Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Positive Feedback Loop Mediated by the Docking Protein Gab1 and Phosphatidylinositol 3-Kinase in Epidermal Growth Factor Receptor Signaling

ABSTRACT The Gab1 protein is tyrosine phosphorylated in response to various growth factors and serves as a docking protein that recruits a number of downstream signaling proteins, including phosphatidylinositol 3-kinase (PI-3 kinase). To determine the role of Gab1 in signaling via the epidermal growth factor (EGF) receptor (EGFR) we tested the ability of Gab1 to associate with and modulate signaling by this receptor. We show that Gab1 associates with the EGFR in vivo and in vitro via pTyr sites 1068 and 1086 in the carboxy-terminal tail of the receptor and that overexpression of Gab1 potentiates EGF-induced activation of the mitogen-activated protein kinase and Jun kinase signaling pathways. A mutant of Gab1 unable to bind the p85 subunit of PI-3 kinase is defective in potentiating EGFR signaling, confirming a role for PI-3 kinase as a downstream effector of Gab1. Inhibition of PI-3 kinase by a dominant-interfering mutant of p85 or by Wortmannin treatment similarly impairs Gab1-induced enhancement of signaling via the EGFR. The PH domain of Gab1 was shown to bind specifically to phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3], a product of PI-3 kinase, and is required for activation of Gab1-mediated enhancement of EGFR signaling. Moreover, the PH domain mediates Gab1 translocation to the plasma membrane in response to EGF and is required for efficient tyrosine phosphorylation of Gab1 upon EGF stimulation. In addition, overexpression of Gab1 PH domain blocks Gab1 potentiation of EGFR signaling. Finally, expression of the gene for the lipid phosphatase PTEN, which dephosphorylates PtdIns(3,4,5)P3, inhibits EGF signaling and translocation of Gab1 to the plasma membrane. These results reveal a novel positive feedback loop, modulated by PTEN, in which PI-3 kinase functions as both an upstream regulator and a downstream effector of Gab1 in signaling via the EGFR.
Objective Human Visual System Based Video Quality Assessment Metric for Low Bit-Rate Video Communication Systems

Quality assessment is crucial to developments of video communication systems. While subjective test yields most accurate results, its expensive cost and human biasness make it an unsatisfactory figure of merit. The peak-signal to noise ratio (PSNR), the most acceptable objective video quality assessment metric, is based on error sensitivity; its failure to capture perceptual errors is well documented. Other perceptual quality metrics fail to detect the localized errors that are common in sequences produced by low bit-rate video communication systems. In this work, a novel perceptual quality assessment metric, the structural similarity (SSIM) metric, is modified to better detect spatial artifacts often seen in video communication systems
Postsynaptic modulation of rectifying electrical synaptic inputs to the LG escape command neuron in crayfish

The lateral giant (LG) tail-flip escape system of crayfish is organized to provide a massive convergence of mechanosensory inputs onto the LG command neuron through electrical synapses from both mechanosensory afferents and interneurons. We used electrophysiological techniques to show that the connections between three major mechanosensory interneurons and LG rectify, and that their inputs to LG can be reduced by postsynaptic depolarization and increased by postsynaptic hyperpolarization. The mechanosensory afferents and interneurons are excited by sensory nerve shock, and the components of the resulting LG PSP can be similarly modulated by the same postsynaptic potential changes. Because these inputs are all made through electrical synapses, we conclude that they are rectifying connections, as well. To test the physical plausibility of this conclusion, we developed an electrical model of the rectifying connection between a mechanosensory interneuron and LG, and found that it can reproduce all the qualitative features of the orthodromic and antidromic experimental responses. The ability of postsynaptic membrane potential to modulate inputs through rectifying electrical synapses is used in the escape system to enhance LG's relative sensitivity to novel, phasic stimuli. Postsynaptic depolarization of LG produced by earlier inputs “reverse-biases” the rectifying input synapses and reduces their strength relative to times when LG is at rest.
Potent Rescue of Human Immunodeficiency Virus Type 1 Late Domain Mutants by ALIX/AIP1 Depends on Its CHMP4 Binding Site

ABSTRACT The release of human immunodeficiency virus type 1 (HIV-1) and of other retroviruses from certain cells requires the presence of distinct regions in Gag that have been termed late assembly (L) domains. HIV-1 harbors a PTAP-type L domain in the p6 region of Gag that engages an endosomal budding machinery through Tsg101. In addition, an auxiliary L domain near the C terminus of p6 binds to ALIX/AIP1, which functions in the same endosomal sorting pathway as Tsg101. In the present study, we show that the profound release defect of HIV-1 L domain mutants can be completely rescued by increasing the cellular expression levels of ALIX and that this rescue depends on an intact ALIX binding site in p6. Furthermore, the ability of ALIX to rescue viral budding in this system depended on two putative surface-exposed hydrophobic patches on its N-terminal Bro1 domain. One of these patches mediates the interaction between ALIX and the ESCRT-III component CHMP4B, and mutations which disrupt the interaction also abolish the activity of ALIX in viral budding. The ability of ALIX to rescue a PTAP mutant also depends on its C-terminal proline-rich domain (PRD), but not on the binding sites for Tsg101, endophilin, CIN85, or for the newly identified binding partner, CMS, within the PRD. Our data establish that ALIX can have a dramatic effect on HIV-1 release and suggest that the ability to use ALIX may allow HIV-1 to replicate in cells that express only low levels of Tsg101.
Post-treatment surveillance in a large cohort of patients with colon cancer.

OBJECTIVES To determine how patients complied with different components of guideline-recommended post-treatment surveillance in a large nationwide population-based cohort of patients with colon cancer. STUDY DESIGN Retrospective cohort study. METHODS We used the linked Surveillance, Epidemiology, and End Results-Medicare database to identify patients 66 years or older diagnosed as having stage I to stage III colon adenocarcinoma between January 2000 and June 2002 with a follow-up duration of at least 3.5 years. After tumor resection, patients who completed at least 2 office visits per year for 3 years, at least 2 carcinoembryonic antigen tests per year (in the first and second years of follow-up), and at least 1 colonoscopy within 3 years were defined as meeting the recommended post-treatment care. RESULTS We identified 7348 patients, with a median follow-up duration of 59 months. Adherence to post-treatment surveillance was 83.9% for office visits, 29.4% for carcinoembryonic antigen tests, and 74.3% for colonoscopy. Younger age at diagnosis, white race/ethnicity, married status, advanced tumor stage, fewer comorbidities, and chemotherapy use were significantly associated with guideline adherence. CONCLUSIONS Adherence to colon cancer posttreatment surveillance was low, although proportions of patients complying with office visits and colonoscopy were reasonably high. Underlying reasons for noncompliance, which varied by type of service, may need further investigation.
The Effectiveness of Long‐Term Psychoanalytic Therapy: A Systematic Review of Empirical Studies

Background: There is a gap in the research literature on the effectiveness of long‐term psychoanalytic therapies (LPT). Aim: To present a systematic review of studies dealing with LPT effectiveness and published from 1970 onward. Methods: A systematic literature search for studies dealing with the effectiveness of individual LPT in ambulatory, adult patients. Data about the overall effectiveness of LPT, its impact on symptom reduction, and its effect on personality changes were pooled both at treatment termination and at follow‐up, using effect sizes (ESs) and success rates. Results: We found 27 studies (n = 5063). Psychotherapy yielded large mean ESs (0.78 at termination; 0.94 at follow‐up) and high mean overall success rates (64% at termination; 55% at follow‐up) in moderate/mixed pathology. The mean ES was larger for symptom reduction (1.03) than for personality change (0.54). In severe pathology, the results were similar. Psychoanalysis achieved large mean ESs (0.87 at termination; 1.18 at follow‐up) and high mean overall success rates (71% at termination; 54% at follow‐up) in moderate pathology. The mean ES for symptom reduction was larger (1.38) than for personality change (0.76). Conclusion: Our data suggest that LPT is effective treatment for a large range of pathologies, with moderate to large effects.
DiST: fully decentralized indexing for querying distributed multidimensional datasets

Grid computing and peer-to-peer (P2P) systems are emerging as new paradigms for managing large scale distributed resources across wide area networks. While grid computing focuses on managing heterogeneous resources and relies on centralized managers for resource and data discovery, P2P systems target scalable, decentralized methods for publishing and searching for data. In large distributed systems, a centralized resource manager is a potential performance bottleneck and decentralization can help avoid this bottleneck, as is done in P2P systems. However, the query functionality provided by most existing P2P systems is very rudimentary, and is not directly applicable to grid resource management. In this paper, we propose a fully decentralized multidimensional indexing structure, called DiST, that operates in a fully distributed environment with no centralized control. In DiST, each data server only acquires information about data on other servers from executing and routing queries. We describe the DiST algorithms for maintaining the decentralized network of data servers, including adding and deleting servers, the query routing algorithm, and failure recovery algorithms. We also evaluate the performance of the decentralized scheme against a more structured hierarchical indexing scheme that we have previously shown to perform well in distributed grid environments
Fourier Analysis of Gamma-Ray Burst Light Curves: Searching for a Direct Signature of Cosmological Time Dilation

We study the power density spectrum (PDS) of light curves of the observed gamma-ray bursts (GRBs) to search for a direct signature for cosmological time dilation in the PDS statistics with the GRBs whose redshifts z are known. The anticorrelation of a timescale measure and a brightness measure is indirect evidence of its effect. On the other hand, we directly demonstrate that a time dilation effect can be seen in GRB light curves. We find that timescales tend to be shorter in bursts with small redshift, as expected from cosmological time dilation effects, and we also find that there may be noncosmological effects contributing to this correlation. We discuss the implications of this result on interpretations of the PDS analysis results. We put forward another caution regarding this kind of analysis when we statistically work with GRBs whose z is unknown.
Novel Injury Mechanism in Anoxia and Trauma of Spinal Cord White Matter: Glutamate Release via Reverse Na+-dependent Glutamate Transport

Spinal cord injury is a devastating condition, with much of the clinical disability resulting from disruption of white matter tracts. Recent reports suggest a component of glutamate excitotoxicity in spinal cord injury. In this study, the role of glutamate and mechanism of release of this excitotoxin were investigated in rat dorsal column slices subjected to 60 min of anoxia or 15 sec of mechanical compression at a force of 2 gm in vitro. The broad-spectrum glutamate antagonist kynurenic acid (1 mm) and the selective AMPA antagonist GYKI52466 (30 microm) were protective against anoxia (compound action potential amplitude recovered to 56 vs 27% without drug). GYKI52466 was also effective against trauma (65 vs 35%). Inhibition of Na(+)-dependent glutamate transport with dihydrokainate or l-trans-pyrrolidine-2,4-dicarboxylic acid (1 mm each) protected against anoxia (65-75 vs 25%) and trauma (70 vs 35%). The depletion of cytosolic glutamate in axon cylinders and oligodendrocytes by anoxia was completely prevented by glutamate transport inhibition. Immunohistochemistry revealed that a large component of injury occurred in the myelin sheath and was prevented by AMPA receptor blockade or glutamate transport inhibitors. We conclude that release of glutamate by reversal of Na(+)-dependent glutamate transport with subsequent activation of AMPA receptors is an important mechanism in spinal cord white matter anoxic and traumatic injury.
Transport and release of chemicals from plastics to the environment and to wildlife

Plastics debris in the marine environment, including resin pellets, fragments and microscopic plastic fragments, contain organic contaminants, including polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons, petroleum hydrocarbons, organochlorine pesticides (2,2′-bis(p-chlorophenyl)-1,1,1-trichloroethane, hexachlorinated hexanes), polybrominated diphenylethers, alkylphenols and bisphenol A, at concentrations from sub ng g–1 to µg g–1. Some of these compounds are added during plastics manufacture, while others adsorb from the surrounding seawater. Concentrations of hydrophobic contaminants adsorbed on plastics showed distinct spatial variations reflecting global pollution patterns. Model calculations and experimental observations consistently show that polyethylene accumulates more organic contaminants than other plastics such as polypropylene and polyvinyl chloride. Both a mathematical model using equilibrium partitioning and experimental data have demonstrated the transfer of contaminants from plastic to organisms. A feeding experiment indicated that PCBs could transfer from contaminated plastics to streaked shearwater chicks. Plasticizers, other plastics additives and constitutional monomers also present potential threats in terrestrial environments because they can leach from waste disposal sites into groundwater and/or surface waters. Leaching and degradation of plasticizers and polymers are complex phenomena dependent on environmental conditions in the landfill and the chemical properties of each additive. Bisphenol A concentrations in leachates from municipal waste disposal sites in tropical Asia ranged from sub µg l–1 to mg l–1 and were correlated with the level of economic development.
Medication Management of Irritable Bowel Syndrome

Background: Irritable bowel syndrome (IBS) is a complex syndrome that is difficult to manage. Here we present the evidence supporting medication treatments for specific IBS symptoms, discuss evidence-based management of IBS with medications including dose regimens and adverse effects and review progress on research for new IBS treatments. Summary: Currently, there is evidence to support improvements in specific IBS symptoms following treatment with loperamide, psyllium, bran, lubiprostone, linaclotide, amitriptyline, trimipramine, desipramine, citalopram, fluoxetine, paroxetine, dicyclomine, peppermint oil, rifaximin, ketotifen, pregabalin, gabapentin and octreotide and there are many new medications being investigated for the treatment of IBS. Key Message: Of the medications with demonstrated improvements for IBS symptoms, rifaximin, lubiprostone, linaclotide, fiber supplementation and peppermint oil have the most reliable evidence supporting their use for the treatment of IBS. Onset of efficacy for the various medications has been noted to be as early as 6 days after initiation; however, the efficacy of most medications was not assessed prospectively at predefined periods. Additional studies of currently available and new medications are ongoing and are needed to better define their place in therapy and expand therapeutic options for the treatment of IBS. The most promising new medications for IBS include a variety of novel pharmacologic approaches, most notably the dual μ-opioid receptor agonist and δ-opioid antagonist, JNJ-27018966.
Musashi 1‐positive cells derived from mouse embryonic stem cells can differentiate into neural and intestinal epithelial‐like cells in vivo

Msi1 (Musashi 1) is regarded as a marker for neural and intestinal epithelial stem cells. However, it is still unclear whether Msi1‐positive cells derived from mouse embryonic stem cells have the ability to differentiate into neural or intestinal epithelial cells. A pMsi1–GFP (green fluorescent protein) reporter plasmid was constructed in order to sort Msi1‐positive cells out of the differentiated cell population. The GFP‐positive cells (i.e. Msi1‐positive cells) were sorted by FACS and were hypodermically engrafted into the backs of NOD/SCID (non‐obese diabetic/severe combined immunodeficient) mice. The presence of neural and intestinal epithelial cells in the grafts was detected. Msi1 was highly expressed in the GFP‐positive cells, but not in the GFP‐negative cells. The markers for neural cells (Nestin and Tubulin β III) and intestinal epithelial cells [FABP2 (fatty acid binding protein 2), Lyz (lysozyme) and ChA (chromogranin A)] were more highly expressed in the grafts from Msi1‐positive cells than those from Msi1‐negative cells (P<0.05). The grafts from the Msi1‐negative cells contained more mesodermal‐like tissues than those from the Msi1‐positive cells. The pMsi1–GFP vector can be used to sort Msi1‐positive cells from a cell population derived from mouse embryonic stem cells. The Msi1‐positive cells can differentiate into neural and intestinal epithelial‐like cells in vivo.
Role of Synaptic Inhibition in Processing of Dynamic Binaural Level Stimuli

We have recently discovered a paradoxical aftereffect associated with inhibition in the gerbil auditory midbrain. Single neurons in the inferior colliculus (IC) were assessed for sensitivity to a virtual motion stimulus produced by modulating the interaural level difference (ILD), a major cue for sound localization. The class of neuron studied was predominantly excited by contralateral stimulation and inhibited by ipsilateral stimulation. Sound pressure level was modulated trapezoidally at the ipsilateral “inhibitory” ear, whereas the contralateral “excitatory” level remained constant. When the inhibitory stimulus was decreased within a range of sound levels that maintained suppression under static conditions, an unexpected discharge was often elicited, apparently because of an aftereffect of synaptic inhibition. In contrast, when the inhibitory stimulus was increased within a range of sound levels that produced only modest suppression under static conditions, neuronal discharge was often profoundly suppressed. In many cases the “conditioned enhancement” or “conditioned suppression” persisted for several seconds after the modulation of ILD, and such conditioned responses were influenced by the modulation depth and rate. To test the effect of inhibition in the IC directly, glycine and GABA were pulsed from a glass recording pipette during a constant monaural excitatory stimulus. The acoustically elicited discharge rate was potentiated markedly if preceded immediately by the brief (0.5–10 sec) application of inhibitory transmitter. Collectively, these results revealed unusually long-lasting effects of inhibition that may establish a new range of acoustic cues to which the neuron responds best. This may have broad implications for processing ensuing auditory stimuli.
A DYNAMIC SPECTRUM ACCESS OPTIMIZATION MODEL FOR COGNITIVE RADIO WIRELESS SENSOR NETWORK

The availability of low cost and tiny sensor devices have resulted in increased adoption of wireless sensor network (WSN) in various industries and organization. The WSN is expected to play a significant role in future internet based application services. WSN has been adopted in healthcare, disaster management, environment monitoring and so on. The low-cost availability of smart devices has led to increased use of wireless devices such as Bluetooth, Wi-Fi etc. Therefore, cognitive radio network plays a significant role in handling spectrum efficiently. The emerging internet access technology such as 4G and 5G network which is expected to come in near future is going to make cognitive spectrum access more challenging. The existing cognitive radio based WSN is not efficient in utilizing spectrum. They induce high collision due to interference and improper channel state information. To address, this work present an efficient distributed opportunistic spectrum access for wireless sensor network. The channel availability of likelihood distribution is computed using continuous-time Markov chain considering primary transmitting users temporal channel usage channel pattern and spatial distribution. The simulation outcome shows the proposed model achieves significant performance improvement over existing model. The proposed model improves the overall spectrum efficiency of cognitive radio wireless sensor network in terms of throughput, packet transmission and collision.
Physical Activity Moderates Effects of Stressor-Induced Rumination on Cortisol Reactivity

Objective: Physically active individuals have lower rates of morbidity and mortality, and recent evidence indicates that physical activity may be particularly beneficial to those experiencing chronic stress. The tendency to ruminate increases and prolongs physiological stress responses, including hypothalamic-pituitary-adrenal (HPA) axis responses as indexed by cortisol reactivity to stressful experiences. We examined the association between ruminating in response to a laboratory stressor task and HPA axis reactivity and recovery and examined whether a physically active life-style moderates the associations between rumination and cortisol output trajectories. Methods: Forty-six postmenopausal women underwent the Trier Social Stress Test, whereas salivary cortisol was repeatedly measured. Twenty-five minutes after the end of the stressor, participants reported level of rumination in response to the stress. Results: Findings indicate that physical activity moderated the initial rate (B = −0.10, standard error = 0.04, p < .05) and curvature (B = −0.03, standard error = 0.01, p = .06) of the relationship between rumination and log-transformed cortisol trajectory. Among sedentary participants, those who responded to the stressor with higher levels of rumination had a more rapid initial increase in cortisol level (0.26 versus 0.21, p < .001), a later peak in cortisol reactivity (56 versus 39 minutes), and a delayed recovery from stress (curvature: −0.07 versus −0.08, p < .001) compared with those with lower levels of rumination. In active participants, cortisol trajectories were equivalent, regardless of the level of rumination. Conclusions: In sum, individuals who maintain a physically active life-style may be protected against the effects of rumination on HPA axis reactivity to and recovery from acute stress.HPA = hypothalamic-pituitary-adrenal; TSST = Trier Social Stress Task; RRS = Ruminative Responses Scale; BMI = body mass index; REML = restricted maximum likelihood; HRT = hormone replacement therapy.