cssi/SciSciGPT-SciSciNet huggingface dataset:
HSP27 and HSP70 interact with CD10 in C4-2 prostate cancer cells.

BACKGROUND CD10 is a ∼100 kDa transmembrane metallo-endopeptidase. CD10 is strongly expressed by normal prostate epithelium. While only 30% of primary prostate tumors express CD10, it is strongly expressed by most lymph node metastases. The function of CD10 and the interaction between CD10 and other cellular proteins in prostate cancer (CaP) is not well defined. Cellular context may ultimately determine its biologic function in CaP. In this study, we compared CD10 mRNA and protein expression between benign and malignant prostate cells and employed proteomic analysis to identify proteins that interact with CD10 in C4-2 prostate cancer cells. METHODS CD10 mRNA and protein expression was compared using RT-PCR and Western blotting. CD10-protein complexes were isolated by immunoprecipitation using anti-CD10 monoclonal antibodies. Eluted fractions were combined, trypsinized, and the resulting peptides analyzed by µLC-ESI-MS/MS. The parent proteins were identified by searching MS/MS spectra against a human protein database using SEQUEST. RESULTS There were no differences in CD10 mRNA length or CD10 protein molecular weight between normal tissue and CaP. We identified 75 proteins unique to or heavily enriched in the CD10 immunoprecipitates by proteomic analysis. The 27 kDa heat shock protein (HSP27) and HSP70 were identified in three separate precipitations. Protein identification by proteomics was confirmed by Western blotting. Protein complexes immunopurified from C4-2 protein extracts using anti-HSP27 and anti-HSP70 antibodies were found to contain CD10. CONCLUSIONS The function of CD10 in prostate cancer is largely unknown. In the C4-2 CaP cell line, CD10 was found to interact with both HSP27 and HSP70. Prostate 67: 714–721, 2007. © 2007 Wiley-Liss, Inc.
Increased Exercise Performance in Patients with Severe COPD Following Inspiratory Resistive Training

Six patients with severe chronic obstructive pulmonary disease underwent a six-week outpatient program to train their respiratory muscles with an inspiratory resistive device. Exercise performance was measured using a cycle ergometer. Maximum exercise capacity, represented by VO2 max, increased 15 percent. The maximum work rate increased 37 percent, and the minute ventilation attained during exercise increased 17 percent after training. Respiratory muscle endurance increased 56 percent. All patients reported an increased ability to perform the activities of daily living. No changes were reported in three patients who underwent sham training.
An Empirical Comparison of Automated Generation and Classification Techniques for Object-Oriented Unit Testing

Testing involves two major activities: generating test inputs and determining whether they reveal faults. Automated test generation techniques include random generation and symbolic execution. Automated test classification techniques include ones based on uncaught exceptions and violations of operational models inferred from manually provided tests. Previous research on unit testing for object-oriented programs developed three pairs of these techniques: model-based random testing, exception-based random testing, and exception-based symbolic testing. We develop a novel pair, model-based symbolic testing. We also empirically compare all four pairs of these generation and classification techniques. The results show that the pairs are complementary (i.e., reveal faults differently), with their respective strengths and weaknesses.
Responses of Lipolysis and Salivary Cortisol to Food Intake and Physical Activity in Lean and Obese Children

This investigation was conducted to determine whether there were differences in lipolytic responses to feeding and physical activity between lean (LN) and obese (OB) children, and if these responses were related to cortisol. Fourteen LN and 11 OB children participated in this study of abdominal lipolysis and salivary cortisol response to breakfast and lunch with an intervening exercise session. Calculated fasting glycerol release was lower in OB than LN (0.645 +/- 0.06 vs. 0.942 +/- 0.11 micromol/ml; P < 0.05). Fasting adipose tissue nutritive flow was lower in OB than in LN subjects, but responses to feeding and exercise were not different. Breakfast elicited a decrease in interstitial glycerol concentration in LN (-33%; P < 0.05), but not in OB (-5%), children, although decreases in glycerol concentration in response to lunch were similar (LN, -41%; OB, -36%). An interaction was evident in the salivary cortisol response to breakfast (LN, no change; OB, increase) and exercise (LN, no change; OB, decrease), but there were no group differences in response to lunch. Alterations in salivary cortisol and lipolysis were not related. These data suggest that salivary cortisol and lipolytic responses are not necessarily linked, but are altered in obesity. Furthermore, prior exercise may improve the antilipolytic response to a meal in OB children.
G04 Brain structure in children at risk for Huntington's disease

Background There has been growing evidence that the aetiology of Huntington9s disease (HD) has an important component of abnormal brain development. To assess this, the current study was designed to evaluate brain structure in children at risk for HD. Methods Children ages 6–18 years who have a parent with HD are enrolled in the study only if they are currently not manifesting symptoms of the disease. Participants are tested for gene-expansion for research purposes only. The sample included 21 children (age range 6–18 years) who were gene-expanded (GE). The gene non-expanded (GNE) group included 22 children. Each at-risk participant was age and sex matched to three healthy control (HC) children. All participants underwent a brain MRI scan with a 3T magnet using the same protocol. To eliminate effects of outliers, non-parametric methods were used to evaluate brain morphology between groups. Measures included intra-cranial volume (ICV), total brain tissue, CSF (divided into surface CSF and ventricular volume), grey and white matter volume of the four cerebral lobes, volume of caudate, putamen, thalamus and cerebellum. Results GE participants had substantially smaller ICV and total brain tissue volumes (a decrease of roughly 5%) compared to controls. Total CSF was increased. After controlling for ICV, the cortex was decreased in volume and this was most prominent in the parietal lobe. The volume of the putamen was also decreased in the GE group however the volume of the caudate and cerebellum were not different than the controls. The GE group had no significant differences compared to the controls in any measure. Conclusion In this sample of children who are gene-expanded yet greater than an estimated 30 years from onset, global measures of brain growth (ICV) as well as regional tissues (cortex, putamen) are different from controls. This supports the notion that aberrant brain development may play an important role in the pathophysiology of the disease.
Detection of delayed gastric emptying from electrogastrograms with support vector machine

A recent study reported a conventional neural network (NN) approach for the noninvasive diagnosis of delayed gastric emptying from the cutaneous electrogastrograms. Using support vector machine, we show that this relatively new technique can be used for detection of delayed gastric emptying and is in fact able to outdo the conventional NN.
Short Communication Effects of Partial Premixing on NOx Emission Indices of Soot-Containing Flames

NOx emission indices (NOxEI) of laminar high-pressure and turbulent liquid-fueled partially premixed flames arc studied as a function of fuel tube equivalence ratio Ob. In both cases. NOxEI behavior appears to be affected by changes in soot production. Soot levels were visually observed to decrease with increasing levels of partial premixing (decreasing φB). The resulting variation in NOxEI with Ob is vastly different from the variation observed for flames with negligible soot. For the soot containing flames. NOBEI increases continuously with increasing levels of partial premixing. The increase in NOBEI becomes more rapid beyond the point at which soot formation is suppressed. with a subsequent sharp reduction in NO;BEl for φB≤ 1.3. Based on these results, we suggest that optiinuni level of partial premixing can be designed to eliminate soot formation without a sleep NOφBEI penalty in high-pressure flames.
Treatment adherence with antipsychotic medications in bipolar disorder

Poor adherence with lithium and anticonvulsantmedications has been found to be a commonoccurrence among individuals with bipolar disor-der (estimates range between 20 and 55%) and isoften associated with negative clinical outcomes(1–4). A variety of factors such as patient age,marital status, gender, educational level, symp-toms, side eﬀects of medications and comorbidsubstance abuse, as well as environmental factorssuch as psychosocial support and access to care areknown to aﬀect treatment adherence amongindividuals with bipolar disorder (1, 5–13). Post-traumatic stress disorder (PTSD), not infrequently
Rationale for Statins in the Chemoprevention of Prostate Cancer

The potential ability of statin medications to prevent cancer has recently received considerable attention. Of all cancers studied, data for prostate cancer are the most promising. Results from studies examining the association between statin use and reduced risk of prostate cancer have been encouraging, particularly in terms of advanced prostate cancer risk. These findings are supported by a strong foundation of scientific evidence demonstrating the potential cholesterol and non-cholesterol-mediated mechanisms through which statins may prevent prostate cancer. In this article, we analyze recent human data regarding the association between statins and prostate cancer, and the basic scientific data supporting the possible antineoplastic mechanisms of statins. We also address the issue of where to best direct future funding and research energies. There is currently insufficient evidence to recommend all men to initiate therapy with a statin medication regardless of cholesterol profile, but the rationale to move forward with research is clear.
Enhancing timing-driven FPGA placement for pipelined netlists

FPGA application developers often use pipelining, C-slowing and retiming to improve the performance of their designs. Unfortunately, registered netlists present a fundamentally different problem to CAD tools, potentially limiting the benefit of these techniques. In this paper we discuss some of the inherent issues pipelined netlists pose to existing timing-driven placement approaches. We then present two algorithmic modifications that reduce post-routing critical path delay by an average of 40%.
Non-photochemical hole burning in the mixed molecular crystal pentacene in benzoic acid

Abstract Non-photochemical hole burning is observed in the mixed molecular crystal pentacene in benzoic acid. The homogeneous linewidth is obtained from photon echo measurements. Hole burning is monitored wrth absorption spectrometry and photon echo detection. Spontaneous hole filling is observed and the rate of hole filling is reported.
High-Performance Ferrite Nanoparticles through Nonaqueous Redox Phase Tuning.

From magnetic resonance imaging to cancer hyperthermia and wireless control of cell signaling, ferrite nanoparticles produced by thermal decomposition methods are ubiquitous across biomedical applications. While well-established synthetic protocols allow for precise control over the size and shape of the magnetic nanoparticles, structural defects within seemingly single-crystalline materials contribute to variability in the reported magnetic properties. We found that stabilization of metastable wustite in commonly used hydrocarbon solvents contributed to significant cation disorder, leading to nanoparticles with poor hyperthermic efficiencies and transverse relaxivities. By introducing aromatic ethers that undergo radical decomposition upon thermolysis, the electrochemical potential of the solvent environment was tuned to favor the ferrimagnetic phase. Structural and magnetic characterization identified hallmark features of nearly defect-free ferrite nanoparticles that could not be demonstrated through po...
Rawlsian Public Reason and the Theological Framework of Martin Luther King's "Letter from Birmingham City Jail"

The ideal of public reason, made prominent by John Rawls, has become a mainstay of discussions about the proper role of religious arguments in a politically liberal society. In particular, Rawls's theory of public reason requires citizens and public officials to refrain from appealing to comprehensive religious and philosophical doctrines in public deliberation on matters of basic justice and constitutional essentials. In this essay, we review the ways in which the public life of Martin Luther King, Jr. — with its frequent appeals to a comprehensive doctrine to justify disobedience to the law — represents a challenge to the ideal of public reason, and we consider several Rawlsian rejoinders. What is missing from the existing body of scholarship on public reason is a thorough analysis of King's philosophical and theological arguments, including the examples of legal injustice he offered in his celebrated “Letter from Birmingham Jail.” As we note, King's specific examples of unjust laws rely on a theological framework that bedevils the attempt to reconcile his Letter with the constructivist underpinnings of Rawls's theory of public reason. Indeed, Rawls is in something of a bind: either King's argument is not acceptable under the terms of public reason or public reason simply cannot limit contemporary public discourse in the way Rawls has in mind. We consider several possible Rawlsian arguments for the accommodation of King's theological rhetoric, but conclude that the Rawlsian idea of public reason remains deeply problematic.
Friendship, Social Interaction and Subjective Well-Being of Older Men in an Institutional Setting:

The relationship of informal social interaction to subjective well-being of older adults was investigated using the PGC Morale Scale, the MACC Behavioral Adjustment Scale, and a sociometric interview which provided measures of peer friendship and frequency of social interaction. Respondents were fifty-four males aged fifty-two to ninety years, who were residents of a Veterans Administration domiciliary. The predicted positive correlation was obtained between morale and frequency of social interaction with persons outside the institution, but men's friendships within the institution were not related to morale. As expected, men who reported overall change in frequency of social interaction scored substantially lower on the PGC Morale Scale than those who perceived no change. Behavioral adjustment ratings of participants made by a staff member were positively correlated with friendship and social interaction scores. The results were thus consistent with a continuity model of aging, in which maintenance of accustomed levels of social interaction is related to subjective well-being.
Pro-active monitoring and establishment of DNA fingerprint database of Salmonella in raw meat food in Henan Province during 2006～2007

Objective: To investigate the situation of Salmonella contamination and antibiotic resistance in raw meat foods and establishing the foodborne Salmonella DNA fingerprint database in Henan province.Methods:The putative Salmonella strain was confirmed by Biolog automated microbial analysis system,the antibiotic susceptibility was tested by using Kirby-Bauer paper flakes diffusion method and the Salmonella DNA fingerprint database was determined through Ribo-Printer Microbial Characterization System.Results:Salmonella was detected in 118 of 399 raw meat food samples which showed the detection rate was 29.57%.The detection rate in 2007 was higher than that in 2006 but no significant difference between two years(χ2=0.18,P0.05).Salmonella detection rate in chicken(38.33%) was higher than that in pork(16.35%) and showed significant difference(χ2 =88.69,P0.05).12 antibiotics were employed to determine the susceptibility of 121 Salmonella and most of strains showed resistance to the antimicrobials used in the test,the amikacin resistance rate(1.69%) was the lowest in all antibiotics,resistance rate to nalidixic acid was the highest,which reached to 88.14%.The antibiotic resistant Salmonella strains in 2007 were much more than that in 2006 to above antimicrobials,7 ESBL and 2 AMPC Salmonellas were found,both the breadth and depth of Salmonella to antibiotic resistance had a obvious upward trend.The DNA fingerprint of 121 Salmonella strains isolated from raw meat food in Henan province in 2006~2007 was determined and the DNA fingerprint database of foodborne Salmonella in Henan province was established preliminarily.Conclusion:Inspection results showed that Salmonella contamination in raw meat foods was serious in Henan province,the isolates expressed extensive resistance to the antibiotics that were commonly used in clinical therapy and have had a threat to public health.The advice was proposed to strengthen the management of additives of livestock and fowl as well as the antimicrobials used in human to protect the antimicrobial resources.
Study of monitoring iodized-salt situation in Suixian County in 2008

Objective: To understand the Iodized-salt use situation in Suixian County to discover problem and adopt related measures to insure that people use qualified iodized-salt to effectively prevent iodine deficiency disorders(IDD).Methods:Sampling and testing methods stipulated by the Scheme for National Iodinated Salt Surveillance were adopted to examine household iodized-salt quality.Results:Iodized-salt coverage rate of Suixian County was 97.64% and qualified iodized-salt use rate was 91.40%.Conclusion:Target of using qualified iodized-salt in local inhabitants has been basically realized.
Differential Antimicrobial Susceptibilities of Granulicatella adiacens and Abiotrophia defectiva

MICs of 25 Abiotrophia defectiva and 109 Granulicatella adiacens isolates were determined by broth microdilution. Using CLSI breakpoints, the susceptibilities of A. defectiva and G. adiacens isolates were, respectively, 24% and 34% to penicillin, 92% and 22% to ceftriaxone, 48% and 3% to cefepime, 72% and 87% to meropenem, 92% and 10% to cefotaxime, 100% and 97% to levofloxacin, 92% and 80% to clindamycin, and 24% and 50% to erythromycin. All isolates were susceptible to vancomycin. In the penicillin-susceptible subgroup, all A. defectiva isolates were susceptible to ceftriaxone; however, 62% of G. adiacens isolates were ceftriaxone nonsusceptible.
Endothelial adenosine transporter characterization in perfused guinea pig hearts

Adenosine (Ado), a smooth muscle vasodilator and modulator of cardiac function, is taken up by many cell types via a saturable transporter, blockable by dipyridamole. To quantitate the influences o...
Results of Obesity Surgery

Assessment of the outcome of obesity operations is exceedingly complex. Currently there is no consensus among bariatric surgeons as to what constitutes successful weight loss. Furthermore, weight loss data must be regularly reevaluated to account for later regaining of lost weight. There is no question that surgically-induced weight loss results in improvement or resolution of obesity-related medical problems in most patients. Yet it is not known whether sustained long-term weight loss will result in extended amelioration of these medical problems. Analysis of outcome is further complicated by difficulties in maintaining consistent long-term follow-up in such a way that the benefits of weight loss can be objectively evaluated. The next decade should provide improvements in a number of these problem areas. The new computer registry of the American Society of Bariatric Surgery has access to thousands of bariatric surgical patients. This registry will hopefully provide for some standardization in analysis and reporting of results of bariatric operations. The registry may eventually be able to provide the type of actuarial analysis of long-term results necessary to assess the true impact of bariatric operations on the morbidity and mortality risks associated with morbid obesity. It is also probable that more sophisticated patient selection methods will improve the likelihood of successful weight loss both by excluding patients who are prone to failure and by identification of patient profiles that are better suited for treatment by one type of operation over another. In the final analysis, there is no question that morbid obesity poses an increased risk to health and longevity. Thus it is only logical that substantial weight loss in this group of patients could be expected to improve both longevity and quality of life, provided that the treatment methods employed are free of serious side-effects. At present, surgery offers the only realistic hope for successful weight loss in the morbidly obese.
Fluidic Processing of High-Performance ZIF-8 Membranes on Polymeric Hollow Fibers: Mechanistic Insights and Microstructure Control

Recently, a methodology for fabricating polycrystalline metal-organic framework (MOF) membranes has been introduced – referred to as interfacial microfluidic membrane processing – which allows parallelizable fabrication of MOF membranes inside polymeric hollow fibers of microscopic diameter. Such hollow fiber membranes, when bundled together into modules, are an attractive way to scale molecular sieving membranes. The understanding and engineering of fluidic processing techniques for MOF membrane fabrication are in their infancy. Here, a detailed mechanistic understanding of MOF (ZIF-8) membrane growth under microfluidic conditions in polyamide-imide hollow fibers is reported, without any intermediate steps (such as seeding or surface modification) or post-synthesis treatments. A key finding is that interfacial membrane formation in the hollow fiber occurs via an initial formation of two distinct layers and the subsequent rearrangement into a single layer. This understanding is used to show how nonisothermal processing allows fabrication of thinner (5 μm) ZIF-8 films for higher throughput, and furthermore how engineering the polymeric hollow fiber support microstructure allows control of defects in the ZIF-8 membranes. The performance of these engineered ZIF-8 membranes is then characterized, which have H2/C3H8 and C3H6/C3H8 mixture separation factors as high as 2018 and 65, respectively, and C3H6 permeances as high as 66 GPU.
An experimental comparison of equivalent terminal and rotational crossbreeding systems in swine: sow and litter performance.

Two hundred sixty-two rotational and F1 sows were mated to Duroc, Yorkshire, or Landrace boars to study performance differences between equivalent three-breed rotational and three-breed terminal crossbreeding systems. Matings were made to maximize heterosis. The sows were fed either 1.8 or 2.7 kg/d (2.25 and 3.15 kg/d in winter months) during gestation. These matings produced 934 litters to determine the effect of crossbreeding system, breed composition within crossbreeding system, and gestation feeding level on litter sizes and weights, sow weight and backfat thickness at weaning, daily feed intake of the sow during lactation, interval from weaning to estrus, and farrowing rate. Feeding level during gestation was not an important source of variation for any of the traits except litter birth weight and daily feed intake of the sow during lactation. Litter size marketed was .37 pigs/litter greater (P .10) by crossbreeding system. Weaning-to-estrus interval was 1.3 d shorter (P < .03) for sows in the terminal crossbreeding system than for those in the rotational system.(ABSTRACT TRUNCATED AT 250 WORDS)
Photoelectron spectroscopy of nitromethane anion clusters

Abstract Nitromethane anion and nitromethane dimer, trimer, and hydrated cluster anions were studied by photoelectron spectroscopy. Vertical detachment energies, estimated electron affinities, and solvation energies were obtained from the photoelectron spectra. Cluster structures were investigated using theoretical calculations. Predicted detachment energies agreed with experiment. Calculations show water binds to nitromethane anion through two hydrogen bonds. The dimer has a non-linear structure with a single ionic C H⋯O hydrogen bond. The trimer has two different solvent interactions, but both involve the weak C H⋯O hydrogen bond.
Hormonal influence on autoimmune expression in lacrimal tissue of MRL/Mp-Ipr/Ipr and NZB/NZW F1 mice

Autoimmune disorders often exhibit gender-related differences, with estrogens increasing disease severity in females and androgens decreasing immunopathology in males [1]. In fact, androgen administration has been utilized to significantly diminish autoimmune symptoms in animal models of systemic lupus erythematosus, thyroiditis, polyarthritis and myasthenia gravis [1]. Quite possibly, androgen therapy may also provide an effective treatment for Sjogren’s syndrome. This syndrome is an autoimmune disorder observed primarily in females and is characterized lymphocytic infiltration in the lacrimal gland, disruption of acinar and ductal tissues and keratoconjunctivitis sicca [2]. Because androgens modulate lacrimal gland immunity and regulate lacrimal structure and function [3], these hormones may have therapeutic value. Therefore, the objective of the current experiments was to determine, by using mouse models of Sjogren’s syndrome, whether androgen administration might ameliorate autoimmune sequelae in the lacrimal gland.
Advances in asthma 2015: Across the lifespan

In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened. Predicting and preventing exacerbations throughout life might help to reduce progressive lung function decrease and disease severity in adulthood. Although allergy has long been linked to asthma exacerbations, a mechanism through which IgE impairs rhinovirus immunity and underlies asthma exacerbations was demonstrated and improved by anti-IgE therapy (omalizumab). Other key molecular pathways underlying asthma exacerbations, such as cadherin-related family member 3 (CDHR3) and orosomucoid like 3 (ORMDL3), were elucidated. New anti-IL-5 therapeutics, mepolizumab and reslizumab, were US Food and Drug Administration approved for the treatment of patients with severe eosinophilic asthma. In a clinical trial the novel therapeutic inhaled GATA3 mRNA-specific DNAzyme attenuated early- and late-phase allergic responses to inhaled allergen. These current findings are significant steps toward addressing unmet needs in asthma prevention, severity modification, disparities, and lifespan outcomes.
Predictors of neurologic and nonneurologic death in patients with brain metastasis initially treated with upfront stereotactic radiosurgery without whole-brain radiation therapy.

Background In this study we attempted to discern the factors predictive of neurologic death in patients with brain metastasis treated with upfront stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT) while accounting for the competing risk of nonneurologic death. Methods We performed a retrospective single-institution analysis of patients with brain metastasis treated with upfront SRS without WBRT. Competing risks analysis was performed to estimate the subdistribution hazard ratios (HRs) for neurologic and nonneurologic death for predictor variables of interest. Results Of 738 patients treated with upfront SRS alone, neurologic death occurred in 226 (30.6%), while nonneurologic death occurred in 309 (41.9%). Multivariate competing risks analysis identified an increased hazard of neurologic death associated with diagnosis-specific graded prognostic assessment (DS-GPA) ≤ 2 (P = .005), melanoma histology (P = .009), and increased number of brain metastases (P<.001), while there was a decreased hazard associated with higher SRS dose (P = .004). Targeted agents were associated with a decreased HR of neurologic death in the first 1.5 years (P = .04) but not afterwards. An increased hazard of nonneurologic death was seen with increasing age (P =.03), nonmelanoma histology (P<.001), presence of extracranial disease (P<.001), and progressive systemic disease (P =.004). Conclusions Melanoma, DS-GPA, number of brain metastases, and SRS dose are predictive of neurologic death, while age, nonmelanoma histology, and more advanced systemic disease are predictive of nonneurologic death. Targeted agents appear to delay neurologic death.
Multi-layer low frequency tissue equivalent phantoms for noninvasive test of shallow implants and evaluating antenna-body interaction

In this work, a tissue equivalent compound phantom with dielectric properties equivalent to an average human body surface has been developed for a low frequency operating range of 30 MHz to 200 MHz. The compound phantom consists of skin, fat, and muscle layers respectively. The phantom is simple to fabricate with low cost components. A custom coaxial test fixture has been developed to characteristic phantom dielectric properties, which eliminates use of a specialized expensive dielectric measurement probe. The proposed composite phantom can be used as a noninvasive technique to evaluate shallow biomedical implants, antenna-body interaction, and specific absorption rate of tissue media.
Expression Profile of Aging Hematopoietic Stem Cells.

A decline in stem cell function has been suggested to contribute to vertebrate aging. Several labs have documented a reduction in transplant efficiency and skewing in lineage contribution when murine bone marrow or hematopoietic stem cells (HSC) from old donors were transplanted into young recipients. Paradoxically, evidence from several labs including ours has shown that the percentage of phenotypically defined HSC in C57Bl/6 mice increases with age (Fig. 1). Within the serum of aged animals, systemic inflammatory markers such as C reactive protein in humans and IL-1 in mice have been shown to steadily increase with age, however it is unclear if systemic inflammation plays a role in these age-related HSC phenotypes. In order to investigate what might account for these functional changes in HSC aging, we have characterized gene expression in aged HSC using Affymetrix microarrays, examining expression profiles of HSC purified from C57Bl/6 mice that are 2-, 6-, 12-, 21-months old. Using polynomial regression over the time course, we have found more than 700 genes that are 2-fold up-regulated and more than 400 genes that are down-regulated with time. We used the Gene Ontology to categorize age-regulated genes, and have identified the category of ‘inflammatory response’ to be significantly enriched in genes that are up-regulated with age. Strikingly, several NF-Kb regulated genes, previously associated in other tissues with aging and inflammation (e.g. P-selectin, Cox-2, and ICAM-1) are up-regulated in aged HSC. The expression patterns of more than 15 genes, including clusterin, serum deprivation response, and growth hormone receptor, have been validated by quantitative real-time PCR. Furthermore, expression of several surface markers, including P-selectin, a protein that plays a role in inflammation, has been validated at the protein level by flow cytometry. In order to determine if the gene expression changes observed in aged HSC is caused by intrinsic or extrinsic factors, we have transplanted HSC from 21-month-old mice into young recipients and are assessing changes in their expression profile compared to young transplanted HSC. These data demonstrate a role for inflammation in HSC-aging, and may identify genes involved in stem cell transplant efficiency, lineage specification, and the onset of organismal aging. ![Figure 1: ][1] Figure 1: Sca-1 enriched Side Population cells at the indicated ages (in months). The percentage of cells residing within the SP increases 9-fold with age. [1]: pending:yes
Meningococcal serogroup B vaccines: Estimating breadth of coverage

Neisseria meningitidis serogroup B (MenB) is an important cause of invasive meningococcal disease. The development of safe and effective vaccines with activity across the diversity of MenB strains ...
A tale of twin Higgs: natural twin two Higgs doublet models

In original twin Higgs model, vacuum misalignment between electroweak and new physics scales is realized by adding explicit $$ {\mathrm{\mathbb{Z}}}_2 $$ breaking term. Introducing additional twin Higgs could accommodate spontaneous $$ {\mathrm{\mathbb{Z}}}_2 $$ breaking, which explains origin of this misalignment. We introduce a class of twin two Higgs doublet models with most general scalar potential, and discuss general conditions which trigger electroweak and $$ {\mathrm{\mathbb{Z}}}_2 $$ symmetry breaking. Various scenarios on realising the vacuum misalignment are systematically discussed in a natural composite two Higgs double model framework: explicit $$ {\mathrm{\mathbb{Z}}}_2 $$ breaking, radiative $$ {\mathrm{\mathbb{Z}}}_2 $$ breaking, tadpole-induced $$ {\mathrm{\mathbb{Z}}}_2 $$ breaking, and quartic-induced $$ {\mathrm{\mathbb{Z}}}_2 $$ breaking. We investigate the Higgs mass spectra and Higgs phenomenology in these scenarios.
Withdrawal From Signals for Imminent Inescapable Electric Shock

Localized visual signals (CSs) for electric shocks (USs) were presented to pigeons pecking a key for intermittent reinforcers. The key was centered above the fulcrum of a tilting floor that indicated the pigeons’ positions (left or right side) in the chamber. CSs always occurred on the side nearer the pigeon at trial onset, and the proportion of trial time spent on the opposite side (withdrawal from CS) was recorded. Similar proportions were obtained on control trials, which contained no CS or US. In Experiment 1, CS-trial proportions were higher than control-trial proportions in all four birds. Even when Uss were discontinued, CSs that supported withdrawal also suppressed key pecking. In Experiment 2, the unconditioned effects of the CSs were assessed prior to US introduction. For three birds, subsequent sessions were the same as in Experiment 1. For two other birds, CSs and USs were unpaired in order to determine whether pigeons in aversive situations generally withdraw from visual events. The unconditioned effects were minimal, and the birds trained as in Experiment 1 performed similarly to birds in that experiment. CSs neither produced withdrawal nor suppressed key pecking in the other birds. Results were discussed in terms of sign-tracking controlled by signals for aversive USs.
Second-Line Therapy for Advanced Colorectal Cancer: EGFR vs. Continuation of VEGF Inhibition

We review second-line biological therapies for metastatic colorectal cancer (mCRC), including their mechanisms of action, adverse events, survival outcomes, optimal chemotherapy combinations, and sequencing of agents. The advent of biological therapeutics targeting vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways has enhanced the benefits afforded by the plethora of chemotherapeutic agents for patients with mCRC over the past 10 years, nearly tripling the median OS. Individual biomarkers predicting prognosis and response to VEGF vs. EGFR therapy have been identified. For patients who progress on first-line VEGF therapy, evidence suggests that continued VEGF inhibition may be as efficacious as changing to EGFR therapy with less adverse effects. However, for patients who progress after first-line EGFR therapy, early studies suggest changing to agents targeting the VEGF pathway. Biological options for patients with mCRC who progressed on first-line concomitant chemotherapy and biologic therapy depend on individual tumor characteristics and choice of first-line therapy. Future research should focus on prognostic and predictive biomarkers to better inform choice of first-line and sequential therapy beyond progression.
CrystalNet: Faithfully Emulating Large Production Networks

Network reliability is critical for large clouds and online service providers like Microsoft. Our network is large, heterogeneous, complex and undergoes constant churns. In such an environment even small issues triggered by device failures, buggy device software, configuration errors, unproven management tools and unavoidable human errors can quickly cause large outages. A promising way to minimize such network outages is to proactively validate all network operations in a high-fidelity network emulator, before they are carried out in production. To this end, we present CrystalNet, a cloud-scale, high-fidelity network emulator. It runs real network device firmwares in a network of containers and virtual machines, loaded with production configurations. Network engineers can use the same management tools and methods to interact with the emulated network as they do with a production network. CrystalNet can handle heterogeneous device firmwares and can scale to emulate thousands of network devices in a matter of minutes. To reduce resource consumption, it carefully selects a boundary of emulations, while ensuring correctness of propagation of network changes. Microsoft's network engineers use CrystalNet on a daily basis to test planned network operations. Our experience shows that CrystalNet enables operators to detect many issues that could trigger significant outages.
Design of estimators for the inverse of the rotor time constant of the induction motor with known flux

The paper discusses two observer designs for estimation of the inverse of the rotor time constant of the induction motor. The paper presents the model and develops a linear and a sliding-mode observer. Estimation is based on the dynamic equation of the flux magnitude in the rotating reference frame. The stationary-frame fluxes are obtained using a voltage model observer — they are used for field orientation and also to compute the flux magnitude. Based on the measured voltages, currents, and with known flux, the paper estimates the rotor time constant inverse using a Pseudo-MRAS sliding mode observer. The paper also presents a linear observer, however, it is shown that this design does not perform. The method proposed is simple and is not highly computational. The sensitivity of the observer to the input quantities and motor parameters is studied. The theory is validated by computer simulations and experimental tests.
Optimal power, power limit and damping of vibration based piezoelectric power harvesters

Power harvesting describes the process of acquiring the ambient energy surrounding a system and converting it into usable electrical energy. Much of the work over the past two decades has focused on the conversion of ambient vibration energy sources using piezoelectric, electromagnetic and electrostatic transduction. Attempts were made to obtain a general model that could be applied to any transduction mechanism. Of the most interest is an electromagnetic generator model that was used by many researchers to model piezoelectric power harvesters. Two major results from the model are the power limit expression and the equal relationship between the electrically induced damping and the mechanical damping to reach the power limit. However, piezoelectric power harvesters cannot be accurately modeled by this electromagnetic model due to the essential difference in physics. There have also been attempts to obtain the power limit expression based on piezoelectric relationships, but they either neglect the piezoelectric backward coupling to the structure, or assume the power limit occurs at the resonance of the system. This paper obtains the power limit expression based on the piezoelectric coupled equations without those assumptions. In addition, the relationship between the electrically induced damping and mechanical damping at the power limit is studied. Furthermore, a closed-form criterion is derived and proposed to define strongly and weakly coupling power harvesters, whose differences in power characteristics are explained through analytical and numerical analysis. While most of the discussion is focused on linear power harvesters connected to a resistive circuit, the aim of this paper is to provide a comprehensive and deep understanding of this simple configuration, answers to important questions, and a starting point to develop a more general theory on power harvesters because similar system characteristics are observed in power harvesters with more complexities.
A methodology for auto-calibrating urban building energy models using surrogate modeling techniques

Owners of large building portfolios such as university campuses have long relied on building energy models to predict potential energy savings from various efficiency upgrades. Traditional calibration procedures for individual building model are time intensive and require specially trained personnel, making their applications to campuses with hundreds of buildings prohibitive. Recently proposed automatic calibration techniques reduce the manual effort during calibration but require hundreds of thousands of energy simulations which increase their cost. To reduce the computational effort of these methods, this paper proposes a methodology that uses a data-driven approximation technique. Instead of brute-force simulations using detailed engineering models, this study employs statistical surrogate models with an optimization algorithm to estimate properties of unknown building parameters. Results demonstrate that when envelope information is available, this workflow yields sufficiently accurate estimates of h...
A Theory of Nonlinear Evolution Equations

A theory of solving nonlinear evolution equations based on three different methods is presented which is independent of C o -semigroups. From the standpoint of applications, its important feature is the possibility of solving nonlinear evolution equations via linearized evolution equations.
20 Hepatitis C in children

Publisher Summary This chapter discusses the prevalence and pathology of hepatitis C in children. Although the incidence of new hepatitis C virus (HCV) infections in the United States is decreasing, the 4 million estimated existing cases are expected to cause an increase in the number of people with end-stage liver disease in the next decade or two. The contribution of pediatric cases to this health care burden is difficult to quantify because the majority of HCV-infected children have probably not yet been identified. In addition, new pediatric infections will primarily be caused by perinatal transmission. Because most HCV-infected women of childbearing potential have probably not yet been recognized or treated and there is as yet no way to prevent perinatal transmission, new childhood infections will continue to occur. For these reasons, elucidation of the mechanisms of perinatal infection, factors affecting progression of disease, and optimal therapies of childhood HCV infection warrant further study.
What Are Governments Spending on Health in East and Southern Africa

Progress toward universal health care (UHC) in Africa will require sustained increases in public spending on health and reduced reliance on out-of-pocket financing. This article reviews trends and patterns of government spending in the East and Southern Africa regions and points out methodological challenges with interpreting data from the World Health Organization's (WHO) Global Health Expenditure Database (GHED) and other sources. Government expenditure for health has increased for most countries, albeit at a slower rate than gross domestic product (GDP). In most countries there has been a prioritization away from health in government budgets, putting the onus on the private sector and donors to fill the gap. Donor support is important in the region but reliance on external spending is not consistent with countries' stated ambitions of universal health coverage. A number of methodological challenges with estimating health expenditures are identified. Capturing health expenditures adequately across agencies and levels of decentralization can be challenging, and off-budget funds and arrears are evasive. Measurement error can be significant because actual expenditure information can be hard to come by and is often dated and unreliable. Furthermore, how external financing is captured will affect government health expenditure estimates. These factors have contributed to differences in expenditure estimates between the WHO GHED and country-specific public expenditure reviews and complicate interpretation. The article concludes that it is critical to strengthen national data capacity and international efforts to promote quality and consistency of data. The GHED is an invaluable resource for monitoring and benchmarking health expenditures. It is best used in combination with deep dive country expenditure assessments.
Amazon deforestation drives malaria transmission, and malaria burden reduces forest clearing: a retrospective study

Abstract Background Deforestation and other forms of land use change are among the most pressing anthropogenic environmental impacts. In Brazil, a recent resurgence of malaria paralleled rapid deforestation and settlement in the Amazon basin, yet empirical evidence of a deforestation-driven increase in malaria remains surprisingly equivocal. We hypothesise that an underlying cause of this ambiguity is that deforestation and malaria influence each other in bidirectional causal relationships, where deforestation increases malaria through ecological mechanisms and malaria simultaneously reduces deforestation through socioeconomic mechanisms. Methods We tested our hypotheses with a large and robust geospatial dataset encompassing 807 municipalities across 13 years and show that deforestation has a strong positive effect on human malaria incidence, controlling for variation over space and time and across gradients of land use intensification. Findings Our results suggest that a 10% increase in deforestation leads to a 3·7% increase in Plasmodium falciparum malaria cases (about 1730 additional cases in 2008). The effect is larger in the interior and absent on the fringe of the Amazon where little forest remains. However, this strong effect is only detectable after controlling for a feedback of malaria burden on forest loss, whereby increased malaria burden significantly reduces forest clearing, possibly mediated by human behaviour or economic development. We estimated that for a 1% increase in P falciparum malaria, we would expect a 1·5% decrease in forest area cleared (about 235 fewer km2 lost in 2008). Interpretation This bidirectional socioecological feedback between deforestation and malaria, which attenuates as land use intensifies, shows the intimate ties between environmental change and human health. Funding US National Science Foundation Postdoctoral Research Fellowship in Biology (#1611767).