Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating Alternative Aftercare Models for Ex-Offenders

This study examined the role played by aftercare following (mainly) inpatient community-based treatment in the outcomes of criminal ex-offenders with substance use disorders. Two hundred seventy individuals who had been released from the criminal justice system were randomly assigned to either a therapeutic community (TC), recovery homes called Oxford Houses (OHs), or usual care settings (UA). The OHs and TCs are residential settings that emphasized socialization and abstinence from drugs and alcohol, but OHs do not include the formal therapeutic change interventions common to TCs, nor do they include any on-site access to drug abuse or health care professionals. UA involved what occurred naturally after completing treatment, which included staying with friends or family members, their own house or apartment, homeless shelters, or other settings. Longer lengths of stay in either the TCs or OHs were associated with increased employment, and reduced alcohol and drug use. Those assigned to the OH condition received more money from employment, worked more days, achieved higher continuous alcohol sobriety rates, and had more favorable cost–benefit ratios.
Ups and Downs of Poised RNA Polymerase II in B-Cells

Recent genome-wide analyses have uncovered a high accumulation of RNA polymerase II (Pol II) at the 5′ end of genes. This elevated Pol II presence at promoters, referred to here as Poll II poising, is mainly (but not exclusively) attributed to temporal pausing of transcription during early elongation which, in turn, has been proposed to be a regulatory step for processes that need to be activated “on demand”. Yet, the full genome-wide regulatory role of Pol II poising is yet to be delineated. To elucidate the role of Pol II poising in B cell activation, we compared Pol II profiles in resting and activated B cells. We found that while Pol II poised genes generally overlap functionally among different B cell states and correspond to the functional groups previously identified for other cell types, non-poised genes are B cell state specific. Focusing on the changes in transcription activity upon B cell activation, we found that the majority of such changes were from poised to non-poised state. The genes showing this type of transition were functionally enriched in translation, RNA processing and mRNA metabolic process. Interestingly, we also observed a transition from non-poised to poised state. Within this set of genes we identified several Immediate Early Genes (IEG), which were highly expressed in resting B cell and shifted from non-poised to poised state after B cell activation. Thus Pol II poising does not only mark genes for rapid expression in the future, but it is also associated with genes that are silenced after a burst of their expression. Finally, we performed comparative analysis of the presence of G4 motifs in the context of poised versus non-poised but active genes. Interestingly we observed a differential enrichment of these motifs upstream versus downstream of TSS depending on poising status. The enrichment of G4 sequence motifs upstream of TSS of non-poised active genes suggests a potential role of quadruplexes in expression regulation.
Clinical trials and late‐stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014

The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here, we review the development of treatments for Alzheimer's disease during the past 30 years, considering the drugs, potential targets, late‐stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late‐stage Alzheimer's disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta‐analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild‐to‐moderate Alzheimer's disease criteria, recently extending to early or prodromal Alzheimer disease or ‘mild cognitive impairment due to Alzheimer's disease’, for drugs considered to be disease modifying. The duration of trials has remained at 6–12 months for drugs intended to improve symptoms; 18‐ to 24‐month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities of daily living, global change and severity ratings have persisted as the primary clinically relevant outcomes. Regulatory guidance and oversight have evolved to allow for enrichment of early‐stage Alzheimer's disease trial samples using biomarkers and phase‐specific outcomes. In conclusion, validated drug targets for Alzheimer's disease remain to be developed. Only drugs that affect an aspect of cholinergic function have shown consistent, but modest, clinical effects in late‐phase trials. There is opportunity for substantial improvements in drug discovery and clinical development methods.
Quantitative Real-Time RT—PCR Analysis of Inflammatory Gene Expression Associated with Ischemia—Reperfusion Brain Injury

Ischemia-reperfusion brain injury initiates an inflammatory response involving the expression of adhesion molecules and cytokines, some of which are regulated by the nuclear transcription factor NF-κB. In this study the authors examined mRNA expression levels for several important genes associated with inflammation at five time points (3, 6, 12, 24, and 72 hours) after transient middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. A sensitive and quantitative technique (TaqMan real-time QRT-PCR) was used to simultaneously measure mRNA levels for key cell adhesion molecules and inflammatory cytokines. Gene expression increased significantly in the injured hemisphere for interleukin (IL)-1β (12-fold increase at 24 hours), IL-6 (25-fold increase at 6 hours) and ICAM-1 (4-fold increase at 24 hours), and the in-terhemispheric differences for these genes were significant for every time point examined (P < 0.05 for all values). Tumor necrosis factor-α mRNA was upregulated in the injured versus uninjured hemisphere from 3 to 24 hours (5-fold increase at 6 hours), while E-selectin showed a significant increase in mRNA levels from 6 to 24 hours after MCAO (10-fold increase at 6 hours) (P < 0.05 for all values). VCAM-1 mRNA levels did not respond differentially to injury at any time point between the two brain hemispheres. At all time points examined, activated NF-κB immunoreactivity was observed in cells throughout the infarct-damaged tissue. These results are consistent with the proinflammatory properties of the induced molecules, which are involved in the initiation of the inflammatory cascade, and may thus contribute to secondary cellular responses that lead to further brain damage.
Haploidentical versus Matched-Sibling Transplant in Adults with Philadelphia-Negative High-Risk Acute Lymphoblastic Leukemia: A Biologically Phase III Randomized Study

Purpose: Although matched-sibling donor (MSD) hematopoietic stem-cell transplantation (HSCT) has an established role in the management of adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1), the effect of haploidentical donor (HID) HSCT as post-remission treatment for this portion of patients is not defined. Experimental Design: Transplantation outcomes from HIDs or MSDs were compared in a disease-specific, biologically phase III randomized, multicenter study. Between July 2010 and December 2013, 210 patients with Philadelphia-negative high-risk ALL in CR1 were assigned to undergo unmanipulated HIDs (121 patients) or MSDs HSCT (89 patients) according to donor availability on an intent-to-treat (ITT) basis. Results: Overall, 24 of the 210 patients had lost transplant eligibility. Therefore, 186 of 210 (88%) patients were finally transplanted from MSD (n = 83) or HID (n = 103). Based on the ITT principle, the 3-year disease-free survival (DFS) did not differ between HID and MSD groups [61%, 95% confidence interval (CI), 52%–70%; vs. 60%, CI, 49%–71%; P = 0.91] from CR, neither did DFS differ between the two groups (68%, CI, 58%–78%; vs. 64%, CI, 52%–76%; P = 0.56) from time of the graft, with cumulative incidence of nonrelapse mortality of 13% (CI, 7%–19%) and 11% (CI, 4%–18%; P = 0.84) and relapse rates of 18% (CI, 10%–26%) and 24% (CI, 14%–34%; P = 0.30), respectively. Conclusions: Haploidentical HSCT achieves outcomes similar to those of MSD-HSCT for Philadelphia-negative high-risk ALL patients in CR1. Such transplantation could be a valid alternative as post-remission treatment for high-risk ALL patients in CR1 lacking an identical donor. Clin Cancer Res; 22(14); 3467–76. ©2016 AACR.
Impurity-induced virtual bound states in d-wave superconductors.

It is shown that a single, strongly scattering impurity produces a bound or a virtual-bound quasiparticle state inside the gap in a {ital d}-wave superconductor. The explicit form of the bound-state wave function is found to decay exponentially with angle-dependent range. These states provide a natural explanation of the second Cu NMR rate arising from the sites close to Zn impurities in the cuprates. Finally, for finite density of impurities in a {ital d}-wave superconductor, we re-examine the growth of these states into an impurity band, and discuss the Mott criterion for the metal-insulator transition in this band.
Thapsigargin‐induced grp78 expression is mediated by the increase of cytosolic free calcium in 9L rat brain tumor cells

Exposure of 9L rat brain tumor cells to 300 nM thapsigargin (TG), a sarcoendoplasmic Ca2+‐ATPases inhibitor, leads to an immediate suppression of general protein synthesis followed by an enhanced synthesis of the 78‐kDa glucose‐regulated protein, GRP78. Synthesis of GRP78 increases significantly and continues to rise after 4 h of treatment, and this process coincides with the accumulation of grp78 mRNA. TG‐induced grp78 expression can be suppressed by the cytosolic free calcium ([Ca2+]c) chelator dibromo‐1,2‐bis(aminophenoxy)ethane N,N,N′,N′‐tetraacetic acid (BAPTA) in a concentration‐dependent manner. Induction of grp78 is completely abolished in the presence of 20 μM BAPTA under which the TG‐induced increase of [Ca2+]c is also completely prevented. By adding ethyleneglycol bis(β‐aminoethyl)ether‐N,N,N′,N′ tetraacetic acid in the foregoing experiments, in a condition such that endoplasmic reticulum calcium ([Ca2+]ER) is depleted and calcium influx from outside is prevented, TG‐induced grp78 expression is also abolished. These data lead us to conclude that increase in [Ca2+]c, together with the depletion of [Ca2+]ER, are the major causes of TG‐induced grp78 expression in 9L rat brain tumor cells. By using electrophoretic mobility shift assays (EMSA), we found that the nuclear extracts prepared from TG‐treated cells exhibit an increase in binding activity toward the extended grp78 promoter as well as the individual cis‐acting regulatory elements, CRE and CORE. Moreover, this increase in binding activity is also reduced by BAPTA. By competitory assays using the cis‐acting regulatory elements as the competitors as well as the EMSA probes, we further show that all of the tested cis elements—CRE, CORE, and C1—are involved in the basal as well as in the TG‐induced expression of grp78 and that the protein factor(s) that binds to the C1 region plays an important role in the formation and maintenance of the transcription complex. J. Cell. Biochem. 78:404–416, 2000. © 2000 Wiley‐Liss, Inc.
Approximate sum rate for massive multiple-input multiple-output two-way relay with Ricean fading

This study considers a multi-pair massive multiple-input multiple-output two-way relay network where the M-antenna relay simultaneously serves K pairs of single-antenna users in the same time–frequency resource. For a more general case of Ricean fading channel, the authors propose a fixed-gain maximum ratio combing/maximum ratio transmission relay scheme. The approximate expressions on the ergodic sum rate with such scheme are derived in two cases: (i) M, which is much larger than the users’ Ricean factors, is large enough; and (ii) if M is large enough but bounded, the Ricean factors of all the users go to infinity. Simulation results show that the approximate results are very tight. Based on the result for the first case, they further discuss the power-scaling laws, which reveal that despite the Ricean fading channel and the interference at the relay, the achievable sum rate can still remain unchanged if the transmitted power at each user or at the relay is or both are made inversely proportional to M.
‘It's my inner strength’: spirituality, religion and HIV in the lives of young African American men who have sex with men

Young black men who have sex with men account for 48% of 13–29-year-old HIV-positive men who have sex with men in the USA. It is important to develop an effective HIV prevention approach that is grounded in the context of young men's lives. Towards this goal, we conducted 31 interviews with 18–30-year-old men who have sex with men in the San Francisco-Oakland Bay Area. This paper examines the roles of religion and spirituality in men who have sex with men's lives, which is central in the lives of many African Americans. Six prominent themes emerged: (1) childhood participation in formal religious institutions, (2) the continued importance of spirituality among men who have sex with men, (3) homophobia and stigmatisation in traditional black churches, (4) tension between being a man who has sex with men and being a Christian, (5) religion and spirituality's impact on men's sense of personal empowerment and coping abilities and (6) treatment of others and building compassion. Findings suggest that integrating spiritual practice into HIV prevention may help programmes be more culturally grounded, thereby attracting more men and resonating with their experiences and values. In addition, faith-based HIV/AIDS ministries that support HIV-positive men who have sex with men may be particularly helpful. Finally, targeting pastors and other church leaders through anti-stigma curricula is crucial.
Reversal of glutamate excitotoxicity by activation of PKC‐associated metabotropic glutamate receptors in cerebellar granule cells relies on NR2C subunit expression

Stimulation of metabotropic glutamate receptors (mGluRs) belonging to group I has been found to reduce N‐methyl‐ d‐aspartate (NMDA) receptor function in terms of both intracellular calcium concentration ([Ca2+]i) rise and neurotoxicity in cultured cerebellar granule cells. In the present study, we investigated whether the mGluR‐elicited modulation of glutamate responses might rely on the heteromeric composition of NMDA receptor channel. NMDA receptors consist of two distinct groups of subunits: NR1, that is ubiquitously in the receptor complexes; and NR2A–D, that differentiate and potentiate NMDA receptor responses by assembling with NR1. Among NR2 subunits, only NR2A and NR2C mRNAs and relative proteins are detected in cerebellar granule cells at 10 days in vitro. To dissect the involvement of the two different subunits in making the NMDA receptor channel sensitive to modulation by group I mGluR agonists, expression of the NR2C subunit was prevented by treating the cells with specific antisense oligodeoxynucleotide (ODN). The capability of the mGluR agonists, trans‐1‐amino‐cyclopentane‐1,3‐dicarboxylic acid (tACPD, 100 μm) or 3 hydroxyphenylglycine (3HPG, 100 μm), and the protein kinase C (PKC) activator, 4β‐phorbol‐12,13‐dibutyrate (PDBu, 1 μm), to inhibit the function of resultant NMDA receptors was then evaluated. We found that depletion of the NR2C subunit abolished the inhibitory effect of group I mGluR stimulation on glutamate‐induced [Ca2+]i rise and neurotoxicity. The antisense ODN treatment also prevented the inhibitory effect of PDBu on glutamate responses. Conversely, in NR2C‐lacking neurons, both group I mGluRs and PKC stimulation enhanced NMDA receptor‐mediated effects. The present findings indicate that the capability of PKC‐associated mGluRs to modulate native NMDA receptor function relies on the heteromeric configuration of the receptor–channel complex. Particularly, expression of the NR2C subunit is required to make the NMDA receptor sensitive to inhibitory modulation by mGluRs or PKC activation.
On the limited ability of superoxide to release iron from ferritin.

Reductive release of iron from ferritin may catalyze cytotoxic radical reactions like the Haber-Weiss reaction. The ability of . O2- to mobilize Fe(II) from ferritin was studied by using the xanthine/xanthine oxidase reaction, with and without superoxide dismutase, and with bathophenanthroline sulphonate as the chelator. Not more than one or two Fe(II)/ferritin molecules could be released by an . O2(-)-dependent mechanism, even after repeated exposures of ferritin to bursts of . O2-. The amount of releaseable iron depended on the size and the age of the iron core, but not on the iron content of the protein shell of ferritin which was manipulated by chelators and addition of FeCl3. The kinetic characteristics of the . O2(-)-mediated iron release indicated the presence of a small pool of readily available iron at the surface of the core. The very limited . O2(-)-dependent release of iron from ferritin is compatible with a protective role of ferritin against toxic iron-catalyzed reactions.
Psychophysical Evaluation of Cochlear Prostheses in a Monkey Model

Functional aspects of cochlear prostheses implanted in the scala tympani were tested in monkeys trained to perform a simple reaction-time task. Thresholds for detection of electrical stimulation and dynamic ranges were tested for a wide range of frequencies of sinusoidal stimulation and for biphasic rectangular pulses of various durations and repetition rates. The results are comparable with available data from implanted human patients and extend these findings, exploring various aspects of electrical stimulation in greater detail.
Poly(ethylene glycol)-lipase complex highly active in ionic liquids

INTRODUCTION A number of studies on enzymatic reactions have been carried out in organic media. These reactions have several benefits compared with conventional organic synthesis, including high enantioselectivity, substrate specificity and low energy consumption. There are, however, several drawbacks in using organic solvents. Volatile organic solvents are often flammable and toxic to the environment and the human body. Moreover, the enantioselectivity of enzymatic reactions in organic solvents has not yet satisfied industrial needs.
Hyaluronic acid induces COX-2 expression via CD44 in orbital fibroblasts from patients with thyroid-associated ophthalmopathy.

PURPOSE The aim of this study was to determine the effect of hyaluronic acid (HA) on cyclooxygenase (COX)-2 expression in orbital fibroblasts from patients with thyroid-associated ophthalmopathy (TAO). METHODS Primary cultured orbital fibroblasts were obtained from patients with TAO and non-TAO subjects. Dermal and conjunctival fibroblasts were cultured from the eyelid skin of subjects undergoing cosmetic lid surgery or cataract surgery, respectively. The cells were treated with HA and the transcriptional and translational levels of COX-2 were measured. The expression of CD44 on each type of cells was determined, and the involvement of CD44 in the HA-induced COX-2 increase in orbital fibroblasts from patients with TAO was evaluated by using CD44 knockdown cells and by pretreatment with neutralizing antibody. The relevance of the mitogen-activated protein kinase (MAPK) or nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated signaling pathway was assessed by immunoblotting for the phosphorylated form of each MAPK or IκB and by using specific inhibitors to these pathways. RESULTS Hyaluronic acid increased COX-2 expression in orbital fibroblasts from patients with TAO, which was not observed in the cells from non-TAO subjects and conjunctival or dermal fibroblasts. Orbital fibroblasts from patients with TAO expressed significantly higher level of CD44 than non-TAO cells, and the increased COX-2 expression by HA in these cells was attenuated by knockdown or neutralizing of CD44. Hyaluronic acid induced MAPK and IκB phosphorylation; and cotreatment with specific MAPK or NF-κB inhibitors halted HA-induced transcription of COX-2, suggesting the involvement of these signaling pathways. CONCLUSIONS Hyaluronic acid induced COX-2 expression in orbital fibroblasts from patients with TAO via CD44 through the MAPK and NF-κB-mediated signaling pathways. These results suggest that HA may have a proinflammatory role in the pathogenesis of TAO by inducing COX-2.
Educating for Empathy in Software Engineering Course

The ability to empathize with end-users is an engineering skill that is as necessary as technical expertise and social competency. In particular, empathy is required when embracing the otherness of a group of people and defining their requirements. Empathy is the first step in the design thinking method, which has garnered interest among software development organisations nowadays for leveraging the design and innovation processes and for better realizing the required end-user experience. The design thinking approach places the customer needs up-front, and emphasizes building empathy with users, observing their behavior, and drawing conclusions about what people want and need. This paper presents preliminary findings of a collaboration between design students and engineering students at the Shenkar College of Engineering, Design and Art. The findings show how engineering students, when coping with a serious, human (as opposed to organizational) wicked problem presented to them, practiced empathy and used emotional language when defining requirements for their solutions. The paper posits that the multidisciplinary learning experience of engineering and design students, gained while practicing the design thinking method, can foster empathy and other skills needed in modern digital culture, which exhibits the confluence of technology, knowledge, and culture.