Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity of the Hypoxia-Activated Prodrug, TH-302, in Preclinical Human Acute Myeloid Leukemia Models

Purpose: Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm. Recent evidence has shown the bone marrow microenvironment in patients with AML to be intrinsically hypoxic. Adaptive cellular responses by leukemia cells to survive under low oxygenation also confer chemoresistance. We therefore asked whether therapeutic exploitation of marrow hypoxia via the hypoxia-activated nitrogen mustard prodrug, TH-302, could effectively inhibit AML growth. Experimental Design: We assessed the effects of hypoxia and TH-302 on human AML cells, primary samples, and systemic xenograft models. Results: We observed that human AML cells and primary AML colonies cultured under chronic hypoxia (1% O2, 72 hours) exhibited reduced sensitivity to cytarabine-induced apoptosis as compared with normoxic controls. TH-302 treatment resulted in dose- and hypoxia-dependent apoptosis and cell death in diverse AML cells. TH-302 preferentially decreased proliferation, reduced HIF-1α expression, induced cell-cycle arrest, and enhanced double-stranded DNA breaks in hypoxic AML cells. Hypoxia-induced reactive oxygen species by AML cells were also diminished. In systemic human AML xenografts (HEL, HL60), TH-302 [50 mg/kg intraperitoneally (i.p.) 5 times per week] inhibited disease progression and prolonged overall survival. TH-302 treatment reduced the number of hypoxic cells within leukemic bone marrows and was not associated with hematologic toxicities in nonleukemic or leukemic mice. Later initiation of TH-302 treatment in advanced AML disease was as effective as earlier TH-302 treatment in xenograft models. Conclusions: Our results establish the preclinical activity of TH-302 in AML and provide the rationale for further clinical studies of this and other hypoxia-activated agents for leukemia therapy. Clin Cancer Res; 19(23); 6506–19. ©2013 AACR.
Intelligence Analysis Based on Social Network

With the development of social networks, more and more terror and insurgency began to penetrate into cyberspace. This paper studies how to use the real-time information on the social network to analyze information, and discuss from the content of, the way to and the handling of collection of information-gathering. With the information of the auxiliary network, the proposed model can be used to identify "the hand behind the senses", even if under anonymous handling this can also play a role.
The Fear of Others: A Pilot Study of Social Anxiety Processes in Paranoia

Background and Aims: There is good reason to consider the role of social anxiety processes in paranoia; both the research and clinical literature indicate significant overlap between the two presentations. The aim of this study was to explore cognition and behaviour that are typically associated with social phobia, in people with paranoia, and then to draw out theoretical and clinical implications. Method: We used a cross-sectional between-subjects design to compare participants with persecutory delusions (without social phobia), social phobia, a clinical control group with panic disorder, and a non-clinical control group. Ten to 15 people were recruited to each of four groups, with a final total of 48 participants. Each person completed measures of automatic thoughts, underlying assumptions, core beliefs and behaviour, and took part in a semi-structured interview designed to assess process (self-consciousness and attentional focus) and metacognitive beliefs. Results: Surprisingly, measures of cognition and behaviour yielded no systematic differences between people with persecutory delusions and social phobia. Conclusions: People with persecutory delusions may experience overt and underlying cognition typically associated with social phobia, and behave in similar ways in response to perceived social threat. These initial results indicate: (i) that larger scale research is now warranted in order to draw firm conclusions about social anxiety processes in paranoia; (ii) more specific hypotheses to be tested; and (iii) a clinical model of paranoia, based on the cognitive model of social phobia, which might now usefully be validated.
Ionic Liquid Electrolytes for Li–Air Batteries: Lithium Metal Cycling

In this work, the electrochemical stability and lithium plating/stripping performance of N-butyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide (Pyr14TFSI) are reported, by investigating the behavior of Li metal electrodes in symmetrical Li/electrolyte/Li cells. Electrochemical impedance spectroscopy measurements and galvanostatic cycling at different temperatures are performed to analyze the influence of temperature on the stabilization of the solid electrolyte interphase (SEI), showing that TFSI-based ionic liquids (ILs) rank among the best candidates for long-lasting Li–air cells.
Expected Estimating Equations for Missing Data, Measurement Error, and Misclassification, with Application to Longitudinal Nonignorable Missing Data

Summary Missing data, measurement error, and misclassification are three important problems in many research fields, such as epidemiological studies. It is well known that missing data and measurement error in covariates may lead to biased estimation. Misclassification may be considered as a special type of measurement error, for categorical data. Nevertheless, we treat misclassification as a different problem from measurement error because statistical models for them are different. Indeed, in the literature, methods for these three problems were generally proposed separately given that statistical modeling for them are very different. The problem is more challenging in a longitudinal study with nonignorable missing data. In this article, we consider estimation in generalized linear models under these three incomplete data models. We propose a general approach based on expected estimating equations (EEEs) to solve these three incomplete data problems in a unified fashion. This EEE approach can be easily implemented and its asymptotic covariance can be obtained by sandwich estimation. Intensive simulation studies are performed under various incomplete data settings. The proposed method is applied to a longitudinal study of oral bone density in relation to body bone density.
β-Endorphin neuronal transplantation into the hypothalamus alters anxiety-like behaviors in prenatal alcohol-exposed rats and alcohol-non-preferring and alcohol-preferring rats.

BACKGROUND Alcohol exposure has adverse effects on stress physiology and behavioral reactivity. This is suggested to be due, in part, to the effect of alcohol on β-endorphin (β-EP)-producing neurons in the hypothalamus. In response to stress, β-EP normally provides negative feedback to the hypothalamic-pituitary-adrenal axis and interacts with other neurotransmitter systems in the amygdala to regulate behavior. We examined whether β-EP neuronal function in the hypothalamus reduces the corticosterone response to acute stress, attenuates anxiety-like behaviors, and modulates alcohol drinking in rats. METHODS To determine whether β-EP neuronal transplants modulate the stress response, anxiety behavior, and alcohol drinking, we implanted differentiated β-EP neurons into the paraventricular nucleus (PVN) of the hypothalamus of normal, prenatal alcohol-exposed, and alcohol-preferring (P) and alcohol-non-preferring (NP) rats. We then assessed corticosterone levels in response to acute restraint stress and other markers of stress response in the brain and anxiety-like behaviors in the elevated plus maze and open-field assays. RESULTS We showed that β-EP neuronal transplants into the PVN reduced the peripheral corticosterone response to acute stress and attenuated anxiety-like behaviors. Similar transplants completely reduced the hypercorticosterone response and elevated anxiety behaviors in prenatal alcohol-exposed adult rats. Moreover, we showed that β-EP reduced anxiety behavior in P rats with minimal effects on alcohol drinking during and following restraint stress. CONCLUSIONS These data further establish a role of β-EP neurons in the hypothalamus for regulating physiological stress response and anxiety behavior and resemble a potential novel therapy for treating stress-related psychiatric disorders in prenatal alcohol-exposed children and those genetically predisposed to increased alcohol consumption.
Can compressive stress be measured experimentally within the annulus fibrosus of degenerated intervertebral discs?

Abstract The aims were to assess the ability of a pressure transducer to measure compressive stress within the annulus fibrosus of degenerated intervertebral discs. Measurements could help to explain the mechanisms of disc failure and low back pain. The methods used were as follows. Thirteen full-depth cores of annulus, 7 mm in diameter, were removed from the middle and outer annuli of two severely degenerated human discs and constrained within a metal cylinder. Then static compressive forces were applied by a planeended metal indenter of diameter 6.8 mm, while a strain-gauged pressure transducer, side mounted in a needle of diameter 0.9 mm and calibrated in saline, was pulled through the issue. The transducer output was converted into stress, and the average measured stress was compared with the nominal applied stress. Measurements were repeated at up to 21 load levels, with the transducer oriented vertically and horizontally. The results showed that the measured and applied stress were linearly related (average r2=0.98) with a mean gradient (calibration factor) of 0.98 (vertical stress) and 0.92 (horizontal stress). Gradients ranged between 1.28 and 0.73. Damaged transducers grossly under-recorded ‘stress’ even though their output remained proportional to applied load. It was concluded that pressure transducers can measure compressive stress inside a degenerated human annulus. The tissue is sufficiently deformable to allow efficient coupling of stress between the matrix and transducer membrane. Damage to the transducer can give misleading results.
Restoration of fragile histidine triad (FHIT) expression induces apoptosis and suppresses tumorigenicity in lung and cervical cancer cell lines

Loss of expression of the Fhit protein is often associated with the development of many human epithelial cancers, including lung and cervical carcinomas. Restoration of Fhit expression in cell lines derived from these tumors has however yielded conflicting results, prompting the need for careful evaluation of the oncosuppressive potential of FHIT. In the present study, we have investigated the effect of Fhit reintroduction in seven lung cancer and three cervical cancer cell lines. To achieve efficient gene transfer and high levels of transgene expression, we have used an adenoviral vector to transduce the FHIT gene. The induction of apoptosis was evaluated by using the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay and propidium iodide staining. Activation of caspases was detected by using Western blot analysis, and tumorigenic potential of transduced cells in the nude mouse was also assessed. Restoration of Fhit expression induced apoptosis in all Fhit-negative cell lines, with Calu-1, H460, and A549 being the most susceptible among the lung cancer cell lines and SiHa cells among cervical carcinomas. Activation of caspase-8 was always associated with Fhit-mediated apoptosis, and in vivo tumorigenicity was either abolished by FHIT gene transfer (in H460 and SK-Mes cells) or strongly suppressed (in A549 and SiHa cells). Our data demonstrate oncosuppressive properties and strong proapoptotic activity of the Fhit protein in lung and cervical cancer cell lines and strengthens the hypothesis of its possible use as a therapeutic tool.
A novel dual-band bandpass filter based on coupling of composite right/left hand CPW and (CSRRs) uses ferrite component

The physical characteristics of the materials perform an important factor in the design of the microwave filters. Several solutions have been proposed to improve the qualities of filtering. In this paper, we propose a new dual band-pass filter based on the coupling of a composite (CRLH) coplanar waveguide with complementary split ring resonators (CSRRs). The (CRLH) CPW is composed of two resonators, each one has an interdigital capacitor (CID) and two short-circuited stubs parallel to top ground plane. On the lower ground plane, we use defected ground structure technology (DGS) to engrave two (CSRRs) offered with different shapes and dimensions. Between the top ground plane and the substrate, we place a ferrite layer to control the electromagnetic coupling between (CRLH) CPW and (CSRRs). The global filter that has coplanar access will have a dual-band bandpass behavior around the magnetic resonances of (CSRRs).
Metabolic labeling and direct imaging of choline phospholipids in vivo

Choline (Cho)-containing phospholipids are the most abundant phospholipids in cellular membranes and play fundamental structural as well as regulatory roles in cell metabolism and signaling. Although much is known about the biochemistry and metabolism of Cho phospholipids, their cell biology has remained obscure, due to the lack of methods for their direct microscopic visualization in cells. We developed a simple and robust method to label Cho phospholipids in vivo, based on the metabolic incorporation of the Cho analog propargylcholine (propargyl-Cho) into phospholipids. The resulting propargyl-labeled phospholipid molecules can be visualized with high sensitivity and spatial resolution in cells via a Cu(I)-catalyzed cycloaddition reaction between the terminal alkyne group of propargyl-Cho and a labeled azide. Total lipid analysis of labeled cells shows strong incorporation of propargyl-Cho into all classes of Cho phospholipids; furthermore, the fatty acid composition of propargyl-Cho-labeled phospholipids is very similar to that of normal Cho phospholipids. We demonstrate the use of propargyl-Cho in cultured cells, by imaging phospholipid synthesis, turnover, and subcellular localization by both fluorescence and electron microscopy. Finally, we use propargyl-Cho to assay microscopically phospholipid synthesis in vivo in mouse tissues.
Complementation hypothesis: the necessity of a monoallelic gene expression mechanism in mammalian development

Gene expression from both parental alleles (biallelic expression) is beneficial in minimizing the occurrence of recessive genetic disorders in diploid organisms. However, imprinted genes in mammals display parent of origin-specific monoallelic expression. As some imprinted genes play essential roles in mammalian development, the reason why mammals adopted the genomic imprinting mechanism has been a mystery since its discovery. In this review, based on the recent studies on imprinted gene regulation we discuss several advantageous features of a monoallelic expression mechanism and the necessity of genomic imprinting in the current mammalian developmental system. We further speculate how the present genomic imprinting system has been established during mammalian evolution by the mechanism of complementation between paternal and maternal genomes under evolutionary pressure predicted by the genetic conflict hypothesis.
The Effectiveness Initiative: I. Medical Practice Guidelines

We examined the impact of the "effectiveness initiative" and medical practice guidelines on the practice of ophthalmology. The effectiveness initiative asserts that much of current medical practice is unnecessary or harmful, too costly, and unresponsive to patient desires. It promotes more critical review of the medical literature, research on outcomes, and stringent practice guidelines. Whereas current practice guidelines are helpful in codifying accepted procedures, they tend to sanction interventions of unproved value. Future guidelines will probably reject unproved interventions, especially if they are expensive. Although such guidelines may limit physicians' freedom of choice, they may protect them against capricious malpractice claims and unreasonable patient expectations.
Lagged macroeconomic variables sensitivity of firm stock returns on an emerging stock market

This study analyses lagged effect of macroeconomic variables on firm stock returns by employing data for the period from 1998 to 2012. The macroeconomic variables investigated in this study include: exchange rate, risk free rate, inflation, money supply and oil prices. For this purpose, generalized autoregressive conditional heteroskedasticity (GARCH) model is applied. The findings declared that lagged effect of economic factors plays considerable role in explaining the firm stock returns. Such that three and four are the most common lags indicating significant and positive impact of exchange rate on firm stock returns. While, two and five lags are the most common lags implying statistically significant but negative relation of exchange rate with firm stock returns. However, it is uncovered that overall the statistically significant lagged effect of risk free rate on stock returns is negative in large and is found to be maximized at lag one. More so, lagged effect of inflation rests on quite worthy outcomes; firstly it is noted that its significant effect is shifted from negative to positive with the increase in lags from lag one to lag four. Secondly, it is established that four lags is the most common lag reflecting statistically significant positive impact of inflation on firm stock returns, while one and two lags are the most common lags displaying negative and significant relationship of inflation with firm stock returns. Taken together, money supply indicates significant positive lagged effect on firm stock returns in majority of the cases, that is subject to maximization either at lag two or lag five. However, largely, documenting significant positive lagged effect of oil prices on firm stock returns, it is established that one and two lags are the most common lags at which oil prices has significant and positive impact on firm stock returns. Finally, this research study sets the intimations to both the policy makers and investors together with some fresh areas for the future research.
Serum Lipocalin2 is a potential biomarker of liver irradiation damage

IL‐6 – IL‐1– lipocalin2 (LCN2) – liver irradiation – oxidative stress – TNF‐a Lipocalin2 (LCN2) is an acute phase protein. The source of its increased serum level in oxidative stress conditions (ROS) remains still unknown. We prospectively evaluate the serum LCN2 increase after single dose liver irradiation along with hepatic LCN2 gene and protein expression.
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections

Purpose of review Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become increasingly important as a cause of skin and soft tissue infections (SSTIs), particularly abscesses, in patients seen in the emergency department setting. The antibiotic sensitivity profile of Staphylococcus aureus isolates from SSTIs has changed over time in many geographic locations. Whether antibiotics are needed in the management of skin abscesses, and, if so, when, is controversial. Recent findings A number of studies have looked at antibiotic therapy in conjunction with incision and drainage in managing abscesses. Factors evaluated were resolution of infection, need for change in antibiotic therapy, hospitalization after initial outpatient management, need for an additional drainage procedure, and recurrence of infection within 30 days after the initial incision and drainage procedure. For abscesses, clinical failure was associated with lack of adequate incision and drainage and not antibiotic use, regardless of the size of the abscess or the choice of antibiotic therapy. For other soft tissue infections, when antibiotic susceptibility data were available for the infection (impetigo or cellulitis with purulent drainage but no abscess), there was no difference in clinical resolution of MRSA infection even if the infecting organism was resistant to the antibiotic chosen for therapy. Summary CA-MRSA has become an important cause of SSTIs. Current data suggest that most abscesses can be treated successfully with incision and drainage alone. Antibiotic choice is more crucial for management of cellulitis and should be guided by the prevalence of CA-MRSA in the community and its antibiotic susceptibility profile.
Thrombin-Hirudin Complex Formation, Thrombin-Antithrombin III Complex Formation, and Thrombin Generation after Intrinsic Activation of Plasma

Summary To investigate the relative importance of direct inhibition of thrombin by complex formation and of inhibition of thrombin generation to the mechanisms by that unfractionated heparin (UH) and recombinant hirudin (rH) exert their anticoagulant effects, thrombin-antithrombin III complex (TAT) and thrombin-hirudin complex (THC) formation was compared with the generation of thrombin and prothrombin fragments 1 + 2 (F 1 + 2). Clotting was initiated by activation of citrated plasma in the absence or presence of UH or rH using partial thromboplastin, ellagic acid and calcium chloride. THC was determined by means of ELISA using specific antibodies to thrombin and rH. Activation of citrated plasma resulted in a sudden onset of thrombin generation after a lag phase of 2 min. Addition of 50 ng rH/ml plasma or 0.1 UH/ml plasma prolonged the clotting time to 3 min. While the peak of thrombin was only slightly decreased in hirudinized plasma, in heparinized plasma thrombin generation was significantly lower than in not anticoagulated plasma. This difference was more pronounced when the lag phase was prolonged to 5 min using 400 ng rH/ml plasma or 0.35 U UH/ml plasma. Using 1200 ng rH/ml or 0.65 U UH/ml to obtain a clotting time of 9 min only a small amount of thrombin could be detected in heparinized plasma, but hirudinized plasma still showed a high peak of thrombin. F 1 + 2 showed essentially the same pattern as thrombin. Prior to the onset of visible clot formation in all experiments using different concentrations of UH about the same values of TAT were observed. In contrast, when samples were anticoagulated with different amounts of rH, a dose dependent increase of THC was detected. When calculated from TAT and THC formation, much more thrombin was bound by rH than by AT III. Our experiments show that after intrinsic activation of plasma UH exerts its anticoagulant effect more by inhibiting thrombin generation, while rH suppresses thrombin generation to a much lesser extent but inhibits clotting more by direct inhibition of thrombin due to the formation of THC.
Effect of treatment with and subsequent withdrawal of exogenous porcine somatotropin on growth and reproductive characteristics of gilts.

Two experiments were conducted to examine responses of gilts to treatment with and withdrawal of exogenous porcine somatotropin (PST). In Exp. 1, 36 prepubertal gilts (79.7 +/- .9 kg; 159.1 +/- .7 d) were allotted randomly to receive daily either 0 micrograms PST (C) or 70 micrograms PST/kg initial BW for either 21 (PST-3) or 42 d (PST-6). Gilts were examined for estrus daily by a mature boar starting on d 22 and continuing for up to 50 d. Gilts that expressed estrus were mated and removed from treatment. PST-treated gilts had higher ADG (P less than .01) and lower feed/gain (P less than .02) than C gilts. Following initiation of boar exposure, C gilts (mean interval to estrus = 2.0 d) exhibited estrus earlier than PST-3 (24.8 d) and PST-6 (24.0 d) gilts (P less than .07); however, only two C gilts were observed in estrus compared with six PST-3 and six PST-6 gilts. In Exp. 2, 40 prepubertal gilts (72.6 +/- 1.0 kg; 141.1 +/- .7 d) were allotted randomly to receive daily either 0 mg PST (C) or 5 mg PST for 30 d. On d 31, half the gilts were comingled with unfamiliar penmates and examined for estrus daily by a mature boar for up to 45 d. Estrual gilts were removed from treatment. (ABSTRACT TRUNCATED AT 250 WORDS)