Miracle-dz/UniFAR-FTUs huggingface dataset:
Malarial Dihydroorotate Dehydrogenase

The malarial parasite relies onde novo pyrimidine biosynthesis to maintain its pyrimidine pools, and unlike the human host cell it is unable to scavenge preformed pyrimidines. Dihydroorotate dehydrogenase (DHODH) catalyzes the oxidation of dihydroorotate (DHO) to produce orotate, a key step in pyrimidine biosynthesis. The enzyme is located in the outer membrane of the mitochondria of the malarial parasite. To characterize the biochemical properties of the malarial enzyme, an N-terminally truncated version of P. falciparum DHODH has been expressed as a soluble, active enzyme in E. coli. The recombinant enzyme binds 0.9 molar equivalents of the cofactor FMN and it has a pH maximum of 8.0 (k cat 8 s−1, K m app DHO (40–80 μm)). The substrate specificity of the ubiquinone cofactor ( CoQ n ) that is required for the oxidation of FMN in the second step of the reaction was also determined. The isoprenoid (n) length of CoQ n was a determinant of reaction efficiency; CoQ4, CoQ6 and decylubiquinone ( CoQD) were efficiently utilized in the reaction, however cofactors lacking an isoprenoid tail (CoQ0 and vitamin K3) showed decreased catalytic efficiency resulting from a 4 to 7-fold increase in K m app . Five potent inhibitors of mammalian DHODH, Redoxal , dichloroallyl lawsone ( DCL ), and three analogs of A77 1726 were tested as inhibitors of the malarial enzyme. All five compounds were poor inhibitors of the malarial enzyme, with IC50's ranging from 0.1–1.0 mm. The IC50 values for inhibition of the malarial enzyme are 102-104-fold higher than the values reported for the mammalian enzyme, demonstrating that inhibitor binding to DHODH is species specific. These studies provide direct evidence that the malarial DHODH active site is different from the host enzyme, and that it is an attractive target for the development of new anti-malarial agents.
DNA Fusion Vaccines Induce Targeted Epitope-Specific CTLs against Minor Histocompatibility Antigens from a Normal or Tolerized Repertoire1

We have designed DNA fusion vaccines able to induce high levels of epitope-specific CD8+ T cells, using linked CD4+ T cell help. Such vaccines can activate effective immunity against tumor Ags. To model performance against minor histocompatibility (H) Ags important in allogeneic hemopoietic stem cell transplantation, responses against the H2Db-restricted Uty and Smcy male HY epitopes have been investigated. Vaccination of females induced high levels of tetramer-specific, IFN-γ-producing CD8+ T cells against each epitope. Vaccines incorporating a single epitope primed effector CTL able to kill male splenocytes in vitro and in vivo, and HYDbUty-specific vaccination accelerated rejection of syngeneic male skin grafts. Priming against either epitope established long-term memory, expandable by injection of male cells. Expanded CD8+ T cells remained specific for the priming HY epitope, with responses to the second suppressed. To investigate vaccine performance in a tolerized repertoire, male mice were vaccinated with the fusion constructs. Strikingly, this also generated epitope-specific IFN-γ-producing CD8+ T cells with cytotoxic function. However, numbers and avidity were lower than in vaccinated females, and vaccinated males failed to reject CFSE-labeled male splenocytes in vivo. Nevertheless, these findings indicate that DNA fusion vaccines can mobilize CD8+ T cells against endogenous minor H Ags, even from a profoundly tolerized repertoire. In the transplantation setting, vaccination of donors could prime and expand specific T cells for in vivo transfer. For patients, vaccination could activate a potentially less tolerized repertoire against similar Ags that may be overexpressed by tumor cells, for focused immune attack.
Gas bubble morphology in small working gaps at spark erosion [micromachining]

The morphology of the gas bubbles in the working gap determines the conditions for the electrical breakdown in spark erosion. Significant modification of the gas bubble structures can be proved by high speed recording if the pulses are changed only in a small parameter field. The investigations carried out are particularly important for the production of precise holes with the spark erosion process. In ED hole sinking, the work gap is smaller than 20 /spl mu/m so that the size and number of gas bubbles are dominant criteria for decontamination of the discharge gap. The gap cleaning effect can be optimized by the specific choice of the pulse parameters, which leads to an essential reduction of the processing time. Comparative investigations with a high speed framing camera (HSFC) indicate that also for single discharges, the gas bubbles are considerably longer than the pulse periods usually used in spark erosion.
Abnormalities of the spleen and liver in patients with hemophilia

Previous studies have demonstrated functional and histologic abnormalities of the liver, and, more recently, splenomegaly in patients with hemophilia. Since these observations usually were derived from hemophiliacs who had received intensive replacement therapy, the question was posed as to whether the frequency of splenic and hepatic abnormalities was secondary to the amount of therapy utilized. In this study, a variety of tests were employed to evaluate spleen and liver size and function to determine if abnormalities in these organs correlated with the intensity of the transfusion program. The study group was comprised of 25 hemophiliacs (mean factor replacement—18,361 U/year; median factor replacement—12,920 U/year). Over 70% of our patients had elevations of aspartate and alanine aminotransferase. Immunoglobulin and complement levels were normal in most subjects. Ninety‐six percent had evidence of exposure to hepatitis B virus. Liver‐spleen imaging suggested significant hepatic abnormalities in most of the patients as evidenced by inhomogeneity of tracer uptake in the liver in 33% and relatively increased colloid uptake in the spleen in 90%. Splenomegaly (palpable spleen or enlargement on liver‐spleen imaging) was detected in 40% of our patients, and tended to occur in the more frequently transfused patients. These findings indicate that significant abnormalities of the spleen and liver can occur in hemophiliacs who have received moderate amounts of replacement therapy and that liver‐spleen imaging may be a useful method for monitoring the development of hepatic and splenic abnormalities.
Reduced Length of Hospital Stay in Colorectal Surgery after Implementation of an Enhanced Recovery Protocol

BACKGROUND:Enhanced recovery after surgery (ERAS) is a multimodal approach to perioperative care that combines a range of interventions to enable early mobilization and feeding after surgery. We investigated the feasibility, clinical effectiveness, and cost savings of an ERAS program at a major U. S. teaching hospital. METHODS:Data were collected from consecutive patients undergoing open or laparoscopic colorectal surgery during 2 time periods, before and after implementation of an ERAS protocol. Data collected included patient demographics, operative, and perioperative surgical and anesthesia data, need for analgesics, complications, inpatient medical costs, and 30-day readmission rates. RESULTS:There were 99 patients in the traditional care group, and 142 in the ERAS group. The median length of stay (LOS) was 5 days in the ERAS group compared with 7 days in the traditional group (P < 0.001). The reduction in LOS was significant for both open procedures (median 6 vs 7 days, P = 0.01), and laparoscopic procedures (4 vs 6 days, P < 0.0001). ERAS patients had fewer urinary tract infections (13% vs 24%, P = 0.03). Readmission rates were lower in ERAS patients (9.8% vs 20.2%, P = 0.02). DISCUSSION:Implementation of an enhanced recovery protocol for colorectal surgery at a tertiary medical center was associated with a significantly reduced LOS and incidence of urinary tract infection. This is consistent with that of other studies in the literature and suggests that enhanced recovery programs could be implemented successfully and should be considered in U.S. hospitals.
The Costs of High School Failure and School Suspensions for the State of California

The Costs of High School Failure and School Suspensions for the State of California Clive R. Belfield Center for Benefit-Cost Studies in Education, Teachers College, Columbia University Department of Economics Queens College, City University of New York October 2014 Commissioned by The Civil Rights Project/Proyecto Derechos Civiles University of California, Los Angeles with support from The Atlantic Philanthropies
Programmed death‐ligand 1 is prognostic factor in esophageal squamous cell carcinoma and is associated with epidermal growth factor receptor

Programmed death‐ligand 1 (PD‐L1) expression either indicates immune inhibitory status or concurrent immune response. Although the relationship between PD‐L1 and clinical outcomes has been studied widely in recent years, its role in prognosis of esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we assessed the significance of PD‐L1 in ESCC and its association with epidermal growth factor receptor (EGFR) and radiation response. We found that PD‐L1 was present both on the surface of tumor cells and tumor‐infiltrating immune cells. Patients with tumor‐infiltrating immune cell PD‐L1 expression had better survival. PD‐L1 expression on immune cells was an independent prognostic factor for patients with ESCC. PD‐L1 expression either on tumor‐infiltrating immune cells or tumor cells was negatively associated with EGFR expression. EGFR/PD‐L1 pairs could separate the survival between EGFR low/PD‐L1 positive and EGFR high/PD‐L1 negative groups. In ESCC cell lines with EGFR high expression, PD‐L1 expression was induced significantly when EGFR signaling was activated by radiation and was dramatically inhibited by an EGFR tyrosine kinase inhibitor. In conclusion, tumor‐infiltrating immune cell PD‐L1 expression is an independent prognostic factor for ESCC, and the association between EGFR and PD‐L1 is vital to determining survival. It is important to consider radiotherapy‐induced imbalance of pro‐tumor and anti‐tumor immune response. A combination of radiotherapy and PD‐L1‐targeted therapy could be a promising therapeutic strategy for ESCC patients.
Modeling and closed-loop control of hypnosis by means of bispectral index (BIS) with isoflurane

A model-based closed-loop control system is presented to regulate hypnosis with the volatile anesthetic isoflurane. Hypnosis is assessed by means of the bispectral index (BIS), a processed parameter derived from the electroencephalogram. Isoflurane is administered through a closed-circuit respiratory system. The model for control was identified on a population of 20 healthy volunteers. It consists of three parts: a model for the respiratory system, a pharmacokinetic model and a pharmacodynamic model to predict BIS at the effect compartment. A cascaded internal model controller is employed. The master controller compares the actual BIS and the reference value set by the anesthesiologist and provides expired isoflurane concentration references to the slave controller. The slave controller maneuvers the fresh gas anesthetic concentration entering the respiratory system. The controller is designed to adapt to different respiratory conditions. Anti-windup measures protect against performance degradation in the event of saturation of the input signal. Fault detection schemes in the controller cope with BIS and expired concentration measurement artifacts. The results of clinical studies on humans are presented.
How Banks Respond to Negative Interest Rates: Evidence from the Swiss Exemption Threshold

We analyze the effect of negative monetary policy rates on banks, using detailed supervisory information from Switzerland. For identification, we compare changes in the behavior of banks that had different fractions of their central bank reserves exempt from negative rates. More affected banks reduce costly reserves and bond financing while maintaining non-negative deposit rates and larger deposit ratios. Higher fee and interest income successfully compensates for squeezed liability margins, but credit and interest rate risk increase. Portfolio rebalancing implies relatively more lending, also compared to an earlier rate cut within positive territory, and risk-taking reduces regulatory capital cushions and liquidity.
Effect of short-term supplementation with rumen-protected fat during the late luteal phase on reproduction and metabolism of ewes.

This study was designed to study the effect of short-term supplementation with rumen-protected fat during the late luteal phase on reproduction and metabolism of sheep during breeding season. Seventy-six ewes (Rahmani, Barki and Awassi × Barki) were allocated to two groups considering genotype: the control ewes (C-group) received a maintenance diet, and the fat-supplemented ewes (F-group) received the maintenance diet plus 50 g/head/day of rumen- protected fat (Megalac) for 9 days during which oestrus was synchronized. The latter had been accomplished using double intramuscular injection of prostaglandin F2α (PGF2α ) 11 days apart. Ovarian activity, serum concentration of cholesterol, glucose, insulin and reproductive performance variables were recorded. Data were analysed considering treatment (group) and genotype. Supplementation had positive effects on the overall mean serum concentrations of cholesterol (p < 0.05), glucose (p < 0.05) on day 6 of nutritional treatment and insulin (p = 0.07) on day 8. Fat supplementation did not affect the total number of follicles, follicle populations and ovulation rate. However, fat-supplemented Rahmani ewes tended to have higher ovulation rate compared with other breeds (treatment × breed interaction, p = 0.06). Treatment also did not affect the mean concentration of serum estradiol or progesterone. Supplemented ewes had higher conception (p = 0.06) and lambing rates (p < 0.05) compared with control. In conclusion, short-term supplementation with rumen-protected fat as a source of energy around breeding time improved metabolism, conception and lambing rates of ewes without effects on steroidogenic capacity and ovarian activity being apparent.
Clinical supervision for nurses in administrative and leadership positions: a systematic literature review of the studies focusing on administrative clinical supervision.

AIM The aim of this systematic literature review was to describe administrative clinical supervision from the nursing leaders', directors' and administrators' perspective. BACKGROUND Administrative clinical supervision is a timely and important topic as organizational structures in health care and nursing leadership are changing in addition to the increasing number of complex challenges present in health care. METHODS The material in this review was drawn from national and international databases including doctoral dissertations, distinguished thesis and peer-reviewed articles. The material was analysed by means of content analysis. The theoretical framework for the analysis was based on the three main functions of clinical supervision: administrative, educational and supportive. FINDINGS The findings demonstrated that the experiences of the administrative clinical supervision and its supportiveness were varying. The intervention was seen to provide versatility of learning experiences and support in challenging work experiences. Administrative clinical supervision effects and assures the quality of care. The effects as a means of development were explained through its resemblance to a leading specialist community. CONCLUSIONS The findings support earlier perceptions concerning the importance and significance of administrative clinical supervision for nursing managers and administrators. However, more research is needed to develop administrative clinical supervision and to increase understanding of theoretical assumptions and relationships of the concepts on the background.
The influence of zonal configurations on macro-level crash modeling

ABSTRACT This study investigated the impacts of zonal configurations on macro-level traffic safety analysis for crashes of different severity levels. Bayesian multivariate Poisson-lognormal models with multivariate conditional auto-regressive priors were developed to account for the spatial autocorrelation between adjacent geographical units and correlations among crash types of four ordinal severity levels, i.e. fatality, severe injury, slight injury and no injury. For the purpose of evaluating the effects of zonal configurations on macro-level traffic safety analysis, the proposed model was calibrated using crash data of four types of geographical units, i.e. block group, traffic analysis zone, census tract and zip code tabulation area, in Hillsborough County of Florida. The study empirically revealed the extensive presence and the significance of MAUP in macro-level safety analysis based on the existing zonal configurations. It gave out a warning and encouraged more research efforts on rational application of macroscopic safety analysis with different zonal configurations.
Retirement income policy and national savings

This paper examines the implications for national savings of three retirement income policy options designed to improve the fiscal sustainability of New Zealand Superannuation (NZS). A simple model is developed that employs population and longevity projections allowing estimation of the contributions that many overlapping age cohorts might make to national savings in response to policy change. Government contributions to national savings, resulting primarily from reduced NZS payments, are also considered. Results suggest that even seemingly modest changes to retirement income policies could lead to substantial cumulative changes in national savings by 2061.
Physical Science Teachers’ Attitudes to and Factors Affecting their Integration of Technology Education in Science Teaching in Benin

Following the calls of international conferences related to the teaching of science and technology, technology education (TE) was integrated as a component of physical sciences programmes in Benin, West Africa. This study investigates physical science teachers’ attitudes towards the integration of TE topics in secondary school science curricula in Benin, and the factors influencing the implementation of the programme. It also proposes solutions to overcome issues of implementation. A quantitative research method was used to collect data. A 67-item questionnaire designed by the researchers was distributed to a convenience sample of 176 physical science teachers in the three largest towns in Benin, and the data were statistically analysed using SPSS 19.0. The results showed that teachers were positive about teaching the TE topics. Many issues affected TE integration in the science curriculum including teachers’ incapacity to design TE lesson plans; the large class sizes; and most importantly students’ inability to understand and speak the instructional language. A variety of solutions were proposed in order to improve the teaching conditions. These included a revision of the TE topics integrated in the programmes, and encouragement of government and school administrators to provide necessary TE teaching materials.
Building with no end in sight: the theory and effects of prison architecture

ABSTRACT The rise of mass incarceration necessitated increased investment in prisons. This increase occurred alongside of policy maker calls for greater government accountability and reliance on evidence-based practices. Despite advances in the understanding of “what works” to reduce crime and recidivism, a notable gap in research exists: What is the evidence that prison architecture influences inmate behavior or reentry outcomes? This article seeks to address that gap and argues that (1) prisons are designed to achieve specific goals, (2) there is minimal empirical evidence that variation in architecture achieves these goals, and (3) the theory by which architecture achieves these goals is inconsistent and unclear. Implications of this assessment for research, theory, and policy are discussed.
Defected ground structure microstrip bandpass filter with multiple finite transmission zeros

A microstrip bandpass filter (BPF) using a defected ground structure (DGS) is presented in this paper. The introduced DGS filter enables three transmission zeros (TZs) to be realized, and the mechanism of realizing TZs is investigated. Centered at 2.0 GHz, a demonstrator filter is optimally designed, fabricated and examined. Experimental verification is provided and good consistency between simulations and measurements is also observed.
The Pattern of Psoriatic Arthritis in Kashmir: A 6-Year Prospective Study

Background: The prevalence, clinical presentation, and patterns of psoriatic arthritis (PsA) vary in different parts of the world. The scenario of PsA in west is different from that of Asia. Moreover, the oligoarticular type which was considered most prevalent earlier has been replaced by polyarticular type. Aim: The study was to the clinical profile of psoriasis patients associated with PsA in Kashmir valley of India. Materials and Methods: This was a noninterventional, observational, prospective, hospital-based study involving 150 successive patients of PsA over a span of 6 years. Severity of the skin and nail involvement was assessed by Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI), respectively. PsA was diagnosed by classification criteria for PsA. The number and pattern of swollen and tender joints was counted and classified by Moll and Wright′s classification criteria. Results: Plaque-type psoriasis was the most common clinical type, observed in 122 (81.33%) patients followed by erythrodermic psoriasis in 10 (6.66%) patients and pustular psoriasis in eight (5.33%) patients. PsA occurred between 30 and 40 years of age in 105 (70%) patients. The cutaneous involvement occurred before joint involvement in 113 (75.33%), while they occurred simultaneously in 30 (20%) cases and the PsA preceded the skin involvement in seven (4.66%) cases. Symmetrical polyarthritis was the commonest clinical presentation and was seen in 90 (60%) patients. Nail involvement due to psoriasis was present in 120 (80%) patients. Commonest nail change found was pitting and seen in 60 (40%) patients. Conclusion: The clinical pattern of PsA varies in different parts of the world. Knowledge of the clinical presentation of PsA in a given area is necessary for the successful management of this disease.
Frequency of in vitro resistance of Pseudomonas aeruginosa to cefepime, ceftazidime, and cefotaxime

The selection frequencies of cefepime (BMY 28142), ceftazidime, and cefotaxime resistance among Pseudomonas aeruginosa strains were determined. Cefepime-resistant mutants were not selected by cefepime (frequency, less than 10(-11)). Ceftazidime- and cefotaxime-resistant mutants were isolated at frequencies of 10(-5) to 10(-10) and were often cross-resistant. However, cefepime resistance among ceftazidime- and cefotaxime-resistant mutants was rare. Selected mutants resistant to cefepime constitutively produced 40- to 450-fold more beta-lactamase than did the parent strain.