Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural variation and immune recognition of the P1.2 subtype meningococcal antigen

Neisseria meningitidis is a globally important cause of bacterial meningitis and septicemia. No comprehensive antimeningococcal vaccine is available, largely as a consequence of the high sequence diversity of those surface proteins that could function as components of a vaccine. One such component is the protein PorA, a major surface porin of this Gram‐negative organism that has been used in a number of experimental and licensed vaccines. Here we describe a series of experiments designed to investigate the consequences for antibody recognition of sequence diversity within a PorA antigen. The binding of a 14‐residue peptide, corresponding to the P1.2 subtype antigen, to the MN16C13F4 monoclonal antibody was sensitive to mutation of five out of the six residues within the epitope sequence. The crystal structure of the antibody Fab fragment, determined in complex with the peptide antigen, shows a remarkably hydrophobic binding site and interactions between the antigen and antibody are dominated by apolar residues. Nine intrachain hydrogen bonds are formed within the antigen which maintain the β‐hairpin conformation of the peptide. These hydrogen bonds involve residues that are highly conserved amongst different P1.2 sequence variants, suggesting that some positions may be conserved for structural reasons in these highly polymorphic regions. The sensitivity of antibody recognition of the antigen towards mutation provides a structural explanation for the widespread sequence variation seen in different PorA sequences in this region. Single point mutations are sufficient to remove binding capability, providing a rationale for the manner in which different meningococcal PorA escape variants arise. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Use of Double Bulk Current Injection for Susceptibility Testing of Avionics

In this paper, possible applications of double bulk current injection for susceptibility testing of spacecraft are investigated and discussed. Two test procedures are proposed: one is suitable for system-level (i.e., onboard) testing, the other for unit-level assessment of avionic equipment interconnected by multiwire shielded bundles. By enforcing equivalence between radiation and injection, both procedures are designed to inject expected electromagnetic interference (EMI) levels in the equipment under test (EUT), connected at the terminations of a wiring harness. The procedure for system-level testing requires amplitude and phase control of the radio-frequency power sources used to feed the injection probes. It allows to correlate the susceptibility effects obtained by injection with those due to a nonuniform electromagnetic field (such as the field generated by internal EMI sources in metallic enclosures). It is, therefore, suited for radiated intrasystem verifications. The procedure for unit-level testing exploits equivalence between radiation and injection in terms of the current distribution along the overshield, and applies to bundles with an arbitrary number of inner conductors. In the case of vertical polarization, this procedure allows for the reconstruction of the interference effects produced in the EUT by conventional radiated-susceptibility tests (e.g., DO-160), requiring direct radiation of the system.
Research Report: The Role of Behavioral Modeling in Computer Skills Acquisition: Toward Refinement of the Model

Recent empirical work by Compeau and Higgins (1995) investigated the role of behavioral modeling training in the development of computer skills. Their efforts have provided insight into our understanding of the role of computer self-efficacy (CSE) and behavioral modeling (BM) techniques with regard to training effectiveness. Contrary to their expectations, however, several of the hypothesized relationships were not supported, especially those relating to outcome expectancy. In this paper, an empirically derived model of the CSE construct proposed by Marakas, Yi, and Johnson (1998) is offered to highlight potential theoretical, methodological, and measurement issues which may have contributed to or exacerbated the unexpected results obtained in the Compeau and Higgins study. The empirical work contained herein is intended to both replicate and extend the work of Compeau and Higgins and to assist in resolving several key issues left unsettled by their seminal work in this area.
The critical temperature in naked man.

Summary. Investigations have begun made on the critical temperature in naked man and the metabolic cost of maintaining an adequate heat balance below this point. The experiments were performed on a bicycle ergo meter in a cold room, by letting the subjects do just enough work to avoid becoming cold. The critical temperature was found to be approximately 26“ C, confirming earlier studies, and below this point the heat production increased approximately in proportion to the body-to-air temperature gradient, conforming with Newton's law of cooling and with data from most other mammals and birds.
Apical Hypertrophic Cardiomyopathy: Clinical and Two-Dimensional Echocardiographic Assessment

Of 965 patients with hypertrophic cardiomyopathy evaluated by echocardiography at the National Institutes of Health during a 7-year period, 23 (2%) had a nonobstructive morphologic form, in which wall thickening occurred predominantly in the apical (distal) portion of the left ventricle. The patients ranged in age from 15 to 69 years (mean, 37) and were predominantly male (14 patients) and white (only 1 was of oriental descent). Fifteen patients had significant functional limitation, which was usually caused by exertional dyspnea and fatigue. Several electrocardiographic patterns were identified in the study group, but only 4 of these patients showed "giant" negative T waves. Only 3 patients had a morphologic expression of apical hypertrophy that closely resembled that described in Japanese patients--that is, hypertrophy that was particularly localized and confined to the true left ventricular apex (2 of these patients had giant negative T waves). Hence, hypertrophy located predominantly in the distal left ventricle was uncommon in our primarily North American patient population with hypertrophic cardiomyopathy. Most of our patients showed morphologic and clinical features that were dissimilar to those found previously in Japanese patients with apical hypertrophy.
Semaphorin 4C Protects against Allergic Inflammation: Requirement of Regulatory CD138+ Plasma Cells

The regulatory properties of B cells have been studied in autoimmune diseases; however, their role in allergic diseases is poorly understood. We demonstrate that Semaphorin 4C (Sema4C), an axonal guidance molecule, plays a crucial role in B cell regulatory function. Mice deficient in Sema4C exhibited increased airway inflammation after allergen exposure, with massive eosinophilic lung infiltrates and increased Th2 cytokines. This phenotype was reproduced by mixed bone marrow chimeric mice with Sema4C deficient only in B cells, indicating that B lymphocytes were the key cells affected by the absence of Sema4C expression in allergic inflammation. We determined that Sema4C-deficient CD19+CD138+ cells exhibited decreased IL-10 and increased IL-4 expression in vivo and in vitro. Adoptive transfer of Sema4c−/− CD19+CD138+ cells induced marked pulmonary inflammation, eosinophilia, and increased bronchoalveolar lavage fluid IL-4 and IL-5, whereas adoptive transfer of wild-type CD19+CD138+IL-10+ cells dramatically decreased allergic airway inflammation in wild-type and Sema4c−/− mice. This study identifies a novel pathway by which Th2-mediated immune responses are regulated. It highlights the importance of plasma cells as regulatory cells in allergic inflammation and suggests that CD138+ B cells contribute to cytokine balance and are important for maintenance of immune homeostasis in allergic airways disease. Furthermore, we demonstrate that Sema4C is critical for optimal regulatory cytokine production in CD138+ B cells.
Assessment and comparison of CHADS2, CHA2DS2-VASc, and HAS-BLED scores in patients with atrial fibrillation in Saudi Arabia

Aims: No previous reports on the utilization of CHADS2, CHA2DS2-VASc, and HAS-BLED scores in atrial fibrillation (AF) patients in Saudi Arabia have been identified in the literature. The main objectives of this study were to assess and compare the distribution of CHADS2, CHA2DS2-VASc, and HAS-BLED scores and to identify the most common risk factors for stroke and bleeding among AF patients attending clinical pharmacists managed anticoagulation clinic. Settings and Design: This cross-sectional study was conducted over 2 months period at clinical pharmacists managed anticoagulation clinic. Methods: CHADS2, CHA2DS2-VASc, and HAS-BLED scores were calculated and compared for all eligible patients. Results: Two hundred and sixty-four patients with AF were included in the analysis. The number of patients at low risk for stroke was found to be 14 (5.3%) using CHADS2 and only 4 (1.5%) using CHA2DS2-VASc. On the other hand, 64 patients (24.2%) were found at moderate risk for stroke using CHADS2 compared with 17 patients (6.4%) using CHA2DS2-VASc. Most of the patients were found to be at high risk for stroke using either the CHADS2 (70.5%) and CHA2DS2-VASc (92%). The study also revealed that most of the patients were at moderate (63.3%) to high (27.7%) risk of bleeding. Conclusions: The results of this study show that the percentage of patients at high risk for stroke and bleeding is very high. The study revealed that this could be attributed to the high prevalence of modifiable risk factors for stroke and for bleeding in Saudi patients with AF.
High Specificity of Combined TRAP and DBA.44 Expression for Hairy Cell Leukemia

Because of marrow fibrosis, bone marrow aspirations are often nonconclusive in patients with hairy cell leukemia (HCL). Therefore, histologic examination is important in HCL but often difficult in cases with low numbers of tumor cells. A combined immunohistochemical positivity for DBA.44 and tartrate-resistant phosphatase was previously found in 100% of HCL and suggested to be specific for this diagnosis. To further assess the diagnostic specificity and sensitivity of this immunohistochemical approach in a higher number of cases, we analyzed 56 HCLs and lymphoma tissue microarrays, including 840 cases of the most frequent non-Hodgkin lymphomas. All HCLs showed combined positivity for these two proteins (100% sensitivity). Both antibodies were often positive in other lymphoma types. DBA.44 reactivity was especially frequent in follicular lymphomas (46%), whereas tartrate-resistant acid phosphatase (TRAP) expression was often seen in mantle cell lymphomas (57%), primary mediastinal large B-cell lymphomas (54%), and chronic lymphocytic leukemia/small lymphocytic lymphoma (41%). A combined DBA.44/TRAP positivity was seen in only 3% of non-HCL non-Hodgkin lymphomas, including cases of diffuse large B-cell lymphomas, follicular lymphomas, chronic lymphatic leukemia/small lymphocytic leukemias, and mantle cell lymphomas. Overall, these data confirm the utility of combined immunohistochemical DBA.44/TRAP expression analysis in confirming the diagnosis of HCL. However, combined positivity for these markers is highly sensitive but not absolutely specific for HCL.
Diversity management practices in the hospitality sector in Zimbabwe : The role of HR

Diversity management has been hyped as the latest fad to occupy management discourse today. This shift to diversity management has been necessitated by the move away from the traditional labour intensive organisations to the modern globalised industries which rely on a diverse array of workers to meet organizational objectives. It is against this background that this study was conducted to identify the diversity management practices in the hospitality sector in Zimbabwe. The study employed a descriptive survey design within the qualitative research paradigm to solicit for the research data. Purposive sampling was used to select the study respondents from hotels across Zimbabwe. The study revealed that HR managers in the hospitality sector in Zimbabwe are practicing a number of strategies to deal with issues of diversity in the hotel industry. These include the use of policies to guide diversity appreciation, building a diverse sensitive culture, and training employees amongst other strategies. It was recommended that players in the hospitality industry should adopt diversity management as a strategic objective to effectively harness its merits.
Engulfed cell remnants, and not cells undergoing apoptosis, constitute the LE-cell phenomenon

The LE cell has been one of the first immunological signs of active systemic lupus erythematosus, included into the ACR criteria. LE cells consist of a phagocyte engulfing material of disputed origin, which was interpreted as either cellular remnants from necrotic cells or as early apoptotic cells. It is well established that LE cell formation is dependent on autoantibodies against the linker histone H1. In view of this fact, we investigated whether anti-histone H1 antibodies and LE cell positive sera bound to cells where apoptosis had been induced by gliotoxin or actinomycin D or which were necrotic after heating. Necrotic cell remnants, but not (early) apoptotic cells were bound by anti-histone H1 antibodies and LE cell positive sera, establishing that the process of LE cell formation, which is dependent on anti-H1 binding, leads to engulfment of necrotic (or late apoptotic) material, but not of early apoptotic cells.
Metabolic and Attentional Energy Costs of Interlimb Coordination

The authors investigated metabolic and attentional energy costs as participants (N = 6) practiced in-phase, antiphase, and 90°-phase cycling (order counterbalanced) on independent bicycle ergometers, with resistance (40 W/ergometer) and frequency (40 rpm) held constant. Coordination stabilized and became more accurate for all 3 cycling modes, as shown by measures of relative phase, but that collective variable could not account for other relevant attributes of the multifaceted motor behavior observed across the 3 coordination modes. In-phase and antiphase cycling were similar in stability and accuracy, but antiphase had the lowest metabolic and attentional energy costs. Because both homologous muscle action and perceptually symmetrical oscillations coincided in the in-phase mode, the absence of predominance of the inphase pattern showed that neither of those musculoskeletal and perceptual factors exclusively determined the strongest attractor of the coordination dynamics. Both metabolic and attentional costs declined with practice, consistent with the hypothesis that adaptive motor behavior is guided by sensory information concerning the energy demands of the task. Attentional cost was influenced not only by the information-processing demands of kinematic stability but also by the metabolic energy demands. Metabolic energy cost appeared to be the crucial determinant of the preferred solution for this coordination task.
Growth and development of tadpoles (Xenopus laevis) exposed to selective serotonin reuptake inhibitors, fluoxetine and sertraline, throughout metamorphosis

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed drugs that are present in sewage effluents and surface waters. The objective of the present study was to determine whether low environmentally relevant concentrations of the SSRIs fluoxetine and sertraline could impair growth and development in tadpoles of the African clawed frog (Xenopus laevis) and to evaluate if such effects may be caused by a disruption of the neuroendocrine system. Tadpoles were exposed to SSRIs at concentrations of 0.1, 1, and 10 μL for 70 d throughout metamorphosis. No effects on deformities were observed. Tadpoles exposed to fluoxetine (10 μL) and sertraline (0.1, 1, and 10 μL) exhibited reduced growth at metamorphosis. Tadpoles exposed to sertraline (0.1 and 1 μL) exhibited an acceleration of development as indicated by an increase in the time to tail resorption. The effects of SSRIs on growth and development in tadpoles were likely driven by reduced food intake. Reduced feeding rates were observed in SSRI‐exposed tadpoles, and nutritional status can influence growth and development in amphibians via effects on the neuroendocrine system. Only sertraline was capable of causing developmental toxicity in tadpoles at environmentally relevant concentrations. These data warrant additional research to characterize the risks to human health and wildlife from pharmaceutical exposures.
Differences in CMV‐Specific T‐Cell Levels and Long‐Term Susceptibility to CMV Infection after Kidney, Heart and Lung Transplantation

Patients after kidney, heart and lung transplantation differ in their immunosuppressive drug regimens and in susceptibility to infectious complications with cytomegalovirus (CMV). In this study, CMV‐specific T‐cell responses were characterized in long‐term transplant recipients and associated with the frequency of infectious complications. CMV‐reactive CD4 T cells from 50 healthy controls, 68 renal, 14 heart and 24 lung transplant recipients were flow cytometrically quantified by the induction of cytokines after specific stimulation. Moreover, the immunosuppressive effect of calcineurin inhibitors on specific T‐cell reactivity was quantified in vitro and compared with responses in vivo. Median CMV‐specific T‐cell frequencies in long‐term renal (1.48%; range 0.06–17.26%) and heart transplant recipients (0.90%; 0.13–12.49%) did not differ from controls (1.82%; 0.26–21.00%). In contrast, CMV‐specific T‐cell levels were significantly lower in lung transplant recipients (0.50%; <0.05–4.98%) and showed a significant correlation with the frequency of infectious episodes (r =−0.57, p = 0.005). The differences within the groups were associated with increasing dosages of immunosuppressive drugs, as exemplified for calcineurin inhibitors that dose dependently reduced specific T‐cell reactivity in vitro. In conclusion, monitoring CMV‐specific CD4 T cells may serve as a measure for long‐term disease susceptibility and may contribute to an improved management of CMV complications after lung transplantation.
Blood and body fluid exposure as a health risk for international travelers.

health risks, mostly from enteric and vector-borne pathogens.1–3 Although less frequent, bloodand body fluid-borne pathogens can also pose a health risk, one which is dependent on the prevalence of the infection in the destination country, and the lifestyle and activities of the traveler. For example, hepatitis B (HBV), hepatitis C (HCV), immunodeficiency virus (HIV), and other sexually transmitted diseases (STDs) are known hazards for international travelers,due to casual sexual activity, or contaminated medical equipment and blood products.4–8 The current fad of tattooing and body piercing among young travelers poses an additional risk for bloodborne pathogens. The objective of our study was to estimate the extent of potential exposure to bloodand body fluidborne pathogens among a group of returned international travelers.
Repeated administration of angiotensin II reduces its dipsogenic effect without affecting saline intake

Angiotensin II (Ang II) acts at central type 1 (AT1) receptors to increase intake of water and saline. In vitro studies demonstrated rapid desensitization of the AT1 receptor after Ang II exposure, and behavioural studies in rats suggest that exposure to Ang II decreases the dipsogenic potency of subsequent Ang II. Nevertheless, the effect of repeated Ang II injections on saline intake remains untested, and a reliable protocol for examining this purported behavioural desensitization has not emerged from the literature. To address these issues, we established a reliable approach to study Ang II‐induced dipsetic desensitization and used this approach to test the requirement of central AT1 receptors and the specificity of the effect for water intake. Rats given a treatment regimen of three injections of Ang II (300 ng, intracerebroventricular), each separated by 20 min, drank less water than control rats after a subsequent test injection of Ang II. The effect was relatively short lasting, dependent on the dose and timing of Ang II, and was almost completely blocked by the AT1 receptor antagonist losartan. In further testing, when rats were given access to both water and 1.5% saline, animals that received an Ang II treatment regimen drank less water than control animals, but saline intake was unaffected. These data support previous suggestions that Ang II‐induced water and saline intakes are separable. Given the role of G protein uncoupling in desensitization of the AT1 receptor, these data are consistent with the emerging hypothesis that AT1 receptor G protein‐dependent intracellular signalling pathways are more relevant for water, but not saline, intake.
Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group.

OBJECTIVE--To evaluate the relationships between dietary intake of carotenoids and vitamins A, C, and E and the risk of neovascular age-related macular degeneration (AMD), the leading cause of irreversible blindness among adults. DESIGN--The multicenter Eye Disease Case-Control Study. SETTING--Five ophthalmology centers in the United States. PATIENTS--A total of 356 case subjects who were diagnosed with the advanced stage of AMD within 1 year prior to their enrollment, aged 55 to 80 years, and residing near a participating clinical center. The 520 control subjects were from the same geographic areas as case subjects, had other ocular diseases, and were frequency-matched to cases according to age and sex. MAIN OUTCOME MEASURES--The relative risk for AMD was estimated according to dietary indicators of antioxidant status, controlling for smoking and other risk factors, by using multiple logistic-regression analyses. RESULTS--A higher dietary intake of carotenoids was associated with a lower risk for AMD. Adjusting for other risk factors for AMD, we found that those in the highest quintile of carotenoid intake had a 43% lower risk for AMD compared with those in the lowest quintile (odds ratio, 0.57; 95% confidence interval, 0.35 to 0.92; P for trend = .02). Among the specific carotenoids, lutein and zeaxanthin, which are primarily obtained from dark green, leafy vegetables, were most strongly associated with a reduced risk for AMD (P for trend = .001). Several food items rich in carotenoids were inversely associated with AMD. In particular, a higher frequency of intake of spinach or collard greens was associated with a substantially lower risk for AMD (P for trend < .001). The intake of preformed vitamin A (retinol) was not appreciably related to AMD. Neither vitamin E nor total vitamin C consumption was associated with a statistically significant reduced risk for AMD, although a possibly lower risk for AMD was suggested among those with higher intake of vitamin C, particularly from foods. CONCLUSION--Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing advanced or exudative AMD, the most visually disabling form of macular degeneration among older people. These findings support the need for further studies of this relationship.