Miracle-dz/UniFAR-FTUs huggingface dataset:
The Emerging Role of Large Immunophilin FK506 Binding Protein 51 in Cancer

FK506 binding protein 51 (FKBP51) is an immunophilin physiologically expressed in lymphocytes. Very recently, aberrant expression of this protein was found in melanoma; FKBP51 expression correlates with melanoma aggressiveness and is maximal in metastatic lesions. FKBP51 promotes NF-κB activation and is involved in the resistance to genotoxic agents, including anthracyclines and ionizing radiation. FKBP51 is a cochaperone with peptidyl-prolyl isomerase activity that regulates several biological processes through protein-protein interaction. There is increasing evidence that FKBP51 hyperexpression is associated with cancer and this protein has a relevant role in sustaining cell growth, malignancy, and resistance to therapy. There is also evidence that FKBP ligands are potent anticancer agents, in addition to their immunosuppressant activity. In particular, rapamycin and its analogs have shown antitumor activity across a variety of human cancers in clinical trials. Although, classically, rapamycin actions are ascribed to inhibition of mTOR, recent studies indicate FKBP51 is also an important molecular determinant of the drug’s anticancer activity. The aim of this article is to review the functions of FKBP51, especially in view of the recent findings that this protein is a potential oncogene when deregulated and a candidate target for signaling therapies against cancer.
BEHAVIOR AS STIMULATED RESPONSE : THE BEHAVIORISTIC LEGACY TO COGNITIVE PSYCHOLOGY

SUMMARY According to conventional psychological wisdom the relationship between perception and action is uni-directional: Perceiving informs an individual about the environment and acting results as a more or less adequate response to the perceived situation. Following Dewey (1896) and others we argue that this is only half of the story. In fact, humans commonly act not in order to respond to, but to produce stimuli. Action is defined as goal-directed movement and goals as intended movement or action-contingent stimulus events. Accordingly, selecting an action must be in terms of the expected action-contingent stimulation the actor aims at. This again implies that action representations must comprise both motor-related codes and codes of sensory action effects. We will present a two-stage model of how these codes are acquired, integrated, and used for intentional action. We also report on a number of studies from our lab concerning the acquisition of acoustic action effects that provide solid ground for our approach.
Intrinsic Protein-Protein Interaction-mediated and Chaperonin-assisted Sequential Assembly of Stable Bardet-Biedl Syndrome Protein Complex, the BBSome*

Background: Bardet-Biedl syndrome proteins form a complex known as the BBSome. The details of BBSome assembly are unknown. Results: The BBSome is assembled via intrinsic protein-protein interactions, some of which involve cytoplasmic chaperonins. Conclusion: BBSome assembly is a regulated stepwise process. Significance: Understanding the assembly process of the BBSome might help to better understand the molecular mechanisms involved in cilia-related diseases. The pleiotropic features of obesity, retinal degeneration, polydactyly, kidney abnormalities, cognitive impairment, hypertension, and diabetes found in Bardet-Biedl syndrome (BBS) make this disorder an important model disorder for identifying molecular mechanisms involved in common human diseases. To date, 16 BBS genes have been reported, seven of which (BBS1, 2, 4, 5, 7, 8, and 9) code for proteins that form a complex known as the BBSome. The function of the BBSome involves ciliary membrane biogenesis. Three additional BBS genes (BBS6, BBS10, and BBS12) have homology to type II chaperonins and interact with CCT/TRiC proteins and BBS7 to form a complex termed the BBS-chaperonin complex. This complex is required for BBSome assembly. Little is known about the process and the regulation of BBSome formation. We utilized point mutations and null alleles of BBS proteins to disrupt assembly of the BBSome leading to the accumulation of BBSome assembly intermediates. By characterizing BBSome assembly intermediates, we show that the BBS-chaperonin complex plays a role in BBS7 stability. BBS7 interacts with BBS2 and becomes part of a BBS7-BBS2-BBS9 assembly intermediate referred to as the BBSome core complex because it forms the core of the BBSome. BBS1, BBS5, BBS8, and finally BBS4 are added to the BBSome core to form the complete BBSome.
Multipath TCP algorithms: theory and design

Multi-path TCP (MP-TCP) has the potential to greatly improve application performance by using multiple paths transparently. We propose a fluid model for a large class of MP-TCP algorithms and identify design criteria that guarantee the existence, uniqueness, and stability of system equilibrium. We characterize algorithm parameters for TCP-friendliness and prove an inevitable tradeoff between responsiveness and friendliness. We discuss the implications of these properties on the behavior of existing algorithms and motivate a new design that generalizes existing algorithms. We use ns2 simulations to evaluate the proposed algorithm and illustrate its superior overall performance.
Body image, mood, and televised images of attractiveness: The role of social comparison.

Heinherg and Thompson (1995) demonstrated that females exposed to a compilation of media images (commercials) reflecting the current societally sanctioned standards of thinness and attractiveness experienced greater mood and body image disturbance than females who viewed a neutral, nonappearance-related control video Social comparison has been offered as one mechanism for the negative outcomes of such media-based exposures. In the current study, social comparison was manipulated by creating three instructional conditions: comparison, distraction, and neutral. Instructional set did not differentially affect recall of appearance or nonappearance aspects of either an appearance-related collection of commercials or a nonappearance video (e.g., Heinberg & Thompson, 1995). However, participants in the comparison condition self-reported a greater degree of self-to-model comparison than participants in the distinction or neutral conditions. A marginally significant three-way interaction between condition, tape, a.
Non-Egalitarian Allocations among Preschool Peers in a Face-to-Face Bargaining Task

In face-to-face bargaining tasks human adults almost always agree on an equal split of resources. This is due to mutually recognized fairness and equality norms. Early developmental studies on sharing and equality norms found that egalitarian allocations of resources are not common before children are 5 or 6 years old. However, recent studies have shown that in some face-to face collaborative situations, or when recipients express their desires, children at much younger ages choose equal allocations. We investigated the ability of 3.5 and 5-year-olds to negotiate face-to-face, whether to collaborate to obtain an equal or an unequal distribution of rewards. We hypothesized that the face-to-face interaction and interdependency between partners would facilitate egalitarian outcomes at both ages. In the first experiment we found that 5-year-olds were more egalitarian than 3.5-year-olds, but neither of the age classes shared equally. In the second experiment, in which we increased the magnitude of the inequality, we found that children at both ages mostly agreed on the unequal distribution. These results show that communication and face-to-face interactions are not sufficient to guarantee equal allocations at 3–5 years of age. These results add to previous findings suggesting that in the context of non-collaboratively produced resources it is only after 5 years of age that children use equality norms to allocate resources.
Rehabilitation Exercise Progression for the Gluteus Medius Muscle with Consideration for Iliopsoas Tendinitis

Background It is common for hip arthroscopy patients to demonstrate significant gluteus medius muscle weakness and concurrent iliopsoas tendinitis. Restoration of gluteus medius muscle function is essential for normal hip function. Hypothesis A progression of hip rehabilitation exercises to strengthen the gluteus medius muscle could be identified that minimize concurrent iliopsoas muscle activation to reduce the risk of developing or aggravating hip flexor tendinitis Study Design Descriptive laboratory study. Methods Electromyography (EMG) signals of the gluteus medius and iliopsoas muscles were recorded from 10 healthy participants during 13 hip rehabilitation exercises. The indwelling fine-wire EMG electrodes were inserted under ultrasound guidance. The average and peak EMG amplitudes, normalized by the peak EMG amplitude elicited during maximum voluntary contractions, were determined and rank-ordered from low to high. The ratio of iliopsoas to gluteus medius muscle activity was calculated for each exercise. Exercises were placed into respective time phases based on average gluteus medius EMG amplitude, except that exercises involving hip rotation were avoided in phase I (phase I, initial 4 or 8 weeks; phase II, subsequent 4 weeks; phase III, final 4 weeks). Results A continuum of hip rehabilitation exercises was identified. Resisted terminal knee extension, resisted knee flexion, and double-leg bridges were identified as appropriate for phase I and resisted hip extension, stool hip rotations, and side-lying hip abduction with wall-sliding for phase II. Hip clam exercises with neutral hips may be used with caution in patients with hip flexor tendinitis. Prone heel squeezes, side-lying hip abduction with internal hip rotation, and single-leg bridges were identified for phase III. Conclusion/Clinical Relevance This study identified the most appropriate hip rehabilitation exercises for each phase to strengthen the gluteus medius muscle after hip arthroscopy and those to avoid when iliopsoas pain or tendinitis is a concern.
L-type calcium channel-mediated plateau potentials in barrelette cells during structural plasticity.

Development and maintenance of whisker-specific patterns along the rodent trigeminal pathway depends on an intact sensory periphery during the sensitive/critical period in development. Barrelette cells of the brain stem trigeminal nuclei are the first set of neurons to develop whisker-specific patterns. Those in the principal sensory nucleus (PrV) relay these patterns to the ventrobasal thalamus, and consequently, to the somatosensory cortex. Thus PrV barrelette cells are among the first group of central neurons susceptible to the effects of peripheral damage. Previously we showed that membrane properties of barrelette cells are distinct as early as postnatal day 1 (PND 1) and remain unchanged following peripheral denervation in newborn rat pups (Lo and Erzurumlu 2001). In the present study, we investigated the changes in synaptic transmission. In barrelette cells of normal PND 1 rats, weak stimulation of the trigeminal tract (TrV) that was subthreshold for inducing Na(+) spikes evoked an excitatory postsynaptic potential-inhibitory postsynaptic potential (EPSP-IPSP) sequence that was similar to the responses seen in older rats (Lo et al. 1999). Infraorbital nerve transection at birth did not alter excitatory and inhibitory synaptic connections of the barrelette cells. These observations suggested that local neuronal circuits are already established in PrV at birth and remain intact after deafferentation. Strong stimulation of the TrV induced a sustained depolarization (plateau potential) in denervated but not in normal barrelette neurons. The plateau potential was distinct from the EPSP-IPSP sequence by 1) a sustained (>80 ms) depolarization above -40 mV; 2) a slow decline slope (<0.1 mV/ms); 3) partially or totally inactivated Na(+) spikes on the plateau; and 4) a termination by a steep decay (>1 mV/ms) to a hyperpolarizing membrane level. The plateau potential was mediated by L-type Ca(2+) channels and triggered by a N-methyl-D-aspartate (NMDA) receptor-mediated EPSP. gamma-aminobutyric acid-A (GABA(A)) receptor-mediated IPSP dynamically regulated the latency and duration of the plateau potential. These results indicate that after neonatal peripheral damage, central trigeminal inputs cause a large and long-lasting Ca(2+) influx through L-type Ca(2+) channels in barrelette neurons. Increased Ca(2+) entry may play a key role in injury-induced structural remodeling, and/or transsynaptic cell death.
Ectopic cyclin E expression induces premature entry into S phase and disrupts pattern formation in the Drosophila eye imaginal disc.

During animal development, cell proliferation is controlled in many cases by regulation of the G1 to S phase transition. Studies of mammalian tissue culture cells have shown that the G1-specific cyclin, cyclin E, can be rate limiting for progression from G1 to S phase. During Drosophila development, down-regulation of cyclin E is required for G1 arrest in terminally differentiating embryonic epidermal cells. Whether cyclin E expression limits progression into S phase in proliferating, as opposed to differentiating, cells during development has not been investigated. Here we show that Drosophila cyclin E (DmcycE) protein is absent in G1 phase cells but appears at the onset of S phase in proliferating cells of the larval optic lobe and eye imaginal disc. We have examined cells in the eye imaginal epithelium, where a clearly defined developmentally regulated G1 to S phase transition occurs. Ectopic expression of DmcycE induces premature entry of most of these G1 cells into S phase. Thus in these cells, control of DmcycE expression is required for regulated entry into S phase. Significantly, a band of eye imaginal disc cells in G1 phase was not induced to enter S phase by ectopic expression of DmcycE. This provides evidence for additional regulatory mechanisms that operate during G1 phase to limit cell proliferation during development. These results demonstrate that the role of cyclin E in regulating progression into S phase in mammalian tissue culture cells applies to some, but not all, cells during Drosophila development. (ABSTRACT TRUNCATED AT 250 WORDS)
A Cdh1HA knock‐in allele rescues the Cdh1−/− phenotype but shows essential Cdh1 function during placentation

The specific roles of classical cadherins at key morphogenetic events during development are still not fully understood. As part of a project to study cadherin function during early mammalian development, we generated mice carrying an HA‐epitope tagged Cdh1 (E‐cadherin) cDNA knocked into the Cdh1 locus, similar to the previously described mouse mutants in which we forced Cdh2 (N‐cadherin) expression in the Cdh1 expression domain. As expected and in contrast to Cdh1Cdh2/Cdh2 and Cdh1−/−, our Cdh1HA/HA mutant embryos form proper trophectoderm, implant and undergo both gastrulation and neurulation. However, Cdh1HA/HA mice display an unexpected phenotype at embryonic day 10.5. Cdh1HA/HA embryos are smaller, paler and suffer from an insufficient nutrient supply. We detected a reduced expression of Cdh1HA specifically in the extraembryonic ectoderm and in the labyrinth layer, whereas expression in the embryo proper was normal. With this approach, we show for the first time that Cdh1 is essential for the correct formation of the placenta. Placentas without Cdh1 expression are impaired and incapable of establishing a proper connection between the embryonic and the maternal blood vessels for efficient nutrient and oxygen transport. Developmental Dynamics 239:2330–2344, 2010. © 2010 Wiley‐Liss, Inc.
Wearable Navigation System for the Visually Impaired and Blind People

A wearable navigation system for visually impaired and blind people in unknown indoor and outdoor environments is presented. This system will map and track the position of the pedestrian during the exploration of the unknown environment. In order to build this system the well known Simultaneous Localization and Mapping (SLAM) from mobile robotics will be implemented. Once a map is created the user can be guided efficiently by a route selecting method. The user will be equipped with a short range laser, an inertial measurement unit (IMU), a wearable computer for data processing and an audio bone headphones. This system does not intent to replace the use of the white cane. However, the purpose is to gather contextual information to aid the user in navigating with the white cane.
Exploring the space of emotional faces of subjects without acting experience

textabstractThe current state of semi-automated facial animation demands better understanding of how facial expressions are produced by real people. As a first step of a series of empirical studies, we investigated snapshots of facial expressions of the six basic emotions, produced by 18 subjects in `out of context' sessions. The MPEG-4 coded vectors were analysed on principal components and canonical variates, which served as a basis to draw conclusions about the (for the negative emotions: lack of) generic characteristics of the six emotions and their mutual distances. Our results are compared to ones obtained by facial image analysis and human perception researchers.
Predictive Heterogeneity-Aware Application Scheduling for Chip Multiprocessors

Single-ISA heterogeneous chip multiprocessor (CMP) is not only an attractive design paradigm but also is expected to occur as a consequence of manufacturing imperfections, such as process variation and permanent faults. Process variation could cause cores to have different maximum frequencies; whereas permanent faults could cause losses of functional units and/or cache banks randomly distributed on cores, resulting in fine-grained heterogeneous CMPs. Hence, application schedulers for CMPs need to be aware of such heterogeneity to avoid pathological scheduling decisions. However, existing heterogeneity-aware scheduling schemes rely on either trial runs or offline profiled information to schedule the applications, which incur significant performance degradation and are impractical to implement. This paper presents a dynamic and predictive application scheduler for single-ISA heterogeneous CMPs. It uses a set of hardware-efficient online profilers and an analytical performance model to simultaneously predict the applications performance on different cores. Based on the predicted performance, the scheduler identifies and enforces near-optimal application assignment for each scheduling interval without any trial runs or offline profiling. We demonstrate that, using only a few kilo-bytes of extra hardware, the proposed heterogeneity-aware scheduler improves the system throughput by an average of 20.8 percent and the weighted speedup by 11.3 percent compared with the commodity OpenSolaris scheduler. Compared with the best known research scheduler, the proposed scheduler also improves the throughput by 11.4 percent and the weighted speedup by 6.8 percent.
CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?

BACKGROUND/AIM Genetic polymorphism of CYP2D6 shows diverse pharmacokinetic and pharmacodynamic variation. Therefore, the present work was designed to study the variation in therapeutic responses to metoprolol (MP) in stage 1 hypertensive patients and also aims to verify the association of CYP2D6*4 polymorphism and response variation in an Indian population for the first time. MATERIALS AND METHODS Clinically, a total of 119 hypertensive patients and 116 healthy individuals as controls were included. Patients were treated with MP extended release 25 mg tablets once daily for 2 weeks. Reduction in systolic blood pressure, diastolic blood pressure, and pulse rate were recorded before and after the treatment. For genotyping, genotypes of 89 hypertensive patients and 71 healthy controls were investigated for CYP2D6*4 polymorphism. RESULTS Based on reduction in systolic blood pressure, 26% of the patients did not respond to the MP treatment. Of the patients that responded, 28% responded very slowly, 35% (19 males, 23 females) responded moderately, and 12% (8 males, 6 females) showed a good response to MP. For genotype analysis, we pooled 89 hypertensive patients and 71 controls. No association was found between CYP2D6*4 polymorphism and MP response. CONCLUSION We found no relationship between MP response and CYP2D6*4 genotype in an Indian population in our study.
Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial.

OBJECTIVE A range of immune system abnormalities have been associated with schizophrenia. Probiotic compounds modulate the immune response and offer a potential treatment strategy for schizophrenia. Probiotic compounds have also been observed to improve gastrointestinal dysfunction, which is a common problem in individuals with schizophrenia. We performed a randomized, double-blind, placebo-controlled trial to examine whether probiotic supplementation can reduce symptom severity in patients with schizophrenia receiving antipsychotic treatment and also whether probiotics are associated with bowel functioning. METHODS Outpatients with schizophrenia (N = 65) meeting DSM-IV criteria and with at least moderately severe psychotic symptoms were enrolled in the study from December 2010-August 2012. Following a 2-week placebo run-in period, patients were randomly assigned to 14 weeks of double-blind adjunctive probiotic (combined Lactobacillus rhamnosus strain GG and Bifidobacterium animalis subsp. lactis strain Bb12) or placebo therapy. Psychiatric symptoms were assessed biweekly with the Positive and Negative Syndrome Scale (PANSS), and patients were queried weekly about their gastrointestinal functioning. RESULTS Repeated-measures analysis of variance showed no significant differences in the PANSS total score between probiotic and placebo supplementation (F = 1.28, P = .25). However, patients in the probiotic group were less likely to develop severe bowel difficulty over the course of the trial (hazard ratio = 0.23; 95% CI, 0.09-0.61, P = .003). CONCLUSIONS Probiotic supplementation may help prevent a common somatic symptom associated with schizophrenia. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01242371.
Female Juvenile Delinquency: A Nineteenth-Century Follow-up

With the mid-nineteenth century's rapid industrialization and great increases in social displacement and crime came the estab lishment of the Industrial School for Girls in Lancaster, Mass. — the first of its kind in the United States. This paper examines the records of the first 250 girls committed to this school, between 1856 and 1861. Follow-up data are available on 184 of these girls, classifying them according to the following categories: good outcome, inadequate or poor outcome, grossly antisocial, chronic mental illness requiring hospitalization, and premature death. Excerpts taken from the girls' background reports are given as examples. Acknowledging the disturbing lack of research on female juvenile offenders, the authors offer this study in the hope that it provides a perspective on the present crisis in the management of young delinquents.