Miracle-dz/UniFAR-FTUs huggingface dataset:
Automated analysis of interatomic contacts in proteins

MOTIVATION New software has been designed to assist the molecular biologist in understanding the structural consequences of modifying a ligand and/or protein. RESULTS Tools are described for the analysis of ligand-protein contacts (LPC software) and contacts of structural units (CSU software) such as helices, sheets, strands and residues. Our approach is based on a detailed analysis of interatomic contacts and interface complementarity. For any ligand or structural unit, these software automatically: (i) calculate the solvent-accessible surface of every atom; (ii) determine the contacting residues and type of interaction they undergo (hydrophobic-hydrophobic, aromatic-aromatic, etc.); (iii) indicate all putative hydrogen bonds. LPC software further predicts changes in binding strength following chemical modification of the ligand. AVAILABILITY Both LPC and CSU can be accessed through the PDB and are integrated in the 3DB Atlas page of all PDB files. For any given file, the tools can also be accessed at http://www.pdb. bnl. gov/pdb-bin/lpc? PDB_ID= and http://www.pdb. bnl. gov/pdb-bin/csu? PDB_ID= with the four-letter PDB code added at the end in each case. Finally, LPC and CSU can be accessed at: http://sgedg.weizmann. ac.il/lpc and http://sgedg.weizmann. ac.il/csu.
Context-dependent synaptic action of glycinergic and GABAergic inputs in the dorsal cochlear nucleus

Cartwheel cells are prominent interneurons in the dorsal cochlear nucleus (DCN) that bear considerable homology to cerebellar Purkinje cells. They contact other cartwheel cells as well as fusiform cells, the principal cells of the DCN. In fusiform cells, the inhibition from cartwheel cells interacts with excitation mediated by granule cells and auditory nerve fibers, and shapes the output of the DCN in its ascent to the inferior colliculi. With intracellular recordings from anatomically identified cells in slices, synaptic inputs to fusiform and cartwheel cells were analyzed pharmacologically. Shocks to the auditory nerve and granule cell domains evoked glutamatergic, glycinergic, and GABA(A)ergic postsynaptic potentials (PSPs) in both cartwheel and fusiform cells. The temporal patterns of spontaneous and evoked glycinergic PSPs in fusiform and cartwheel cells were similar and mirrored the pattern of firing of cartwheel cells, probably reflecting the anatomical connections between these cell types and supporting the conclusion that cartwheel cells are glycinergic. In fusiform cells, glycinergic and GABA(A)ergic IPSPs evoked with shocks reversed at -68 mV on average. In marked contrast, glycinergic and GABA(A)ergic PSPs in cartwheel cells, as well as responses to exogenous application of 50–100 mM glycine or 100 microns muscimol, were depolarizing. Reversal potentials of PSPs and responses to glycine and muscimol were similar and averaged -52 mV. Glycinergic and GABA(A)ergic PSPs could elicit firing from cartwheel cells at their resting potentials, but could also reduce rapid firing during strong depolarizations. Thus, the action of glycinergic and GABA(A)ergic inputs on cartwheel cells depends on the electrophysiological context in which they occur.
Guided depth filtering to improve the quality of experience for autostereoscopic displays

One of the drawbacks of current 3DTV systems are the glasses required to separate the 3D views. This problem can be solved by using autostereoscopic 3D displays, which generates a 3D scene from different viewpoints. These viewpoints are synthesized in the display based on depth information of the scene. However, currently no depth information is available for stereoscopic video. Therefore, depth estimation based on the stereoscopic input is required. This depth estimation should be low-complex and real-time for consumer electronic devices. Due to this low-complexity requirement, the quality of such depth maps will be limited. In this paper, we propose a guided depth filter, which filters the estimated depth map by using the downsampled chroma signal of the corresponding texture view as a guide. This allows to refine the borders of objects which reduces visible inpainting artifacts caused by the view synthesis. The proposed algorithm has been evaluated by expert viewing to show that it is independent of the depth map estimation and view synthesis of the autostereoscopic display.
Automated Spatio-Temporal Abstraction in Reinforcement Learning

1 Introduction Reinforcement learning is a machine learning framework in which an agent manipulates its environment through a series of actions, receiving a scalar feedback signal or reward after each action. The agent learns to select actions so as to maximize the expected total reward. The nature of the rewards and their distribution across the environment decides the task that the agent learns to perform. Consider a generic agent solving multiple tasks in a common environment. The effectiveness of such an agent increases with its ability to reuse past experience in new tasks. Identifying similar representations between tasks paves the way for a possible transfer of knowledge between such tasks. A sufficiently broad definition of similarity and an ability to effectively store and reuse previous experience can greatly increase the long-term performance of a multipurpose agent. An automated task-independent abstraction method is introduced that generalizes over tasks sharing the same state-space topology and similar dynamics. New tasks performed on this common environment are able to reuse skills acquired over previous tasks. Pruning techniques are identified for specific situations to identify relevant skills. The interaction of the agent with the environment is modeled as a dynamical system. Identification of metastable regions in the agent dynamics leads to a partitioning of the state space. Transitions between metastable regions, events of low probability during a random-walk on the state space, are identified as useful skills. Curiosity drives human-beings to understand the environment around them. In the process of interacting with the environment and exploring it, often accomplishing tasks such as searching for food or shelter, we construct abstract models of the environment. These models are built independent of specific tasks, but mirror the environment. Such an internal representation of the world remains consistent across tasks and enables us to reuse skills across different tasks. The skills that we learn over time enable us to gain greater control over the environment in the long term. To mirror this approach in the design of software agents, there is a need to design algorithms that can automatically construct task-independent state abstractions and define skills in terms of these abstractions. Such skills will enable an agent to generalize across tasks and reuse experience more effectively. The Reinforcement Learning framework is used to model a problem-solving software agent able to interact with an environment. Tasks are specified in terms of Markov Decision Processes (MDPs) [15]. Given a collection …
Parametric Imaging of Rat Mammary Tumors In Vivo for the Purposes of Tissue Characterization

Objective. To estimate the average scatterer properties from ultrasonic backscatter in tissues for evaluating differences between neoplastic and healthy tissues. Methods. Parametric images of 8 retired breeder rats in which spontaneous mammary tumors had developed were created by superimposing color‐coded pixels related to the estimated average scatterer properties on conventional gray scale B‐mode images. Results. The images showed a distinct difference between the tumors and surrounding healthy tissues. Analysis of the average scatterer diameters and acoustic concentrations showed a statistically significant difference (P < .05) between estimates inside and outside the tumors for most of the cases. Scatterer sizes inside the tumors were on average 30% larger than scatterer sizes in surrounding normal tissues. A feature analysis plot showed that there was a distinct difference between results obtained inside and outside the tumors. Conclusions. Parametric imaging that uses estimates of scatterer properties in tissues may lead to detection and characterization (diagnosis) of diseased tissues on conventional sonographic scanning systems.
Performance evaluation of automated manufacturing systems using generalized stochastic Petri nets

Generalized stochastic Petri net (GSPN) modules are used as basic building blocks to model and analyze complex manufacturing systems. This modular approach facilitates model construction and helps manage the complexity of modeling large manufacturing systems. The structural analysis ensures that the model is live and bounded, which guarantees that the equivalent Markov chain (MC) is ergodic. The temporal analysis is used to derive performance measures such as average production rates and average in process inventories. The main advantage of Petri nets (PNs) over MCs is that the number of places and transitions increases only slightly as the manufacturing system complexity increases, whereas the number of states in the MC increases exponentially. In addition, there is no need to enumerate all the possible states manually since they are automatically generated from the GSPN model. As a result, PN models can still be easily obtained for complicated interconnected systems. The straightforward application of this approach is demonstrated and reviewed for several manufacturing case studies. For serial transfer lines it is proven that this modular approach results in live and bounded GSPN models. Comparisons are made with deterministic and reduced state-space models. Examples containing as many as 9614 states are presented. >
A comprehensive R-package for studying families, based on the social relations model

SRM components: Actor effect (for each role) i.e. cross-relational consistency in the ratings of a particular person e.g. a traumatized child may experience relationship anxiety towards all family members Partner effect (for each role) i.e. cross-relational consistency of the ratings about one person e.g. a cold and emotionally distant father may elicit fear of rejection Relationship effects i.e. unique adaptation of one person towards another, controlled for both actor and partner effects e.g. an extramarital affair causes that the wife experiences fear of rejection in relation to her husband Family effect i.e. characteristics that causes all family members to be similar 1.2. Additional analyses
UvA-DARE ( Digital Academic Repository ) A close-up of colon cancer

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The NTCP‐inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics

Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate cotransporting polypeptide (SLC10A1). We investigated the effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 19.2‐fold without signs of cholestasis. The rise in conjugated bile acids was up to 124‐fold (taurocholic acid). Coadministration of tenofovir with myrcludex B revealed no relevant changes in tenofovir pharmacokinetics. CYP3A activity slightly but significantly decreased by 29% during combination therapy. Myrcludex B caused an asymptomatic but distinct rise in plasma bile acid concentrations and had no relevant impact on tenofovir pharmacokinetics. Changes in CYP3A activity might be due to alterations in bile acid signaling. Long‐term effects of elevated bile acids will require critical evaluation.
Small cell neuroendocrine carcinoma of the ureter: A case report and literature review

Small cell neuroendocrine carcinoma arising in the ureter is extremely rare; only a few cases have been previously reported in the literature. The current study reports the case of a 65-year-old female who presented with right-sided back pain. A mass was identified in the right ureter, and a nephroureterectomy was performed. The microscopic examination revealed that the mass was composed of a monotonous population of small cells and that the cells of the carcinoma were positive for cluster of differentiation 56, chromogranin A and synaptophysin. The tumor was diagnosed as a ureteral neuroendocrine small cell carcinoma. The patient returned 4 months later with recurrences in the retroperitoneum. Chemotherapy was administered and following 80 mg/m2 intravenous irinotecan on days 1 and 8 and 25 mg/m2 cisplatin on days 1–3, every 21 days for 4 cycles, the tumor was considerably smaller. During the regular follow-up examinations, the tumor remained stable.
Predicting mutual intelligibility of Chinese dialects from multiple objective linguistic distance measures

Abstract This paper predicts the mutual intelligibility of 15 Chinese dialects from multiple objective distance measures. Empirical mutual intelligibility measures were obtained from functional intelligibility tests at the sentence level from 15 listeners for each of 15 Chinese dialects. We computed various proximity measures on the basis of shared phonemes and tones in the sound inventories of the 15 dialects. Next, Levenshtein (string-edit) distance measures were computed on the 764 common syllabic units (zi in Pinyin, i.e., a meaningful character or morpheme with a complete transcription of segments and tone) shared by the same 15 Chinese dialects in the Dialect Sound Database of Modern Chinese (compiled by the Chinese Academy of Social Sciences). Unweighted and perceptually weighted Levenshtein distance measures were computed. We also included objective similarity measures of phonological correspondence, based on the Zihui character list and of lexical affinity, based on the Cihui cross-dialect lexical database with all cognate and non-cognate expressions of 905 core concepts) that have been published by Cheng (1997). The best single predictor of mutual intelligibility between a pair of dialects was the percentage of cognates shared between them (r2 = .548). Including all predictors afforded a highly accurate prediction of mutual intelligibility (R2 = .874). A very reasonable prediction is afforded if we just add the lexical frequency of finals (syllable rhymes) shared by a pair of dialects (R2 = .611).
An optically trapped mirror for reaching the standard quantum limit

The preparation of a mechanical oscillator driven by quantum back-action is a fundamental requirement to reach the standard quantum limit (SQL) for force measurement, in optomechanical systems. However, thermal fluctuating force generally dominates a disturbance on the oscillator. In the macroscopic scale, an optical linear cavity including a suspended mirror has been used for the weak force measurement, such as gravitational-wave detectors. This configuration has the advantages of reducing the dissipation of the pendulum (i.e., suspension thermal noise) due to a gravitational dilution by using a thin wire, and of increasing the circulating laser power. However, the use of the thin wire is weak for an optical torsional anti-spring effect in the cavity, due to the low mechanical restoring force of the wire. Thus, there is the trade-off between the stability of the system and the sensitivity. Here, we describe using a triangular optical cavity to overcome this limitation for reaching the SQL. The triangular cavity can provide a sensitive and stable system, because it can optically trap the mirror's motion of the yaw, through an optical positive torsional spring effect. To show this, we demonstrate a measurement of the torsional spring effect caused by radiation pressure forces.
Recovery of Sensorimotor Gating without G Protein Adaptation after Repeated D2-Like Dopamine Receptor Agonist Treatment in Rats

Sensorimotor gating, a neural process severely disrupted in patients with schizophrenia, can be measured by assessing prepulse inhibition (PPI) of acoustic startle responses. PPI is disrupted in experimental animals by stimulation of D2-like dopamine receptors in the nucleus accumbens (NAc). We examined the effect of repeated treatment with a selective dopamine D2-like receptor agonist, quinpirole, and characterized the molecular substrates of the resulting PPI adaptation. Animals were treated once daily for 10 or 28 consecutive days with quinpirole (0.0, 0.05, 0.1, or 0.3 mg/kg, s.c.), and the effect on PPI was assessed throughout the treatment period. PPI was reduced after acute quinpirole administration, but gradually increased with repeated treatment. Quinpirole-induced PPI disruption was attenuated after 10 days of treatment at lower doses, but complete recovery was not apparent until the treatment period was extended to 28 days. Since chronic drug exposure can alter the dopamine system, we sought to characterize the effects of repeated quinpirole treatment on G proteins coupled to D2-like receptors in the NAc. Guanosine 5′-O-(3-[35S]thiotriphosphate) ([35S]GTPγS) binding and Western blot analysis revealed that repeated quinpirole treatment had no effect on NAc D2-like receptor G protein function or G protein levels. These data indicate that repeated activation of D2-like receptors by quinpirole produces tolerance in the absence of receptor or G protein changes, suggesting that the locus of dopaminergic adaptation might be at the intracellular level.
Androgen Receptor Gene Tagging Single Nucleotide Polymorphisms are not Associated with Polycystic Ovary Syndrome in South Indian Women

Impaired steroidogenesis at gonads or defect in the receptors mediating the actions of those hormones is being reported as an etiological factor for Polycystic ovary syndrome (PCOS). Of the various factors, variations in the expression of androgen receptor (AR) gene have been shown as a risk factor for women with PCOS; however the findings were not consistent among populations studied. Therefore, the present study was aimed to screen the prevalence of AR gene haplotype tagging single nucleotide polymorphisms (SNP) and its association with PCOS in south Indian women. The study population consists of a total of 198 subjects, of which 97 were women with PCOS and 101 healthy women as controls. Genotyping of SNPs for AR rs5919393 (C/T), rs5919411 (A/G) and rs12014709 (G/T) were carried out by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and DNA sequencing. Out of three SNPs examined, the rs5919393 (C/T) and rs5919411 (A/G) are monomorphic in both PCOS and controls. Whereas, rs12014709 (G/T) was observed <2% in controls samples in the present study. The results did not show any evidence of association of polymorphisms rs5919393 (C/T), rs5919411 (A/G) and rs12014709 (G/T) in AR gene with PCOS in south Indian women.
Infection of Epstein‐Barr virus‐transformed lymphoblastoid B cells by the human immunodeficiency virus: evidence for a persistent and productive infection leading to B cell phenotypic changes

Four Epstein‐Barr virus‐positive lymphoblastoid cell lines (LCL) were successfully infected in vitro with immunodeficiency virus type 1 (HIV‐1) as demonstrated by reverse transcriptase activity and p24 HIV antigen in culture supernatants, positive cell staining for gag‐encoded HIV proteins, presence of viral HIV genome by Southern blot analysis and ulstrastructural observations. In addition, both HIV‐1‐infected B cells and their supernatants efficiently transactivated the chloramphenicol acetyl transferase reporter gene which is under the control of the HIV‐1 long terminal repeat.
Theta power modulations during the explicit recognition of unfamiliar 3-D objects explored haptically

APPARATUS AND TASKS. A haptic tachistoscope that hid the objects from sight was used for stimulus presentation (see Figure 2). The apparatus included an adjustable force-sensitive sensor located at the center of the presentation platform, below the place where the object was presented. This piezo-electric board was interfaced with a computer. Exploration time was recorded by triggers sent by a pressure sensor to the computer while participants explored the stimulus haptically. Two foot-pedals were used for collecting the responses.
Non‐linear increase in GLP‐1 levels in response to DPP‐IV inhibition in healthy adult subjects

Aim: Dipeptidyl peptidase‐IV (DPP‐IV) inhibitors represent a new promising therapeutic intervention for the treatment of type 2 diabetes mellitus. The aim of this study was to investigate the effects of DPP‐IV inhibition by PF‐00734200, a potent competitive DPP‐IV inhibitor, on the dynamics of DPP‐IV activity and glucagon‐like peptide‐1 (GLP‐1) kinetics in healthy adult subjects.
Protein Kinase Inhibitors: Insights into Drug Design from Structure

Protein kinases are targets for treatment of a number of diseases. This review focuses on kinase inhibitors that are in the clinic or in clinical trials and for which structural information is available. Structures have informed drug design and have illuminated the mechanism of inhibition. We review progress with the receptor tyrosine kinases (growth factor receptors EGFR, VEGFR, and FGFR) and nonreceptor tyrosine kinases (Bcr-Abl), where advances have been made with cancer therapeutic agents such as Herceptin and Gleevec. Among the serine-threonine kinases, p38, Rho-kinase, cyclin-dependent kinases, and Chk1 have been targeted with productive results for inflammation and cancer. Structures have provided insights into targeting the inactive or active form of the kinase, for targeting the global constellation of residues at the ATP site or less conserved additional pockets or single residues, and into targeting noncatalytic domains.
The occurrence of diffuse axonal injury in the brain: associated with the accumulation and clearance of myelin debris

The accumulation of myelin debris may be a major contributor to the inflammatory response after diffuse axonal injury. In this study, we examined the accumulation and clearance of myelin debris in a rat model of diffuse axonal injury. Oil Red O staining was performed on sections from the cerebral cortex, hippocampus and brain stem to identify the myelin debris. Seven days after diffuse axonal injury, many Oil Red O-stained particles were observed in the cerebral cortex, hippocampus and brain stem. In the cerebral cortex and hippocampus, the amount of myelin debris peaked at 14 days after injury, and decreased significantly at 28 days. In the brain stem, the amount of myelin debris peaked at 7 days after injury, and decreased significantly at 14 and 28 days. In the cortex and hippocampus, some myelin debris could still be observed at 28 days after diffuse axonal injury. Our findings suggest that myelin debris may persist in the rat central nervous system after diffuse axonal injury, which would hinder recovery.
Sharing is caring

One of the main shortcomings of the traditional methods for combining theories is the complexity of guessing the arrangement of the variables shared by the individual theories. This paper presents a reformulation of the Nelson-Oppen method that takes into account explicit equality propagation and can ignore pairs of shared variables that the theories do not care about. We show the correctness of the new approach and present care functions for the theories of uninterpreted functions and the theory of arrays. The effectiveness of the new method is illustrated by experimental results demonstrating a dramatic performance improvement on benchmarks combining arrays and bit-vectors.