Miracle-dz/UniFAR-FTUs huggingface dataset:
Androgen receptor mutations in androgen-independent prostate cancer: Cancer and Leukemia Group B Study 9663.

PURPOSE The mechanisms responsible for prostate cancer androgen independence are diverse. Mutations of the androgen receptor (AR) gene that broaden ligand specificity have been implicated. Bone marrow specimens containing prostate tumor were obtained from men undergoing antiandrogen withdrawal for AR sequence analysis and clinical correlation. MATERIALS AND METHODS Eligible men enrolled on a trial of antiandrogen withdrawal had a minimum prostate-specific antigen (PSA) level of 5 ng/dL that was increasing on castration therapy including an antiandrogen. With informed consent, marrow biopsies were obtained to collect prostate tumor. Additional samples were obtained from men enrolled on chemotherapy trials. AR cDNA or DNA was polymerase chain reaction-amplified, cloned, and sequenced. The AR CAG repeat length was recorded. RESULTS One hundred eighty-four bone marrow biopsies were obtained, and 48 had prostate tumor detected by light microscopy. The ARs from these 48 samples were sequenced. Overall, five (10%) of 48 tumors had mutated ARs. AR point mutations were detected in the hormone-binding domain involved in transcription factor binding. Three mutations were novel in prostate cancer. One tumor sample had a CAG repeat length of 21, compared with germline length of 22 repeats. There was no association between detectability of AR mutations and antiandrogen withdrawal response or survival. CONCLUSION These data suggest that AR mutations are present in approximately 10% of patients with prostate cancer who experience treatment failure with hormone therapy that included an antiandrogen. Mutations in the AR likely confer a growth advantage for a subset of progressive prostate cancers. Correlation of AR mutation with antiandrogen withdrawal response or survival could not be made.
Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program.

BACKGROUND AND METHODS Allogeneic bone marrow transplantation is curative in a substantial number of patients with hematologic cancers, marrow-failure disorders, immunodeficiency syndromes, and certain metabolic diseases. Unfortunately, only 25 to 30 percent of potential recipients have HLA-identical siblings who can act as donors. In 1986 the National Marrow Donor Program was created in the United States to facilitate the finding and procurement of suitable marrow from unrelated donors for patients lacking related donors. RESULTS During the first four years of the program, 462 patients with acquired and congenital lymphohematopoietic disorders or metabolic diseases received marrow transplants from unrelated donors. The probability of engraftment by 100 days after transplantation was 94 percent, although 8 percent of patients later had secondary graft failure. The probability of grade II, III, or IV acute graft-versus-host disease was 64 percent, and the probability of chronic graft-versus-host disease at one year was 55 percent. The rate of disease-free survival at two years among patients with leukemia and good prognostic factors was 40 percent and among patients at higher risk, 19 percent. Twenty-nine percent of the patients with aplastic anemia were alive at two years, and the rate of two-year disease-free survival among patients with myelodysplasia was 18 percent. For patients with congenital immunologic or nonimmunologic disorders, the probability of survival was 52 percent. CONCLUSIONS The National Marrow Donor Program has benefited a substantial number of patients in need of marrow transplants from closely HLA-matched unrelated donors and has facilitated the recruitment of unrelated donors into the donor pool and the access to suitable marrow.
Biogeochemical time lags may delay responses of streams to ecological restoration

1. Mounting interest in ecological restoration of streams and rivers, including that motivated by the Water Framework Directive, has stimulated examination of whether management and restoration measures in streams and their catchments have yielded measurable improvements in ecological status (‘health’). Evidence for the efficacy of diffuse-source pollution reduction (including best management practices on land) has proven elusive. 2. Several hydrological and biogeochemical processes delay the responses of streams and rivers to a decrease in nutrient and sediment inputs, potentially for decades. The implications of such time lags in response to restoration may not be well appreciated by restoration ecologists, regulators, sponsors of restoration work or the broader community. 3. The groundwater time lag results from the long residence time of ground water. This is particularly important with respect to nitrate, but is increasingly important for phosphorus (P) as well. Isotopic tracers and groundwater age dating suggest that stream water often is more than a decade old, and that several decades are required to flush most soluble contaminants from groundwater reservoirs. 4. Sediment movement through river networks can be protracted because of storage and remobilisation processes involving stream beds, impounded reaches and fringing bars and floodplains. In lowland streams and rivers, sediment accretion can be rapid, but its removal is often far slower and can take decades to centuries. 5. Phosphorus availability is subject to time lags because P tends to associate with minerals, resulting in a potentially large yet exchangeable P reserve in upland soils and alluvial and stream-bed sediments. Thus, soils and sediments can remain rich in P for decades after new inputs are reduced, potentially acting as a source of P to surface waters. Phosphorus saturation of soils along ground water percolation pathways can lead to even longer time lags. Restoration measures that inundate previously dry soils or desiccate previously inundated sediments can induce high rates of P release. 6. These hydrological and biogeochemical time lags can obscure the short-term responses of streams and rivers to restoration measures. In many eutrophic waters, large decreases in nutrient availability would be required to return the ecosystem to a natural nutrient-limited state, and this could take decades.
Identification of N-acetylneuraminic acid and its 9-O-acetylated derivative on the cell surface of Cryptococcus neoformans: influence on fungal phagocytosis

Sialic acids from sialoglycoconjugates present at the cell surface of Cryptococcus neoformans yeast forms were analyzed by high-performance thin-layer chromatography, binding of influenza A and C virus strains, enzymatic treatment, and flow cytofluorimetry with fluorescein isothiocyanate-labeled lectins. C. neoformans yeast forms grown in a chemically defined medium contain N-acetylneuraminic acid and its 9-O-acetylated derivative. A density of 3 x 10(6) residues of sialic acid per cell was found in C. neoformans. Sialic acids in cryptococcal cells are glycosidically linked to galactopyranosyl units as inferred from the increased reactivity of neuraminidase-treated yeasts with peanut agglutinin. N-Acetylneuraminic acids are alpha-2,6 and alpha-2,3 linked, as indicated by using virus strains M1/5 and M1/5 HS8, respectively, as agglutination probes. The alpha-2,6 linkage markedly predominated. These findings were essentially confirmed by the interaction of cryptococcal cells with the lectins Sambucus nigra agglutinin and Maackia amurensis agglutinin. We also investigated whether the sialyl residues present in C. neoformans are involved in the fungal interaction with a cationic solid-phase substrate and with mouse resident macrophages. Adhesion of yeast cells to poly-L-lysine was mediated, in part, by sialic acid residues, since the number of adherent cells was markedly reduced after treatment with bacterial neuraminidase. The enzymatic removal of sialic acids also made C. neoformans yeast cells more susceptible to endocytosis by macrophages. The results show that sialic acids are components of the cryptococcal cell surface that contribute to its negative charge and protect yeast forms against phagocytosis.
Ca2+‐dependence of the depolarization‐inducible Na+ current of Xenopus oocytes

The role of Ca2+ on the depolarization‐induced appearance of a Na+ current in Xenopus oocytes was studied. Oocytes were voltage‐clamped and the induction of the Na+ current was tested under various conditions. In oocytes pre‐injected with 400 pmol EGTA to increase the intracellular Ca2+ buffering power, the current was significantly reduced. Conversely, when intracellular Ca2+ was made to increase by injecting an analogue of inositol 1,4,5‐trisphosphate (3‐F InsP3), to cause Ca2+ release from internal stores, the induction of the Na+ current was potentiated. The depolarization‐inducible Na+ channels of the Xenopus oocyte membrane appear, therefore, to be Ca2+ sensitive, as well as depolarization‐activated. J. Cell. Physiol. 174:154–159, 1998. © 1998 Wiley‐Liss, Inc.
COL1A1 Sp1 variation and bone phenotypes in an Italian population.

BACKGROUND Osteoporosis is the most common metabolic bone disorder of the elderly, affecting the normal bone turnover with an increased bone resorption and subsequent higher risk of fragility fractures. Collagen type 1 is the most represented protein in bone matrix. A genetic variation (Sp1) in intron 1 of COL1A1 gene has been associated to modulation of expression of the alpha 1 chain of collagen type 1 and it is considered a candidate polymorphism for predisposition to osteoporosis status and fragility fractures. Association studies, in ethnically different populations, are needed to strongly confirm the role of this polymorphism in bone metabolism. MATERIALS AND METHODS We enrolled over 2,000 Italian individuals and studied their bone mineral density (BMD) and fractures in relation to age, sex and body mass index (BMI). Moreover, we analyzed the distribution of Sp1 polymorphism in these individuals and associated it to normal bone status, osteopenic condition or osteoporosis diagnosis, BMD and the presence of low-trauma fractures. RESULTS The most rare ss genotype showed a trend for osteoporosis diagnosis with respect to both normal and osteopenic status. The same genotype resulted to be associated to lower values of BMD both at spine and femur sites. No association was found with fractures. DISCUSSION In conclusion the presence of the homozygote ss genotype seemed to predispose to osteoporosis diagnosis and to be more frequent in subjects with lower spine and femur BMD values.
Quantile Curve Estimation and Visualization for Nonstationary Time Series

There is an increasing interest in studying time-varying quantiles, particularly for environmental processes. For instance, high pollution levels may cause severe respiratory problems, and large precipitation amounts can damage the environment, and have negative impacts on the society. In this article we address the problem of quantile curve estimation for a wide class of nonstationary and/or non-Gaussian processes. We discuss several nonparametric quantile curve estimates, give asymptotic results, and propose a data-driven procedure for the selection of smoothing parameters. This methodology provides a statistically reliable and computationally efficient graphical tool that can be used for the exploration and visualization of the behavior of time-varying quantiles for nonstationary time series. A Monte Carlo simulation study and two applications to ozone time series illustrate our method. R codes with the algorithm for selection of smoothing parameters (described in Section 3) are available in the online supplements.
Human Bipedalism, Evolved from Arboreal Locomotion of Two-arm Brachiation

Among all kinds of apes, only gibbons have the slim body as human. Gibbons can move in the forest by cross arm swing, what was the locomotion mode of our arboreal ancestor? Since our ancestor had much heavier body but weaker arms than gibbons, we suppose they had to move with two-arm brachiation. Such mode of locomotion can account reasonably for the transition to bipedalism. Firstly, it needed our ancestor to straighten knee and hip joints and flex their lumbar spine; secondly, it evolved our ancestor’s feet with longitudinal arches; and most importantly, it made the ratio of the length of the upper limbs to that of the lower limbs unsuitable for quadruped walking.
Treatment of nasal polyps with intranasal beclomethasone dipropionate aerosol

In a double‐blind trial thirty‐five patients with moderately‐severe nasal polyposis were treated with intranasal beclomethasone dipropionate aerosol for 3 weeks. The dose given (400 γg/day) had only local effect on the symptoms. Judged by diary card scores the nasal symptoms were reduced to 52% of the pre‐trial level for the whole group. Corrected for the placebo effect the percentage was 68. The reduction of symptoms was equally apportioned to the three symptoms, sneezing, nasal secretion and blockage.
System control and DC voltage control method for stacom based on hybrid multilevel H-bridge converter

This paper presents an improved structure for static synchronous compensator (STATCOM) system based on hybrid multilevel H-bridge converter. In the new structure, the chosen of dc capacitor capacitance is considered for every module, which will reduce the dc capacitor capacitance and reduce the cost of the system. A novel system control and dc capacitor voltage balance control strategy is presented for the new system. The control includes two levels. Upper level use direct current control realize inactive current control, and lower level use a PLL of compensating current realize the dc voltage control. Simulation results show that the new control method can not only compensate reactive power but also can maintain dc voltage at a given value.
Reconciling float-based and tracer-based estimates of eddy 1 diffusivities

7 Lateral diffusivities are computed from synthetic particles and tracers advected by a 8 velocity field derived from sea surface height measurements from the South Pacific, in a 9 region west of Drake Passage. Three different estimates are compared: (1) the tracer-based 10 “effective diffusivity” of Nakamura (1996), (2) the growth of the second moment of a cloud of 11 tracer and (3) the single and two-particle Lagrangian diffusivities. The effective diffusivity 12 measures the cross-stream component of eddy mixing, so the manuscript focusses on the 13 meridional diffusivities for the others, as the mean flow (the ACC) is zonally-oriented in the 14 region. 15 After an initial transient of a few weeks the effective diffusivity agrees well with the 16 meridional diffusivity estimated both from the tracer cloud and from the particles. This 17 proves that particle and tracer based estimates of eddy diffusivities are equivalent, despite 18 recent claims to the contrary. Convergence among the three estimates requires that the 19 Lagrangian diffusivities are estimated via their asymptotic values, not their maximum values. 20 The former are generally much lower than the latter in the presence of a mean flow. 21
Post-quantum message authentication cryptography based on error-correcting codes

in this paper we analyse possibilities of application of post-quantum code based signature schemes for message authentication purposes. An error-correcting code based digital signature algorithm is presented. There also shown results of computer simulation for this algorithm in case of Reed-Solomon codes and the estimated efficiency of its software implementation. We consider perspectives of error-correcting codes for message authentication and outline further research directions.
Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial.

PURPOSE We investigated the safety and efficacy (response rates, time to disease progression, survival) of trastuzumab, carboplatin, gemcitabine, and paclitaxel in advanced urothelial carcinoma patients and prospectively evaluated human epidermal growth factor receptor-2 (Her-2/neu) overexpression rates. PATIENTS AND METHODS Advanced urothelial carcinoma patients were screened for Her-2/neu overexpression. Eligibility for therapy required human epidermal growth factor receptor-2 (Her-2/neu) overexpression by immunohistochemistry (IHC), gene amplification and/or elevated serum Her-2/neu, no prior chemotherapy for metastasis, and adequate organ function including a normal cardiac function. Treatment consisted of trastuzumab (T) 4 mg/kg loading dose followed by 2 mg/kg on days 1, 8, and 15; paclitaxel (P) 200 mg/m2 on day 1; carboplatin (C; area under the curve, 5) on day 1; and gemcitabine (G) 800 mg/m2 on days 1 and 8. The primary end point was cardiac toxicity. RESULTS Fifty-seven (52.3%) of 109 registered patients were Her-2/neu positive, and 48.6% were positive by IHC. Her-2/neu-positive patients had more metastatic sites and visceral metastasis than did Her-2/neu negative patients. Forty-four of 57 Her-2/neu-positive patients were treated with TPCG. The median number of cycles was six (range, 1 to 12 cycles). The most common grade 3/4 toxicity was myelosuppression. Grade 3 sensory neuropathy occurred in 14% of patients, and 22.7% experienced grade 1 to 3 cardiac toxicity (grade 3, n = 2: one left ventricular dysfunction, one tachycardia). There were three [corrected] therapy-related deaths. Thirty-one (70%) of 44 patients responded (five complete and 26 partial), and 25 (57%) of 44 were confirmed responses. Median time to progression and survival were 9.3 and 14.1 months, respectively. CONCLUSION We prospectively characterized Her-2/neu status in advanced urothelial carcinoma patients. TPCG is feasible; cardiac toxicity rates were higher than projected, but the majority were grade two or lower. Determining the true contribution of trastuzumab requires a randomized trial.
Prehistoric Blood Residues: Detection on Tool Surfaces and Identification of Species of Origin

Blood residues from several animal species have been discovered on the surfaces of chert, basalt, and obsidian prehistoric tools (1000 to 6000 years old) from open-air sites along the western coast and in the northern boreal forest of Canada. A screening test has been developed to detect residual blood. Hemoglobin has been crystallized from the residues, and the species of origin determined.
Diazoxide blocks glutamate desensitization and prolongs excitatory postsynaptic currents in rat hippocampal neurons.

1. The effects of diazoxide (DZ) on synaptic transmission and upon responses to exogenously applied glutamate agonists were examined in cultured hippocampal neurons. 2. DZ reversibly increased the peak amplitude of evoked excitatory postsynaptic currents (EPSCs) to 150 +/‐ 100% of control and prolonged the EPSC decay time constant (tau) from 5.9 +/‐ 1.2 ms to 14 +/‐ 6.2 ms (240% of control). 3. Peak and steady‐state glutamate (Glu) and quisqualate (QA) currents activated by exogenous application were dramatically increased by DZ at concentrations which did not influence N‐methyl‐D‐aspartate (NMDA), kainate (KA), or GABA currents. These effects were rapidly and completely reversible. Active and passive membrane properties were unaffected by DZ. 4. Inhibitory postsynaptic currents (IPSCs) were unaffected by the same DZ concentrations. 5. These experiments indicate that desensitization plays an important role in terminating excitatory transmission between mammalian central neurons. DZ and perhaps related compounds will ultimately help us identify the regions of the AMPA/KA receptor responsible for desensitization.
Pathological changes in the lungs and mammary glands of sheep and their relationship with maedi-visna infection

Maedi-visna, a multisystemic disease of adult sheep, was first described in Spain in 1984. To get an idea of the seroprevalence of the disease locally and to estimate the number of seropositive animals with lesions, samples of blood, lungs and mammary glands were taken from 124 randomly selected sheep killed in the main slaughterhouse of Zaragoza. In the agar gel immunodiffusion test, 74 (59.7 per cent) of the sheep were positive and 50 were negative. Among the 74 seropositive animals, 19 (25.6 per cent) had no lesions in any organ, 12 (16.2 per cent) had lesions in the lungs only, 15 (20.2 per cent) had lesions in the mammary glands and 28 (37.8 per cent) had lesions in both organs. In the lungs hyperplasia of lymphoid follicles was more evident than an interstitial infiltrate but in the mammary glands this relationship was not observed. Even when the lesions occurred in both organs, they did not show the expected proportion in terms of either type or severity. Among the 50 seronegative sheep, eight (16 per cent) showed maedi-like lesions, formed exclusively by the hyperplasia of lymphoid follicles.
Universal versus genotype-guided use of direct oral anticoagulants in atrial fibrillation patients: a decision analysis.

AIM This study aims to compare clinical and economic outcomes of CYP2C9 and VKORC1 genotype-guided (PG-DOAC) versus universal use of direct oral anticoagulant (DOAC) for stroke prevention in patients with atrial fibrillation (AF). METHODS Outcomes of oral anticoagulation therapy were simulated using life-long Markov modeling. In PG-DOAC, patients with genotype of high or low warfarin sensitivity were treated with DOAC, and patients with normal warfarin sensitivity genotype received warfarin. RESULTS Expected quality-adjusted life-years (QALYs) and cost of DOAC were higher than PG-DOAC. Incremental cost per QALY (ICER) of DOAC versus PG-DOAC was 314,129 USD/QALY, exceeding willingness-to-pay threshold (50,000 USD/QALY). CONCLUSION Using individual genotype to guide the use of DOAC versus warfarin appears to be the preferred strategy.
Microsatellite DNA evidence for genetic drift and philopatry in Svalbard reindeer

Mainland populations of Arctic reindeer and caribou Rangifer tarandus often undergo extensive movements, whereas populations on islands tend to be isolated and sedentary. To characterize the genetic consequences of this difference, levels of genetic diversity and subdivision of Svalbard reindeer (R. t. platyrhynchus) from two adjacent areas on Nordenskjiöldland, Spitsbergen were estimated using data from up to 14 microsatellites. The mean number of alleles per locus in Svalbard reindeer was 2.4 and mean expected heterozygosity per locus was 0.36. The latter value was significantly lower than in Canadian caribou and Norwegian reindeer but higher than in some other cervid species. Large samples of females (n = 743) and small samples of males (n = 38) from two sites ≈ 45 km apart showed genetic subdivision, which could be due to local population fluctuations or limited gene flow. To our knowledge, this is the first study to report significant differentiation at microsatellite loci in Rangifer at such short geographical distances. Neither population showed genetic evidence for recent population bottlenecks when loci unbiased with respect to heterozygosity were analysed. In contrast, false signals of a recent bottleneck were detected when loci upwardly biased with respect to heterozygosity were analysed. Thus, Svalbard reindeer appeared to conform to the paradigm of island populations made genetically depauperate by genetic drift.