Miracle-dz/UniFAR-FTUs huggingface dataset:
Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome

Genetic alterations disrupting the transcription factor IKZF1 (encoding IKAROS) are associated with poor outcome in B lineage acute lymphoblastic leukemia (B-ALL) and occur in >70% of the high-risk BCR-ABL1+ (Ph+) and Ph-like disease subtypes. To examine IKAROS function in this context, we have developed novel mouse models allowing reversible RNAi-based control of Ikaros expression in established B-ALL in vivo. Notably, leukemias driven by combined BCR-ABL1 expression and Ikaros suppression rapidly regress when endogenous Ikaros is restored, causing sustained disease remission or ablation. Comparison of transcriptional profiles accompanying dynamic Ikaros perturbation in murine B-ALL in vivo with two independent human B-ALL cohorts identified nine evolutionarily conserved IKAROS-repressed genes. Notably, high expression of six of these genes is associated with inferior event–free survival in both patient cohorts. Among them are EMP1, which was recently implicated in B-ALL proliferation and prednisolone resistance, and the novel target CTNND1, encoding P120-catenin. We demonstrate that elevated Ctnnd1 expression contributes to maintenance of murine B-ALL cells with compromised Ikaros function. These results suggest that IKZF1 alterations in B-ALL leads to induction of multiple genes associated with proliferation and treatment resistance, identifying potential new therapeutic targets for high-risk disease.
WikiLeaks: Inside Julian Assange's War on Secrecy

It was the biggest leak in history. WikiLeaks infuriated the world's greatest superpower, embarrassed the British royal family and helped cause a revolution in Africa. The man behind it was Julian Assange, one of the strangest figures ever to become a worldwide celebrity. Was he an internet messiah or a cyber-terrorist? Information freedom fighter or sex criminal? The debate would echo around the globe as US politicians called for his assassination. Award-winning "Guardian" journalists David Leigh and Luke Harding have been at the centre of a unique publishing drama that involved the release of some 250,000 secret diplomatic cables and classified files from the Afghan and Iraq wars. At one point the platinum-haired hacker was hiding from the CIA in David Leigh's London house. Now, together with the paper's investigative reporting team, Leigh and Harding reveal the startling inside story of the man and the leak.
Fragile X mice: Reduced long‐term potentiation and N‐Methyl‐D‐Aspartate receptor‐mediated neurotransmission in dentate gyrus

Fragile X syndrome (FXS) is a monogenic mental retardation syndrome that frequently includes autism. The Fmr1‐knockout (Fmr1‐KO) mouse, like FXS‐affected individuals, lacks the fragile X mental retardation protein (FMRP) and models autism as well as FXS. Limited human data and several mouse models have implicated the hippocampal dentate gyrus (DG) in autism. We therefore investigated whether the Fmr1‐KO mouse exhibited functional changes in DG. We found diminished medial perforant path‐granule cell long‐term potentiation (LTP), complementing previous investigations of synaptic plasticity in Fmr1‐KO demonstrating impaired LTP in CA1, neocortex, and amygdala and exaggerated long‐term depression in CA1. We also found that peak amplitude of NMDA receptor‐mediated excitatory postsynaptic currents (EPSCs) was smaller in Fmr1‐KO than control. AMPA receptor‐mediated EPSCs were comparable in the two strains, yielding a lower NMDA/AMPA ratio in Fmr1‐KO mice and suggesting one mechanism by which absent FMRP might contribute to diminished LTP. The clinical hallmarks of autism include both excessive adherence to patterns and impaired detection of socially important patterns. The DG has a putative role in pattern separation (for time, space, and features) that has been attributed to granule cell number, firing rates, adult neurogenesis, and even perforant path LTP. DG also contributes to pattern completion in CA3 via its mossy fiber efferents, whose terminals include abundant FMRP in “fragile X granules. ” Together with the present data, these observations suggest that DG is a candidate region for further investigation in autism and that the Fmr1‐KO model may be particularly apt. © 2010 Wiley‐Liss, Inc.
Extinction of the HPV18 upstream regulatory region in cervical carcinoma cells after fusion with non‐tumorigenic human keratinocytes under non‐selective conditions.

‘Universal fuser’ clones of a human papillomavirus type 16 positive cervical carcinoma cell line (SiHa) were established to study the effect of a non‐tumorigenic fusion partner on the regulation of a stably integrated chloramphenicol acetyltransferase (CAT) gene controlled by the HPV18 upstream regulatory region under non‐selective conditions. The CAT expressing cells were fused with both non‐tumorigenic, spontaneously immortalized human keratinocytes (HaCaT) and non‐modified SiHa cells. The resulting hybrids were characterized by restriction enzyme fragment length polymorphism analysis and flow cytometry. While the non‐selectable, HPV18‐driven indicator gene is constitutively expressed in SiHa cells, the CAT activity is extinguished in SiHa ×HaCaT cells, but still present in SiHa ×SiHa hybrids. Examination of the cytokeratin expression pattern reveals that the keratinocyte phenotype seems not only to be dominant in terms of the extinction of the HPV18 regulatory region but also by the conservation of most of the differentiation markers of the non‐tumorigenic fusion partner. Cycloheximide treatment and intracellular competition experiments using the transient COS7 fusion‐amplification technique are accompanied by the reactivation of the marker gene in previously CAT‐ SiHa ×HaCaT hybrids. These data strongly suggest that trans‐acting negative regulatory factors derived from the non‐malignant human keratinocytes are responsible for the extinction phenomenon.
The effect of tibial plateau leveling osteotomy position on cranial tibial subluxation: an in vitro study.

OBJECTIVES To compare centered versus distal tibial plateau leveling osteotomy (TPLO) position on cranial tibial subluxation, postoperative tibial plateau angle (TPA), and tibial long axis shift (TLAS). STUDY DESIGN In vitro biomechanical evaluation. ANIMALS Six pairs of canine cadaveric hind limbs. METHODS One limb of each pair was randomly assigned to the distal (TPLO-D) or centered (TPLO-C) osteotomy group. Cranial tibial subluxation (CTS) under load was quantified sequentially under 3 conditions: intact, after cranial cruciate ligament transection, and after TPLO; a corrected CTS value was also calculated. Postoperative TPA and TLAS were measured. Comparisons were made using 1-way repeated measures ANOVA with a Tukey's multiple comparison post hoc test for CTS, and a Wilcoxon's sign rank test for TPA and TLAS. Significance was set at P<. 05. RESULTS TPLO-C had a significantly lower mean CTS than TPLO-D (P<.01). Corrected CTS was also significantly lower in TPLO-C than in TPLO-D (P<.001). Postoperative TPA and TLAS were less in TPLO-C than in TPLO-D (P=.0312). CONCLUSION Our results confirm that distal centering of the TPLO leads to craniodistal translation of the tibial plateau, TLAS, and a postoperative TPA that is greater than expected. This geometric effect has the biomechanical effect expected of inadequate tibial plateau leveling, namely incomplete neutralization of cranial tibial thrust. CLINICAL RELEVANCE The centered osteotomy position is geometrically more precise, and biomechanically more effective than the distal position.
Work-related factors, job satisfaction and intent to leave the current job among United States nurses.

AIMS AND OBJECTIVES To examine the relationships of work-related factors (e.g., autonomy, work schedule, supervisory and peer support) to nurses' job satisfaction and intent to leave their current position. BACKGROUND Low job satisfaction and high turnover of nurses are major problems for health care. To improve nurse retention, work-related factors associated with job satisfaction and intent to leave should be investigated. DESIGN A cross-sectional secondary data analysis. METHODS Data were obtained in 2004 from Wave 3 of the Nurses' Worklife and Health Study. A random sample of 5000 actively licenced nurses in Illinois and North Carolina (two U.S. states) were sent the survey in wave 1, of which 1641 actively working bedside nurses participated in wave 3. We examined associations of various work-related factors with job satisfaction and intent to leave the current position. RESULTS Nurses who were dissatisfied with their job reported significantly higher psychological demands and lower autonomy than nurses who were satisfied. Nurses were significantly less satisfied with their jobs when they worked longer hours with inadequate breaks or sick days. Lack of support from peers and supervisors was also related to significantly lower odds of job satisfaction. For intention to leave, nurses who said they planned to leave their current job reported significantly lower autonomy and less support from their peers than nurses who intended to stay. CONCLUSION A variety of modifiable work-related factors were significantly related to job satisfaction and intention to leave the current job among nurses. Future research should focus on developing interventions that could mitigate these factors (e.g., by improving work schedules, increasing autonomy and/or nurse support). The impact of such interventions on job satisfaction and intention to leave the current position could then be evaluated. RELEVANCE TO CLINICAL PRACTICE To increase nurse retention, improved schedules, autonomy and supportive work environments should be promoted.
A buffer value index to evaluate effects of buffers on ruminal milieu in cows fed high or low concentrate, silage, or hay diets.

Our objective was to develop a buffer value index that would incorporate alterations in both ruminal fluid pH and buffering capacity as indicators of the influence of dietary buffering and alkalinizing agents on ruminal acid-base status. This index was evaluated using ruminal fluid from four lactating Holstein cows fed either sorghum silage or alfalfa hay in high or low concentrate diets. Ruminal fluid was incubated in vitro for 1, 2, 3, 4, or 5 h with no buffer or with 7.1 g of either NaHCO3, sodium sesquicarbonate, or a multielement buffer added per liter of ruminal fluid. Ruminal fluid pH was lower for diets based on high concentrate or alfalfa; buffering capacity between pH 5 and 7 was greater for high concentrate diets but was not affected by forage type. Ruminal fluid pH was higher for sesquicarbonate than for NaHCO3, the multielement buffer, or the control; however, ruminal fluid H+ concentration was similar between sesquicarbonate and NaHCO3, and both were lower than for the multielement buffer. Hydrogen ion concentration for the multielement buffer was lower than for the control. Buffering capacity was highest for NaHCO3, followed by sesquicarbonate, the multielement buffer, and the control. The buffer value index, which accounted for alterations in both H+ concentration and buffering capacity, was highest for NaCHO3, followed by sesquicarbonate, the multielement buffer, and the control. The poor response to the multielement buffer may be attributable to our relatively short incubation interval (less than 5 h). Dietary buffers increase both ruminal fluid pH and buffering capacity; both of these responses are beneficial. (ABSTRACT TRUNCATED AT 250 WORDS)
Hyperventilation‐induced hypocapnic alkalosis slows the adaptation of pulmonary O2 uptake during the transition to moderate‐intensity exercise

The effect of voluntary hyperventilation‐induced hypocapnic alkalosis (RALK) on pulmonary O2 uptake () kinetics and muscle deoxygenation was examined in young male adults (n= 8) during moderate‐intensity exercise. Subjects performed five repetitions of a step‐transition in work rate from 20 W cycling to a work rate corresponding to 90% of the estimated lactate threshold during control (CON; , ∼40 mmHg) and during hyperventilation (RALK; , ∼20 mmHg). was measured breath‐by‐breath and relative concentration changes in muscle deoxy‐ (ΔHHb), oxy‐ (ΔO2Hb) and total (ΔHbtot) haemoglobin were measured continuously using near‐infrared (NIR) spectroscopy (Hamamatsu, NIRO 300). The time constant for the fundamental, phase 2, response (τ) was greater (P < 0.05) in RALK (48 ± 11 s) than CON (31 ± 9 s), while τHHb was similar between conditions (RALK, 12 ± 4 s; CON, 11 ± 4 s). The ΔHbtot was lower (P < 0.05) in RALK than CON, prior to (RALK, −3 ± 5 μmol l−1; CON, −1 ± 4 μmol l−1) and at the end (RALK, 1 ± 6 μmol l−1; CON, 5 ± 5 μmol l−1) of moderate‐intensity exercise. Although slower adaptation of during RALK may be related to an attenuated activation of PDH (and other enzymes) and provision of oxidizable substrate to the mitochondria (i.e. metabolic inertia), the present findings also suggest a role for a reduction in local muscle perfusion and O2 delivery.
Implementation of ‘CLICK into Activity’ in South Somerset: Social prescribing through primary care referral of ‘at risk’ populations to community leisure services: Full evaluation report

In March 2013, Sport England launched a Lottery-funded initiative called ‘Get Healthy Get Active’ (GHGA), investing in numerous UK-based projects designed to tackle inactivity through participation in sport. CLICK into Activity, a social prescribing initiative based in South Somerset, was one of sixteen projects to receive backing in 2015 from Sport England during round two of GHGA funding. The preventive approach taken through CLICK into Activity was to refer inactive people from general practice and encourage individuals to play a central role in engaging with exercise specialists in community leisure services to improve health and wellbeing and support them to become more physically active. A mixed methods evaluation using the RE-AIM framework was conducted that aimed to evaluate the impact of CLICK into Activity. This full report presents study methods, results and recommendations of the evaluation.
Effect of Cold Storage on Larval and Adult Anastrepha ludens (Diptera: Tephritidae) Viability in Commercially Ripe, Artificially Infested Persea americana ‘Hass’

ABSTRACT Commercially ripe ‘Hass’ avocados, Persea americana Mill, artificially exposed to wild Anastrepha ludens (Loew) (Diptera: Tephritidae) females 24 h after harvest were placed in a cold storage facility to determine the effect of low temperature on larval survival and adult viability. Fruit were left for 3, 6, 9, and 12 d in a cold room at 5°C followed by a 20 -25-d period at ambient temperature to allow for larval development and pupation. Hass avocados and grapefruit, Citrus paradisi Macfadyen, maintained at ambient temperature served as controls. Overall, only 0.23% of the Hass avocados and 19.30% of the grapefruit were infested. The number of infested fruit increased with decreasing exposure time to cold. Puparia from cold-treated Hass avocados were significantly smaller than those stemming from cold-treated grapefruit. Hass avocados exposed for 12 d to 5°C yielded no puparia, and those exposed for 6 and 9 d yielded 22 and two puparia, respectively, but no adults. Although Hass avocados exposed to cold temperature for 3 d yielded adults that reached sexual maturity (N = 16), females laid in viable eggs. Grapefruit exposed to cold for 12 d yielded normal-sized puparia (but no adults), whereas those exposed over 9 d yielded females able to lay viable eggs. We conclude that exposing fruit to cold storage after packing and during transport represents an effective risk-mitigating procedure in the highly improbable event that a gravid A. ludens female might lay eggs in a commercially ripe Hass avocado that had been left unprotected in a packinghouse.
Phosphorylation-Mediated Negative Regulation of RIG-I Antiviral Activity

ABSTRACT Recognition of invading viruses by the host is elicited by cellular sensors which trigger signaling cascades that lead to type I interferon (IFN) gene expression. Retinoic acid-inducible gene I (RIG-I) has emerged as a key receptor for the detection of viral RNA in the cytosol, inducing IFN-mediated innate immune responses to limit viral replication through its interaction with MAVS (also called IPS-1, CARDIF, or VISA). Upon the recognition of viral RNA, the Lys-172 residue of RIG-I undergoes ubiquitination induced by tripartite motif protein 25 (TRIM25), an essential protein for antiviral signal transduction. Here we demonstrate that phosphorylation represents another regulatory mechanism for RIG-I-mediated antiviral activity. Using protein purification and mass spectrometry analysis, we identified three phosphorylation sites in the amino-terminal caspase recruitment domains (CARDs) of RIG-I. One of these residues, Thr-170, is located in close proximity to Lys-172, and we speculated that its phosphorylation may affect Lys-172 ubiquitination and functional activation of RIG-I. Indeed, a RIG-I mutant carrying a phosphomimetic Glu residue in place of Thr-170 loses TRIM25 binding, Lys-172 ubiquitination, MAVS binding, and downstream signaling ability. This suggests that phosphorylation of RIG-I at Thr-170 inhibits RIG-I-mediated antiviral signal transduction. Immunoblot analysis with a phospho-specific antibody showed that the phosphorylation of the RIG-I Thr-170 residue is present under normal conditions but rapidly declines upon viral infection. Our results indicate that Thr-170 phosphorylation and TRIM25-mediated Lys-172 ubiquitination of RIG-I functionally antagonize each other. While Thr-170 phosphorylation keeps RIG-I latent, Lys-172 ubiquitination enables RIG-I to form a stable complex with MAVS, thereby inducing IFN signal transduction.
Wage offers and on‐the‐job search

We study the wage-setting problem of an employer with private information about demand for its product when workers can engage in costly on-the-job search. Employers understand that low wage offers may convey bad news that induces workers to search. The unique perfect sequential equilibrium wage strategy is characterized by: (i) pooling by intermediate-revenue employers on a common wage that just deters search; (ii) discontinuously lower revealing offers by low-revenue employers for whom the benefit of deterring search fails to warrant the required high pooling wage; and (iii) high revealing offers by high-revenue employers seeking to deter aggressive poachers.
Reliability Evaluation of Conventional and Interleaved DC–DC Boost Converters

Obviously for the correct operation of conventional boost converters, all components should work correctly. Interleaved boost converters having several stages, can be used to increase the reliability. So in this paper, a reliability comparison is done between the conventional boost converter and the interleaved structure. Two different operation modes are defined for the interleaved boost converter: half-power and full-power operation modes. The reliability calculation is based on the Markov model of the converters. The power loss effect of converter components on their failure rates, and therefore, on the reliability of converter has been assessed. For the first time different failure rates have been considered for different operation modes. Also a laboratory prototype of a two-stage interleaved boost dc-dc converter has been built up and the failure rate of components in different operation modes are calculated practically. Results show that in addition to other benefits, interleaved structure has higher reliability and as the power increases, there will be a decrease in the reliability.
Design of band-gap engineered silicon-germanium Junctionless Double-gate FET for ZRAM application

In this paper, we design a single transistor and zero-capacitor dynamic random access memory (DRAM or ZRAM) using band-gap engineered silicon-germanium (SiGe) Junctionless Double Gate Field Effect Transistor (JL-DGFET) device structure through 2D Sentaurus TCAD numerical simulations. We see that the inadequate charge storage capability of silicon-based 1T-DRAM is the main reason for short retention time. However, our simulations show that the performance can be further improved by replacing silicon substrate with silicon-germanium material. Moreover, a reduced breakdown voltage and hysteresis IDS-VDS characteristics are observed by putting SiGe as a bulk. Furthermore, the thickness of oxide and bulk material, and doping concentration are varied and their impacts are shown on the hysteresis output characteristic. High value of bipolar gain (β) is attained in designed band-gap engineered Si(1−x)Gex JL-DGFET transistors, which can be employed for enhancement of sensing margin in dynamic memories.
Cost-Effectiveness of Routine Rapid Human Immunodeficiency Virus Antibody Testing Before DNA-PCR Testing for Early Diagnosis of Infants in Resource-Limited Settings

Background: Infants born to HIV-infected women should receive HIV testing to allow early diagnosis and treatment. Recommendations for resource-limited settings stress laboratory-based virologic assays. While effective, these tests are logistically complex and expensive. This study explored the cost-effectiveness of incorporating initial screening with rapid HIV tests (RHT) into the conventional testing algorithm to screen-out HIV-uninfected infants, thereby reducing the need for costly virologic testing. Methods: Data on HIV prevalence, RHT sensitivity and specificity, and costs were collected from 820 HIV-exposed children (1.5–18 months) attending 2 postnatal screening programs in Uganda during July 2005 to December 2006. Cost-effectiveness models compared the conventional testing algorithm DNA polymerase chain reaction (DNA-PCR with Roche Amplicor v1.5) with a modified algorithm (initial RHT to screen-out HIV-uninfected infants before DNA-PCR). Results: The model estimated that the conventional algorithm would identify 94.3% (91.8%–94.7%) of HIV-infected infants, compared with 87.8% (79.4%–90.5%) for a modified algorithm using RHT (HIV 1/2 Determine) and excluding the need for DNA-PCR for HIV antibody-negative infants. Costs per infant were $23.47 ($23.32–$23.76) for the conventional algorithm and between $22.75 ($21.89–$23.31) and $7.58 ($6.41–$10.75) for the modified algorithm, depending on infant age and symptoms. Compared with the conventional algorithm, costs per HIV-infected infant identified using the modified algorithm were higher in 1.5- to 3-month-old infants, but significantly lower in 3-month-old and older infants. Models replicating the whole infant testing program showed the modified algorithm would have marginally lower sensitivity, but would reduce total program costs by 27% to 40%, producing an incremental cost-effectiveness ratio of $1489 ($686–$6781) for the conventional versus modified algorithms. Conclusions: Screening infants with RHT before DNA-PCR is cost-effective in infants 3 months old or older. Incorporating RHT into early infant testing programs could improve cost-effectiveness and reduce program costs.