Miracle-dz/UniFAR-FTUs huggingface dataset:
An Oncolytic Adenovirus Vector Combining Enhanced Cell-to-Cell Spreading, Mediated by the ADP Cytolytic Protein, with Selective Replication in Cancer Cells with Deregulated Wnt Signaling

We have constructed a novel oncolytic adenovirus (Ad) vector named VRX-009 that combines enhanced cell spread with tumor-specific replication. Enhanced spread, which could significantly increase antitumor efficacy, is mediated by overexpression of the Ad cytolytic protein named ADP (also known as E3–11.6K). Replication of VRX-009 is restricted to cells with a deregulated wnt signal transduction pathway by replacement of the wild-type Ad E4 promoter with a synthetic promoter consisting of five consensus binding sites for the T-cell factor transcription factor. Tumor-selective replication is indicated by several lines of evidence. VRX-009 expresses E4ORF3, a representative Ad E4 protein, only in colon cancer cell lines. Furthermore, VRX-009 replicates preferentially in colon cancer cell lines as evidenced by virus productivity 2 orders of magnitude higher in SW480 colon cancer cells than in A549 lung cancer cells. Replication in primary human bronchial epithelial cells and human umbilical vein endothelial cells was also significantly lower than in SW480 cells. When tested in human tumor xenografts in nude mice, VRX-009 effectively suppressed the growth of SW480 colon tumors but not of A549 lung tumors. VRX-009 may provide greater level of antitumor efficacy than standard oncolytic Ad vectors in tumors in which a defect in wnt signaling increases the level of nuclear β-catenin.
Mitochondrial Biogenesis in Skeletal Muscle: Exercise and Aging

Mitochondria are abundantly present in mammalian cells. Their fraction varies from tissue to tissue, ranging from <1% (volume) in white blood cells to 35% in heart muscle cells. However, mitochondria should not be thought of as single entities, but rather a dynamic network that continuously undergoes fission and fusion processes. In skeletal muscle, mitochondria exist as a reticular membrane network. The subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria are located in distinct subcellular regions, and they possess subtle differences in biochemical and functional properties that are characterized by their anatomical locations. SS mitochondria lie directly beneath the sarcolemmal membrane and the IMF mitochondria are located in close contact with the myofibril. Their different properties are likely to influence their capacity for adaptation. SS mitochondria account for 10-15% of the mitochondrial volume and this population has been shown to be more susceptible to adaptation than the IMF mitochondria. However, the IMF mitochondria were found to have higher rates of protein synthesises, enzyme activities and respiration (1).
Studying the Evolution of Promoter Sequences: A Waiting Time Problem

To gain a better understanding of the evolutionary dynamics of regulatory DNA sequences, we address the following questions: (1) How long does it take until a given transcription factor (TF) binding site emerges at random in a promoter sequence? and (2) How does the composition of a TF binding site affect this waiting time? Using two different probabilistic models (an i.i.d. model and a neighbor dependent model), we can compute the expected waiting time for every k-mer, k ranging from 5 to 10, until it appears in a promoter of a species. Our findings indicate that new TF binding sites can be created on a short evolutionary time scale, i.e. in a time span below the speciation time of human and chimp. Furthermore, one can conclude that the composition of a TF binding site plays a crucial role concerning the waiting time until it appears and that the CpG methylation-deamination substitution process probably accelerates the creation of new TF binding sites. A screening of existing TF binding sites moreover reveals that k-mers predicted to have short waiting times occur more frequently than others. Supplementary Material is available at www.libertonline. com/cmb .
A Preliminary Descriptive Model of Expertise Related Competence in Child Sexual Offending

Child sexual offending is a great area of concern to the public and researchers alike. The damaging effects of Child Sexual Abuse are numerous and frequently enduring. Research in sexual offending has tended to focus on therapeutic interventions and effectiveness as well as the aetiological aspects of offending. Much of this research has focused on offender deficits associated with sexual crimes that are the target of intervention programs. There has been little attention paid to the view that sexual offenders appear to learn from their previous offending and in some cases acquire a considerable degree of offence related competency. In other words, some sexual offenders appear to develop high levels of expertise. The purpose of this study was to investigate whether there are 'expert' offenders within the child sexual offending arena who display greater competence in utilising grooming techniques, selecting targets, interpreting and evaluating social and environmental cues, and who possess extensive offence scripts. In this exploratory study, 47 male child sexual offenders were interviewed in New Zealand prison based Sexual Offender Rehabilitation Units about their offences as well as their lives prior to and post offending. Semi-structured interviews were conducted and analysed using Grounded Theory to generate a model of offence specific decision making. Results indicated that child sex offenders vary on the above dimensions and effectively span the range from 'novice' to 'expert' offenders with respect to the quality of their decision making and their domain relevant knowledge structures. By using the general principles of expertise as a conceptual framework, a developmental model of expertise in child sex offenders in New Zealand was constructed. The implications of the constructed model for theory and treatment are discussed and suggestions are made for the direction of future research.
The Other Side of Silence: Sign Language and the Deaf Community in America

Arden Neisser's classic on American Sign Language (ASL) is again available, with a new prologue. The Other Side of Silence chronicles the culture and issues of the Deaf community through telling interviews and research from across the country. In widely varying encounters, Neisser heard Deaf individuals recall how teachers suppressed the use of ASL in the school, how linguists fostered conflicting theories, and how various institutions diluted ASL to suit hearing patrons. This seminal book reveals the warmth, creativity, and resilience of Deaf people, and culminates in an update of the community today.
High‐yield secretion of recombinant proteins from the microalga Chlamydomonas reinhardtii

Summary Microalga‐based biomanufacturing of recombinant proteins is attracting growing attention due to its advantages in safety, metabolic diversity, scalability and sustainability. Secretion of recombinant proteins can accelerate the use of microalgal platforms by allowing post‐translational modifications and easy recovery of products from the culture media. However, currently, the yields of secreted recombinant proteins are low, which hampers the commercial application of this strategy. This study aimed at expanding the genetic tools for enhancing secretion of recombinant proteins in Chlamydomonas reinhardtii, a widely used green microalga as a model organism and a potential industrial biotechnology platform. We demonstrated that the putative signal sequence from C. reinhardtii gametolysin can assist the secretion of the yellow fluorescent protein Venus into the culture media. To increase the secretion yields, Venus was C‐terminally fused with synthetic glycomodules comprised of tandem serine (Ser) and proline (Pro) repeats of 10 and 20 units [hereafter (SP)n, wherein n = 10 or 20]. The yields of the (SP)n‐fused Venus were higher than Venus without the glycomodule by up to 12‐fold, with the maximum yield of 15 mg/L. Moreover, the presence of the glycomodules conferred an enhanced proteolytic protein stability. The Venus‐(SP)n proteins were shown to be glycosylated, and a treatment of the cells with brefeldin A led to a suggestion that glycosylation of the (SP)n glycomodules starts in the endoplasmic reticulum (ER). Taken together, the results demonstrate the utility of the gametolysin signal sequence and (SP)n glycomodule to promote a more efficient biomanufacturing of microalgae‐based recombinant proteins.
Retrieval-induced forgetting and recognition memory: insights from behavioral and electrophysiological experiments

Retrieving a subset of previously studied items can impair later recognition of related items. Using the remember/know procedure (Experiment 1 and 5), the ROC procedure (Experiments 2-4), and analysis of EEG old/new effects (Experiment 5), it was investigated how such retrieval-induced forgetting can be explained in terms of single-process and dual-process accounts of recognition memory. Across experiments, dual-process analysis yielded a complex pattern of results which suggests that retrieval practice can affect familiarity and - less reliably - also recollection of the unpracticed material. Assuming that recognition is entirely based on a single source of memorial information, single-process analysis led to an excellent description of the data and suggests that retrieval practice reduced unpracticed items' general memory strength in each of the experiments. This suggestion is consistent with prior work on free recall, cued recall, associative recognition, and response latencies, and agrees with the inhibitory account of retrieval-induced forgetting. Recognition of unpracticed material was further characterized by reduced theta power in the EEG, indicating that unpracticed material triggered only relatively weak memory signals. It is argued that the detrimental effect of retrieval practice is best characterized as a weakening of the unpracticed item's inherent memory representation. Analysis of inter-electrode synchronisation further revealed a novel type of recognition correlate in the theta frequency range.
ARSENIC ADSORPTION AND REDUCTION IN IRON-RICH SOILS NEARBY LANDFILLS IN NORTHWEST FLORIDA

In Florida, soils are mainly composed of Myakka, an acid soil characterized by a subsurface accumulation of humus and Al(III) and Fe(III) oxides. Downgradient of the landfills in Northwest Florida, elevated levels of iron and arsenic observations had been made in the groundwater from monitoring wells, which was attributed to the geomicrobial iron and arsenic reduction. There is thus an immediate research need for a better understanding of the reduction reactions that are responsible for the mobilization of iron and arsenic in the subsurface soil nearby landfills. Owing to the high Fe(III) oxide content, As(V) adsorption reactions with Fe(III) oxide surfaces are particularly important, which may control As(V) reduction. This research focused on the investigation of the biogeochemical processes of the subsurface soil nearby landfills of Northwest Florida. Arsenic and iron reduction was studied in batch reactors and quantified based on Monod-type microbial kinetic growth simulations. As(V) adsorption in iron-rich Northwest Floridian soils was further investigated to explain the reduction observations. It was demonstrated in this research that solubilization of arsenic in the subsurface soil nearby landfills in Northwest Florida would likely occur under conditions favoring Fe(III) dissimilatory reduction.
Secure source coding with a public helper

We consider secure multi-terminal source coding problems in the presence of a public helper. Two main scenarios are studied: 1) source coding with a helper where the coded side information from the helper is eavesdropped by an external eavesdropper, 2) triangular source coding with a helper where the helper is considered as a public terminal. We are interested in how the helper can support the source transmission subject to a constraint on the amount of information leaked due to its public nature. We characterize the tradeoff between transmission rate, incurred distortion, and information leakage rate at the helper/eavesdropper in the form of a rate-distortion-leakage region for various classes of problems.
Knockdown Epithelial Membrane Protein 1 Suppresses Human Degenerative Intervertebral Disc–Derived Nucleus Pulposus Cell Proliferation

Objective: Our previous work showed that epithelial membrane protein 1 (EMP1) is highly expressed in nucleus pulposus of the human degenerative intervertebral disc. The present study was designed to investigate the role of EMP1 in nucleus pulposus cells in intervertebral disc degeneration (IDD). Design: Human nucleus pulposus cells derived from degenerative intervertebral discs were cultured. EMP1 expression was knocked down by lentivirus-mediated specific interfering RNA. Cell morphology was observed, and cell proliferation, apoptosis, and cycle were evaluated. Results: Knockdown of EMP1 inhibited cell proliferation, caused cells to shrink, and accelerated the apoptosis induced by serum deprivation or addition of cycloheximide but did not evoke apoptosis in normal culture conditions. Conclusions: These findings suggest that EMP1 promoted chondrocyte proliferation, survival, and morphological change of cells during IDD, implying that EMP1 may be a target for biological therapy for IDD.
Cell-Edge Multi-User Relaying with Overhearing

Carefully designed protocols can turn overheard interference into useful side information to allow simultaneous transmission of multiple communication flows and increase the spectral efficiency in interference-limited regime. We propose a novel scheme in a typical cell-edge scenario. By exploiting the overhearing link through proper relay precoding and adaptive receiver processing, rate performance can be significantly improved compared to the conventional transmission which does not utilize overhearing.
On orthogonality and learning recurrent networks with long term dependencies

It is well known that it is challenging to train deep neural networks and recurrent neural networks for tasks that exhibit long term dependencies. The vanishing or exploding gradient problem is a well known issue associated with these challenges. One approach to addressing vanishing and exploding gradients is to use either soft or hard constraints on weight matrices so as to encourage or enforce orthogonality. Orthogonal matrices preserve gradient norm during backpropagation and may therefore be a desirable property. This paper explores issues with optimization convergence, speed and gradient stability when encouraging or enforcing orthogonality. To perform this analysis, we propose a weight matrix factorization and parameterization strategy through which we can bound matrix norms and therein control the degree of expansivity induced during backpropagation. We find that hard constraints on orthogonality can negatively affect the speed of convergence and model performance.
The SAFE project: ‘plant food allergies: field to table strategies for reducing their incidence in Europe’ an EC‐funded study

The true prevalence of food allergy as an IgE mediated reaction is still under discussion. Using apple as a model allergen source a multidisciplinary consortium worked together at developing various strategies for reducing the incidence of fruit allergies in an EC‐funded project. Patient allergen profiles were established using in vitro and in vivo tests with respect to geographic area and mild or severe symptoms. Apple allergens (Mal d 1–Mal d 4) were characterised, variants identified, cloned and sequenced. These individual allergens were used to increase the sensitivity and specificity of diagnosis. Furthermore, they provided better prognosis of disease severity. RT‐PCR and ELISA were developed for determining the allergen specific mRNA and expressed allergenic protein in a large number of apple cultivars. Similarly, changes in allergen characteristics from harvest through storage to processing and the impact of agronomic practices were investigated. Allergen genes were mapped on a molecular linkage map of apple. The biological function of Mal d 1 was studied using the RNA interference strategy. Finally, consumer attitudes in Northern, Central and Southern Europe were gauged on the acceptability of low allergen cultivars or a GMO and its impact on product quality.
CARACTERÍSTICAS DE PERSONALIDAD EN SUJETOS DROGODEPENDIENTES

Characteristics of personality in addicts to drugs (personality and heroin abuse). In this article there's a study of the possible differences that exist between a group of addicts to heroin and a group of subjects without any problems of addiction to drugs, after supplying both groups with the questionnarie 16PF of Catell. The results show scarce differences between both groups in which the punctuations of the primary factors of the 16PF. The final conclusion is the difficulty in establishing the characteristics of personality that define the addicts to heroin.
Mutation of Glutamate 155 of the GABAA Receptor β2 Subunit Produces a Spontaneously Open Channel: A Trigger for Channel Activation

Protein movements underlying ligand-gated ion channel activation are poorly understood. The binding of agonist initiates a series of conformational movements that ultimately lead to the opening of the ion channel pore. Although little is known about local movements within the GABA-binding site, a recent structural model of the GABAA receptor (GABAAR) ligand-binding domain predicts that β2Glu155 is a key residue for direct interactions with the neurotransmitter (Cromer et al., 2002). To elucidate the role of the β2Ile154-Asp163 region in GABAAR activation, each residue was individually mutated to cysteine and coexpressed with wild-type α1 subunits in Xenopus laevis oocytes. Seven mutations increased the GABA EC50 value (8- to 3400-fold), whereas three mutations (E155C, S156C, and G158C) also significantly increased the 2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl) pyridazinium (SR-95531) KI value. GABA, SR-95531, and pentobarbital slowed N-biotinylaminoethyl methanethiosulfonate modification of T160C and D163C, indicating that β2Thr160 and β2Asp163 are located in or near the GABA-binding site and that this region undergoes structural rearrangements during channel gating. Cysteine substitution of β2Glu155 resulted in spontaneously open GABAARs and differentially decreased the GABA, piperidine-4-sulfonic acid (partial agonist), and SR-95531 sensitivities, indicating that the mutation perturbs ligand binding as well as channel gating. Tethering thiol-reactive groups onto β2E155C closed the spontaneously open channels, suggesting that β2Glu155 is a control element involved in coupling ligand binding to channel gating. Structural modeling suggests that the β2 Ile154-Asp163 region is a protein hinge that forms a network of interconnections that couples binding site movements to the cascade of events leading to channel opening.
A Screen of Approved Drugs Identifies the Androgen Receptor Antagonist Flutamide and Its Pharmacologically Active Metabolite 2-Hydroxy-Flutamide as Heterotropic Activators of Cytochrome P450 3A In Vitro and In Vivo

Once thought to be an artifact of microsomal systems, atypical kinetics with cytochrome P450 (CYP) enzymes have been extensively investigated in vitro and found to be substrate and species dependent. Building upon increasing reports of heterotropic CYP activation and inhibition in clinical settings, we screened a compound library of clinically approved drugs and various probe compounds to identify the frequency of heterotropism observed with different drug classes and the associated CYP enzymes thereof (1A2, 2C9, 2D6, and 3A4/5). Results of this screen revealed that the prescribed androgen receptor antagonist flutamide activated the intrinsic midazolam hydroxylase activity of CYP3A in human hepatic microsomes (66%), rat and human hepatocytes (36 and 160%, respectively), and in vivo in male Sprague-Dawley rats (>2-fold, combined area under the curve of primary rat in vivo midazolam metabolites). In addition, a screen of the pharmacologically active metabolite 2-hydroxy-flutamide revealed that this principle metabolite increased CYP3A metabolism of midazolam in human microsomes (30%) and hepatocytes (110%). Importantly, both flutamide and 2-hydroxy-flutamide demonstrated a pronounced increase in the CYP3A-mediated metabolism of commonly paired medications, nifedipine (antihypertensive) and amiodarone (antiarrhythmic), in multispecies hepatocytes (100% over baseline). These data serve to highlight the importance of an appropriate substrate and in vitro system selection in the pharmacokinetic modeling of atypical enzyme kinetics. In addition, the results of our investigation have illuminated a previously undiscovered class of heterotropic CYP3A activators and have demonstrated the importance of selecting commonly paired therapeutics in the in vitro and in vivo modeling of projected clinical outcomes.
How to use a gestalt interpretation for ventilation-perfusion lung scintigraphy.

UNLABELLED The use of a so-called gestalt interpretation, an integration of different sets of criteria and the physician's own experience, has been advocated in the interpretation of lung scintigraphs of patients with clinically suspected pulmonary embolism. However, data on the reliability of this approach are limited. The aim of this study was to investigate the observer variability and accuracy of the gestalt interpretation of perfusion scintigraphy (combined with chest radiography) as well as the impact of adding ventilation scintigraphy and clinical pretest information. METHODS Three experienced observers independently reviewed the chest radiograph and ventilation-perfusion scans of 101 consecutive patients with clinically suspected pulmonary embolism. All datasets were reviewed twice by each observer, using a visual analog scale to indicate the estimated probability of pulmonary embolism. The results of the gestalt interpretations were analyzed against the presence or absence of pulmonary embolism. RESULTS All 3 gestalt interpretations had a good-to-excellent interobserver variability (intraclass correlation coefficient [ICC], 0.73-0.89), with similar intraobserver agreement (ICC, 0.76-0.95). The performance of all 3 readers was comparable. The areas under the curve (AUCs) of all 3 observers were high and similar (for observer 1, the AUCs were 0.96 [95% confidence interval (CI)], 0.93-1.00), 0.96 (95% CI, 0.93-1.00), and 0.95 (95% CI, 0.90-1.00), respectively, for the 3 gestalt interpretations). CONCLUSION A gestalt interpretation is a useful classification scheme with good-to-excellent intra- and interobserver variability. However, the interpretation and the consequences of this result are dependent on the observer. Unexpectedly, the addition of information on ventilation scintigraphy and clinical information did not affect the overall assessment.