Miracle-dz/UniFAR-FTUs huggingface dataset:
Studies on the virulence of hospital strains of Pseudomonas aeruginosa.

Surmmary The virulence of 36 strains of Pseudomonas aeruginosa was studied by intravenous injection into mice; the strains were found to fall into three broad groups, of high, medium and low virulence. This difference could not be related to any biochemical property studied, pyocine type nor antibiotic sensitivity pattern. It was found that 24 of the 30 strains of the high and medium virulence group produced large colonies on agar while 5 of the 6 strains of the low virulence group produced small colonies when plated under similar conditions. To test this observation a further series was collected and the strains were allocated to the high or low virulence category on colonial appearance. Mouse challenge with these fresh strains showed that the prediction was accurate. The large colony type had a faster growth rate on agar and in broth than the small. When a strain was grown in agar it was found to be more virulent than when harvested from broth (P = 0.02–0.01). Chromatography studies on slime derived from all three categories showed that they were apparently chemically similar. The amount of slime produced by a standard number of bacteria was measured for agar and broth grown cultures. The yields for the two media were approximately the same with large-colony forms. Small-colony forms produced similar amounts to the large forms on plates, but up to 15 times as much when grown in broth. The ability to kill mice was derived in part from early toxic death; the remainder died of renal disease. Study of the initiation of kidney infection showed that large-colony types were more successful in maintaining their numbers in the kidneys over the first 5 hr. Strains grown on nutrient agar did not give higher counts in the kidney than those from broth in the first 5 hr but after 24 hr they grew faster, infected more kidneys and killed more mice.
Gas thermal conductivity measurement based on the three-omega method

Preliminary investigations have been conducted to discuss the possibility of using a micro-machined suspended wire as a 3ω based sensor for the measurement of gas thermal conductivities. Thermal responses of various pure gases and helium-nitrogen mixtures have been measured using a 3ω setup and compared to an one-dimensional analytical model derived by Yusibani et al. Deviation of the measured thermal conductivities compared to reference values led us to consider an empirical approach which offers the possibility of estimating the studied gas thermal conductivity by measuring the out-of-phase cut-off frequency.
Olanzapine for the treatment of bipolar disorder in children and adolescents

Background: The second-generation antipsychotic olanzapine has been shown to be efficacious as a treatment for adults with bipolar disorder and is approved by the United States Food and Drug Administration for the treatment of acute manic or mixed episodes as well as for maintenance treatment in bipolar adults. Objective: This review examines the use of olanzapine for the treatment of children and adolescents with bipolar disorder and presents a discussion of the mechanism of action, pharmacokinetic and pharmacodynamic properties of olanzapine in children and adolescents. In addition, efficacy and safety data are reviewed and the risks and benefits of using olanzapine in bipolar youth are summarized. Methods: Articles published in English were identified using a search of the National Library of Medicine from 1990 to 2007 with manual review of references of each article as well as review of the US Clinical Trials database. Articles describing the use of olanzapine in children or adolescents were included. Conclusions: Olanzapine appears to have a rapid onset of action for mixed and manic episodes, but is associated with metabolic side effects including hyperprolactinemia, diabetes and weight gain. Therefore, olanzapine may best be used in the acute treatment of children and adolescents experiencing a manic or mixed episode as its side-effect profile may limit its use as a maintenance agent in this population.
Targeted drug delivery by in vivo coupling to endogenous albumin: an albumin-binding prodrug of methotrexate (MTX) is better than MTX in the treatment of murine collagen-induced arthritis

Objective: To examine the effect of an albumin-binding prodrug of methotrexate (MTX) in the treatment of murine collagen-induced arthritis (CIA). Methods: The prodrug AWO54 with the formula EMC-d-Ala-Phe-Lys-Lys-MTX binds selectively to the cysteine-34 position of endogenous albumin, which acts as a macromolecular drug carrier for MTX to the site of inflammation. The CIA model was used to evaluate the anti-arthritic effect of the compound after intravenous application. Results: The albumin-bound form of AWO54 was efficiently cleaved by cathepsin B and plasmin, two proteases that are overexpressed in rheumatoid arthritis, and release a MTX lysine derivative. AWO54 suppressed CIA in a dose-dependent manner and was significantly better than MTX. To obtain a similar effect only about 20% of the MTX-equivalent dose of AWO54 had to be given. The efficacy of the drug was tested in two different stages of CIA: while both, MTX and AWO54 inhibited arthritis in an early stage of the disease, in a later stage only AWO54 showed a significant inhibitory effect in comparison with control. Conclusion: Targeted drug delivery by in vivo coupling of a prodrug of MTX to endogenous albumin is better than MTX in the treatment of CIA.
Determination of Nonylphenol Polyethoxylates and Their Lipophilic Metabolites in Sewage Effluents by Normal-Phase High-Performance Liquid Chromatography and Fluorescence Detection.

Analytical procedures using normal-phase high-performance liquid chromatography (HPLC) with fluorescence detection, suitable for the routine determination of alkylphenol polyethoxylate (APnEO) surfactants and their lipophilic metabolites in sewage effluents at sub-microgram per litre level, have been developed. The parent nonylphenol polyethoxylates (NPnEO), covering oligomer range of 1-18 ethoxy units per molecule, were extracted from water samples using solid-phase extraction on graphitised carbon black (GCB), while their lipophilic metabolites, including nonylphenol monoethoxylate (NP1EO), nonylphenol diethoxylate (NP2EO) and nonylphenol (NP), were extracted by liquid-liquid extraction into n-hexane. The extracts were analysed by normal-phase HPLC using amino-silica columns and fluorescence detection at 228/305 nm. This allowed reliable quantitative determination of individual oligomers down to 0.1 mu g/l. Analyses of sewage effluents collected in several sewage treatment plants of the Canton of Zurich, Switzerland, indicated that NPnEO occur at significant concentrations (96-430 mu g/l) despite the partial ban introduced in 1986. Oligomer distributions found in analysed sewage samples revealed that the major part of toxic lipophilic metabolites, including NP, still originate from detergent-derived NPnEO.
Relative frequency of various forms of primary cutaneous lymphomas.

BACKGROUND Data on the relative frequency of the various forms of primary cutaneous lymphomas (PCLs) are largely limited to European institutions. OBJECTIVE Our purpose was to document the relative frequencies of various PCLs seen at 3 US institutions with active cutaneous lymphoma programs and to compare those with the European data. METHODS Included in this study are newly registered patients seen at MCP Hahnemann University, New York University, and the University of California, San Francisco from July 1, 1995 to June 30, 1998. RESULTS A total of 755 patients were seen. The frequency distribution of the major diagnostic groups was as follows: mycosis fungoides/Sézary syndrome, 82.3%; lymphomatoid papulosis, 12.6% (including patients with associated mycosis fungoides/Sézary syndrome); CD30(+) anaplastic large-cell lymphoma, 0.9%; peripheral T-cell lymphomas, 2.9%; B-cell lymphoma, 4.5%. CONCLUSION The most striking finding is the much lower relative frequency of primary cutaneous B-cell lymphomas at US institutions (4.5%) versus the approximately 20% reported by European groups. The reason for this difference requires further study.
Expression patterns and changes of the LCN2 gene in the testes of induced cryptorchidism and busulfan-treated mice

ABSTRACT Lipocalin-2 (LCN2) was known to play various roles in different type cells; however, little was known about the effect of LCN2 in male fertility. In this study, we aimed to explore the expression pattern of LCN2 with increasing age in mice, and to obtain insight into the role of LCN2 in mice testes by induced cryptorchidism and busulfan-treated infertility. In situ hybridization showed that LCN2 was localized primarily in Leydig cells, but was absent in Sertoli and germ cells. Its expression in testes exhibited an age-related increase from day 1 to 8 months, then reduced by the twelth month. The mRNA and protein levels of LCN2 in the testes of both infertile models increased as measured by real-time PCR and western blotting, respectively. LCN2 mRNA and protein levels were higher (p<0.05) in busulfan treated mice than that of cryptorchidism. These observations have shown that LCN2 is developmentally regulated and highly expressed in the Leydig cells of mouse testes.
Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum

Abstract We have previously presented evidence that two human kallikrein-related peptidases, KLK5 (hK5, stratum corneum tryptic enzyme, SCTE) and KLK7 (hK7, stratum corneum chymotryptic enzyme, SCCE), which are abundant in the stratum corneum, may be involved in desquamation. Since we had noted that not all trypsin-like activity in the plantar stratum corneum could be ascribed to KLK5, we set out to identify other skin proteases with similar primary substrate specificity. Here we describe purification of a protease identified as KLK14 from plantar stratum corneum, and show that this enzyme may be responsible for as much as 50% of the total trypsin-like activity in this tissue, measured as activity towards a chromogenic substrate cleaved by a wide variety of enzymes with trypsin-like specificity. This was in spite of very low levels of KLK14 protein compared to KLK5 and KLK7. KLK14 could be detected by immunoblotting in normal superficial stratum corneum of all individuals examined. The majority of KLK14 in the plantar stratum corneum is present in its catalytically active form. KLK14 could be immunohistochemically detected in sweat ducts, preferentially in the intraepidermal parts (the acrosyringium), and in sweat glands. The role played by this very efficient protease under normal and disease conditions in the skin remains to be elucidated.
Survival With Emergency Tourniquet Use to Stop Bleeding in Major Limb Trauma

Objective:The purpose of this study was to determine if emergency tourniquet use saved lives. Summary Background Data:Tourniquets have been proposed as lifesaving devices in the current war and are now issued to all soldiers. Few studies, however, describe their actual use in combat casualties. Methods:A prospective survey of injured who required tourniquets was performed over 7 months in 2006 (NCT00517166 at ClinicalTrials.gov). Follow-up averaged 28 days. The study was at a combat support hospital in Baghdad. Among 2838 injured and admitted civilian and military casualties with major limb trauma, 232 (8%) had 428 tourniquets applied on 309 injured limbs. We looked at emergency tourniquet use, and casualties were evaluated for shock (weak or absent radial pulse) and prehospital versus emergency department (ED) tourniquet use. We also looked at those casualties indicated for tourniquets but had none used. We assessed survival rates and limb outcome. Results:There were 31 deaths (13%). Tourniquet use when shock was absent was strongly associated with survival (90% vs. 10%; P < 0.001). Prehospital tourniquets were applied in 194 patients of which 22 died (11% mortality), whereas 38 patients had ED application of which 9 died (24% mortality; P = 0.05). The 5 casualties indicated for tourniquets but had none used had a survival rate of 0% versus 87% for those casualties with tourniquets used (P < 0.001). Four patients (1.7%) sustained transient nerve palsy at the level of the tourniquet. No amputations resulted solely from tourniquet use. Conclusions:Tourniquet use when shock was absent was strongly associated with saved lives, and prehospital use was also strongly associated with lifesaving. No limbs were lost due to tourniquet use. Education and fielding of prehospital tourniquets in the military environment should continue.
MDV3100 effects on androgen receptor (AR) signaling and bone marrow testosterone concentration modulation: Apreliminary report.

4501 Background: "Intracrine" androgen signaling is linked to castrate-resistant prostate cancer (CRPC) and a "credentialed" therapy target. MDV3100 a novel AR inhibitor is effective in CRPC (Scher et al Lancet 2010). We hypothesize that MDV3100 will modulate androgen signaling in a target specific manner. METHODS Study patients (pts) had progressive CRPC with <50 ng/dl serum testosterone (T) by radioimmunoassay, bone metastases and agreed to serial bone marrow (BM) biopsies. Pts received oral MDV3100 160 mg QD. RESULTS 47 pts, median age 68 yrs (Range 40-89), PS-ECOG 1 (range 0-2) and baseline PSA concentration 51.5 ng/dl (range 2.9-4248), enrolled. 21 (44.6%) had DES and/or ketoconazole, 40 (85.1%) prior chemotherapy [≥2 regimens: 15 (31.9%)]. 32 (68.1%) had ≥20 bone lesions, 16 (34%) lesions in lymphnodes and 6 (12.7%) visceral metastases. To date maximum PSA decline of ≥50% and ≥90% was observed in 19 (43.18%) and 7/44 (15.9 %) evaluable pts respectively, at ≥ 8 weeks of treatment. Plasma (p value <0.0001) and BM (p value 0.001) T and plasma (p value 0.008) dihydrotestosterone (DHT) assessed by electrospray tandem mass spectrometry consistently increased at 8 weeks of MDV3100 as compared to baseline. Mean BM T rose from 0.026 ng/ml (range 0.00-0.057) to 0.04 (range 0.00-0.10) in 28 evaluable pts. Mean plasma T rose from 0.041 ng/ml range (0.00-0.1) to 0.066 (range 0.00-0.18) in 40 evaluable pts. Higher pretreatment BM and plasma T are associated with PSA response (p value <0.05). BM infiltration was present in 24 (51.1%) pts. Pretreatment nuclear AR was present in all samples and expression ranged 40-100% of tumor cells. PSA response is associated with reduction in BM dissemination and reduced or unchanged nuclear AR expression (p value 0.031). CONCLUSIONS Our findings support the hypothesis that MDV3100 efficacy in CRPC is attributed to potent AR inhibition. MDV3100 increases BM T and decreases nuclear AR, whereas Abiraterone acetate, an androgen biosynthesis inhibitor, was previously reported to decrease T and increase AR copy number (Efstathiou et al, ASCO 2010). Taken together these data suggest evaluation of these two androgen signaling inhibitors in combination.
Dose-dependent release of endogenous tissue factor pathway inhibitor by different low molecular weight heparins

Tissue factor pathway inhibitor (TFPI) is released to circulating blood after intravenous and subcutaneous injections of heparins, and may thus contribute to the antithrombotic effect of heparins. A previous study suggested different abilities of various low molecular weight heparins (LMWH) to release endogenous TFPI, but the dose–response relationship was not determined. In the present study, the dose–response relationship for escalating doses of two LMWHs, dalteparin and enoxaparin, on the release of endogenous TFPI was investigated. Six healthy male participants were given 50, 100 and 200 U/kg dalteparin and 0.5, 1.0 and 2.0 mg/kg enoxaparin as a single subcutaneous injection. The study was a randomized, cross-over design with a 1-week wash-out period between each injection. Peak free TFPI antigen and TFPI activity were detected after only 1 h, whereas anti-activated factor X (anti-FXa) and anti-activated factor II (anti-FIIa) activities were detected after 2–6 h. Putative therapeutic equivalent doses of dalteparin and enoxaparin gave similar release of endogenous TFPI, but dissimilar effects on anti-FXa and anti-FIIa activities.
Interleukin-1 cluster and tumor necrosis factor-alpha gene polymorphisms in polymyalgia rheumatica.

OBJECTIVE To investigate whether polymorphisms in the interleukin (IL)-1 locus (human chrom. 2q13) and TNF-alpha gene are associated with susceptibility to or severity of polymyalgia rheumatica (PMR). METHODS The study included 92 consecutive PMR patients diagnosed over a 5-year period who were prospectively followed-up for at least one year and 79 healthy controls over the age of 50 residing in the same area. All the patients and controls were Caucasians of Italian origin. We tested the allelic distribution of IL-1A (+4845), IL-B (-511), IL-B (+3954), IL-1RN Intron 2 VNTR and TNFA (-308). Frequencies were compared in the patient and control groups. RESULTS A statistically significant association between PMR patients and the IL1RN*2 allele in the homozygous state was found [OR 8.46 (95% CI 1.05-68.31)]. The polymorphisms in the other genes of the IL-1 gene cluster did not reveal any association with PMR when compared with controls. A weak association between PMR patients and the TNF2 allele was also present [OR 2.09 (95% CI 1.0-4.17)]. None of the gene variants studied was associated with the disease severity of PMR. CONCLUSION Our findings show that IL1RN*2 allele, particularly in the homozygous state, is associated with susceptibility to, but not with the severity of, PMR.
Genome-Wide Association Analyses Based on Broadly Different Specifications for Prior Distributions, Genomic Windows, and Estimation Methods

A currently popular strategy (EMMAX) for genome-wide association (GWA) analysis infers association for the specific marker of interest by treating its effect as fixed while treating all other marker effects as classical Gaussian random effects. It may be more statistically coherent to specify all markers as sharing the same prior distribution, whether that distribution is Gaussian, heavy-tailed (BayesA), or has variable selection specifications based on a mixture of, say, two Gaussian distributions [stochastic search and variable selection (SSVS)]. Furthermore, all such GWA inference should be formally based on posterior probabilities or test statistics as we present here, rather than merely being based on point estimates. We compared these three broad categories of priors within a simulation study to investigate the effects of different degrees of skewness for quantitative trait loci (QTL) effects and numbers of QTL using 43,266 SNP marker genotypes from 922 Duroc–Pietrain F2-cross pigs. Genomic regions were based either on single SNP associations, on nonoverlapping windows of various fixed sizes (0.5–3 Mb), or on adaptively determined windows that cluster the genome into blocks based on linkage disequilibrium. We found that SSVS and BayesA lead to the best receiver operating curve properties in almost all cases. We also evaluated approximate maximum a posteriori (MAP) approaches to BayesA and SSVS as potential computationally feasible alternatives; however, MAP inferences were not promising, particularly due to their sensitivity to starting values. We determined that it is advantageous to use variable selection specifications based on adaptively constructed genomic window lengths for GWA studies.
Monte carlo dose calculations in conventional thorax fields for 60Co photons.

PURPOSE Our purpose was to apply the MCNP4C Monte Carlo (MC) code for dose calculations in the thorax region and compare the results with those of measurements and a conventional treatment planning system (TPS). MATERIALS AND METHODS We modeled a Theratron 780E 60Co unit and benchmarked our modeling with percent depth doses (PDDs), beam profiles, and output factors measured in a water phantom. For PDDs and beam profiles, the differences between measurements and MC calculations were less than 1% and 2%, respectively. We used an anatomic thorax phantom for evaluation of a conventional TPS and our MC calculation results. RESULTS In comparing the results of calculations and measurements for our thorax geometries, the errors of conventional and MC methods were 20% and 2%, respectively. For the anterior mediastinal field and large thorax field the accuracy of the conventional method was acceptable, but for small fields of lateral thorax irradiation, the error of the conventional method was as high as to 20%. In all MC calculations, discrepancy from the measurements was less than 2%. CONCLUSION Our results showed that the MCNP4C MC code could be used in dose calculations in treatment planning for 60Co photon irradiation. In addition, the application of the MC method for dose calculations in radiotherapy with 60Co photons was recommended.
COPPER DEFICIENCY IN THE DEVELOPING RAT BRAIN: EVIDENCE FOR ABNORMAL MITOCHONDRIA 1

Abstract— Copper deficiency was produced in developing rats by feeding a low copper diet to rats during gestation and lactation and providing the offspring the same diet. The progeny developed similar to those of an earlier model based on preconception depletion followed by marginal supplementation during gestation. Copper levels were greatly reduced in the brain, iron levels were slightly depressed, and no differences in zinc content were found. Electron microscopic examination of brain tissue revealed the presence of enlarge mitochondria from copper‐deficient animals. Isolated mitochondria from copper‐deficient rats showed a 30% reduction in the rate of both succinate and glutamate oxidation, and for glutamate, the respiratory control ratio (RCR) was decreased by 60%. Difference spectra displayed a four‐fold reduction in cytochrome a+a3 and slight increases in cytochrome b, c1 and c. Enzyme analysis of isolated mitochondria revealed a five‐fold decrease in cytochrome oxidase, slight increases in succinic dehydrogenase and fumarase, and small decreases in hexokinase and monoamine oxidase. No difference in peroxidation of brain lipids was evident. Determination of metabolites from fast frozen tissue suggested that the copper‐deficient brain was in a more reduced state based on a doubling of both the lactate/pyruvate and α‐glycerol‐P/dihydroxyacetone‐P ratios. Creatine‐P, ATP, and ADP levels were not different.
The numerical study on the unsteady flow of gas in a semi-infinite porous medium using an RBF collocation method

In this paper, we study a nonlinear two-point boundary value problem on semi-infinite interval that describes the unsteady gas equation. The solution of the mentioned ordinary differential equation (ODE) is investigated by means of the radial basis function (RBF) collocation method. The RBF reduces the solution of the above-mentioned problem to the solution of a system of algebraic equations and finds its numerical solution. To examine the accuracy and stability of the approach, we transform the mentioned problem into another nonlinear ODE which simplifies the original problem. The comparisons are made between the results of the present work and the numerical method by shooting method combined with the Runge–Kutta technique. It is found that our results agree well with those by the numerical method, which verifies the validity of the present work.