Insight into hydrogen production through molecular simulation of an electrode-ionomer electrolyte system.

In this work, we examine metal electrode-ionomer electrolyte systems at high voltage (negative surface charge) and at high pH to assess factors that influence hydrogen production efficiency. We simulate the hydrogen evolution electrode interface investigated experimentally in the work of Bates et al. [J. Phys. Chem. C 119, 5467 (2015)] using a combination of first principles calculations and classical molecular dynamics. With this detailed molecular information, we explore the hypotheses posed in the work of Bates et al. In particular, we examine the response of the system to increased bias voltage and oxide coverage in terms of the potential profile, changes in solvation and species concentrations away from the electrode, surface concentrations, and orientation of water at reactive surface sites. We discuss this response in the context of hydrogen production.

Extraction studies of uranium(VI), plutonium(IV) and americium(III) from nitric acid using the bi-functional carbamoyl methyl sulfoxide ligands.

The extraction behavior of new bi-functional ligands containing sulfoxide and amide groups viz. N,N'-dibutyl carbamoyl methyl phenyl sulfoxide (L1) and N,N'-dibutyl carbamoyl methyl benzyl sulfoxide (L2) towards the U(VI), Pu(IV) and Am(III) ions from nitric acid was studied. Both of these extractants showed appreciable extractions for U(VI) and Pu(IV) from 1 to 9.5 M nitric acid concentrations. Am(III) did not show an appreciable extraction under the conditions studied. The species extracted from a nitric acid medium correspond to the compositions of [UO2(NO3)(2).2L] and [Pu(NO3)4.2L] for L1 and a mixture of [UO2(NO3)(2).2L], [UO2(NO3)2.L] and [Pu(NO3)(4).2L] for the L2. The conditional extraction constant (Kex) values for the Pu(IV) with L1 and L2 were estimated for the first time, and found to be 6.21 x 10(2) and 5.64 x 10(2) mol(-4) dm, respectively.

"Poor man's risk factor": correlation between high sensitivity C-reactive protein and socio-economic class in patients of acute coronary syndrome.

OBJECTIVE: Inflammation has been proposed as one of the factors responsible for the development of coronary artery disease (CAD) and high sensitivity C-reactive protein (hs CRP) at present is the strongest marker of inflammation. We did a study to assess the correlation of hs-CRP with socio-economic status (SES) in patients of CAD presenting as acute coronary syndrome (ACS). METHODS: Baseline hs-CRP of 490 patients of ACS was estimated by turbidimetric immunoassay. Patients were stratified by levels of hs-CRP into low (<1 mg/L); intermediate (1-3 mg/L) or high (>3 mg/L) groups and in tertiles of 0-0.39 mg/L, 0.4-1.1 mg/L and >1.1 mg/L, respectively. Classification of patient into upper (21.4%), middle (45.37 percent) and lower (33.3%) SES was based on Kuppuswami Index which includes education, income and profession. Presence or absence of traditional risk factors for CAD diabetes, hypertension, dyslipidemia and smoking was recorded in each patient. RESULTS: Mean levels of hs-CRP in lower, middle and upper SES were 2.3 +/- 2.1 mg/L, 0.8 +/- 1.7 mg/L and 1.2 +/- 1.5 mg/L, respectively. hs-CRP levels were significantly higher in low SES compared with both upper SES (p = 0.033) and middle SES (p = 0.001). Prevalence of more than one traditional CAD risk factors was seen in 13.5%, 37.5% and 67.67 percent; in patient of lower, middle and upper SES. It was observed that multiple risk factors had a linear correlation with increasing SES. Of the four traditional risk factors of CAD, smoking was the only factor which was significantly higher in lower SES (73%) as compared to middle (51.67 percent;) and upper (39.4%) SES. We found that 62.3%, 20.8% and 26.5% patients of low, middle and upper SES had hs-CRP values in the highest tertile. Median value of the Framingham risk score in low, middle and upper SES as 11, 14 and 18, respectively. We observed that at each category of Framingham risk, low SES had higher hs-CRP. CONCLUSION: We conclude from our study that patient of lower SES have significantly higher levels of hs-CRP despite the fact that they have lesser traditional risk factors and lower Framingham risk. These findings add credit to our belief that inflammation may be an important link in the pathophysiology of atherosclerosis and its complications especially in patients of low SES who do not have traditional risk factors.

Techniques to assess cross-border air pollution and application to a US-Mexico border region.

A year-long assessment of cross-border air pollution was conducted in the eastmost section of the US-Mexico border region, known as the Lower Rio Grande Valley, in South Texas. Measurements were conducted on the US side and included fine particle mass (PM2.5) and elemental composition, volatile organic compounds (VOCs) and meteorology. Wind sector analyses of chemical tracers and diagnostic ratios, in addition to principal component analysis (PCA), were initially applied to assess cross-border and overall air shed influences. Linear-angular correlation statistics [Biometrika, 63, (1976), 403-405] and nonparametric multiple comparisons between wind sectors were computed with the particle element data using principal component scores from PCA to determine the direction of source classes. Findings suggest crustal particles and salts carried or stirred by sea breeze winds from a southerly and southeasterly direction from the Gulf of Mexico heavily influenced the elemental composition of the particulate samples. Pair-wise comparisons of wind directions for the principal component scores suggest possible oil combustion influences from utilities or boilers coming from the south and possible coal combustion influences from the north and northwest. The techniques discussed can provide a methodology to assess future ambient levels and cross-border influences in the Valley as conditions change.

Preliminary assessments of spatial influences in the Ambos Nogales region of the US-Mexican border.

Ambient air measurements collected from 1994 to 1995 were used in a preliminary assessment of potential source and spatial influences in the Ambos Nogales border region (Nogales, Arizona, USA and Nogales, Sonora, Mexico). In this assessment, volatile organic compounds (VOC) and particulate matter (PM) species were used from four sites, two on either side of the border. An examination of median levels and principal component analysis indicated the dominance of soil dusts and mobile sources. Pairwise comparisons of sites for VOCs associated with mobile sources revealed statistically significant differences between sites in the central Nogales area vs. the two sites furthest from the border. Particulate lead at Mexican sites was higher and significantly different vs. US sites. Although further analyses are necessary, findings suggest that local and immediate mobile/other anthropogenic and soil dust influences are present throughout Nogales, with particulate lead from leaded motor vehicle exhaust or soldering operations being a possible influence on the Mexican side.

Functional cooperation between T helper cell determinants.

The immune response to T helper (Th) cell determinants of a variety of antigens is often poor and limits severely the potential efficacy of current therapeutic measures through vaccination. Here, we report that an immunologically silent tumor determinant can be rendered immunogenic if linked with a dominant determinant of a parasite antigen, suggesting the existence of functional Th-Th cooperation in vivo. This phenomenon could be mimicked in part by signaling either through CD40 to the antigen-presenting cells or through OX40 to the tumor-determinant reactive T cells, with maximal effects obtained by combined anti-CD40 and anti-OX40 treatment in vivo. The data suggest that CD4 T cells reactive with a dominant determinant provide help to other CD4 T cells through up-regulating the costimulatory ability of antigen-presenting cells, in much the same way as help for CD8 cells. CD4 help for CD4 T cells represents a new immunological principle and offers new practical solutions for vaccine therapy against cancer and other diseases in which antigenic help is limiting.

Identification of the immunoreactive peptide sequence for AgSK1, an adenocarcinoma-restricted antigen.

SK1, a human immunoglobulin M (IgM) monoclonal antibody was derived from regional nodal lymphocytes of a Dukes B colon carcinoma patient. The antigen recognized by the human monoclonal antibody (HuMab) SK1, termed AgSK1, was shown to be a two-chain glycoprotein with an apparent molecular weight range of 42-46 kDa and preferentially expressed by human adenocarcinomas, particularly human gastrointestinal malignancies. To identify the gene encoding the AgSK1 antigenic epitope, a cDNA expression library constructed in lambda gt22A using mRNA from the colon carcinoma cell line HT29 was screened and one of the isolated clones encoding a 1.5-kb cDNA, which showed strong immunoreactivity with HuMab SK1, was selected for further analysis. This clone consisted of an amino terminal open reading frame of 54 amino acids and the carboxyl terminal 20 amino acids of this protein coding region contained the antigenic epitope recognized by HuMab SK1.

Co-expression of tumor antigens and their modulation by pleiotrophic modifiers enhance targeting of human monoclonal antibodies to pancreatic carcinoma.

Cocktails of human monoclonal antibodies (HuMAbs) have been used to increase the likelihood of identifying heterogeneous cancer cells. We utilized 3 HuMAbs termed SK-1, GM4, and GMA1, which recognized a 42-46 kDa two chain structure, a 57 kDa antigen, and the ganglioside GD3, respectively. An estimated two dozen cell lines were tested for the coexpression of these antigens and this was found to be present only on pancreatic carcinoma cell line, PANC-1; A 24 hr treatment of PANC-1 cells with interferon gamma (IFN gamma; 100 units), interferon beta (IFN beta; 1000 units), as well as interferon alpha (IFN alpha; 1000 units) resulted in roughly a four fold increase in the co-expression of the 42-46 kDa/GD3 antigens as well as the 42-46 kDa/57 kDa antigens. After a 4 day incubation the co-expression of these antigens progressed and IFN alpha treatment had the most pronounced effect, which was 8 fold higher than background for the 42-46 kDa/57 kDa antigens, whereas IFN beta resulted in a five fold antigen upregulation. The pronounced effect of vinblastine on the co-expression of the 42-46 kDa/GD3 antigens (4 fold on day 1 and, 10 fold on day 4) and 42-46 kDa/57 kDa antigens on PANC-1 (5 fold on day 1 and 7 fold over background on day 4) cells can be seen at concentrations as low as 10(-7)M. Colchicine and vincristine dramatically enhanced co-expression of these tumor antigens on day 4 but not on day 1 PANC-1 cells. The expression of these antigens was also found to be cell cycle dependent.

Characterization of human IgG1 monoclonal antibody against gangliosides expressed on tumor cells.

A human IgG1.k monoclonal antibody (MAb) designated GMA1 was developed by fusing pooled lymph node lymphocytes from cancer patients with the human lymphoblastoid cell line, SHFP-1. The GMA1 MAb reacted with several melanoma and neuroblastoma cell lines. Normal tissue derived from human brain and tumor-cell lines derived from colon, ovary, and breast were not reactive. FACS analysis performed using live cells demonstrated that the antibody recognizes a cell-surface antigen. Enzyme immunoassay (EIA) and thin layer chromatography (TLC) immunostaining with purified gangliosides indicated that the antibody has specificity for the major tumor associated gangliosides GD3, GM3, and GD2. GMA1 heavy and light chain genes were isolated by RT-PCR and a recombinant derivative of this human antibody was expressed in Chinese hamster ovary (CHO) cells. High-level antibody synthesis and secretion was achieved using a vector designed to maximize expression. FACS analysis and TLC immunostaining indicated recombinant GMA1 reacted with human tumor cell lines and gangliosides GD3, GM3, GD2 in a manner similar to the antibody produced by the hybridoma cell line, demonstrating that the specificity of the antibody was not altered during molecular cloning.

Immunoscreening protocols for the identification of clinically useful antibodies and antigens.

The antigen-antibody interaction is a powerful tool for the immuno-screening of several diseases, including cancer and genetic disorders. The high specificity of monoclonal antibodies (mAbs) enables them to target antigens and form complexes that can be detected with enzymes, radionuclides, fluorescent dyes or other markers. The antibody molecule, which has an antigen binding site, can be used as an intact molecule or as a fragment, for example, F(ab)(2), Fab, Fv or scFv. Similarly, the antigen can also be varied. In this review, immuno-screening techniques that can be used to detect clinically relevant antibody-antigen interactions will be discussed.

Cloning and expression of the human tumor-specific antibody GM4.

The human monoclonal antibody GM4 was generated by fusing pooled lymphocytes from cancer patients with the lymphoblastoid cell line SHFP-1. Immunohistochemical staining of tumor and normal tissue indicated that this human IgG4 antibody preferentially reacted with melanomas and neuroblastomas. In this study, we demonstrate that GM4 recognizes a "vimentin-like" peptide sequence that we have termed AgGM4. To generate a recombinant derivative of this human antibody, we isolated and expressed the complete heavy and light chain genes. The entire coding sequence for both the heavy and light chains was isolated by RT-PCR using a set of degenerate 5' signal sequence specific primers and a 3' constant region primer. High level antibody synthesis and secretion was achieved in Chinese hamster ovary (CHO) cells using a vector designed to maximize expression. Western blot and FACS analysis indicated recombinant GM4 reacted with human tumor cell lines and AgGM4 in a manner similar to the antibody produced by the hybridoma cell line, demonstrating that the specificity of the antibody was not altered during molecular cloning.

Surgery in India.

Surgical practice in India is mostly managed by the central and state governments and is totally government financed, offering free medical aid. However, with the economic growth and affluence of the middle-class population in urban areas, more and more hospitals, nursing homes, and clinics managed by the private sector are arising in cities and towns. Privately owned hospitals are built and managed by large industrial houses and trusts. It is essential, according to government directives, for these hospitals to have certain numbers of general beds that will provide for the economically weaker sections of the population. Medical insurance is popular amongst the urban population; in addition to well-established insurance companies, many new medical service reimbursement organizations are forming. Surgical care standards are uniformly high in the larger teaching institutions and hospitals run by the private sector in major cities in India, in which superspecialty surgical care that meets worldwide standards is available in addition to general surgical care. These hospitals are manned by surgeons holding master's degrees in general surgery, superspecialties, and subspecialties. In the hospitals and dispensaries in rural areas, only basic surgical facilities are available; for major surgical procedures, the patients are referred to the closest urban hospitals. Therefore, the government of India is placing more and more emphasis on building hospitals that offer better surgical facilities away from the cities and towns. A diploma course in surgery is run by the National Board of Surgery, and these diplomates are encouraged to practice more in rural areas and small hospitals. Economic constraints and the population explosion are the biggest hurdles to progress in surgical care, teaching, and research activities. With the advancement in education and growth of the economy, more and more multinationals are walking into the field of medical care, which is proving to be a great boon and providing a rapid increase in the health care expansion in this country. The World Health Organization and the World Bank are providing considerable aid for disease prevention, health care provision, and research activities.

Polypeptide levels increase during acute onset of hepatic porphyrias.

Hepatic porphyrias are characterized by neurological symptoms manifested by abdominal pain, neuropathies and mental aberrations. Porphyrins are ubiquitous and essential biochemical constituents of living beings acting as mediators of oxidation reaction in the metabolism of the steroid, drugs, environmental chemicals or as a mean of exchanging gases, such as oxygen and carbon dioxide between the environment and the tissue of the body using endogenous polypeptide properties. The different porphyrins arising from the arrangement of normal heme synthesis are characterized by an accumulation and excretion of specific intermediate porphyrins and/or of precursors exerting toxic effect, initiating cascades of generations of polypeptides, neurotransmitters and gut-brain axis peptide responsible for the symptoms of clinical status. We studied polypeptide levels in 27 patients (19 females, 8 males) presenting acute attack of hepatic porphyria: 2 with ALA dehydratase-deficient porphyria; 9 with acute intermittent porphyria; 12 with porphyria cutanea tarda and 4 with variegate porphyria. During acute attacks of porphyria, polypeptides were found to be constantly increased: vasoactive intestinal polypeptide (VIP); neurotensin (NT); substance P; pancreatic polypeptide; gastrin-releasing peptide; gastrin and motilin. Administration of the somatostatin (antagonizing polypeptide), which was undetectable or low before treatment, apparently alleviated the acute symptomatology. Elevated levels of polypeptides, at least partly, contribute to appearance of acute symptoms in porphyria patients.

Isotype-directed enrichment of B cells by magnetic beads in the generation of immunoreactive human monoclonal antibodies.

Pooled lymphocytes collected from cancer patients were mixed with a biotinylated murine MAb specific to human IgG4. To this were added streptavidin-conjugated magnetic beads. After magnetically separating the bead-lymphocyte complex, the B cells were washed and fused with the WIL-2 derived human fusion partner, SHFP-1. Subsequently derived human-human hybridomas were screened for IgG4 immunoreactivity to target tumor cell lines. Several hybridomas reacted with a variety of malignant cell types, including melanoma, neuroblastoma, and pancreatic tumor cells. One hybridoma in particular, designated SC-GM4, recognized an antigen by Western blot with an apparent molecular weight of 57 kDa. This facile approach of magnetically separating selected populations of lymphocytes should be relatively simple to apply to other antigens and antibodies to preselect the type, class, and properties of the desired MAb.

Impaired antioxidant defense at the onset of psychosis.

Previous studies found peripheral activities of antioxidant enzymes to be abnormal in schizophrenic patients. It is not understood whether this is integral to the disease process or a result of long-term treatment with neuroleptics. Red blood cell activities of three antioxidant enzymes--superoxide dismutase, glutathione peroxidase, and catalase--were therefore examined in 14 drug-naive, first episode patients with a diagnosis of schizophrenia or schizophreniform disorder and 10 normal subjects. The patients had an average duration of psychosis of 4.46 days (SD 2.5). Superoxide dismutase activity was significantly lower in patients than in normal controls, with no difference between the groups in activities of the other two enzymes. Lower superoxide dismutase activity was associated with deterioration of school functioning from childhood to early adolescence and a history of poorer school functioning during early adolescence. These findings indicate a compromised antioxidant defense at the onset of psychosis, and suggest that oxidative injury might contribute to adverse developmental events in the pathogenic cascade of schizophrenia.

Do waste incinerators induce adverse respiratory effects? An air quality and epidemiological study of six communities.

The purpose of the study presented here was to simultaneously measure air quality and respiratory function and symptoms in populations living in the neighborhood of waste incinerators and to estimate the contribution of incinerator emissions to the particulate air mass in these neighborhoods. We studied the residents of three communities having, respectively, a biomedical and a municipal incinerator, and a liquid hazardous waste-burning industrial furnace. We compared results with three matched-comparison communities. We did not detect differences in concentrations of particulate matter among any of the three pairs of study communities. Average fine particulate (PM2.5) concentrations measured for 35 days varied across study communities from 16 to 32 micrograms/m3. Within the same community, daily concentrations of fine particulates varied by as much as eightfold, from 10 to 80 micrograms/m3, and were nearly identical within each pair of communities. Direct measurements of air quality and estimates based on a chemical mass balance receptor model showed that incinerator emissions did not have a major or even a modest impact on routinely monitored air pollutants. A onetime baseline descriptive survey (n = 6963) did not reveal consistent community differences in the prevalence of chronic or acute respiratory symptoms between incinerator and comparison communities, nor did we see a difference in baseline lung function tests or in the average peak expiratory flow rate measured over a period of 35 days. Based on this analysis of the first year of our study, we conclude that we have no evidence to reject the null hypothesis of no acute or chronic respiratory effects associated with residence in any of the three incinerator communities.