Is the C-terminal flanking peptide of rat cholecystokinin double sulphated?

AbstractA specific radioimmunoassay was developed to the predicted nine amino acid C-terminal flanking peptide of cholecystokinin (peptide serine serine, PSS). In aqueous extracts of rat brain, PSS was undetectable unless the extracts were first treated with arylsulphatase, which also resulted in desulphation of cholecystokinin. The reverse-phase HPLC analysis of partially desulphated extracts showed the presence of two peaks intermediate to the naturally occurring and the completely desulphated forms. It is therefore proposed that the CCK-flanking peptide PSS has both tyrosine residues sulphated

Compact spherical neutron polarimeter using high-T-c YBCO films

We describe a simple, compact device for spherical neutron polarimetry measurements at small neutron scattering angles. The device consists of a sample chamber with very low (<0.01 G) magnetic field flanked by regions within which the neutron polarization can be manipulated in a controlled manner. This allows any selected initial and final polarization direction of the neutrons to be obtained. We have constructed a prototype device using high-Tc superconducting films and mu-metal to isolate regions with different magnetic fields and tested device performance in transmission geometry. Finite-element methods were used to simulate the device’s field profile and these have been verified by experiment using a small solenoid as a test sample. Measurements are reported using both monochromatic and polychromatic neutron sources. The results show that the device is capable of extracting sample information and distinguishing small angular variations of the sample magnetic field. As a more realistic test, we present results on the characterization of a 10 μm thick Permalloy film in zero magnetic field, as well as its response to an external magnetic field

Estimation of Radiation Doses in the Marshall Islands Based on Whole Body Counting of Cesium-137 (137Cs) and Plutonium Urinalysis

Under the auspices of the U.S. Department of Energy (USDOE), researchers from the Lawrence Livermore National Laboratory (LLNL) have recently implemented a series of initiatives to address long-term radiological surveillance needs at former nuclear test sites in the Republic of the Marshall Islands (RMI). The aim of this radiological surveillance monitoring program (RSMP) is to provide timely radiation protection for individuals in the Marshall Islands with respect to two of the most important internally deposited fallout radionuclides-cesium-137 ({sup 137}Cs) and long-lived isotopes 239 and 240 of plutonium ({sup 239+240}Pu) (Robison et al., 1997 and references therein). Therefore, whole-body counting for {sup 137}Cs and a sensitive bioassay for the presence of {sup 239+240}Pu excreted in urine were adopted as the two most applicable in vivo analytical methods to assess radiation doses for individuals in the RMI from internally deposited fallout radionuclides (see Hamilton et al., 2006a-c; Bell et al., 2002). Through 2005, the USDOE has established three permanent whole-body counting facilities in the Marshall Islands: the Enewetak Radiological Laboratory on Enewetak Atoll, the Utrok Whole-Body Counting Facility on Majuro Atoll, and the Rongelap Whole-Body Counting Facility on Rongelap Atoll. These whole-body counting facilities are operated and maintained by trained Marshallese technicians. Scientists from LLNL provide the technical support and training necessary for maintaining quality assurance for data acquisition and dose reporting. This technical basis document summarizes the methodologies used to calculate the annual total effective dose equivalent (TEDE; or dose for the calendar year of measurement) based on whole-body counting of internally deposited {sup 137}Cs and the measurement of {sup 239+240}Pu excreted in urine. Whole-body counting provides a direct measure of the total amount (or burden) of {sup 137}Cs present in the human body at the time of measurement. The amount of {sup 137}Cs detected is often reported in activity units of kilo-Becquerel (kBq), where 1 kBq equals 1000 Bq and 1 Bq = 1 nuclear transformation per second (t s{sup -1}). [However, in the United States the Curie (Ci) continues to be used as the unit of radioactivity; where 1 Ci = 3.7 x 10{sup 10} Bq.] The detection of {sup 239}Pu and {sup 240}Pu in bioassay (urine) samples indicates the presence of internally deposited (systemic) plutonium in the body. Urine samples that are collected in the Marshall Islands from volunteers participating in the RSMP are transported to LLNL, where measurements for {sup 239+240}Pu are performed using a state-of-the-art technology based on Accelerator Mass Spectrometry (AMS) (Hamilton et al., 2004, 2007; Brown et al., 2004). The urinary excretion of plutonium by RSMP volunteers is usually described in activity units, expressed as micro-Becquerel ({micro}Bq) of {sup 239+240}Pu (i.e., representing the sum of the {sup 239}Pu and {sup 240}Pu activity) excreted (lost) per day (d{sup -1}), where 1 {micro}Bq d{sup -1} = 10{sup -6} Bq d{sup -1} and 1 Bq = 1 t s{sup -1}. The systemic burden of plutonium is then estimated from biokinetic relationships as described by the International Commission on Radiological Protection (e.g., see ICRP, 1990). In general, nuclear transformations are accompanied by the emission of energy and/or particles in the form of gamma rays ({gamma}), beta particles ({beta}), and/or alpha particles ({alpha}). Tissues in the human body may adsorb these emissions, where there is a potential for any deposited energy to cause biological damage. The general term used to quantify the extent of any radiation exposure is referred to as the dose. The equivalent dose is defined by the average absorbed dose in an organ or tissue weighted by the average quality factor for the type and energy of the emission causing the dose. The effective dose equivalent (EDE; as applied to the whole body), is the sum of the average dose equivalent for each tissue weighted by each applicable tissue-specific weighing factor (which equates to the sensitivity of that tissue to damage by the equivalent radiation dose it receives). The SI unit of effective dose equivalent is the joule per kilogram (J kg{sup -1}), named the Sievert (Sv). The unit often used by federal and state agencies in the United States to describe EDE continues to be the more historical radiation equivalent man (rem); where 1 rem = 0.01 Sv

Perceived family economic hardship and student engagement among junior high schoolers in Ghana

Research has shown that several factors influence student engagement, but little is known about the predictive role of family economic hardships on student engagement, particularly in the sub-Saharan African context. This study used data from junior high school students in Ghana to examine the association between perceived family economic hardship and students' classroom engagement, and the intervening role of future intentions. The structural equation modeling results indicate that perceived economic hardship is associated with behavioral engagement in school in two ways. The first is the direct positive link from perceived economic hardship to engagement (i.e., the motivational pathway). The second is a more nuanced channel whereby perceived economic difficulties are negatively associated with students' participation in academic work, but only through the inconsistent mediating (suppression) role of students' future intentions (i.e., the demoralizing pathway). The nuanced psychological and behavioral outcomes suggest the need for programs that cultivate educational resilience among young people

Deep learning with electronic health records for short-term fracture risk identification : crystal bone algorithm development and validation

Background: Fractures as a result of osteoporosis and low bone mass are common and give rise to significant clinical, personal, and economic burden. Even after a fracture occurs, high fracture risk remains widely underdiagnosed and undertreated. Common fracture risk assessment tools utilize a subset of clinical risk factors for prediction, and often require manual data entry. Furthermore, these tools predict risk over the long term and do not explicitly provide short-term risk estimates necessary to identify patients likely to experience a fracture in the next 1-2 years. Objective: The goal of this study was to develop and evaluate an algorithm for the identification of patients at risk of fracture in a subsequent 1- to 2-year period. In order to address the aforementioned limitations of current prediction tools, this approach focused on a short-term timeframe, automated data entry, and the use of longitudinal data to inform the predictions. Methods: Using retrospective electronic health record data from over 1,000,000 patients, we developed Crystal Bone, an algorithm that applies machine learning techniques from natural language processing to the temporal nature of patient histories to generate short-term fracture risk predictions. Similar to how language models predict the next word in a given sentence or the topic of a document, Crystal Bone predicts whether a patient’s future trajectory might contain a fracture event, or whether the signature of the patient’s journey is similar to that of a typical future fracture patient. A holdout set with 192,590 patients was used to validate accuracy. Experimental baseline models and human-level performance were used for comparison. Results: The model accurately predicted 1- to 2-year fracture risk for patients aged over 50 years (area under the receiver operating characteristics curve [AUROC] 0.81). These algorithms outperformed the experimental baselines (AUROC 0.67) and showed meaningful improvements when compared to retrospective approximation of human-level performance by correctly identifying 9649 of 13,765 (70%) at-risk patients who did not receive any preventative bone-health-related medical interventions from their physicians. Conclusions: These findings indicate that it is possible to use a patient’s unique medical history as it changes over time to predict the risk of short-term fracture. Validating and applying such a tool within the health care system could enable automated and widespread prediction of this risk and may help with identification of patients at very high risk of fracture

Individual Radiological Protection Monitoring of Utrok Atoll Residents Based on Whole Body Counting of Cesium-137 (137Cs) and Plutonium Bioassay

This report contains individual radiological protection surveillance data developed during 2006 for adult members of a select group of families living on Utrok Atoll. These Group I volunteers all underwent a whole-body count to determine levels of internally deposited cesium-137 ({sup 137}Cs) and supplied a bioassay sample for analysis of plutonium isotopes. Measurement data were obtained and the results compared with an equivalent set of measurement data for {sup 137}Cs and plutonium isotopes from a second group of adult volunteers (Group II) who were long-term residents of Utrok Atoll. For the purposes of this comparison, Group II volunteers were considered representative of the general population on Utrok Atoll. The general aim of the study was to determine residual systemic burdens of fallout radionuclides in each volunteer group, develop data in response to addressing some specific concerns about the preferential uptake and potential health consequences of residual fallout radionuclides in Group I volunteers, and generally provide some perspective on the significance of radiation doses delivered to volunteers (and the general Utrok Atoll resident population) in terms of radiological protection standards and health risks. Based on dose estimates from measurements of internally deposited {sup 137}Cs and plutonium isotopes, the data and information developed in this report clearly show that neither volunteer group has acquired levels of internally deposited fallout radionuclides specific to nuclear weapons testing in the Marshall Islands that are likely to have any consequence on human health. Moreover, the dose estimates are well below radiological protection standards as prescribed by U.S. regulators and international agencies, and are very small when compared to doses from natural sources of radiation in the Marshall Islands and the threshold where radiation health effects could be either medically diagnosed in an individual or epidemiologically discerned in a group of people. In general, the results from the whole-body counting measurements of 137Cs are consistent with our knowledge that a key pathway for exposure to residual fallout contamination on Utrok Atoll is low-level chronic uptake of {sup 137}Cs from the consumption of locally grown produce (Robison et al., 1999). The error-weighted, average body burden of {sup 137}Cs measured in Group I and Group II volunteers was 0.31 kBq and 0.62 kBq, respectively. The associated average, annual committed effective dose equivalent (CEDE) delivered to Group I and Group II volunteers from {sup 137}Cs during the year of measurement was 2.1 and 4.0 mrem. For comparative purposes, the annual dose limit for members of the public as recommended by the National Council on Radiation Protection and Measurements (NCRP) and the International Commission on Radiological Protection (ICRP) is 100 mrem. Consequently, specific concerns about elevated levels of {sup 137}Cs uptake and higher risks from radiation exposure to Group I volunteers would be considered unfounded. Moreover, the urinary excretion of plutonium-239 ({sup 239}Pu) from Group I and Group II volunteers is statistically indistinguishable. In this case, the error-weighted, average urinary excretion of {sup 239}Pu from Group I volunteers of 0.10 {mu}Bq per 24-h void with a range between -0.01 and 0.23 {mu}Bq per 24-h void compares with an error-weighted average from Group II volunteers of 0.11 {mu}Bq per 24-h void with a range between -0.20 and 0.47 {mu}Bq per 24-h void. The range in urinary excretion of {sup 239}Pu from Utrok Atoll residents is very similar to that observed for other population groups in the Marshall Islands (Bogen et al., 2006; Hamilton et al., 2006a; 2006b; 2006c, 2007a; 2007b; 2007c) and is generally considered representative of worldwide background

Double-Layer Systems at Zero Magnetic Field

We investigate theoretically the effects of intralayer and interlayer exchange in biased double-layer electron and hole systems, in the absence of a magnetic field. We use a variational Hartree-Fock-like approximation to analyze the effects of layer separation, layer density, tunneling, and applied gate voltages on the layer densities and on interlayer phase coherence. In agreement with earlier work, we find that for very small layer separations and low layer densities, an interlayer-correlated ground state possessing spontaneous interlayer coherence (SILC) is obtained, even in the absence of interlayer tunneling. In contrast to earlier work, we find that as a function of total density, there exist four, rather than three, distinct noncrystalline phases for balanced double-layer systems without interlayer tunneling. The newly identified phase exists for a narrow range of densities and has three components and slightly unequal layer densities, with one layer being spin polarized, and the other unpolarized. An additional two-component phase is also possible in the presence of sufficiently strong bias or tunneling. The lowest-density SILC phase is the fully spin- and pseudospin-polarized ``one-component'' phase discussed by Zheng {\it et al.} [Phys. Rev. B {\bf 55}, 4506 (1997)]. We argue that this phase will produce a finite interlayer Coulomb drag at zero temperature due to the SILC. We calculate the particle densities in each layer as a function of the gate voltage and total particle density, and find that interlayer exchange can reduce or prevent abrupt transfers of charge between the two layers. We also calculate the effect of interlayer exchange on the interlayer capacitance.Comment: 35 pages, 19 figures included. To appear in PR

IRF4 and BATF are critical for CD8(+) T-cell function following infection with LCMV.

CD8(+) T-cell functions are critical for preventing chronic viral infections by eliminating infected cells. For healthy immune responses, beneficial destruction of infected cells must be balanced against immunopathology resulting from collateral damage to tissues. These processes are regulated by factors controlling CD8(+) T-cell function, which are still incompletely understood. Here, we show that the interferon regulatory factor 4 (IRF4) and its cooperating binding partner B-cell-activating transcription factor (BATF) are necessary for sustained CD8(+) T-cell effector function. Although Irf4(-/-) CD8(+) T cells were initially capable of proliferation, IRF4 deficiency resulted in limited CD8(+) T-cell responses after infection with the lymphocytic choriomeningitis virus. Consequently, Irf4(-/-) mice established chronic infections, but were protected from fatal immunopathology. Absence of BATF also resulted in reduced CD8(+) T-cell function, limited immunopathology, and promotion of viral persistence. These data identify the transcription factors IRF4 and BATF as major regulators of antiviral cytotoxic T-cell immunity

Drug–drug Interactions in Hospitalized Cardiac Patients

Drug–drug interactions (DDIs) are defined as two or more drugs interacting in such a manner that the effectiveness or toxicity of one or more drugs is altered. DDI in patients receiving multidrug therapy is a major concern. The aim of the present study was to assess the incidence and risk factors of DDIs in patients admitted in cardiology unit of a teaching hospital. A prospective, observational study was carried out for a period of 3 months (April–July 2009). During the study period, a total of 600 prescriptions were analyzed and it was found that 88 patients had at least one DDI. The percentage of DDIs was higher in females compared to males (56.82% vs. 43.18%). DDIs were observed more in the age group of 60 years and above (57.96). Patients with more than 10 prescribed drugs developed DDIs more frequently [58 (65.91%)]. Heparin [55 (62.25%)] and aspirin [42 (47.72%)] were the most common drugs responsible for DDIs. Bleeding was the commonest clinical consequence [76 (86.63%)] found in this study population. On assessment of severity of DDIs, majority of the cases were classified as moderate in severity (61.36%). Aging, female gender and increase in concurrent medications were found to be associated with increased DDIs. Patients having these risk factors can be actively monitored during their stay in the cardiology department to identify DDIs

Solar Wind Turbulence and the Role of Ion Instabilities

International audienc