized T cell responses to mitogens differing from PHA with regard to the cell surface molecules utilized for signal transduction. The activation system included colchicine, which limits the cells to one round of division, masking stimulatory factors that enhance proliferation by boosting the number of divisions per culture period. A distinctive modulatory pattern characterized T cell responses to each of 4 mitogens tested (PHA, anti-CD3 monoclonal antibody, desialyzed oxidized erythrocytes (DOE), pokeweed mitogen). Enhanced proliferative responses to anti-CD3 and DOE were observed in the presence of serum, and reflected an increased percentage of T cells expressing CD25. These findings suggest that concerns regarding a negative impact of plasma components on T cell responsiveness, wh...
Controllability and trajectory tracking for classes of cascade-form second order nonholonomic systems

We discuss classes of nonlinear systems with drift that can be reduced to the cascade of a linear system and a drift-free nonholonomic system. Building on previous work with amplitude-modulated sinusoids for trajectory tracking in drift-free systems, we present algorithms for configuration trajectory tracking in these dynamic settings. Results are demonstrated in simulation for representative examples.
Standardizing the standards.

Mol Syst Biol. 2: 2006.0010 The nice thing about standards is that there are so many to choose from. Andrew S Tannenbaum One of the most daunting aspects of using genomic technologies—including microarray, proteomic, metabolomic, and other approaches—is the sheer quantity of data that they produce. With thousands of biologically relevant molecules surveyed across (increasingly) large numbers of samples, interpretation of the data requires the use of computational approaches. And while many researchers thought that storing the data could simply build on our experiences with genome sequencing, it quickly became apparent that if one was to make sense of the results from any analysis, there was a need to store much more complex ancillary data than would be necessary for genome sequence. In 1999, as microarrays were establishing themselves as a truly viable technology, the Microarray Gene Expression Data Society (MGED; http://www.mged.org) arranged to define the critical information necessary to effectively analyze a microarray experiment and to describe a means of encoding that information. Through a series of discussions between interested parties, public presentations, and working group meetings, what emerged were the Minimal Information About a Microarray Experiment (MIAME) (Brazma et al , 2001; Ball et al , 2002, 2004) and MAGE‐ML (Spellman et al , 2002), an XML‐based markup language used for describing a microarray experiment. The early success of MIAME and its widespread adoption by scientific journals also exposed some of its weaknesses, including the need to develop domain‐specific extensions of MIAME to capture information about the experimental design and sample characteristics necessary for interpreting data coming, for example, from toxicology experiments (MIAME‐Tox; Sansone et al , 2005) and extensions to other domains such as in situ hybridizations (MISFISHIE, the Minimum Information Specification For In Situ Hybridization …
Communication avoiding successive band reduction

The running time of an algorithm depends on both arithmetic and communication (i.e., data movement) costs, and the relative costs of communication are growing over time. In this work, we present both theoretical and practical results for tridiagonalizing a symmetric band matrix: we present an algorithm that asymptotically reduces communication, and we show that it indeed performs well in practice.The tridiagonalization of a symmetric band matrix is a key kernel in solving the symmetric eigenvalue problem for both full and band matrices. In order to preserve sparsity, tridiagonalization routines use annihilate-and-chase procedures that previously have suffered from poor data locality. We improve data locality by reorganizing the computation, asymptotically reducing communication costs compared to existing algorithms. Our sequential implementation demonstrates that avoiding communication improves runtime even at the expense of extra arithmetic: we observe a 2x speedup over Intel MKL while doing 43% more floating point operations.Our parallel implementation targets shared-memory multicore platforms. It uses pipelined parallelism and a static scheduler while retaining the locality properties of the sequential algorithm. Due to lightweight synchronization and effective data reuse, we see 9.5x scaling over our serial code and up to 6x speedup over the PLASMA library, comparing parallel performance on a ten-core processor.
An interrater reliability study of the Luria-Nebraska Neuropsychological Battery Form-II quantitative scoring system☆

This study provides information on the interrater reliability of the quantitative scoring system of the Luria-Nebraska Neuropsychological Battery Form II (LNNB-II). The accuracy of each rater following a training procedure was also evaluated. Six college students served as raters, and participated in a 20-22-hour training procedure. This training procedure utilized a protocol similar to one used in previous interrater reliability studies performed with Form I. Following the training procedure, raters were asked to score two videotaped LNNB-II administrations in which a confederate portrayed test performance that was relatively straightforward to score, as well as more ambiguous test performance. Excellent interrater agreement and accuracy were found on the quantitative scoring on both tapes. Implications for training in administration and scoring are discussed.
Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state

Current models of stem cell biology assume that normal and neoplastic stem cells reside at the apices of hierarchies and differentiate into nonstem progeny in a unidirectional manner. Here we identify a subpopulation of basal-like human mammary epithelial cells that departs from that assumption, spontaneously dedifferentiating into stem-like cells. Moreover, oncogenic transformation enhances the spontaneous conversion, so that nonstem cancer cells give rise to cancer stem cell (CSC)-like cells in vitro and in vivo. We further show that the differentiation state of normal cells-of-origin is a strong determinant of posttransformation behavior. These findings demonstrate that normal and CSC-like cells can arise de novo from more differentiated cell types and that hierarchical models of mammary stem cell biology should encompass bidirectional interconversions between stem and nonstem compartments. The observed plasticity may allow derivation of patient-specific adult stem cells without genetic manipulation and holds important implications for therapeutic strategies to eradicate cancer.
Potentiation of lead-induced cell death in PC12 cells by glutamate: Protection by N-acetylcysteine amide (NACA), a novel thiol antioxidant

Oxidative stress has been implicated as an important factor in many neurological diseases. Oxidative toxicity in a number of these conditions is induced by excessive glutamate release and subsequent glutamatergic neuronal stimulation. This, in turn, causes increased generation of reactive oxygen species (ROS), oxidative stress, excitotoxicity, and neuronal damage. Recent studies indicate that the glutamatergic neurotransmitter system is involved in lead-induced neurotoxicity. Therefore, this study aimed to (1) investigate the potential effects of glutamate on lead-induced PC12 cell death and (2) elucidate whether the novel thiol antioxidant N-acetylcysteine amide (NACA) had any protective abilities against such cytotoxicity. Our results suggest that glutamate (1 mM) potentiates lead-induced cytotoxicity by increased generation of ROS, decreased proliferation (MTS), decreased glutathione (GSH) levels, and depletion of cellular adenosine-triphosphate (ATP). Consistent with its ability to decrease ATP levels and induce cell death, lead also increased caspase-3 activity, an effect potentiated by glutamate. Exposure to glutamate and lead elevated the cellular malondialdehyde (MDA) levels and phospholipase-A(2) (PLA(2)) activity and diminished the glutamine synthetase (GS) activity. NACA protected PC12 cells from the cytotoxic effects of glutamate plus lead, as evaluated by MTS assay. NACA reduced the decrease in the cellular ATP levels and restored the intracellular GSH levels. The increased levels of ROS and MDA in glutamate-lead treated cells were significantly decreased by NACA. In conclusion, our data showed that glutamate potentiated the effects of lead-induced PC12 cell death by a mechanism involving mitochondrial dysfunction (ATP depletion) and oxidative stress. NACA had a protective role against the combined toxic effects of glutamate and lead by inhibiting lipid peroxidation and scavenging ROS, thus preserving intracellular GSH.
A Morphological Appraisal of Wild Species in Section Arachis of Peanuts

Abstract The cultivated peanut, Arachis hypogaea L., is a member of section Arachis nom. nud. along with its tetraploid progenitor, A. monticola Krap. et Rig., four validly described diploid species, eight diploid species whose names have never been validly published, and a large collection of taxa discovered since 1975. Systematic relationships and possible species circumscriptors are assessed in section Arachis by means of numerical taxonomy. Seventy-three accessions were grown in the field and three randomly selected specimens of each accession were evaluated. Numerical techniques in the form of cluster and principal components analyses were used on 56 characters, including 20 reproductive, 30 vegetative, and six created variables. Most variation was observed for leaflet size and shape, followed by branching habits and flower size. Although grouping of accessions did not always conform to expectations based on published species descriptions, general relationships among taxa are evident from the analyse...
High signal-to-noise detection of rotational Raman scattering through refluorescent and dispersive atomic filters

We introduce new methods for capturing rotational Raman scattering that simultaneously suppress background scattering and have exceedingly high spectral dispersion at low wavenumbers. These methods are based on resonant absorption and refractive index dispersion of atomic vapor, and take advantage of the availability of tunable lasers. Three different configurations are presented. The first is an atomic notch transmission filter which is based on refluorescence from an optically thick atomic vapor cell. This configuration is demonstrated in air using mercury vapor at 254 nm. The second configuration is an atomic resonance prism cell which is demonstrated in CO2 using mercury vapor, again at 254 nm. The third configuration is a density gradient atomic vapor cell which uses rubidium vapor at 780 nm. In the last two configurations, the atomic cell simultaneously blocks the elastic scattering while spatially dispersing the rotational Raman lines. In each case, a tunable Ti : sapphire laser was employed as an illuminating source. Copyright ” 2000 John Wiley & Sons, Ltd.
Icteric-type hepatoma: magnetic resonance imaging and magnetic resonance cholangiographic features.

Background: We evaluated the imaging features of magnetic resonance imaging (MRI) and magnetic resonance cholangiography (MRC) of icteric-type hepatoma and correlated these with the findings of endoscopic retrograde cholangiography (ERC), percutaneous cholangiography, and surgery.
Combustion Synthesis of Nanoparticulate LiMgxMn1-xPO4 (x=0, 0.1, 0.2) Carbon Composites

A combustion synthesis technique was used to prepare nanoparticulate LiMgxMn1−xPO4 (x = 0, 0.1, 0.2)/carbon composites. Powders consisted of carbon-coated particles about 30 nm in diameter, which were partly agglomerated into larger secondary particles. The utilization of the active materials in lithium cells depended most strongly on the post-treatment and the Mg content and was not influenced by the amount of carbon. Best results were achieved with a hydrothermally treated LiMg0.2Mn0.8PO4/C composite, which exhibited close to 50% utilization of the theoretical capacity at a C/2 discharge rate.
Evidence for a Role of Endogenous Nesfatin-1 in the Control of Water Drinking

Nesfatin-1, a post-translational product of the nucleobindin-2 (NucB2) gene, is produced in several brain areas known to be important in neuroendocrine, autonomic and metabolic function, including the hypothalamus and medulla. The hallmark action of the peptide is its ability at picomole doses to inhibit food and water intake in rodents and, indeed, the effect on water intake is more pronounced than that on food intake. In preliminary studies, we observed a decrease in hypothalamic NucB2 expression in response to overnight water deprivation even when food was present, which reversed when water was returned to the animals. We therefore hypothesised that the effect of nesfatin-1 on water drinking was independent of its anorexigenic action. Indeed, rats administered nesfatin-1 i.c.v. consumed significantly less water than controls in response to a subsequent, dipsogenic dose of angiotensin II, or upon return of water bottles after 18 h of fluid restriction (food present), or in response to a hypertonic challenge. Pretreatment with an antisense oligonucleotide against nesfatin-1 significantly reduced levels of immunoreactive nesfatin-1 in the hypothalamic paraventricular nucleus and resulted in exaggerated drinking responses to angiotensin II. The results obtained in the present study suggest that locally produced nesfatin-1 may be an important component of the hypothalamic mechanisms controlling fluid and electrolyte homeostasis.
Recent advances in functional neuroimaging.

New functional imaging techniques, including positron emission tomography, transcranial magnetic stimulation and functional magnetic resonance imaging, promise to allow the noninvasive study of haemodynamic, metabolic and activation parameters during acute migraine attacks in humans. These technique
Effect of Family and Nitrogen Fertilizer on Growth and Foliar Nutrients of Douglas-fir Saplings

Family x fertilizer-inter actions were evaluated in a split-plot experiment involving 12 open-pollinated families of Douglas-fir (Ps eudotsuga menziesii (Mirb.) Franco). The fertilizer treatment was applied when trees were 12 years of age, and response was measured as cumulative volume growth during the next 4 years. Volume growth varied among families and was increased by an average of 7 percent by application of 224 kg ha -1 N as urea. Foliar concentrations of some nutrients also differed significantly (P ::5 0.05) among families and between fertilizer treatments. The family x fertilizer interaction was not significant for any growth or foliar nutrient variable. FOREST SCI. 32:643-652.
Abstract 46: Putting Class IIB Recommendations to the Test - The Influence of Unwitnessed and Non-VT/VF Arrests on Resource Consumption and Outcomes in Therapeutic Hypothermia

Background. Therapeutic hypothermia (TH) improves survival for patients with out-of-hospital (OOH) cardiac arrest. Largely studied in witnessed VT/VF populations, recent data may support broader application for other forms of arrest. Many institutions are electing to expand their inclusion criteria in response. However, no studies have described changes in patient characteristics, resource use, or outcomes that may result with such expansion. Methods. We studied consecutive patients receiving TH at UNC Hospital from Sep 2009 - Jan 2012. Protocol #1 provided TH for witnessed OOH arrest with VT/VF only. In Nov 2010, criteria were expanded to include all cardiac rhythms and un-witnessed events ( protocol #2 ). Baseline demographics, resource use, and survival were compared between protocol groups. Multivariable logistic regression was used to identify key variables associated with in-hospital mortality. Results. The arrest population cooled at our institution had numerous comorbidities. The median age was 57 (IQR 49,70) years and median BMI was 28 (IQR 25,32) kg/m2. The majority were male (55%), white (70%), and had history of hypertension (57%). In addition, there was a high prevalence of baseline diabetes (28%), CAD (34%), chronic kidney disease (19%), and heart failure (28%). Despite nominally greater representation of male patients (63 v. 41%) in the expanded protocol population, there were no significant differences in baseline characteristics between protocol #1 and #2. Most arrest events were witnessed, but there were more unwitnessed episodes with the protocol #2 (30 v. 0%, p =0.01). The initial cardiac rhythm was most commonly VT/VF, but there were greater rates of PEA (6 v. 17%, p=0.01) with protocol #2. This was a resource intensive population, with all patients mechanically ventilated, 1/3 receiving cardiac catheterization and anti-arrhythmic drug therapy, and 2/3 treated with vasopressor medications; however, only the rate of aspirin use differed among protocol groups (35 v. 67% for protocol #2, p=0.04). Overall, 68% of all patients died in the hospital. While there was higher mortality with the expanded protocol, this did not reach statistical significance (59 v. 73%, p=0.31). Not a single unwitnessed arrest survived, and age was also independently associated with mortality (OR per 10y = 2.52, 95% CI 1.26-5.05, p=0.009). Conclusions. No matter the inclusion criteria, patients who receive TH for OOH cardiac arrest have multiple comorbidities and consume numerous resources. However, there were no significant differences when comparing our two protocol populations. Mortality does seem to be increasing with broader application of TH, and future attention should focus on the unwitnessed arrests in particular, none of whom survived their hospitalization.
Optimization of RAPD technique of fingerprinting analysis of Pelodiscus sinensis populations

Four populations of Pelodiscus sinensis from Yellow River,Taihu Lake,Taiwan and Japan were used to optimize PCR amplification conditions to develop DNA fingerprinting technology by RAPD primers.The results showed 20 RAPD primers could amplify PCR products in four different poplations under the optimization conditions.The result also demonstrated that PCR products amplified by RAPD primer S105 in sinensis population Yellow River were different from those in other three populations,while RAPD primers S327 and S474 could differeniate Japan and Taiwan populations from other three populations,respectively.Therefore,the optimization of annealling temperature and cycles numbers is beneficial to the development of RAPD technique of P.sinensis.Meanwhile,the reasonablity and its affecting factors of RAPD technique was also briefly discussed in this paper,which can provide the interest information for similar researches.
ASCAT and QuikSCAT Azimuth Modulation of Backscatter Over East Antarctica

For most land and ice surfaces, the measured radar backscatter at the spatial resolution of a wind scatterometer is insensitive to the azimuth angle. However, for regions of East Antarctica, the backscatter strongly depends on the azimuth angle. This relationship between backscatter and azimuth angle is often modeled with a Fourier series. Although previous work has separately examined the data from QuikSCAT, a Ku-band scatterometer, and the Advanced Scatterometer (ASCAT), a C-band scatterometer, this letter compares the two on the same high-resolution grid. We find that, although QuikSCAT has superior azimuth angle coverage (due to its measurement geometry) compared to ASCAT, both are suitable to estimate the radar backscatter azimuth angle modulation of East Antarctica. The ASCAT data exhibit a much larger azimuth modulation than the QuikSCAT data. This is attributed to the different wavelengths of the microwave signal: At C-band (5.7 cm), East Antarctica has features that show radar backscatter to be more dependent on azimuth angle than at Ku-band (2.2 cm). This letter also examines the ASCAT and QuikSCAT azimuth modulation over previously identified regions of wind glaze. Although azimuth modulation is expected to be minimal over wind glaze, we find the wind-glaze regions to contain more structure than previously suggested.
The Mucus Barrier to Inhaled Gene Therapy

Recent evidence suggests that the airway mucus gel layer may be impermeable to the viral and synthetic gene vectors used in past inhaled gene therapy clinical trials for diseases like cystic fibrosis. These findings support the logic that inhaled gene vectors that are incapable of penetrating the mucus barrier are unlikely to provide meaningful benefit to patients. In this review, we discuss the biochemical and biophysical features of mucus that contribute its barrier function, and how these barrier properties may be reinforced in patients with lung disease. We next review biophysical techniques used to assess the potential ability of gene vectors to penetrate airway mucus. Finally, we provide new data suggesting that fresh human airway mucus should be used to test the penetration rates of gene vectors. The physiological barrier properties of spontaneously expectorated CF sputum remained intact up to 24 hours after collection when refrigerated at 4 °C. Conversely, the barrier properties were significantly altered after freezing and thawing of sputum samples. Gene vectors capable of overcoming the airway mucus barrier hold promise as a means to provide the widespread gene transfer throughout the airway epithelium required to achieve meaningful patient outcomes in inhaled gene therapy clinical trials.
Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia: a clinicopathologic and molecular analysis of a distinct entity

Sclerosing mucoepidermoid carcinoma with eosinophilia is a rare thyroid neoplasm of uncertain pathogenesis that resembles salivary gland mucoepidermoid carcinoma. This multi-institutional study characterizes the clinicopathologic and molecular features of this tumor by utilizing next-generation sequencing to assess common mutations and gene fusions involved in thyroid carcinogenesis as well as fluorescence in-situ hybridization for MAML2 translocations typical of salivary gland mucoepidermoid carcinoma. Nine cases (6 females and 3 males, mean age: 59 years, range 30-77 years) were identified. All cases were comprised of nests and strands of tumor cells with both squamous and mucinous differentiation embedded in a fibrohyaline stroma with an inflammatory infiltrate replete with eosinophils. All cases were p63 positive, thyroglobulin negative and showed variable expression of TTF-1. All nine cases were negative for MAML2 rearrangements. Five cases successfully tested by next-generation sequencing (ThyroSeq v.2 assay) were negative for mutations and translocations commonly involved in thyroid carcinogenesis. NTRK1 showed overexpression but no evidence of translocation. On follow-up, one patient died of persistent disease, whereas one of four remaining patients with available follow-up (mean: 7.3 years, range 4-11 years) demonstrated recurrence at 4 years. Thus, we show that sclerosing mucoepidermoid carcinoma with eosinophilia appears molecularly and morphologically distinct from follicular and C-cell-derived thyroid tumors as well as from salivary gland mucoepidermoid carcinoma. The overall and recurrence-free survival for these patients may be lower than for other well-differentiated thyroid cancers.
Adaptive walk detection algorithm using activity counts

Accelerometers have been the dominant device used for physical activity assessment studies. They are comfortable to wear at different locations and can accurately measure acceleration. Although, accurate methods for detecting walking in the lab and free-living condition using raw acceleration data exist, these algorithms are not useful for determining indoor movements that correspond to short walking bouts (< 2 minutes). In this paper, we present a new method that is adaptive to a small window of activity count data (10–15 seconds) and robust to within and between subject variability. The adaptive walking detection algorithm is evaluated using 22 adults and walks with a variety of durations ranging from 10 seconds to 8 minutes. The proposed algorithm showed high accuracy for all the walking periods and was significantly better for intervals shorter than 2 minutes.
Treatment of Pediatric Chronic Kidney Disease-Mineral and Bone Disorder

In this paper, we review the pathogenesis and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD), especially as it relates to pediatric CKD patients. Disordered regulation of bone and mineral metabolism in CKD may result in fractures, skeletal deformities, and poor growth, which is especially relevant for pediatric CKD patients. Moreover, CKD-MBD may result in extra-skeletal calcification and cardiovascular morbidity. Early increases in fibroblast growth factor 23 (FGF23) levels play a key, primary role in CKD-MBD pathogenesis. Therapeutic approaches in pediatric CKD-MBD aim to minimize complications to the growing skeleton and prevent extra-skeletal calcifications, mainly by addressing hyperphosphatemia and secondary hyperparathyroidism. Ongoing clinical trials are focused on assessing the benefit of FGF23 reduction in CKD. CKD-MBD is a systemic disorder that has significant clinical implications. Treatment of CKD-MBD in children requires special consideration in order to maximize growth, optimize skeletal health, and prevent cardiovascular disease.
Simulation-Based Systems Engineering

Systems engineering (SE) is understood as an interdisciplinary collaborative approach to derive, evolve, and verify a life cycle balanced system solution. Satisfying customer expectations has become more complicated and complex, as we are no longer designing systems optimized for a single point, but instead are focusing on systems which are sustainable, resilient, flexible, and even antifragile. Simulation is established to support analysis and testing of systems. Recent developments—the use of executable architecture concepts allowing for dynamic evaluation of system concepts, and the use of agent-based implementation to support learning and adaptive system behavior—allow better support of an agile enterprise. To support these ideas, simulation must be fully integrated into SE paradigm. We must establish simulation as an integrated discipline within the SE methodology. Research is needed to support validation and verification of self-modifying systems, as well as improved heuristics for computationally complex problems. This chapter proposes detailed visions and identifies a research agenda needed to realize these visions accordingly.
The dilemma of ‘racial profiling’: an abolitionist police history#

While the conquest of the world by the concept of ‘racial profiling’ was a major victory for activists, real victory for racial justice at the hands of the police was foreclosed, for the notion is ...
Use of a model for A1c formation to estimate average glucose operative between short-interval measurements of %A1c.

BACKGROUND Estimated average glucose (AG) is generally reported along with hemoglobin A1c measurements according to a standard calculation. Given a normal red blood cell lifetime of 120 days, serial A1c measurements at intervals <120 days are not completely independent. For short interval measurements, a change in AG (ΔAG) necessarily underestimates the change in average glucose operative during the interval (ΔG). We use a model for kinetics of HbA1c to evaluate the theoretical relationship between ΔAG and ΔG for HbA1c measurements made at intervals between 0 and 120 days. METHODS From any given starting point for A1c, step changes in G were simulated using model calculations to determine the extent to which A1c could change as a function of the interval of exposure. Values for ΔAG were compared to the operative ΔG as a function of the interval between A1c measurements. RESULTS Results of model simulations are a single graph for relationship of ΔAG to ΔG as a function of the interval between A1c measurements. ΔAG for (15, 30, 45, 60, 76, and 90) day intervals underestimated operative ΔG by (73, 51, 34, 21, 11, and 5)%, respectively. CONCLUSIONS Model calculations predict the relationship between changes in estimated average glucose to changes in operative glucose for serial A1c measurements made at intervals <120 days. Given that serial measurements of A1c made at short intervals are not uncommon in practice, physicians may find this information to be useful.
An educational intervention to improve human papilloma virus (HPV) and cervical cancer knowledge among African American college students.

Abstract Objectives Misinformation and lack of formal education about cervical cancer may contribute to disparities. The objective of this study was to assess the role of an educational intervention in improving knowledge about Human papilloma virus (HPV) and cervical cancer among African American female college students. Methods We completed a total of 5 lectures at 4 different historically Black Colleges in North Carolina, Virginia, and West Virginia. Each 60min lecture reviewed basic female anatomy, HPV pathogenesis, cervical dysplasia, cervical cancer, HPV vaccination and cervical cancer screening. Participants completed pre- and post-lecture surveys assessing knowledge, attitudes and beliefs related to cervical cancer screening, HPV, and the HPV vaccine. Results A total of 72 students attended the lectures and 57 students completed the surveys. 96% of students reported knowledge of the HPV vaccine, however only 52% reported receiving the vaccine, and 42% completed the 3-shot series. About 77% of students over 21years of age reported having a Pap smear. Of the 16 knowledge-based questions, correct response rates significantly increased (74% v. 91%, p =0.005) with the intervention. At the completion of the intervention, 94% affirmed plans to get regular Pap smears and 87% affirmed plans to get the HPV vaccine. Conclusions Primary prevention and early detection are key interventions for reducing disparities in cervical cancer incidence and treatment. Community outreach efforts play an important role in reducing inequities in cancer among high-risk groups. The educational intervention utilized in this study was successful in improving knowledge about HPV and cervical cancer.