The angular distribution of the reaction νˉe+p→e++n\bar{\nu}_e + p \to e^+ + n

The reaction $\bar{\nu}_e + p \to e^+ + n$ is very important for low-energy ($E_\nu \lesssim 60$ MeV) antineutrino experiments. In this paper we calculate the positron angular distribution, which at low energies is slightly backward. We show that weak magnetism and recoil corrections have a large effect on the angular distribution, making it isotropic at about 15 MeV and slightly forward at higher energies. We also show that the behavior of the cross section and the angular distribution can be well-understood analytically for $E_\nu \lesssim 60$ MeV by calculating to ${\cal O}(1/M)$, where $M$ is the nucleon mass. The correct angular distribution is useful for separating $\bar{\nu}_e + p \to e^+ + n$ events from other reactions and detector backgrounds, as well as for possible localization of the source (e.g., a supernova) direction. We comment on how similar corrections appear for the lepton angular distributions in the deuteron breakup reactions $\bar{\nu}_e + d \to e^+ + n + n$ and $\nu_e + d \to e^- + p + p$. Finally, in the reaction $\bar{\nu}_e + p \to e^+ + n$, the angular distribution of the outgoing neutrons is strongly forward-peaked, leading to a measurable separation in positron and neutron detection points, also potentially useful for rejecting backgrounds or locating the source direction.Comment: 10 pages, including 5 figure

tat Exon 1 Exhibits Functional Diversity during HIV-1 Subtype C Primary Infection

Human immunodeficiency virus type 1 (HIV-1) Tat is a mediator of viral transcription and is involved in the control of virus replication. However, associations between HIV-1 Tat diversity and functional effects during primary HIV-1 infection are still unclear. We estimated selection pressures in tat exon 1 using the mixed-effects model of evolution with 672 viral sequences generated from 20 patients infected with HIV-1 subtype C (HIV-1C) over 500 days postseroconversion. tat exon 1 residues 3, 4, 21, 24, 29, 39, and 68 were under positive selection, and we established that specific amino acid signature patterns were apparent in primary HIV-1C infection compared with chronic infection. We assessed the impact of these mutations on long terminal repeat (LTR) activity and found that Tat activity was negatively affected by the Ala21 substitution identified in 13/20 (65%) of patients, which reduced LTR activity by 88% (±1%) (P < 0.001). The greatest increase in Tat activity was seen with the Gln35/Lys39 double mutant that resulted in an additional 49% (±14%) production of LTR-driven luciferase (P = 0.012). There was a moderate positive correlation between Tat-mediated LTR activity and HIV-1 RNA in plasma (P = 0.026; r = 0.400) after 180 days postseroconversion that was reduced by 500 days postseroconversion (P = 0.043; r = 0.266). Although Tat activation of the LTR is not a strong predictor of these clinical variables, there are significant linear relationships between Tat transactivation and patients' plasma viral loads and CD4 counts, highlighting the complex interplay between Tat mutations in early HIV-1C infection

Effect of P to A Mutation of the N-Terminal Residue Adjacent to the Rgd Motif on Rhodostomin: Importance of Dynamics in Integrin Recognition

Rhodostomin (Rho) is an RGD protein that specifically inhibits integrins. We found that Rho mutants with the P48A mutation 4.4–11.5 times more actively inhibited integrin α5β1. Structural analysis showed that they have a similar 3D conformation for the RGD loop. Docking analysis also showed no difference between their interactions with integrin α5β1. However, the backbone dynamics of RGD residues were different. The values of the R2 relaxation parameter for Rho residues R49 and D51 were 39% and 54% higher than those of the P48A mutant, which caused differences in S2, Rex, and τe. The S2 values of the P48A mutant residues R49, G50, and D51 were 29%, 14%, and 28% lower than those of Rho. The Rex values of Rho residues R49 and D51 were 0.91 s−1 and 1.42 s−1; however, no Rex was found for those of the P48A mutant. The τe values of Rho residues R49 and D51 were 9.5 and 5.1 times lower than those of P48A mutant. Mutational study showed that integrin α5β1 prefers its ligands to contain (G/A)RGD but not PRGD sequences for binding. These results demonstrate that the N-terminal proline residue adjacent to the RGD motif affect its function and dynamics, which suggests that the dynamic properties of the RGD motif may be important in Rho's interaction with integrin α5β1

Barriers to the acceptance of electronic medical records by physicians from systematic review to taxonomy and interventions

<p>Abstract</p> <p>Background</p> <p>The main objective of this research is to identify, categorize, and analyze barriers perceived by physicians to the adoption of Electronic Medical Records (EMRs) in order to provide implementers with beneficial intervention options.</p> <p>Methods</p> <p>A systematic literature review, based on research papers from 1998 to 2009, concerning barriers to the acceptance of EMRs by physicians was conducted. Four databases, "Science", "EBSCO", "PubMed" and "The Cochrane Library", were used in the literature search. Studies were included in the analysis if they reported on physicians' perceived barriers to implementing and using electronic medical records. Electronic medical records are defined as computerized medical information systems that collect, store and display patient information.</p> <p>Results</p> <p>The study includes twenty-two articles that have considered barriers to EMR as perceived by physicians. Eight main categories of barriers, including a total of 31 sub-categories, were identified. These eight categories are: A) Financial, B) Technical, C) Time, D) Psychological, E) Social, F) Legal, G) Organizational, and H) Change Process. All these categories are interrelated with each other. In particular, Categories G (Organizational) and H (Change Process) seem to be mediating factors on other barriers. By adopting a change management perspective, we develop some barrier-related interventions that could overcome the identified barriers.</p> <p>Conclusions</p> <p>Despite the positive effects of EMR usage in medical practices, the adoption rate of such systems is still low and meets resistance from physicians. This systematic review reveals that physicians may face a range of barriers when they approach EMR implementation. We conclude that the process of EMR implementation should be treated as a change project, and led by implementers or change managers, in medical practices. The quality of change management plays an important role in the success of EMR implementation. The barriers and suggested interventions highlighted in this study are intended to act as a reference for implementers of Electronic Medical Records. A careful diagnosis of the specific situation is required before relevant interventions can be determined.</p

Attenuated allergic airway hyperresponsiveness in C57BL/6 mice is associated with enhanced surfactant protein (SP)-D production following allergic sensitization

BACKGROUND: C57BL/6 mice have attenuated allergic airway hyperresponsiveness (AHR) when compared with Balb/c mice but the underlying mechanisms remain unclear. SP-D, an innate immune molecule with potent immunosuppressive activities may have an important modulatory role in the allergic airway response and the consequent physiological changes. We hypothesized that an elevated SP-D production is associated with the impaired ability of C57BL/6 mice to develop allergic AHR. METHODS: SP-D mRNA and protein expression was investigated during development of allergic airway changes in a model of Aspergillus fumigatus (Af)-induced allergic inflammation. To study whether strain dependency of allergic AHR is associated with different levels of SP-D in the lung, Balb/c and C57BL/6 mice were compared. RESULTS: Sensitization and exposure to Af induced significant airway inflammation in both mouse strains in comparison with naïve controls. AHR to acetylcholine however was significantly attenuated in C57BL/6 mice in spite of increased eosinophilia and serum IgE when compared with Balb/c mice (p < 0.05). Af challenge of sensitized C57BL/6 mice induced a markedly increased SP-D protein expression in the SA surfactant fraction (1,894 ± 170% of naïve controls) that was 1.5 fold greater than the increase in Balb/c mice (1,234 ± 121% p < 0.01). These changes were selective since levels of the hydrophobic SP-B and SP-C and the hydrophilic SP-A were significantly decreased following sensitization and challenge with Af in both strains. Further, sensitized and exposed C57BL/6 mice had significantly lower IL-4 and IL-5 in the BAL fluid than that of Balb/c mice (p < 0.05). CONCLUSIONS: These results suggest that enhanced SP-D production in the lung of C57BL/6 mice may contribute to an attenuated AHR in response to allergic airway sensitization. SP-D may act by inhibiting synthesis of Th2 cytokines

Long-Term Persistence of Exhausted CD8 T Cells in Chronic Infection Is Regulated by MicroRNA-155

Persistent viral infections and tumors drive development of exhausted T (TEX) cells. In these settings, TEX cells establish an important host-pathogen or host-tumor stalemate. However, TEX cells erode over time, leading to loss of pathogen or cancer containment. We identified microRNA (miR)-155 as a key regulator of sustained TEX cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection. Genetic deficiency of miR-155 ablated CD8 T cell responses during chronic infection. Conversely, enhanced miR-155 expression promoted expansion and long-term persistence of TEX cells. However, rather than strictly antagonizing exhaustion, miR-155 promoted a terminal TEX cell subset. Transcriptional profiling identified coordinated control of cell signaling and transcription factor pathways, including the key AP-1 family member Fosl2. Overexpression of Fosl2 reversed the miR-155 effects, identifying a link between miR-155 and the AP-1 transcriptional program in regulating TEX cells. Thus, we identify a mechanism of miR-155 regulation of TEX cells and a key role for Fosl2 in T cell exhaustion. During persistent viral infections, exhausted T cells (TEX) erode quantitatively and qualitatively and therefore fail to provide protection. Stelekati et al. identified microRNA (miR)-155 as a key molecule that can enhance and sustain TEX responses long-term during chronic viral infection

The Ty1 integrase protein can exploit the classical nuclear protein import machinery for entry into the nucleus

Like its retroviral relatives, the long terminal repeat retrotransposon Ty1 in the yeast Saccharomyces cerevisiae must traverse a permanently intact nuclear membrane for successful transposition and replication. For retrotransposition to occur, at least a subset of Ty1 proteins, including the Ty1 integrase, must enter the nucleus. Nuclear localization of integrase is dependent upon a C-terminal nuclear targeting sequence. However, the nuclear import machinery that recognizes this nuclear targeting signal has not been defined. We investigated the mechanism by which Ty1 integrase gains access to nuclear DNA as a model for how other retroelements, including retroviruses like HIV, may utilize cellular nuclear transport machinery to import their essential nuclear proteins. We show that Ty1 retrotransposition is significantly impaired in yeast mutants that alter the classical nuclear protein import pathway, including the Ran-GTPase, and the dimeric import receptor, importin-α/β. Although Ty1 proteins are made and processed in these mutant cells, our studies reveal that an integrase reporter is not properly targeted to the nucleus in cells carrying mutations in the classical nuclear import machinery. Furthermore, we demonstrate that integrase coimmunoprecipitates with the importin-α transport receptor and directly binds to importin-α. Taken together, these data suggest Ty1 integrase can employ the classical nuclear protein transport machinery to enter the nucleus

Long-term multiwavelength monitoring and reverberation mapping of NGC 2617 during a changing-look event

We present the results of photometric and spectroscopic monitoring campaigns of the changing look AGN NGC~2617 carried out from 2016 until 2022 and covering the wavelength range from the X-ray to the near-IR. The facilities included the telescopes of the SAI MSU, MASTER Global Robotic Net, the 2.3-m WIRO telescope, Swift, and others. We found significant variability at all wavelengths and, specifically, in the intensities and profiles of the broad Balmer lines. We measured time delays of ~ 6 days (~ 8 days) in the responses of the H-beta (H-alpha) line to continuum variations. We found the X-ray variations to correlate well with the UV and optical (with a small time delay of a few days for longer wavelengths). The K-band lagged the B band by 14 +- 4 days during the last 3 seasons, which is significantly shorter than the delays reported previously by the 2016 and 2017--2019 campaigns. Near-IR variability arises from two different emission regions: the outer part of the accretion disc and a more distant dust component. The HK-band variability is governed primarily by dust. The Balmer decrement of the broad-line components is inversely correlated with the UV flux. The change of the object's type, from Sy1 to Sy1.8, was recorded over a period of ~ 8 years. We interpret these changes as a combination of two factors: changes in the accretion rate and dust recovery along the line of sight.Comment: 14 pages, 15 figures, accepted by the MNRA