Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity-Dependent A-to-I RNA Editing in Rat Cortical Neurons

Changes in neural activity influence synaptic plasticity/scaling, gene expression, and epigenetic modifications. We present the first evidence that short-term and persistent changes in neural activity can alter adenosine-to-inosine (A-to-I) RNA editing, a post-transcriptional site-specific modification found in several neuron-specific transcripts. In rat cortical neuron cultures, activity-dependent changes in A-to-I RNA editing in coding exons are present after 6 hr of high potassium depolarization but not after 1 hr and require calcium entry into neurons. When treatments are extended from hours to days, we observe a negative feedback phenomenon: Chronic depolarization increases editing at many sites and chronic silencing decreases editing. We present several different modulations of neural activity that change the expression of different mRNA isoforms through editing.
Human leukocyte antigen‐DRB1*1101 correlates with less severe hepatitis in Taiwanese male carriers of hepatitis B virus

Human leukocyte antigen (HLA) class II molecules are associated with host immune responses against hepatitis B virus infection. Male gender is the apparent host factor when someone encounters with the severity of hepatitis. The aim of this study was to investigate the association of the most polymorphic HLA class II allele, human leukocyte antigen—DRB1, with the severity of hepatitis in male carriers of hepatitis B virus. In this prospective cohort study, a total of 204 carriers of hepatitis B virus (131 men and 73 women) who have been followed‐up for more than 1 year at the outpatient clinic of a university hospital were collected consecutively. Fifty carriers of hepatitis B virus (group I) with alanine aminotransferase <2× upper limit of normal (mean follow‐up 83.6 months) were compared with 154 chronic hepatitis B patients (group II) with alanine aminotransferase ≥2× upper limit of normal (mean follow‐up 81.3 months). Alleles of HLA‐DRB1 were typed by the polymerase chain reaction—sequence specific oligonucleotide probe hybridization and genotypes of hepatitis B virus by melting curve analysis. HLA‐DRB1*1101 was found in 18% of group I versus 8% of group II in male carriers (OR 0.23, P = 0.020, after adjustment for age) and 4% versus 9.4% in female carriers (P = 0.094). In male carriers harboring DRB1*1101, the distribution of hepatitis B viral genotype was comparable between the two groups. HLA‐DRB1*1101 correlates with less severe hepatitis in Taiwanese male carriers of hepatitis B virus. J. Med. Virol. 81:588–593, 2009 © 2009 Wiley‐Liss, Inc.
Expression Profile of Osteoblast Lineage at Defined Stages of Differentiation*

The inherent heterogeneity of bone cells complicates the interpretation of microarray studies designed to identify genes highly associated with osteoblast differentiation. To overcome this problem, we have utilized Col1a1 promoter-green fluorescent protein transgenic mouse lines to isolate bone cells at distinct stages of osteoprogenitor maturation. Comparison of gene expression patterns from unsorted or isolated sorted bone cell populations at days 7 and 17 of calvarial cultures revealed an increased specificity regarding which genes are selectively expressed in a subset of bone cell types during differentiation. Furthermore, distinctly different patterns of gene expression associated with major signaling pathways (Igf1, Bmp, and Wnt) were observed at different levels of maturation. Some of our data differ from current models of osteoprogenitor cell differentiation and emphasize components of the pathways that were not revealed in studies based on a total cell population. Thus, applying methods to generate more homogeneous populations of cells at a defined level of cellular differentiation from a primary osteogenic culture is feasible and leads to a novel interpretation of the gene expression associated with increasing levels of osteoprogenitor maturation.
A Novel Spectrally Efficient Wireless CDMA Transmission Scheme: System Design and Robustness to Channel Imperfections

When compared to the traditionally considered Gaussian capacity limit, creating appropriate non-Gaussian multiuser interference in CDMA transmission with single-user decoding can increase the channel capacity limit several times. We have recently designed a coded M-ary CDMA transmission scheme that can practically achieve large part of this capacity increase and improve significantly spectral efficiency of CDMA systems. The main objective of this paper is to explore the robustness of this scheme to wireless channel imperfections. We consider two potential CDMA channel impairments, i.e., imperfect power control at the transmitter and power-limited amplifiers at the receiver. Simulation results for 16-ary CDMA network transmission show that under ideal conditions, spectral efficiency of 1.45 bits per CDMA chip (i.e., more than twice the conjectured Gaussian capacity limit) is achieved. The simulation results also show that the scheme is robust to 1 dB power control error and a power limit at the receiver amplifier
B2EIS-RG: Biometric-based Bucket Encrypting Index Structure with Random Generator

The proliferation in the popularity of the cloud-based data storage services motivated the data owners to store a huge amount of confidential files on the remote servers in an encrypted format. The users/clients can send their queries to the database owner to retrieve the data files in the encrypted database while protecting privacy of both the queries and the database. The database owners can outsource their enormous biometric data and identification tasks to the cloud server such as Amazon to avoid high storage and computation costs. However, this adds potential threats to the privacy of users. This paper presents a combined Biometric-based Bucket Encrypting Index Structure with Random Generator (B2EIS-RG) for efficient and privacy-preserving biometric identification outsourcing in the cloud. The encryption process includes multi-keyword query processing along with the conjunction and disjunction logic queries to ensure high privacy guarantee against the keyword attacks. Experimental evaluation over a large dataset demonstrates that the proposed scheme can achieve modest time efficiency, and they are practical for use in the huge encrypted database systems. The proposed scheme is found to be highly secure even if the attackers can forge the biometric identification requests.
Nuclear Envelope Lamin-A Couples Actin Dynamics with Immunological Synapse Architecture and T Cell Activation

Communication between the nuclear lamina protein lamin-A and the actin cytoskeleton is required for optimal T cell responses. Nuclear Support for T Cell Activation A-type lamins are filamentous proteins that form the nuclear lamina inside the inner nuclear membrane. As well as maintaining the mechanical integrity of the nucleus, A-type lamins physically connect the nucleus and the actin cytoskeleton by associating with the linker of nucleoskeleton and cytoskeleton (LINC) complex. González-Granado et al. found that the abundance of lamin-A was rapidly and transiently increased in mouse and human CD4+ T cells in response to stimulation of the T cell receptor. Lamin-A enhanced F-actin polymerization at the immunological synapse between the T cells and antigen-presenting cells, thereby boosting T cell activation. Disruption of the interaction between lamin-A and the LINC complex also decreased T cell activation in culture, and mice lacking lamin-A in immune cells exhibited reduced T cell activation in response to antigen. These results suggest that the nuclear skeleton communicates with the cytoskeleton to enable optimal T cell activation. In many cell types, nuclear A-type lamins regulate multiple cellular functions, including higher-order genome organization, DNA replication and repair, gene transcription, and signal transduction; however, their role in specialized immune cells remains largely unexplored. We showed that the abundance of A-type lamins was almost negligible in resting naïve T lymphocytes, but was increased upon activation of the T cell receptor (TCR). The increase in lamin-A was an early event that accelerated formation of the immunological synapse between T cells and antigen-presenting cells. Polymerization of F-actin in T cells is a critical step for immunological synapse formation, and lamin-A interacted with the linker of nucleoskeleton and cytoskeleton (LINC) complex to promote F-actin polymerization. We also showed that lamin-A expression accelerated TCR clustering and led to enhanced downstream signaling, including extracellular signal–regulated kinase 1/2 (ERK1/2) signaling, as well as increased target gene expression. Pharmacological inhibition of the ERK pathway reduced lamin-A–dependent T cell activation. Moreover, mice lacking lamin-A in immune cells exhibited impaired T cell responses in vivo. These findings underscore the importance of A-type lamins for TCR activation and identify lamin-A as a previously unappreciated regulator of the immune response.
Use of Human Embryonic Stem Cell-based Models for Male Reproductive Toxicity Screening

Male reproductive toxicity examines harmful effects of various agents on all aspects and developmental stages of the male reproductive system, including germ cell development and spermatogenesis. In developing a model for reproductive toxicity screening it is important to define the developmental stage that this model is going to recreate in vitro and to identify critical molecular targets of this stage. In this review we focus our discussion on the potential for using embryonic stem cell (ESC)-derived models for male reproductive toxicity screening. The rationale for developing novel toxicity models is that despite significant advances in our biological understanding and clinical treatment of infertility, many unresolved cases still remain. This is likely due to our lack of knowledge about environmental influences on the critical stages of gamete development. Many practical and ethical difficulties are associated with the collection of human tissue samples to explore the unknown causes of infertility. Thus, a readily available in vitro model that mimics human gamete development would be an extremely valuable research tool for establishing novel toxicity assays. ESC exhibit a high degree of similarity with primordial germ cells (PGC) at the level of gene expression and molecular signaling. In addition, recent evidence shows that ESC can be differentiated into PGC and spermatids in culture. Multiple lines of evidence point to the differences between mouse and human ESC (hESC). In light of these data, we present the case that hESC are better suited as in vitro toxicity screening models than their mouse counterparts. We then describe some of the most promising hESC-based systems that are used today to model certain aspects of male gamete development and that have a potential to be used for toxicity screening. We conclude by discussing the potential of these existing models in toxicology studies and the possibilities for their improvement in the future.
Exploring the Factors That Influence Functional Performance Among Nursing Home Residents

Objective: To promote healthy aging in older nursing home (NH) residents, it is important to identify factors that impact functional performance. Using the Disablement Process Model, it was hypothesized that variables from all levels of the model would significantly impact the ability of a NH resident to get up from a chair. Method: A stepwise multiple logistic regression model was used to test the impact of sociodemographic, physiologic, physical, psychosocial, and environmental factors on chair rise. Results: Analysis indicated that three factors, strength, gait, and self-efficacy, were significantly associated with chair-rise ability and together explained approximately 64% of the variance and successfully classified 88.4% of the chair-rise cases. Discussion: These findings indicate that identifying physical and psychosocial variables early in the disablement process will help health care providers tailor medical and restorative care interventions that may help older adults maintain the ability to chair rise.
Gene-body hypermethylation controlled cryptic promoter and miR26A1-dependent EZH2 regulation of TET1 gene activity in chronic lymphocytic leukemia

The Ten-eleven-translocation 1 (TET1) protein is a member of dioxygenase protein family that catalyzes the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine. TET1 is differentially expressed in many cancers, including leukemia. However, very little is known about mechanism behind TET1 deregulation. Previously, by characterizing global methylation patterns in CLL patients using MBD-seq, we found TET1 as one of the differentially methylated regions with gene-body hypermethylation. Herein, we characterize mechanisms that control TET1 gene activity at the transcriptional level. We show that treatment of CLL cell lines with 5-aza 2´-deoxycytidine (DAC) results in the activation of miR26A1, which causes decrease in both mRNA and protein levels of EZH2, which in turn results in the decreased occupancy of EZH2 over the TET1 promoter and consequently the loss of TET1 expression. In addition, DAC treatment also leads to the activation of antisense transcription overlapping the TET1 gene from a cryptic promoter, located in the hypermethylated intronic region. Increased expression of intronic transcripts correlates with decreased TET1 promoter activity through the loss of RNA Pol II occupancy. Thus, our data demonstrate that TET1 gene activation in CLL depends on miR26A1 regulated EZH2 binding at the TET1 promoter and silencing of novel cryptic promoter by gene-body hypermethylation.
Sulfation of R(--)-apomorphine in the human liver and duodenum, and its inhibition by mefenamic acid, salicylic acid and quercetin

1. The aims were to study the sulfation of R-(--)-apomorphine (hereafter apomorphine) in the human liver and duodenum, and to study the rate of inhibition of apomorphine sulphation by mefenamic acid, salicylic acid and quercetin also in the human liver and duodenum. 2. A rapid and sensitive method was developed to measure the sulfation rate of apomorphine in the human liver and duodenum. The method was based on the use of 0.4 µM 3'-phosphoadenosine-5'-phosphosulfate- [35 S] (PAPS) and 50µM apomorphine. The unreacted PAPS was precipitated with barium hydroxide, barium acetate and zinc sulfate. 3. The rate of apomorphine sulfation (mean ± SD and median) was 261 ± 82 and 242 pmol min -1 mg -1, respectively (liver), and 433 ± 157 and 443 pmol min -1 mg -1, respectively (duodenum). The apomorphine sulfation rate was higher in the duodenum than in the liver (p = 0.0005). 4. Apomorphine sulfation was correlated with SULT1A1 activity in the liver (r 2 = 0.363, p = 0.005) and duodenum (r 2 = 0.494, p = 0.0005), but it did not correlate with SULT1A3 activity both in the liver and duodenum. 5. The K m estimate of apomorphine sulfation rate was 20 ± 3.6 (liver) and 6.5 ± 0.2 µM (duodenum, p = 0.024), and the V max estimate was 248 ± 99 (liver) and 636 ± 104 pmol min -1 mg -1 (duodenum, p = 0.018). 6. Mefenamic acid, salicylic acid and quercetin were potent inhibitors of apomorphine sulfation rate in the liver, and the IC 50 estimates were 16 ± 0.2 nM, 54 ± 8.6 µM and 18 ± 2.8 nM, respectively. These compounds were poor inhibitors of apomorphine sulfation in the duodenum. 7. Apomorphine is sulfated by the human liver and duodenum, the highest activity being associated with the duodenum. The K m of apomorphine sulfotransferase is in the order of µM both in the liver and duodenum. The non-steroidal anti-inflammatory drug mefenamic acid and the natural flavonoid quercetin inhibit the hepatic sulfation of apomorphine with an IC 50 in the order of nM.
Excessive muscular fatigue in the postpoliomyelitis syndrome

To investigate anterior tibial muscle fatigability and metabolism in postpoliomyelitis syndrome patients and controls, we performed measurements of force and relaxation time, as well as 31P magnetic resonance spectroscopy, during intermittent, low-intensity, isometric, voluntary exercise. Both maximum voluntary contraction and tetanic force declined significantly more during exercise and subsequently recovered less in patients compared with controls, indicating greater fatigue in patients. However, intracellular pH and phosphocreatine were not different in the two groups at rest or during exercise or recovery, suggesting that the greater fatigue of the patients was not due to an excessive change of metabolites. Moreover, the pre-exercise half-relaxation time of the tetanus was significantly prolonged in patients compared with controls, and the decline in tetanic force during exercise was linearly related to the half-relaxation time of tetanus, suggesting impaired calcium kinetics. Taken together, the findings of increased fatigability, delayed recovery, and prolonged half-relaxation time, without differences in metabolites, suggest that the fatigue in postpoliomyelitis syndrome may be due to impaired activation beyond the muscle membrane.
Afterword Maintaining Social Order

The starting point of most discussions of the law is compliance, since the purpose of creating laws and empowering legal authorities is to establish and maintain social order by regulating public behavior. The issue addressed by Why People Obey the Law is how such compliance can best be achieved. During the past several decades the dominant approach to securing compliance has been through the threat or use of punishment—that is, via deterrence. The use of deterrence was ubiquitous at the time this book was written in the 1980s, and it has remained the dominant approach to maintaining social order into the twenty-first century (Nagin 1998). Deterrence strategies are one example of instrumental strategies, which are based upon the assumption that the primary factors motivating human behavior are incentives and sanctions. In the context of regulation, this vision leads to a deterrence strategy, linking sanctions to rule breaking, while in the organizational literature it leads to a view that performance is enhanced via incentives, with desired performance linked to the provision of rewards (Tyler and Blader 2000). One argument in favor of using deterrence as an approach to securing com pliance is that it is a strategy that works. Interestingly, as research has accumulated about the influence of risk assessments on law-related behavior, this general assertion has been widely qualified. Studies suggest that deterrence sometimes significantly influences law-related behavior, and sometimes does not. In fact, one finding of Why People Obey the Law, a result typical of studies in this area, is that once other factors are accounted for, there is no significant influence of risk-related judgments on compliance with the law. Further, even when risk is found to have an influence, the magnitude of that influence is small. For example, in a review of studies of drug use, MacCoun (1993) estimates that only around 5 percent of the variance in drug-use behavior is explainable through variations in risk estimates. In addition to mixed evidence regarding effectiveness, the widespread use of deterrence approaches has led to serious negative side effects (Tyler 1997a, 1998, 2003). One such side effect is the dramatic growth in the American prison population, leading the United States to be a world leader in the proportion of its population that is incarcerated. Further, since deterrence policies are directed primarily at the disadvantaged, their use has undermined police-community relations in ur-
Absence of Cocaine- and Amphetamine-Regulated Transcript Results in Obesity in Mice Fed a High Caloric Diet.

Cart (cocaine- and amphetamine-regulated transcript) was first identified to be a major brain mRNA up-regulated by cocaine and amphetamine. The CART protein has been established as a satiety factor closely associated with the action of leptin. To assess CART’s role as an anorexigenic signal, we have generated CART-deficient mice by gene targeting. On a high fat diet, CARTdeficient and female heterozygous mice, but not male heterozygous mice, showed statistically significant increases in weekly food consumption, body weight, and fat mass compared with their wild-type littermates. Furthermore, CART-deficient and female heterozygous mice were significantly heavier when fed a high fat diet than on a regular chow diet at 17 wk of age and at the 14th wk of the feeding studies. However, wild-type or male heterozygous mice showed no weight variations attributable to caloric contents of the diet at that age. Contrary to the obese phenotypes shown in MC4R-, proopiomelanocortin-, or leptindeficient mice, our results showed that CART deficiency predisposed mice to become obese on a calorically dense diet. The results also show that CART may not be a major anorectic signal compared with proopiomelanocortin or leptin in the regulation of energy homeostasis. (Endocrinology 142: 4394–4400, 2001)
Pressure-Dependent, Infrared-Emitting Phenomenon in Hypervelocity Impact

A series of hypervelocity impact experiments were conducted with variable target chamber atmospheric pressure ranging from 0.9 to 21.5 Torr. Using a two-stage light-gas gun, 5.7 mg nylon 6/6 right-cylinders were accelerated to speeds ranging between 6.0 and 6.3 km/s to impact 1.5 mm thick 6061-T6 aluminum plates. Full-field images of near-IR emission (0.9 to 1.7 μm) were measured using a high-speed spectrograph system with image exposure times of 1 μs. The radial expansion of an IR-emitting impact-generated phenomenon was observed to be dependent upon the ambient target chamber atmospheric pressures. Higher chamber pressures demonstrated lower radial expansions of the subsequently measured IR-emitting region uprange of the target. Dimensional analysis, originally presented by Taylor to describe the expansion of a hemispherical blast wave, is applied to describe the observed pressure-dependence of the IR-emitting cloud expansion. Experimental results are used to empirically determine two dimensionless constants for the analysis. The maximum radial expansion of the observed IR-emitting cloud is described by the Taylor blast-wave theory, with experimental results demonstrating the characteristic nonlinear dependence on atmospheric pressure. Furthermore, the edges of the measured IR-emitting clouds are observed to expand at extreme speeds ranging from approximately 13 to 39 km/s. In each experiment, impact ejecta and debris are simultaneously observed in the visible range using an ultrahigh-speed laser shadowgraph system. For the considered experiments, ejecta and debris speeds are measured between 0.6 and 5.1 km/s. Such a disparity in observed phenomena velocities suggests the IR-emitting cloud is a distinctly different phenomenon to both the uprange ejecta and downrange debris generated during a hypervelocity impact.