cssi/SciSciGPT-SciSciNet huggingface dataset:
In vitro studies on strain-dependent production of thymus-specific autoantibodies.

In vitro cultures of spleen cells (S) from normal 8–10-wk-old DBA/2J mice were shown to develop a small number of plaque-forming cells (PFC) that released antibodies lytic to syngenic and autologous thymus cells as well as to syngenic lymphoma L5178Y cells used as the target in the PFC assay. A marked increase in the number of PFC detectable on L5178Y target cells was demonstrated on day 4 in the cultures of S cells to which syngenic or autologous thymus cells had been added (S+T) at time 0, whereas the PFC detectable on thymus cells in such cultures remained at a level similar to that in S cultures. This suggested that two populations of PFC participated in the observed phenomena. No PFC developed in the culture of thymus cells (T). The addition of the cell-free supernatants of 24-h cultures of T or of L5178Y cells to syngenic S cultures also caused a specific increase in the number of the PFC detectable on L5178Y, which suggested that certain immunogenic factors released from the T cells stimulated the response observed in the S+T cultures. Antibodies of IgM nature were detected in the supernatants of S+T cultures by means of cytolysis in agar of L5178Y cells. Although such antibodies did not cause lysis of thymus cells, they could be completely removed by absorption with normal adult or fetal thymus cells of syngenic origin. Still, the absorbing capacity of L5178Y was much higher than that of thymus cells. The absorption was more efficient at 4°C than at 22°C, and hardly any absorption occurred at 37°C. The tissue distribution of the antigen under study seemed to be restricted to thymus cells since no other murine tissue cells tested removed the antibodies. The thymic antigen under study was not restricted to strain DBA/2J and could be demonstrated on thymus cells of all other strains tested. On the other hand, the ability of spleen cells to respond in vitro to this antigen has thus far been observed only in DBA/2J mice. Spleen cells of strains C57BL/6J and NZB/BINJ as well as (DBA/2 x NZB)F1 failed to show any significant increase in the PFC response detectable on the L5178Y target when syngenic thymus cells or DBA/2J thymus cells were added. An intravenous injection of syngenic thymus cells to DBA/2J mice also caused the appearance in their spleens of PFC detectable on the L5178Y target. The described in vitro system may provide a good means of studying the cellular basis of generation of self-tolerance and of its breakdown.
An Assessment and Care Planning Strategy for Nursing Home Residents with Dementia

Dementia is extremely common among nursing home patients, and it takes many forms. Accurate assessment by staff is crucial in providing appropriate care to these patients. Equally important is the ability to establish care priorities. Current staging models are so general, however, that their usefulness is limited. Thus, this paper proposes a strategy that, using basic assessment data, categorizes dementia residents according to four key determinants of care needs: activities of daily living status, behavioral problems, communication abilities, and physical transition.
Automated inspection of machine parts

Describes a CAD-model-based machine vision system for dimensional inspection of machined parts, with emphasis on the theory behind the system. The original contributions of the work are: the use of precise definitions of geometric tolerances suitable for use in image processing, the development of measurement algorithms corresponding directly to these definitions; the derivation of the uncertainties in the measurement tasks; and the use of this uncertainty information in the decision-making process. Experimental results have verified the uncertainty derivations statistically and proved that the error probabilities obtained by propagating uncertainties are lower than those obtainable without uncertainty propagation. >
Randomized Support Vector Forest

Based on the structural risk minimization principle, the linear SVM aiming at finding the linear decision plane with the maximal margin in the input space has gained increasing popularity due to its generalizability, efficiency and acceptable performance. However, rarely training data are evenly distributed in the input space [1], which leads to a high global VC confidence [4], downgrading the performance of the linear SVM classifier. Partitioning the input space in tandem with local learning may alleviate the unevenly data distribution problem. However, the extra model complexity introduced by partitioning frequently leads to overfitting. To solve this problem, we proposed a new supervised learning algorithm, Randomized Support Vector Forest (RSVF): Many partitions of the input space are constructed with partitioning regions amenable to the corresponding linear SVMs. The randomness of the partitions is injected through random feature selection and bagging. This partition randomness prevents the overfitting introduced by the over-complicated partitioning. We extensively evaluate the performance of the RSVF on several benchmark datasets, originated from various vision applications, including the four UCI datasets, the letter dataset, the KTH and the UCF sports dataset, and the Scene-15 dataset. The proposed RSVF outperforms linear SVM , kernel SVM, Random Forests (RF), and a local learning algorithm, SVM-KNN, on all of the evaluated datasets. The classification speed of the RSVF is comparable to linear SVM.
Two unlike patterns of random-ratio responding associated with different eating habits in rhesus monkeys.

Four rhesus monkeys were exposed to an identical series of schedules that specified a uniform probability of reinforcement for every response. As probability was lowered slowly in 10 steps of 20 sessions each from 1.0 through 0.01, two distinct patterns of responding emerged. Two subjects showed high, pause-free response rates that increased with each successive reduction in reinforcement probability. The other two showed consistent post-reinforcement pausing at all probabilities, including 1.0, and substantially lower response rates that peaked at the moderate probability values of 0.04 and 0.03. This low-rate pattern was found to be correlated with a pre-experimental preference in the two subjects for mouthing and chewing food pellets one at a time, while the former high-rate, pause-free pattern was linked to a long-standing habit of “pouch feeding” in the other monkeys. These idiosyncratic collateral behaviors that differentiated the schedule performances appeared neither superstitious in origin, nor useful in the case of the low-rate monkeys.
Synchronous motors for AC adjustable-speed drives

Many power engineers have struggled with ideas of standard and special synchronous motor designs as those concepts relate to LCI (load commutators inverter) drives. Today many engineers accept the premise that LCI motors belong in a category unto themselves, different from 'standard' synchronous motors. Some points of view bearing upon this theme are discussed. Operating principles, application methodologies and criteria, machine design, and field experience are reviewed. Some concepts of standard motor design are described and compared to corresponding aspects of LCI motor designs. >
Tumor necrosis factor alpha production from CD8+ T cells mediates oviduct pathological sequelae following primary genital Chlamydia muridarum infection.

The immunopathogenesis of Chlamydia trachomatis-induced oviduct pathological sequelae is not well understood. Mice genetically deficient in perforin (perforin−/− mice) or tumor necrosis factor alpha (TNF-α) production (TNF-α−/− mice) displayed comparable vaginal chlamydial clearance rates but significantly reduced oviduct pathology (hydrosalpinx) compared to that of wild-type mice. Since both perforin and TNF-α are effector mechanisms of CD8+ T cells, we evaluated the role of CD8+ T cells during genital Chlamydia muridarum infection and oviduct sequelae. Following vaginal chlamydial challenge, (i) mice deficient in TAP I (and therefore the major histocompatibility complex [MHC] I pathway and CD8+ T cells), (ii) wild-type mice depleted of CD8+ T cells, and (iii) mice genetically deficient in CD8 (CD8−/− mice) all displayed similar levels of vaginal chlamydial clearance but significantly reduced hydrosalpinx, compared to those of wild-type C57BL/6 mice, suggesting a role for CD8+ T cells in chlamydial pathogenesis. Repletion of CD8−/− mice with wild-type or perforin−/−, but not TNF-α−/−, CD8+ T cells at the time of challenge restored hydrosalpinx to levels observed in wild-type C57BL/6 mice, suggesting that TNF-α production from CD8+ T cells is important for pathogenesis. Additionally, repletion of TNF-α−/− mice with TNF-α+/+ CD8+ T cells significantly enhanced the incidence of hydrosalpinx and oviduct dilatation compared to those of TNF-α−/− mice but not to the levels found in wild-type mice, suggesting that TNF-α production from CD8+ T cells and non-CD8+ cells cooperates to induce optimal oviduct pathology following genital chlamydial infection. These results provide compelling new evidence supporting the contribution of CD8+ T cells and TNF-α production to Chlamydia-induced reproductive tract sequelae.
Generalized Norton-Simon models of tumour growth.

This paper considers the analysis of serial data on the growth of tumours in laboratory rodents. I propose a model - a generalization of the tumour growth model of Norton and Simon - that leads to a rich family of growth and decay curves. The model assumes that unperturbed growth follows the generalized logistic form; it accommodates time-varying treatment effects through an effective dose function. I fit two such models to data on a human prostate tumour growing in nude mice and compare the fitted curves and dose functions with a non-parametric curve and dose function estimated from a cubic spline model. All three models account for both random animal effects and autocorrelation. Monte Carlo results suggest that (a) maximum likelihood estimates of growth parameters are biased, although not severely, and (b) standard errors are conservative in small samples but become increasingly accurate in larger samples.
Growing Up Under a Shadow: Key Issues in Research on and Treatment of Children Born of Rape

Children born of wartime rape are particularly vulnerable and their case is complex as their needs intertwine with the needs of their mothers or their cultural community. To analyse the status of children born of rape and identify both risk factors and key issues, a systematic search among medical and psychological research articles was performed. In addition, historical, sociological and human rights literature was explored. Risk factors for the wellbeing of children born of rape are: pregnancy and delivery; poor parent-child relationships; discrimination and stigmatisation; and identity issues. Three key issues which should direct research and clinical practice are formulated: perceiving children born of rape as secondary rape victims; the existence of multiple perpetrators; and competing rights and interests. To assist children born of rape, clinicians, as well as researchers, are confronted with the challenge to develop a comprehensive perspective that considers the needs and rights of both children and mothers. Copyright © 2013 John Wiley & Sons, Ltd. ‘Three key issues which should direct research and clinical practice are formulated’ Key Practitioner Messages Children born of rape face serious mental health risks. Perceiving children born of rape as secondary rape victims is of importance as this highlights the risk of confrontation with the direct trauma of the mother via the mother-child relationship. Acknowledging the existence of multiple perpetrators creates the opportunity to hold those involved accountable for their behaviour. Clinicians have to develop a comprehensive perspective that considers the needs and rights of both children and mothers. ‘A comprehensive perspective that considers the needs and rights of both children and mothers’
Enhancing coherent anti-Stokes Raman scattering sensitivity by maximizing quantum coherence

Summary form only given. We develop the enhancement of coherent anti-Stokes Raman scattering (CARS) in terms of maximizing the coherence by stimulated Raman adiabatic passage and chirped pulse adiabatic rapid passage. This technique can be readily extended to a femtosecond time scale for rapid identification and trace of impurities.
EFFECT OF 3-AMINOPROPANOL ON CHOLINE-DEFICIENCY IN RATS.

Summary3-Aminopropanol, like 2-amino-2-methylpropanol, increased the incidence of hemorrhagic kidneys and the level of liver fat of weanling male rats consuming a low-choline diet. Choline, dimethylethanolamine and monomethylethanolamine prevented the antilipotropic action of 3-aminopropanol. In the presence of 3AP betaine and methionine prevented the occurrence of kidney hemorrhages but only partially reduced the liver fat. Ethanolamine had little influence on the occurrence of hemorrhagic kidneys and only partially reduced the liver fat. Betaine and ethanolamine together in the diet were quite effective, whereas, methionine and ethanolamine together were only moderately effective. The inhibitory action of 3-aminopropanol was not as great as that of 2-amino-2-methyl-propanol.
Factors influencing failure to return to work due to traumatic brain injury

About 63% of all traumatic brain injuries (TBI) occur in teenagers and adults aged 15-64 years, the primary working population. Since reports of failure to return to work (FTRTW) vary, understanding the factors that influence FTRTW is key to improving work outcomes for this primarily working-age population. Our study sample consists of 343 previously employed persons who were hospitalized following TBI and had either returned to work at 1 year or had failed to return to work because of their injury (injury-related FTRTW). Medical records were reviewed and participants were interviewed by telephone at 1 year post-discharge. Individuals with injury-related FTRTW were far more likely to report dependence or modified independence on the Functional Independence Measure (FIM) than those who were employed at 1 year. The joint distribution of motor and cognitive items suggests that, for a given level of cognitive function, the addition of a motor limitation will result in greater injury-related FTRTW. In addition as motor function declines, FTRTW is further increased. Injury-related FTRTW is also associated with being unmarried and not completing high school. While the importance of behavioural, economic, and psychosocial factors should not be minimized, services aimed at improving function can be expected to have an impact on RTW after TBI.
A study of selected object-projection skills performed by subjects above average in skill.

Abstract The purpose of this study was to determine if factor patterns of selected sports skills were similar for two samples, a skilled sample and one consisting of a wide range of skills. Comparisons were also made with kinesiological evidence regarding the patterning of basic sports skills. Data consisting of performance scores on various sports skills were available for 166 high school girls. Out of this sample, a smaller sample was drawn consisting of 69 girls who were above average in skill. Two factor models, alpha and incomplete image analysis, were used in the analysis of this data. The factor pattern of selected sports skills performed by subjects above average in skill was similar in many respects to that of a sample which included a wide range of skill. The primary difference lay in the clustering of overarm skills which appeared in the above-average factor pattern. The overarm and push patterns of the above-average sample resembled the patterns of skill obtained through kinesiological analysi...
Purification of anthranilate 5-phosphoribosylpyrophosphate phosphoribosyltransferase from Salmonellatyphimurium using affinity chromatography: Resolution of monomeric and dimeric forms

Abstract Anthranilate 5-phosphoribosylpyrophosphate phosphoribosyltransferase (PRT) as the unaggregated enzyme, has been purified to 90–95 percent homogeneity using affinity and ion-exchange chromatography. The affinity matrix consisted of anthranilate coupled to succinylamidohexamethylimino-Sepharose via its free amino group. Electrophoresis of the purified PRT on gels of varying polyacrylamide concentrations resolved a faster-moving minor band at concentrations above 8 percent. Both the major and minor bands were found to possess PRT activity. The minor band was found to have a molecular weight one-half that of the major band. Electrophoresis of the enzyme in the presence of sodium dodecyl sulfate resulted in almost complete conversion to the lower molecular weight form.
Historical Overview and Demographic Analysis of Human Trafficking in the USA

Understanding factors that may be connected to human trafficking in the US can help people in the US and other nations better understand and combat the problem. A better understanding of human trafficking can benefit anti-trafficking efforts of public administrators in governmental agencies and private citizens in non-governmental organizations. Prior research has examined various countries regarding human trafficking on a national or macro level. This study extends prior research by examining the role of human trafficking in the United States on a state level. In addition, a brief history of slavery, from past to present, is presented, including public and private sector efforts to combat the problem. Among notable historical efforts to end slavery are those of William Wilberforce and his Christian allies in the British Parliament in the early 1800s, the Emancipation Proclamation of 1863 by U.S. President Lincoln, and current efforts by Christian-based organizations such as International Justice Mission and World Relief. Findings of the demographic analysis indicate that locations with higher rates of corruption and higher population are associated with higher rates of human trafficking per capita. Anti-trafficking efforts, in the US and other countries, could be more effective by focusing on such areas.
Electron Spin Resonance Spectra of Polymer Radicals in Aqueous Solution.

Mixing of aqueous polymer solutions containing Ti3+ and H2O2 in a rapid flow mixer produced radicals by abstraction, OH + RH → R · + H2O, which were observed by electron spin resonance. Oscillation of segments was sufficient to narrow the lines to 0.5-2.0 g. Polymers and radicals identified with more or less certainty were polyacrylic acid, 〰CH(CO2H)ĊHCH(CO2H)〰, polymethacrylic acid, 〰C(CH3)(CO2H)ĊHC(CH3)(CO2H)〰, polyvinyl alcohol, 〰CHOHĊHCHOH〰, and one indefinite, polyethylene imine, 〰CH2ṄCH2〰 or 〰CH2ṄOCH2〰, polyethylene oxide, 〰CH2OĊHCH2O〰. Radicals from polypropylene oxide, dextran, dextrin, soluble starch, and the disaccharide maltose were unidentified; the last three were strikingly similar. Products of secondary C-C scission were not observed with certainty. It is presumed that such reactions are slow compared to the time-scale of the experiment, 10 msec. However, some evidence exists for a very rapid β-OH loss in carbohydrate radicals and a slow C-O scission in polyethylene oxide radicals. A large number of related small molecule radicals were investigated, and hyperfine splittings and g-values are reported.
Sarcinomyces Inkin in Brasil

Sarcinomyces Inkin Oho (1919) was first isolated and described from a scrotal lesion somewhat resembling eczema marginatum of Hebra in Formosa and the lesion was reproduced experimentally on a human volunteer by rubbing the organism into excoriations on the scrotum. A search of the literature has not revealed other cases; apparently the two cases reported here are the second and third cases known. Since Sarcinomyces infections respond to treatment similar to that used in eczema marginatum caused by Epidermophyton floccosum (Harz) Langeron & Milochevitch, perhaps cases have been diagnosed and treated by physicians without isolating the etiologic agent and hence other cases of Sarcin0omt?vces infection hlave inot been recognlize(l.
Immune regulatory effects of Fingolimod (FTY720) on T cells (THER7P.959)

FTY720 is the functional analogue of sphingosine and is the first oral treatment for relapsing remitting MS. We investigated the immune regulatory effects of Fingolimod (FTY720) on T cells in Multiple Sclerosis (MS) and controls. FTY720 function by blocking immune cell trafficking and prevents relapses in Multiple Sclerosis. We found that T cells activated in the presence of FTY-720 were less inflammatory with decreased proliferation and cytokines expression. FTY720 treated T cells have decreased expression of granzyme B and induced less neuronal cytotoxicity. We showed, FTY720 treated T cells have unique anti-inflammatory immune gene profile. The anti-inflammatory effect of FTY720 on T cells is dependent upon increased expression of a regulatory transcription factor TCF1 (Transcription factor 1). TCF1 has been previously linked to T- cell differentiation and lineage specification in mice. We show that the TCF1 could regulate human T cell differentiation. Knock down of TCF1 gene expression in human T cells switched anti-inflammatory T cells to pro-inflammatory T cell phenotype. In summary, we showed that FTY720 could regulate human T cells differentiation and its immune regulatory function is dependent upon the expression of regulatory transcription factor TCF1.
Shiga toxin 1-induced activation of c-Jun NH2-terminal kinase and p38 in the human monocytic cell line THP-1: possible involvement in the production of TNF-α

Shiga toxin-producing enterohemorrhagic E. coli infections cause bloody diarrhea, which may progress to life-threatening complications such as the hemolytic-uremic syndrome (HUS). HUS patients frequently have elevated levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) detectable in urine. Thus, sequelae may develop following the localized production of proinflammatory cytokines within the kidneys. A possible source of these cytokines are macrophages, which respond to the toxins by producing TNF-alpha. We have shown previously that THP-1 cells produce soluble TNF-alpha in response to the toxins, whose production requires host-cell tyrosine-kinase activity and toxin-enzymatic activity. To further examine signaling pathways involved in TNF-alpha expression, we determined that JNK1 and -2 and p38, but not ERK1 or -2, were phosphorylated following toxin exposure. Blockade of p38 activation reduced TNF-alpha production following Shiga toxin 1 treatment. Finally, we present a model of the ribotoxic stress response triggered in human macrophages by Shiga toxins.
Ceftazidime-avibactam (CTZ-AVI) as a treatment for hospitalized adult patients with complicated intra-abdominal infections

Avibactam, a novel β-lactamase inhibitor, has recently been co-formulated with ceftazidime and approved for use in patients with complicated intra-abdominal and urinary tract infections, where no better treatment alternative exists. The basis for its FDA approval has been the extensive clinical experience with ceftazidime and the demonstration in vitro and in animal models that the addition of avibactam reverses resistance to ceftazidime in extended-spectrum β-lactamase and some carbapenemase-producing Enterobacteriaceae. Early clinical data are promising, with efficacy demonstrated in patients with complicated intra-abdominal and urinary tract infections. This review will summarize the in vitro, animal and clinical data available on this agent to date.
151 CLINICAL OUTCOMES OF PATIENTS WITH MODERATE OR HIGH PRE-TEST PROBABILITY AND NEGATIVE D-DIMER TESTS

Purpose The diagnosis of pulmonary embolism (PE) remains elusive due to the non-specific presentation of patients with the disease. The D-dimer blood test has been proven effective in ruling-out PE in patients stratified into a low-risk category, yet no study has confirmed its effectiveness in those with a moderate or high pre-test probability (PTP). This study attempts to determine the clinical outcomes of patients categorized as moderate to high risk for PE who had negative D-dimer test results (≤500 ng/mL.) Methods A prospective study was performed based on the current University of Colorado Hospital protocol for patients suspected of PE between 1/24/03 and 8/4/04. Patients were enrolled when a D-dimer test was ordered for suspected PE and a research assistant was available. Two physicians (attending and senior resident) ranked PTP on a validated point scale and on their clinical gestalt. Subsequent tests were reviewed and ≥3-month follow-up was performed on all patients with moderate or high PTP and negative D-dimer results. Results Among the 259 patients enrolled in the study between 1/24/03 and 8/4/04, 44 had a non-low PTP according to Wells assessment by the attending physician. Seventeen of these patients had radiological imaging studies during their visit (15 CTPE, 2 V/Q). All of these studies were negative for acute PE. Twenty-four patients (73%), out of a possible 33 for whom a 3-month window had elapsed, were available for follow-up. None of these patients were diagnosed with PE in the interim. Conclusions The results suggest that a negative D-dimer result safely rules out acute PE in non-low PTP patients.
The application of BED-CEIA in the estimate of HIV-1 new infections rates among key AIDS surveillance population in Jiangxi province

Objective BED-CEIA was applied for the detection of serum from sentinel hospitals,in order to calculate the new infection of human immunodeficiency virus( HIV) type 1 in Jiangxi province's key crowd from 2011 to 2013. Methods Of HIV sentinel surveillance in 8 focus groups,a total of 131 562 blood samples were collected,among which samples were detected by immunoblotting as positive,the Western blot positive blood samples,with the application of BED-CEIA,were used to distinguish the new infections and past infections,using the formula I =( F ×( 365 / W) × R) /( N + F*( 365 / W) × R /2) × 100% to estimate the rate of new HIV-1 infections. Results From 2011 to 2013 HIV sentinel surveillance of key population HIV-1infection rate was respectively 0. 21%,0. 23%,0. 14%. New infections mainly occurred in male behavior crowd( MSM),the new infection rate was the highest,in 2011 the new infection rate was 4. 77%( 1. 46% ~ 8. 07%),5. 33%( 2. 63% ~ 8. 03%)in 2012,1. 87%( 0. 49% ~ 3. 26%) in 2013,the rest of the population is low. Conclusion In Jiangxi province MSM is higher compared to other groups of HIV-1 infection rate,of the crowd AIDS epidemic situation is relatively serious,should be reevaluated intervention strategy at present,increase the intensity of intervention in this population.
Characteristics of Share-Gaining Marketing Strategies for Smaller-Share Firms: Literature Review and Synthesis

According to the literature, a successful share-gaining marketing strategy for a smaller-share firm is one which does not directly attack a large competitor, or does so only if the large competitor is vulnerable in some important way. If this necessary condition is satisfied, in order for the smaller-share firm’s marketing strategy to be successful it must also (1) neutralize the competition’s ability to respond quickly, (2) achieve a significant product/service difference, and (3) use a distribution strategy that will provide it with longer term protection against competitive retaliation.
Total anomalous pulmonary venous connection in infancy Ten years’ experience including studies of postoperative ventricular function

The surgical experience with total anomalous pulmonary venous connection (TAPVC) at the Vanderbilt Hospital between the years 1969 and 1979 was reviewed. Twenty-five patients with TAPVC were studied. All but one patient presented at less than 1 year of age, and 11 patients were operated upon in the first 2 weeks of life. Operative mortality rate was 20% (5/25). Four of the five deaths were in critically ill neonates requiring preoperative ventilatory support. All operative deaths were in patients with pulmonary venous obstruction. All operative survivors have been followed for a mean 4.5 years (6 months to 10 years). There have been no late deaths or cases of symptomatic pulmonary venous obstruction. All children have had normal growth patterns. Ten patients have been recatheterized. Pulmonary artery systolic pressure, which was markedly elevated prior to operation, fell to normal levels after operation. Ventricular function has been evaluated by quantitative angiocardiography in nine patients before and after operation. Left ventricular size and function were markedly depressed preoperatively and rose to normal levels in postoperative survivors. Left atrial maximal volume was found to be 94% of normal values. These data support the contention that preoperative pulmonary venous obstruction is the single risk factor predicting higher risk of operative death. The presence of severe depression of left ventricular size and function preoperatively does not predict a higher operative risk, and postoperative survivors can expect normal ventricular function.
Snapshot Hyperspectral Light-Sheet Imaging of Signal Transduction in Live Pancreatic Islets

Abstract The observation of ionic signaling dynamics in intact pancreatic islets has contributed greatly to our understanding of both α - and β -cell function. Insulin secretion from β -cells depends on the firing of action potentials and consequent rises of intracellular calcium activity ([Ca 2+ ] i ). Zinc (Zn 2+ ) is cosecreted with insulin, and has been postulated to play a role in cell-to-cell cross talk within an islet, in particular inhibiting glucagon secretion from α -cells. Thus, measuring [Ca 2+ ] i and Zn 2+ dynamics from both α - and β -cells will elucidate mechanisms underlying islet hormone secretion. [Ca 2+ ] i and intracellular Zn 2+ can be measured using fluorescent biosensors, but the most efficient sensors have overlapping spectra that complicate their discrimination. Hyperspectral imaging can be used to distinguish signals from multiple fluorophores, but available hyperspectral implementations are either too slow to measure the dynamics of ionic signals or not suitable for thick samples. We have developed a five-dimensional ( x , y , z , t , λ ) imaging system that leverages a snapshot hyperspectral imaging method, image mapping spectrometry, and light-sheet microscopy. This system provides subsecond temporal resolution from deep within multicellular structures. Using a single excitation wavelength (488 nm) we acquired images from triply labeled samples with two biosensors and a genetically expressing fluorescent protein (spectrally overlapping with one of the biosensors) with high temporal resolution. Measurements of [Ca 2+ ] i and Zn 2+ within both α - and β -cells as a function of glucose concentration show heterogeneous uptake of Zn 2+ into α -cells that correlates to the known heterogeneities in [Ca 2+ ] i . These differences in intracellular Zn 2+ among α -cells may contribute to the inhibition in glucagon secretion observed at elevated glucose levels.
An Introduction to Mergers, Acquisitions, and Other Restructuring Activities

This chapter explores the underlying dynamics of mergers and acquisitions (M&As) in the context of an increasingly interconnected world and views M&As as change agents in the context of corporate restructuring. The focus is on M&As, why they happen, and why they tend to cluster in waves. The chapter also introduces a variety of legal structures and strategies that are employed to restructure corporations. Moreover, the role of the various participants in the M&A process is explained. Reflecting the latest empirical studies, this chapter addresses the questions of whether mergers pay off for the target and acquiring company shareholders and bondholders, as well as for society.
In Vivo Imaging of the Human Retinal Pigment Epithelial Mosaic Using Adaptive Optics Enhanced Indocyanine Green Ophthalmoscopy.

PURPOSE The purpose of this study was to establish that retinal pigment epithelial (RPE) cells take up indocyanine green (ICG) dye following systemic injection and that adaptive optics enhanced indocyanine green ophthalmoscopy (AO-ICG) enables direct visualization of the RPE mosaic in the living human eye. METHODS A customized adaptive optics scanning light ophthalmoscope (AOSLO) was used to acquire high-resolution retinal fluorescence images of residual ICG dye in human subjects after intravenous injection at the standard clinical dose. Simultaneously, multimodal AOSLO images were also acquired, which included confocal reflectance, nonconfocal split detection, and darkfield. Imaging was performed in 6 eyes of three healthy subjects with no history of ocular or systemic diseases. In addition, histologic studies in mice were carried out. RESULTS The AO-ICG channel successfully resolved individual RPE cells in human subjects at various time points, including 20 minutes and 2 hours after dye administration. Adaptive optics-ICG images of RPE revealed detail which could be correlated with AO dark-field images of the same cells. Interestingly, there was a marked heterogeneity in the fluorescence of individual RPE cells. Confirmatory histologic studies in mice corroborated the specific uptake of ICG by the RPE layer at a late time point after systemic ICG injection. CONCLUSIONS Adaptive optics-enhanced imaging of ICG dye provides a novel way to visualize and assess the RPE mosaic in the living human eye alongside images of the overlying photoreceptors and other cells.
MGH cylindrical PET detector characteristics

A cylindrically shaped PET (positron emission tomography) camera designed to utilize cross-plane events is being developed. A two-dimensional BGO scintillation detector was designed for the camera. It uses a rectangular array of detector elements and a hex array of PM tubes that are supported by a thin cylindrical light guide-eight detector elements/PM tube. The detector is 60 cm in diameter by 12 cm axially. The BGO elements are 3-mm*5.7-mm*30-mm-deep and form 20 rings of 640 elements. A narrow light distribution is achieved. To decrease the system deadtime, scintillation events are processed using only near neighbor PM tube signals. The goal is to achieve high sensitivity and high resolution in energy, time, and space. The preliminary data obtained from the camera indicate that the design goals will be achieved. Algorithms that equalize the PM tube gains will improve energy resolution, spatial resolution, and stability. >
High-content DNA damage assay: Simultaneous measurement of H2AX phosphorylation, ATM activation, and DNA content

A17 The ability to reliably and quantitatively detect DNA damage is critical to cancer research. Multi-parameter cytometric measurements of the levels of γH2AX and activated ATM expression allow estimation of the extent of DNA damage caused by multiple factors such as ionizing radiation, carcinogenic agents, anti-cancer drugs and correlation of this damage with the cell cycle phase. Using laser scanning cytometry (LSC) technology we measured globally per nucleus and by enumeration of immunofluorescence (IF) foci γH2AX expression and ATM activation (ATM-Ser1981 phosphorylation; pATM). In dual-label γH2AX/DNA and pATM/DNA content studies, we validated quantification of the number of foci representing individual double strand breaks (DSBs) per nucleus in relation to the cell cycle phase. At low levels of DSBs, both pH2AX and pATM presented as distinct foci, reporting the number of DSBs per nucleus. At higher levels, when foci were too dense for individual enumeration, the overall immunofluorescence integrated over the nucleus was successfully applied as a measure of the pH2AX activation. After establishing background (constitutive) levels of DNA damage in cell lines, we administered treatment with topoisomerase inhibitor camptothecin (CPT), which showed that cells in S-phase were all saturated with γH2AX, while individual foci could be enumerated in cells in G1 and G2. We also demonstrated that the number of foci was reduced after treatment with 2-deoxy-D-glucose, implicating metabolically generated oxidants as the cause of the DSBs. Dual-label pATM/DNA content studies showed similar results, with pATM aggregating in foci within nuclei in response to oxidative stress. Finally, we established a high-content DNA damage assay comprising simultaneous measurement of pH2AX, pATM (expression levels and individual foci counts for both) and DNA content. This novel multi-parameter biomarker assay allows simultaneous assessment of ATM activation, H2AX phosphorylation and correlation with the cell cycle phase. It is particularly well suited for detection of low levels of DNA damage, such as occurring constitutively. Our results suggest that activated ATM foci are fewer and more diffuse than those of γH2AX. However, since ATM activation is upstream of H2AX phosphorylation in the DNA DSB repair pathway, it could serve as a useful early marker for these lesions. We will present the results of several screens for compounds that induce or inhibit DNA damage, as well as an assessment of DNA protective properties of “antioxidants” available in general health stores.
Correction: Insulin dimer dissociation and unfolding revealed by amide I two-dimensional infrared spectroscopy

Correction for 'Insulin dimer dissociation and unfolding revealed by amide I two-dimensional infrared spectroscopy' by Ziad Ganim et al., Phys. Chem. Chem. Phys., 2010, 12, 3579-3588.
Wie spiegelt Keratansulfat im Serum den Proteoglykanmetabolismus des Knorpels wider

Knorpelgewebe enthalt eine geringe Anzahl von Zellen (Chondrozyten), die in eine wasserreiche Matrix mit hohem Gehalt an Kollagenen und Proteoglykanen eingebettet sind [6]. Die meisten Proteoglykane bestehen aus einem Proteinzentralfilament (core protein), an das kovalent zahlreiche Ketten aus Chondroitinsulfat, Keratansulfat und Oligosaccharide gebunden sind [6]. Viele dieser Proteoglykanmonomere verbinden sich extrazellular mit Molekulen des Link-Proteins und einem einzigen Hyaluronanstrang zu Aggregaten, die fest in das Netzwerk aus unloslichen Kollagenfasern eingebettet sind [6]. Im normalen Knorpel des Erwachsenen ist der Proteoglykangehalt relativ stabil: Molekule, die beim normalen Umsatz abgebaut werden (Katabolismus), werden durch neu synthetisierte Proteoglykane ersetzt (Anabolismus). Fragmente, die beim proteolytischen Abbau der Proteoglykane wahrend des normalen Umsatzes entstehen, treten schnell aus dem Gewebe aus und erscheinen in den Korperflussigkeiten, in denen sie weiter abgebaut werden konnen, bevor sie uber Leber und Niere ausgeschieden werden [14].
Health in All Social Work Programs: Findings From a US National Analysis.

Objectives. To establish a baseline of health content in 4 domains of US social work education—baccalaureate, master’s, doctoral, and continuing education programs—and to introduce the Social Work Health Impact Model, illustrating social work’s multifaceted health services, from clinical to wide-lens population health approaches.Methods. We analyzed US social work programs’ Web site content to determine amount and types of health content in mission statements, courses, and specializations. Coding criterion determined if content was (1) health or health-related (HHR) and (2) had wide-lens health (WLH) emphasis. A second iteration categorized HHR and WLH courses into health topics.Results. We reviewed 4831 courses. We found broad HHR content in baccalaureate, master’s, and continuing education curricula; doctoral programs had limited health content. We identified minimal WLH content across all domains. Topical analysis indicated that more than 50% of courses concentrated on 3 areas: mental and behavioral he...
Using synthetic CT for partial brain radiation therapy: Impact on image guidance

Abstract Purpose Recent advancements in synthetic computed tomography (synCT) from magnetic resonance (MR) imaging data have made MRI-only treatment planning feasible in the brain, although synCT performance for image guided radiation therapy (IGRT) is not well understood. This work compares geometric equivalence of digitally reconstructed radiographs (DRRs) from CTs and synCTs for brain cancer patients and quantifies performance for partial brain IGRT. Methods and materials Ten brain cancer patients (12 lesions, 7 postsurgical) underwent MR-SIM and CT-SIM. SynCTs were generated by combining ultra-short echo time, T1, T2, and fluid attenuation inversion recovery datasets using voxel-based weighted summation. SynCT and CT DRRs were compared using patient-specific thresholding and assessed via overlap index, Dice similarity coefficient, and Jaccard index. Planar IGRT images for 22 fractions were evaluated to quantify differences between CT-generated DRRs and synCT-generated DRRs in 6 quadrants. Previously validated software was implemented to perform 2-dimensional (2D)–2D rigid registrations using normalized mutual information. Absolute (planar image/DRR registration) and relative (differences between synCT and CT DRR registrations) shifts were calculated for each axis and 3-dimensional vector difference. A total of 1490 rigid registrations were assessed. Results DRR agreements in anteroposterior and lateral views for overlap index, Dice similarity coefficient, and Jaccard index were >0.95. Normalized mutual information results were equivalent in 75% of quadrants. Rotational registration results were negligible ( 2 mm in affected quadrants). Conclusions DRR synCT geometry was robust. Although statistically significant differences were observed between CT and synCT registrations, results were not clinically significant. Future work will address synCT generation in postsurgical settings.
Whole-exome sequencing reveals microsatellite DNA markers for response to dofetilide initiation in patients with persistent atrial fibrillation: A pilot study.

BACKGROUND Dofetilide is a class III antiarrhythmic drug effective for the treatment of atrial fibrillation (AF). Dofetilide initiation (DI) associates with corrected QT interval (QTc) prolongation. Significant QTc prolongation during DI mandates dose adjustment or discontinuation of the drug. Microsatellite DNA are novel genetic markers associated with congenital and acquired health conditions. HYPOTHESIS DNA microsatellite polymorphism may associate with QTc response to dofetilide initiation in patients with persistent AF. METHODS We performed whole-exome sequencing in a cohort of patients with persistent AF undergoing DI. Electrocardiographic variables and clinical data were assessed. We defined patients as eligible for DI when no significant QTc prolongation (>20% compared with baseline) was seen with a 500-μg dose. We defined patients as ineligible for DI when significant QTc prolongation was seen during DI with 500 μg. We investigated polymorphisms for 11 919 DNA microsatellite loci in relation to QTc response to DI. RESULTS During the study, 14 consecutive patients with persistent AF presenting for DI were enrolled. Whole-exome sequencing revealed 14 different microsatellite loci in the 2 groups. All genes or proximal genes that harbor these loci are known to have expression in the human heart. Two genes, MYH6 and TRAK2, are known to have expression in the atria. TRAK2 is known to interact with KCNJ2, the inward-rectifier potassium channel 1. CONCLUSIONS Microsatellite DNA polymorphisms seem to associate with QTc response to DI therapy in patients with persistent AF who are deemed otherwise eligible for dofetilide therapy.
Blocking the 5′ splice site of exon 4 by a morpholino oligomer triggers APOL1 protein isoform switch

APOL1 risk alleles G1 or G2 are associated with a kidney disease phenotype exclusively in people of recent African ancestry. Here we show that exon 4 encoding a part of the APOL1 signal peptide is constitutively spliced in major APOL1 transcripts expressed in kidney glomerular and tubular cells. We demonstrate that constitutive splicing of exon 4 results from a suboptimal hnRNP A1 binding motif found in exon 4. Accordingly, a robust binding of hnRNP A1 protein to a consensus hnRNP A1 cis-acting element in exon 4 results in almost complete exclusion of exon 4 from the APOL1 minigene transcripts. Blocking the 5' splice site at the exon 4/intron boundary with a specific antisense morpholino oligonucleotide excludes exon 4 from the splicing pattern of endogenous APOL1 transcripts. These transcripts are fully functional and produce APOL1 protein isoform that is not normally detectable in podocytes. Together with our previous data showing no cytotoxicity of overexpressed APOL1 isoform lacking exon 4, we propose that morpholino-induced APOL1 isoform switch may provide a new tool to identify in vivo molecular mechanism(s) by which risk alleles promote or mediate the kidney disease phenotype.
Assessing the drivers of the collapse of Winter Flounder: Implications for management and recovery

Abstract Winter Flounder populations have declined throughout the southern New England/Mid-Atlantic (SNE/MA) region since the 1980s, and evidence suggests near extirpation of some local populations. Previous research has focused on the correlation between temperature and declining stock-productivity, supporting the hypothesis that a warming climate is a primary driver of the species decline. Our objective was to critically investigate several potential drivers of Winter Flounder's regional decline and collapse in the SNE/MA region by evaluating them in relation to management actions, spawning stock biomass (SSB), recruitment, productivity (PROD) and fishing mortality (F). Results indicate that the SNE/MA stock has remained below the 40% unfished biomass threshold (B40%) since 1984, and that F was above the maximum sustainable fishing rate (FMSY) for most of the period between 1995 and 2010. We found a negative relationship between F and SSB between 1981 and 2000. Correlative analysis between young-of-the-year PROD and a number of biological and physical parameters resulted in 8 (out of 21) significant relationships. However, after correcting for multiple comparisons only two, the abundance of Striped Bass and Summer Flounder, remained significant. The PROD and recruitment analyses did not indicate strong environmental drivers and suggested recruitment compensation during the early 2000s in some surveys. In summary, we did not find evidence of a global environmental driver, such as temperature, explaining the decline of Winter Flounder. Rather, our analysis indicates that long-term overexploitation and failure of management to control harvest rates preceded and was likely a primary driver in the species decline and lack of recovery. Finally, following decades of overfishing, attempts to rebuild the Winter Flounder fishery likely will require a longer-term commitment than management has shown to date.
Airflow Vibrato: Dependence on Pitch and Loudness.

Abstract Objective To describe the airflow vibrato characteristics at various pitches and loudness levels during vocal vibrato production. Method This descriptive case series research design included four subjects: 1 baritone, 1 tenor, and 2 sopranos. The extent and rate of airflow vibrato and fundamental frequency vibrato were measured by analyzing /pa:pa:pa:p/ strings with at least 3-4 cycles of vibrato during the vowels. Comparison was made within and between the subjects at different pitches and loudness levels. Result Airflow vibrato was quite evident for all subjects. Mean airflow vibrato extents were larger in female than male singers. Increase in airflow vibrato extent was observed with increase in pitch, and it was statistically significant when comparison was made within each subject, within males (for P2, M = 74.55 cc/s, S.D = 27.44 cc/s, p Conclusion This study shows that the characteristics of airflow vibrato are similar to F0 vibrato; i.e., airflow vibrato also has extent, rate, regularity, and waveform complexity. However, airflow vibrato waveforms were seen to be more complex in waveshape than F0 vibrato waveforms. Studies on the sources of airflow vibrato are necessary.
Abstract 390: A New Humanized Mouse Model to Study Lipid Abnormalities and HDL Function in Poorly Controlled Type 1 Diabetes Mellitus

Elevated plasma triglycerides (TG) and VLDL are often present in poorly controlled type 1 diabetes mellitus (T1DM). Furthermore, T1DM patients exhibit an increased risk of cardiovascular disease (C...