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INTRODUCTION A. Adoption of Influenza Vaccine Mandates I. WHY VACCINATE HEALTH CARE WORKERS AGAINST INFLUENZA? II: MANDATING VACCINES A. First Steps: Voluntary Mandates in Hospitals B. State Mandates C. Employer-initiated [...]

The problem faced in the spatialization of information systems is the determination of geometry, that is, dimensionality and metric. The use of geometric information latent in a system 's navigational record is discussed.

The rates of numerous activated reactions between neutral species increase at low temperatures through quantum mechanical tunneling of light hydrogen atoms. Although tunneling processes involving molecules or heavy atoms are well known in the condensed phase, analogous gas-phase processes have never been demonstrated experimentally. Here, we studied the activated CH + CO2→ HCO + CO reaction in a supersonic flow reactor, measuring rate constants that increase rapidly below 100 K. Mechanistically, tunneling is shown to occur by CH insertion into the C–O bond, with rate calculations accurately reproducing the experimental values. To exclude the possibility of H-atom tunneling, CD was used in additional experiments and calculations. Surprisingly, the equivalent CD + CO2reaction accelerates at low temperature as zero-point energy effects remove the barrier to product formation. In conclusion, heavy-particle tunneling effects might be responsible for the observed reactivity increase at lower temperatures for the CH + CO2reaction, while the equivalent effect for the CD + CO2reaction results instead from a submerged barrier with respect to reactants.

This article presents the Applied Technology Council (ATC) team’s observations following the 2017 Mw7.1 Puebla–Morelos, Mexico earthquake. The team was deployed in Mexico City to collect seismological, geotechnical, structural, and overall performance information. The focus was on non-ductile concrete structures, to support implementation of recently published FEMA P-2018 procedures and to identify study buildings for incorporation into NIST-funded ATC-134 ongoing project. This article presents seismological data with 71 strong-motion records processed and ready for use in engineering analysis, geotechnical observations, and characterization of sites visited. Analyses of the response of representative soil profiles are presented in the form of acceleration response spectra and seismic amplification at the ground surface. A comparison of the same analysis using records from the 1985 Michoacán Ms8.1 (approximately Mw8.0) earthquake is also discussed. The ATC team composed GIS maps with structural and geotechnical characteristics of the inspected sites, including color-coded damage of inspected buildings and estimated soil fundamental period to correlate observed behavior with potential soil–structure interaction resonance effects. Recommendations on further detailed studies based on this comprehensive set of case histories are proposed.

Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed ‘lung cancer likelihood in plasma’ (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.

Occurring in hops (Humulus lupulus) and beer as a racemic mixture, (2R,2S)-8-prenylnaringenin (8-PN) is a potent phytoestrogen in hop dietary supplements used by women as alternatives to conventional hormone therapy. With a half-life exceeding 20 h, 8-PN is excreted primarily as 8-PN-7-O-glucuronide or 8-PN-4′-O-glucuronide. Human liver microsomes and 11 recombinant human UDP-glucuronosyltransferases (UGTs) were used to catalyze the formation of the two oxygen-linked glucuronides of purified (2R)-8-PN and (2S)-8-PN, which were subsequently identified using mass spectrometry and nuclear magnetic resonance spectroscopy. Formation of (2R)- and (2S)-8-PN-7-O-glucuronides predominated over the 8-PN-4′-O-glucuronides except for intestinal UGT1A10, which formed more (2S)-8-PN-4′-O-glucuronide. (2R)-8-PN was a better substrate for all 11 UGTs except for UGT1A1, which formed more of both (2S)-8-PN glucuronides than (2R)-8-PN glucuronides. Although several UGTs conjugated both enantiomers of 8-PN, some conjugated just one enantiomer, suggesting that human phenotypic variation might affect the routes of metabolism of this chiral estrogenic constituent of hops.

The potential energy curves (PECs) for the interaction of 3CH2with 3O2in singlet and triplet potential energy surfaces (PESs) leading to singlet and triplet Criegee intermediates (CH2OO) are studied using electronic structure calculations. The bonding mechanism is interpreted by analyzing the ground state multireference configuration interaction (MRCI) wave function of the reacting species and at all points along the PES. The interaction of 3CH2with 3O2on the singlet surface leads to a flat long-range attractive PEC lacking any maxima or minima along the curve. The triplet surface stems into a maximum along the curve resulting in a transition state with an energy barrier of 5.3 kcal/mol at CASSCF(4,4)/cc-pVTZ level. The resulting 3CH2OO is less stable than the 1CH2OO. In this study, the biradical character (β) is used as a measure to understand the difference in the topology of the singlet and triplet PECs and the relation of the biradical nature of the species with their structures. The 3CH2OO has a larger biradical character than 1CH2OO, and because of the larger bond order of 1CH2OO, the C–O covalent bond becomes harder to break, thereby stabilizing 1CH2OO. Thus, this study provides insights into the shape of the PEC obtained from the reaction between 3CH2and 3O2in terms of their bonding nature and from the shape of the curves, the temperature dependence or independence of the rate of the reaction is discussed.

Applications of learning analytics (LA) can raise concerns from students about their privacy in higher education contexts. Developing effective privacy-enhancing practices requires a systematic understanding of students’ privacy concerns and how they vary across national and cultural dimensions. We conducted a survey study with established instruments to measure privacy concerns and cultural values for university students in five countries (Germany, South Korea, Spain, Sweden, and the United States; N= 762). The results show that students generally trusted institutions with their data and disclosed information as they perceived the risks to be manageable even though they felt somewhat limited in their ability to control their privacy. Across the five countries, German and Swedish students stood out as the most trusting and least concerned, especially compared to US students who reported greater perceived risk and less control. Students in South Korea and Spain responded similarly on all five privacy dimensions (perceived privacy risk, perceived privacy control, privacy concerns, trusting beliefs, and non-self-disclosure behavior), despite their significant cultural differences. Culture measured at the individual level affected the antecedents and outcomes of privacy concerns. Perceived privacy risk and privacy control increase with power distance. Trusting beliefs increase with a desire for uncertainty avoidance and lower masculinity. Non-self-disclosure behaviors rise with power distance and masculinity and decrease with more uncertainty avoidance. Thus, cultural values related to trust in institutions, social equality and risk-taking should be considered when developing privacy-enhancing practices and policies in higher education.

The reaction system formed by the methanethiol molecule (CH3SH) and a hydrogen atom was studied via three elementary reactions, two hydrogen abstractions and the C–S bond cleavage (CH3SH + H → CH3S + H2(R1); → CH2SH + H2(R2); → CH3+ H2S (R3)). The stable structures were optimized with various methodologies of the density functional theory and the MP2 method. Two minimum energy paths for each elementary reaction were built using the BB1K and MP2 methodologies, and the electronic properties on the reactants, products, and saddle points were improved with coupled cluster theory with single, double, and connected triple excitations (CCSD(T)) calculations. The sensitivity of coupling the low and high-level methods to calculate the thermochemical and rate constants were analyzed. The thermal rate constants were obtained by means of the improved canonical variational theory (ICVT) and the tunneling corrections were included with the small curvature tunneling (SCT) approach. Our results are in agreement with the previous experimental measurements and the calculated branching ratio for R1:R2:R3 is equal to 0.96:0:0.04, with kR1= 9.64 × 10–13cm3molecule–1s–1at 298 K.

The physiologic role of free 25-hydroxyvitamin D [25(OH)D] in humans is unclear.

The reaction of methanol (CH3OH) with atomic nitrogen was studied considering three elementary reactions, the hydrogen abstractions from the hydroxyl or methyl groups (R1 and R3, respectively) and the C–O bond break (R2). Thermochemical properties were obtained using ab initiomethods and density functional theory approximations with aug-cc-pVXZ (X = T and Q) basis sets. The minimum energy path was built with a dual-level methodology using the BB1K functional as the low-level and the CCSD(T) as the high-level. This surface was used to calculate the thermal rate constants in the frame of variational transitional state theory considering the tunneling effects. Our results indicate the dehydrogenation of the methyl group (R3) as the dominant path with kR3= 7.5 × 10–27cm3·molecule–1·s–1at 300 K. The thermal rate constants were fitted to a modified Arrhenius equation for use in mechanism studies of the methanol decomposition.

Vitamin D deficiency disproportionately affects nonwhite individuals. Controversy persists over how to best restore low 25D levels, and how to best define vitamin D status [total (protein bound plus free) vs free 25D].

25-Hydroxyvitamin D (25D) circulates bound primarily to serum vitamin D binding protein (DBP), with DBP showing higher binding affinity for 25D3 than 25D2. We therefore hypothesized that vitamin D2 (D2) promotes higher serum levels of unbound 25D (free 25D), with different functional responses, relative to vitamin D3 (D3). Week 3 C56BL/6 mice were placed on diets containing either D2 or D3 alone (both 1000 IU/kg). At week 8 and week 16, D2 mice had only 25D2 in circulation (26.6 ± 1.9 and 33.3 ± 4.4 ng/mL), and D3 mice had only 25D3 (28.3 ± 2.0 and 31.7 ± 2.1 ng/mL). At week 8 (44.5 ± 6.4 vs 62.4 ± 11.6 pg/mL, P< .05) and week 16 (78.4 ± 12.6 vs 95.5 ± 11.6), D2 mice had lower serum 1,25-dihydroxyvitamin D relative to D3 mice. By contrast, measured free 25D was significantly higher in D2 mice at week 8 (16.8 ± 0.65 vs 8.4 ± 0.63 pg/mL, P< .001) and week 16 (17.4 ± 0.43 vs 8.4 ± 0.44, P< .001). A two-way ANOVA of bone histomorphometry showed that week 8 D2 mice had significantly higher osteoclast surface/bone surface, eroded surface/bone surface, and mineral apposition rate compared with D3 mice. Osteoblast surface/bone surface was higher in week 8 D2 females but not week 8 D2 males. At week 16, D2 mice had significantly higher bone volume/total volume and trabecular number compared with D3 mice. Differences in bone phenotype were observed despite D2 mice reaching similar serum 25D levels and lower 1,25D levels compared with D3 mice. These data indicate that 25D2 binds less well to DBP than 25D3, with resulting higher levels of free 25D promoting differential effects on bone in mice exposed to D2 alone.

Context:Controversy persists over: 1) how best to restore low serum 25-hydroxyvitamin D (25D) levels (vitamin D2 [D2] vs vitamin D3 [D3]); 2) how best to define vitamin D status (total [protein-bound + free] vs free 25D); and 3) how best to assess the bioactivity of free 25D.Objective:To assess: 1) the effects of D2 vs D3 on serum total and free 25D; and 2) whether change in intact PTH (iPTH) is more strongly associated with change in total vs free 25D.Design:Participants previously enrolled in a D2 vs D3 trial were matched for age, body mass index, and race/ethnicity. Participants received 50 000 IU of D2 or D3 twice weekly for 5 weeks, followed by a 5-week equilibration period. Biochemical assessment was performed at baseline and at 10 weeks.Setting and Participants:Thirty-eight adults (19 D2 and 19 D3) ≥18 years of age with baseline 25D levels <30 ng/mL were recruited from an academic ambulatory osteoporosis clinic.Outcome Measures:Serum measures were total 25D, free 25D (directly measured), 1,25-dihydroxyvitamin D, calcium, and iPTH. Urine measure was fasting calcium:creatinine ratio.Results:Baseline total (22.2 ± 3.3 vs 23.3 ± 7.2 ng/mL; P= .5) and free (5.4 ± 0.8 vs 5.3 ± 1.7 pg/mL; P= .8) 25D levels were similar between D2 and D3 groups. Increases in total (+27.6 vs +12.2 ng/mL; P= .001) and free (+3.6 vs +6.2 pg/mL; P= .02) 25D levels were greater with D3 vs D2. Percentage change in iPTH was significantly associated with change in free (but not total) 25D, without and with adjustment for supplementation regimen, change in 1,25-dihydroxyvitamin D, and change in calcium.Conclusions:D3 increased total and free 25D levels to a greater extent than D2. Free 25D may be superior to total 25D as a marker of vitamin D bioactivity.

Context:Total 25-hydroxyvitamin D (25OHD) is a marker of vitamin D status and is lower in African Americans than in whites. Whether this difference holds for free 25OHOD (f25OHD) is unclear, considering reported genetic-racial differences in vitamin D binding protein (DBP) used to calculate f25OHD.Objectives:Our objective was to assess racial-geographic differences in f25OHD and to understand inconsistencies in racial associations with DBP and calculated f25OHD.Design:This study used a cross-sectional design.Setting:The general community in the United States, United Kingdom, and The Gambia were included in this study.Participants:Men in Osteoporotic Fractures in Men and Medical Research Council studies (N = 1057) were included.Exposures:Total 25OHD concentration, race, and DBP (GC) genotype exposures were included.Outcome Measures:Directly measured f25OHD, DBP assessed by proteomics, monoclonal and polyclonal immunoassays, and calculated f25OHD were the outcome measures.Results:Total 25OHD correlated strongly with directly measured f25OHD (Spearman r = 0.84). Measured by monoclonal assay, mean DBP in African-ancestry subjects was approximately 50% lower than in whites, whereas DBP measured by polyclonal DBP antibodies or proteomic methods was not lower in African-ancestry. Calculated f25OHD (using polyclonal DBP assays) correlated strongly with directly measured f25OHD (r = 0.80–0.83). Free 25OHD, measured or calculated from polyclonal DBP assays, reflected total 25OHD concentration irrespective of race and was lower in African Americans than in US whites.Conclusions:Previously reported racial differences in DBP concentration are likely from monoclonal assay bias, as there was no racial difference in DBP concentration by other methods. This confirms the poor vitamin D status of many African-Americans and the utility of total 25OHD in assessing vitamin D in the general population.

The complete active space self-consistent field (CASSCF) method is a cornerstone in modern excited-state quantum chemistry providing the starting point for most common multireference computations. However, CASSCF, when used with a minimal active space, can produce significant errors (>2 eV) even for the excitation energies of simple hydrocarbons if the states of interest possess ionic character. After illustrating this problem in some detail, we present a diagnostic for ionic character, denoted as Qat, that is readily computed from the transition density. A set of 11 molecules is considered to study errors in vertical excitation energies. State-averaged CASSCF obtains a mean absolute error (MAE) of 0.87 eV for the 34 singlet states considered. We highlight a strong correlation between the obtained errors and the Qatdiagnostic, illustrating its power to predict problematic cases. Conversely, using multireference configuration interaction with single and double excitations and Pople’s size extensivity correction (MR-CISD+P), excellent results are obtained with an MAE of 0.11 eV. Furthermore, correlations with the Qatdiagnostic disappear. In summary, we hope that the presented diagnostic will facilitate reliable and user-friendly multireference computations on conjugated organic molecules.

In this contribution, we report on the microscopic and spectroscopic characterization of lead chalcogenide nanoparticles. PbSe and PbTe nanoparticles were synthesized by chemical methods, using different molar ratios of Pb, Se, and Te precursors and varying the reaction time. These nanoparticles were characterized by means of transmission electron microscopy and their related techniques: electron diffraction, energy dispersive X-ray spectroscopy (EDXS), electron energy loss spectroscopy (EELS), and aberration corrected scanning transmission electron microscopy (AC-STEM), to obtain information related to their morphology, crystal structure, and composition. They were also characterized by means of Fourier transform infrared (FTIR) absorption spectroscopy to assess the functional groups found on the surface of the nanoparticles, depending on the synthesis conditions. The results obtained showed that the synthesized nanoparticles always display a higher concentration of Pb compared to that of the chalcogen. Moreover, the final concentration of Pb depended on the original ratio between the Pb precursor and the chalcogen precursor used in the synthesis. These variations in the composition influenced the FTIR absorption characteristics of the nanoparticles. EDXS, EELS, and AC-STEM results indicate that this excess of Pb is located on the surface of the nanoparticles, particularly in the amorphous capping layer. These results as well as those obtained from FTIR spectroscopy suggest that the protective layer is mostly made of lead oleate.

ABSTRACTCoagulase-negative staphylococci (CoNS) are a major cause of sepsis in neonatal intensive care units (NICU) worldwide. Infecting strains of these commensal bacteria may originate from NICU personnel. Therefore, we studied the characteristics of CoNS isolates from NICU personnel and compared them to those of isolates from the general population and from sepsis patients. Furthermore, we studied the epidemiological effect on CoNS carriage of NICU personnel after a period of absence. In our study, we isolated CoNS from the thumbs of NICU personnel every 2 weeks during the summer of 2005 and sampled personnel returning from vacation and a control group from the general population. Furthermore, we collected sepsis isolates from this period. Isolates were tested for antibiotic resistance, mecAand icaAcarriage, biofilm production, and genetic relatedness. We found that mecAand icaAcarriage as well as penicillin, oxacillin, and gentamicin resistance were significantly more prevalent in CoNS strains from NICU personnel than in community isolates. Similar trends were observed when postvacation strains were compared to prevacation strains. Furthermore, genetic analysis showed that 90% of the blood isolates were closely related to strains found on the hands of NICU personnel. Our findings revealed that CoNS carried by NICU personnel differ from those in the general population. Hospital strains are replaced by community CoNS after a period of absence. NICU personnel are a likely cause for the cross-contamination of virulent CoNS that originate from the NICU to patients.

ABSTRACTMade of more than 40 subunits, the rotenone-sensitive NADH:ubiquinone oxidoreductase (complex I) is the most intricate membrane-bound enzyme of the mitochondrial respiratory chain. In vascular plants, fungi, and animals, at least seven complex I subunits (ND1, -2, -3, -4, -4L, -5, and -6; ND is NADH dehydrogenase) are coded by mitochondrial genes. The role of these highly hydrophobic subunits in the enzyme activity and assembly is still poorly understood. In the unicellular green alga Chlamydomonas reinhardtii, the ND3 and ND4L subunits are encoded in the nuclear genome, and we show here that the corresponding genes, called NUO3and NUO11, respectively, display features that facilitate their expression and allow the proper import of the corresponding proteins into mitochondria. In particular, both polypeptides show lower hydrophobicity compared to their mitochondrion-encoded counterparts. The expression of the NUO3and NUO11genes has been suppressed by RNA interference. We demonstrate that the absence of ND3 or ND4L polypeptides prevents the assembly of the 950-kDa whole complex I and suppresses the enzyme activity. The putative role of hydrophobic ND subunits is discussed in relation to the structure of the complex I enzyme. A model for the assembly pathway of the Chlamydomonasenzyme is proposed.

Replication of the human immunodeficiency virus type 1 (HIV-1) is inhibited by interferons (IFNs), in part through activity of the IFN-inducible protein kinase PKR. To escape this antiviral effect, HIV-1 has developed strategies for blocking PKR function. We have previously shown that the HIV-1 Tat protein can associate with PKR in vitro and in vivo and inhibit PKR activity. Here we present evidence that Tat can inhibit PKR activity by both RNA-dependent and RNA-independent mechanisms. Tat inhibited PKR activation by the non-RNA activator heparin, and also suppressed PKR basal level autophosphorylation in the absence of RNA. However, when Tat and dsRNA were preincubated, the amount of Tat required to inhibit PKR activation by dsRNA depended on the dsRNA concentration. In addition to its function in vitro, Tat can also reverse translation inhibition mediated by PKR in COS cells. The Tat amino acid sequence required for interaction with PKR was mapped to residues 40–58, overlapping the hydrophobic core and basic region of HIV-1 Tat. Alignment of amino acid sequences of Tat and eIF-2α indicates similarity between the Tat-PKR binding region and the residues around the eIF-2α phosphorylation site, suggesting that Tat and eIF-2α may bind to the same site on PKR.

Central pattern generators (CPGs) are neuronal circuits that drive active repeated movements such as walking or swimming. Although CPGs are, by definition, active in isolated central nervous systems, sensory input is thought play an important role in adjusting the output of the CPGs to meet specific behavioral requirements of intact animals. We investigated, in freely behaving snails (Lymnaea stagnalis), how the buccal CPG is used during two different behaviors, feeding and egg laying. Analysis of the relationship between unit activity recorded from buccal nerves and the movements of the buccal mass showed that electrical activity in laterobuccal/ventrobuccal (LB/VB) nerves was as predicted from in vitro data, but electrical activity in the posterior jugalis nerve was not. Autodensity and interval histograms showed that during feeding the CPG produces a much stronger rhythm than during egg laying. The phase relationship between electrical activity and buccal movement changed little between the two behaviors. Fitting the spike trains recorded during the two behaviors with a simple model revealed differences in the patterns of electrical activity produced by the buccal system during the two behaviors investigated. During egg laying the bursts contained less spikes, and the number of spikes per burst was significantly more variable than during feeding. The time between two bursts of in a spike train was longer during egg laying than during feeding. The data show what the qualitative and quantitative differences are between two motor patterns produced by the buccal system of freely behaving Lymnaea stagnalis.

Fouling of heat transfer equipment poses a major problem in the food and especially the dairy industry. A review of recent progress made in the study and understanding of fouling and cleaning mechanisms in relation to exchangers and heat exchange surfaces in contact with milk components is given.The first part describes the different materials and methods used in the study of fouling and cleaning, from laboratory to pilot-plant and industrial scale.The second part concerns the different fouling dynamics observed with milk and dairy products, and gives an interpretation of the different behaviours which occur, on the basis of the most recent results on the composition and structure of the deposits and the biochemical mechanisms of fouling.The last part is a complete review of cleaning of milk deposits, taking into account the chemical reaction approach to cleaning as a mass transfer phenomenon.

PURPOSE: We categorized the various types of postobstetric injuries of the anorectum and vagina encountered in a five-year period. The operative procedures used to repair these injuries and the functional outcome after surgery were assessed. METHODS: Between 1986 and 1991, 52 patients were surgically treated for obstetric injuries of the anorectum and vagina; 48 patients were available for follow-up study. Four clinical injury types were identified: Type I, incontinent anal sphincter (11 patients); Type II, rectovaginal fistula (16 patients); Type III, rectovaginal fistula and incontinent anal sphincter (11 patients); and Type IV, cloaca-like defect (10 patients). The mean age of the patients was 30 years, the mean duration of symptoms before surgery was 13 months, and the mean follow-up period was 16 months. The major component of surgical repair for each injury type was: Type I, overlap repair of external anal sphincter; Type II, rectal mucosal advancement flap; Type III, overlap repair of external anal sphincter and rectal mucosal advancement flap; and Type IV, overlap repair of external anal sphincter, anterior levatorplasty, and anal and vaginal mucosal reconstruction. Fecal diversion was not performed in any patient. Specific questions were asked at the most recent follow-up assessment to determine results. RESULTS: Continence status postoperatively was classified as perfect, impaired, or poor; poor was defined as no improvement or worse. Postoperative continence (perfect, impaired, or poor) was, respectively: Type I (11 patients), 64 percent, 36 percent, and 0 percent; Type II (16 patients), 56 percent, 0 percent, and 44 percent; Type III (11 patients), 64 percent, 36 percent, and 0 percent; and Type IV (10 patients), 90 percent, 10 percent, and 0 percent. Vaginal discharge of stool was eliminated in all patients with a rectovaginal fistula. Subjectively, 92 percent of the patients had excellent or good results. Complications included wound hematoma (n=2), fecal impaction (n=2), urinary retention (n=1), and urinary tract infection (n=1). CONCLUSION: Patients with Type II injuries had the worst results (P< 0.001). These patients should be evaluated for anal incontinence before surgery to assess the need for a concomitant sphincteroplasty.

With the ever-increasing pressure on environmental resources, strong interest has developed for river-basin models that simulate proposed-policy alternatives. Traditionally, the development of these models has been a time-consuming and expensive endeavor. In addition, these models typically addressed a limited range of problems and were often not readily extensible. Combining an object-oriented network representation of river basins with principles of visual programming, however, allows for the rapid construction of modifiable river-simulation models. The RSS (River Simulation System) is a construction kit for the visual programming of river-basin models. It provides the basic tools necessary to construct a variety of river- basin models from a set of primitive water and information objects. These objects are linked to form a network to model the topology of the river basin. The objects (nodes) exchange information such as flows, demands of water, or other types of information necessary to simulate the processes in the river.

Freeze-drying is a discontinuous process mainly used in the food and pharmaceutical industry to preserve the initial properties of raw products after dehydration. To date, the freeze-drying process has been monitored according to time-dependent empirical rules. Several authors have attempted to develop measuring systems for the on-line determination of the dehydration rate (freeze-drying kinetics) and the sublimation end-point. Of the various measurement systems tested, the measurement of the partial pressure of water vapour by a moisture sensor appears to be the best. Nevertheless, no theoretical background has been advanced to explain the relationship existing between the moisture measurement and the freeze-drying kinetics. This can be achieved using the standard laws of mass transfer corresponding to either a diffusion-driven process or diffusion through a stagnant medium. Moreover, estimation of the sublimation end-point is rigorously possible by referring to these mass-transfer laws. A time-dependent function requiring only the measurement of the operating conditions, and particularly the partial pressure of water vapour inside the apparatus, has been established.

Tumor necrosis factor α (TNFα) has pleiotropic effects on cellular metabolism. One of the signaling paths from the TNFα receptor induces a stress-activated protein kinase cascade. Components within this TNFα kinase cascade include mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1) and stress-activated protein kinase/extracellular signal-regulated kinase kinase (SEK), which regulate the activity of c-Jun N-terminal kinase 1 (JNK1). Currently, molecules upstream of MEKK1 that link TNFα receptor to downstream kinases are not well understood. Besides TNFα, many other stimuli including several oncoproteins can activate JNK1. In most cases, the signaling cascade(s) leading from oncoproteins to JNK1 is poorly elucidated. We report here that the human T-cell lymphotrophic virus, type I (HTLV-I) oncoprotein, Tax, can activate JNK1. We isolated a novel human cell factor, G-protein pathway suppressor 2 (GPS2), by its ability to bind the HTLV-I oncoprotein, and we show that this factor can potently suppress Tax activation of JNK1. In trying to understand the mechanism of GPS2 activity, we found that it also suppressed TNFα activation of JNK1 but not TNFα activation of p38 kinase nor phorbol activation of extracellular signal-regulated kinase 2. Because GPS2 has minimal effect on MEKK1- or SEK-regulated JNK1 activity, it could act at a point between the TNFα receptor and MEKK1 in the initial step(s) of this kinase cascade. Alternatively, it is not excluded that GPS2 could work in a parallel pathway that leads from TNFα to JNK1. GPS2 represents a new molecule that could contribute important insights toward how cytokine- and oncoprotein-mediated signal transduction might converge.

The egg-laying behaviour of gastropod molluscs is controlled by peptidergic neuroendocrine cells and has provided an important experimental system for behavioural neurobiology. The genes that code for multiple peptides have been sequenced and the peptides themselves have been identified, thus enabling us to investigate how they act on the nervous system to produce the overt behavioural pattern (reviewed by Geraerts et al. 1988). The two animals that have been studied most extensively are the opisthobranch Aplysia californica and the pulmonate Lymnaea stagnalis. In both cases, the peptidergic neurones controlling egg laying are normally electrically silent (both in vivo and in vitro; Kupfermann, 1967; Pinsker and Dudek, 1977; Kits, 1980; Ter Maat et al. 1986) and produce multiple peptides (Rothman et al. 1983; Geraerts et al. 1985; Sigvardt et al. 1986), which are cleaved from a common protein precursor (Scheller et al. 1983; Vreugdenhil et al. 1988). Before egg laying, the cells produce a long-lasting discharge of action potentials (Pinsker and Dudek, 1977; Ter Maat et al. 1986). This electrical discharge initiates egg-laying behaviour, and during it the peptides (one of which initiates ovulation) are released into the blood. The demonstration, in Aplysia californica, that these peptides could have various effects on the activity of central neurones (reviewed by Mayeri and Rothman, 1985) led to the hypothesis that egg-laying behaviour is a neuroendocrine fixed action pattern controlled and coordinated by the concerted actions of the released peptides (Scheller and Axel, 1984). This hypothesis is also thought to apply to Lymnaea stagnalis (Vreugdenhil et al. 1988) because of the structural similarities between precursors of Aplysia californica and Lymnaea stagnalis egg-laying hormones. In this paper we investigate how the sequence of the various components of the egg-laying behaviour pattern is achieved.

The carboxyl-terminal domain (CTD) of RNA polymerase (RNAP) II contains multiple repeats with a heptapeptide consensus: Tyr-Ser-Pro-Thr-Ser-Pro-Ser. It has been proposed that phosphorylation of this CTD facilitates clearance and elongation of transcription complexes initiated at the promoters. However, not all transcribed promoters require RNAP II with full-length CTD. Furthermore, different activators can promote capably the transcriptional activity of polymerase II mutants deleted in the CTD. Thus, the role of the RNAP II CTD in transcription and in response to activators remains incompletely understood. To study the role of CTD in the regulated transcription of human retroviruses human-T cell lymphotropic virus I and human immunodeficiency virus 1, we used an α-amanitin-resistant system developed previously (Gerber, H. P., Hagmann, M., Seipel, K., Georgiev, O., West, M. A., Litingtung, Y., Schaffner, W., and Corden, J. L. (1995) Nature374, 660-662). We found that transcription directed by the human T-cell lymphotropic virus I activator protein Tax was strongly promoted by CTD-deficient RNA polymerase II. By contrast, the human immunodeficiency virus 1 activator Tat, which is recruited to the promoter by tethering to a nascent leader RNA, requires CTD-containing polymerase II for transcriptional activity. Biochemically, we characterized that Tat associated with a cellular CTD kinase activity, whereas Tax did not. Concordantly, we found that cellular transcription factor Sp1, which can activate CTD-deficient polymerase II with an efficiency similar to Tax, also failed to bind a CTD kinase. Taken together, these observations address mechanistic corollaries between activators with(out) a linked CTD kinase and regulated transcription by RNA polymerase II moieties with(out) a CTD.

Human chemokine receptor 5 (CCR5) functions as a co-receptor for Human immunodeficiency virus (HIV-1) infection. CCR5 is a seven-transmembrane cell surface receptor. Recently, a naturally occurring mutation of CCR5, ccr5Δ32, has been described. A small number of Caucasians are homozygouslyccr5Δ32/ccr5Δ32, while a larger number of individuals are heterozygously CCR5/ccr5Δ32. Theccr5Δ32/ccr5Δ32genotype has been linked to a phenotype that is “highly” protected from HIV-1 infection. On the other hand, several studies have shown that the CCR5/ccr5Δ32genotype confers “relative” protection from AIDS with onset of disease being delayed by 2–4 years. Although it is known that peripheral blood lymphocytes from heterozygous individuals (CCR5/ccr5Δ32) support ex vivoHIV-1 replication at a reduced level compared with CCR5/CCR5cells, the molecular basis for this observation is unknown. Here we report on events that post-translationally modify CCR5. We show that CCR5 progresses through the endoplasmic reticulum prior to appearing on the cell surface. Mature CCR5 can be post-translationally modified by phosphorylation and/or co-translationally by multimerization. By contrast, mutant ccr5Δ32, although retaining the capacity for multimerization, was incapable of being phosphorylated. ccr5Δ32 heterocomplexes with CCR5, and this interaction retains CCR5 in the endoplasmic reticulum resulting in reduced cell surface expression. Thus, co-expression in cells of ccr5Δ32 with CCR5 produces a trans-inhibition by the former of ability by the latter to support HIV-1 infection. Taken together, our findings suggest CCR5/ccr5Δ32 heterodimerization as a molecular explanation for the delayed onset of AIDS inCCR5/ccr5Δ32individuals.

BACKGROUND: One of the aims of the World Health Organization/Alcohol, Drug Abuse, and Mental Health Administration joint program on psychiatric diagnosis and classification is the development and standardization of diagnostic assessment instruments for use in clinical research worldwide. The International Personality Disorder Examination (IPDE) is a semistructured clinical interview compatible with the International Classification of Diseases, Tenth Revision, and the DMS-III-R classification systems. This is the first report of the results of a field trial to investigate the feasibility of using the IPDE to assess personality disorders worldwide. METHODS: The IPDE was administered by 58 psychiatrists and clinical psychologists to 716 patients enrolled in clinical facilities at 14 participating centers in 11 countries in North America, Europe, Africa, and Asia. To determine interrater reliability, 141 of the IPDEs (20%) were independently rated by a silent observer. To determine temporal stability, 243 patients (34%) were reexamined after an average interval of 6 months. RESULTS: The IPDE proved acceptable to clinicians and demonstrated an interrater reliability and temporal stability roughly similar to instruments used to diagnose the psychoses, mood, anxiety, and substance use disorders. CONCLUSION: It is possible to assess personality disorders with reasonably good reliability in different nations, languages, and cultures using a semistructured clinical interview that experienced clinicians find relevant, meaningful, and user-friendly.

A unique aspect of the retrovirus life cycle is the obligatory integration of the provirus into host cell chromosomes. Unlike viruses that do not integrate, retroviruses must conserve an ability to activate transcription from a chromatin context. Human immunodeficiency virus (HIV)-1 encodes an unusual and an unusually potent transcriptional transactivator, Tat, which binds to a nascent viral leader RNA, TAR. The action of Tat has been well studied in various reductive model systems; however, the physiological mechanism through which Tat gains access to chromatin-associated proviral long terminal repeats (LTRs) is not understood. We show here that a nuclear histone acetyltransferase activity associates with Tat. Intracellularly, we found that Tat forms a ternary complex with p300 and P/CAF, two histone acetyltransferases (HATs). A murine cell defect in Tat transactivation of the HIV-1 LTR was linked to the reduced abundance of p300 and P/CAF. Thus, overexpression of p300 and P/CAF reconstituted Tat transactivation of the HIV-1 LTR in NIH3T3 cells to a level similar to that observed for human cells. By using transdominant p300 or P/CAF mutants that lack enzymatic activity, we delineated a requirement for the HAT component from the latter but not the former in Tat function. Finally, we observed that Tat-associated HAT is preferentially important for transactivation of integrated, but not unintegrated, HIV-1 LTR.

A series of three polybenzazoles containing hexafluoroisopropylidene (HFIP-PBZs) were produced in order to study the effect of including the HFIP group into the rigid PBZ backbone. The monomers, 2,5-diamino-1,4-benzenedithiol dihydro-chloride and 4,6-diamino-1,3-benzenediol dihydrochloride, were synthesized and puri-fied. The monomer 1,2,4,5-tetraaminobenzene tetrahydrochloride is commercially avail-able and was purified by recrystallization. These mononmers were polymerized with 2,2-his(4-carboxyphenyl)-I1,,1,3,3,3-hexafluoropropane (6F-diacid) by a polycondensation reaction in polyphosphoric acid employing the P205adjustment method to give polymers in good yields with inherent viscosities ranging from 0.33 to 1.18 dl/g. These polymers show an increase in solubility over non-HFIlP containing PBZs and display excellent thermal stability by thermogravimetric analysis (540-568°C in argon). Isothermal aging in air of the polymers for 300 h afforded weight losses between 3.27 and 12.0%.

The retention of five major flavour components of cultivated mushrooms during freeze-drying was studied and the effect of process conditions on the kinetics of loss of these components was investigated. The loss of volatiles was independent of the volatility of the compound and the relative loss observed for 1-octen 3-ol was more important than that of other components, whatever the operating conditions. Optimum freeze-drying conditions were outlined for a maximum retention of flavour components in the dry product. 1-octen 3-ol is considered as the most important mushroom flavour. From the study of retention of this component the optimum operating conditions with a varying heating plate temperature and chamber pressure were outlined. Copyright 1993, 1999 Academic Press

We present evidence that the HIV-1 Tat protein and the RNA-dependent cellular protein kinase, PKR, interact with each other bothin vitroandin vivo.Using GST fusion chromatography, we demonstrate that PKR, interacts directly with the HIV-1 Tat protein. The region in Tat sufficient for binding PKR maps within amino acids 20 to 72. Inin vitroassays, the two-exon form of Tat (Tat 86) was phosphorylated by PKR, while the one exon form of Tat (Tat 72) inhibited PKR autophosphorylation and substrate phosphorylation. The ability of Tat to interact with PKR was demonstrated in both yeast and mammalian cells. Expression of PKR in yeast results in a growth suppressor phenotype which was reversed by coexpression of a one exon form of Tat. Expression of Tat 72 in HeLa cells resulted in direct interaction with PKR as detected by coimmunprecipitation with a Tat antibody. Tat and PKR also form a coimmunoprecipitable complex in cell-free extracts prepared from productively infected T lymphocytes. The interaction of Tat with PKR provides a potential mechanism by which HIV could suppress the interferon system.

Science means research. Current research in suicidology, however, needs development. Therefore, a task force was established by the International Academy for Suicide Research (IASR) to make recommendations for future study of suicide. These consultations are offered only as current thoughts to assist, not only in research, but also to aid in preventing suicide.

ABSTRACTWe previously reported (K. T. Jeang, R. Chun, N. H. Lin, A. Gatignol, C. G. Glabe, and H. Fan, J. Virol. 67:6224–6233, 1993) that human immunodeficiency virus type 1 (HIV-1) Tat and Sp1 form a protein-protein complex. Here, we have characterized the physical interaction and a functional consequence of Tat-Sp1 contact. Using in vitro protein chromatography, we mapped the region in Tat that contacts Sp1 to amino acids 30 to 55. We found that in cell-free reactions, Tat augmented double-stranded DNA-dependent protein kinase (DNA-PK)-mediated Sp1 phosphorylation in a contact-dependent manner. Tat mutants that do not bind Sp1 failed to influence phosphorylation of the latter. In complementary experiments, we also found that Tat forms protein-protein contacts with DNA-PK. We confirmed that in HeLa and Jurkat cells, Tat expression indeed increased the intracellular amount of phosphorylated Sp1 in a manner consistent with the results of cell-free assays. Furthermore, using two phosphatase inhibitors and a kinase inhibitor, we demonstrated a modulation of reporter gene expression as a consequence of changes in Sp1 phosphorylation. Taken together, these findings suggest that activity at the HIV-1 promoter is influenced by phosphorylation of Sp1 which is affected by Tat and DNA-PK.

Jansen, Rene F., Anton W. Pieneman, and Andries ter Maat.Behavior-dependent activities of a central pattern generator in freely behaving Lymnaea stagnalis. J. Neurophysiol.78: 3415–3427, 1997. Cyclic or repeated movements are thought to be driven by networks of neurons (central pattern generators) that are dynamic in their connectivity. During two unrelated behaviors (feeding and egg laying), we investigated the behavioral output of the buccal pattern generator as well as the electrical activity of a pair of identified interneurons that have been shown to be involved in setting the level of activity of this pattern generator (PG). Analysis of the quantile plots of the parameters that describe the behavior (movements of the buccal mass) reveals that during egg laying, the behavioral output of the PG is different compared with that during feeding. Comparison of the average durations of the different parts of the buccal movements showed that during egg laying, the duration of one specific part of buccal movement is increased. Correlated with these changes in the behavioral output of the PG were changes in the firing rate of the cerebral giant neurons (CGC), a pair of interneurons that have been shown to modulate the activity of the PG by means of multiple synaptic contacts with neurons in the buccal ganglion. Interval- and autocorrelation histograms of the behavioral output and CGC spiking show that both the PG output and the spiking properties of the CGCs are different when comparing egg-laying animals with feeding animals. Analysis of the timing relations between the CGCs and the behavioral output of the PG showed that both during feeding and egg laying, the electrical activity of the CGCs is largely in phase with the PG output, although small changes occur. We discuss how these results lead to specific predictions about the kinds of changes that are likely to occur when the animal switches the PG from feeding to egg laying and how the hormones that cause egg laying are likely to be involved.

Hermann, Petra M., Robert P. J. de Lange, Anton W. Pieneman, Andries ter Maat, and Rene F. Jansen.Role of neuropeptides encoded on CDCH-1 gene in the organization of egg-laying behavior in the pond snail, Lymnaea stagnalis. J. Neurophysiol.78: 2859–2869, 1997. Egg laying in the pond snail Lymnaea stagnalisis triggered by a discharge of the neuroendocrine caudodorsal cells (CDCs). The CDCs expresses three different caudorsal cell hormone (CDCH) genes. This gene family expresses, in total, 11 different peptides among which is the ovulation hormone. Besides the CDCs, the CDCH gene family is expressed in other central and peripheral neurons. In this study, we investigated the roles the different CDCH peptides play in the organization of egg-laying behavior. Egg-laying behavior is a sequence of stereotyped movements in which three phases can be distinguished: resting, turning, and oviposition. We have used the excitation of right pedal N (RPeN) motor neurons as a simple analogue of shell-turning behavior, one of the elements of egg-laying behavior. RPeN motor neurons were inhibited during the resting phase of egg laying but were subsequently excited at the onset of and during the turning phase. The excitatory effect could be evoked by application of beta3-CDCP on RPeN motor neurons in the CNS as well as in isolation but not by the ovulation hormone, alpha-CDCP or Calfluxin, the other CDCH-1 peptides tested. The ovulation hormone itself caused inhibition of RPeN motor neurons. Anti-CDCH–1 positive fiber tracts were found close to the cell bodies and axons of the RPeN motor neurons. Electrical stimulation of a nerve that contains these fibers resulted in excitation of the RPeN motor neurons. The effects of injection of CDCH-1 peptides into intact animals correlated well with the effects of these peptides on RPeN motor neurons. Injection of beta3-CDCP or alpha-CDCP into intact animals resulted in immediate turning behavior in the absence of egg laying itself. The ovulation hormone and Calfluxin had no immediate effect on the behavior. Furthermore, our data indicate that the individual CDCH-1 peptides act on different targets.

Propellants based on HTPB/AP (hydroxyl-terminated polybutadiene/ammonium perchlorate) are the most commonly used in most of the rocket engines used by the Brazilian Armed Forces. This work aimed at the possibility of extending its useful life (currently in 10 years) by performing chemical kinetic analysis of the energetic material via differential scanning calorimetry (DSC) and also performing computer simulation of aging process using the software Large-scale Atomic/Molecular Massively Parallel Simulator. The simulations presented the experimental behavior of the aging process, showing the bending and cross-link of the binder with the volume contraction and the energetic stabilization. Thermal analysis via DSC was performed in triplicate and in 3 heating ratios (5 °C, 10 °C and 15 °C) of rocket motor with 11-year shelf-life, using the Arrhenius equation to obtain its activation energy, using Ozawa and Kissinger kinetic methods, allowing comparison with manufacturing period data (standard motor). The obtained activation energies were 126.67 kJ/mol (Ozawa) and 122.85 kJ/mol (Kissinger), much higher than that of the aged propellants (~ 78 kJ/mol, based on literature data), showing that the propellant has not yet aged significantly. In addition, the kinetic parameters of internal pressure of the combustion chamber in 8 rocket engines with 11 years of shelf-life were also acquired, for comparison purposes with the engine start-up data.

Presents the poem "Migrant off the Stream," by Rene F. Cardenas. First Line: Shoulders down, caps furled tight above the ears, Last Line: looking for work, meester, looking for work.