Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphocreatine resynthesis is not affected by creatine loading.

PURPOSE Oral creatine supplementation has been shown to improve power output during high intensity intermittent muscle contractions. Facilitated muscle phosphocreatine (PCr) resynthesis, by virtue of elevated intracellular PCr concentration, might contribute to this ergogenic action. Therefore, the effect of creatine loading (C: 25 g X d(-1) for 5 d) on muscle PCr breakdown and resynthesis and muscle performance during high intensity intermittent muscle contractions was investigated. METHODS A double-blind randomized cross-over study was performed in young healthy male volunteers (N = 9). 31P-NMR spectroscopy of the m. gastrocnemius and isokinetic dynamometry of knee-extension torque were performed before and after 2 and 5 d of either placebo (P) or C administration. RESULTS Compared with P, 2 and 5 d of C increased (P < 0.05) resting muscle PCr concentration by 11% and 16%, respectively. Furthermore, torque production during maximal intermittent knee extensions, including the first bout of contractions, was increased (P < 0.05) by 5-13% by either 2 or 5 d of C. However, compared with P, the rate of PCr breakdown and resynthesis during intermittent isometric contractions of the calf was not significantly affected by C. CONCLUSION Creatine loading raises muscle PCr concentration and improves performance during rapid and dynamic intermittent muscle contractions. Creatine loading does not facilitate muscle PCr resynthesis during intermittent isometric muscle contractions.
Nonlinear effects resulting from the interaction of a large-scale Alfvén wave with a density filament

This analytic study investigates the nonlinear plasma response when a shear Alfven wave of large transverse scale interacts with a field-aligned density perturbation whose transverse scale is comparable to the electron skin depth. The interaction between the large-scale wave and the density perturbation produces a small-scale shear mode [T. Drozdenko and G. J. Morales, Phys. Plasmas 7, 823 (2000)], which facilitates the transfer of energy to the plasma particles. The beat of the large-scale wave with the small-scale wave can lead to ponderomotive forces and flows in the plasma, or, if the field amplitudes of the small-scale wave are large enough to produce oscillatory velocities comparable to the electron thermal velocity, a streaming instability may develop. In this study, it is demonstrated that nonlinear effects arise in regions remote from the seed perturbation, and estimates of the amplitude of the large-scale wave necessary to produce significant ponderomotive density changes or trigger significant .
Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer.

PURPOSE Topotecan and paclitaxel were evaluated in a randomized, multicenter study of patients with advanced epithelial ovarian carcinoma who had progressed during or after one platinum-based regimen. PATIENTS AND METHODS Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 112) or paclitaxel (175 mg/m2) infused over 3 hours every 21 days (n = 114). Patients had bidimensionally measurable disease and were assessed for efficacy and toxicity. RESULTS Response rate was 23 of 112 (20.5%) in topotecan-treated patients and 15 of 114 (13.2%) in paclitaxel-treated patients (P = .138). Disease stabilization for at least 8 weeks was noted in 30% of patients with topotecan and 33% of patients with paclitaxel. Median durations of response to topotecan and paclitaxel were 32 and 20 weeks, respectively (P = .222) and median times to progression were 23 and 14 weeks, respectively (P = .002). Median survival was 61 weeks for topotecan and 43 weeks for paclitaxel (P = .515). Response rates for topotecan and paclitaxel were 13.3% versus 6.7% (P = .303) in resistant patients (not responded to prior platinum-based therapy or progressed within 6 months of an initial response) and 28.8% versus 20.0% (P = .213) in sensitive patients (progressed > 6 months after response). Neutropenia was significantly more frequent on the topotecan arm 79% versus paclitaxel arm 23% (P < .01). It was short-lasting and noncumulative in both arms. Nonhematologic toxicities were generally mild (grades 1 to 2) for both agents. CONCLUSION Topotecan has efficacy at least equivalent to paclitaxel manifested by the higher response rate and significantly longer time to progression.
Generation of iPSCs from Genetically Corrected Brca2 Hypomorphic Cells: Implications in Cell Reprogramming and Stem Cell Therapy

Fanconi anemia (FA) is a complex genetic disease associated with a defective DNA repair pathway known as the FA pathway. In contrast to many other FA proteins, BRCA2 participates downstream in this pathway and has a critical role in homology‐directed recombination (HDR). In our current studies, we have observed an extremely low reprogramming efficiency in cells with a hypomorphic mutation in Brca2 (Brca2Δ27/Δ27), that was associated with increased apoptosis and defective generation of nuclear RAD51 foci during the reprogramming process. Gene complementation facilitated the generation of Brca2Δ27/Δ27 induced pluripotent stem cells (iPSCs) with a disease‐free FA phenotype. Karyotype analyses and comparative genome hybridization arrays of complemented Brca2Δ27/Δ27 iPSCs showed, however, the presence of different genetic alterations in these cells, most of which were not evident in their parental Brca2Δ27/Δ27 mouse embryonic fibroblasts. Gene‐corrected Brca2Δ27/Δ27 iPSCs could be differentiated in vitro toward the hematopoietic lineage, although with a more limited efficacy than WT iPSCs or mouse embryonic stem cells, and did not engraft in irradiated Brca2Δ27/Δ27 recipients. Our results are consistent with previous studies proposing that HDR is critical for cell reprogramming and demonstrate that reprogramming defects characteristic of Brca2 mutant cells can be efficiently overcome by gene complementation. Finally, based on analysis of the phenotype, genetic stability, and hematopoietic differentiation potential of gene‐corrected Brca2Δ27/Δ27 iPSCs, achievements and limitations in the application of current reprogramming approaches in hematopoietic stem cell therapy are also discussed. Stem Cells 2014;32:436–446
The Impact of IOS-Enabled Business Process Change on Business Outcomes: Transformation of the Value Chain of Japan Airlines

This paper explores the relationship between IOS-enabled business process change and business outcomes. A generic framework for analyzing IT-enabled business process change is applied to a case study analysis of Japan Airlines (JAL). Drawing on a resource-based view of the firm, we investigate the ways in which IOS not only contributed to JAL's improved competitiveness but also enabled it more fully to leverage its strategic value chain as an engine of growth and a new source of competitive advantage. Our focus is on JAL's strategic use of the AXESS Computer Reservation System and Electronic Data Interchange, developed with a clear strategic intention to support JAL's emerging strategies on customer service, sales, value chain logistics coordination, and cost reduction. JAL's collaboration with the IOS-transformed virtual value chain firms significantly contributed to JAL's business growth and competitiveness. JAL's time-based competitiveness has been improved through its IOS-enabled interfirm joint product innovation cycle time reduction.
“Toward a Social Profile of the Aged Black Population in the United States: An Exploratory Study”

A stratified random sample of black men and women aged 70 and over was developed in two high rise age segregated urban housing units. Normative activity was classified in terms of three life styles: alone, reciprocal, and nonreciprocal. An internal comparison was made with a black sample and an external comparison with a white sample differing on several major demographic characteristics. Although the modal activity pattern was to do things alone, the findings were equivocal with respect to the disengagement framework. Involvement with others tended to increase with age, and was usually of a religious or leisure time nature. Findings of this study suggest the desirability for encouraging flexible life style options.
Procalcitonin used as a marker of infection in the intensive care unit.

OBJECTIVE To determine the value of procalcitonin (ProCT) as a marker of infection in critically ill patients. DESIGN Prospective, observational study. SETTING Medicosurgical department of intensive care (31 beds). PATIENTS One hundred eleven infected and 79 noninfected patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS ProCT and C-reactive protein (CRP) concentrations were monitored daily. The best cutoff values for ProCT and CRP were 0.6 ng/mL and 7.9 mg/dL, respectively. Compared with CRP, ProCT had a lower sensitivity (67.6 vs. 71.8), specificity (61.3 vs. 66.6), and area under the receiver operating characteristic curve (0.66 vs. 0.78, p < .05). The combination of ProCT and CRP increased the specificity for infection to 82.3%. In the infected patients, plasma ProCT, but not CRP, values were higher in nonsurvivors than in survivors. Infected patients with bacteremia had higher ProCT concentrations than those without bacteremia, but similar CRP concentrations. ProCT levels were particularly high in septic shock patients. CONCLUSIONS ProCT is not a better marker of infection than CRP in critically ill patients, but it can represent a useful adjunctive parameter to identify infection and is a useful marker of the severity of infection.
Media Advocacy: Lessons from Community Experiences

Media advocacy is the strategic use of mass media and community organizing as a resource for advancing a social or public policy initiative. Across the United States, communities are using media advocacy to promote healthier public policies and environments. The U.S. Center for Substance Abuse Prevention commissioned numerous case studies of media advocacy on alcohol and tobacco issues in a diverse array of communities, including efforts in African-American and Latino communities or using computer-based electronic communication systems. The paper describes these efforts briefly, and summarizes lessons learned, including: media advocacy can lead to larger victories when used as a complement to community organizing in the context of a larger strategic vision for policy change; like policy advocacy, media advocacy is best done in the context of clear long-term goals; conscious framing, guiding the choice of spokespeople, visuals, and messages, can alter media coverage and public debate of health policies; advocates need to respect the media but also remember that they have power in relation to the media; and media advocacy is often controversial and not suited to every situation. The case studies show that media advocacy is a potent tool for public health workers, making an important contribution to campaigns to promote healthier public policies.
An Altered T Cell Repertoire in MECL-1-Deficient Mice1

Immunoproteasome subunits low-molecular mass polypeptide (LMP)2 and LMP7 affect Ag presentation by MHC class I molecules. In the present study, we investigated the function of the third immunosubunit LMP10/multicatalytic endopeptidase complex-like (MECL)-1 (β2i) in MECL-1 gene-targeted mice. The number of CD8+ splenocytes in MECL-1−/− mice was 20% lower than in wild-type mice. Infection with lymphocytic choriomeningitis virus (LCMV) elicited a markedly reduced cytotoxic T cell (CTL) response to the LCMV epitopes GP276–286/Db and NP205–212/Kb in MECL-1−/− mice. The weak CTL response to GP276–286/Db was not due to an impaired generation of this epitope but was attributed to a decreased precursor frequency of GP276–286/Db-specific T cells. The expansion of TCR-Vβ10+ T cells, which contain GP276–286/Db-specific cells, was reduced in LCMV-infected MECL-1−/− mice. Taken together, our data reveal an in vivo function of MECL-1 in codetermining the T cell repertoire for an antiviral CTL response.
Accumulation of heavy‐metal ions by Zoogloea ramigera

Biomass has been produced from glucose using the organism Zoogloea ramigera 115. This biomass has been used to remove copper, cadmium, and uranyl ions from water solutions. The metal uptake was studied with two different methods: either by spectrophotometric measurements on the solutions after flocculation or by potentiometric measurements with amalgam electrodes in order to follow the entire complex formation. The metal–biopolymer interaction in 0.1M NaClO4 is practically the same as when no neutral salt is added. The metal uptake is dependent on pH and is selective. A reversible process suitable for metal complexation is described.
Semon's Law Revisited: An Electromyographic Analysis of Laryngeal Synkinesis

Felix Semon's fascination with vocal fold paralysis led to his theory attributing medialization to isolated abductor paralysis. Later, the Wagner-Grossman hypothesis explained the vocal fold position on the basis of cricothyroid muscle activity. Other authors since that time have dispelled the notion of a role for the cricothyroid muscle in vocal fold position with paralysis. Utilizing laryngeal electromyography, several authors have found electrical activity suggestive of variable reinnervation and synkinesis. This current study included patients with persistent vocal fold immobility. Fourteen patients were studied: half with good voice and half with poor voice. The patients with good voice had a relatively normal arytenoid position and evidence of synkinesis. The group with poor voice had an arytenoid that tipped into the laryngeal inlet and had denervation or poor reinnervation. This suggests that the medialization and upright position of the arytenoid is due to synkinesis.
An ATM- and Rad3-related (ATR) Signaling Pathway and a Phosphorylation-Acetylation Cascade Are Involved in Activation of p53/p21Waf1/Cip1 in Response to 5-Aza-2′-deoxycytidine Treatment*

Most agents that damage DNA act through posttranslational modifications of p53 and activate its downstream targets. However, whether cellular responses to nucleoside analogue-induced DNA damage also operate through p53 posttranslational modification has not been reported. In this study, the relationship between p53 activation and its posttranslational modifications was investigated in the human cancer cell lines A549 and HCT116 in response to 5-aza-2′-deoxycytidine (5-aza-CdR) or cytarabine treatment. 5-Aza-CdR induces p53 posttranslational modifications through activation of an ATM- and Rad3-related (ATR) signaling pathway, and 5-aza-CdR-induced association of replication protein A with chromatin is required for the binding of ATR to chromatin. Upon treatment with 5-aza-CdR, ATR activation is clearly associated with p53 phosphorylation at Ser15, but not at Thr18, Ser20, or Ser37. This specific p53 phosphorylation at Ser15 in turn results in acetylation of p53 at Lys320 and Lys373/Lys382 through transcriptional cofactors p300/CBP-associated factor and p300, respectively. These p53 posttranslational modifications are directly responsible for 5-aza-CdR induced p21Waf1/Cip1 expression because the binding activity of acetylated p53 at Lys320/Lys373/Lys382 to the p21Waf1/Cip1 promoter, as well as p21Waf1/Cip1 expression itself are significantly increased after 5-aza-CdR treatment. It is of interest that p53 phosphorylation at Ser15 and acetylations at Lys320/Lys373/Lys382 mutually interact in the 5-aza-CdR induced p21Waf1/Cip1 expression shown by transfection of artificially mutated p53 expression vectors including S15A, K320R, and K373R/K382R into p53-null H1299 cells. These data taken together show for the first time that 5-aza-CdR activates the ATR signaling pathway, which elicits a specific p53 phosphorylation-acetylation cascade to induce p21Waf1/Cip1 expression.
Statistically Speaking

Delivering definitive airway management using rapid sequence induction in a pre-hospital setting can indeed be a daunting task with little margin for error. Minor infractions at any step in the sequence can rapidly culminate to create an airway catastrophe. Nowhere else would the aggregation of marginal gains [1] reap more benefit than in such adverse conditions. In this issue of Anaesthesia, Angerman and colleagues [2] evaluated the effect of introducing a videolaryngoscope and a bougie into a standardised protocol for airway management. They demonstrated > 12% increase in first-attempt tracheal intubation success in a ‘before and after’ comparison. As it is widely accepted that airway complications increase with the increased number of attempts, this would represent a potentially significant improvement in patient care [3].
Species-specific PCR detection of malaria parasites by microtiter plate hybridization: clinical study with malaria patients

A simple and convenient PCR method that amplifies the 18S rRNA genes has been developed for the purpose of detecting and differentiating four species causing malaria in humans. The advantage of the assay is that the biotinylated PCR product is visualized following hybridization with specific probes which are immobilized on plate wells (microtiter plate hybridization). This method has been previously evaluated in a field study and was found to be sensitive and specific for the detection of Plasmodium falciparum and Plasmodium vivax. In the current study, the microtiter plate hybridization PCR method was evaluated by using blood specimens from malaria patients. All of 36 cases of falciparum malaria, 26 of 27 cases of vivax malaria, all of 11 cases of ovale malaria, and 2 cases of malariae malaria were diagnosed species specifically by the PCR method. There were four smear-negative, PCR-positive cases that seemed to correspond to the convalescent stage of malaria. In contrast, 30 cases for which the diagnosis of malaria has been excluded on the basis of microscopy and clinical courses showed negative PCR results. By comparing parasite densities and PCR results following antimalarial treatment of some patients, it was revealed that the PCR results largely paralleled the parasite densities and that PCR could detect as few as 10 parasites per microliter of blood. We conclude that this PCR method is highly sensitive and specific for the detection of all four parasite species and can serve as a useful supplement to microscopy for the clinical management of malaria.
Differential Interaction of Tomosyn with Syntaxin and SNAP25 Depends on Domains in the WD40 β-Propeller Core and Determines Its Inhibitory Activity*

Background: Tomosyn's WD40 domain affects its ability to inhibit exocytosis. Results: Unstructured loops in the WD40 domain are involved in tomosyn's diffusion and organization on the plasma membrane. Conclusion: These key loops mediate tomosyn's binding to the SNARE protein SNAP25. Significance: Novel findings regarding tomosyn's membranal distribution and interactions shed new light on regulation of exocytosis by the SNARE complex and tomosyn. Neuronal exocytosis depends on efficient formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes and is regulated by tomosyn, a SNARE-binding protein. To gain new information about tomosyn's activity, we characterized its mobility and organization on the plasma membrane (PM) in relation to other SNARE proteins and inhibition of exocytosis. By using direct stochastic optical reconstruction microscopy (dSTORM), we found tomosyn to be organized in small clusters adjacent to syntaxin clusters. In addition, we show that tomosyn is present in both syntaxin-tomosyn complexes and syntaxin-SNAP25-tomosyn complexes. Tomosyn mutants that lack residues 537–578 or 897–917 from its β-propeller core diffused faster on the PM and exhibited reduced binding to SNAP25, suggesting that these mutants shift the equilibrium between tomosyn-syntaxin-SNAP25 complexes on the PM to tomosyn-syntaxin complexes. As these deletion mutants impose less inhibition on exocytosis, we suggest that tomosyn inhibition is mediated via tomosyn-syntaxin-SNAP25 complexes and not tomosyn-syntaxin complexes. These findings characterize, for the first time, tomosyn's dynamics at the PM and its relation to its inhibition of exocytosis.
Antiplatelet Therapy Recent Advances

Haemostatic function of platelets is vital & their pathological role is potentially lethal. In pathological states there is over activation and aggregation of blood platelets resulting in atherothrombosis causes various states from angina to acute coronary syndromes, stroke and peripheral artery diseases. Platelets are anuclear subcellular fragments derived from megakaryocytes that circulate in blood as small anucleate ovoid discs. Under normal conditions they do not interact with the intact endothelial cell lining throughout the vasculature. Disruption of this well-regulated balance leads to pathologic conditions, such as thrombosis and bleeding. Although controlled plug formation is desired for the prevention of excessive blood loss and for promoting wound healing, several pathological conditions may result in the formation of occlusive thrombi leading to severe clinical complications, including myocardial infarction and ischemic stroke. The formation of a stable platelet plug occurs in three different stages: platelet adhesion, amplification of platelet activation and platelet aggregation. Many strategies have been pursued to lower the risk of pathological thrombus formation by interfering either with platelet adhesion, activation or aggregation. We here review clinically established antiplatelet targets and promising new antiplatelet strategies that are under investigation.
Perinatal mortality and morbidity--the Scottish perspective.

Although perinatal mortality has continued to fall in Scotland during the last decade, there has been little change during the last three years i.e. 8.9, 8.9, 8.7 per thousand births respectively. Many deaths still result from antepartum haemorrhage and unknown causes so the Scottish Perinatal Mortality group is undertaking a confidential enquiry into the deaths of all normally formed infants of birthweight greater than 2500 g. The other major cause of prenatal death i.e. preterm delivery is also associated with a significant risk of neurological impairment. Results from the Scottish Low Birthweight Study show that 5.7 per cent and 9.5 per cent of very low birthweight infants have severe and moderate disability respectively, reveal once again the importance of research into the primary and secondary prevention of preterm delivery and the care of the preterm neonate.
Training with a mirror in rehabilitation of the hand

Treatment with a mirror gives an illusion of function in a missing or non-functioning hand. The method is based on the concept that the central representation of phantoms and body image can change rapidly, and has been described in the treatment of phantom pain and stroke. We show in three pilot cases new applications for the use of the mirror in rehabilitation after hand surgery.