Miracle-dz/UniFAR-FTUs huggingface dataset:
Determination of the rate-limiting segment of aminoglycoside nucleotidyltransferase 2''-I by pH and viscosity-dependent kinetics.

Aminoglycoside nucleotidyltransferase 2''-I follows a Theorell-Chance kinetic mechanism in which turnover is controlled by the rate-limiting release of the final product (Q), a nucleotidylated aminoglycoside [Gates, C. A. , & Northrop, D. B. (1988) Biochemistry (second of three papers in this issue)]. The effects of viscosity on the kinetic constants of netilmicin, gentamicin C1, and sisomicin aminoglycoside substrates are as follows: no change in the substrate inhibition constants of all three antibiotics, a small but significant and highly unusual increase in Vmax/Km for netilmicin but large, normal decreases for gentamicin C1 and sisomicin, and marked decreases in the maximal velocities for all three. The lack of effect on substrate inhibition provides essential control experiments, signifying that glycerol does not interfere with binding of aminoglycosides to EQ and that the steady-state distribution of EQ does not increase as the release of Q is slowed by a viscosogen. The decrease in the Vmax/Km of better substrates indicates dominance by a diffusion-controlled component in the catalytic segment, attributed to the release of pyrophosphate. The presence of an increase in the Vmax/Km of the poor substrate, however, is inexplicable in terms of either single or multiple diffusion-controlled steps. Instead, it is here attributed to an equilibrium between conformers of the enzyme-nucleotide complex in which glycerol favors the conformation necessary for binding of aminoglycosides. The decrease in Vmax is consistent with the diffusion-controlled release of the final product determining enzymatic turnover. (ABSTRACT TRUNCATED AT 250 WORDS)
Electrical Stimulation of Dorsal Root Entry Zone Attenuates Wide‐Dynamic‐Range Neuronal Activity in Rats

Recent clinical studies suggest that neurostimulation at the dorsal root entry zone (DREZ) may alleviate neuropathic pain. However, the mechanisms of action for this therapeutic effect are unclear. Here, we examined whether DREZ stimulation inhibits spinal wide‐dynamic‐range (WDR) neuronal activity in nerve‐injured rats.
Modeling and Optimization of a Zero-Voltage Switching Inverter for High Efficiency and Miniaturization

In a zero-voltage switching (ZVS) inverter, high conversion efficiency and miniaturization are expected since switching loss can be dramatically reduced with proper design. In order to realize ZVS condition, auxiliary components such as inductors, capacitors, and switches are embedded in the inverter to implement the function. Since the design of auxiliary components is critical to the ZVS inverter, it is impossible to realize maximum efficiency or minimum size by following the conventional design procedure. This paper introduces an optimized design methodology for a three-phase ZVS inverter with objectives of both high efficiency and miniaturization. Based on the loss models of different commercial IGBT modules under different ZVS conditions, as well as the loss models of auxiliary components and filter inductors, the issue of pursuing highest efficiency and power density is transformed into solving a constrained nonlinear multivariable problem. According to the proposed design methodology, all parameters that influence the efficiency and physical dimensions are considered simultaneously. Thus, the optimized selection of the IGBT module, the parameters of the auxiliary components and the filter inductors would be obtained. A 30-kW three-phase ZVS inverter prototype is built to verify the proposed design method. With proposed design method, the improved prototype has achieved both smaller passive components volume and higher efficiency compared to the former prototype.
On the origin and specificity of antibodies to neuromuscular blocking (muscle relaxant) drugs: an immunochemical perspective

Following the demonstration 25 years ago that substituted ammonium groups on neuromuscular blocking drugs (NMBDs) are the main allergenic structures recognized by IgE antibodies in the sera of some patients who experience anaphylaxis during anaesthesia, immunoassays for these drugs were quickly applied to supplement skin tests in the diagnostic assessment of suspected adverse reactions to anaesthetic agents. Many subjects who react to an NMBD do so on first exposure and this led to the speculation that the origin of allergic sensitization is an environmental agent(s) or another drug containing an ammonium ion. Direct antibody binding and hapten inhibition studies revealed that morphine, which contains a tertiary amino group, was strongly recognized by IgE in sera from anaphylactic patients and a morphine‐solid phase immunoassay was found to be superior to NMBD‐based assays for the detection of NMBD‐reactive IgE antibodies. Extensive inhibition experiments indicate the likelihood of antibody combining site heterogeneity with recognition at the fine structural level of features additional, and adjacent to, ammonium ions. Further quantitative investigations are needed to identify these neighbouring groups on different NMBDs. Recent work has implicated the morphine analogue pholcodine as the sensitizing agent in Norway where, unlike Sweden, anaphylactic reactions to NMBDs are not uncommon and the medicament is available over‐the‐counter. This has led to the suggestion that allergenic sensitization to the ammonium group of pholcodine may account for the different incidences of anaphylaxis during anaesthesia in the two countries. This work is subjected to critical review and some alternative speculations on the nature and origin of the sensitizing agent(s) are presented.
Measurement and impact of co-morbidity in elderly patients with advanced non-small cell lung cancer treated with chemotherapy. A phase II study of weekly paclitaxel

Background. Aging is associated with an increasing of comorbidity and at the time of lung cancer diagnosis patients present one or more other serious disease. The aim of the study is to evaluate tolerability, response and survival of weekly paclitaxel in elderly patients with advanced NSCLC and concomitant diseases. Methods. Patients with advanced NSCLC who were poor candidates to platinum-based therapy because of age >65 years and coexistent illnesses received weekly paclitaxel over 1 hour at a dose of 80 mg/m2. Comorbidity was evaluated according to the Charlson scale, Kaplan-Feinstein index and the Cumulative Illness Rating Scale. Results. A total of 57 patients (median age, 74 years; range, 65–84) were included. The overall response rate was 44%. Median survival was 7.8 months. Grade 3–4 toxicity was uncommon: neutropenia 1.8%, thrombocytopenia 1.8%, neuropathy 7%, hypersensitivity reaction 1.8%. Comorbidity indexes were useful to characterize better the population of elderly patients, but did not define a subgroup with worse prognosis. Conclusions. The low toxicity profile and efficacy of low-dose weekly paclitaxel justified its usage in this group of poor prognosis elderly patients with advanced NSCLC and comorbidities. A comorbidity index should be introduced in prospective oncological studies in the elderly to ensure compatibility.
La propensión a la promoción del consumidor: una nueva perspectiva basada en beneficios

La promocion de ventas ha incrementado su importancia en los ultimos anos tanto desde un punto de vista cualitativo como cuantitativo. Ha pasado de ser simplemente una herramienta tactica con la que conseguir incrementos de ventas a corto plazo, a ser considerada y utilizada por numerosas empresas como una herramienta estrategica. En este espectacular crecimiento ha influido sin duda la actitud que han mostrado los consumidores respecto a las acciones promocionales. Por tanto, el interes de este trabajo reside en estudiar nuevos determinantes de la propension a la promocion que nos permitan comprender mejor este comportamiento. Ademas, tendremos en cuenta la influencia de la categoria de producto en la propension a la promocion, y las consecuencias de esta tendencia en la evaluacion que se realiza de la misma. Para ello, se ha disenado un experimento en el que han participado 132 individuos. Los resultados obtenidos ponen de manifiesto que la propension a la promocion esta determinada por el conjunto de beneficios que ofrece dicha accion promocional, y por el tipo de producto promocionado. Tambien se demuestra que los individuos mas propensos a la promocion realizan una evaluacion mas positiva de esta.
Training characteristics of qualifiers for the U.S. Olympic Marathon Trials.

PURPOSE To describe and compare training characteristics of the 2004 U.S. Olympic Marathon Trials qualifiers. METHODS All qualifiers (104 men, 151 women) received questionnaires. Ninety-three (37 men, 56 women) responded and were categorized as elite (men <2 hours 15 min, women <2 hours 40 min) or national class. RESULTS Men and women ran 75% and 68% of their weekly training distance, respectively, below marathon race pace. Men trained longer than women (12.2 +/- 5.3 vs 8.8 +/- 5.6 years), ran more often (8.7 +/- 2.8 vs 7.1 +/- 2.5 times/wk), and ran farther (145.3 +/- 25.6 vs 116.0 +/- 26.5 km/wk). Elite women ran more than national-class women (135.8 +/- 31.5 vs 111.3 +/- 23.3 km/wk). Distances run at specific intensities were similar between sexes. For men and women, respectively, 49% and 31% did not have a coach and 65% and 68% trained alone. Marathon performance correlated to 5-km, 10-km, and half-marathon performance and to years training, average and peak weekly distance, number of weekly runs, and number of runs > or = 32 km for women. CONCLUSIONS Among U.S. Olympic Marathon Trials qualifiers, there is no consensus as to how to prepare for the marathon beyond running at a pace slower than race pace. Weekly training distance seems to influence women's marathon performance more than it does men's. Because many of these athletes train alone and without a coach, further research is warranted on the reasons that these athletes train the way they do.
[Structural equation modeling on burnout in clinical nurses based on CS-CF model].

PURPOSE The purpose of this study was to construct and test a structural equation modeling on burnout of clinical nurses based on CS-CF model. METHODS A survey using a structured questionnaire was conducted with 557 clinical nurses. Data were analyzed using structural equation modeling. RESULTS The modified hypothetical model yielded the following χ(2)=289.70, p<. 001, RMSEA=. 09, GFI=. 93, TLI=. 91, CFI=. 94, PCFI=. 65, AIC=363.21, SRMR=. 05 or less and showed good fit indices. Nursing work environment, patient safety culture and resilience showed indirect effects on burnout while compassion fatigue and compassion satisfaction had direct effects. CONCLUSION Results of this study suggest that compassion fatigue must be decreased and compassion satisfaction has to be increased, while burnout is lowered by enhancing the clinical nursing work environment, patient safety culture and resilience. In addition, more variables and longitudinal studies are necessary to validate the clear cause-and-effect relationship between the relevant variables.
Whisker motor cortex reorganization after superior colliculus output suppression in adult rats

The effect of unilateral superior colliculus (SC) output suppression on the ipsilateral whisker motor cortex (WMC) was studied at different time points after tetrodotoxin and quinolinic acid injections, in adult rats. The WMC output was assessed by mapping the movement evoked by intracortical microstimulation (ICMS) and by recording the ICMS‐evoked electromyographic (EMG) responses from contralateral whisker muscles. At 1 h after SC injections, the WMC showed: (i) a strong decrease in contralateral whisker sites, (ii) a strong increase in ipsilateral whisker sites and in ineffective sites, and (iii) a strong increase in threshold current values. At 6 h after injections, the WMC size had shrunk to 60% of the control value and forelimb representation had expanded into the lateral part of the normal WMC. Thereafter, the size of the WMC recovered, returning to nearly normal 12 h later (94% of control) and persisted unchanged over time (1–3 weeks). The ICMS‐evoked EMG response area decreased at 1 h after SC lesion and had recovered its baseline value 12 h later. Conversely, the latency of ICMS‐evoked EMG responses had increased by 1 h and continued to increase for as long as 3 weeks following the lesion. These findings provide physiological evidence that SC output suppression persistently withdrew the direct excitatory drive from whisker motoneurons and induced changes in the WMC. We suggest that the changes in the WMC are a form of reversible short‐term reorganization that is induced by SC lesion. The persistent latency increase in the ICMS‐evoked EMG response suggested that the recovery of basic WMC excitability did not take place with the recovery of normal explorative behaviour.
Arabidopsis thaliana VTC4 Encodes L-Galactose-1-P Phosphatase, a Plant Ascorbic Acid Biosynthetic Enzyme*

In plants, a proposed ascorbate (vitamin C) biosynthesis pathway occurs via GDP-d-mannose (GDP-d-Man), GDP-l-galactose (GDP-l-Gal), and l-galactose. However, the steps involved in the synthesis of l-Gal from GDP-l-Gal in planta are not fully characterized. Here we present evidence for an in vivo role for l-Gal-1-P phosphatase in plant ascorbate biosynthesis. We have characterized a low ascorbate mutant (vtc4-1) of Arabidopsis thaliana, which exhibits decreased ascorbate biosynthesis. Genetic mapping and sequencing of the VTC4 locus identified a mutation (P92L) in a gene with predicted l-Gal-1-P phosphatase activity (At3g02870). Pro-92 is within aβ-bulge that is conserved in related myo-inositol monophosphatases. The mutation is predicted to disrupt the positioning of catalytic amino acid residues within the active site. Accordingly, l-Gal-1-P phosphatase activity in vtc4-1 was ∼50% of wild-type plants. In addition, vtc4-1 plants incorporate significantly more radiolabel from [2-3H]Man into l-galactosyl residues suggesting that the mutation increases the availability of GDP-l-Gal for polysaccharide synthesis. Finally, a homozygous T-DNA insertion line, which lacks a functional At3g02870 gene product, is also ascorbate-deficient (50% of wild type) and deficient in l-Gal-1-P phosphatase activity. Genetic complementation tests revealed that the insertion mutant and VTC4-1 are alleles of the same genetic locus. The significantly lower ascorbate and perturbed l-Gal metabolism in vtc4-1 and the T-DNA insertion mutant indicate that l-Gal-1-P phosphatase plays a role in plant ascorbate biosynthesis. The presence of ascorbate in the T-DNA insertion mutant suggests there is a bypass to this enzyme or that other pathways also contribute to ascorbate biosynthesis.
Proceedings from the ice hockey summit on concussion: a call to action.

OBJECTIVE The objective of this proceeding is to integrate the concussion in sport literature and sport science research on safety in ice hockey to develop an action plan to reduce the risk, incidence,severity, and consequences of concussion in ice hockey. methods: A rationale paper outlining a collaborative action plan to address concussions in hockey was posted for review two months prior to the Ice Hockey Summit: Action on Concussion. Focused presentations devoted specifically to concussion in ice hockey were presented during the Summit and break out sessions were used to develop strategies to reduce concussion in the sport. This proceedings and a detailed scientific review (a matrix of solutions) were written to disseminate the evidence based information and resulting concussion reduction strategies. The manuscripts were reviewed by the authors, advisors and contributors to ensure that the opinions and recommendations reflect the current level of knowledge on concussion in hockey. RESULTS Six components of a potential solution were articulated in the Rationale paper and became the topics for breakout groups that followed the professional, scientific lectures. Topics that formed the core of the action plan were: metrics and databases; recognizing,managing, and return to play; hockey equipment and ice arenas;prevention and education; rules and regulations; and expedient communication of the outcomes. The attendees in breakout sessions identified action items for each section. The most highly ranked action items were brought to a vote in the open assembly, using an Audience Response System (ARS). The strategic planning process was conducted to assess: Where are we at? ; Where must we get to? ; and What strategies are necessary to make progress on the prioritized action items? CONCLUSIONS Three prioritized action items for each component of the solution and the percentage of the votes received are listed in the body of this proceeding.
The association between physical fitness and academic achievement in Texas state house legislative districts: an ecologic study.

BACKGROUND The association of physical fitness with cognitive function in children and adolescents is unclear. The purpose of this ecological study was to describe the association between academic achievement, body mass index (BMI), and cardiovascular fitness (CVF) in a large sample of elementary, middle, and high school students in Texas. METHODS FITNESSGRAM(®) results for 2,550,144 students were matched with standardized composite academic test (TAKS) results from 2008 to 2009. Analyses were conducted on the percent of students meeting TAKS standards by BMI and CVF quintiles. Analyses of variance with Tukey adjustment examined differences between the most favorable 5th quintile (referent) and all other quintiles. RESULTS The prevalence of students meeting the TAKS standard was significantly higher in the highest fitness category for BMI and CVF compared to all other categories, regardless of sex or grade category (p < .05). Linear modeling suggested a 5% increase in the prevalence of students meeting healthy BMI and CVF standards would result in a 2.25% and 0.65% increase in the prevalence of students meeting the TAKS standard (both p < .05). CONCLUSION Findings suggest a healthy BMI and CVF are associated with higher academic achievement, and the need for additional research examining the role of potential confounders and/or effect modifiers longitudinally.
Wound Healing and Anti-inflammatory Effects of Topical Hyaluronic Acid Injection in Surgical-Site Infection Caused by Staphylococcus aureus

Surgical-site infection (SSI) is a common postoperative complication, primarily caused by Staphylococcus aureus. S aureus produces hyaluronidase which degrades hyaluronic acid (HA). HA prevents bacterial proliferation and has anti-inflammatory effects to promote wound healing. We evaluated the effect of HA injection with systemic antibiotics for prevention and treatment of SSIs caused by S aureus. An open wound was created on the dorsum of 40 rats. The wound bed was sutured with S aureus inoculated thread. The test group was injected with HA (HA group), and the control group received a subcutaneous injection of normal saline (NS group). All groups were then treated with intraperitoneal cefazolin injection. The sutures were removed 2 days after the procedure. Gross pathology, bacterial count, and wound histology were assessed at days 2, 4, 6, and 8 postprocedure. The HA group showed a significant reduction in the wound area compared with the control group on gross pathology (at days 8 postprocedure, 36.54% ± 6.12% vs 50.59% ± 5.50%, P < .001). The HA group showed significantly better wound healing than the control group on histological analysis, including assessment of abscess, neutrophilic infiltration, and necrosis (4.2 ± 1.2 vs 11.5 ± 2.1, P < .001). The HA group showed a lower bacterial count compared with the NS group, but the result was not significant statistically (at days 6 postprocedure, 5.11 ± 0.31 vs 5.91 ± 0.35 logCFU/mL, P = .706). In conclusion, immediate local injection of HA in wounds can reduce SSI occurrence and promote wound healing in an animal model.
Analysis of the ZAR 1 Immune Complex Reveals Determinants for Immunity and Molecular Interactions 1 [ OPEN ]

Plants depend on innate immunity to prevent disease. Plant pathogenic bacteria, like Pseudomonas syringae and Xanthomonas campestris, use the type III secretion system as a molecular syringe to inject type III secreted effector (T3SE) proteins in plants. The primary function of most T3SEs is to suppress immunity; however, the plant can evolve nucleotide-binding domain-leucine-rich repeat domain-containing proteins to recognize specific T3SEs. The AtZAR1 NLR induces strong defense responses against P. syringae and X. campestris. The P. syringae T3SE HopZ1a is an acetyltransferase that acetylates the pseudokinase AtZED1 and triggers recognition by AtZAR1. However, little is known about the molecular mechanisms that lead to AtZAR1-induced immunity in response to HopZ1a. We established a transient expression system in Nicotiana benthamiana to study detailed interactions among HopZ1a, AtZED1, and AtZAR1. We show that the AtZAR1 immune pathway is conserved in N. benthamiana and identify AtZAR1 domains, and residues in AtZAR1 and AtZED1, that are important for immunity and protein-protein interactions in planta and in yeast (Saccharomyces cerevisiae). We show that the coiled-coil domain of AtZAR1 oligomerizes, and this domain acts as a signal to induce immunity. This detailed analysis of the AtZAR1-AtZED1 protein complex provides a better understanding of the immune signaling hub controlled by AtZAR1.
Lacto-N-biosidase Encoded by a Novel Gene of Bifidobacterium longum Subspecies longum Shows Unique Substrate Specificity and Requires a Designated Chaperone for Its Active Expression*

Background: Phenotypically lacto-N-biosidase-positive Bifidobacterium longum JCM1217 does not possess a gene homologous to previously identified lacto-N-biosidase. Results: Hypothetical proteins BLLJ_1505 and BLLJ_1506 encode lacto-N-biosidase and its designated chaperone, respectively. Conclusion: The enzyme showed unique and unexpected substrate specificity. Significance: The enzyme is important for understanding how B. longum consumes human milk oligosaccharides and also may serve as a new tool in glycobiology. Infant gut-associated bifidobacteria possess species-specific enzymatic sets to assimilate human milk oligosaccharides, and lacto-N-biosidase (LNBase) is a key enzyme that degrades lacto-N-tetraose (Galβ1–3GlcNAcβ1–3Galβ1–4Glc), the main component of human milk oligosaccharides, to lacto-N-biose I (Galβ1–3GlcNAc) and lactose. We have previously identified LNBase activity in Bifidobacterium bifidum and some strains of Bifidobacterium longum subsp. longum (B. longum). Subsequently, we isolated a glycoside hydrolase family 20 (GH20) LNBase from B. bifidum; however, the genome of the LNBase+ strain of B. longum contains no GH20 LNBase homolog. Here, we reveal that locus tags BLLJ_1505 and BLLJ_1506 constitute LNBase from B. longum JCM1217. The gene products, designated LnbX and LnbY, respectively, showed no sequence similarity to previously characterized proteins. The purified enzyme, which consisted of LnbX only, hydrolyzed via a retaining mechanism the GlcNAcβ1–3Gal linkage in lacto-N-tetraose, lacto-N-fucopentaose I (Fucα1–2Galβ1–3GlcNAcβ1–3Galβ1–4Glc), and sialyllacto-N-tetraose a (Neu5Acα2–3Galβ1–3GlcNAcβ1–3Galβ1–4Gal); the latter two are not hydrolyzed by GH20 LNBase. Among the chromogenic substrates examined, the enzyme acted on p-nitrophenyl (pNP)-β-lacto-N-bioside I (Galβ1–3GlcNAcβ-pNP) and GalNAcβ1–3GlcNAcβ-pNP. GalNAcβ1–3GlcNAcβ linkage has been found in O-mannosyl glycans of α-dystroglycan. Therefore, the enzyme may serve as a new tool for examining glycan structures. In vitro refolding experiments revealed that LnbY and metal ions (Ca2+ and Mg2+) are required for proper folding of LnbX. The LnbX and LnbY homologs have been found only in B. bifidum, B. longum, and a few gut microbes, suggesting that the proteins have evolved in specialized niches.