Transition from Beam-Target to Thermonuclear Fusion in High-Current Deuterium Z-Pinch Simulations.

Fusion yields from dense, Z-pinch plasmas are known to scale with the drive current, which is favorable for many potential applications. Decades of experimental studies, however, show an unexplained drop in yield for currents above a few mega-ampere (MA). In this work, simulations of DD Z-Pinch plasmas have been performed in 1D and 2D for a constant pinch time and initial radius using the code Lsp, and observations of a shift in scaling are presented. The results show that yields below 3 MA are enhanced relative to pure thermonuclear scaling by beamlike particles accelerated in the Rayleigh-Taylor induced electric fields, while yields above 3 MA are reduced because of energy lost by the instability and the inability of the beamlike ions to enter the pinch region.

Promotion of Influenza Vaccination in the Emergency Department.

BACKGROUND: Influenza vaccine uptake is low among underserved populations whose primary health care access occurs in emergency departments. We sought to determine whether implementation of two interventions would increase 30-day influenza vaccine uptake in unvaccinated patients in the emergency department. METHODS: This three-group, prospective, cluster-randomized controlled trial compared two interventions with a control group in noncritically ill, adult patients in the emergency department who were not vaccinated for influenza in the current vaccine season. The unit of randomization was individual calendar days. Participants received either Intervention M (an influenza vaccine messaging platform consisting of a video, one-page flyer, and scripted message, followed by a vaccine acceptance question and provider notification if participants indicated vaccine acceptance), Intervention Q (no messaging but the vaccine acceptance question and provider notification), or control (usual care/no intervention). The primary outcome was receipt of an influenza vaccine at 30 days ascertained by electronic health record review and telephone follow-up, comparing the Intervention M group with the control group. Secondary outcomes included comparisons of 30-day vaccine uptake in Intervention Q versus control and Intervention M versus Intervention Q. RESULTS: Between October 2022 and February 2023, a total of 767 trial participants were enrolled at six emergency departments in five U.S. cities. Median age was 46 years; 353 (46%) participants were female, 274 (36%) were African American, and 158 (21%) were Latinx; 126 (16%) lacked health insurance, and 244 (32%) lacked primary care. The Intervention M, Intervention Q, and control groups had 30-day vaccine uptakes of 41%, 32%, and 15%, respectively (P<0.0001 for Intervention M vs. control). Comparing Intervention M versus Intervention Q, the adjusted difference in 30-day vaccine uptake was 8.7 percentage points (95% confidence interval, -0.1 to 17.6 percentage points). CONCLUSIONS: Implementation of influenza vaccine messaging platforms (video clips, printed materials, and verbal scripts) improved 30-day vaccine uptake among unvaccinated patients in the emergency department. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05836818.).

Impact of anti-tobacco warning labels on behaviour of tobacco users in one of the cities of Gujarat, India.

BACKGROUND: Tobacco use continues to be the leading global cause of preventable deaths, killing nearly 6 million people worldwide each year. Tobacco control must be given the high priority by scaling up tobacco control measures. In India under Control of Tobacco Product Act, it is mandatory to keep the warning labels over all kind of tobacco products in order to minimise the use of tobacco. OBJECTIVES: Review of the knowledge regarding warning labels printed on tobacco products among its users and to evaluate the impact of them on addicting behaviour. METHODOLOGY: A Cross Sectional study was carried out among the group of people using tobacco in any form. Total 776 tobacco users were enrolled in the study. RESULTS: Mean age of tobacco user was 41.4 years. Out of total 776 tobacco users, 561 (72.3%) had ever noticed warning signals over the tobacco products. Among those who have noticed warning labels, 64.4 % became aware about health effects and 66% have thought to quit tobacco. Tobacco users of young age group (15-45) were more aware regarding warning labels. Females were less aware. As level of education increases number of tobacco users who tried to quit or reduced the daily quantity of tobacco intake were also increases. CONCLUSIONS: Positive impact of warning labels has been seen among the tobacco users who have noticed them. Not all the tobacco users were aware regarding the presence of warning labels as per the findings of present study.

Subunit composition of pre-T cell receptor complexes expressed by primary thymocytes: CD3 delta is physically associated but not functionally required.

Maturation of immature CD4-CD8- (DN) thymocytes to the CD4+CD8+ (DP) stage of development is driven by signals transduced through a pre-T cell receptor (TCR) complex, whose hallmark is a novel subunit termed pre-T alpha (pT alpha). However, the precise role of pre-TCRs in mediating the DN to DP transition remains unclear. Moreover, progress in understanding pre-TCR function has been hampered thus far because previous attempts to demonstrate expression of pT alpha-containing pre-TCRs on the surface of normal thymocytes have been unsuccessful. In this report, we demonstrate for the first time that pT alpha-containing pre-TCR complexes are expressed at low levels on the surface of primary thymocytes and that these pre-TCR complexes comprise a disulfide-linked pT alpha-TCR-beta heterodimer associated not only with CD3-gamma and -epsilon, as previously reported, but also with zeta and delta. Interestingly, while CD3-delta is associated with the pre-TCR complex, it is not required for pre-TCR function, as evidenced by the generation of normal numbers of DP thymocytes in CD3-delta-deficient mice. The fact that any of the signaling components of the pre-TCR are dispensable for pre-TCR function is indeed surprising, given that few pre-TCR complexes are actually expressed on the surface of primary thymocytes in vivo. Thus, pre-TCRs do not require the full array of TCR-associated signaling subunits (gamma, delta, epsilon, and zeta), possibly because pT alpha itself possesses signaling capabilities.

Regulation of lineage commitment distinct from positive selection.

Developing alphabeta T cells diverge into the CD4 and CD8 lineages as they mature in the thymus. It is unclear whether lineage commitment is mechanistically distinct from the process that selects for the survival of T cells with useful T cell receptor (TCR) specificities (positive selection). In HD mice, which lack mature CD4+ T cells, major histocompatibility complex (MHC) class II-restricted T cells are redirected to the CD8 lineage independent of MHC class I expression. However, neither TCR-mediated signaling nor positive selection is impaired. Thus, the HD mutation provides genetic evidence that lineage commitment may be mechanistically distinct from positive selection.

Risk factors of occupation related back pain and neck pain among patients attending tertiary care hospital, Ahmedabad, India.

INTRODUCTION: Neck/back pain is one of the common health problems associated with significant impact on health resulting in sickness absenteeism. Neck/back pain is one of important causes of disability adjusted life years worldwide. The objectives of study were: To identify various occupations related risk factors and their possible role in occurrence of back pain/neck pain and visual analogue scale(VAS) assessment of their perceived pain. METHODS: The study was conducted at one of the tertiary care hospital at Ahmedabad city, India. All patients above age of 18 years attending physiotherapy department for treatment of back pain/neck pain and gave consent were taken as study participants. Information about certain body postures in their lifestyle or at workplace which can have effects on back pain/neck pain were asked. VAS for perceived pain was anchored by "no pain" (score 0) and "pain as bad as it could be" (score 100). Data were entered in MS Excel and analyzed by frequency, contingency coefficient and Goodman and Kruskal's Gamma test. RESULTS AND CONCLUSION: Total of 512 participants were included in study, among which(10.3%)and 392 (76.6%) participants had neck pain and back pain alone, respectively, while 67 (13.1%) participants had both neck and back pain. Age, marital status, socioeconomic class, body mass index and type of occupation revealed statistically significant association with severity of pain. Among participants with prolonged computer usage, back rest fitting to natural back curve and adjustable height of chair were significant factors for occurrence of neck pain. Various body postures like prolonged sitting/ standing, frequent bending at waist/knee, pulling/pushing heavy objects, frequent weight lifting > 10 kg and repetitive movements of back/neck revealed as statistically significant risk factors for back/neck pain.

Non-invasive early detection of acute transplant rejection via nanosensors of granzyme B activity.

The early detection of the onset of transplant rejection is critical for the long-term survival of patients. The diagnostic gold standard for detecting transplant rejection involves a core biopsy, which is invasive, has limited predictive power and carries a morbidity risk. Here, we show that nanoparticles conjugated with a peptide substrate specific for the serine protease granzyme B, which is produced by recipient T cells during the onset of acute cellular rejection, can serve as a non-invasive biomarker of early rejection. When administered systemically in mouse models of skin graft rejection, these nanosensors preferentially accumulate in allograft tissue, where they are cleaved by granzyme B, releasing a fluorescent reporter that filters into the recipient's urine. Urinalysis then discriminates the onset of rejection with high sensitivity and specificity before features of rejection are apparent in grafted tissues. Moreover, in mice treated with subtherapeutic levels of immunosuppressive drugs, the reporter signals in urine can be detected before graft failure. This method may enable routine monitoring of allograft status without the need for biopsies.

Differentiated Care Preferences of Stable Patients on Antiretroviral Therapy in Zambia: A Discrete Choice Experiment.

BACKGROUND: Although differentiated service delivery (DSD) models for stable patients on antiretroviral therapy (ART) offer a range of health systems innovations, their comparative desirability to patients remains unknown. We conducted a discrete choice experiment to quantify service attributes most desired by patients to inform model prioritization. METHODS: Between July and December 2016, a sample of HIV-positive adults on ART at 12 clinics in Zambia were asked to choose between 2 hypothetical facilities that differed across 6 DSD attributes. We used mixed logit models to explore preferences, heterogeneity, and trade-offs. RESULTS: Of 486 respondents, 59% were female and 85% resided in urban locations. Patients strongly preferred infrequent clinic visits [3- vs. 1-month visits: ß (ie, relative utility) = 2.84; P < 0.001]. Milder preferences were observed for waiting time for ART pick-up (1 vs. 6 hours.; ß = -0.67; P < 0.001) or provider (1 vs. 3 hours.; ß = -0.41; P = 0.002); "buddy" ART collection (ß = 0.84; P < 0.001); and ART pick-up location (clinic vs. community: ß = 0.35; P = 0.028). Urban patients demonstrated a preference for collecting ART at a clinic (ß = 1.32, P < 0.001), and although most rural patients preferred community ART pick-up (ß = -0.74, P = 0.049), 40% of rural patients still preferred facility ART collection. CONCLUSIONS: Stable patients on ART primarily want to attend clinic infrequently, supporting a focus in Zambia on optimizing multimonth prescribing over other DSD features-particularly in urban areas. Substantial preference heterogeneity highlights the need for DSD models to be flexible, and accommodate both setting features and patient choice in their design.

Reprogrammable recognition codes in bicoid homeodomain-DNA interaction.

We describe experiments to determine how the homeodomain of the Drosophila morphogenetic protein Bicoid recognizes different types of DNA sequences found in natural enhancers. Our chemical footprint analyses reveal that the Bicoid homeodomain makes both shared and distinct contacts with a consensus site A1 (TAATCC) and a nonconsensus site X1 (TAAGCT). In particular, the guanine of X1 at position 4 (TAAGCT) is protected by Bicoid homeodomain. We provide further evidence suggesting that the unique arginine at position 54 (Arg 54) of the Bicoid homeodomain enables the protein to recognize X1 by specifically interacting with this position 4 guanine. We also describe experiments to analyze the contribution of artificially introduced Arg 54 to DNA recognition by other Bicoid-related homeodomains, including that from the human disease protein Pitx2. Our experiments demonstrate that the role of Arg 54 varies depending on the exact homeodomain framework and DNA sequences. Together, our results suggest that Bicoid and its related homeodomains utilize distinct recognition codes to interact with different DNA sequences, underscoring the need to study DNA recognition by Bicoid-class homeodomains in an individualized manner.

Target selectivity of bicoid is dependent on nonconsensus site recognition and protein-protein interaction.

We describe experiments to compare the activities of two Drosophila homeodomain proteins, Bicoid (Bcd) and an altered-specificity mutant of Fushi tarazu, Ftz(Q50K). Although the homeodomains of these proteins share a virtually indistinguishable ability to recognize a consensus Bcd site, only Bcd can activate transcription from natural enhancer elements when assayed in both yeast and Drosophila Schneider S2 cells. Our analysis of chimeric proteins suggests that both the homeodomain of Bcd and sequences outside the homeodomain contribute to its ability to recognize natural enhancer elements. We further show that, unlike the Bcd homeodomain, the Ftz(Q50K) homeodomain fails to recognize nonconsensus sites found in natural enhancer elements. The defect of a chimeric protein containing the homeodomain of Ftz(Q50K) in place of that of Bcd can be preferentially restored by converting the nonconsensus sites in natural enhancer elements to consensus sites. Our experiments suggest that the biological specificity of Bcd is determined by combinatorial contributions of two important mechanisms: the nonconsensus site recognition function conferred by the homeodomain and the cooperativity function conferred primarily by sequences outside the homeodomain. A systematic comparison of different assay methods and enhancer elements further suggests a fluid nature of the requirements for these two Bcd functions in target selection.

Genome-wide responses to mitochondrial dysfunction.

Mitochondrial dysfunction can lead to diverse cellular and organismal responses. We used DNA microarrays to characterize the transcriptional responses to different mitochondrial perturbations in Saccharomyces cerevisiae. We examined respiratory-deficient petite cells and respiratory-competent wild-type cells treated with the inhibitors of oxidative phosphorylation antimycin, carbonyl cyanide m-chlorophenylhydrazone, or oligomycin. We show that respiratory deficiency, but not inhibition of mitochondrial ATP synthesis per se, induces a suite of genes associated with both peroxisomal activities and metabolite-restoration (anaplerotic) pathways that would mitigate the loss of a complete tricarboxylic acid cycle. The array data suggested, and direct microscopic observation of cells expressing a derivative of green fluorescent protein with a peroxisomal matrix-targeting signal confirmed, that respiratory deficiency dramatically induces peroxisome biogenesis. Transcript profiling of cells harboring null alleles of RTG1, RTG2, or RTG3, genes known to control signaling from mitochondria to the nucleus, suggests that there are multiple pathways of cross-talk between these organelles in yeast.

Relationship of spasticity to knee angular velocity and motion during gait in cerebral palsy.

This study investigated the effects of spasticity in the hamstrings and quadriceps muscles on gait parameters including temporal spatial measures, knee position, excursion and angular velocity in 25 children with spastic diplegic cerebral palsy (CP) as compared to 17 age-matched peers. While subjects were instructed to relax, an isokinetic device alternately flexed and extended the left knee at one of the three constant velocities 30 degrees/s, 60 degrees/s and 120 degrees/s, while surface electromyography (EMG) electrodes over the biceps femoris and the rectus femoris recorded muscle activity. Patients then participated in 3D gait analysis at a self-selected speed. Results showed that, those with CP who exhibited heightened stretch responses (spasticity) in both muscles, had significantly slower knee angular velocities during the swing phase of gait as compared to those with and without CP who did not exhibit stretch responses at the joint and the tested speeds. The measured amount (torque) of the resistance to passive flexion or extension was not related to gait parameters in subjects with CP; however, the rate of change in resistance torque per unit angle change (stiffness) at the fastest test speed of 120 degrees/s showed weak to moderate relationships with knee angular velocity and motion during gait. For the subset of seven patients with CP who subsequently underwent a selective dorsal rhizotomy, knee angular extension and flexion velocity increased post-operatively, suggesting some degree of causality between spasticity and movement speed.

Signal amplification by rolling circle amplification on DNA microarrays.

While microarrays hold considerable promise in large-scale biology on account of their massively parallel analytical nature, there is a need for compatible signal amplification procedures to increase sensitivity without loss of multiplexing. Rolling circle amplification (RCA) is a molecular amplification method with the unique property of product localization. This report describes the application of RCA signal amplification for multiplexed, direct detection and quantitation of nucleic acid targets on planar glass and gel-coated microarrays. As few as 150 molecules bound to the surface of microarrays can be detected using RCA. Because of the linear kinetics of RCA, nucleic acid target molecules may be measured with a dynamic range of four orders of magnitude. Consequently, RCA is a promising technology for the direct measurement of nucleic acids on microarrays without the need for a potentially biasing preamplification step.

Gene rearrangement patterning and DNase-I hypersensitive sites within the T-cell receptor J alpha locus.

For several years, the relationship between alpha beta and gamma delta T-cell progenitors has been a topic of debate. Some argue that a subset of T-cell progenitors is "pre-committed" to the alpha beta lineage and is thus programmed to rearrange alpha, but not delta genes. It is further argued that the deletion of the delta locus by a unique rearrangement, delta rec-psi J alpha, may be the critical forerunner to V-J alpha joins in alpha beta committed cells and that a hypersensitive site (HS) termed 5'TEA might regulate such rearrangement. Here we present an alternative hypothesis. We first emphasize that directed J alpha gene rearrangements do not exclusively target the psi J alpha gene, but that clustered gene rearrangements occur throughout the J alpha locus during T-cell development. We describe the existence of not one, but at least two HS sites distributed along the J alpha locus which might serve as regulators for the gene rearrangement event. Finally, we suggest that progenitor T-cells are not committed to a particular delta or alpha gene rearrangement, but that a flexible progenitor responds to complex interactions between environmental signals and multiple regulatory elements interspersed among delta/alpha genes.

Synthesis of sputter deposited CuO nanoparticles and their use for decontamination of 2-chloroethyl ethyl sulfide (CEES).

We report the synthesis of copper oxide (CuO) nanoparticles by dc magnetron sputtering for adsorptive degradation of 2-chloroethyl ethyl sulfide (CEES), a simulant of well-known chemical warfare agent sulfur mustard (HD). The synthesized CuO nanoparticles were characterized by XRD, TEM, FE-SEM, N2-BET, FT-IR and TGA. The average particle size calculated from XRD pattern was found to be 7 nm for as-deposited and varied up to 86 nm after postannealing. The particle size was also calculated through TEM analysis. The surface area of the particles (∼110-36 m(2)/g) is found to be enhanced significantly in comparison with reported in the literature. Degradation kinetics of CEES was investigated over the CuO nanoparticles and it was found that dc sputtered CuO nanoparticles give superior decontamination properties against CEES. The reactions seemed to be first order with rate constant (k) and half-life (t(1/2)) values in the range of 0.434-0.134 h(-1) and 1.59-5.17 h respectively. The reaction products were characterized by GC-MS and verified through FT-IR. The data reveal the role of hydrolysis reactions in the decontamination of CEES.

Restricted usage of T-cell receptor V alpha sequence and variable-joining pairs after normal T-cell development and bone marrow transplantation.

TCR V alpha 3 and V alpha 5 transcripts in PBLs from healthy individuals of multiple age groups and from BMT recipients were analyzed. PCR, cloning, and sequencing studies revealed significant V-J junctional diversity among TCR transcripts from all tested blood samples, as provided both by N/P-region addition and exonuclease activity. However, results illustrated restrictions in TCR alpha diversity at several additional levels. First, V alpha 5 and V alpha 3 gene families, which were expected to be composed of multiple members, were dominated in each case by a single sequence at the transcript level. Second, restrictions existed in V-J pairing in that J alpha genes, which were encoded toward the 5' region of the locus, were rearranged frequently with V alpha 3 and rarely with V alpha 5. Conversely, J alpha genes encoded toward the 3' region of the locus preferentially rearranged with V alpha 5. Healthy individuals showed few differences with regard to V-J pairing patterns, while one of three BMT recipients demonstrated a skewed usage of 3' J alpha genes. In total, results demonstrated qualitative restrictions that may limit the working TCR repertoire in human peripheral tissues, both among BMT recipients and their healthy donors.

Lead increases inositol 1,4,5-trisphosphate levels but does not interfere with calcium transients in primary rat astrocytes.

Alteration of receptor-mediated signal transduction pathways by inorganic lead (Pb) has been postulated to contribute to the neurotoxicity of this environmental toxicant, some of these effects involving astrocytes. As Pb is known to mimic Ca2+ in various biological systems or alter Ca(2+)-mediated cellular processes, we analyzed the effect of Pb exposure on alpha 1 receptor activated astrocytic phosphoinositide metabolism and Ca2+ responses in primary astrocyte cultures prepared from cerebral cortex of 1-day-old rats. Exposure to norepinephrine (NE; 10-100 microM) resulted in a significant increase in astrocytic inositol 1,4,5-trisphosphate levels, concomitant with an increase in intracellular Ca2+ levels. Fifteen minute exposure to Pb (10 microM lead acetate) significantly increased inositol 1,4,5-trisphosphate generation compared with controls, both in the presence and absence of NE. However, the inositol 1,4,5-trisphosphate-mediated Ca2+ transients following NE stimulation was unaltered in the presence of Pb (1-100 microM). NE-evoked intracellular Ca2+ responses, both in the presence and absence of extracellular Ca2+ did not differ between control and Pb-treated astrocytes. Additional studies failed to demonstrate the occurrence of Pb influx into astrocytes within the first 12 min of exposure such that Ca2+ responses would be directly affected. It therefore appears unlikely that astrotoxic effects of Pb are mediated via direct changes in intracellular Ca2+ transients.

Extensive nevus comedonicus.

A 19-year-old woman had an extensive nevus comedonicus affecting the left arm, trunk, and leg. Her condition was complicated by episodes of recurrent cyst formation and secondary infection. These were reduced in extent and frequency during 14 months of treatment with a combined progesterone-estrogen contraceptive preparation, and the appearance of the lesions affecting the leg was improved. The clinical features, histogenesis, histology, and treatment of nevus comedonicus are discussed.

Lichen sclerosus et atrophicus following radiation therapy.

Several years after postmastectomy radiation therapy, lichen sclerosus et atrophicus (LSA) developed in two patients within the radiation fields. This sequence, to our knowledge, has not previously been described. The etiology of LSA is largely unknown, but trauma has been implicated as a provoking factor in some cases, and LSA might be an isomorphic response to the trauma of radiation therapy.