Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamics of Memory B-Cell Populations in Blood, Lymph Nodes, and Bone Marrow during Antiretroviral Therapy and Envelope Boosting in Simian Immunodeficiency Virus SIVmac251-Infected Rhesus Macaques

ABSTRACT Human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection causes B-cell dysregulation and the loss of memory B cells in peripheral blood mononuclear cells (PBMC). These effects are not completely reversed by antiretroviral treatment (ART). To further elucidate B-cell changes during chronic SIV infection and treatment, we investigated memory B-cell subpopulations and plasma cells/plasmablasts (PC/PB) in blood, bone marrow, and lymph nodes of rhesus macaques during ART and upon release from ART. Macaques previously immunized with SIV recombinants and the gp120 protein were included to assess the effects of prior vaccination. ART was administered for 11 weeks, with or without gp120 boosting at week 9. Naïve and resting, activated, and tissue-like memory B cells and PC/PB were evaluated by flow cytometry. Antibody-secreting cells (ASC) and serum antibody titers were assessed. No lasting changes in B-cell memory subpopulations occurred in bone marrow and lymph nodes, but significant decreases in numbers of activated memory B cells and increases in numbers of tissue-like memory B cells persisted in PBMC. Macaque PC/PB were found to be either CD27+ or CD27− and therefore were defined as CD19+ CD38hi CD138+. The numbers of these PC/PB were transiently increased in both PBMC and bone marrow following gp120 boosting of the unvaccinated and vaccinated macaque groups. Similarly, ASC numbers in PBMC and bone marrow of the two macaque groups also transiently increased following envelope boosting. Nevertheless, serum binding titers against SIVgp120 remained unchanged. Thus, even during chronic SIV infection, B cells respond to antigen, but long-term memory does not develop, perhaps due to germinal center destruction. Earlier and/or prolonged treatment to allow the generation of virus-specific long-term memory B cells should benefit ART/therapeutic vaccination regimens.
Passive and Active Inclusion of Host Proteins in Human Immunodeficiency Virus Type 1 Gag Particles during Budding at the Plasma Membrane

ABSTRACT Human immunodeficiency virus type 1 particles form by budding at the surface of most cell types. In this process, a piece of the plasma membrane is modified into an enveloped virus particle. The process is driven by the internal viral protein Pr55gag. We have studied how host proteins in the membrane are dealt with by Pr55gag during budding. Are they included in or excluded from the particle? The question was approached by measuring the relative concentrations of host and viral proteins in the envelope of Pr55gag particles and in their donor membranes in the cell. We observed that the bulk of the host proteins, including actin and clathrin, were passively included into the virus-like Gag particles. This result suggests that budding by Pr55gag proceeds without significant alteration of the original host protein composition at the cell membrane. Nevertheless, some proteins were concentrated in the particles, and a few were excluded. The concentrated proteins included cyclophilin A and Tsg-101. These were recruited to the plasma membrane by Pr55gag. The membrane-bound cyclophilin A was concentrated into particles as efficiently as Pr55gag, whereas Tsg-101 was concentrated more efficiently. The latter finding is consistent with a role for Tsg-101 in Gag particle release.
Comparative Pharmacokinetics of Intramuscular Artesunate and Artemether in Patients with Severe Falciparum Malaria

ABSTRACT The first-dose pharmacokinetic properties of intramuscular (i.m.) artesunate (ARTS; 2.4 mg/kg immediately [stat], followed by 1.2 mg/kg i.m. daily) and artemether (ARM; 3.2 mg/kg i.m. stat, followed by 1.6 mg/kg i.m. daily) were compared in Vietnamese adults with severe falciparum malaria. A total of 19 patients were studied; 9 received ARTS, and 10 received ARM. ARTS was absorbed very rapidly; concentrations in plasma peaked between 1,362 and 8,388 nmol/liter (median, 5,710 nmol/liter) within 20 min of injection and then declined with a median (range) half-life (t1/2) of 30 (3 to 67) min. ARTS was hydrolyzed rapidly and completely to the biologically active metabolite dihydroartemisinin (DHA). Peak DHA concentrations in plasma ranged between 1,718 and 7,080 nmol/liter (median, 3,060 nmol/liter) and declined with a t1/2 of 52 (26 to 69) min. In contrast, ARM was slowly and erratically absorbed. The absorption profile appeared biphasic. Maximum ARM concentrations in plasma ranged between 67 nmol/liter (a value close to the 50% inhibitory concentration for some Plasmodium falciparum isolates) and 1,631 nmol/liter (median, 574 nmol/liter) and occurred at a median (range) of 10 (1.5 to 24) h. There was relatively little conversion to DHA. After i.m. injection in cases of severe malaria, absorption of the water-soluble ARTS is rapid and extensive, whereas the oil-based ARM is slowly and erratically absorbed, with relatively little conversion to the more active DHA. On the basis of this pharmacological study, parenteral ARTS is preferable to ARM as an initial antimalarial therapy, particularly in the most seriously ill patients. These findings should be formally assessed by a randomized clinical trial.
Delineating IT Resources and Capabilities to Obtain Competitive Advantage and Improve Firm Performance

This article develops a research model of the relationships between IT resources, IT capabilities, IT competitive advantage, and the financial performance of an organization. This model is empirically tested with data collected from IT managers and executives in the U.S. The results suggest that while tangible IT resources offer little competitive advantage, intangible IT resources are positively associated with IT capabilities that ultimately lead to IT competitive advantage and the improved financial performance of the organization.
Correlation of the primary Gleason pattern on prostate needle biopsy with clinico-pathological factors in Gleason 7 tumors.

OBJECTIVES To correlate the primary Gleason pattern among patients with biopsy-derived Gleason 7 tumors with the radical prostatectomy specimen Gleason grading and other clinical and pathologic outcomes. METHODS AND MATERIALS Among 474 patients who underwent radical prostatectomy for clinically localized prostate cancer between 1997-2001, 205 (43%) had Gleason 7/10 tumors on pre-operative needle biopsy. Among theses patients, 148 (72.2%) were assigned a primary Gleason 3 pattern (3+4 = 7) and 57 (27.8%) were assigned a primary Gleason 4 pattern (4+3 = 7). The two groups were compared with respect to age, serum PSA levels, Gleason grade in the radical prostatectomy specimen, pathological stage and surgical margin status. RESULTS Among patients with 3+4 tumors on needle biopsy, 64% remained primary Gleason grade 3 while 35% were up-graded to a primary pattern 4 following analysis of the radical prostatectomy specimen. Patients with 4+3 tumors on needle biopsy remained primary Gleason grade 4 in 51% of patients, while 49% of patients had their tumors down-graded to a primary 3 pattern (p = 0.09). There were no differences between patients with needle biopsy 3+4 and 4+3 patterns with respect to total Gleason score in the radical prostatectomy specimen (p = 0.42), pTNM stage (p = 0.36), extra-prostatic extension (p = 0.88), surgical margin involvement (p = 0.16), and seminal vesicle invasion (p = 0.19). In contrast, the primary Gleason pattern in the radical prostatectomy specimen correlated significantly with pTNM stage (p = 0.02) and seminal vesicle invasion (p= 0.003), but not with extra-prostatic extension (p = 0.32) and surgical margin involvement (p = 0.17). CONCLUSIONS Among patients with Gleason 7 adenocarcinoma of the prostate, the biopsy-derived primary Gleason pattern does not appear to correlate with important clinical and pathologic outcomes. The utility of distinguishing a primary Gleason pattern on needle biopsy among patients with Gleason 7 tumors remains unclear given the limited and conflicting literature addressing this issue.
Structural, electronic, and dielectric properties of amorphous ZrO2 from ab initio molecular dynamics

Realistic models of amorphous ZrO2 are generated in a “melt-and-quench” fashion using ab initio molecular dynamics in a plane-wave pseudopotential formulation of density-functional theory. The structural properties of the resulting amorphous models are analyzed, with special attention to coordination statistics. The vibrational and dielectric properties of one of these models are then investigated from first principles using linearresponse methods. The electronic dielectric constant and Born effective charges are found to be very similar to those of the crystalline phases. Encouragingly, the predicted total static dielectric constant is ,22, comparable to that of the monoclinic phase. This work is motivated by the search for improved gate dielectric materials for sub-0.1-mm complementary metal oxide semiconductor technology, and may also have implications for HfO2 and for silicates of ZrO2 and HfO2.
The Physiological Specification of American English Vowels

Use of a new opto-elcctronic device showed that the stressed vowels produced by a native speaker of English could be clearly differentiated according to tongue position. The distance of the tongue from four sensors located along the hard palate was measured in multiple tokens of vowels in a /b_b/ context. There was little token-to-token variability (standard deviations of less than 1.0 mm). With the exception of a reversal between the onglide of/e1/ and /∊/, the height of the tongue differed according to phonological height as expected. The tongue was lower in back vowels than corresponding front vowels, suggesting a biomechanical linkage between tongue height and frontness-backness. Schwa differed from all other vowels, from the “average” tongue configuration seen in stressed vowels, and from the “neutral” configuration in pauses. The talker, a Southerner, diphthongized /I/ and /∊/, but showed relatively little tongue movement in /aU/(compared to that in /aI/ and /OI/). Relatively little tongue movement was also seen in the /aU/ spoken by a second talker, who showed a significantly greater change in upper lip position in producing /aU/ than in /aI/ or /oI/. This finding suggests that lip rounding and tongue movement may “trade off” as articulatory means for producing the rapid spectral change in diphthongs.
Therapy of community-acquired acute bacterial meningitis: the clock is running

Despite antibiotic therapy and supportive intensive medical care, bacterial meningitis remains a disease with high mortality and morbidity. Rapid recognition of symptoms is crucial to direct physicians quickly towards appropriate diagnostic measures and, initially, empiric antibiotic therapy. It has become evident that time from arrival at the hospital to application of the first dose of antibiotics is a crucial independent factor that influences outcome. Here, we review the clinical and laboratory presentation of community-acquired bacterial meningitis and the antibiotic regiments that are currently recommended for its treatment; future therapeutic options are also discussed. Finally, suggestions for the approach to a patient with suspected bacterial meningitis are presented.
Is temporal variation of seedling communities determined by environment or by seed arrival? A test in a neotropical forest

1 Both spatial and temporal processes are assumed to play an important role in driving seedling dynamics. We assessed the magnitude of these two processes in a neotropical forest in French Guiana. We first quantified temporal changes in seedling community structure, then evaluated the relative importance of environmental heterogeneity and temporal fluctuations in seed arrival in determining seedling dynamics. 2 We monitored the seedling dynamics of 6244 seedlings by censusing 370 1‐m2 seedling plots in 160 stations over 20 months. At each station, we quantified environmental variability (light availability, soil resources, litter depth, topography), and measured temporal fluctuations in seed input by sampling seed arrival into seed traps located in each station. 3 Temporal changes in seedling density and diversity between four consecutive censuses were compared with those predicted by a neutral model assuming random recruitment and mortality. Seedling density fluctuations were considerably more variable over time than expected under the neutral assumption. Diversity changes showed less consistent results. For the two first census intervals, seedling diversity was more constant than under the neutral expectations. For the last census interval, seedling diversity was more variable than expected under neutrality. 4 Seedling recruitment, mortality and diversity of recruits were modelled against environmental variables and seed arrival. Sites with higher light availability and soil fertility had more diverse recruits (P < 0.01) but lower seedling survival (P < 0.05). Both density and diversity of local seed arrival had a positive effect, respectively, on density and diversity of recruited seedlings (P < 0.05). 5 Our results show that temporal pulses in seedling community are mainly driven by large temporal fluctuations in seedling recruitment. Annual variation in seedfall and environmental filtering both contribute to explaining spatio‐temporal variation in seedling dynamics to a large degree. Irrespective of species identity, tropical seedling communities are both seed‐ and establishment‐limited. The temporal component of seed‐limitation appears to be of critical relevance in the structuring of tropical seedling communities.
Protecting documents against disasters and theft : the challenge before the public libraries in KwaZulu-Natal, South Africa

All forms of documentary materials are prone to disasters and theft. Security and disaster management are keys to the protection of library materials from theft and risks. However, librarians often overlook disaster preparedness and security control yet they are fundamental aspects of preservation management as they make it possible for people to have access to library materials, and to respond to and recover from disasters. A cross-sectional survey carried out between December 2005 and February 2006 in public libraries of KwaZulu-Natal revealed that the libraries were not adequately prepared for protecting documents against disasters and theft. Furthermore, most of the public libraries did not have disaster plans, adequate procedures for disaster response and recovery, satisfactory theft management strategies and sufficient staff with disaster management knowledge and skills.
Analysis of Consumer Preferences and Willingness-to-Pay for Organic Food Products in Germany

This study employs a choice experiment approach to investigate consumers’ preferences and WTP for organic food products. We use mixed logit models to examine preference heterogeneity. The results revealed significant heterogeneity in preferences for organic apples, milk, and beef product attributes among consumers. The willingness-to-pay (WTP) results obtained from mixed logit indicate gender-specific differences for the examined products of this study. Female respondents have a higher WTP for apple attributes, while higher WTP values for milk and beef attributes are observed for male respondents.
Risk of recurrent coronary events in relation to use and recent initiation of postmenopausal hormone therapy.

BACKGROUND The finding from the Heart and Estrogen/Progestin Replacement Study (HERS) of increased coronary risk restricted to the first year after starting postmenopausal hormone therapy raises new questions about the role of hormone therapy in women with coronary heart disease. We assessed the risk of recurrent myocardial infarction or coronary heart disease death associated with the use and recent initiation of hormone therapy in women who survived a first myocardial infarction. METHODS The setting for this population-based inception cohort study was Group Health Cooperative, a health maintenance organization. We studied 981 postmenopausal women who survived to hospital discharge after their first myocardial infarction between July 1, 1986, and December 31, 1996. We obtained information on hormone use from the Group Health Cooperative computerized pharmacy database and identified recurrent coronary events by medical record review. RESULTS During median follow-up of 3.5 years, there were 186 recurrent coronary events. There was no difference in the risk of recurrent coronary events between current users of hormone therapy and other women (adjusted relative hazard [RH], 0.96; 95% confidence interval [CI], 0.62-1.50). Relative to the risk in women not currently using hormones, there was a suggestion of increased risk during the first 60 days after starting hormone therapy (RH, 2.16; 95% CI, 0.94-4.95) and reduced risk with current hormone use for longer than 1 year (RH, 0.76; 95% CI, 0.42-1.36). CONCLUSION These results are consistent with the findings from the HERS, suggesting a transitory increase in coronary risk after starting hormone therapy in women with established coronary heart disease and a decreased risk thereafter.
Acute effects of 17beta-estradiol on left internal mammary graft after coronary artery bypass grafting.

BACKGROUND Vasospasm of arterial conduits used for coronary surgical procedures is an important cause of postoperative graft failure. Mounting experimental evidence suggests that estrogen reverses acetylcholine-induced vasospasm of the coronary arteries in animals and humans. Estrogen also affects endothelium-derived constrictor factors. We therefore investigated the in vivo vasomotor responses to transdermal 17beta-estradiol of the left internal mammary artery (LIMA) grafted on the anterior descending coronary artery. METHODS We studied 20 women, mean age of 62 +/- 7.2 years (range, 48 to 73 years), who had undergone cardiopulmonary bypass for coronary artery bypass grafting. They received transdermal 17beta-estradiol on the fifth day after operation. The diameter, cross-sectional area, and blood flow of the LIMA graft were measured by transthoracic color Doppler echography before (basal values) and after the transdermal administration of 50 microg of 17beta-estradiol (control). RESULTS LIMA graft vasodilation after the administration of 17beta-estradiol was observed. A significant increase in diameter (2.06 +/- 0.4 mm versus 2.37 +/- 0.28 mm; p = 0.035) and cross-sectional area (3.45 +/- 1. 2 mm2 versus 4.24 +/- 1 mm2; p = 0.039) was registered. The LIMA graft mean flow increased by 49% (44.76 +/- 27.19 mL/min versus 56.62 +/- 27.69 mL/min), but this increase was not statistically significant (p = 0.06). CONCLUSIONS The acute postoperative transdermal administration of 17beta-estradiol induced a significant increase of LIMA graft diameter and cross-sectional area in postmenopausal women who underwent coronary artery bypass grafting. The LIMA graft vasodilation was also associated with an improvement in LIMA blood flow.
A Physiological Measure of Preoperative Anxiety

&NA; A 2cc/min infusion of 2.5% thiopental sodium was administered to 10 female patients on the afternoon preceding, and again immediately before, operation. The dosages required to cause stabilization of the spontaneous skin conductance responses were found to correlate significantly both with IPAT Anxiety Scale Questionnaire scores and with the points of disappearance of the eyelid reflexes. Results showed the test‐retest reliability to be significantly high, and it is concluded that this skin conductance anxiety test (SCAT) has unique value in providing a reliable, valid, and precisely quantitative index of patient anxiety in both general and psychiatric hospital situations.
Hepatitis B Virus X Protein Modulates Apoptosis in Primary Rat Hepatocytes by Regulating both NF-κB and the Mitochondrial Permeability Transition Pore

ABSTRACT The hepatitis B virus (HBV) X protein (HBx) is a multifunctional protein that regulates numerous cellular signal transduction pathways, including those that modulate apoptosis. However, different HBx-dependent effects on apoptosis have been reported; these differences are likely the consequence of the exact conditions and cell types used in a study. Many of the previously reported studies that analyzed HBx regulation of apoptosis were conducted in immortalized or transformed cells, and the alterations that have transformed or immortalized these cells likely impact apoptotic pathways. We examined the effects of HBx on apoptotic pathways in cultured primary rat hepatocytes, a biologically relevant system that mimics normal hepatocytes in the liver. We analyzed the effects of HBx on apoptosis both when HBx was expressed in the absence of other HBV proteins and in the context of HBV replication. HBx stimulation of NF-κB inhibited the activation of apoptotic pathways in cultured primary rat hepatocytes. However, when HBx-induced activation of NF-κB was blocked, HBx stimulated apoptosis; blocking the activity of the mitochondrial permeability transition pore inhibited HBx activation of apoptosis. These results suggest that HBx can be either proapoptotic or antiapoptotic in hepatocytes, depending on the status of NF-κB, and confirm previous studies that link some HBx activities to modulation of the mitochondrial permeability transition pore. Overall, our studies define apoptotic pathways that are regulated by HBx in cultured primary hepatocytes and provide potential mechanisms for the development of HBV-associated liver cancer.
Mitochondrial Single-stranded DNA-binding Protein from Drosophila Embryos

Using a stringent purification procedure on single-stranded DNA cellulose, we have isolated the mitochondrial single-stranded DNA-binding protein from Drosophila melanogaster embryos. Its identity is demonstrated by amino-terminal sequencing of the homogeneous protein and by its localization to a mitochondrial protein fraction. The mitochondrial protein is immunologically and biochemically distinct from the previously characterized nuclear replication protein A from Drosophila (Mitsis, P. G., Kowalczykowski, S. C., and Lehman, I. R.(1993) Biochemistry 32, 5257-5266; Marton, R. F. , Thömmes, P., and Cotterill, S. (1994) FEBS Lett. 342, 139-144). It consists of a single polypeptide of 18 kDa, which is responsible for the DNA binding activity. Sedimentation analysis suggests that D. melanogaster mitochondrial single-stranded DNA-binding protein exists as a homo-oligomer, possibly a tetramer, in solution. The protein binds to DNA in its single-stranded form with a strong preference over double-stranded DNA or RNA, and binds to polypyrimidines preferentially over polypurines. Drosophila mitochondrial single-stranded DNA-binding protein exhibits a greater affinity for long oligonucleotides as compared to short ones, yet does not show high cooperativity. Its binding site size, determined by competition studies and by fluorescence quenching, is approximately 17 nucleotides under low salt conditions, and increases in the presence of greater than 150 mM NaCl. The homogeneous protein stimulates the activity of mitochondrial DNA polymerase from D. melanogaster embryos, increasing dramatically the rate of initiation of DNA synthesis on a singly primed DNA template.