Miracle-dz/UniFAR-FTUs huggingface dataset:
An Alphavirus Replicon Particle Chimera Derived from Venezuelan Equine Encephalitis and Sindbis Viruses Is a Potent Gene-Based Vaccine Delivery Vector

ABSTRACT Alphavirus replicon particle-based vaccine vectors derived from Sindbis virus (SIN), Semliki Forest virus, and Venezuelan equine encephalitis virus (VEE) have been shown to induce robust antigen-specific cellular, humoral, and mucosal immune responses in many animal models of infectious disease and cancer. However, since little is known about the relative potencies among these different vectors, we compared the immunogenicity of replicon particle vectors derived from two very different parental alphaviruses, VEE and SIN, expressing a human immunodeficiency virus type 1 p55Gag antigen. Moreover, to explore the potential benefits of combining elements from different alphaviruses, we generated replicon particle chimeras of SIN and VEE. Two distinct strategies were used to produce particles with VEE-p55gag replicon RNA packaged within SIN envelope glycoproteins and SIN-p55gag replicon RNA within VEE envelope glycoproteins. Each replicon particle configuration induced Gag-specific CD8+ T-cell responses in murine models when administered alone or after priming with DNA. However, Gag-specific responses varied dramatically, with the strongest responses to this particular antigen correlating with the VEE replicon RNA, irrespective of the source of envelope glycoproteins. Comparing the replicons with respect to heterologous gene expression levels and sensitivity to alpha/beta interferon in cultured cells indicated that each might contribute to potency differences. This work shows that combining desirable elements from VEE and SIN into a replicon particle chimera may be a valuable approach toward the goal of developing vaccine vectors with optimal in vivo potency, ease of production, and safety.
Crohn's disease activity assessed by fecal calprotectin and lactoferrin: Correlation with Crohn's disease activity index and endoscopic findings

Background: Correlation of endoscopic Crohn's disease activity with fecal calprotectin and lactoferrin is insufficiently studied. We evaluated the clinical significance of these neutrofil‐derived proteins in assessment of Crohn's disease activity by comparing them with endoscopic disease activity and with Crohn's disease activity index (CDAI) and serum CRP. Methods: A total of 77 CD patients underwent one or more ileocolonoscopies (n = 106) with scoring of Crohn's disease index of severity (CDEIS). Patients provided stool samples for calprotectin and lactoferrin measurements and blood samples for CRP. Clinical activity was based on the CDAI. Results: Both fecal calprotectin and lactoferrin correlated significantly with CDEIS (Spearman's r 0.729 and 0.773, P < 0.001). With a cutoff level of 200 &mgr;g/g for a raised fecal calprotectin concentration, sensitivity was 70%, specificity 92%, positive predictive value (PPV) 94%, and negative predictive value (NPV) 61% in predicting endoscopically active disease (CDEIS ≥ 3). A fecal lactoferrin concentration of 10 &mgr;g/g as the cutoff value gave a sensitivity, specificity, PPV, and NPV of 66%, 92%, 94%, and 59%. Sensitivity of CDAI ≥ 150 to detect endoscopically active disease was only 27%, specificity 94%, PPV 91%, and NPV 40%. A raised serum CRP (> 5 mg/l) gave a sensitivity, specificity, PPV, and NPV of 48%, 91%, 91%, and 48%. Conclusions: For evaluation of Crohn's disease activity, based on endoscopic findings, more sensitive surrogate markers than is CDAI or CRP are fecal calprotectin and lactoferrin. These prove to be useful tools for estimation of disease activity in Crohn's disease.
Diverse seed banks favour adaptation of microalgal populations to future climate conditions.

Selection of suitable genotypes from diverse seed banks may help phytoplankton populations to cope with environmental changes. This study examines whether the high genotypic diversity found in the Baltic cyst pool of the toxic dinoflagellate Alexandrium ostenfeldii is coupled to phenotypic variability that could aid short-term adaptation. Growth rates, cellular toxicities and bioluminescence of 34 genetically different clones isolated from cyst beds of four Baltic bloom sites were determined in batch culture experiments along temperature and salinity gradients covering present and future conditions in the Baltic Sea. For all parameters a significant effect of genotype on the response to temperature and salinity changes was identified. General or site-specific effects of the two factors remained minor. Clones thriving at future conditions were different from the best performing at present conditions, suggesting that genotypic shifts may be expected in the future. Increased proportions of highly potent saxitoxin were observed as a plastic response to temperature increase, indicating a potential for higher toxicity of future blooms. The observed standing variation in Baltic seed banks of A. ostenfeldii suggests that the population is likely to persist under environmental change.
Comparative Analysis of Antibiotic Resistance Characteristics of Gram‐negative Bacteria Isolated from Laying Hens and Eggs in Conventional and Organic Keeping Systems in Bavaria, Germany

By investigating the prevalence and resistance characteristics of Gram‐negative bacteria from organic and conventional kept laying hens against 31 (Campylobacter: 29) different antibiotics using the microdilution method, we determined to what extent different keeping systems influence bacterial resistance patterns. For this purpose, samples from 10 organic and 10 conventional flocks in Bavaria (Germany) were investigated four times between January 2004 and April 2005. Altogether, 799 cloacal swabs and 800 eggs (contents and shells) were examined. The bacterial investigation performed with standardized cultural methods showed prevalence for all bacteria groups in about the same order of magnitude in the two different keeping systems: Salmonella spp. 3.5% (organic [org]) versus 1.8% (conventional [con]); Campylobacter spp. 34.8%org versus 29.0%con and E. coli 64.4%org versus 69.0%con. Coliforms (Citrobacter, Enterobacter, Pantoea) were only isolated in single cases. In eggs, generally less bacteria were detected, predominantly Escherichia; Salmonella and Campylobacter were only scarcely isolated. Salmonella enterica ssp. enterica serovar Typhimurium (n = 10) were resistant to up to nine, S. of the serogroup B (n = 4) up to six antibiotics. All tested Salmonella (n = 23) proved to be resistant to spectinomycin. Escherichia coli (n = 257org and 276con) from organic layers showed significant lower resistance rates and higher rates of susceptible isolates to nine agents, namely amoxicillin/clavulanic acid, ampicillin, cefaclor, cefoxitin, cefuroxime, doxycycline, mezlocillin, neomycin and piperacillin. In contrast, only two antibiotics turned out to be more effective in conventional isolates (gentamicin and tobramycin). In the case of Campylobacter jejuni (n = 118org and 99con), statistically significantly better rates were observed for isolates from organic flocks concerning imipenem and amoxicillin/clavulanic acid, whereas fosfomycin was more potent in strains from conventional flocks. Results of this study indicate that both resistance rates and mean minimum inhibitory concentrations of bacteria isolated from organic keeping systems have lower values than those from conventional ones, particularly recognizable for E. coli. Thus, organic livestock farming with its restrictions and additional requirements contributes to further effectiveness of antibiotics.
An MIMO Random Channel Generator for Indoor Power-Line Communication

Multiple-input multiple-output (MIMO) technology has already been used in power-line communication (PLC). An accurate description of MIMO channels for PLC network topologies is of great interest and importance in the development and testing of digital communication algorithms. However, the considerable variability of PLC networks makes this task quite difficult. In this regard, a random channel generator for a single-input single-output (SISO) configuration has been presented in the literature. The procedure was applied to a set of measured channels that were interestingly divided into nine classes. In this paper, an MIMO random channel generator based on the aforementioned SISO configuration is proposed. An MIMO channel is considered as the superposition of correlated SISO channels so we attempt to describe an MIMO channel using the nine classes obtained with the SISO configuration. An additional parameter, related to the correlation factor, had to be taken into account. It is shown that when this parameter is obtained from probabilistic distribution with properly chosen standard deviations for each of the nine classes, the European MIMO PLC field measurements can be accurately reproduced by the random channel generator.
Comparison of laboratory and clinical wear rates of resin composites.

OBJECTIVE The purpose of this study was to use wear simulation to develop wear rates for two modern composite systems and then compare these rates with clinical studies on the same materials. METHOD AND MATERIALS A spring-loaded piston wear simulator was used to generate localized wear rates for P50 and Z100 at 100,000, 200,000, 300,000, and 400,000 cycles. Clinical studies on P50 and Z100 conducted at Creighton University and the Catholic University of Leuven were used for comparison of clinical wear to the laboratory values. Regression analysis was employed to define the wear rates. RESULTS The laboratory wear rates determined with simulation for P50 and Z100 were similar. Clinical occlusal contact area (OCA) wear for P50 and Z100 had small differences and were pooled to provide comparison with laboratory data. Wear rates determined from linear regression analysis provided equivalency factors between laboratory localized wear and clinical OCA wear that could be used for future studies. Further regression analysis comparing OCA and generalized clinical wear allowed a conversion factor of 4.5 to be determined. CONCLUSION Localized wear from laboratory simulation may be a useful predictor of localized clinical wear and also clinical generalized wear using a conversion factor.
Differences and effects of medium and large adult cuffs on blood pressure readings in individuals with muscular arms

ObjectiveThis study analyzed systolic and diastolic blood pressure (SBP and DBP) reading differences in individuals with muscular arms, using medium and large adult cuffs. Materials and methodsResting blood pressures (BPs) were measured in bodybuilders competing at the Mexican National Bodybuilding and Fitness Championship. The means of two bilateral simultaneous arm BP measurements were obtained using two different cuff sizes, 12 cm (medium adult) and 16 cm (large adult). ResultsA total of 193 bodybuilders completed the measurements. With an arm circumference greater than 33 cm, the SBP and DBP average taken with the medium adult cuff was higher than that obtained with the large adult cuff, 8.2±10.6 and 1.6±7.4 mmHg, respectively; however, a significant difference was observed only with the SBP. With the medium adult cuff, 48 of 144 individuals showed SBP at least 140 mmHg, whereas with the large adult cuff there were only 17 of 144 individuals. In those participants with an arm circumference less than 33 cm, the BP was nonsignificantly lower with the large cuff, −4.24±9.2 and −2.24±5.4 mmHg for the SBP and DBP, respectively. ConclusionIncorrect cuffing of a muscular arm leads to significant errors in the measurement of SBP and DBP, similar to that observed in miscuffing of nonmuscular arms.
MP1 Encodes an Abundant and Highly Antigenic Cell Wall Mannoprotein in the Pathogenic Fungus Penicillium marneffei

ABSTRACT We cloned the MP1 gene, which encodes an abundant antigenic cell wall mannoprotein from the dimorphic pathogenic fungusPenicillium marneffei. MP1 is a unique gene without homologs in sequence databases. It codes for a protein, Mp1p, of 462 amino acid residues, with a few sequence features that are present in several cell wall proteins of Saccharomyces cerevisiae andCandida albicans. It contains two putative N glycosylation sites, a serine- and threonine-rich region for O glycosylation, a signal peptide, and a putative glycosylphosphatidylinositol attachment signal sequence. Specific anti-Mp1p antibody was generated with recombinant Mp1p protein purified from Escherichia coli to allow further characterization of Mp1p. Western blot analysis with anti-Mp1p antibody revealed that Mp1p has predominant bands with molecular masses of 58 and 90 kDa and that it belongs to a group of cell wall proteins that can be readily removed from yeast cell surfaces by glucanase digestion. In addition, Mp1p is an abundant yeast glycoprotein and has high affinity for concanavalin A, a characteristic indicative of a mannoprotein. Furthermore, ultrastructural analysis with immunogold staining indicated that Mp1p is present in the cell walls of the yeast, hyphae, and conidia of P. marneffei. Finally, it was observed that infected patients develop a specific antibody response against Mp1p, suggesting that this protein represents a good cell surface target for host humoral immunity.
How Can Financial Constraints Force a Central Bank to Exit a Currency Peg? An Application to the Swiss Franc Peg

Recent research recognize that two balance sheet constraints can be of particular concern for an independent central bank: central bank equity cannot turn negative without any political and credibility risk, and central banks should avoid going insolvent if they want to maintain control over inflation. In this paper, we analyze how such constraints can weigh on a central bank's decision to exit a temporary currency peg, such as the one put in place in Switzerland between 2011 and 2015. We show that negative equity or insolvency concerns can force a central bank to exit such a peg earlier than it would have done absent such concerns. We detail under which conditions such reasoning can apply for a traditional inflation-averse central bank. We then build an exchange market pressure model fi tting with current peg reality to forecast both the central bank future bond holdings under a peg as well as its future losses. Applying our model to the Swiss franc peg, we show that negative equity concerns could have motivated the Swiss central bank early and puzzling peg exit in 2015, thereby providing a potential explanation for the "Frankenshock". ECB QE policy appears as a potential key driver of this decision. The paper adds to the literature on the limits of foreign exchange interventions for the particular case of central banks fi ghting appreciation pressures, which is a highly under-researched area.
Management of pain of post lumbar surgery syndrome: one-year results of a randomized, double-blind, active controlled trial of fluoroscopic caudal epidural injections.

BACKGROUND Post lumbar surgery syndrome represents a cluster of nomenclature and syndromes following spine surgery wherein the expectations of the patient and spine surgeon are not met, with persistent pain following lumbar surgery. Multiple causes have been speculated to cause pain after lumbar surgery. Epidural steroid injections are most commonly used in managing post surgical pain in the lumbar spine. However, there is a paucity of evidence of epidural injections in managing chronic low back pain with or without lower extremity pain in post surgery syndrome. STUDY DESIGN A randomized, double-blind, active controlled trial. SETTING An interventional pain management practice, a specialty referral center, a private practice setting in the United States. OBJECTIVES To evaluate the effectiveness of caudal epidural injections in patients with chronic low back and lower extremity pain after surgical intervention with post lumbar surgery syndrome. METHODS One-hundred forty patients were randomly assigned to one of 2 groups; Group I patients received caudal epidural injections with local anesthetic (lidocaine 0.5%), whereas Group II patients received caudal epidural injections with 0.5% lidocaine 9 mL mixed with 1 mL of 6 mg non-particulate Celestone. Randomization was performed by computer-generated random allocation sequence by simple randomization. OUTCOMES ASSESSMENT Multiple outcome measures were utilized which included the Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment status, and opioid intake with assessment at 3 months, 6 months, and 12 months post-treatment. Significant pain relief and disability reduction were described as 50% or more reduction in scores from baseline. RESULTS Combined pain relief (>/=50%) and disability reduction was recorded in 53% of the patients in the local anesthetic group, and 59% of patients in the local anesthetic and steroid group with no significant differences noted with or without steroid over a period of one-year. However, the data from the successful group showed improvement in 70% of patients in Group I and 75% of patients in Group II. The average procedures per year were 4 with an average total relief per year of 38.1 ± 14.5 weeks in Group I and 38.4 ± 13.2 weeks in Group II over a period of 52 weeks in the successful group. LIMITATIONS The results of this study are limited by the lack of a placebo group and one-year outcomes. CONCLUSION Caudal epidural injections in chronic function-limiting low back pain in post surgery syndrome without facet joint pain may be effective in a significant proportion of patients with improvement in functional status and significant pain relief. CLINICAL TRIAL NCT00370799.
Epidural insertion simulator of higher insertion resistance & drop rate after puncture

Accidents such as dural puncture remain one of the problems of epidural anesthesia, and unskilled doctors can repeat such accidents. The purpose of the current research was to provide a new simulator for epidural insertion training. No reference data regarding the resistance force used when inserting a needle into patients have been reported. A comparative study was conducted to aid in the development of a new simulator. Pork loin (n=5) were employed as a substitute for patients. Thickness was set at 2 cm so as to improve the reproducibility. The authors took the conventional simulator apart, and picked a block as an analogue of muscle and ligamentum flavum. A new simulator was made of a melamine foam resin block and a latex rubber sheet. An epidural needle fixed on a motorized stage was inserted at the speed of 2 mm per second. The reaction force was measured while the needle was inserted into each specimen. Waveform of the pork loin exhibited two slopes of different inclines up to peaks and then falls after puncture. The conventional simulator showed a simple increase up to peak and a slow fall after puncture. In contrast, the new simulator showed two slopes up to peak and then a sudden fall after puncture. The insertion resistances were 2.5 N/s for the porcine, 0.8 N/s for the conventional and 2.1 N/s for the new simulator. The drop rates were 5 N/s for the porcine, 0.6 N/s for the conventional and 24 N/s for the new simulator. The higher insertion resistance and drop rate for the new simulator than the conventional simulator will be suitable for epidural insertion training.
Do Health Insurers Contract the Best Providers? Provider Networks, Quality, and Costs

We provide a modeling framework to analyze selective contracting in the health-care sector. Two health-care providers differ in quality and costs. When buying health insurance, consumers observe neither provider quality nor costs. We derive an equilibrium where health insurers signal provider quality through their choice of provider network. Selective contracting focuses on low-cost providers. Contracting both providers signals high quality. Market power reduces the scope for signaling, thereby leading to lower quality and inefficiency.
BRAIN CYCLOSPORIN A LEVELS ARE DETERMINED BY ONTOGENIC REGULATION OF MDR1A EXPRESSION

Cyclosporin A (CyA) toxicity is a common occurrence in pediatric organ transplant patients. We hypothesized that reduced mdr1a expression in newborn and developing mice would affect CyA accumulation within organs and/or toxicity. For functional studies, CyA was administered (5 mg kg–1 i.p.) to 1-, 12-, and 19-day, and adult male and female mdr1a+/+ and mdr1a–/– mice. Peak blood CyA was lower in 1-, 12-, and 19-day-old (1000 ng ml–1) versus adult (1500 ng ml–1) mice but was similar in mdr1a+/+ and mdr1a–/– mice. Kidney mdr1a expression (measured by quantitative polymerase chain reaction) increased 2.5-fold in 19-day-old male and female mice and increased another 4-fold in adult females compared with adult males. Liver mdr1a expression increased 6-fold by day 12 compared with neonatal mice. Thereafter, maintenance of hepatic mdr1a expression in females and a reduction to neonatal levels in males was observed. Kidney/blood (8- to 9-fold) and liver/blood (12- to 15-fold) CyA levels were highest on days 12 and 19 and were not dependent on maturational changes in mdr1a mRNA levels. Adults had higher brain expression of mdr1a mRNA (3-fold), a corresponding 5-fold increase in immunodetectable P-glycoprotein, and 80% lower brain accumulation of CyA compared with 1-day-old mice. Conversely, in mdr1a-null mice, brain/blood CyA was similar in newborn and adult mice. A similar pattern was observed for the brain accumulation of the mdr1a substrate 3H-digoxin. We conclude that the risk for central nervous system drug toxicity could be higher in neonates or young children as a consequence of underdeveloped P-glycoprotein.
Local Sparsity Divergence for Hyperspectral Anomaly Detection

Anomaly detection (AD) has increasingly become important in hyperspectral imagery (HSI) owing to its high spatial and spectral resolutions. Many anomaly detectors have been proposed, and most of them are based on a Reed-Xiaoli (RX) detector, which assumes that the spectrum signature of HSI pixels can be modeled with Gaussian distributions. However, recent studies show that the Gaussian and other unimodal distributions are not a good fit to the data and often lead to many false alarms. This letter proposes a novel hyperspectral AD algorithm based on local sparsity divergence (LSD) without any distribution hypothesis. Our algorithm exploits the fact that targets and background lie in different low-dimensional subspaces and that targets cannot be effectively represented by their local surrounding background. A sliding dual-window strategy is first adopted to construct local spectral and spatial dictionaries, which enable the extraction of the sparse coefficients of each HSI pixel. Then, a consistent sparsity divergence index is proposed to compute the LSD map at each spectral band separately. Finally, joint segmentation of LSD maps over different bands is performed for AD. Experimental results on both simulated data and recorded data demonstrate the effectiveness of the proposed algorithm.