Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidermal Receptor Activator of NF-κB Ligand Controls Langerhans Cells Numbers and Proliferation12

Langerhans cells (LC) are the dendritic APC population of the epidermis, where they reside for long periods and are self-replicating. The molecular signals underlying these characteristics are unknown. The TNF superfamily member receptor activator of NF-κB ligand (RANKL, TNFSF11) has been shown to sustain viability of blood dendritic cells in addition to its role in promoting proliferation and differentiation of several cell types, notably osteoclasts. In this study, we have studied expression of the RANKL system in skin and have defined a key role for this molecule in LC homeostasis. In vitro and in vivo, human KC expressed RANKL and epidermal LC expressed cell surface RANK. In vitro, RANKL sustained CD34+ progenitor-derived LC viability following 72-h cultures in cytokine-free medium (79.5 ± 1% vs 55.2 ± 5.7% live cells, respectively; n = 4; p < 0.05). In vivo, RANKL-deficient mice displayed a marked reduction in epidermal LC density (507.1 ± 77.2 vs 873.6 ± 41.6 LC per mm2; n = 9; p < 0.05) and their proliferation was impaired without a detectable effect on apoptosis. These data indicate a key role for the RANKL system in the regulation of LC survival within the skin and suggest a regulatory role for KC in the maintenance of epidermal LC homeostasis.
Cyclic di-GMP Modulates Gene Expression in Lyme Disease Spirochetes at the Tick-Mammal Interface To Promote Spirochete Survival during the Blood Meal and Tick-to-Mammal Transmission

ABSTRACT Borrelia burgdorferi, the Lyme disease spirochete, couples environmental sensing and gene regulation primarily via the Hk1/Rrp1 two-component system (TCS) and Rrp2/RpoN/RpoS pathways. Beginning with acquisition, we reevaluated the contribution of these pathways to spirochete survival and gene regulation throughout the enzootic cycle. Live imaging of B. burgdorferi caught in the act of being acquired revealed that the absence of RpoS and the consequent derepression of tick-phase genes impart a Stay signal required for midgut colonization. In addition to the behavioral changes brought on by the RpoS-off state, acquisition requires activation of cyclic di-GMP (c-di-GMP) synthesis by the Hk1/Rrp1 TCS; B. burgdorferi lacking either component is destroyed during the blood meal. Prior studies attributed this dramatic phenotype to a metabolic lesion stemming from reduced glycerol uptake and utilization. In a head-to-head comparison, however, the B. burgdorferi Δglp mutant had a markedly greater capacity to survive tick feeding than B. burgdorferi Δhk1 or Δrrp1 mutants, establishing unequivocally that glycerol metabolism is only one component of the protection afforded by c-di-GMP. Data presented herein suggest that the protective response mediated by c-di-GMP is multifactorial, involving chemotactic responses, utilization of alternate substrates for energy generation and intermediary metabolism, and remodeling of the cell envelope as a means of defending spirochetes against threats engendered during the blood meal. Expression profiling of c-di-GMP-regulated genes through the enzootic cycle supports our contention that the Hk1/Rrp1 TCS functions primarily, if not exclusively, in ticks. These data also raise the possibility that c-di-GMP enhances the expression of a subset of RpoS-dependent genes during nymphal transmission.
Noise and drift characterization of direct laser to RF conversion scheme for the laser based synchronization system for FLASH at DESY

Next generation FELs (Free Electron Lasers) require a long and short term stable synchronization of RF reference signals with an accuracy of 10 fs. To overcome the limitations of a coaxial cable based system, an optical synchronization system is being developed for FLASH at DESY. It is based on the distribution of sub-ps optical pulses, where the timing information is encoded in the precise repetition rate. The optical pulse train has to be converted into an RF signal to provide a local reference for calibration and operation of RF based devices. The drift and jitter performance of the optical to RF converter influences directly the phase stability of the accelerator. Three different methods for optical to RF converters, namely the direct detection using a photodiode, injection locking of a DRO, and a sagnac-loop interferometer are currently under investigation. In this paper we concentrate on the jitter and drift performance of the direct photodiode conversion and show its limitations.
The Effects of Triiodothyronine Augmentation on Antithrombin III Levels in Sepsis

Sepsis and multisystem organ failure are often associated with disseminated intravascular coagulation and consumption of coagulation inhibitors such as antithrombin III (ATIII). The “sick euthyroid syndrome” is also seen in association with significant illnesses and consists of decreased levels of circulating triiodothyronine (T3). We evaluated whether T3 supplementation would affect ATIII levels in septic rats. Thirty Sprague-Dawley rats were divided into three groups: sham laparotomy (S) plus saline, cecal ligation and puncture (CLP) plus saline, and CLP plus T3 (3 ng/hour) via an osmotic minipump. Twenty-four hours after laparotomy blood was drawn, and T3 and ATIII levels were then compared with baseline values. T3 supplementation partially negated the sepsis-induced decrease in circulating T3 levels. The levels are expressed as percentage change from the levels before surgery (S, -12.9 ± 3.1; CLP, -60.0 ± 5.3; CLP + T3, -34.9 ± 4.3; mean ± standard error; P < 0.05). T3 supplementation also statistically changed the percentage difference in ATIII levels toward the control (S, 9.6 ± 2.8; CLP, - 37.9 ± 5.4; CLP + T3, -16.0 ± 4.5; mean ± standard error; P < 0.01). T3 supplementation reduced the sepsis-induced decrease in ATIII levels. Whether this was accomplished by decreased consumption or increased production of ATIII via the direct anabolic effect of T3 on acute-phase protein synthesis in the liver is unknown and warrants further investigation.
Dissociation between unconscious motor response facilitation and conflict in medial frontal areas

Masked prime tasks have shown that sensory information that has not been consciously perceived can nevertheless modulate behavior. The neuronal correlates of behavioral manifestations of visuomotor priming remain debated, particularly with respect to the distribution and direction (i.e. increase or decrease) of activity changes in medial frontal areas. Here, we predicted that these discrepant results could be accounted for by two automatic and unconscious processes embedded in this task: response conflict and facilitation. We used event‐related functional magnetic resonance imaging (fMRI), as 24 healthy participants had to respond, as fast as possible, to a target arrow presented immediately after a subliminal masked prime arrow. There were three experimental conditions defined by the prime–target relationship: compatible, incompatible, and neutral. The classical visuomotor priming effect was reproduced, with relatively longer reaction times (RTs) in incompatible trials. Longer RTs in incompatible than in neutral trials were specifically associated with stronger blood oxygen level‐dependent (BOLD) activity in a conflict‐related network comprising the anterior cingulate cortex and right frontal associative areas. Motor response facilitation as shown by shorter RTs in compatible than in neutral trials was associated with reduced activation in a motor preparation network including the medial and lateral premotor cortices, as a result of the repetition suppression of the fMRI BOLD signal. The present results provide new insights into automatic and unconscious visuomotor priming processes, suggesting an involvement of either a cognitive or motor network, depending on the prime–target relationship.
Standardization of Low Molecular Weight Heparins : A Collaborative Study

Summary A collaborative study was carried out, in which eight laboratories each assayed eight low molecular weight (LMW) heparins against the International Standard (IS) for heparin. APTT assays and three types of anti-Xa method were used. The results of this study showed that: 1. LMW heparins cannot be validly assayed against the IS by APTT or anti-Xa methods. 2. Potencies of LMW heparins vs. the IS differed considerably between the four types of assay method used and also between different laboratories using the same type of method. 3. Adoption of a single LMW heparin standard would improve validity, improve inter-laboratory variation, and largely abolish the differences between the three types of anti-Xa method. However, since calibration of a LMW heparin standard against the IS would give potencies that differ widely by the different assay methods, a single assay method such as the anti-Xa amidolytic, plasma, would need to be chosen for this calibration.
Exercise effects on the size and metabolic properties of soleus fibers in hindlimb-suspended rats.

The soleus atrophies rapidly when a rat is subjected to hindlimb suspension (HS), probably as a result of a decrease in the force encountered by the muscle. To test this premise, adult female rats were HS and half the rats were exercised (HS-EX) on a treadmill for 1.5 h.d-1 at 20 m.min-1 and a 30% grade. After 4 weeks, the midbelly of the soleus was prepared for histochemical analysis. Fibers were typed as dark or light staining for myosin ATPase, alkaline preincubation. Fiber size and quantitative histochemical enzyme activities of succinate dehydrogenase (SDH) were determined using a computer enhanced image processing system. In comparison to age-matched controls, the soleus wet weight was 69 and 30% smaller in HS and HS-EX rats. The mean cross sectional area of the dark ATPase fibers was reduced by 46 and 18% and light ATPase fibers by 69 and 48% in the HS and HS-EX, respectively. The percent dark ATPase fibers increased from 10% in the control rats to 19 and 17% in the HS and HS-EX. In both suspended groups, SDH activities in light ATPase fibers were 40% higher than control. The SDH activity of the dark ATPase fibers of HS-EX was 20% higher than control, while the dark ATPase fibers of HS were similar to control. To determine the degree to which these increases in SDH could be related to reductions in fiber size rather than increases in the actual amount of protein, integrated activity (activity/min x area) was calculated per fiber. (ABSTRACT TRUNCATED AT 250 WORDS)
Screening pneumococci for penicillin resistance

Eighty-four pneumococci with various MICs of penicillin (38 with MICs of less than or equal to 0.06 micrograms/ml [susceptible], 35 with MICs of 0.12 to 1.0 micrograms/ml [relatively resistant], and 11 with MICs of greater than 1.0 micrograms/ml [resistant] ) were screened by a disk diffusion test using oxacillin and methicillin to see how well they distinguished penicillin-susceptible strains from those with decreased susceptibility to penicillin. The effects of Mueller-Hinton agar plus 5% sheep blood and Trypticase soy agar plus 5% sheep blood and two atmospheres, ambient air and a candle extinction jar (increased CO2), were compared. There were no obvious differences between the effects of the two media, but zones were generally larger in ambient air than in increased CO2. Although the oxacillin test can separate penicillin-susceptible and -resistant strains, it cannot separate penicillin-resistant from relatively penicillin-resistant strains by using the breakpoint of less than 20 mm recommended by the National Committee for Clinical Laboratory Standards. When the 20-mm breakpoint was applied to methicillin, 12% of the relatively resistant strains tested were erroneously classified as susceptible. When different breakpoints were used for methicillin, there was better separation of the two classes of penicillin-resistant isolates, but a few relatively resistant strains were still classified as susceptible. We recommend that oxacillin, not methicillin, be used as the screening agent with Mueller-Hinton sheep blood agar and ambient air incubation and that the breakpoint be less than 20 mm to indicate resistance or relative resistance.
Identification of an RNA-binding Site in the ATP Binding Domain of Escherichia coli Rho by H2O2/Fe-EDTA Cleavage Protection Studies*

Transcription factor Rho is a ring-shaped, homohexameric protein that causes transcript termination through actions on nascent RNAs that are coupled to ATP hydrolysis. The Rho polypeptide has a distinct RNA binding domain of known structure as well as an ATP binding domain for which a structure has been proposed based on homology modeling. Treatment of Rho with H2O2 in the presence of Fe-EDTA caused single-cut cleavage at a number of points that coincide with solvent-exposed loops in both the known and predicted structures, thereby providing support for the validity of the tertiary and quaternary structural models of Rho. The binding of ATP caused one distinct change in the cleavage pattern, a strong protection at a cleavage point in the P-loop of the ATP binding domain. Binding of RNA and single-stranded DNA (poly(dC)) caused strong protection at several accessible parts of the oligosaccharide/oligonucleotide binding (OB) fold in the RNA binding domain. RNA molecules but not DNA molecules also caused a strong, ATP-dependent protection at a cleavage site in the predicted Q-loop of the ATP binding domain. These results suggest that Rho has two distinct binding sites for RNA. Besides the site composed of multiples of the RNA binding domain, to which single-stranded DNA as well as RNA can bind, it has a separate, RNA-specific site on the Q-loop in the ATP binding domain. In the proposed quaternary structure of Rho, the Q-loops from the six subunits form the upper entrance to the hole in the ring-shaped hexamer through which the nascent transcript is translocated by actions coupled to ATP hydrolyses.
Radiofrequency ablation for the treatment of liver tumors in the caudate lobe.

PURPOSE To evaluate the effectiveness of radiofrequency (RF) ablation for liver tumors located in the caudate lobe. MATERIALS AND METHODS Ten patients (46-79 years of age; median, 70 y), eight with hepatocellular carcinoma (HCC) and cirrhosis and two with colorectal metastases in the caudate lobe, were treated with 5.8% NaCl tissue-perfused monopolar (n=7) or bipolar (n=3) RF ablation. The median tumor diameter was 41 mm (range, 25-70 mm). Procedures were performed under ultrasound and computed tomography (CT) guidance in eight and two patients, respectively. One month later, the treatment response was assessed by CT. RESULTS Transhepatic right intercostal and transomental anterior epigastric routes were used for tumor puncture in eight and two patients, respectively. The entire RF ablation treatment required one or two procedures (median, 1.5), including two to 15 electrode repositionings (median, 6). After RF ablation procedure, one patient experienced jaundice that resolved spontaneously. In one patient, CT follow-up showed asymptomatic segmental biliary duct dilations. Median total hospital stay was 3 days (range, 2-9 d). Complete ablation was achieved in nine of 10 tumors. In one patient, ethanol ablation was necessary to complete RF ablation treatment. After a median follow up of 9.5 months (range, 5-25 mo), three patients remained tumor-free and seven had tumor relapse: two local, four distant, and one mixed. Repeat RF ablation was successfully performed in four cases. CONCLUSION RF ablation of liver tumors located in the caudate lobe is effective despite the deep location of tumors and the vicinity of major vessels.
Age-Specific Survival and Probable Causes of Mortality in Female Lesser Prairie-Chickens

Abstract Long-term population declines and habitat reductions have increased concern over the status of the lesser prairie-chicken (Tympanuchus pallidicinctus). Robust estimates of demographic parameters are essential for identifying population declines and planning effective management. We evaluated the effects of age and season on the survival of female lesser prairie-chickens at 2 sites in southwestern Kansas, USA. Using telemetry data from a 7-year field study (from 1997 to 2003), we estimated seasonal (Apr–Sep) and annual (Apr–Mar) survival. We also examined daily survival rates of females attending nests during the 26-day incubation period and young during the 14-day early brood-rearing period. We evaluated the probable mortality causes of radiomarked birds by examining evidence at recovery sites. We captured 227 female lesser prairie-chickens (87 yearlings, 117 ad, and 23 age undetermined) and fitted them with radiotransmitters. Estimates of 12-month survival were lower among yearlings (Ŝ12 = 0.429, SE = 0.117) and adults at site I (Ŝ12 = 0.302, SE = 0.080) than among yearlings (Ŝ12 = 0.588, SE = 0.100) and adults at site II (Ŝ12 = 0.438, SE = 0.083). The patterns in timing of mortality and age-specific 6-month survival were consistent with those of 12-month estimates at site I from 1998 to 2002, with a peak in mortality during May and June. Females tending to nests or to prefledged chicks had lower daily survival (DŜRtend = 0.993, SE = 0.001) than females not involved in these activities (DŜRfailed-breeder = 0.997, SE = 0.002). We recorded 92 mortalities from April 1997 to March 2003, and 59% and 11% were attributed to predation by mammals and raptors, respectively. Our research suggests that predation during the nesting season can have a major impact on lesser prairie-chicken demography, and conservation efforts should focus on enhancing female survival during the nesting and brood-rearing seasons.
Von Willebrand Factor Does not Vary during Normal Menstrual Cycle

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Cultural Competence: Its Promise for Reducing Healthcare Disparities

Healthcare disparities have reached such disproportionate levels of disease burden for certain groups that the issue has become a national priority. This article examines the most recent iteration of the healthcare disparities movement, the aggressive legislative steps by the federal government to disrupt its destructive path and the promise that cultural competence holds for healthcare providers and the healthcare industry as a whole in placing the patient back at the center of healthcare treatment. Such efforts, it is argued, will be instrumental in helping to reduce healthcare disparities and make the healthcare delivery experience a more positive outcome for all patients.
Burden of Wet Age-Related Macular Degeneration and Its Economic Implications in Singapore in the Year 2030

ABSTRACT Purpose: To estimate the prevalence of wet age-related macular degeneration (AMD) in Singapore in the year 2030. This projection will help in planning appropriate care provision and build health services capacity to cater to the increasing healthcare demand in 2030. Methods: The number of AMD patients aged 40–79 years from all Singaporeans was estimated using prevalence rates from a local study and using the United Nations population projections for Singapore to 2030. Age-specific mortality was accounted for. Additionally, two main scenarios were presented: (1) Projected number of wet AMD cases if patients were not taking preventive antioxidant vitamins; (2) projected number of wet AMD cases if patients were taking preventive antioxidant vitamins. Based on these scenarios, the economic burden was calculated. The number of quality-adjusted life years (QALYs) gained as a result of improvement in visual acuity (VA) due to anti-vascular endothelial growth factor (VEGF) treatment was also calculated. Results: An estimated growth of 42% in the number of wet AMD cases is expected by 2030. The estimated economic burden of wet AMD in 2030 for scenarios 1 and 2 is Singapore $203.1 million and $162.9 million, respectively. The QALYs gained as a result of improved VA from wet AMD treatment ranged from 10,114.4 to 14,058.8 over a 5-year period for the 2030 cohort. Conclusion: The burden of wet AMD is set to increase over the next 15 years. Appropriate measures to build healthcare capacity and plan for this expected surge in patients should be a priority in Singapore.
Identification of Kluyveromyces lactisTelomerase: Discontinuous Synthesis along the 30-Nucleotide-Long Templating Domain

ABSTRACT Telomeres in the budding yeast Kluyveromyces lactisconsist of perfectly repeated 25-bp units, unlike the imprecise repeats at Saccharomyces cerevisiae telomeres and the short (6- to 8-bp) telomeric repeats found in many other eukaryotes. Telomeric DNA is synthesized by the ribonucleoprotein telomerase, which uses a portion of its RNA moiety as a template. K. lactistelomerase RNA, encoded by the TER1 gene, is ∼1.3 kb long and contains a 30-nucleotide templating domain, the largest ever examined. To examine the mechanism of polymerization by this enzyme, we identified and analyzed telomerase activity from K. lactiswhole-cell extracts. In this study, we exploited the length of the template and the precision of copying by K. lactistelomerase to examine primer elongation within one round of repeat synthesis. Under all in vitro conditions tested, K. lactistelomerase catalyzed only one round of repeat synthesis and remained bound to reaction products. We demonstrate that K. lactistelomerase polymerizes along the template in a discontinuous manner and stalls at two specific regions in the template. Increasing the amount of primer DNA-template RNA complementarity results in stalling, suggesting that the RNA-DNA hybrid is not unpaired during elongation in vitro and that lengthy duplexes hinder polymerization through particular regions of the template. We suggest that these observations provide an insight into the mechanism of telomerase and its regulation.
Human Papillomavirus Vaccine Stages of Change Among Male and Female University Students: Ready or Not?

Abstract Objective: To examine gender differences in human papillomavirus (HPV) vaccine stages of change following the recommendations for permissive use of HPV vaccine in males. Participants: Students aged 18–26 attending a large, public, Midwest university in April 2010. Methods: Participants completed a self-administered, online questionnaire. HPV vaccine stage of change was assessed according to core constructs of the Transtheoretical Model of Behavior Change. Logistic regression was used to identify associations of HPV-related beliefs and attitudes with stage of change. Results: Although most (80.5%) of the 4,019 participants had at least contemplated HPV vaccination, more females had taken observable steps towards vaccination. Significant differences between genders in HPV-related beliefs and attitudes were observed, particularly perceived parental or perceived health care provider approval of HPV vaccination. Conclusions: University students generally agreed with the benefits of HPV vaccination, both for themselves and for society, and these attitudes were significantly associated with having at least contemplated vaccination.