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Bacterial wilt disease in brinjal caused by Ralstonia solanacearumis a major production constraint in Coastal regions of India. Among various management strategies, cultivation of resistant varieties is the most effective one. In this study, we screened 17 recombinant inbred lines for bacterial wilt resistance in green house followed by evaluation in the field for two years. Fifteen lines showed resistance to bacterial wilt. Two lines, 27-7-2 and 42-7-1 designated as Goa Brinjal-5 and Goa Brinjal-6 were released for bacterial wilt management as they exhibited 0 to 0.83% wilt and a yield of 0.76–0.84 Kg/plant. Field evaluation of six bacterial wilt resistant varieties for 2 years indicated that the wilt incidence was less than 3% while it was above 95% in the susceptible cultivars. Demonstration of six varieties in farmer’s field indicated that wilt incidence was less than 4% in the varieties compared to 77–82% in susceptible cultivars.

The US National Institute of Allergy and Infectious Diseases (NIAID) convened a virtual workshop in July 2022 to address the research landscape and identify gaps and opportunities in the understanding of durable vaccine protection.

Cultivation of brinjal in Coastal regions of India is severely affected by bacterial wilt disease caused by Ralstonia solanacearum. In this study, recombinant inbred lines were developed and screened for bacterial wilt resistance. Seventeen promising resistant lines were evaluated in the field for two years and the results indicated these lines were resistant to bacterial wilt. Lines 262-4, 5-12-1, 66-8-1, 205-1, 12-2-4 and 28-8-5 were promising among the purple types (0 to 4 % wilt and yield 0.51 to 0.93 kg/ plant). Among the green types, lines 5-8-1, 93-8-1 and 92-3-7 were promising (0 to 5 % wilt and yield 0.64 to 0.79 kg/ plant). Demonstration of eight lines in farmer’s field indicated that lines 262-4, 5-12-1, 205-1, 5-8-1 and 12-2-4 were least infected (3 to 17 %). Based on these studies, four purple lines 262-4, 5-12-1, 66-8-1 and 205-1 were released as bacterial wilt resistant brinjal varieties in the State of Goa.

Researchers report the development of a technique to measure the immune system response to antibodies against HIV. Virus neutralizing antibodies have prevented infection after exposure to HIV-like viruses in chimpanzees and mice. Patients who remain healthy despite HIV infection may have high levels of viral neutralizing antibodies in their blood. A molecular assay using a polymerase chain reaction (PCR) technique may be used to detect HIV neutralization by antibodies.

In New South Wales, a coordinated extracorporeal membrane oxygenation (ECMO) retrieval program has been in operation since 2007. This study describes the characteristics and outcomes of patients transported by this service. We performed a retrospective observational study and included patients who were transported on ECMO to either of two adult tertiary referral hospitals in Sydney, New South Wales, between February 28, 2007 and February 29, 2016. One hundred and sixty-four ECMO-facilitated transports occurred, involving 160 patients. Of these, 118 patients (74%) were treated with veno-venous (VV) ECMO and 42 patients (26%) were treated with veno-arterial ECMO. The mean (standard deviation, SD) age was 40.4 (15.0) years. Seventy-seven transports (47%) occurred within metropolitan Sydney, 52 (32%) were from rural or regional areas within NSW, 17 (10%) were interstate transfers and 18 (11%) were international transfers. Transfers were by road (58%), fixed wing aircraft (27%) or helicopter (15%). No deaths occurred during transport. The median (interquartile range) duration of ECMO treatment was 8.9 (5.2–15.3) days. One hundred and nineteen patients (74%) were successfully weaned from ECMO and 109 (68%) survived to hospital discharge or transfer. In patients treated with VV ECMO, age, sequential organ failure assessment score, pre-existing immunosuppressive disease, pre-existing diabetes, renal failure requiring dialysis and failed prone positioning prior to ECMO were independently associated with increased mortality. ECMO-facilitated patient transport is feasible, safe, and results in acceptable short-term outcomes. The NSW ECMO Retrieval Service provides specialised support to patients with severe respiratory and cardiovascular illness, who may otherwise be too unstable to undergo inter-hospital transfer to access advanced cardiovascular and critical care services.

A 60 year old man had asymptomatic progressive pigmentation of the palms (fig 1), fingertips (fig 2), and soles for the last 20 years. Besides this, he had discoloration of [...]

Donor livers are precious resources and it is, therefore, ethically imperative that we employ optimally sensitive and specific transplant selection criteria. Current selection criteria, the Milan criteria, for liver transplant candidates with hepatocellular carcinoma (HCC) are primarily based on radiographic characteristics of the tumor. Although the Milan criteria result in reasonably high survival and low-recurrence rates, they do not assess an individual patient’s tumor biology and recurrence risk. Consequently, it is difficult to predict on an individual basis the risk for recurrent disease. To address this, we employed microarray profiling of microRNA (miRNA) expression from formalin fixed paraffin embedded tissues to define a biomarker that distinguishes between patients with and without HCC recurrence after liver transplant. In our cohort of 64 patients, this biomarker outperforms the Milan criteria in that it identifies patients outside of Milan who did not have recurrent disease and patients within Milan who had recurrence. We also describe a method to account for multifocal tumors in biomarker signature discovery.

Health-related quality of life (HRQOL) is often much reduced among individuals with multiple sclerosis (MS), and incidences of depression, fatigue, and anxiety are high. We examined effects of a mindfulness-based intervention (MBI) compared to usual care (UC) upon HRQOL, depression, and fatigue among adults with relapsing-remitting or secondary progressive MS.

We used an external quality assurance (EQA) panel to assess laboratory competency and comparability when performing ELISPOT assays in support of human immunodeficiency virus type 1 (HIV-1) vaccine trials. Cell recovery, viability, and frequency of interferon-γ (IFN-γ)-secreting cells after antigen stimulation were obtained from 11 laboratories on a coded panel of 11 peripheral blood mononuclear cell samples. The median recovery and viability before plating for all samples were 35% and 86%, respectively, with notable interlaboratory and intrasample variability. Empirical as well as statistical analysis methods were used to define positive ELISPOT responses. Remarkable concordance between laboratories was obtained in defining a qualitative assessment of responder/nonresponder status to antigens, but the frequency of responding cells varied among the laboratories. This study highlights the need for better standardization of protocols and reagents to obtain reliable and reproducible data that may support immunogenicity studies, vaccine regulatory submissions, and licensure.

The identification of sequence patterns involved in gene regulation and expression is a major challenge in molecular biology. In this paper we describe a novel algorithm and the software for searching nucleotide and protein sequences for complex nucleotide patterns including potential secondary structure elements, also allowing for mismatches/mispairings below a user-fixed threshold, and assessing the statistical significance of their occurrence through a Markov chain simulation.

CNI-1493, a newly developed, water-soluble tetravalent guanylhydrazone, is a powerful inhibitor of tumor necrosis factor (TNF) and interleukin-1 (IL-1) synthesis. Microencapsulation of drugs into microcapsules that target macrophages has improved the effectiveness of both TNF and IL-1 neutralizing antibodies in experimental models of septic shock. It is the purpose of this study to determine if microencapsulation of CNI-1493 will improve cytokine inhibition. CNI-1493 was microencapsulated using albumin into 1 μm spheres. Comparable amounts of CNI-1493 in solution and in microencapsulated form were added to 1 ml aliquots of whole blood along with 100 ng of endotoxin. TNF and IL-1 were measured by ELISA. Microencapsulated CNI-1493 was also given to rats with endotoxic shock (15 mg/kg Escherichia coli endotoxin) and rats with peritonitis induced by peritoneally injecting 1010 CFU E. coli. Equivalent amounts of encapsulated and solution CN I-493 were given intravenously. Endotoxin 15 mg/kg was also given to rats 6 and 24 h after a dose of encapsulated CNI-1493 to determine the duration of action of encapsulated drug. The microencapsulated CNI-1493 produced significantly greater inhibition of TNF and IL-1 at all doses in the whole blood model. There was significantly improved survival and cytokine inhibition in the endotoxic shock model as well as the peritonitis model in rats treated with microencapsulated CNI-1493. There was also 83% survival in rats given endotoxin 24 h after a dose of encapsulated CNI-1493. From these data, we conclude that CNI-1493 is a potent inhibitor of cytokine production and is greatly potentiated by microencapsulation, which transports the drug to macrophages.

Abstract: Corner tests on assemblies of protected polystyrene foam showed that the addition of any covering material to the insulation having a flame spread classification of less than 150 as measured by the 7.6-m tunnel test was beneficial in terms of reducing the rate of early fire spread.

A limited number of flammability tests of foamed plastics indicates that the ASTM E162 radiant panel test will rank thermosetting foamed plastics in a plausible merit sequence. The method attributes undue merit, however, to the influence of the low emissivity of aluminum-foil-facing and rates thermoplastic foams very favorably because of their melting and dripping characteristics.

The adult and fetal forms of human intestinal alkaline phosphatase (ALPase; orthophosphoric-monoester phosphohydrolase, EC 3.1.3.1) are indistinguishable by a variety of analytical procedures. However, they differ electrophoretically and can be differentiated by binding studies with monoclonal antibodies. In this report, these two enzymes along with placental and liver ALPases are compared by the technique of CNBr peptide mapping, and the role of carbohydrate in generating these patterns is investigated. NaDodSO4/PAGE of CNBr digests of radiolabeled ALPases from fetal and adult intestine shows that these two isozymes share five of seven common-sized CNBr fragments. Placental ALPase shares only one common-sized fragment with either intestinal enzyme. Liver ALPase has no CNBr fragments in common with any of the others. These data indicate that fetal intestinal ALPase is not a heterodimer of one subunit each of intestinal ALPase and placental ALPase as has been postulated. CNBr digests of neuraminidase-treated enzymes reveal a change of mobility of only one CNBr band in each of fetal intestinal, placental, and liver ALPases, indicating the presence of sialic acid residues in these fragments. Periodic acid/Schiff reagent staining (specific for carbohydrate) of CNBr digests of fetal and adult intestinal ALPases reacts with only one band in each enzyme, which is the same band from the fetal enzyme shown to contain sialic acid. However, fetal and adult intestinal ALPases each contain at least one CNBr fragment of unique size that is apparently nonglycosylated.

Lactoperoxidase-catalyzed radioiodination was used to study the arrangement of the component peptides of succinate-cytochrome c reductase with respect to the aqueous phases on each side of the mitochondrial inner membrane. Mitochondria depleted of their outer membrane and inside-out vesicles purified from submitochondrial particles by the lectin-affinity procedure (D'Souza, M. P., and Lindsay, J. G. (1981) Biochim. Biophys. Acta 640, 463-472) were iodinated using immobilized preparations of lactoperoxidase. The labeled membranes were solubilized in detergent and the succinate-cytochrome c reductase was purified by immunoprecipitation with specific IgG. Analysis of the radioiodine distribution after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and comparison with peptide stain patterns show that bands 2 (64 kilodaltons), 6 (30 kilodaltons), 9 (15 kilodaltons), and 11 (less than 10 kilodaltons) are labeled from the cytoplasmic surface of the membrane. Bands 1 (72 kilodaltons), 4 (48 kilodaltons), and 8 (20 kilodaltons) appear to be labeled on the matrix side of the membrane, while bands 3 (52 kilodaltons), 5 (35 kilodaltons), 7 (25 kilodaltons), and 10 (11 kilodaltons) are labeled from both sides of the membrane. Tentative identification of the labeled bands suggests that band 1 is the large subunit of succinate dehydrogenase. Bands 3 and 4 represent proteins which have been referred to as core proteins I and II. Bands 5 and 6 are the proteins associated with cytochromes b and c1, respectively; band 7 is the Rieske iron-sulfur protein.

Diabetic patients often have a kidney or pancreas allograft requiring cyclosporine A (CsA) to prevent transplant rejection. These patients usually take p.o. hypoglycemic agents to control their diabetes. Because of the reported adverse effects of CsA on glucose metabolism as well as its potential use in Type II diabetics, we were interested in evaluating the in vivo effect of CsA on the activity of p.o. hypoglycemic agents. We also wanted to determine if tolbutamide produced any adverse effects on the pharmacokinetics of CsA. Male, Holtzman rats were administered CsA (p.o.) followed 1 hr later with the hypoglycemic agent. Two hours later, blood samples were obtained to determine blood glucose levels. Animals treated with CsA alone produced a significant hyperglycemia. The hypoglycemic effects produced by tolbutamide and glyburide were inhibited in animals treated concomitantly with CsA. This inhibitory effect was not observed during the first 3 hr of CsA-treatment, could not be overcome by increasing the dose of the hypoglycemic agent and occurred using small doses. CsA did not, however, interfere with the activity of exogenous NPH insulin. Tolbutamide was found to have no effect on the acute pharmacokinetics of CsA. The distribution of CsA was similar to controls in all tissues studied except the liver in which CsA levels were less in tolbutamide-treated animals. These studies demonstrate that CsA interferes with the effects of p.o. hypoglycemic agents and, therefore, blood glucose levels should be monitored closely in Type II diabetic patients taking combinations of these drugs.

Composite assemblies of materials of sharply different thermal properties cannot be listed in a flammability merit sequence intended to have a wide range of application. For such assemblies, relative flammabilities depend on the time scale of the flammability test utilized. Metal-foil-faced foamed plastics exhibit this effect to a marked degree.

Abstract: Corner wall and tunnel testing of foamed thermosetting plastics has suggested that the E-84 anomaly can be resolved by the use of a rate index in the range of 0 to 77.5, where a distance criterion currently prevails. Inherent inaccuracies, however, might continue to require occasional corner wall testing.

The discovery that HIV requires a chemokine co-receptor to invade host cells has prompted many investigations into therapeutic strategies that target these receptors in an attempt to block HIV entry. In this review, Scott Cairns and Patricia D'Souza discuss these potentially powerful approaches and how they complement existing antiretroviral drug therapy.

Lysosomal membrane proteins solubilized with octyl beta-D-glucopyranoside were reconstituted into proteoliposomes using acetone/ether-washed phospholipids from Escherichia coli. Assays of the quenching of acridine orange fluorescence showed that addition of both ATP and valinomycin to K+-loaded proteoliposomes led to the formation of a pH gradient that was acidic inside. ATP-driven acidification took place in the absence of permeant anions and was inhibited by the "protonophore", carbonylcyanide p-trifluoromethoxyphenylhydrazone, indicating that only H+ was transported actively. Proton translocation was readily blocked by N-ethylmaleimide (10 microM gave 50% inhibition of fluorescence quenching) but was unaffected by oligomycin (50 nM), orthovanadate (50 microM), or ouabain (0.5 mM); similarly, only N-ethylmaleimide affected ATP hydrolysis by proteoliposomes (88% inhibition). Other work showed that reconstitution of ATP-driven proton translocation required the presence of glycerol during protein solubilization and that optimal recovery depended on the use of both glycerol and phospholipid at this stage. We conclude that acidification of the lysosome is mediated by an ATPase capable of electrogenic H+ translocation without molecular coupling to other ionic species.

The ros chromosomal gene is present in octopine and nopaline strains of Agrobacterium tumefaciens as well as in Rhizobium meliloti. This gene encodes a 15.5-kDa protein that specifically represses the virC and virD operons in the virulence region of the Ti plasmid. The ros gene was cloned from a genomic bank by electroporation and complementation in Agrobacterium cells. Reporter fusion to the ros gene indicates that the level of transcription is controlled in part by autoregulation. A consensus inverted repeat sequence present in the ros promoter and in the virC and virD promoters of pTiC58, pTiA6, and pRiA4b suggests that a specific Ros binding site exists in these promoters. In the virC and virD promoter region, this binding site is within a cluster of vir box consensus sequences in which the VirG protein binds. This suggests possible binding competition between Ros and VirG at the virC and virD promoters. That the Ros protein binds DNA is suggested by the presence of a 'zinc finger' consensus sequence in the protein.

The high temperature reaction of methane in a flow system was investigated analytically using a reaction scheme consisting of 24 reaction steps and involving 15 species. Over the range of conditions considered the predicted role of H2CO compared favourably with the experimental evidence available in the literature. The results also indicated the importance of H2O2 in the low temperature oxidation of methane particularly within the pre-ignition stage. Calculated values of the induction period were generally in good agreement with experimental results reported in the literature.

The WIT (What Is There) (http://wit.mcs.anl.gov/WIT2/) system has been designed to support comparative analysis of sequenced genomes and to generate metabolic reconstructions based on chromosomal sequences and metabolic modules from the EMP/MPW family of databases. This system contains data derived from about 40 completed or nearly completed genomes. Sequence homologies, various ORF-clustering algorithms, relative gene positions on the chromosome and placement of gene products in metabolic pathways (metabolic reconstruction) can be used for the assignment of gene functions and for development of overviews of genomes within WIT. The integration of a large number of phylogenetically diverse genomes in WIT facilitates the understanding of the physiology of different organisms.

SENTRA, available via URL http://wit.mcs.anl.gov/WIT2/Sentra/, is a database of proteins associated with microbial signal transduction. The database currently includes the classical two-component signal transduction pathway proteins and methyl-accepting chemotaxis proteins, but will be expanded to also include other classes of signal transduction systems that are modulated by phosphorylation or methylation reactions. Although the majority of database entries are from prokaryotic systems, eukaroytic proteins with bacterial-like signal transduction domains are also included. Currently SENTRA contains signal transduction proteins in 34 complete and almost completely sequenced prokaryotic genomes, as well as sequences from 243 organisms available in public databases (SWISS-PROT and EMBL). The analysis was carried out within the framework of the WIT2 system, which is designed and implemented to support genetic sequence analysis and comparative analysis of sequenced genomes.

The UK health reforms, among other things, have allowed some family practitioners (‘fundholders’) to control part of the budget used to purchase secondary care for the patients registered with their practices. Some feared that this change in organization might threaten the equity of the National Health Service (NHS) by giving advantages to the patients of fundholding general practitioners (GPs). This has led to the formation of the first large GP ‘Multifund’ in the UK. Whilst the first small fundholding co-operatives were conceived simply as a way of improving the business efficiency of ordinary fundholding, the much larger Kingston and Richmond (K&R) Multifund is a professional co-operative of fund-holding family practitioners who share a common management allowance, which controls £32.6 million per annum, about 20% of the public funds devoted to health care in its locality, and has a broader agenda. It sets out to end any two-tier system discriminating between the patients of fundholding and other practitioners within a locality by making it possible for all GPs to become fundholders within an open, democratic doctors' co-operative. Its declared aims are to maintain equity and clinical integrity, to plan health care and to undertake scientific evaluation. Its overall goal is to preserve and improve upon the economic and ethical success of the British NHS. A brief evaluation is included which suggests that Multifund members believe their organization is currently meeting most of these aims. The essay argues for GP-led Multifund systems centred on outcome evidence. A new generalized global tool for measuring outcome, is being developed to assist in this process and it is briefly described here and is designed to facilitate: (1) the selection of cost-effective interventions, (2) the negotiation of appropriate funding from government and (3) the demonstration of ethical behaviour in rationing health provision within a limited budget. It is envisaged that the Multifund's scope will be extended, to administer the majority of the funds available for health care, by involving all local primary health providers and becoming a ‘careholding’ consortium. This would mean obtaining local accountability through new community health forums and improving mutual trust through public professional affirmations. If all this is successful multifunding could become a community-centred model for the management of health service money which may in turn have international application.

The results of a controlled trial of murtiphasic screening in general practice are presented. In 1967, 7,229 individuals aged between 40 and 64 years were randomly allocated into either a Screening or Control group. The Screening group were invited to attend two screening sessions held about two years apart while the Control group continued to receive conventional medical care. Both groups were then invited to undergo a health survey in 1972–73 which revealed no significant differences in morbidity between the two groups. Careful follow-up permitted detailed Screening-Control comparisons of various outcome measures-consultation and hospital admission rates, certified sickness absence from work, and mortality. Nine years after the initial screening, no significant differences were found between the two groups in any of the outcome measures. It is estimated that a similar screening programme for the entire middle-aged UK population would cost �142 million at 1976 prices.

A collaborative study was organized to identify monoclonal antibodies (MAbs) that may be broadly and potently neutralizing for a panel of human immunodeficiency virus type 1 (HIV-1) low-passaged adult and pediatric primary isolates in peripheral blood mononuclear cells. Five laboratories evaluated a coded panel of seven human MAbs to HIV-1 subtype B envelope V3, CD4 binding region, gp41, and other conformationally sensitive determinants. Each laboratory measured neutralizing activity of the MAbs against the laboratory isolate HIVMN and a panel of 9 subtype B primary isolates. Antibodies were classified as suitable candidates for future clinical studies if they could neutralize at least half of the 9 primary isolates at a concentration of ≤25 µg/mL for 90% viral inhibition. The study identified three MAbs that met stated performance criteria: IgG1b12, 2G12, and 2F5. These results may provide a rationale for examining the clinical efficacy, either singly or in combination, of the three MAbs.