GAPDOCK: A genetic algorithm approach to protein docking in CAPRI round 1

As part of the first Critical Assessment of PRotein Interactions, round 1, we predict the structure of two protein-protein complexes, by using a genetic algorithm, GAPDOCK, in combination with surface complementarity, buried surface area, biochemical information, and human intervention. Among the five models submitted for target 1, HPr phosphocarrier protein (B. subtilis) and the hexameric HPr kinase (L. lactis), the best correctly predicts 17 of 52 interprotein contacts, whereas for target 2, bovine rotavirus VP6 protein-monoclonal antibody, the best model predicts 27 of 52 correct contacts. Given the difficult nature of the targets, these predictions are very encouraging and compare well with those obtained by other methods. Nevertheless, it is clear that there is a need for improved methods for distinguishing between correct and plausible but incorrect complexes. Proteins 2003;52:10-14

Final design report of a personnel launch system and a family of heavy lift launch vehicles

The objective was to design both a Personnel Launch System (PLS) and a family of Heavy Lift Launch Vehicles (FHLLVs) that provide low cost and efficient operation in missions not suited for the Shuttle. The PLS vehicle is designed primarily for space station crew rotation and emergency crew return. The final design of the PLS vehicle and its interior is given. The mission of the FHLLVs is to place large, massive payloads into Earth orbit with payload flexibility being considered foremost in the design. The final design of three launch vehicles was found to yield a payload capacity range from 20 to 200 mt. These designs include the use of multistaged, high thrust liquid engines mounted on the core stages of the rocket

PAMELA, DAMA, INTEGRAL and Signatures of Metastable Excited WIMPs

Models of dark matter with ~ GeV scale force mediators provide attractive explanations of many high energy anomalies, including PAMELA, ATIC, and the WMAP haze. At the same time, by exploiting the ~ MeV scale excited states that are automatically present in such theories, these models naturally explain the DAMA/LIBRA and INTEGRAL signals through the inelastic dark matter (iDM) and exciting dark matter (XDM) scenarios, respectively. Interestingly, with only weak kinetic mixing to hypercharge to mediate decays, the lifetime of excited states with delta < 2 m_e is longer than the age of the universe. The fractional relic abundance of these excited states depends on the temperature of kinetic decoupling, but can be appreciable. There could easily be other mechanisms for rapid decay, but the consequences of such long-lived states are intriguing. We find that CDMS constrains the fractional relic population of ~100 keV states to be <~ 10^-2, for a 1 TeV WIMP with sigma_n = 10^-40 cm^2. Upcoming searches at CDMS, as well as xenon, silicon, and argon targets, can push this limit significantly lower. We also consider the possibility that the DAMA excitation occurs from a metastable state into the XDM state, which decays via e+e- emission, which allows lighter states to explain the INTEGRAL signal due to the small kinetic energies required. Such models yield dramatic signals from down-scattering, with spectra peaking at high energies, sometimes as high as ~1 MeV, well outside the usual search windows. Such signals would be visible at future Ar and Si experiments, and may be visible at Ge and Xe experiments. We also consider other XDM models involving ~ 500 keV metastable states, and find they can allow lighter WIMPs to explain INTEGRAL as well.Comment: 22 pages, 7 figure

Population-Attributable Risk Estimates for Risk Factors Associated with Campylobacter Infection

In 2001-2002, a multicenter, prospective case-control study involving 1,714 participants ≥5 years of age was conducted in Australia to identify risk factors for Campylobacter infection. Adjusted population-attributable risks (PARs) were derived for eac

12．グルタミン酸ナトリウムはglucagon like peptide-1の食後早期の分泌を促進し, 食後血糖の上昇を抑制する

The purpose of this study was to compare the growth and nutritional status of infants fed different diets, some of whom received a low-fat formula. Beginning at four to six months of age, 101 infants were fed whole cow\u27s milk, one of two low-fat follow-up formulas, or a standard infant formula until 12 months of age. Weight, recumbent length, and head circumference were measured at one-month intervals. Analyses of status (values at an age) for all examinations showed no significant differences among the feeding groups in status for weight or recumbent length, but there were significant differences in head circumference for boys and for girls after adjustments for the initial values. Head circumferences were smaller in those fed whole cow\u27s milk and relatively large in those fed follow-up formula, but these differences were small and not of clinical significance. Comparisons with national reference data showed growth in weight, recumbent length, and head circumference was normal regardless of feeding group. These results indicate that, during the second half year of infancy, the use of lower fat concentrations in the follow-up formulas did not retard growth in weight, recumbent length, or head circumference

Glyconanoparticles for colorimetric bioassays

Carbohydrate molecules are involved in many of the cellular processes that are important for life. By combining the specific analyte targeting of carbohydrates with the multivalent structure and change of solution colour as a consequence of plasmonic interactions with the aggregation of metal nanoparticles, glyconanoparticles have been used extensively for the development of bioanalytical assays. The noble metals used to create the nanocore, the methodologies used to assemble the carbohydrates on the nanoparticle surface, the carbohydrate chosen for each specific target, the length of the tether that separates the carbohydrate from the nanocore and the density of carbohydrates on the surface all impact on the structural formation of metal based glyconanoparticles. This tutorial review highlights these key components, which directly impact on the selectivity and sensitivity of the developed bioassay, for the colorimetric detection of lectins, toxins and viruses

Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome : A 24-Week, Phase III Study

Background This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome-associated intestinal failure (SBS-IF). Methods A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a >= 20% reduction in parenteral support (PS) from baseline at week 24. Results All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98% and 100% of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2%), 18 (69.2%), and 1 (11.1%) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P <0.05 vs SOC). Both 0.025-mg/kg and 0.05-mg/kg teduglutide groups showed clinically significant reductions in PS volume (P <0.05 vs SOC), PS calories, days per week and hours per day of PS infusions, and increases in enteral nutrition and plasma citrulline at week 24 compared with baseline. Two (8.3%, 0.025 mg/kg teduglutide) and 3 patients (11.5%, 0.05 mg/kg teduglutide) achieved enteral autonomy. Conclusion The safety profile of teduglutide was similar to that reported previously in children and adults. Treatment with teduglutide was associated with significant reductions in PS for pediatric patients with SBS-IF over 24 weeks.Peer reviewe

In vitro antibacterial activity of unconjugated and conjugated bile salts on Staphylococcus aureus

Bile salts are potent antimicrobial agents and are an important component of innate defenses in the intestine, giving protection against invasive organisms. They play an important role in determining microbial ecology of the intestine and alterations in their levels can lead to increased colonization by pathogens. We have previously demonstrated survival of the opportunistic pathogen Staphylococcus aureus in the human colonic model. Thus investigating the interaction between S. aureus and bile salts is an important factor in understanding its ability to colonize in the host intestine. Harnessing bile salts may also give a new avenue to explore in the development of therapeutic strategies to control drug resistant bacteria. Despite this importance, the antibacterial activity of bile salts on S. aureus is poorly understood. In this study, we investigated the antibacterial effects of the major unconjugated and conjugated bile salts on S. aureus. Several concentration-dependent antibacterial mechanisms were found. Unconjugated bile salts at their minimum inhibitory concentration (cholic and deoxycholic acid at 20 and 1 mM, respectively) killed S. aureus, and this was associated with increased membrane disruption and leakage of cellular contents. Unconjugated bile salts (cholic and deoxycholic acid at 8 and 0.4 mM, respectively) and conjugated bile salts (glycocholic and taurocholic acid at 20 mM) at their sub inhibitory concentrations were still able to inhibit growth through disruption of the proton motive force and increased membrane permeability. We also demonstrated that unconjugated bile salts possess more potent antibacterial action on S. aureus than conjugated bile salts

Safety Findings in Pediatric Patients During Long-Term Treatment With Teduglutide for Short-Bowel Syndrome-Associated Intestinal Failure : Pooled Analysis of 4 Clinical Studies

Background This analysis assessed combined safety data from 4 clinical studies of teduglutide in pediatric patients with short-bowel syndrome-associated intestinal failure (SBS-IF). Methods Safety data from teduglutide-treated patients in 4 clinical trials were pooled. The completed 12-week and 24-week phase 3 core studies (NCT01952080/EudraCT 2013-004588-30 and NCT02682381/EudraCT 2015-002252-27) enrolled children aged 1-17 years with SBS-IF. Patients could elect to enroll in ongoing open-label extensions (NCT02949362/EudraCT 2016-000863-17 and NCT02954458/EudraCT 2016-000849-30). Interim data from ongoing studies were included. Results Safety data are reported for 89 pediatric patients treated with teduglutide for a median (range) of 51.7 (5.0-94.7) weeks. Adverse events (AEs) were reported in all patients; the most common were vomiting (51.7%), pyrexia (43.8%), upper respiratory tract infection (41.6%), and cough (33.7%). Thirty-five patients (39.3%) had AEs considered related to teduglutide treatment; abdominal pain and vomiting were most frequent (5.6% each). Three serious AEs in 3 patients (3.4%) were considered related to teduglutide treatment: ileus, d-lactic acidosis, and gastrointestinal obstruction due to hard stools. All 3 events resolved. One cecal polyp was detected, which was not biopsied or found on repeat colonoscopy. No cases of neoplasia occurred. Conclusion Based on integrated data from 4 clinical studies, including long-term follow-up forPeer reviewe