An experiment to detect gut monopoles

Recent advances in the development of Grand Unification Theories have led to several interesting predictions. One of these states that Grand Unification Monopoles (GUMs) exist as solutions in may nonabelian gauge theories. Another consequence of Unification is the possibility of baryon decay. The efficiency of the water tank detector in registering a Rubakov type decay will vary with both the interaction length and the GUM's velocity, expressed in terms of beta ( 0.01). The efficiency decreases at large values of because of the limited resolving time of the detector (approx. 50 ns). At lower values of Beta the time between interactions is such that the criterion of 4 events in 2 mu s can no longer be satisfied. The Rubakov experiment has now been in operation for almost 2 years with an estimated live time of 80%. During this time no candidate events have been observed leading to an estimated upper limit on the flux of 7.82 x 0.00001 m(-2) d(-1) Sr(-1). The ionization loss detection system has only recently come on line and as yet no results are available from this experiment

Vascular uptake of rehydration fluids in hypohydrated men at rest and exercise

The purpose of this study was to formulate and to evaluate rehydration drinks, which would restore total body water and plasma volume (PV), for astronauts to consume before and during extravehicular activity, a few hours before reentry, and immediately after landing. In the first experiment (rest, sitting), five healthy men (23-41 yr), previously dehydrated for 24 hr., drank six (1a, 2, 4, 5, 6, 7) fluid formulations (one each at weekly intervals) and then sat for 70 min. Pre-test PV were measured with Evans blue dye and changes in PV were calculated with the hematocrit-hemoglobin transformation equation. This rest experiment simulated hypohydrated astronauts preparing for reentry. The second experiment (exercise, supine) followed the same protocol except four healthy men (30-46 yr) worked for 70 min. in the supine position on a cycle ergometer at a mean load of 71+/-1 percent of their peak aerobic work capacity. This exercise experiment simulated conditions for astronauts with reduced total body water engaging in extravehicular activity

Novel pyrrolobenzodiazepine benzofused hybrid molecules inhibit NF-κB activity and synergise with bortezomib and ibrutinib in hematological cancers

Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are incurable hematological malignancies that are pathologically linked with aberrant NF-κB activation. In this study, we identified a group of novel C8-linked benzofused Pyrrolo[2,1-c][1,4]benzodiazepines (PBD) monomeric hybrids capable of sequence-selective inhibition of NF-κB with low nanomolar LD50 values in CLL (n=46) and MM cell lines (n=5). The lead compound, DC-1-192, significantly inhibited NF-κB DNA binding after just 4h exposure and demonstrating inhibitory effects on both canonical and non-canonical NF-κB subunits. In primary CLL cells, sensitivity to DC-1-192 was inversely correlated with RelA subunit expression (r2=0.2) and samples with BIRC3 or NOTCH1 mutations showed increased sensitivity (P=0.001). RNA-sequencing and gene set enrichment analysis confirmed the over-representation of NF-κB regulated genes in the down-regulated gene list. Furthermore, In vivo efficacy studies in NOD/SCID mice, using a systemic RPMI 8226 human multiple myeloma xenograft model, showed that DC-1-192 significantly prolonged survival (P=0.017). In addition, DC1-192 showed synergy with bortezomib and ibrutinib; synergy with ibrutinib was enhanced when CLL cells were co-cultured on CD40L-expressing fibroblasts in order to mimic the cytoprotective lymph node microenvironment (P = 0.01). Given that NF-κB plays a role in both bortezomib and ibrutinib resistance mechanisms, these data provide a strong rationale for the use of DC-1-192 in the treatment of NF-κB-driven cancers, particularly in the context of relapsed/refractory disease

Correlated variability of Mkn 421 at X-ray and TeV wavelengths on timescales of hours

Mkn 421 was observed for about two days with BeppoSAX, prior to and partly overlapping the start of a 1 week continuous exposure with ASCA in April 1998, as part of a world-wide multiwavelength campaign. A pronounced, well defined, flare observed in X-rays was also observed simultaneously at TeV energies by the Whipple Observatory's 10 m gamma-ray telescope. These data provide the first evidence that the X-ray and TeV intensities are well correlated on time-scales of hours.Comment: 4 pages, 1 figure, presented at the VERITAS Workshop on the TeV Astrophysics of Extragalactic Object

Seven-Year Efficacy of RTS,S/AS01 Malaria Vaccine among Young African Children

Background The RTS,S/AS01 malaria vaccine candidate is being evaluated for implementation. Methods We conducted 7 years follow-up of children who were randomized at age 5 to 17 months to receive three doses of either the RTS,S/AS01 vaccine or control vaccine (rabies). The endpoint was clinical malaria (temperature ≥37.5°C and infection with Plasmodium falciparum of ≥2500 parasites per µl). Each child’s malaria exposure was estimated using the prevalence of malaria among residents within a 2km radius of their homestead. Vaccine efficacy was defined as 1 minus the hazard ratio (HR) or incidence rate ratios (IRR) of the RTS,S/AS01 vaccinated versus rabies vaccinated groups. Results We identified 1002 clinical malaria episodes among 223 children randomized to RTS,S/AS01 and 992 clinical malaria episodes among 224 children randomized to control vaccination over seven years follow-up. Intention-to-treat vaccine efficacy (VE) was 4.4% (95%CI: -17 to 21.9, p value=0.67) and per-protocol VE was 7.0% (95%CI -14.5 to 24.6%, p=0.5) by negative binomial regression. VE waned over time (p=0.006 for the interaction between vaccination and time), including negative efficacy during the fifth year among children at higher malaria parasite exposure (-43.5%, 95%CI: -100.3 to -2.8, p value=0.033 by intention-to-treat and -56.8%, 95%CI -118.7 to -12.3, p=0.008 per-protocol). Conclusion A 3-dose vaccination with RTS,S/AS01 is initially protective against clinical malaria, but this is offset by rebound in later years in areas with higher malaria parasite exposure. Further data are needed on longer-term outcomes following four-dose vaccinations. </p

Hercules X-1: Pulsed gamma-rays detected above 150 GeV

The 1.24 second binary pulsar Her X-1, first observed in X-rays in 1971 by UHURU has now been seen as a sporadic gamma ray source from 1 TeV up to at least 500 TeV. In addition, reprocessed optical and infrared pulses are seen from the companion star HZ Herculis. Thus measurements of the Her X-1/HZ Herculis system span 15 decades in energy, rivaling both the Crab pulsar and Cygnus X-3 in this respect for a discrete galactic source

Locating very high energy gamma ray sources with arc minute accuracy

The angular accuracy of gamma-ray detectors is intrinsically limited by the physical processes involved in photon detection. Although a number of point-like sources were detected by the COS-B satellite, only two were unambiguously identified by time signature with counterparts at longer wavelengths. By taking advantage of the extended longitudinal structure of Very High Energy gamma-ray showers, measurements in the TeV energy range can pinpoint source coordinates to arc minute accuracy. This was demonstrated using Cerenkov air shower imaging techniques. With two telescopes in coincidence, the individual event circular probable error will be 0.13 deg. The half-cone angle of the field of view is effectively 1 deg

A Growth Reference for Mid Upper Arm Circumference for Age among School Age Children and Adolescents, with Validation for Mortality in Two Cohorts

OBJECTIVES: To construct growth curves for mid-upper-arm circumference (MUAC)-for-age z score for 5-19 year olds that accord with the World Health Organization growth standards, and to evaluate their discriminatory performance for subsequent mortality. DESIGN: Growth curve construction and longitudinal cohort study. SETTING: United States and international growth data, and cohorts in Kenya, Uganda, and Zimbabwe. PARTICIPANTS The Health Examination Survey (HES)/National Health and Nutrition Examination Survey (NHANES) US population datasets (age 5-25 years), which were used to construct the 2007 WHO growth reference for body mass index in this age group, were merged with an imputed dataset matching the distribution of the WHO 2006 growth standards age 2-6 years. Validation data were from 685 HIV infected children aged 5-17 years participating in the Antiretroviral Research for Watoto (ARROW) trial in Uganda and Zimbabwe; and 1741 children aged 5-13 years discharged from a rural Kenyan hospital (3.8% HIV infected). Both cohorts were followed-up for survival during one year. MAIN OUTCOME MEASURES: Concordance with WHO 2006 growth standards at age 60 months and survival during one year according to MUAC-for-age and body mass index-for-age z scores. RESULTS: The new growth curves transitioned smoothly with WHO growth standards at age 5 years. MUAC-for-age z scores of −2 to −3 and less than−3, compared with −2 or more, was associated with hazard ratios for death within one year of 3.63 (95% confidence interval 0.90 to 14.7; P=0.07) and 11.1 (3.40 to 36.0; P<0.001), respectively, among ARROW trial participants; and 2.22 (1.01 to 4.9; P=0.04) and 5.15 (2.49 to 10.7; P<0.001), respectively, among Kenyan children after discharge from hospital. The AUCs for MUAC-for-age and body mass index-for-age z scores for discriminating subsequent mortality were 0.81 (95% confidence interval 0.70 to 0.92) and 0.75 (0.63 to 0.86) in the ARROW trial (absolute difference 0.06, 95% confidence interval −0.032 to 0.16; P=0.2) and 0.73 (0.65 to 0.80) and 0.58 (0.49 to 0.67), respectively, in Kenya (absolute difference in AUC 0.15, 0.07 to 0.23; P=0.0002). CONCLUSIONS: The MUAC-for-age z score is at least as effective as the body mass index-for-age z score for assessing mortality risks associated with undernutrition among African school aged children and adolescents. MUAC can provide simplified screening and diagnosis within nutrition and HIV programmes, and in research