Miracle-dz/UniFAR-FTUs huggingface dataset:
CcpA Mediates Proline Auxotrophy and Is Required for Staphylococcus aureus Pathogenesis

ABSTRACT Human clinical isolates of Staphylococcus aureus, for example, strains Newman and N315, cannot grow in the absence of proline, albeit their sequenced genomes harbor genes for two redundant proline synthesis pathways. We show here that under selective pressure, S. aureus Newman generates proline-prototrophic variants at a frequency of 3 × 10−6, introducing frameshift and missense mutations in ccpA or IS1811 insertions in ptsH, two regulatory genes that carry out carbon catabolite repression (CCR) in staphylococci and other Gram-positive bacteria. S. aureus Newman variants with mutations in rocF (arginase), rocD (ornithine aminotransferase), and proC (Δ1-pyrroline 5-carboxylate [P5C] reductase) are unable to generate proline-prototrophic variants, whereas a variant with a mutation in ocd (ornithine cyclodeaminase) is unaffected. Transposon insertion in ccpA also restored proline prototrophy. CcpA was shown to repress transcription of rocF and rocD, encoding the first two enzymes, but not of proC, encoding the third and final enzyme in the P5C reductase pathway. CcpA bound to the upstream regions of rocF and rocD but not to that of proC. CcpA's binding to the upstream regions was greatly enhanced by phosphorylated HPr. The CCR-mediated proline auxotrophy was lifted when nonpreferred carbohydrates were used as the sole carbon source. The ccpA mutant displayed reduced staphylococcal load and replication in a murine model of staphylococcal abscess formation, indicating that carbon catabolite repression presents an important pathogenesis strategy of S. aureus infections.
Stroke-Associated Pneumonia: Major Advances and Obstacles

Background: Stroke-associated pneumonia (SAP) has been implicated in the morbidity, mortality and increased medical cost after acute ischemic stroke. The annual cost of SAP during hospitalization in the United States approaches USD 459 million. The incidence and prognosis of SAP among intensive care unit (ICU) patients have not been thoroughly investigated. We reviewed the pathophysiology, microbiology, incidence, risk factors, outcomes and prophylaxis of SAP with special attention to ICU studies. Methods: To determine the incidence, risk factors and prognosis of acute SAP, PubMed was searched using the terms ‘pneumonia' AND ‘neurology intensive unit' and the MeSH terms ‘stroke' AND ‘pneumonia'. Non-English literature, case reports and chronic SAP studies were excluded. Studies were classified into 5 categories according to the setting they were performed in: neurological intensive care units (NICUs), medical intensive care units (MICUs), stroke units, mixed studies combining more than one setting or when the settings were not specified and rehabilitation studies. Results: The incidences of SAP in the following settings were: NICUs 4.1-56.6%, MICUs 17-50%, stroke units 3.9-44%, mixed studies 3.9-23.8% and rehabilitation 3.2-11%. The majority of NICU and MICU studies were heterogeneous including different neurovascular diseases, which partly explains the wide range of SAP incidence. The higher incidence in the majority of ICU studies compared to stroke units or acute floor studies is likely explained by the presence of mechanical ventilation, higher stroke severity causing higher rates of aspiration and stroke-induced immunodepression among ICU patients. The short-term mortality of SAP was increased among the mixed and stroke unit studies ranging between 10.1 and 37.3%. SAP was associated with worse functional outcome in the majority of stroke unit and floor studies. Mortality was less consistent among NICU and MICU studies. This difference could be due to the heterogeneity of ICU studies and the effect of small sample size or other independent risk factors for mortality such as the larger neurological deficit, mechanical ventilation, and age, which may simultaneously increase the risk of SAP and mortality confounding the outcomes of SAP itself. The pathophysiology of SAP is likely explained by aspiration combined with stroke-induced immunodepression through complex humeral and neural pathways that include the hypothalamic-pituitary-adrenal axis, parasympathetic and sympathetic systems. Conclusions: A unified definition of SAP, strict inclusion criteria, and the presence of a long-term follow-up need to be applied to the future prospective studies to better identify the incidence and prognosis of SAP, especially among ICU patients.
Free energy mapping of class I MHC molecules and structural determination of bound peptides

Free energy maps of the binding site are constructed for class I major histocompatibility complex (MHC) proteins, by rotating and translating amino acid probes along the cleft, and performing a side‐chain conformational search at each position. The free energy maps are used to determine favorable residue positions that are then combined to form docked peptide conformations. Because the generic backbone structural motif of peptides bound to class I MHC is known, the mapping is restricted to appropriate regions of the site, but allows for the sometimes substantial variations in backbone and side‐chain conformations. In a test demonstrating the quality of predictions for a known MHC site using only a rotational and conformational search, we started from the crystal structure of the HIV‐1 gp120/HLA‐A2 complex, and predicted the HLA‐A2 bound structures of peptides from the influenza matrix protein, the HIV‐1 reverse transcriptase, and the human T cell leukemia virus. The calculated peptides are at 1.6, 1.3, and 1.4 Å all‐atom RMSDs from their respective crystal structures (Madden DR, Garboczi DN, Wiley DC, 1993). A further test, which also included a local translational search, predicted structures across MHCs. In particular, we obtained the Kb/SEV‐9 complex (Fremont DH et al., 1992, Science 257:919‐927) starting with the complex between HLA‐B27 and a generic peptide (Madden DR, Gorga JC, Strominger JL, Wiley DC, 1991, Nature (Lond) 555:321‐325), with an all‐atom RMSD of 1.2 Å, indicating that the docking procedure is essentially as effective for predictions across MHCs as it is for determinations within the same MHC, although at substantially greater computational cost. The requirements for further improvement in accuracy are identified and discussed briefly.
Therapy of aggressive pituitary tumors

Introduction: Aggressive tumors of the pituitary gland are classically defined as pituitary tumors with a massive invasion of the surrounding anatomical structures and rapid growth. They are notoriously difficult to manage and are associated with poor prognosis because the therapeutic options are limited and the tumors are generally unresponsive to therapy. Areas covered: This review focuses on treatment options for aggressive pituitary tumors, including surgery, radiotherapy and medical treatment, as well as focusing on the promising therapeutic options for aggressive pituitary tumors, evaluating the literature of the last 15 years. With the exception of prolactinomas, surgery is the first-line option, but most aggressive pituitary tumors often require repeated surgery. Pharmacotherapies are useful when surgery is unlikely to improve symptoms, or as an adjunct therapy to surgery. In prolactinomas, dopamine agonists are the first-line treatment and normalize prolactin levels in most patients, even those with macroprolactinomas. Somatostatin analogs are effective agents for primary therapy, pre-operatively or post-operatively to control tumor re-expansion of pituitary adenomas. However, dopamine agonists and somatostatin analogs are not as effective as they are for the treatment of non-aggressive adenomas. When surgery and pharmacotherapy fail, radiotherapy is a useful third-line strategy. Conventional chemotherapy is poorly effective but recent case reports with the temozolomide, an alkylating agent, have provided better results in the short term. Expert opinion: Aggressive pituitary tumors are associated with poor prognosis as therapeutic options are limited. Moreover, they tend to recur quickly after initial treatment, are generally unresponsive to therapy, and are difficult to manage. To improve the overall response rate, the early application of current therapeutic approaches with the incorporation of new therapeutic developments is mandatory.
Prevalence of Anaemia among Adolescents under Ibsy in Rural Block of a Dist. of Northern India

Research Question: What is the prevalence of Anaemia among adolescents under Indira Bal Swasthya Yojna in rural block of a dist. of northern India? Objective: To determine prevalence of Anaemia among adolescents under Indira Bal Swasthya Yojna in rural block of a dist. of northern India Study design: Cross-sectional, descriptive Settings: Government schools under CHC Chiri block of Dist. Rohtak. Statistical analysis: Percentage, simple proportion, chi square test Participants: 1650 participants covered under IBSY. Results: The overall prevalence of anaemia was 67.7%. 1116 out of 1650 students had varying severity of anaemia while anaemia was absent in 534 participants. Out of the 1650 students, 663 (40.2%) were mildly anaemic, 450 (27.3%) were moderately anaemic and 3 (0.2%) were severely anaemic. Conclusion: the present study revealed anaemia to be a major public health problem among adolescents.
Stimulation of Enterotoxin B Production I. Stimulation by Fractions from a Pancreatic Digest of Casein

Chromatography on Dowex 50-X2 of Protein Hydrolysate Powder (Mead Johnson International, Evansville, Ind.), a pancreatic digest of casein, yielded 18 fractions. Five fractions stimulated enterotoxin production in greater amounts than were produced in the basal medium when it contained Protein Hydrolysate Powder. The stimulatory effect was due to the presence of peptides in the fractions. Many of these peptides contained large amounts of proline. Apparently, the primary structure of the peptides was important in the stimulation effect.
RF-Over-Fiber Links With Very Low Noise Figure

Previously published analytical models for the noise figure of an amplifierless fiber-optic link fail to predict the measured performance, with a discrepancy of 1.1 dB at 1 GHz that increases to 2.3 dB by 12 GHz. We use an equivalent circuit to derive the effect of an additional source of noise not accounted for in earlier models: thermal noise arising from loss in the modulator's traveling-wave electrodes. The electrode thermal noise has a frequency dependence matching that of the link's noise figure, such that predictions using the improved model match the measured 1-12 GHz performance of a link with record low noise figure to within ~ 0.4 dB across this band.
Individualized Low-Load Motor Control Exercises and Education versus a High-Load Lifting Exercise and Education to Improve Activity, Pain Intensity, and Physical Performance in Patients with Low Back Pain: A Randomized Controlled Trial

STUDY DESIGN Randomized controlled trial. BACKGROUND Low back pain is a common disorder. Patients with low back pain frequently have aberrant and pain-provocative movement patterns that often are addressed with motor control exercises. OBJECTIVE To compare the effects of low-load motor control (LMC) exercise and those of a high-load lifting (HLL) exercise. METHODS Seventy participants with recurrent low back pain, who were diagnosed with nociceptive mechanical pain as their dominating pain pattern, were randomized to either LMC or HLL exercise treatments. Participants were offered 12 treatment sessions over an 8-week period. All participants were also provided with education regarding pain mechanisms. METHODS Participants were assessed prior to and following treatment. The primary outcome measures were activity (the Patient-Specific Functional Scale) and average pain intensity over the last 7 days (visual analog scale). The secondary outcome measure was a physical performance test battery that included 1 strength, 3 endurance, and 7 movement control tests for the lumbopelvic region. RESULTS Both interventions resulted in significant within-group improvements in pain intensity, strength, and endurance. The LMC group showed significantly greater improvement on the Patient-Specific Functional Scale (4.2 points) compared with the HLL group (2.5 points) (P<.001). There were no significant between-group differences in pain intensity (P=.505), strength, and 1 of the 3 endurance tests. However, the LMC group showed an increase (from 2.9 to 5.9) on the movement control test subscale, whereas the HLL group showed no change (from 3.9 to 3.1) (P<.001). CONCLUSION An LMC intervention may result in superior outcomes in activity, movement control, and muscle endurance compared to an HLL intervention, but not in pain intensity, strength, or endurance. Registered at ClinicalTrials.gov (NCT01061632). LEVEL OF EVIDENCE Therapy, level 2b-.
Clinical and microbiological analysis of Elizabethkingia meningoseptica bacteremia in adult patients in Taiwan

A limited number of reports have documented bacteremia caused by Elizabethkingia meningoseptica (Chryseobacterium meningosepticum) in adults. Most cases have occurred in Taiwan. This study investigated the clinical features and risk factors for mortality from E. meningoseptica bacteremia and the antimicrobial susceptibilities of the isolates. Patients with E. meningoseptica bacteremia were retrospectively analyzed at a medical center/teaching hospital in northern Taiwan over a 3-y period. We analyzed clinical features and outcomes of patients and antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE) results of the isolates. 28 patients had nosocomial bacteremia and 4 patients had healthcare associated bacteremia. The isolates exhibited variable susceptibilities to levofloxacin, ciprofloxacin, piperacillin-tazobactam, tigecycline, and trimethoprim-sulfamethoxazole. PFGE demonstrated that most isolates were epidemiologically unrelated. The 28-d mortality rate was 41%. Multivariate analysis indicated that shock and use of inappropriate antibiotics were independent risk factors for mortality. In conclusion, nosocomial bloodstream infection due to E. meningoseptica is an increasing problem in Taiwan. Our study indicates that patients with E. meningoseptica bacteremia face poor prognoses, with shock and use of inappropriate antibiotics as the main risk factors for mortality. Further clinical study is needed to establish the optimal therapy for E. meningoseptica bacteremia.
Flexible Implantable Microtemperature Sensor Fabricated on Polymer Capillary by Programmable UV Lithography With Multilayer Alignment for Biomedical Applications

In this paper, we present and develop a programmable UV lithography system with multilayer alignment for cylindrical substrates. By using this system various microstructures with different patterns can be fabricated on the capillary surface, and ±1 μm alignment precision can be realized. A home-made spray coating system is also developed for capillary substrates. A flexible implantable microtemperature sensor for hyperthermia application has been designed and fabricated on the polymer capillary with 330 μm diameter. The finite-element transient simulation indicates the sensor can realize ~ 2 ms quick response. Magnetron sputtered platinum film is used as the sensing material considering its good resistance-temperature effect. The test temperature coefficient of resistance of the fabricated flexible microsensors is 0.0035/°C, which is close to the industry standard value of the bulk Pt resistor sensor. The current-voltage curves of the sensor at different temperatures have been tested. The test sensitivity of the temperature sensor is 1.485 Ω/°C. The present flexible implantable microtemperature sensor is promising to be used as an important interventional monitoring device for biomedical applications.
Rethinking international financial centres through the politics of territory: renminbi internationalisation in London's financial district

This paper revisits canonical thinking on international financial centres (IFCs) that understands them as being primarily sustained through: market liquidity; economies of competition and cooperation between financial and related professional services; and acting as interpretative nodes within global finance. In contrast, I explore the implications of foregrounding questions of power and politics in the (re)production of IFCs. Drawing on the case of the development of offshore renminbi markets in London’s financial district, I argue the state plays a vital, yet comparatively neglected, role in shaping the development and changing nature of international financial centres. In so doing, the paper calls for work in economic geography and cognate social sciences to understand finance as a political as well as an economic, social and cultural relation.
Credibility Analysis of Non-Profit Organisations

One of the key motives for the functioning of all entities in a market economy is to achieve its economic goals and to ensure an influence on other entities. This is the reason why the market does not function as the sole criterion for checking the effects of the entities on the society. The effectiveness of the functioning of all economic entities remains a constant requirement and also covers entities in the non-profit sector. The paper discusses the current topic of streamlining the functioning of the non-profit sector. Its objective is to introduce a multi-criteria methodology through which the providers of funds (ministries, foundations, donors, etc.) would be able to evaluate whether non-profit organisations applying for funding are the most credible among the providers, guaranteeing the use of the resources provided to meet the organisations’ declared objectives. The methodology is called “credibility analysis of non-profit organisations”. The methodology was tested in the area of cultural non-profit organisations. The first step of the research included 95 cultural non-profit organisations. We plan to develop this pilot research in other areas of non-profit activities.
An approach to risk forecast of project bidding based on SLS-SVM

Due to the uncertainty, there are all kinds of risks during project bidding. In order to analyze and control the risk of project bidding better, it is necessary to forecast the risk of project bidding, and then help the decision-maker to manage it effectly. For this reason, this paper has put forward the method of sparse least squares support vector machine(SLS-SVM) and used it to forecast the risk of project bidding. For the sparse least squares support vector machine the sparseness is imposed by pruning and one can find the sparse solutions during less time. The experiments result illustrated how a significant amount of support vectors can be reduced without loss of performance in the case of small and large overlap of the underlying distributions and misclassified data.
An Investigation of the Relationship between Earnings Management and Financial Ratios (Panel Data Approach)

Earnings management is regarded as conscious actions taken by manager to achieve certain objectives at the framework of accounting procedures. Management, compared to others, has access to information which is not accessible for others. If mangers tend to transmit information introducing actual value of commercial units using earnings management, it is acceptable, however, concern is created when the goal of earnings management is considered as a factor deviating users from information pertaining to the company’s performance. In this regard, this article attempts to investigate the effect of earnings management on some variables such as accounts payable, debt ratio, and gross profit to sale ratio. To this end, data related to companies listed in Tehran stock exchange during 2009-2015 was employed and analyzed with the aid of the panel data regression method. According to the research findings, discretionary accruals-based earnings management has the highest effect on accounts payable.
Variability in anterior pituitary size within members of a family with GH deficiency due to a new splice mutation in the GHRH receptor gene

objective Mutations in the GHRH receptor (GHRHR) gene (GHRHR) cause autosomal recessive isolated GH deficiency (IGHD), and are usually associated with anterior pituitary hypoplasia (APH) (defined as pituitary height more than 2 SDS below normal). We searched for GHRHR mutations and studied pituitary morphology in three prepubertal sibs with severe IGHD, who were born from consanguineous parents.
Identifying An At-Risk Population of Children With Recurrent Near-Fatal Asthma Exacerbations

Background. Children are frequently admitted to hospitals for treatment of severe asthma exacerbations. Anecdotally, a cohort of these children are thought to have multiple readmissions to the intensive care unit (ICU), yet this group of children has not been characterized. The purpose of this study was to examine the factors related to recurrent ICU admissions in children with asthma. Methods. The authors conducted a retrospective study of all children admitted to the pediatric ICU for asthma between April 1997 and December 2007. Children with more than one ICU admission were defined as having recurrent near-fatal asthma exacerbations. Results. During this period, 306 children with asthma were admitted to the ICU on 350 occasions; 269 children had only one ICU admission and 33 children (11%) had two or more ICU admissions. To predict who might require readmission, the authors compared the first hospitalization of all children. When compared with children admitted to the ICU only once, children admitted to the ICU more than once were more likely to be overweight (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.1, 4.9), to have public insurance (OR 3.6; 95% CI 1.5, 8.5), and less likely to be Caucasian (OR 0.34; 95% CI 0.14, 0.86). There was no difference in Nation Heart, Lung and Blood Institute (NHLBI) asthma classification, admission illness severity, durations of therapy, or length of stay (LOS) that might identify those who would require readmission. To determine the effect of readmission analysis on subsequent hospitalization, the authors used multiple logistic regression to identify factors associated with increased LOS in all hospitalizations of the subset of children with recurrent near-fatal asthma exacerbations. In this analysis, LOS was most closely associated with admission severity of illness (p = .002), but not with number of hospitalizations. Conclusions. In this single hospital cohort, there were identifiable factors in children admitted to the ICU that are associated with an increased risk of developing recurrent near-fatal asthma exacerbations. Specifically, overweight children with public insurance were more likely and Caucasian children less likely to be readmitted to the ICU for asthma. These children may represent a group to which specific interventions should be targeted prospectively to prevent readmission.