Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity and tolerability of the Bruton's tyrosine kinase (Btk) inhibitor PCI-32765 in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): Interim results of a phase Ib/II study.

6508 Background: Btk is essential to B-cell development and function. Btk is highly-expressed in CLL and its inhibition by the potent irreversible inhibitor PCI32765 (P) promotes apoptosis and inhibition of cytokine, chemokine, microenvironment-mediated signaling, proliferation, and chemotaxis ex vivo. We report interim results of a large Phase Ib/II trial of P in CLL/SLL. METHODS Two cohorts (previously untreated [PU] >65 yrs old and relapsed/refractory [R/R] disease following at least 2 prior therapies [Rx] including fludarabine) of CLL patients (pts) were treated with oral P administered daily for 28-d cycles until progression of disease (PD). Doses of 420mg (24 PU and 27 R/R) and 840 QD (31 R/R) were examined. RESULTS Of the 78 pts enrolled, data from the first 39 pts will be sufficiently mature as of May 2011 to assess IWCLL2008/Cheson response criteria. R/R pts had a median age of 64, 37% were Rai III/IV, and median of 3 (range 2-10) prior Rx. 87% had at least one poor-risk molecular feature: del(17p)-30%, del(11q)-21%, IgVH un-mutated 70%. Treatment has been well tolerated with grade >3 AEs potentially related to P in 26% of pts. >Gr 3 cytopenias have been noted in <5% of pts. No pts have had LFT elevations. In evaluable pts with lymphadenopathy, the rate of nodal response (LNR; >50% reduction in target lesions) is 89% (25/28 pts). An increase in absolute lymphocyte counts (ALC) occurred in 75% of pts and has decreased over time in the vast majority. At a median follow-up of 4 months, 17 (44%) have a PR (n=15, 39%) or CR/CRu (n=2, 5%). Response has been similar in all genomic groups. Notably, 4 of 12 pts with del(17p) have responded and 7 others remain on P Rx with improving SD. Mature response data will be updated. At a median follow-up of 4 months, 34/39 pts in the 420 mg cohort remain on P therapy with only one PD. CONCLUSIONS PCI32765 is highly active and well tolerated in CLL/SLL pts irrespective of high risk genomic abnormalities. Although follow-up is short, the high response rate and very low progression rate suggests that PCI-32765 may be an important new targeted treatment approach for CLL pts, including those with del(17p).
Ten Years of File Sharing and Its Effect on International Physical and Digital Music Sales

Music consumption is arguably at a historic high. File sharing technology would undoubtedly be welfare-improving provided that it did not displace music sales. Yet music purchases have decayed sharply since the introduction of file sharing a decade ago. This paper seeks to measure the effect of peer-to-peer file sharing on music sales. I use a long panel of twelve years of country-level data containing information on both physical and digital music sales and on Internet and broadband penetration. This database includes not only information going back to a period when peer-to-peer downloading did not exist, but also includes more recent information up to 2008. I employ Internet connectedness and the speed of Internet connections as proxies for unauthorized downloading, and study whether physical and total country-level music purchases have decayed more rapidly in countries experiencing faster increases in the adoption of file swapping technology. This paper uses the increase in broadband penetration replacing dial-up in order to isolate the effect of file sharing from any other possible Internet impact on music sales. My results indicate that peer-to-peer file-sharing can explain a reduction in music sales that ranges from half of the actual decrease in sales up to the entire decrease.
Thermal characterization and modelling of a gallium arsenide power amplifier MMIC

Thermal characterization of high power microwave devices is important for determining their reliability. Exceeding the optimal temperature will have a detrimental effect on the performance and reliability of these devices. However, temperature characterization of submicron features is often challenging and numerical simulations are often used. In this paper, a detailed finite element thermal model of a power amplifier Monolithic Microwave Integrated Circuit (MMIC) was developed and analyzed to obtain the peak operating junction temperature. Although detailed models would give more accurate results, they usually require more computational effort and time. Hence, a simplified finite element thermal model was also developed and its results compared with those for the detailed model. It was found that the results from the simplified model are higher than those from the detailed model by about 3°C to 8°C at 1W/mm and 1.5W/mm respectively. The temperature distributions of actual power amplifier MMIC devices were measured using IR thermography and thermoreflectance (TR) thermography. It was found that the temperature measured using TR thermography agreed very well with the FEA results but those obtained using IR thermography did not.
Dynamin 2 and c-Abl Are Novel Regulators of Hyperoxia-mediated NADPH Oxidase Activation and Reactive Oxygen Species Production in Caveolin-enriched Microdomains of the Endothelium*

Reactive oxygen species (ROS) generation, particularly by the endothelial NADPH oxidase family of proteins, plays a major role in the pathophysiology associated with lung inflammation, ischemia/reperfusion injury, sepsis, hyperoxia, and ventilator-associated lung injury. We examined potential regulators of ROS production and discovered that hyperoxia treatment of human pulmonary artery endothelial cells induced recruitment of the vesicular regulator, dynamin 2, the non-receptor tyrosine kinase, c-Abl, and the NADPH oxidase subunit, p47phox, to caveolin-enriched microdomains (CEMs). Silencing caveolin-1 (which blocks CEM formation) and/or c-Abl expression with small interference RNA inhibited hyperoxia-mediated tyrosine phosphorylation and association of dynamin 2 with p47phox and ROS production. In addition, treatment of human pulmonary artery endothelial cells with dynamin 2 small interfering RNA or the dynamin GTPase inhibitor, Dynasore, attenuated hyperoxia-mediated ROS production and p47phox recruitment to CEMs. Using purified recombinant proteins, we observed that c-Abl tyrosine-phosphorylated dynamin 2, and this phosphorylation increased p47phox/dynamin 2 association (change in the dissociation constant (Kd) from 85.8 to 6.9 nm). Furthermore, exposure of mice to hyperoxia increased ROS production, c-Abl activation, dynamin 2 association with p47phox, and pulmonary leak, events that were attenuated in the caveolin-1 knock-out mouse confirming a role for CEMs in ROS generation. These results suggest that hyperoxia induces c-Abl-mediated dynamin 2 phosphorylation required for recruitment of p47phox to CEMs and subsequent ROS production in lung endothelium.
Case Studies in Co-Teaching in the Content Areas

This article presents recent findings from several long-term qualitative investigations of co-teaching in science and social studies content-area classes, in which collaborating teachers and students with and without disabilities were observed and interviewed regarding effective practices and challenges associated with inclusion. In some sites, collaborating teachers were provided with research-based effective strategies and materials for including students with disabilities in specific activities. Results were equivocal in that in some cases, collaboration was extremely effective and conducive for promoting success for students with disabilities in inclusive classes. In others, challenges remained that presented barriers for successful collaboration and inclusion for students with disabilities. Important mediating variables were identified as academic content knowledge, high-stakes testing, and co-teacher compatibility. Findings are discussed with respect to both successes and remaining challenges.
Mouse Model of Human Congenital Heart Disease: Progressive Atrioventricular Block Induced by a Heterozygous Nkx2-5 Homeodomain Missense Mutation

Background—Heterozygous human NKX2-5 homeodomain (DNA-binding domain) missense mutations are highly penetrant for varied congenital heart defects, including progressive atrioventricular (AV) block requiring pacemaker implantation. We recently replicated this genetic defect in a murine knockin model, in which we demonstrated highly penetrant, pleiotropic cardiac anomalies. In this study, we examined postnatal AV conduction in the knockin mice. Methods and Results—A murine knockin model (Arg52Gly, Nkx2-5+/R52G) in a 129/Sv background was analyzed by histopathology, surface, and telemetry ECG, and in vivo electrophysiology studies, comparing with control Nkx2-5+/+ mice at diverse postnatal stages, ranging from postnatal day 1 (P1) to 17 months. PR prolongation (first degree AV block) was present at 4 weeks, 7 months, and 17 months of age, but not at P1 in the mutant mice. Advanced AV block was also occasionally demonstrated in the mutant mice. Electrophysiology studies showed that AV nodal function and right ventricular effective refractory period were impaired in the mutant mice, whereas sinus nodal function was not affected. AV nodal size was significantly smaller in the mutant mice than their controls at 4 weeks of age, corresponding to the presence of PR prolongation, but not P1, suggesting, at least in part, that the conduction abnormalities are the result of a morphologically atrophic AV node. Conclusions—The highly penetrant and progressive AV block phenotype seen in human heterozygous missense mutations in NKX2-5 homeodomain was replicated in mice by knocking in a comparable missense mutation.
A 800 Mbps and 12.37 ps Jitter Bidirectional Mixed-Voltage I/O Buffer With Dual-Path Gate-Tracking Circuit

This paper proposes a high speed bidirectional mixed-voltage I/O buffer using 90 nm 1.2 V standard CMOS process. By using a dynamic gate bias generator to provide appropriate gate drive voltages for the output stage, the I/O buffer can transmit/receive 2 × VDD voltage level signal without any gate-oxide overstress hazard. Most important of all, the gate-oxide overstress hazard is eliminated by adopting a dual-path gate-tracking circuit. The maximum data rate and jitter are measured to be 800 Mbps/12.37 ps and 704 Mbps/14.79 ps for 1.2 V and 2.5 V signal voltage, respectively, with a given capacitive load of 20 pF.
Maîtrise du risque aflatoxique : utilisation d'extraits naturels et mise en évidence de leurs mécanismes d'action

L’aflatoxine B1 (AFB1) est une mycotoxine contaminant de nombreux substrats agricoles, notamment les cereales, arachides, pistaches, graines de coton et autres fruits secs. Elle est genotoxique, agit comme un initiateur de la cancerogenese et elle est classee par le CIRC (Centre International de Recherche sur le Cancer) dans le groupe I des molecules carcinogenes pour les hommes et les animaux. Cette toxine est produite par des especes fongiques appartenant essentiellement au genre Aspergillus et a la section Flavi ; A. flavus etant l’espece la plus preoccupante. Cette espece peut se developper a la fois au champ ou lors du stockage des matieres premieres apres recolte. Plusieurs etudes montrent qu’un grand nombre de denrees alimentaires destinees a l’alimentation humaine et animale sont contaminees par les aflatoxines mettant en evidence la faible efficacite ou l’insuffisance des strategies actuelles utilisees pour la maitrise de cette contamination. L’objectif principal de cette etude est le developpement d’une strategie alternative basee sur l’utilisation de produits naturels et visant a reduire la production de la toxine par les moisissures aflatoxinogenes. Grâce a l’elaboration d’un outil moleculaire regroupant un ensemble de genes impliques directement ou indirectement dans la biosynthese de l’AFB1, ce travail permet de mieux comprendre le mecanisme d’action moleculaire de composes anti-aflatoxinogenes. Des extraits aqueux de plantes mediterraneennes ont ete testes pour leur efficacite a inhiber l’aflatoxinogenese. Ainsi, l’extrait aqueux d’hysope, Micomeria graeca, presente des proprietes anti-aflatoxinogenes importantes sans modification de la croissance fongique. Son effet inhibiteur sur plusieurs souches productrices d’aflatoxines ainsi que son mecanisme d’action ont ete caracterises. Ce dernier semble impliquer des genes pivots dans la regulation des metabolismes fongiques primaire et secondaire ainsi que des voies impliquees dans la reponse cellulaire au stress oxydatif. Ces travaux permettent de valider l’utilisation d’extraits naturels comme strategie alternative de lutte contre la contamination des aliments par les aflatoxines.
Toward Realistic Simulation of Intervehicle Communication

The quality of intelligent transportation systems strongly depends on the underlying communication protocols and techniques. In this article, we discuss the current state of the art, trends, and open problems in the area of simulation techniques used to study intervehicle communication (IVC). Here, we touch on a broad range of topics but focus on three aspects that have a strong influence on the degree of realism and hence the reliability of simulation results: the need to integrate microscopic mobility models, the used evaluation metrics, and the impact of human driver behavior on a macroscopic scale. We study and discuss the state of the art of simulation-based performance evaluation of IVC protocols and applications. In the scope of this article, we concentrate on the most recent advances and findings by outlining selected models, techniques, and issues that are specifically related to IVC, with a strong focus on aspects beyond network simulation issues. The main objective is to determine the degree to which available simulation techniques produce realistic results.
Pacific Salmon at the Crossroads: Stocks at Risk from California, Oregon, Idaho, and Washington

Abstract The American Fisheries Society herein provides a list of depleted Pacific salmon, steelhead, and sea-run cutthroat stocks from California, Oregon, Idaho, and Washington, to accompany the list of rare inland fishes reported by Williams et al. (1989). The list includes 214 native naturally-spawning stocks: 101 at high risk of extinction, 58 at moderate risk of extinction, 54 of special concern, and one classified as threatened under the Endangered Species Act of 1973 and as endangered by the state of California. The decline in native salmon, steelhead, and sea-run cutthroat populations has resulted from habitat loss and damage, and inadequate passage and flows caused by hydropower, agriculture, logging, and other developments; overfishing, primarily of weaker stocks in mixed-stock fisheries; and negative interactions with other fishes, including nonnative hatchery salmon and steelhead. While some attempts at remedying these threats have been made, they have not been enough to prevent the broad decl.
Optochin in the Identification of Str. pneumoniae

In 1911 Morgenroth and Levy showed that mice could be protected against pneumococcal infection with "optochin " (ethylhydrocupreine hydrochloride). The clinical use of this agent was soon abandoned as it was found to be toxic and, in doses which could be tolerated, did not influence the course of lobar pneumonia (Moore and Chesney, 1917; White, 1938). Subsequent in vitro studies showed that of the streptococci, Str. pneumoniae was the most sensitive (Moore, 1915), and that as low a concentration as 1 in 50,000 incorporated in blood agar would inhibit growth (M0rch, 1943). Bile solubility has been generally regarded as the most reliable test for the differentiation of pneumococci from other haemolytic streptococci (Wilson and Miles, 1946). The test, however, is time-consuming and sometimes gives equivocal results. This paper describes an investigation to determine whether " optochin " sensitivity can be used for the identification of Str. pneumoniae in place of the bile solubility test. A large number of alpha haemolytic streptococci were examined to ascertain the correlation between these tests. Mouse virulence was used as the final criterion of the clinical significance of some of the strains.
A Novel Lipase Belonging to the Hormone-sensitive Lipase Family Induced under Starvation to Utilize Stored Triacylglycerol in Mycobacterium tuberculosis*

Twenty-four putative lipase/esterase genes of Mycobacterium tuberculosis H37Rv were expressed in Escherichia coli and assayed for long-chain triacylglycerol (TG) hydrolase activity. We show here that the product of Rv3097c (LIPY) hydrolyzed long-chain TG with high specific activity. LIPY was purified after solubilization from inclusion bodies; the enzyme displayed a Km of 7.57 mm and Vmax of 653.3 nmol/mg/min for triolein with optimal activity between pH 8.0 and pH 9.0. LIPY was inhibited by active serine-directed reagents and was inactivated at temperatures above 37 °C. Detergents above their critical micellar concentrations and divalent cations inhibited the activity of LIPY. The N-terminal half of LIPY showed sequence homology with the proline glutamic acid-polymorphic GC-rich repetitive sequences protein family of M. tuberculosis. The C-terminal half of LIPY possesses amino acid domains homologous with the hormone-sensitive lipase family and the conserved active-site motif GDSAG. LIPY shows low sequence identity with the annotated lipases of M. tuberculosis and with other bacterial lipases. We demonstrate that hypoxic cultures of M. tuberculosis, which had accumulated TG, hydrolyzed the stored TG when subjected to nutrient starvation. Under such conditions, lipY was induced more than all lipases, suggesting a central role for it in the utilization of stored TG. We also show that in the lipY-deficient mutant, TG utilization was drastically decreased under nutrient-deprived condition. Thus, LIPY may be responsible for the utilization of stored TG during dormancy and reactivation of the pathogen.
Prolyl endopeptidase purified from granulomatous inflammation in mice

Activity of prolyl endopeptidase (EC 3.4.21.26) which hydrolyses the Pro7‐Phe8 bond in angiotensin II has been found to elevate in experimentally produced granulomatous inflammation in liver and skin. We purified the enzyme 1,536‐fold by 6 steps from murine hepatic granulomas. The purified enzyme has a molecular weight of 79 kDa and physiocochemical properties equivalent to those previously reported for prolyl endopeptidase purified from other sources. By HPLC analysis, the cleavage of Phe8‐Leu10 and Phe8 from angiotensin I and II, respectively, was detected and quantified. Monospecific IgG was prepared from serum of rabbits injected with purified enzyme. Concentration of the enzyme was immunohistochemically detected in cells which form granulomatous organization, but not in inflammatory cells surrounding the foci. The antibody, however, cross reacted with the enzyme in adjacent liver cells and weakly stained their cytoplasm. The findings indicate that this enzyme, in addition to angiotensin converting enzyme, may serve as a useful biochemical marker for granulomatous tissue reactions.
Regional comparison of prolactin gene expression in the human decidualized endometrium in early and term pregnancy.

Prolactin (PRL) is known to be expressed in the decidualized human endometrium and secreted into amniotic fluid. Although the site of synthesis of endometrial PRL is known to be the decidual cells, the difference in PRL gene expression within each area of decidua, i.e. decidua basalis, decidua parietalis and decidua capsularis, during pregnancy is not clear. We have applied an in situ hybridization histochemistry technique using a radiolabeled RNA probe to compare the difference in expression of PRL gene within each area of the decidualized endometrium. Specific hybridization signals were distributed over the decidual cells in early and term pregnancy. More intense hybridization signals were always detected in the tissues of early pregnancy than in those of term pregnancy. In the decidua capsularis of early pregnancy, labeled cells were concentrated close to the amniotic cavity, whereas cells were concentrated close to the maternal surface of the fetal membrane in term pregnancy. In the decidua parietalis, almost all decidual cells were labeled, but no specific labeling was seen in the endometrial glands or capillary endothelium in both groups. In the decidua basalis, most decidual cells showed hybridization signals whereas no hybridization signal was seen over the trophoblast cells. These results show that there are regional and periodic differences in PRL gene expression in the decidual cells during pregnancy.
CNT array capacitive MEM switches for reconfigurable interconnects

This paper reports, for the first time, the wafer-level technology and characteristics of RF MEMS capacitive switches based on CNT arrays. A surface micromachining fabrications process using grown horizontal CNT membranes from pre-patterned catalysts is validated and fully functional devices are reported. The RF characteristics of the CNT capacitive switches up to 6GHz show very low actuation voltage (6V) and power consumption and an isolation of 10dB at 5GHz. The CNT membranes present an equivalent Young's modulus of 8.5GPa and a resistivity of 0. 0083Ωcm, extracted from the DC characterization. Their features are promising and support the idea that, once the CNT horizontal interconnect will become a reality, their reconfigurability at high frequency is possible with switches based on CNTs, exploiting the same CNT material as the long horizontal interconnects.
Thyroid dysfunction during late gestation is associated with excessive iodine intake in pregnant women.

CONTEXT Adequate iodine intake during pregnancy is essential for both the synthesis of maternal thyroid hormones and the maintenance of normal fetal brain development. Scant evidence is available on the effects of excessive iodine intake during pregnancy. OBJECTIVE The study assesses the relationship between iodine nutritional status and thyroid function of pregnant women with excessive iodine intake during late gestation. DESIGN AND PARTICIPANTS A cross-sectional study of 384 pregnant women was carried out in Tianjin and Haixing from April to October in 2010. MAIN OUTCOME MEASURES Morning urine samples and blood samples were obtained from all subjects. Serum levels of free T(3), free T(4), and sensitive TSH and urinary iodine concentration were measured. RESULTS The median urinary iodine concentration of pregnant women with excessive iodine intake was significantly higher than those with adequate iodine intake (P < 0.001). The prevalence of thyroid disease, especially subclinical hypothyroidism, in pregnant women with excessive iodine intake was significantly higher than in those with adequate iodine intake (P < 0.05). Subclinical hypothyroidism was the most frequent pattern of thyroid disease for pregnant women and those with positive or negative thyroid autoantibodies. Living with high water iodine content and having urinary iodine concentration higher than 250 μg/liter are associated risk factors for subclinical hypothyroidism in pregnant women (OR(1) = 41.822, OR(2) = 6.202; P < 0.05, where OR(1) is the odds ratio for living with high water iodine content and hypothyroidism and OR(2) is the odds ratio for urinary iodine concentration >250 μg/liter and hypothyroidism). CONCLUSIONS Excessive iodine intake during late pregnancy may lead to maternal thyroid dysfunction, particularly subclinical hypothyroidism. The appropriate measurements should be performed to monitor the onset of hypothyroidism in pregnant women with excessive iodine intake.