Miracle-dz/UniFAR-FTUs huggingface dataset:
Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

ABSTRACT Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD). However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (≥2-fold, P < 0.05) of many taxa at exacerbation and after treatment were observed. Microbiota members that were increased at exacerbation were primarily of the Proteobacteria phylum, including nontypical COPD pathogens. Changes in the bacterial composition after treatment for an exacerbation differed significantly among the therapy regimens clinically prescribed (antibiotics only, oral corticosteroids only, or both). Treatment with antibiotics alone primarily decreased the abundance of Proteobacteria, with the prolonged suppression of some microbiota members being observed. In contrast, treatment with corticosteroids alone led to enrichment for Proteobacteria and members of other phyla. Predicted metagenomes of particular microbiota members involved in these compositional shifts indicated exacerbation-associated loss of functions involved in the synthesis of antimicrobial and anti-inflammatory products, alongside enrichment in functions related to pathogen-elicited inflammation. These trends reversed upon clinical recovery. Further larger studies will be necessary to determine whether specific compositional or functional changes detected in the airway microbiome could be useful indicators of exacerbation development or outcome.
RNase treatment of yeast and mammalian cell extracts affects in vitro substrate methylation by type I protein arginine N-methyltransferases.

Type I protein arginine N-methyltransferases catalyze the formation of omega-NG-monomethylarginine and asymmetric omega-NG, NG-dimethylarginine residues using S-adenosyl-l-methionine as the methyl donor. In vitro these enzymes can modify a number of soluble methyl-accepting substrates in yeast and mammalian cell extracts including several species that interact with RNA. We treated normal and hypomethylated Saccharomyces cerevisiae and RAT1 cell extracts with RNase prior to in vitro methylation by recombinant protein N-arginine methyltransferases and found that the methylation of certain polypeptides is enhanced up to 12-fold whereas that of others is diminished. 2-D gel electrophoresis of RNase-treated yeast extracts allowed us to tentatively identify the glycine- and arginine-rich (GAR) domain-containing proteins Gar1, Nop1, Sbp1, and Npl3 as major methyl-acceptors based on their known isoelectric points and apparent molecular weights. These results suggest that the methylation and RNA-binding of GAR domain-containing proteins in vivo may regulate protein-nucleic acid or protein-protein interactions.
Time Allocation Patterns of Craftsmen and Administrative Entrepreneurs: Implications for Financial Performance

This paper considers how one of the major resources of a new venture, the time of the entrepreneur, is allocated. Building upon conceptual frameworks from the occupational choice and entrepreneurial typology literatures, it develops four hypotheses. These relate to entrepreneurial time allocation, the antecedents of that behavior, and venture performance. A longitudinal sample of 391 firms is analyzed, using path analysis and OLS regression. Entrepreneurial time allocation was found to be related to primary goals at time of founding, which, in turn, were related to level of prior management experience. There was also support for relationships between time allocation and venture performance.
A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. The Dutch AIDS Treatment Group.

BACKGROUND Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) is recommended for patients with human immunodeficiency virus (HIV) infection if their CD4 cell counts are below 200 per cubic millimeter (0.2 x 10(9) per liter). Either aerosolized pentamidine or trimethoprim-sulfamethoxazole (co-trimoxazole) is commonly prescribed for prophylaxis, but the relative efficacy and toxicity of these agents are unknown. METHODS We conducted a multicenter trial involving 215 HIV-infected patients with no history of PCP but with CD4 cell counts below 200 per cubic millimeter. The patients were randomly assigned to one of three regimens: aerosolized pentamidine once a month, 480 mg of trimethoprim-sulfamethoxazole once a day (80 mg of trimethoprim and 400 mg of sulfamethoxazole), or 960 mg of trimethoprim-sulfamethoxazole once a day (160 mg and 800 mg, respectively). The cumulative incidence of PCP was estimated by Kaplan-Meier survival analysis. RESULTS After a mean follow-up of 264 days, 6 of the 71 patients in the pentamidine group had a confirmed first episode of PCP (11 percent), whereas none of the 142 patients in the two trimethoprim-sulfamethoxazole groups had PCP (P = 0.002). However, adverse events that required discontinuation of the medication were much more frequent in the trimethoprim-sulfamethoxazole groups (17 and 18 patients) than in the pentamidine group (2 patients). The adverse reactions occurred significantly sooner in the group given 960 mg of trimethoprim-sulfamethoxazole than in the group given 480 mg (mean time, 16 vs. 57 days; P = 0.02). CONCLUSIONS For patients with HIV infection, trimethoprim-sulfamethoxazole taken once a day is more effective as primary prophylaxis against PCP than aerosolized pentamidine administered once a month, although adverse drug reactions are more frequent with trimethoprim-sulfamethoxazole.
Androgenicity and venous endothelial function in post-menopausal women.

BACKGROUND Endothelial dysfunction is one of the early signs of cardiovascular damage. High androgen levels have been related to inflammatory endothelial markers in pre- and post-menopausal women. AIM This cross-sectional study aimed at investigating whether free androgen index (FAI) [estimated by dividing total testosterone (nmol/l) by SHBG (nmol/l) x 100] is related to endothelial function during post-menopause. SUBJECTS AND METHODS Twenty-six post-menopausal women were assessed with the dorsal hand vein compliance technique. Acetylcholine (Ach) and sodium nitroprusside (SNP) dose-response curves were constructed to test endothelium-dependent and independent relaxation, respectively. RESULTS Mean age was 54 yr (+/-4) and median time since menopause was 6 yr (interquartile range: 3-9). Patients were stratified according to FAI levels into two groups: FAI greater than or less than the group median of 2.5. Waist-to-hip ratio (WHR) was significantly higher in the group with FAI>2.5, as well as median dose of Ach for maximal vasodilation [720 (360-3600) ng/min with FAI>2.5 vs 36 (0.36-360) ng/min with FAI<or=2.5; p=0.005]. Maximal vasodilation with SNP was similar in both groups. Positive correlations were observed between Ach doses and maximal vasodilation and FAI (r=0.473, p=0.015), waist (r=0.510, p= 0.011), and WHR (r=0.479, p=0.021). SHBG was negatively correlated with Ach doses (rs=-0.400, p=0.043). CONCLUSIONS This study suggests that FAI, even within normal limits, is related to early changes in endothelial function in healthy post-menopausal women. Longitudinal studies are required to determine the clinical relevance of these findings.
Safety and efficacy of donepezil hydrochloride in patients with mild to moderate Alzheimer's disease: Findings of an observational study

Background: Alzheimer's disease (AD), a progressive brain disorder, is the most common cause of dementia among the elderly. Donepezil hydrochloride is a potent, reversible, and highly selective inhibitor of acetylcholinesterase (AChE). It is chemically distinct from other cholinesterase (ChE) inhibitors which are effective in the treatment of AD. Objectives: To evaluate the safety and efficacy of donepezil hydrochloride therapy over a 12 weeks period in patients with mild to moderate AD in Indian population. Materials and Methods: In this post-marketing study, patients with mild to moderate AD received oral donepezil hydrochloride 5 mg/day for 4 weeks followed by 10 mg/day for 8 weeks. Patients were assessed 4 times weekly for cognition on ‘Mini Mental Status Examination (MMSE) scale’, and function on ‘Activities of Daily Living (ADL) index’. Clinicians and caregivers assessment of safety and efficacy was assessed on a 5-point rating scale. Results: One hundred and seventy two of one hundred and eighty two patients completed 12 weeks of study period. MMSE score significantly improved (P<0.0001) from 16.72 at baseline to 19.77 after 12 weeks, and there was significant improvement (P<0.05) in ADL index in 13 of 17 domains after 12 weeks. Caregivers and clinicians rated the therapy as very good to good in >80% and >90% patients, respectively. Adverse events were consistent with the known pharmacological and safety profile of donepezil. Conclusions: Donepezil is well tolerated in Indian patients with mild to moderate AD with significant improvement in cognition and function.
Putative copper‐ and zinc‐binding motifs in Streptococcus pneumoniae identified by immobilized metal affinity chromatography and mass spectrometry

The aim of metalloproteomics is to identify and characterize putative metal‐binding proteins and metal‐binding motifs. In this study, we performed a systematical metalloproteomic analysis on Streptococcus pneumoniae through the combined use of efficient immobilized metal affinity chromatography enrichment and high‐accuracy linear ion trap‐Orbitrap MS to identify metal‐binding proteins and metal‐binding peptides. In total, 232 and 166 putative metal‐binding proteins were respectively isolated by Cu‐ and Zn‐immobilized metal affinity chromatography columns, in which 133 proteins were present in both preparations. The putative metalloproteins are mainly involved in protein, nucleotide and carbon metabolisms, oxidation and cell cycle regulation. Based on the sequence of the putative Cu‐ and Zn‐binding peptides, putative Cu‐binding motifs were identified: H(X)mH (m=0–11), C(X)2C, C(X)nH (n=2–4, 6, 9), H(X)iM (i=0–10) and M(X)tM (t=8 or 12), while putative Zn‐binding motifs were identified as follows: H(X)mH (m=1–12), H(X)iM (i=0–12), M(X)tM (t=0, 3 and 4), C(X)nH (n=1, 2, 7, 10 and 11). Equilibrium dialysis and inductively coupled plasma‐MS experiments confirmed that the artificially synthesized peptides harboring differential identified metal‐binding motifs interacted directly with the metal ions. The metalloproteomic study presented here suggests that the comparably large size and diverse functions of the S. pneumoniae metalloproteome may play important roles in various biological processes and thus contribute to the bacterial pathologies.
Differential responses of bovine oocytes and preimplantation embryos to heat shock

The authors sought to determine whether developmental differences in the magnitude of embryonic mortality caused by heat stress in vivo are caused by changes in resistance of embryos to elevated temperature. In this regard, responses of oocytes, two‐cell embryos, four‐ to eight‐cell embryos, and compacted morulae to heat shock were compared. An additional goal was to define further the role of cumulus cells and glutathione in thermoprotection of oocytes. In experiment 1, heat shock (41°C for 12 hr) decreased the number of embryos developing to the blastocyst stage for two‐cell (26% vs. 0%) and four‐ to eight‐cell (25% vs. 10%) embryos but did not affect morulae (37% vs. 42%). In experiment 2, exposure of two‐cell embryos to 41°C for 12 hr reduced the number of four‐ to eight‐cell embryos present 24 hr after the end of heat shock (88% vs. 62%). In experiment 3, heat shock reduced the number of two‐cell embryos developing to blastocyst (49% vs. 8%) but did not affect subsequent development of oocytes when heat shock occurred during the first 12 hr of maturation (46% vs. 41% development to blastocyst); membrane integrity was not altered. In experiment 4, oocytes were cultured with an inhibitor of glutathione synthesis, DL‐buthionine‐[S,R]‐sulfoximine (BSO), for 24 hr and exposed to 41°C for the first 12 hr of maturation. Percentages of blastocysts were 35% (39°C), 18% (41°C), 17% (39°C+BSO), and 11% (41°C+BSO). For experiment 5, oocytes were either denuded or left with cumulus intact and were then radiolabeled with [35S]methionine and [35S]cysteine at 39°C or 41°C for 12 hr. Exposure of oocytes to 41°C for 12 hr reduced overall synthesis of 35S‐labeled TCA‐precipitable intracellular proteins (18,160 vs. 14,594 dpm/oocyte), whereas presence of cumulus increased synthesis (9,509 vs. 23,246). Analysis by two‐dimensional SDS PAGE and fluorography revealed that heat shock protein 68 (HSP68) and two other putative heat shock proteins, P71 and P70, were synthesized by all oocytes regardless of treatment. Heat shock did not alter the synthesis of HSP68 or P71 but decreased amounts of newly synthesized P70. Cumulus cells increased synthesis of P71 and P70. Results indicate there is a biphasic change in resistance to elevations in temperature as oocytes mature, become fertilized, and develop. Resistance declines from the oocyte to the two‐cell stage and then increases. Evidence suggests a role for cumulus cells in increasing HSP70 molecules and protein synthesis. Data also indicate a role for glutathione in oocyte function. Mol Reprod Dev 46:138–145, 1997. © 1997 Wiley‐Liss, Inc.
THE EFFECT OF TED TALKS VIDEO TOWARDS STUDENTS’ SPEAKING ABILITY AT ENGLISH STUDY PROGRAM OF FKIP UIR

In University level, speaking is one of important skill that used be mastered by the English Students, because it is necessary for them to improve their ability to communicate orally by presenting their ideas in real life. Hence, TED is a series of informative, educational, inspiring and sometimes jaw-dropping talks that present „Ideas Worth Spreading‟. There is an emphasis on informing, educating and opening people‟s eyes to new ideas, making them perfect for the classroom. Therefore, the students will have the opportunity to develop their spoken language competence. In relation to this, the researcher was interested in conducting a study which was focused on the effect of TED Talks Video toward students‟ speaking ability at the third semester of English Study Program FKIP UIR. The researchers used experimental research and also used speaking test for pre-test and post-test in both of experiment class and control class as a collecting data of research. Based on the result, it can be seen that the value of t-obs was higher than that of t-table (3,217>2.056). In addition, the value of probability significance (2-tailed) column shows 0.002<0.05. Based on the analysis, those two criteria of rejection are fulfilled. Therefore, it can be concluded that the null hypothesis was rejected and alternative hyphotesis was accepted. Consequently, it could be seen that there was a significant mean difference between the experimental and the control groups. In summary, there was a significant effect of TED Talks video toward students‟ speaking ability at English Study Program FKIP UIR
High Light-Dependent Phosphorylation of Photosystem II Inner Antenna CP29 in Monocots Is STN7 Independent and Enhances Nonphotochemical Quenching1

Phosphorylation of a monomeric antenna protein correlates with increased photoprotective energy dissipation in monocots and is controlled by distinct enzymes compared with trimeric major antennae. Phosphorylation of the photosystem II antenna protein CP29 has been reported to be induced by excess light and further enhanced by low temperature, increasing resistance to these stressing factors. Moreover, high light-induced CP29 phosphorylation was specifically found in monocots, both C3 and C4, which include the large majority of food crops. Recently, knockout collections have become available in rice (Oryza sativa), a model organism for monocots. In this work, we have used reverse genetics coupled to biochemical and physiological analysis to elucidate the molecular basis of high light-induced phosphorylation of CP29 and the mechanisms by which it exerts a photoprotective effect. We found that kinases and phosphatases involved in CP29 phosphorylation are distinct from those reported to act in State 1-State 2 transitions. In addition, we elucidated the photoprotective role of CP29 phosphorylation in reducing singlet oxygen production and enhancing excess energy dissipation. We thus established, in monocots, a mechanistic connection between phosphorylation of CP29 and nonphotochemical quenching, two processes so far considered independent from one another.
Analysis, control and modeling of cascaded multilevel converter-based IPC

This paper proposes a novel interphase power controller (IPC) based on multilevel cascaded H-bridge converters, which are fed by diode bridge sources. In the proposed structure the fundamental modulation scheme is applied to decrease the switching loss in the converters. Furthermore, in this paper the mathematical model of IPC is derived. Based on this model a new method with the aid of MATLAB Simulinkreg Control Design is proposed to determine the controller parameters. Analytical methods to obtain the nonlinear system transfer functions are complicated and time consuming. The proposed method gives the capability to find the system transfer functions, and study the system behavior for determination of the appropriate controller. The performance of proposed system is explored by simulation in PSCAD, with assuming that the IPC is connected to 230 kV power system transmission network of Iran.
Mechanisms linking traffic-related air pollution and atherosclerosis

Purpose of review Recent discoveries in the field of air pollution toxicology highlight the potential impact of specific sources of air pollution, especially related to roadway emissions, on acute and chronic cardiovascular disease. This review covers potential mechanisms, both in terms of biological pathways and chemical drivers, to explain these observations. Recent findings Air pollution is associated with chronic progression of cardiovascular disease. Roadway exposures appear to have a strong correlation to these adverse outcomes. Controlled toxicological studies highlight potential interactions between vehicle-source emissions and adverse vascular outcomes. Mechanistically, a role for both innate and adaptive immune responses is emerging, with important recent findings demonstrating that immunomodulatory pattern-recognition receptors such as Toll-like receptor-4 and lectin-like oxidized LDL receptor-1 may play a role in communicating airway exposures to cardiovascular outcomes. Summary An improved understanding of the sources and mechanisms underlying adverse cardiovascular health outcomes of air pollution would enhance our ability to manage vulnerable populations and establish precise, effective regulatory policies.
Protein-Coding Genes’ Retrocopies and Their Functions

Transposable elements, often considered to be not important for survival, significantly contribute to the evolution of transcriptomes, promoters, and proteomes. Reverse transcriptase, encoded by some transposable elements, can be used in trans to produce a DNA copy of any RNA molecule in the cell. The retrotransposition of protein-coding genes requires the presence of reverse transcriptase, which could be delivered by either non-long terminal repeat (non-LTR) or LTR transposons. The majority of these copies are in a state of “relaxed” selection and remain “dormant” because they are lacking regulatory regions; however, many become functional. In the course of evolution, they may undergo subfunctionalization, neofunctionalization, or replace their progenitors. Functional retrocopies (retrogenes) can encode proteins, novel or similar to those encoded by their progenitors, can be used as alternative exons or create chimeric transcripts, and can also be involved in transcriptional interference and participate in the epigenetic regulation of parental gene expression. They can also act in trans as natural antisense transcripts, microRNA (miRNA) sponges, or a source of various small RNAs. Moreover, many retrocopies of protein-coding genes are linked to human diseases, especially various types of cancer.
Emergence, dominance, and possible decline of CXCR4 chemokine receptor usage during the course of HIV infection

Binding to a chemokine receptor, either CCR5 or CXCR4, by the gp120 glycoprotein is an essential step in the pathway by which HIV enters host cells. Recently, CCR5 antagonists have been developed that obstruct binding of CCR5 by gp120, thus inhibiting host cell entry. Resistance to such CCR5 antagonists may emerge, however, through the selection of viral strains capable of utilizing CXCR4 receptors. This study explores the evolutionary context of emergence, and in many cases decline, of dominant CXCR4‐usage (X4) during disease progression within a number of individuals. Of seven individuals exhibiting a switch to dominant CXCR4 usage, such dominance is transient in five of them with CCR5‐usage (R5) re‐emerging to dominate the viral population later in disease progression. Three individuals conform to documented X4 transience in that the re‐emergence of R5 dominance is an outgrowth from the predominant R5 strain. However, in two individuals we observe a novel pathway for R5 re‐emergence in that R5 strains emerge to dominate late in disease progression through continued evolution of the X4 population. This suggests that the molecular mechanism of such switches between R5 and X4‐usage is strain specific and that no single mechanism is shared between individuals. These findings have implications for the understanding of the mechanisms of potential emergence of resistance to CCR5 antagonists through use of the CXCR4 receptor and support the importance to have an appropriately optimized background therapy for use with entry inhibitors and, as for all HAART, to monitor drug resistance in a comprehensive manner. J. Med. Virol. 82:2004–2012, 2010. © 2010 Wiley‐Liss, Inc.
Molecular and structural basis of polo-like kinase 1 substrate recognition: Implications in centrosomal localization

Polo-like kinase (Plk1) is crucial for cell cycle progression through mitosis. Here we present the molecular and structural mechanisms that regulate the substrate recognition of Plk1 and influence its centrosomal localization and activity. Our work shows that Plk1 localization is controlled not only by the polo box domain (PBD); remarkably, the kinase domain is also involved in Plk1 targeting mechanism to the centrosome. The crystal structures of the PBD in complex with Cdc25C and Cdc25C-P target peptides reveal that Trp-414 is fundamental in their recognition regardless of its phosphorylation status. Binding measurements demonstrate that W414F mutation abolishes molecular recognition and diminishes centrosomal localization. Therefore, Plk1 centrosomal localization is not controlled by His-538 and Lys-540, the residues involved in phosphorylated target binding. The different conformations of the loop, which connects the polo boxes in the apo and the PBD-Cdc25C and PBD-Cdc25C-P complex structures, together with changes in the proline adjacent to the phosphothreonine in the target peptide, suggest a regulatory mechanism to detect binding of unphosphorylated or phosphorylated target substrates. Altogether, these data propose a model for the interaction between Plk1 and Cdc25C.