Effect of neonatal rat bisphenol a exposure on performance in the Morris water maze.
Bisphenol A (BPA), an environmental estrogen, is a component of many food and beverage containers and can leach into the container contents over time. Due to its estrogenic properties, exposure to BPA during development could alter the appropriate maturation of pathways essential for normal cognitive function at later ages. To investigate this, the effects of repeated postnatal exposure of male and female rats to BPA on spatial learning and memory were investigated using a Morris water maze. Breeders and offspring were maintained on a standard phytoestrogen-free diet. Oral administration of 72 microg/kg 17 beta-estradiol (E(2)), 100 microg/kg BPA (low BPA), 250 microg/kg BPA (high BPA), or the safflower oil vehicle was performed daily from postnatal d 1 (PND1) through PND14. There were no treatment-related effects on swimming ability or motivation (PND33) or on acquisition of maze solution (PND34-37). However, acquisition of maze performance was significantly better in control males than in control females. Treatment with E(2) and low BPA disrupted this normal gender-dependent pattern of acquisition, while treatment with high BPA did not. In a probe trial (PND40), females treated with high BPA spent significantly less time in the escape quadrant. These data indicate that E(2) and low dosages of BPA can alter the normal gender-dependent pattern of acquisition, while higher dosages of BPA alter the retention of spatial information without significantly affecting acquisition.


Optical layout and mechanical structure of polarimeter-interferometer system for Experimental Advanced Superconducting Tokamak.
A Far-InfaRed (FIR) three-wave POlarimeter-INTerferometer (POINT) system for measurement current density profile and electron density profile is under development for the EAST tokamak. The FIR beams are transmitted from the laser room to the optical tower adjacent to EAST via ∼20 m overmoded dielectric waveguide and then divided into 5 horizontal chords. The optical arrangement was designed using ZEMAX, which provides information on the beam spot size and energy distribution throughout the optical system. ZEMAX calculations used to optimize the optical layout design are combined with the mechanical design from CATIA, providing a 3D visualization of the entire POINT system.


Investigating the Effects of Fiber Reinforced Concrete on the Performance of End-Zone of Pre-Stressed Beams.
This paper presents the results of the behavior of end zone of post-tensioned (PT) beams made of fiber reinforced concrete (FRC). The principal aim of using FRC was to enhance the ductility and post-cracking behavior of end-zone of post-tensioned beams. A stronger and tougher end-zone of PT-beams is necessary when it is subjected to dynamic loading. Post-tensioned (PT) beams are typically used for the construction of bridges and industrial buildings, which are often subjected to vibrations and cyclic loading. Pre-mature cracking of the end zone (EZ) of a PT-beam is considered the type of problem that may cause the structural collapse. In this research program, polyvinyl alcohol (PVA) and copper-coated steel (CCS) fibers were used in concrete for improving the EZ performance of PT-beams. The use of FRC caused a 50% reduction in the shear reinforcement within the end zone of the PT-beam, which also avoided the congestion of steel in the end zone. Hence, the concrete was placed homogeneously, and smooth finished surfaces of the beams were obtained. FRC controlled the bursting of the end zone during the transfer of the full pre-stress force, and approximately 25% increment in the strain energy of the end zone was observed, which was also found efficient in strain diminution along the length of the beam.


New techniques for management of the crooked nose.
The crooked or twisted nose results from a complex deformity of the bony pyramid, the upper and lower cartilaginous vaults, and the septum and causes functional and aesthetic problems. The forces of scar contracture coupled with long-standing cartilage deformation may make the crooked nose resistant to conventional surgical intervention. The middle vault of the nose may exhibit deformities that are due to atrophy, deviations, and skewing in relationship to the other regions of the nose. We report a series of 79 cases of significantly crooked noses to highlight 5 techniques not widely discussed in the facial plastic surgery literature.


Use of physiologically based kinetic (PBK) modeling to study interindividual human variation and species differences in plasma concentrations of quercetin and its metabolites.
Biological activities of flavonoids in vivo ultimately depend on the systemic bioavailability of the aglycones and their metabolites. We aimed to develop physiologically based kinetic (PBK) models to predict plasma concentrations of the flavonoid quercetin and its metabolites in individual human subjects and to define species differences compared with male rat. The human models were developed based on in vitro metabolic parameters derived from incubations with pooled and 20 individual human tissue fractions and by fitting kinetic parameters to available in vivo data. The outcomes obtained were compared to a previously developed model for quercetin and its metabolites formation in male rat. Quercetin-3'-O-glucuronide was predicted to be the major circulating metabolite in 19 out of 20 individuals, while in male rat di- and tri-conjugates of quercetin containing a glucuronic acid, sulfate and/or methyl moieties are the major metabolites. Significant species differences occur in major circulating metabolites of quercetin suggesting that rat is not an adequate model to study effects of quercetin in man. The defined PBK models can be used to guide the experimental design of in vitro experiments with flavonoids, especially to better take into account the relevance of metabolism and the contribution of metabolites to the biological activity in humans.


γδTCR immunoglobulin constant region domain exchange in human αβTCRs improves TCR pairing without altering TCR gene-modified T cell function.
The adoptive genetic transfer of T cell receptors (TCRs) has been shown to be overall feasible and offer clinical potential as a treatment for different types of cancer. However, this promising clinical approach is limited by the serious potential consequence that exogenous TCR mispairing with endogenous TCR chains may lead to the risk of self-reactivity. In the present study, domain‑exchange and three‑dimensional modeling strategies were used to create a set of chimeric TCR variants, which were used to exchange the partial or complete constant region of αβTCR with corresponding γδTCR domains. The expression, assembly and function of the chimeric TCR variants were examined in Jurkat T cells and peripheral mononuclear blood cells (PBMCs). Genetically‑encoded chimeras were fused with a pair of fluorescent proteins (ECFP/EYFP) to monitor expression and the pairing between chimeric TCRα chains and TCRβ chains. The fluorescence energy transfer based on confocal laser scanning microscopy showed that the introduction of γδTCR constant sequences into the αβTCR did not result in a global reduction of mispairing with endogenous TCR. However, the TCR harboring the immunoglobulin‑like domain of the γδTCR constant region (i.e., TCR∆IgC), showed a higher expression and preferential pairing, compared with wild‑type (wt)TCR. The function analysis showed that TCR∆IgC exhibited the same levels of interferon-γ production and cytotoxic activity, compared with wtTCR. Furthermore, these modified TCR-transduced T cells retained the classic human leukocyte antigen restriction of the original TCR. The other two chimeric TCRs, had either exchange of the cp+tm+ic domain or exchange of the whole C domain (Fig. 1). Ultimately, exchange of these domains demonstrated defective function in the transduced T cells. Taken together, these findings may provide further understanding of the γδTCR constant domain with implications for the improvement of TCR gene transfer therapy.


A calcium-dependent tyrosine kinase splice variant in human monocytes. Activation by a two-stage process involving adherence and a subsequent intracellular signal.
Freshly isolated human monocytes do not express p125(FAK) but upon adherence to substrata activate the highly related calcium-dependent tyrosine kinase (CADTK), also known as Pyk2, CAKbeta, RAFTK, and FAK2. The monocyte CADTK was 5 kDa smaller than protein from epithelial cells; isolation and sequencing of the monocyte CADTK cDNA revealed a predicted 42-amino acid deletion between the two proline-rich domains of the enzyme. The nucleic acid sequence suggests that the deletion is caused by alternative RNA splicing. This species was also found in T and B lymphocytes and appears to be the predominant form of cytoskeletal associated tyrosine kinase in non-neoplastic, circulating, hematopoietic cells. CADTK was not activated when monocytes maintained in suspension were treated with agents that produce an intracellular calcium (thapsigargin) or protein kinase C (phorbol 12-myristate 13-acetate) signal including a chemokine, RANTES, that binds to the HIV co-receptor, CCK5. In contrast, monocyte adherence to tissue culture plastic-stimulated CADTK tyrosine phosphorylation, a process that was enhanced by thapsigargin, phorbol 12-myristate 13-acetate, and RANTES but that was completely blocked by preincubation with cytochalasin D. When compared with plastic, adherence to fibronectin- or collagen-coated surfaces produced only minimal CADTK activation but permitted significant stimulation by added thapsigargin. These data suggest that in a cell type that lacks p125(FAK), CADTK plays an early role in post-adherence signaling. Its activation involves two stages, cytoskeletal engagement, which is permissive, and co-stimulatory signals (calcium or protein kinase C) generated by extensive cell surface engagement, agonists, or inflammatory chemokines.


TIMP-2 and IGFBP7 in human kidney biopsies in renal disease.
Tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are markers of tubular stress and urinary [TIMP-2]*[IGFBP7] is an established biomarker for risk assessment of acute kidney injury. There are no studies of expression profiles or localization of these markers in human renal tissue with confirmed renal disease. We analysed 37 kidney biopsies of patients with renal disease and 10 non-diseased control biopsies for TIMP-2 and IGFBP7 expression using immunohistochemistry. Changes in glomerular morphology were evaluated by a semi-quantitative glomerulosclerosis score (GSI) and tubular interstitial changes were graded by the tubular injury score (TSI) using periodic acid-Schiff-stained paraffin sections. Interstitial fibrosis and tubular atrophy (IF/TA) were graded according to the Banff classification. Urinary [TIMP-2]*[IGFBP7] was collected at the time of biopsy. TIMP-2 and IGFBP7 had significantly greater expression in kidney biopsies from patients with renal disease compared with control tissue, especially in the tubular compartment. Here, IGFBP7 was detected in proximal and distal tubules while TIMP-2 was predominantly localized in the collecting ducts. Renal injury significantly correlated with staining intensity for TIMP-2 and IGFBP7: GSI weakly correlated with glomerular TIMP-2 (r = 0.36) and IGFBP7 (r = 0.35) and TSI correlated with tubular TIMP-2 (r = 0.41) and IGFBP7 (r = 0.43). Urinary [TIMP-2]*[IGFBP7] correlated weakly with the histopathological damage score but not with glomerular and tubular expression. Our findings underline the role of TIMP-2/IGFBP7 as an unspecific marker of renal injury that is already in use for early detection of acute kidney injury.


Aberrant methylation-mediated silencing of microRNAs contributes to HPV-induced anchorage independence.
Cervical cancer and a subset of anogenital and head-and-neck carcinomas are caused by high-risk types of the human papillomavirus (hrHPV). During hrHPV-induced malignant transformation keratinocytes become able to grow anchorage independently, a tumorigenic trait at least partly associated with inactivation of tumor suppressor genes. We used hrHPV-containing keratinocytes to investigate the role of DNA methylation-mediated silencing of microRNAs (miRNAs) in the acquisition of anchorage independence.Anchorage dependent (n=11) and independent passages (n=19) of 4 hrHPV-immortalized keratinocyte cell lines were treated with 2'-deoxy-5-azacytidine (DAC). Genome-wide miRNA expression profiles before and after treatment were compared to identify miRNAs silenced by methylation. Bisulfite sequencing and methylation-specific PCR showed increased methylation of hsa-mir-129-2/-137/-935/-3663/-3665 and -4281 in anchorage independent HPV-transformed keratinocytes and cervical cancer cell lines. Mature miRNAs derived from hsa-mir-129-2/-137/-3663 and -3665 showed functional relevance as they decreased anchorage independence in cervical cancer cell lines. Cervical (pre)cancerous lesions demonstrated increased methylation of hsa-mir-129-2/-935/-3663/-3665 and -4281, underlining the clinical relevance of our findings.In conclusion, methylation-mediated silencing of tumor suppressive miRNAs contributes to acquisition of an anchorage independent phenotype. This study further substantiates the importance of miRNAs during early stages of carcinogenesis and underlines their potential as both disease markers and therapeutic targets.


In vivo studies of repair of 2-aminopurine in Escherichia coli.
The repair of the base analog 2-aminopurine has been studied in vivo by using a temperature-sensitive mutant of the cloned mutH gene of Escherichia coli. Our results suggest that the lethal event in killing of dam mutants by 2-aminopurine does not result simply from incorporation of 2-aminopurine into the DNA and its subsequent repair. Furthermore, a 10-fold increase in the level of 2-aminopurine incorporated into the DNA of a dam mutH double mutant has little effect on the mutation frequency of this strain. An alternative mechanism for the mutagenicity of 2-aminopurine in E. coli is proposed.


First 10,000 chorionic villus samplings performed on singleton pregnancies by a single operator.
Chorionic villus sampling (CVS) was performed in 10,000 consecutive singleton pregnancies by a single principal operator, working in two institutions. The procedure was performed between 8 and 32 gestational weeks: transabdominal (TA) sampling was carried out in 8479 cases and transcervical (TC) in 1521. Patients were referred for chromosomal risk in 89.1 per cent of cases, Mendelian disorders in 10.5 per cent, and DNA investigations for paternity or infectious agents in 0.4 per cent of cases. The sampling success rate for both TA and TC techniques by the second insertion was 99.8 and 99.2 per cent, respectively. TA sampling succeeded in a higher number of cases at the first insertion (98 per cent vs. 86.8 per cent) and was associated with smaller samples (< 10 mg) in fewer cases (3.2 per cent vs. 4.9 per cent). Cytogenetic analysis was highly successful (99.4 per cent) and accurate; however, in one case a de novo structural rearrangement of chromosome I was not recognized. Mosaicism or rare trisomies were reported in 1.30 per cent of cases. Five diagnostic errors in DNA investigation (0.51 per cent) ended with the birth of affected fetuses. Fetal loss through 28 weeks' gestation in the pregnancies intended to continue was 2.58 per cent; the rate increased with maternal age (1.22 per cent at less than 30 years to 3.8 per cent at 40 years or more), while gestational age affected the abortion rate only at 8 weeks (odds ratio=2.22, P<0.05). Rates of premature delivery, low birth weight, and perinatal mortality did not differ from the Italian standards. By comparison with the Italian Birth Defects Registry data, no differences were found for the major malformations, including transverse limb reduction defects (TLRDs) (4.34 vs. 3.28 x 10,000). Total malformations and TLRDs did not show any pattern relation to either maternal age or gestational age.


Out-of-hospital rescue medication in dogs with emergency seizure disorders: an owner perspective.
Emergency seizure disorders such as status epilepticus and cluster seizures are unlikely to cease spontaneously while prolonged seizure activity become progressively more resistant to treatment. Early administration of rescue medication in canine epileptic patients, in particular benzodiazepines, at seizure onset by the owners can be life-saving and brain protecting. Clinical studies in dogs evaluating the use of rescue medication in hospital environment exist, however, the owner perspective has not been assessed to date. To evaluate the use of rescue medication in dogs with seizure emergencies by the owner at home. Observational study based on online surveys of owners of dogs with emergency seizure disorders. The questionnaire was answered by 1,563 dog owners, of which 761 provided complete and accurate answers suitable for analysis. Of these, 71% administered diazepam, 19% midazolam, 6% levetiracetam, 3% lorazepam, and 4% more than one rescue or other medication. Overall, the success rates based on owners' perspective for intranasal midazolam and rectal diazepam were 97 and 63%, respectively. Owners reported a compliance level of 95 and 66% for intranasal midazolam and rectal diazepam administration, respectively. Even though rectal diazepam was the most used rescue medication in this survey population, intranasal midazolam was perceived by the owners as a better option regarding effectiveness, time to seizure cessation and owner compliance.


How Workers Fared under the ACA.
Many politicians, policy makers, and analysts have debated whether the Affordable Care Act (ACA) would have negative effects on the labor market, such as reducing employment, earnings, or hours worked. Building on the existing literature, we investigated how workers' coverage changed under the ACA and whether coverage gains were associated with changes in labor market outcomes across occupations through 2017. We also examined whether occupations experiencing increased coverage through nonemployment sources (i.e., Medicaid or individual plans purchased on the ACA's Marketplaces) also experienced offsetting declines in employer-sponsored insurance (ESI) coverage. Finally, we investigated whether the employer mandate was associated with changes in ESI offers to workers. Among workers in occupations experiencing larger coverage gains under the ACA, we found no evidence that employment, hours worked, or earnings fell relative to workers in occupations that had little change in coverage rates over the same period. Moreover, ESI offers remained stable, even among workers in firms likely subject to the employer mandate. Overall, we found that predictions that the coverage provisions and mandates of the ACA would lead to adverse labor market effects did not materialize.


Low prevalence of Neospora caninum and Toxoplasma gondii antibodies in dogs in Jilin, Henan and Anhui Provinces of the People's Republic of China.
Neospora caninum and Toxoplasma gondii are important pathogens of worldwide distribution. N. caninum is a major cause of abortion in cattle and dogs are main reservoirs because they excrete the environmentally resistant oocysts. Toxoplasmosis is a worldwide zoonosis and dogs are considered as sentinels for this parasite because of their close contact with people and cats; additionally dog meat is also used for human consumption in China. The aim of the present study was to assess the prevalence of N. caninum and T. gondii infection in dogs from China. A total of 425 countryside dog hearts in Jilin, Henan and Anhui provinces of the People's Republic of China were collected from slaughter houses in two batches; the first batch of 96 in October 2013, and the second batch of 329 in April 2014. Serum samples extracted from 96 dog hearts were tested for antibodies to N. caninum and from 425 dog hearts were tested for T. gondii antibodies in the modified agglutination tests (cut-off 1:25 for both), using respective antigens. Antibodies to N. caninum were 6 of 96 (6.25%) of dogs with titers of 1:25 in 2, 1:50 in 3, and 1:100 in 1. All seropositive dogs were more than 1 year old. Antibodies to T. gondii were found in 35 of 425 (8.24%) dogs with titers of 1:25 in 15, 1:50 in 14; and 1:100 in 6. The results of the present study indicated low prevalence of N. caninum and T. gondii antibodies in dogs of China, compared with Europe and America. Identification of the risk factors that underlie these differences may help prevention of neosporosis and toxoplasmosis. This is the first report of N. caninum infection in dogs from China.


Assessing the fecal microbiota: an optimized ion torrent 16S rRNA gene-based analysis protocol.
Assessing the distribution of 16S rRNA gene sequences within a biological sample represents the current state-of-the-art for determination of human gut microbiota composition. Advances in dissecting the microbial biodiversity of this ecosystem have very much been dependent on the development of novel high-throughput DNA sequencing technologies, like the Ion Torrent. However, the precise representation of this bacterial community may be affected by the protocols used for DNA extraction as well as by the PCR primers employed in the amplification reaction. Here, we describe an optimized protocol for 16S rRNA gene-based profiling of the fecal microbiota.


Insights into the Structural Chemistry of Anhydrous and Hydrous Hexavalent Uranium and Neptunium Dinitrato, Trinitrato, and Tetranitrato Complexes.
A systematic investigation is presented which examines the structural chemistry of anhydrous and hydrous ternary hexavalent uranium and neptunium dinitrato, trinitrato, and tetranitrato complexes. Using slow evaporation methods under acidic conditions the uranium and neptunium nitrate complexes γ-K[UO2(NO3)3], K2[UO2-cis-(NO3)4], [NpO2(NO3)2(H2O)2]·4H2O, and Cs[NpO2(NO3)3] have been synthesized and their structures refined using single-crystal X-ray diffraction data. γ-K[UO2(NO3)3] adopts an orthorhombic structure in space group Pbca consisting of antiparallel aligned [UO2(NO3)3]- moieties. K2[UO2-cis-(NO3)4] adopts a monoclinic structure in space group P21/c consisting of [UO2(NO3)4]2- moieties with two monodentate and two bidentate nitrate ligands that are arranged in a cis configuration about the uranyl, UO22+, center. Previous investigations have only identified trans variants of this monoclinic structure, and this is the first report of the cis form and also the occurrence of geometric isomerism in uranyl nitrates. [NpO2(NO3)2(H2O)2]·4H2O adopts an orthorhombic structure in space group Cmc21 consisting of parallel aligned [NpO2(NO3)2(H2O)2] moieties that are in a trans configuration with respect to the bidentate nitrate ligands. Cs[NpO2(NO3)3] adopts a hexagonal structure in space group R3c consisting of parallel aligned [NpO2(NO3)3]- moieties. It was found that despite using a Np(V) nitrate solution as the starting reagent, Np(VI) nitrate structures were consistently recovered under acidic conditions. These observations are discussed and rationalized with respect to standard reduction potentials, particularly how redox conditions and acidity affect the oxidation state of Np and subsequent structure formation. The structures uncovered in this investigation are discussed comparatively and systematically in detail with other reported anhydrous and hydrous ternary hexavalent uranium and neptunium dinitrato, trinitrato, and tetranitrato complexes, particularly with respect to how synthesis conditions, including pH and geometric isomerism, affect the structural chemistry.


Correlates of the Attitude Toward Life-Sustaining Treatment: A Study With Older Adults in South Korea.
The goal of the present study was to examine factors associated with the attitude toward life-sustaining treatment among older adults in South Korea. Focus was given to sociodemographic characteristics (age, gender, education, financial status, and religious affiliation), family-related variables (presence of a spouse, children, and a living parent [or in-law]), and health-related variables (chronic conditions, functional disability, and self-rated health). Using data from 6,895 participants (aged 65-97) in the 2014 Korean National Elderly Survey, logistic regression model was tested. The proportion of the sample that endorsed a strong disagreement with the provision of life-sustaining treatment was 53.2%. The increased odds of having a strong disagreement was found in those with younger age (<75), higher education, a living parent (or in-law), and more favorable ratings of health. Findings shed light on programs and services on end-of-life care planning for older adults in South Korea.


Comparison of the NCRA and NAACCR Strategic Management Plans.
The Strategic Management Plans of the National Cancer Registrars Association (NCRA) and the North American Association of Central Cancer Registries (NAACCR) were compared, and differences noted. No uncovered subject areas were found.


Low-cost, multimodal, portable screening system for early detection of oral cancer.
Oral cancer is an important global health problem. There is an urgent need for improved methods to detect oral cancer and its precursors, because early detection is the best way to reduce oral cancer mortality and morbidity. In this work, we describe simple modifications to a surgical headlight system that enables direct visualization and digital image acquisition from oral tissue in multiple imaging modalities including fluorescence, white-light reflectance, and orthogonal polarization reflectance. Images obtained with the system in-vivo demonstrate that it is an attractive technology to explore for oral cancer screening in low-resource environments where clinical expertise is often unavailable.


[Evolution of the mortality rate of newborn infants transferred to a Parisian intensive care service from 1969 to 1978].
This study reports on the trend in neonatal death rates in a Paris intensive care unit between 1969 and 1978. Three time-periods were compared: 1969-1971, 1972-1974, and 1975-1978. These limits were chosen to take into account the introduction of continuous airway positive pressure in the unit in 1972, and the gradual implementation, from 1972 onwards, of a new perinatal care policy in France. The mortality rate was significantly lower in the second period than in the first, after adjustment on birthweight and type of disease. This trend varied according to type of disease: the death decreased significantly in case of membrane disease or foetal distress, but not in case of admission for amniotic inhalation or congenital anomalies. The gradual improvement in newborn's condition on arrival in the unit played a part in the improvement in survival, as well as the use of the continuous airway positive pressure.


Sociological histories on epilepsy as "causes for disqualification" stipulated in the Japanese Road Traffic Act of 1960 and Revised Road Traffic Act of 2001.
In the wake of successive cases of fatal accidents caused by patients behind the wheel whose driving was likely to be hindered due to paroxysmal diseases, including epilepsy, there has been an outcry from victims demanding stricter criminal penalties against the perpetrators due to negligence. As a result of this action, a revised Road Traffic Act was put into effect in Japan on June 14, 2013. This act established new penal provisions against any person who provides false statements on his/her medical condition(s) when acquiring or renewing a driver's license. In this paper, the social circumstances will be introduced regarding road traffic in Japan when the Road Traffic Act, the origin of today's revised Road Traffic Act, was enacted in 1960. An overview of the reasons behind the enactment of the original act will be provided. Additionally, the handling of patients with "provisions for disqualification," whose driving is likely to be hindered due to paroxysmal diseases, including "epilepsy," will be reviewed. This handling attracted repeated controversy during the enactment of the original act and will also be reviewed. One significant change in wording from "absolute causes for disqualification" in the Road Traffic Act of 1960 to "relative causes for disqualification" in the Revised Road Traffic Act of 2001 also will be discussed from a medical sociology perspective. Finally, the social status and socio-economic position of drivers with paroxysmal diseases, as it pertains to influences on lawmakers, will be discussed.


Automatic Selection of Order Parameters in the Analysis of Large Scale Molecular Dynamics Simulations.
Given the large number of crystal structures and NMR ensembles that have been solved to date, classical molecular dynamics (MD) simulations have become powerful tools in the atomistic study of the kinetics and thermodynamics of biomolecular systems on ever increasing time scales. By virtue of the high-dimensional conformational state space that is explored, the interpretation of large-scale simulations faces difficulties not unlike those in the big data community. We address this challenge by introducing a method called clustering based feature selection (CB-FS) that employs a posterior analysis approach. It combines supervised machine learning (SML) and feature selection with Markov state models to automatically identify the relevant degrees of freedom that separate conformational states. We highlight the utility of the method in the evaluation of large-scale simulations and show that it can be used for the rapid and automated identification of relevant order parameters involved in the functional transitions of two exemplary cell-signaling proteins central to human disease states.


Massive Transfusion Protocol in a 69 Year Old Woman with Alloantibodies.
Unlike routine blood transfusions that are managed by attending providers and rely on compatibility testing, massive transfusions are managed by the trauma team members, who usually do not have immediate access to compatibility testing. Incompatible C or E antigens, when present in uncrossmatched O positive blood, require transfusion support so that health care professionals can manage potential causes for extravascular hemolysis. Herein, we describe a massive transfusion situation in which immediate patient management was required to mitigate potentially fatal clinical consequences of transfused red blood cell antibodies. In addition, this case study shows how the utility of chemistry and hematology laboratory results can illustrate the complexities of massive transfusion management in the context of incompatible C or E antigens.


The CD8+ dendritic cell subset selectively endocytoses dying cells in culture and in vivo.
Dendritic cells (DCs) are able in tissue culture to phagocytose and present antigens derived from infected, malignant, and allogeneic cells. Here we show directly that DCs in situ take up these types of cells after fluorescent labeling with carboxyfluorescein succinimidyl ester (CFSE) and injection into mice. The injected cells include syngeneic splenocytes and tumor cell lines, induced to undergo apoptosis ex vivo by exposure to osmotic shock, and allogeneic B cells killed by NK cells in situ. The CFSE-labeled cells in each case are actively endocytosed by DCs in vivo, but only the CD8+ subset. After uptake, all of the phagocytic CD8+ DCs can form major histocompatibility complex class II-peptide complexes, as detected with a monoclonal antibody specific for these complexes. The CD8+ DCs also selectively present cell-associated antigens to both CD4+ and CD8+ T cells. Similar events take place with cultured DCs; CD8+ DCs again selectively take up and present dying cells. In contrast, both CD8+ and CD8- DCs phagocytose latex particles in culture, and both DC subsets present soluble ovalbumin captured in vivo. Therefore CD8+ DCs are specialized to capture dying cells, and this helps to explain their selective ability to cross present cellular antigens to both CD4+ and CD8+ T cells.


Brain tumors.
This synthesis of the literature on radiotherapy for brain tumors, ie, cancer originating in the central nervous system (CNS), is based on 81 scientific articles, including 25 randomized studies, 13 prospective studies, and 25 retrospective studies. These studies involve 11,081 patients. A more comprehensive chapter on brain tumors may be ordered from SBU. Curative treatment is not available for patients with highly malignant glioma (grades III and IV). Postoperative radiotherapy for highly malignant glioma extends patients' survival, with good quality of life, by several weeks to several months. Virtually all patients die from this disease. Although the clinical benefits from radiotherapy, measured as survival, appear to be modest, it is more effective than any chemotherapy tested thus far. The clinical effects of radiotherapy for highly malignant glioma are improved only marginally by altering factors such as absorbed dose, fractionation, irradiated tissue volume, radiation quality, or by adding radiosensitizing substances. Radiotherapy alone usually provides a clear but temporary improvement in patients with highly malignant glioma, hence it clearly has a palliative benefit. Postoperative radiotherapy for low-grade malignant gliomas (grades I and II) may extend survival. It also reduces tumor volume. No evidence shows that radiotherapy alone or postoperatively can lead to cure. In patients who have undergone subtotal meningioma resection, postoperative radiotherapy substantially reduces the risk for recurrence and extends life, and is thereby indicated. Radiotherapy is not indicated following macroscopic radical meningioma surgery. Patients with brain metastases experience rapid neurological improvement following radiotherapy to the whole brain, and this palliative effect often remains throughout the remainder of the patient's life. Palliative radiotherapy, often to large volumes of the CNS, is therefore motivated in a large proportion of the patient groups. In a smaller group of patients with solitary metastases, radiotherapy may be given postoperatively following radical neurosurgery. Life may be extended in this group, otherwise radiotherapy does not influence survival. Stereotactic radiotherapy of solitary, mainly spherical metastases in the brain is often superior to other known methods with respect to palliation and survival. The number of patients is, however, relatively small.


Mitral Valve-In-Valve: Defining the Indication Limits by in vitro Hydrodynamic Tests in a Brazilian Transcatheter Prosthesis.
Reoperations in cardiac surgery represent a clinical challenge, particularly because of the higher rate of perioperative morbidity and mortality. Mitral valve reoperation owing to bioprosthesis dysfunction, transcatheter treatment with a prosthesis implantation over the prosthesis has emerged as an alternative, especially for patients with a previous approach. In this study, we analyzed the hydrodynamic behavior of transcatheter prosthesis implantation in conventional mitral bioprostheses through hydrodynamic tests and produced a recommendation for the size of transcatheter valve most adequate for valve-in-valve procedure. Mitral bioprostheses were attached to a flow duplicator and different combinations of transcatheter prostheses were implanted inside. The equipment simulates the hydrodynamic behavior of the valves submitted in vitro and determines transvalvular pressures and flow parameters. All tests could be performed. Better hydrodynamic performance occurred for transcatheter prostheses 1 mm smaller than bioprostheses, except for the 27-mm bioprostheses. Effective valve areas (cm²) and transvalvular gradients (mmHg) were, respectively: Bioprosthesis × Inovare: 27 × 28 mm: 1.65 and 5.95/29 × 28 mm and 31 × 30 mm: 2.15 and 3.6. The mitral valve-in-valve implantation proved to be feasible in vitro. The use of 27-mm bioprostheses should be judicious, with preference for a 26-mm transcatheter valve. In the 29 and 31-mm bioprostheses, the implantation was very satisfactory, with good effective valve areas and transvalvular gradients, with preference for smaller transcatheter valves.


Creation of a linked cohort of children and their parents in a large, national electronic health record dataset.
To examine which parental health care and health factors are most strongly associated with a child's receipt of recommended care we must be able to link children to their parents in electronic health record data. Yet, there is not an easy way to link these data.To identify a national cohort of children that link to at least one parent in the same electronic health record dataset and describe their demographics.Methodology to link parents and children in electronic health records and descriptive sociodemographic data.Children with at least one encounter with a primary care clinician between Januray 1, 2007 and December 12, 2018 to a community health center in the OCHIN national network. We identified parents of these children who also had at least one encounter to a community health center in the network using emergency contact and guarantor record fields.A total of 227,552 children had parents with a linkable patient record. After exclusions, our final cohort included 213,513 distinct children with either one or two parent-links. 82% of children linked to a mother only, 14% linked to a father only, and 4% linked to both a mother and a father. Most families consisted of only one linked child (61%).We were able to link 33% of children to a parent in electronic health record data from a large network of community health centers across the United States. Further analyses utilizing these linkages will allow examination of the multi-level factors that impact a child's receipt of recommended health care.


Bone buffering of acid and base in humans.
The sources and rates of metabolic acid production in relation to renal net acid excretion and thus acid balance in humans have remained controversial. The techniques and possible errors in these measurements are reviewed, as is the relationship of charge balance to acid balance. The results demonstrate that when acid production is experimentally increased among healthy subjects, renal net acid excretion does not increase as much as acid production so that acid balances become positive. These positive imbalances are accompanied by equivalently negative charge balances that are the result of bone buffering of retained H+ and loss of bone Ca2+ into the urine. The data also demonstrate that when acid production is experimentally reduced during the administration of KHCO3, renal net acid excretion does not decrease as much as the decrease in acid production so that acid balances become negative, or, in opposite terms, there are equivalently positive HCO3- balances. Equivalently positive K+ and Ca2+ balances, and thus positive charge balances, accompany these negative acid imbalances. Similarly, positive Na+ balances, and thus positive charge balances, accompany these negative acid balances during the administration of NaHCO3. These charge balances are likely the result of the adsorption of HCO3- onto the crystal surfaces of bone mineral. There do not appear to be significant errors in the measurements.


[Study on risk factors of 292 pregnant women infected with HCMV].
This paper is to determine the risk factors of reactivation by HCMV during pregnancy for improving child birth and bringing-up. A total of 292 paired sera were collected from mothers and their infants in Shanghai and were tested for IgG and IgM by ELISA. The positive rates of HCMV IgG and IgM were 98.97%, 96.97% and 3.77%, 1.71%, respectively in mothers and infants. The rate of IgM was 1.49% in infants whose mothers' education were above the high school level, whereas it was 4.17% whose mothers' educational degree was lower than that grade, and the relative ratio (RR) was 2.8. The number of previous pregnancies were closely associated with the positive rate of IgM. In infants born to mothers at first pregnancy, the positive rate was 1.96%, whereas in infants born to mothers at third pregnancy it increased to 3.70%, RR was 1.89. In pregnant women who were known to have postmortem or premature deliveries before the positive rate was 9.09%, whereas it was 2.53% in pregnant women at first pregnancy, the RR was 3.59. The rates of their infants were 3.03% and 1.90%, respectively, the RR was 1.59. The frequency of IgM antibody in 292 sera of mothers was correlated with that in their infants. It showed that HCMV might be transmitted from mother to fetus.


The prevalence and associated factors of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in aging males.
To investigate the prevalence and associated factors of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) in Chinese aging males. Data downloaded from the China Health and Retirement Longitudinal Study (CHARLS) was subjected to descriptive statistics followed by univariate logistic regression and multivariate logistic regression. A total of 8563 participants with an overall LUTS/BPH prevalence of 11.97% were enrolled. With aging, the LUTS/BPH prevalence increased (p < 0.001). Men aged over 70 years suffered the highest prevalence of 22.70%. Marital status did nothing to the suffering of LUTS/BPH. Subjects receiving more education or assessed as depression displayed higher incidence of LUTS/BPH (p < 0.001). In rural villages, settlers showed lower prevalence of 10.00% compared to 16.49% for urban residents. Smoking, sleeping time and alcohol consumption seemed to play a protective role in the occurrence of LUTS/BPH. One who slept more than 8 h, was smoking, and drank more than once a month had the lowest prevalence (p ≤ 0.001). For Chinese aging population, LUTS/BPH prevalence increased with aging and was interfered by educational level, depression, sleeping time, geographical region, smoke and alcohol consumption.


[Antiviral activity of sulfated polysaccharide from the brown algae Laminaria japonica against avian influenza A (H5N1) virus infection in the cultured cells].
The antiviral activity of the sulfated polysaccharide fucoidan from the brown sea algae Laminaria japonica against infection caused by highly virulent avian influenza virus (Alduck/Novosibirsk/02/05, H5N1) in the sensitive pig embryo kidney cell cultures was studied. Fucoidan was ascertained to have no cytotoxic activity and to show virucidal activity against influenza A/H5N1 virus. When given at concentrations of 50 to 500 microg/ml, fucoidan protected the cell cultures from the cytopathogenic activity of influenza virus in a dose of 0.01 TCID50/1.0 ml and was able to suppress influenza A/H5N1 virus production within 24 hours of infection when prophylactic and therapeutic-and-prophylactic treatment regimens were used.


Semantic access dysphasia resulting from left temporal lobe tumours.
Unlike semantic degradation disorders, the mechanisms and the anatomical underpinnings of semantic access disorders are still unclear. We report the results of a case series study on the effects of temporal lobe gliomas on semantic access abilities of a group of 20 patients. Patients were tested 1-2 days before and 4-6 days after the removal of the tumour. Their semantic access skills were assessed with two spoken word-to-picture matching tasks, which aimed to separately control for rate of presentation, consistency and serial position effects (Experiment 1) and for word frequency and semantic distance effects (Experiment 2). These variables have been held to be critical in characterizing access in contrast to degraded-store semantic deficits, with access deficits characterized by inconsistency of response, better performance with slower presentation rates and with semantically distant stimuli, in the absence of frequency effects. Degradation deficits show the opposite pattern. Our results showed that low-grade slowly growing tumours tend not to produce signs of access problems. However, high-grade tumours especially within the left hemisphere consistently produce strong semantic deficits of a clear access type: response inconsistency and strong semantic distance effects in the absence of word frequency effects were detected. However, effects of presentation rate and serial position were very weak, suggesting non-refractory behaviour in the tumour patients tested. This evidence, together with the results of lesion overlapping, suggests the presence of a type of non-refractory semantic access deficit. We suggest that this deficit could be caused by the disconnection of posterior temporal lexical input areas from semantic system.


Dynamics of macaque MT cell responses to grating triplets.
Neurons in area MT are sensitive to the direction of motion of gratings and of plaids made by summing 2 gratings moving in different directions. MT component direction-selective (CDS) neurons respond to the individual gratings of a plaid. Pattern direction-selective (PDS) neurons on the other hand, combine component information and respond selectively to the resulting pattern motion. Adding a third grating creates a "triplaid," which contains 3 grating and 3 plaid motions and is perceptually multistable. To examine how direction-selective mechanisms parse the motion signals in triplaids, we recorded MT responses of anesthetized and awake macaques to stimuli in which 3 identical moving gratings whose directions were separated by 120° were introduced in 3 successive epochs, going from grating to plaid to triplaid. CDS and PDS neurons-selected based on their responses to gratings and plaids-had strikingly different tuning properties in the triplaid epoch. CDS neurons were strongly tuned for the direction of motion of individual gratings, but PDS neurons nearly lost their selectivity for either the gratings or the plaids in the stimulus. We explain this reduced motion selectivity with a model that relates pattern selectivity of PDS neurons to a broad pooling of V1 afferents with a near-cosine weighting profile. Because PDS neurons signal both component and pattern motion in gratings and plaids, their reduced selectivity for motion in triplaids may be what makes these stimuli perceptually multistable.


Estimating freshwater turtle mortality rates and population declines following hook ingestion.
Freshwater turtle populations are susceptible to declines following small increases in the mortality of adults, making it essential to identify and understand potential threats. Freshwater turtles ingest fish hooks associated with recreational angling, and this is likely a problem because hook ingestion is a source of additive mortality for sea turtles. We used a Bayesian-modeling framework, observed rates of hook ingestion by freshwater turtles, and mortality of sea turtles from hook ingestion to examine the probability that a freshwater turtle in a given population ingests a hook and subsequently dies from it. We used the results of these analyses and previously published life-history data to simulate the effects of hook ingestion on population growth for 3 species of freshwater turtle. In our simulation, the probability that an individual turtle ingests a hook and dies as a result was 1.2-11%. Our simulation results suggest that this rate of mortality from hook ingestion is sufficient to cause population declines. We believe we have identified fish-hook ingestion as a serious yet generally overlooked threat to the viability of freshwater turtle populations.


[Antitumor effect of interferons with chemotherapeutic agents].
The combined effect of human interferons and chemotherapeutic agents on human gastric cancer cell lines and a human pancreatic cancer cell line was studied in vitro. Interferons, when used as a single drug, showed inhibitory effects in the order, gamma greater than beta greater than alpha. However, there was no significant difference between the effects of natural and recombinant interferon. In combination therapy, the chemotherapeutic agents should be administered first, followed by administration of interferon(s), since this method showed the most inhibitory effect. Low concentration of 5-FU (0.001-0.01 microgram/ml) or methotrexate (0.01-1 microgram/ml) was able to inhibit the growth of cell lines when combined with interferon. These results suggested that in clinical use, low amounts of chemotherapeutic agents followed by administration of interferon(s) could be available with minimum side effects and with more pronounced anticancer effects.


An Eimeriid origin of isosporoid coccidia with Stieda bodies as shown by phylogenetic analysis of small subunit ribosomal RNA gene sequences.
Morphological and life cycle features of the tissue cyst-forming coccidia have been difficult to interpret in devising taxonomic classifications for the various genera. In this study, we amplified the full small subunit rRNA gene sequence of Isospora robini McQuistion and Holmes, 1988, and the partial sequence of Isospora gryphoni Olsen, Gissing, Barta, and Middleton, 1998 by PCR. Both of these species vary from Isospora species of mammals in having Stieda bodies on the sporocysts. The sequences were cloned and sequenced and were incorporated into an alignment with other Isospora species lacking Stieda bodies as well as with other coccidia. Maximum parsimony analysis of these sequences produced a single most parsimonious tree that placed I. robini and I. gryphoni in a clade containing various other eimeriid species. The Isospora species lacking Stieda bodies were in the sarcocystid clade. Similar results were found by maximum likelihood analysis. These findings indicate that the genus Isospora as defined by several authors is polyphyletic. Taxonomic changes to the genus Isospora would have to incorporate the 2 major clades found by molecular phylogenetic analysis. Isospora species with Stieda bodies should be classified in the family Eimeriidae, whereas those without Stieda bodies should remain in the family Sarcocystidae.


Do elections matter for private-sector healthcare management in Brazil? An analysis of municipal health policy.
This study analyzed several political determinants of increased private-sector management in Brazilian health care. In Brazil, the poor depend almost exclusively on the public Unified Health System (the SUS), which remains severely underfunded. Given the overhead costs associated with privately contracted health services, increased private management is one driver of higher expenditures in the system. Although left parties campaign most vocally in support of greater public control of the SUS, the extent to which their stated positions translate into health care policy remains untested. Drawing on multiple publicly available data sources, we used linear regression to analyze how political party-in-power and existing private sector health care contracting affect the share of privately managed health care services and outsourcing in municipalities. Data from two election periods-2004 to 2008 and 2008 to 2012-were analyzed. Our findings showed that although private sector contracting varies greatly across municipalities, this variation is not systematically associated with political party in power. This suggests that electoral politics plays a relatively minor role in municipal-level health care administration. Existing levels of private sector management appear to have a greater effect on the public-private makeup of the Brazilian healthcare system, suggesting a strong role of path dependence in the evolution of Brazilian health care delivery. Despite campaign rhetoric asserting distinct positions on privatization in the SUS, factors other than political party in power have a greater effect on private-sector health system management at the municipal-level in Brazil. Given the limited effect of elections on this issue, strengthening participatory bodies such as municipal health councils may better enfranchise citizens in the fundamental debate over public and private roles in the health care sector.


[Diagnosis and treatment of pharyngoesophageal diverticulum].
To investigate the diagnosis, differential diagnosis and the treatment of Zenker diverticulum (pharyngo esophagus diverticulum) in thyroid operation. Seven cases suffering from thyroid masses diagnosed Zenker diverticulum in thyroid operation between July 2001 and December 2011 were reviewed. Zenker diverticula in the patients were resected. Only one case was complicated with the formation of false capsular bag, infection and fistula postoperatively, but cured with draining eventually. Zenker diverticulum may exist in some patients with thyroid mass. Resection of diverticulum may be performed in thyroid operation, with a good prognosis.


[New developments on the serotonin hypothesis of depression: shunt of tryptophan].
Since the late 1960s, the serotonin deficiency, as demonstrated in major depression, was related to an increased activity of the liver enzyme tryptophan-pyrrolase stimulated by an excess of circulating corticosteroids, which would shift the metabolism of tryptophan from serotonin to kynurenine production. The finding that the kynurenine causes different effects in central nervous system suggested that an up-regulation of the tryptophan-kynurenine pathway determined not only a deficiency of serotonin, but could also play a role in the development of anxiety, psychotic symptoms and cognitive impairment associated with depression. This review aims to evaluate the different hormonal and genetic factors regulating the metabolism of tryptophan via kynurenine, and to highlight how this metabolic pathway may be involved in depression pathogenesis. Rate-limiting enzymes of kynurenine formation are two: tryptophan 2,3-dioxygenas (TDO) activated by stress hormones, and indoleamine 2,3-dioxygenase (IDO), activated by proinflammatory cytokines. The increased expression of the genes that produce inflammatory cytokines (interferon-gamma and tumor necrosis factor alpha) would determine a genetic predisposition to develop depression by up-regulating the IDO pathway, while environmental stressors would activate TDO via hormonal activation. Therefore, it can be reasonably assumed that the pathway of tryptophan-kynurenine represents one of the main melting points of the interaction between genetic and environmental factors involved in the pathophysiology of depression, as well as new targets for future antidepressant strategies.


Fabrication of Hierarchical Co9S8@ZnAgInS Heterostructured Cages for Highly Efficient Photocatalytic Hydrogen Generation and Pollutants Degradation.
In the present study, a hierarchical Co9S8@ZnAgInS heterostructural cage was developed for the first time which can photocatalytically produce hydrogen and degrade organic pollutants with high efficiency. First, the Co9S8 dodecahedron was synthesized using a metal-organic framework (MOFs) material, ZIF-67, as a precursor, then two kinds of metal sulfide semiconductors were elaborately integrated into a hierarchical hollow heterostructural cage with coupled heterogeneous shells and 2D nanosheet subunits. The artfully designed hollow heterostructural composite exhibited remarkable photocatalytic activity without using any cocatalysts, with a 9395.3 μmol g-1 h-1 H2 evolution rate and high degradation efficiency for RhB. The significantly enhanced photocatalytic activity can be attributed to the unique architecture and intimate-contact interface between Co9S8 and ZnAgInS, which promote the transfer and separation of the photogenerated charges, increase light absorption, and offer large surface area and active sites. This work presents a new strategy to design highly active semiconductor photocatalysts by using MOF materials as precursors and coupling of metal sulfide semiconductors to form hollow architecture dodecahedron cages with an intimate interface.


Human and entomologic investigations of chikungunya outbreak in Mandera, Northeastern Kenya, 2016.
Chikungunya is a reemerging vector borne pathogen associated with severe morbidity in affected populations. Lamu, along the Kenyan coast was affected by a major chikungunya outbreak in 2004. Twelve years later, we report on entomologic investigations and laboratory confirmed chikungunya cases in northeastern Kenya. Patient blood samples were received at the Kenya Medical Research Institute (KEMRI) viral hemorrhagic fever laboratory and the immunoglobulin M enzyme linked immunosorbent assay (IgM ELISA) was used to test for the presence of IgM antibodies against chikungunya and dengue. Reverse transcription polymerase chain reaction (RT-PCR) utilizing flavivirus, alphavirus and chikungunya specific primers were used to detect acute infections and representative PCR positive samples sequenced to confirm the circulating strain. Immature mosquitoes were collected from water-holding containers indoors and outdoors in the affected areas in northeastern Kenya. A total of 189 human samples were tested; 126 from Kenya and 63 from Somalia. 52.9% (100/189) tested positive for Chikungunya virus (CHIKV) by either IgM ELISA or RT-PCR. Sequence analysis of selected samples revealed that the virus was closely related to that from China (2010). 29% (55/189) of the samples, almost all from northeastern Kenya or with a history of travel to northern Kenya, tested positive for dengue IgM antibodies. Entomologic risk assessment revealed high house, container and Breteau indices of, 14.5, 41.9 and 17.1% respectively. Underground water storage tanks were the most abundant, 30.1%, of which 77.4% were infested with Aedes aegypti mosquitoes. These findings confirm the presence of active chikungunya infections in the northeastern parts of Kenya. The detection of dengue IgM antibodies concurrently with chikungunya virus circulation emphasizes on the need for improved surveillance systems and diagnostic algorithms with the capacity to capture multiple causes of arbovirus infections as these two viruses share common vectors and eco-systems. In addition sustained entomological surveillance and vector control programs targeting most productive containers are needed to monitor changes in vector densities, for early detection of the viruses and initiate vector control efforts to prevent possible outbreaks.


Beta-Lactam antibiotic resistance in gram-positive bacterial pathogens of the upper respiratory tract: a brief overview of mechanisms.
Streptococcus pneumoniae and Group A Streptococci are frequent colonizers and major causative agents of disease in the upper respiratory tract of humans. In spite of the immense and common selective pressure of beta-lactam antibiotics against both of these bacterial species during the last four to five decades, penicillin-resistant strains of group A streptococci have not been described in the clinical literature as of 1994. This is particularly puzzling since penicillin-resistant mutants of this bacterium have been isolated repeatedly in the laboratory and such mutants carry altered penicillin-binding proteins (PBPs) with reduced drug affinities, i.e., a basic mechanism identical to the one seen in penicillin-resistant isolates of Streptococcus pneumoniae that have emerged in large numbers and at numerous locations and have spread explosively all over the globe by the beginning of the 1990s. The reasons for this contrasting situation are not clear. In Streptococcus pneumoniae the resistance mechanism to penicillin appears to originate in recombinational events between ancestral pneumococcal cells and as yet unidentified extra species DNA donors and probably involves the process of genetic transformation for which this bacterium has a remarkable hormonally controlled mechanism. The integration of foreign DNA sequences in the pneumococcal PBP genes leads to the remodeling of at least four of the five PBPs that change in their kinetic properties and increase in the penicillin resistance level of the bacteria also seems to involve increased production of the low-affinity binding proteins.


Longitudinal study of parasite-induced mortality of a long-lived host: the importance of exposure to non-parasitic stressors.
Hosts face mortality from parasitic and environmental stressors, but interactions of parasitism with other stressors are not well understood, particularly for long-lived hosts. We monitored survival of flour beetles (Tribolium confusum) in a longitudinal design incorporating cestode (Hymenolepis diminuta) infection, starvation and exposure to the pesticide diatomaceous earth (DE). We found that cestode cysticercoids exhibit increasing morphological damage and decreasing ability to excyst over time, but were never eliminated from the host. In the presence of even mild environmental stressors, host lifespan was reduced sufficiently that extensive degradation of cysticercoids was never realized. Median host lifespan was 200 days in the absence of stressors, and 3-197 days with parasitism, starvation and/or DE. Early survival of parasitized hosts was higher relative to controls in the presence of intermediate concentrations of DE, but reduced under all other conditions tested. Parasitism increased host mortality in the presence of other stressors at times when parasitism alone did not cause mortality, consistent with an interpretation of synergy. Environmental stressors modified the parasite numbers needed to reveal intensity-dependent host mortality, but only rarely masked intensity dependence. The longitudinal approach produced observations that would have been overlooked or misinterpreted if survival had only been monitored at a single time point.


Mapping healthcare systems: a policy relevant analytic tool.
In the past decade, an international consensus on the value of well-functioning systems has driven considerable health systems research. This research falls into two broad categories. The first provides conceptual frameworks that take complex healthcare systems and create simplified constructs of interactions and functions. The second focuses on granular inputs and outputs. This paper presents a novel translational mapping tool - the University of California, San Francisco mapping tool (the Tool) - which bridges the gap between these two areas of research, creating a platform for multi-country comparative analysis. Using the Murray-Frenk framework, we create a macro-level representation of a country's structure, focusing on how it finances and delivers healthcare. The map visually depicts the fundamental policy questions in healthcare system design: funding sources and amount spent through each source, purchasers, populations covered, provider categories; and the relationship between these entities. We use the Tool to provide a macro-level comparative analysis of the structure of India's and Thailand's healthcare systems. As part of the systems strengthening arsenal, the Tool can stimulate debate about the merits and consequences of different healthcare systems structural designs, using a common framework that fosters multi-country comparative analyses.


O-to-S Substitution Enables Dovetailing Conflicting Cyclizability, Polymerizability, and Recyclability: Dithiolactone vs. Dilactone.
Developing chemically recyclable polymers represents a greener alternative to landfill and incineration and offers a closed-loop strategy toward a circular materials economy. However, the synthesis of chemically recyclable polymers is still plagued with certain fundamental limitations, including trade-offs between the monomer's cyclizability and polymerizability, as well as between polymer's depolymerizability and properties. Here we describe the subtle O-to-S substitution, dithiolactone monomers derived from abundant feedstock α-amino acids can demonstrate appealing chemical properties different from those of dilactone, including accelerated ring closure, augmented kinetics polymerizability, high depolymerizability and selectivity, and thus constitute a unique class of polythioester materials exhibiting controlled molecular weight (up to 100.5 kDa), atactic yet high crystallinity, structurally diversity, and chemical recyclability. These polythioesters well addresses the formidable challenges of developing chemically recyclable polymers by having an unusual set of desired properties, including easy-to-make monomer from ubiquitous feedstock, and high polymerizability, crystallinity and precise tunability of physicochemical performance, as well as high depolymerizability and selectivity. Computational studies explain why O-to-S modification of polymer backbone enables dovetailing desirable, but conflicting, performance into one polymer structure.


Oxidation of Secondary Methyl Ethers to Ketones.
We present a mild way of converting secondary methyl ethers into ketones using calcium hypochlorite in aqueous acetonitrile with acetic acid as activator. The reaction is compatible with various oxygen- and nitrogen-containing functional groups and afforded the corresponding ketones in up to 98% yield. The use of this methodology could expand the application of the methyl group as a useful protecting group.


Pain assessment in cerebral palsy: a systematic review of measurement properties and evaluation using the COSMIN checklist.
This systematic literature review aims to analyse the methodological quality of instruments available to assess pain in Cerebral Palsy (CP), according to the COSMIN guidelines and checklist. Electronic literature searches were conducted in PubMed, ScienceDirect, Web of Science, PEdro, Scielo, Scopus and Academic Search Complete (EBSCO host) for articles on measurement properties of self-report, proxy or observational instruments. A total of 14 instruments were identified. Of these, 8 were self-report instruments, 4 were observational instruments and 2 could be used both as self-report or proxy-report. The quality of the manuscripts was inadequate or doubtful in 45.5%, adequate in 15.9% and very good in 38.6% of the cases. No instrument was assessed for all the properties recommended by COSMIN. The quality of the evidence for the measurement properties of the pain assessment instruments ranged from very low to moderate. There is scarce and low-quality evidence on the measurement properties of instruments used to assess pain in individuals with cerebral palsy. Further research is needed designed in line with the COSMIN recommendations.Implications for rehabilitationThere is scarce and low-quality evidence on the measurement properties of instruments used to assess pain in individuals with cerebral palsy;Clinicians need to carefully choose instruments to assess pain in individuals with cerebral palsy as there is insufficient evidence on the quality of instruments;Self-report pain intensity scales may be a useful instrument for a subgroup of individuals with cerebral palsy.


Therapeutic Approach to Patients with Heart Failure with Reduced Ejection Fraction and End-stage Renal Disease.
Several risk factors including Ischemic heart disease, uncontrolled hypertension, high output Heart Failure (HF) from shunting through vascular hemodialysis access, and anemia, contribute to development of HF in patients with End-Stage Renal Disease (ESRD). Guidelinedirected medical and device therapy for Heart Failure with Reduced Ejection Fraction (HFrEF) has not been extensively studied and may have limited safety and efficacy in patients with ESRD. Maintenance of interdialytic and intradialytic euvolemia is a key component of HF management in these patients but often difficult to achieve. Beta-blockers, especially carvedilol which is poorly dialyzed is associated with cardiovascular benefit in this population. Despite paucity of data, Angiotensin-converting Enzyme Inhibitors (ACEI) or Angiotensin II Receptor Blockers (ARBs) when appropriately adjusted by dose and with close monitoring of serum potassium can also be administered to these patients who tolerate beta-blockers. Mineralocorticoid receptors in patients with HFrEF and ESRD have been shown to reduce mortality in a large randomized controlled trial without any significantly increased risk of hyperkalemia. Implantable Cardiac-defibrillators (ICDs) should be considered for primary prevention of sudden cardiac death in patients with HFrEF and ESRD who meet the implant indications. Furthermore in anemic iron-deficient patients, intravenous iron infusion may improve functional status. Finally, mechanical circulatory support with leftventricular assist devices may be related to increased mortality risk and the presence of ESRD poses a relative contraindication to further evaluation of these devices.


Disorders on cardiovascular parameters in rats and in human blood cells caused by Lachesis acrochorda snake venom.
In Colombia, Lachesis acrochorda causes 2-3% of all snake envenomations. The accidents promote a high mortality rate (90%) due to blood and cardiovascular complications. Here, the effects of the snake venom of L. acrochorda (SVLa) were analyzed on human blood cells and on cardiovascular parameters of rats. SVLa induced blood coagulation, as measured by the prothrombin time test, but did not reduce the cell viability of neutrophils and platelets evaluated by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay and by the lactate dehydrogenase (LDH) enzyme assay. In fact, SVLa increased the absorbance in tests made with platelets subjected to the MTT assay. SVLa induced platelet aggregation whose magnitude was comparable to that of the positive control adenosine diphosphate (ADP), and occurred earlier with increasing SVLa concentration. Acetylsalicylic acid (ASA, a cyclooxygenase inhibitor) or clopidogrel (an ADP receptor blocker) inhibited the aggregating effect of SVLa. Inhibition of SVLa-elicited platelet aggregation also resulted from the treatment with disodium ethylenediaminetetraacetate (Na2-EDTA; metalloproteinase inhibitor) and with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF, serine protease inhibitor). In isolated right atrium of rats, SVLa increased slightly, but significantly, the magnitude of the spontaneous contractions and, in isolated rat aorta, SVLa relaxed KCl- or phenylephrine-induced contractions. In vivo, SVLa induced hypotension and bradycardia in rats, with detection of hemorrhage in pulmonary and renal tissues. Altogether, under experimental conditions, SVLa induced blood coagulation, platelet aggregation, hypotension and bradycardia. Part of the effects presented here may be explained by the presence of snake venom metalloproteinases (SVMPs) and snake venom serine proteases (SVSPs), constituents of SVLa.


Is screening and intervention for microalbuminuria worthwhile in patients with insulin dependent diabetes?
To analyse the cost-benefit of screening for and antihypertensive treatment of early renal disease indicated by microalbuminuria in patients with insulin dependent diabetes mellitus. Previously published data were used to estimate transition probabilities for each step from normoalbuminuria until death. The effect of intervention on urinary albumin excretion rate by antihypertensive treatment was arbitrarily set at three different levels. All direct costs (screening, antihypertensive treatment, treatment of end stage renal failure) were included in the cost-benefit analysis by using real discount rates of 2.5% and 6%. Computer simulation. Simulated cohort of 8000 patients. Mortality, incidence of diabetic nephropathy, incidence of end stage renal failure, and costs versus savings. Assuming treatment effects of 33% and 67% median life expectancy increased by four to 14 years, respectively, and the need for dialysis or transplantation decreased by 21% to 63%. Costs and savings would balance if the annual rate of increase of albuminuria was decreased from 20% to 18% a year. Screening and intervention programmes are likely to have life saving effects and lead to considerable economic savings.


Arsenic trioxide and tetraarsenic oxide induce cytotoxicity and have a synergistic effect with cisplatin in paclitaxel-resistant ovarian cancer cells.
Background: Arsenic compounds (As2O3 and As4O6) have demonstrated anticancer effects in various malignancies. In this study, the cytotoxicity of arsenic compounds on ovarian cancer cell lines and the anticancer activity of the combination of arsenic compounds and cisplatin IN chemoresistant ovarian cancer cells were investigated.Methods: We investigated the cytotoxicity of As2O3 and As4O6 and their combinations with cisplatin in the paclitaxel-sensitive ovarian cancer cell lines SKOV3ip1 and HeyA8 and paclitaxel-resistant ovarian cancer cell lines SKOV3TRip2 and HeyA8-MDR. Growth and apoptosis were evaluated by MTT assay and annexin V assay using flow cytometry, respectively. For detection of apoptotic cells, immunofluorescence was performed using a cleaved caspase-3 antibody. Cell-cycle distribution was determined by propidium iodide staining and flow cytometry.Results: Treatment of each cell line with As2O3 or As4O6 led to a marked dose-dependent inhibition of cell growth. As2O3 and As4O6 treatment induced caspase-3-dependent apoptosis in all cell lines compared to the respective control groups (p < .05). As2O3 and As4O6 induced apoptosis of paclitaxel-sensitive and -resistant cancer cell lines following G2/M cell cycle arrest (p < .05). A synergistic effect was achieved by combining cisplatin with As2O3 or As4O6 in the paclitaxel-resistant ovarian cancer cell lines.Conclusions: As2O3 and As4O6 can inhibit cell growth and induce apoptosis in paclitaxel-sensitive and -resistant ovarian cancer cell lines. Their combination with cisplatin resulted in a synergistic effect in paclitaxel-resistant cancer cell lines. These results suggest that arsenic compounds may be given in monotherapy or combination therapy with cisplatin for treating paclitaxel-resistant ovarian cancer.


Motor performance in the third, not the second month, predicts further motor development.
The aim was to verify if motor performance at second or third month of life better predicts further development. The global motor development was assessed by a neurologist and by a physiotherapist in 111 children at 2, 3, 6, and 9 months. At 2 and 3 months a physiotherapist also performed the assessment of qualitative elements. The physiotherapeutic assessment in the third month showed higher compatibility with the neurological assessment. Proper motor performance at third month could ensure the level of at least 7 months in the ninth month of life. Qualitative score above 7 of 15 points in the third month ensured proper development in ninth month. Third month of life is a better predictor of further motor development.


Factor analysis and reliability of the Movement Imagery Questionnaire.
The purpose of this work was to analyze the factor structure, estimate reliability of the Movement Imagery Questionnaire of Hall and Pongrac, and examine differences between men and women on factor scores. The results for 63 men and 47 women supported the bifactorial structure and reliability of this self-report and its adequacy in comparisons of visual and kinesthetic imagery scores.


Indications of Recruitment Challenges in Research with U.S. Military Service Members: A ClinicalTrials.gov Review.
The success of military-relevant health research often depends on recruiting adequate numbers of U.S. military service members as research participants. Researchers have reported difficulties in recruiting service member research participants. Reviews of ClinicalTrials.gov, an online clinical trial registry of publicly and privately sponsored studies, have identified challenges in participant recruitment and barriers to study completion in various research populations. The purpose of this study was to identify indications of difficulty recruiting U.S. military service members as research participants based on data from study records in ClinicalTrials.gov. Records of studies starting between 2005 and 2014 were collected from ClinicalTrials.gov and updated through January 2016. Three hundred and two studies that included ≥25% U.S. military service member research participants were (1) compared to a comparison group of 302 studies, each with <5% service member participants and (2) compared by the proportion of service member participants within studies in the military group ("many" ≥25% but <100% service members and "all" 100% service members). Groups were evaluated and compared for recruitment status; reasons for study withdrawal, termination, or suspension; achievement of ≥85% of the anticipated enrollment; and differences in achieving recruitment goals according to study sponsor. Twelve percent of studies in the military group had been withdrawn, terminated, or suspended; enrollment and funding problems were the most common reasons. The comparison group had 11% of studies withdrawn, terminated, or suspended; the most common reasons were enrollment problems and sponsor decision. All study groups had indications of difficulty adequately achieving participant enrollment goals. Among studies with known anticipated and actual enrollment, approximately half in both the military group (47.9%) and comparison group (50.3%) achieved ≥85% of the anticipated enrollment (p = 0.722). Half of studies with many service members and 44% of studies with all service members achieved ≥85% of the anticipated enrollment (p = 0.600). In comparing the many and all service member subgroups, significant differences were found in the median values for anticipated enrollment and actual enrollment, even when accounting for Bonferroni correction. Evaluations of mean values did not show a statistical difference between the military subgroups. There were no significant differences according to study sponsor (military, academic, Veterans Affairs, National Institutes of Health, nonprofit organization, or industry) for a study achieving or not achieving ≥85% of the anticipated enrollment. This review supports anecdotal reports of difficulty recruiting service members as research participants. However, the findings also indicate that in many regards, there is not much difference in the difficulties recruiting service members versus other research participants. Findings suggest that it is often difficult to recruit research participants regardless of the specific population or type of study sponsor, and that studies with either many or all service member participants have similar achievement of recruitment goals. Findings in this study may be useful for those who design research that includes service members or for those who are apprehensive about including service members in their research.


Endogenous acid releases secretin in man.
In search of a physiological stimulus for secretin release, the effect of gastric acid secretion was investigated. In six healthy volunteers, pentagastrin (1.5 microgram/kg, hr i.v.) was administered without and with aspiration of gastric contents, and plasma secretin was estimated by radioimmunoassay. Administration of pentagastrin without aspiration of gastric juice resulted in steadily increasing plasma secretion which was significantly elevated at the end of 60 min of pentagastrin infusion and also in the post-infusion hour. These results are compatible with the concept that endogenous acid being delivered from the stomach to the duodenum does contribute to the release of secretin which in turn may serve as a physiological stimulus for pancreatic bicarbonate secretion.


RELATEDNESS AND POPULATION STRUCTURE OF THE PRIMITIVELY EUSOCIAL BEE LASIOGLOSSUM ZEPHYRUM (HYMENOPTERA: HALICTIDAE) IN KANSAS.
Lasioglossum zephyrum is a primitively eusocial bee, which nests in small colonies of up to 20 individuals. The nests occur in patchily distributed aggregations of from a few to over 1,000 nests along periodically disturbed stream and river banks in eastern North America. We used five polymorphic allozyme loci to test for geographic structure and estimate relatedness in eight patches of nests from five aggregations in Douglas Co., Kansas. Autocorrelation analysis of gene frequencies, plus a multilocus G test, revealed a low but significant tendency for differentiation among nests within patches, among patches within aggregations, and among aggregations. Small numbers of nests restricted estimation of relatedness to three patches, of which only one had a sample size large enough to yield confidence limits narrow enough to be informative. The limits from this patch of 20 nests are 0.64 < 0.8245 < 1.01. While these limits are consistent with the true value being 0.75 (that expected under male-haploidy if each nest results from the reproduction of a single, once-mated female), the occurrence of some nests with three or more genotypes shows that nest makeup is more complex than this, so that a lower value, say 0.7, is more plausible. This value is sufficiently high to indicate that kin selection is probably important in these populations.


3D RuO₂ Microsupercapacitors with Remarkable Areal Energy.
Large areal capacitance electrodes made of ruthenium oxide on highly porous gold current collectors are realized by an attractive approach. The hybrid structure exhibits a capacitance in excess of 3 F cm(-2) and an areal energy density for all-solid-state microsupercapacitors that is comparable to those of microbatteries.


[Prevalence of microtia and anotia at the maternity of the University of Chile Clinical Hospital].
Microtia is a congenital defect characterized by disturbances in the size and form of the ear lobe. Anotia corresponds to the absence of the ear lobe. To study the prevalence of microtia and anotia at the Maternity of the University of Chile Clinical Hospital. Analysis of the database of the Latin American Collaborative Study of Congenital Defects (ECLAMC). All newborns and stillborns with congenital defects are incorporated to this database. The prevalence of microtia-anotia in the period 1982-2001 was 8.7 per 10,000 born alive. Chilean hospitals have an uniform prevalence of 5.2 per 10,000 born alive. Thirty seven percent presented as isolated malformations and the rest were associated to other defects. Eighty six percent of non isolated cases were part of a syndrome. Sixty eight percent were mild or moderate forms and the rest, severe forms. Two cases were stillborns and two newborns died before hospital discharge. The prevalence of microtia in this hospital and in the rest of Chilean hospitals is significantly higher than in the rest of non Chilean hospitals participating in the ECLAMC, that is 4.1 per 10,000 born alive.


An Ovarian Protein Involved in Passive Avoidance of an Endoparasitoid To Evade Its Host Immune Response.
Through a combination of transcriptomic and proteomic analyses, we identified 817 secreted ovarian proteins from an endoparasitoid wasp, Cotesia chilonis, of which five proteins are probably involved in passive evasion. The results of an encapsulation assay revealed that one of these passive evasion-associated proteins (Crp32B), a homologue of a 32-kDa protein (Crp32) from C. rubecula, could protect resin beads from being encapsulated by host hemocytes in a dose-dependent manner. Crp32B is transcribed in ovarian cells, nurse cells, follicular cells, and oocytes, and the protein is located throughout the ovary and on the egg surface. Moreover, Crp32B has antigenic similarity to several host components. These results indicate that C. chilonis may use molecular mimicry as a mechanism to avoid host cellular immune response.


[Study on the immuno-effects of recombinant hepatitis B vaccination in adults].
To evaluate the immuno-effects of hepatitis B (HB) vaccination in adults. Five groups were sampled by means of cluster sampling, and serum HBsAg, anti-HBs and anti-HBc were tested in every group at people aged from 18 to 50. Recombinant HB vaccine was injected to the ones that HBsAg, anti-HBs and anti-HBc were all negative. Concentration of anti-HBs in serum was tested after one year and three years of vaccination. Immuno-effects of recombinant HB vaccination in adults at different ages and between sexes, were then calculated. Good immuno-effects of recombinant HB vaccination in adults were noticed. After one year and three years of vaccination with 5 micro g recombinant HB vaccine, the anti-HBs positive rates were 82.76%, 70.77% while the serum concentrations of anti-HBs were 55.91 mIU/ml and 35.41 mIU/ml respectively. When 10 micro g was used, the concentrations were 83.74%, 72.22%, 56.89 mIU/ml and 30.29 mIU/ml respectively. The effects did not show significant differences between different doses on 10 micro g and of 5 micro g. Concentration of anti-HBs reduced when time went by. The factors such as age and sex influenced the effects of immunity on recombinant HB vaccination. Good immunity could be obtained when recombinant hepatitis B was vaccinated in vulnerable population aged 18 to 50.


Longitudinal models for studying multivariate changes and dynamics.
In this paper, we describe a longitudinal modeling approach for examining multivariate changes and dynamics. This technique is based on latent change scores and is executed using a structural equation modeling framework. We provide an overview of the model, describing desirable features for identifying dynamics among multiple processes. We then illustrate its application using empirical data consisting of longitudinal processes and conclude the paper with some potential steps for advancing the modeling possibilities.


Integrated Oxidized-Hyaluronic Acid/Collagen Hydrogel with β-TCP Using Proanthocyanidins as a Crosslinker for Drug Delivery.
The susceptibility of guided bone regeneration (GBR) material to infection by pathogens at wound sites during bone healing has often been overlooked. The objective of this study was the synthesis and characterization of a potential material for antibacterial GBR application. In the current study, the mechanical strength and biocompatibility of a composite restoration material-made of oxidized hyaluronic acid (HA)/type I collagen hydrogel integrated with tricalcium phosphate (β-TCP) using a natural crosslinking agent, oligomeric proanthocyanidins (OPCs)-were evaluated. The suitability of the material as a carrier matrix for antibacterial applications was evaluated by following the drug-release profile of tetracycline loaded within the composite. Results indicated that this composite material had a high swelling ratio of 420% and mechanical strength of 25 kPa while remaining at more than 60% of the weight after 30 days of an in vitro degradation test with good biocompatibility in promoting the proliferation of MG-63 cells. Drug release studies further showed that 93% of the tetracycline was released after 5 days, which supports this GBR material's capability to release antibacterial drugs while keeping other required GBR material design functions.


Megakaryocytes and platelets in myeloproliferative disorders.
Increased megakaryocyte (MK) proliferation in bone marrow is a feature common to the three Ph-negative myeloproliferative disorders (MPDs), i.e. essential thrombocythaemia (ET), polycythaemia vera (PV), and myelofibrosis with splenic myeloid metaplasia (MMM), and to chronic myelocytic leukaemia (CML). Enlarged MKs with multilobulated nuclei and cell clustering in close proximity are the hallmark of all the Ph negative MPDs. Clonality of haematopoietic cells, based on X chromosome inactivation, can now be studied in a majority of female patients in all nucleated cell fractions as well as in platelets. Cytofluorometric studies have demonstrated a shift towards higher ploidy classes in PV and ET MKs which may be useful in discriminating between both primary and reactive thrombocytosis and CML patients which show a significant shift to lower MK ploidy values. The role of MK proliferation on the evolution of myelofibrosis common to MPDs has been firmly established. Implication of platelet-derived growth factor (PDGF) in myelofibrosis has already been demonstrated. More recently transforming growth factor beta (TGF beta) synthesized and secreted by MK has been implicated in fibroblasts stimulation. A significant increase in circulating colony-forming units of MKs (CFU-MK) has been repeatedly observed in MPDs as well as a spontaneous MK colony formation in a majority of ET patients. Hypersensitivity to thrombopoietin (TPO) in relation to a functional defect of the TPO-MPL pathway may play a major role in spontaneous MK growth. There is no currently available test of platelet functions able to predict the risk of occurrence of thrombotic or haemorrhagic complications in MPD patients. However, the role of platelet activation in the pathogenesis of ischaemic erythromelalgia has been established and a correlation between presenting haemorrhagic manifestations and platelet counts in excess of 1000 x 10(9)/l has been found.


Acquired hepatocerebral degeneration: report of an atypical case.
A case of acquired hepatocerebral degeneration secondary to biliary cirrhosis is described. It differs from the conventional type because of the clinical predominance of cerebellar symptomatology and because the principal neuropathological abnormalities were restricted to the pallidum and to the cerebellum.


Differentiation of specific DNA binding activity of SLE sera from non-specific binding by an addition of dextran sulfate and calcium chloride to the Farr assay system.
A new method for differentiation of specific DNA-binding by human sera from non-specific binding was evaluated with sera from patients with systemic lupus erythematosus in different stages of the disease. An addition of dextran sulfate or calcium chloride to Farr's radioimmunoassay mixture reduced non-specific binding of thermally denatured [3H]DNA of the patient sera without much effect on the specific binding. The measurement of DNA-binding value by the sera in these addition systems provides accurate information with regard to the pathophysiological state of the disease.


Alview: Portable Software for Viewing Sequence Reads in BAM Formatted Files.
The name Alview is a contraction of the term Alignment Viewer. Alview is a compiled to native architecture software tool for visualizing the alignment of sequencing data. Inputs are files of short-read sequences aligned to a reference genome in the SAM/BAM format and files containing reference genome data. Outputs are visualizations of these aligned short reads. Alview is written in portable C with optional graphical user interface (GUI) code written in C, C++, and Objective-C. The application can run in three different ways: as a web server, as a command line tool, or as a native, GUI program. Alview is compatible with Microsoft Windows, Linux, and Apple OS X. It is available as a web demo at https://cgwb.nci.nih.gov/cgi-bin/alview. The source code and Windows/Mac/Linux executables are available via https://github.com/NCIP/alview.


Kinetics and Energetics of Ultrafast Bimolecular Photoinduced Electron Transfer Reactions in Pluronic-Surfactant Supramolecular Assemblies.
Understanding the kinetics and energetics of photoinduced electron transfer (PET) reactions in constrained media has attracted considerable research interest, as constrained media provide a handle to tune the microenvironments and consequently the mechanisms of PET reactions. In this study, PET reactions between excited 7-aminocoumarin acceptors and ground-state N,N-dimethylaniline (DMAN) donor have been investigated in mixed micellar media composed of triblock copolymer, P123, and anionic surfactant, sodium dodecyl sulfate (SDS), with varying SDS-to-P123 molar ratios (n values). The objective is to elucidate the role of the n values in the rates and energetics of PET reactions over the entire time range from the subpicosecond to the subnanosecond domain, especially in regard to the applicability of the two-dimensional ET (2DET) mechanism. It is observed that by changing the n values, there is a significant change in the hydration characteristics of the SDS-P123 mixed micelles, which in turn changes the kinetics to energetic correlations for the PET reactions. Fluorescence from the excited coumarin acceptors undergoes substantial quenching due to PET from DMAN donor in all of the studied micelles as evidenced from steady-state, subnanosecond time-resolved (TR) and ultrafast (subpicosecond/femtosecond) fluorescence up-conversion measurements. The quenching rate constants (kq), estimated from subnanosecond TR fluorescence studies, and the individual component-wise decay rates (τi-1), estimated from up-conversion measurements, increase gradually with increasing n value, corroborating well with the sequentially increased micropolarity of the mixed micelles. Interestingly, it is observed that the correlations of either kq (from subnanosecond studies) or τi-1 (from femtosecond studies) with the reaction exergonicity (-ΔG°) show the noteworthy Marcus inversion (MI) behavior in a very consistent and similar manner for the entire time window, from subpicoseconds to subnanoseconds. The onset of MI always appears at an exergonicity (-ΔG°MI) much lower than solvent reorganization energy (λs), suggesting the involvement of 2DET mechanism throughout the subpicosecond to subnanosecond time domains. The present results thus provide a comprehensive picture of the kinetics and energetics of the PET reactions in constrained media for the whole time span and unequivocally establish the applicability of 2DET mechanism for the PET reactions in constrained media, eliminating any apprehensions about the effect of time resolution of the subnanosecond setup on the observed Marcus inversion behavior. This is indeed an important finding, providing valuable insights for PET reactions in constrained media, which has not been explored explicitly in any of the previous studies. Observation of MI behavior and the modulations in the PET reactions by simply changing the composition of SDS in the SDS-P123 mixed micelles are noteworthy findings of the present study and are expected to find suitable applications for better utilization and outcome of the PET reactions.


CTL Attenuation Regulated by PS1 in Cancer-Associated Fibroblast.
Objective: Cancer-associated fibroblasts (CAFs) were associated with tumor progression in the tumor microenvironment (TME). However, their immunosuppressive roles in protecting cancer cells from the attack by cytotoxic T lymphocytes (CTLs) are not fully clear. In this study, we investigated whether and how CAFs regulate tumor-infiltrating lymphocytes as well as their role in tumor immunosuppression. Methods: Eighty-three cases of ovarian cancer and 10 controls were analyzed for CAFs and CD8+ tumor-infiltrating lymphocytes by gene array and immunohistochemistry. We evaluated presenilin 1 (PS1) expression in CAFs, CTL penetration, tumor burden, dendritic cell function, and migration of tumor-infiltrating lymphocytes and their function in vivo and in vitro after silencing PS1. In addition, the pathway via which PS1 affects the TME was also evaluated. Results: PS1 was highly expressed in CAFs, and its silencing significantly promoted CD8+ CTL proliferation and penetration in multiple ovarian models (p < 0.05), resulting in tumor regression and growth inhibition. Interleukin (IL)-1β was identified as a major immune inhibitor in the TME, and it was significantly decreased after PS1 silencing (p < 0.05), which was regulated by the WNT/β-catenin pathway. It was also showed that high expression of IL-1β in CAFs inhibits CTL penetration significantly (p < 0.05). Conclusion: Highly expressed PS1 in CAFs plays a crucial role in regulating tumor-infiltrating lymphocyte populations in the TME via the WNT/β-catenin pathway. Targeting PS1 may retrieve functional CTLs in the TME and improve the efficacy of current immunotherapies.


Effect of ethnicity on weight loss after bariatric surgery.
Previous studies have reported better weight loss after bariatric surgery among non-Hispanic whites (NHW) versus non-Hispanic blacks (NHB) and Hispanics. The majority of these studies took place in areas where NHW are the majority. This study aimed to compare post-surgery weight outcomes by ethnicity in a geographic area where Hispanics are the majority. A retrospective medical chart review of 3268 patients (1561 Hispanic, 660 NHB, and 1047 NHW) who underwent Roux-en-Y gastric bypass (RYGB) or Adjustable Gastric Band (AGB) placement from 2002 to 2012 were analyzed. Percentages of excess weight loss (EWL) and body mass index (BMI) changes at 6, 12, and 24 months post-surgery were compared by ethnic group. At 6 months, EWL was significantly different by ethnicity (52.7 ± 15.9 Hispanics, 49.7 ± 15.7 NHW, 43.0 ± 17.3 NHB, P < 0.001). These differences remained at 1 year (66.0 ± 20.3 Hispanics, 64.0 ± 20.3 NHW, 54.1 ± 21.3 NHB, P < 0.001) and 2 years (68.6 ± 24.1 Hispanics, 69.5 ± 21.2 NHW, 57.6 ± 25.4 NHB, P < 0.001). Ethnic group changes in BMI were similar to EWL changes. Analysis stratified by gender, type of surgery, and BMI category (<40, 40-49.99, ≥50 kg/m(2)) showed lower EWL in NHB than Hispanics and NHW. NHW had higher EWL than Hispanics only when they underwent AGB and had a BMI >40 kg/m(2). Up to 2 years after RYGB, mean EWL and BMI reduction patterns are similar among NHW and Hispanics and significantly better than NHB. These patterns were comparable but not as pronounced among patients with AGB surgery. Our findings suggest that social factors may contribute to successful weight loss after bariatric surgery.


A Green Approach to High-Performance Supercapacitor Electrodes: The Chemical Activation of Hydrochar with Potassium Bicarbonate.
Sustainable synthesis schemes for the production of porous carbons with appropriate textural properties for use as supercapacitor electrodes are in high demand. In this work a greener option to the widely used but corrosive KOH is proposed for the production of highly porous carbons. Hydrochar products are used as carbon precursors. It is demonstrated that a mild alkaline potassium salt such as potassium bicarbonate is very effective to generate porosity in hydrochar to lead to materials with large surface areas (> 2000 m(2) g(-1) ) and a tunable pore size distribution. Furthermore, the use of KHCO3 instead of KOH gives rise to a significant 10 % increase in the yield of activated carbon, and the spherical morphology of hydrochar is retained, which translates into better packing properties and reduced ion diffusion distances. These features lead to a supercapacitor performance that can compete with, and even surpass, that of KOH-activated hydrochar in a variety of electrolytes.