Miracle-dz/UniFAR-FTUs huggingface dataset:
Necessity is the Mother of Invention: Reconstructing Missing Sensory Information in Multiple, Concurrent Reference Frames for Eye–Hand Coordination

When aligning the hand to grasp an object, the CNS combines multiple sensory inputs encoded in multiple reference frames. Previous studies suggest that when a direct comparison of target and hand is possible via a single sensory modality, the CNS avoids performing unnecessary coordinate transformations that add noise. But when target and hand do not share a common sensory modality (e.g., aligning the unseen hand to a visual target), at least one coordinate transformation is required. Similarly, body movements may occur between target acquisition and manual response, requiring that egocentric target information be updated or transformed to external reference frames to compensate. Here, we asked subjects to align the hand to an external target, where the target could be presented visually or kinesthetically and feedback about the hand was visual, kinesthetic, or both. We used a novel technique of imposing conflict between external visual and gravito-kinesthetic reference frames when subjects tilted the head during an instructed memory delay. By comparing experimental results to analytical models based on principles of maximum likelihood, we showed that multiple transformations above the strict minimum may be performed, but only if the task precludes a unimodal comparison of egocentric target and hand information. Thus, for cross-modal tasks, or when head movements are involved, the CNS creates and uses both kinesthetic and visual representations. We conclude that the necessity of producing at least one coordinate transformation activates multiple, concurrent internal representations, the functionality of which depends on the alignment of the head with respect to gravity.
Simultaneous laparoscopic nephroureterectomy and cystectomy: a preliminary report.

PURPOSE Patients with muscle-invasive bladder cancer and concomitant upper urinary tract tumors may be candidates for simultaneous cystectomy and nephroureterectomy. Other clinical conditions such as dialysis-dependent end-stage renal disease and non-functioning kidney are also indications for simultaneous removal of the bladder and kidney. In the present study, we report our laparoscopic experience with simultaneous laparoscopic radical cystectomy (LRC) and nephroureterectomy. MATERIALS AND METHODS Between August 2000 and June 2007, 8 patients underwent simultaneous laparoscopic radical nephroureterectomy (LNU) (unilateral-6, bilateral-2) and radical cystectomy at our institution. Demographic data, pathologic features, surgical technique and outcomes were retrospectively analyzed. RESULTS The laparoscopic approach was technically successful in all 8 cases (7 males and 1 female) without the need for open conversion. Median total operative time, including LNU, LRC, pelvic lymphadenectomy and urinary diversion, was 9 hours (range 8-12). Median estimated blood loss and hospital stay were 755 mL (range 300-2000) and 7.5 days (range 4-90), respectively. There were no intraoperative complications but only 1 major and 2 minor postoperative complications. The overall and cancer specific survival rates were 37.5% and 87.5% respectively at a median follow-up of 9 months (range 1-45). CONCLUSIONS Laparoscopic nephroureterectomy with concomitant cystectomy is technically feasible. Greater number of patients with a longer follow-up is required to confirm our results.
Towards a conceptual framework for visual analytics of time and time-oriented data

Time is an important data dimension with distinct characteristics that is common across many application domains. This demands specialized methods in order to support proper analysis and visualization to explore trends, patterns, and relationships in different kinds of time-oriented data. The human perceptual system is highly sophisticated and specifically suited to spot visual patterns. For this reason, visualization is successfully applied in aiding these tasks. But facing the huge volumes of data to be analyzed today, applying purely visual techniques is often not sufficient. Visual analytics systems aim to bridge this gap by combining both, interactive visualization and computational analysis. In this paper, we introduce a concept for designing visual analytics frameworks and tailored visual analytics systems for time and time-oriented data. We present a number of relevant design choices and illustrate our concept by example.
A new paradigm for electrostatic catalysis of radical reactions in vitamin B12 enzymes

The catalytic power of enzymes containing coenzyme B12 cofactor has been, in some respects, the “last bastion” for the strain hypothesis. The present work explores the origin of this effect by using simulation methods that overcome the sampling difficulties of previous energy minimization studies. It is found that the major part of the catalytic effect is due to the electrostatic interaction between the ribose and the protein, and that the strain contribution is very small. Remarkably, enzymes can use electrostatic effects even in a radical process, when the charge distribution of the reacting fragments does not change significantly during the reaction. Electrostatic catalysis can, in such cases, be obtained by attaching a polar group to the leaving fragment and designing an active site that interacts more strongly with this group in the product state than in the reactant state. The finding that evolution had to use this trick provides further evidence to the observation that it is extremely hard to catalyze enzymatic reactions by nonelectrostatic factors. The trick used by B12 enzymes may, in fact, be a very powerful new strategy in enzyme design.
Identifying endophenotypes of autism: a multivariate approach

The existence of an endophenotype of autism spectrum condition (ASC) has been recently suggested by several commentators. It can be estimated by finding differences between controls and people with ASC that are also present when comparing controls and the unaffected siblings of ASC individuals. In this work, we used a multivariate methodology applied on magnetic resonance images to look for such differences. The proposed procedure consists of combining a searchlight approach and a support vector machine classifier to identify the differences between three groups of participants in pairwise comparisons: controls, people with ASC and their unaffected siblings. Then we compared those differences selecting spatially collocated as candidate endophenotypes of ASC.
Hsp110 Is a Bona Fide Chaperone Using ATP to Unfold Stable Misfolded Polypeptides and Reciprocally Collaborate with Hsp70 to Solubilize Protein Aggregates*

Background: Hsp110s are considered as mere nucleotide exchange factors of the Hsp70s. Results: Human cytosolic Hsp110s can use ATP to unfold misfolded polypeptides and act as equal partner with Hsp70 to solubilize stable protein aggregates. Conclusion: Hsp110s are Hsp70-like polypeptide unfolding chaperones. Significance: Hsp110s are powerful disaggregating chaperones that can collaborate with Hsp70s to detoxify misfolding proteins in degenerative diseases. Structurally and sequence-wise, the Hsp110s belong to a subfamily of the Hsp70 chaperones. Like the classical Hsp70s, members of the Hsp110 subfamily can bind misfolding polypeptides and hydrolyze ATP. However, they apparently act as a mere subordinate nucleotide exchange factors, regulating the ability of Hsp70 to hydrolyze ATP and convert stable protein aggregates into native proteins. Using stably misfolded and aggregated polypeptides as substrates in optimized in vitro chaperone assays, we show that the human cytosolic Hsp110s (HSPH1 and HSPH2) are bona fide chaperones on their own that collaborate with Hsp40 (DNAJA1 and DNAJB1) to hydrolyze ATP and unfold and thus convert stable misfolded polypeptides into natively refolded proteins. Moreover, equimolar Hsp70 (HSPA1A) and Hsp110 (HSPH1) formed a powerful molecular machinery that optimally reactivated stable luciferase aggregates in an ATP- and DNAJA1-dependent manner, in a disaggregation mechanism whereby the two paralogous chaperones alternatively activate the release of bound unfolded polypeptide substrates from one another, leading to native protein refolding.
Reaction–diffusion wave model for self-assembled network formation of poly(dA)·poly(dT) DNA on mica and HOPG surfaces

Deoxyribonucleic acid (DNA) is a vital molecule for life since it contains genetic information. However, DNA has recently been reported to have unique properties that make it suitable for bionanoelectronic applications, such as the possibility of electrical conductivity and self-organisation. Self-assembled DNA network structures have been observed on several substrates, but the detailed self-assembly mechanism has yet to be determined. The present study investigates self-assembled structures of DNA both theoretically and experimentally. We developed a reaction–diffusion model and used it to investigate pattern formations observed by atomic force microscopy. The computational results qualitatively replicate the network patterns of DNA molecules based on a quantitative agreement with the surface size and timescale. The model can account for the effect of the DNA concentration on pattern formation. Furthermore, peculiar geometric patterns are simulated for mica and highly oriented pyrolytic graphite surfaces.
Integration of Proteomics and Genomics in Platelets

Platelets, while anucleate, contain RNA, some of which is translated into protein upon activation. Hypothesising that the platelet proteome is reflected in the transcriptome, we identified 82 proteins secreted from activated platelets and compared these, as well as published proteomic data, to the transcriptional profile. We also compared the transcriptome of platelets to other tissues to identify platelet-specific genes and used ontology to determine gene categories over-represented in platelets. RNA was isolated from highly pure platelet preparations for hybridization to Affymetrix oligonucleotide arrays. We identified 2,928 distinct messages as being present in platelets. The platelet transcriptome was compared with the proteome by relating both to UniGene clusters. Platelet proteomic data correlated well with the transcriptome, with 69% of secreted proteins detectable at the mRNA level, and similar concordance was obtained using two published datasets. While many of the most abundant mRNAs are for known platelet proteins, messages were detected for proteins not previously reported in platelets. Some of these may represent residual megakaryocyte messages; however, proteomic analysis confirmed the expression of many previously unreported genes in platelets. Transcripts for well-described platelet proteins are among the most platelet-specific messages. Ontological categories related to signal transduction, receptors, ion channels, and membranes are over-represented in platelets, while categories involved in protein synthesis are depleted. Despite the absence of gene transcription, the platelet proteome is mirrored in the transcriptome. Conversely, transcriptional analysis predicts the presence of novel proteins in the platelet. Transcriptional analysis is relevant to platelet biology, providing insights into platelet function and the mechanisms of platelet disorders.
Functional Properties of Sensory Nerve Terminals of the Mouse Cornea.

Purpose To define the firing properties of sensory nerve terminals innervating the adult mouse cornea in response to external stimuli of differing modality. Methods Extracellular electrical activity of single corneal sensory nerve terminals was recorded in excised eyes of C57BL/6J mice. Eyes were placed in a recording chamber and were continuously superfused with warm saline solution. Nerve terminal impulse (NTI) activity was recorded by means of a glass pipette (tip ∼ 50 μm), applied on the corneal surface. Nerve terminal impulse discharges were stored in a computer for offline analysis. Results Three functionally distinct populations of nerve terminals were identified in the mouse cornea. Pure mechanonociceptor terminals (9.5%) responded phasically and only to mechanical stimuli. Polymodal nociceptor terminals (41.1%) were tonically activated by heat and hyperosmolal solutions (850 mOsm·kg-1), mechanical force, and/or TRPV1 and TRPA1 agonists (capsaicin and allyl isothiocyanate [AITC], respectively). Cold-sensitive terminals (49.4%) responded to cooling. Approximately two-thirds of them fired continuously at 34°C and responded vigorously to small temperature reductions, being classified as high-background activity, low-threshold (HB-LT) cold thermoreceptor terminals. The remaining one-third exhibited very low ongoing activity at 34°C and responded weakly to intense cooling, being named low-background activity, high-threshold (LB-HT) cold thermoreceptor terminals. Conclusions The mouse cornea is innervated by trigeminal ganglion (TG) neurons that respond to the same stimulus modalities as corneal receptors of other mammalian species. Mechano- and polymodal endings underlie detection of mechanical and chemical noxious stimuli while HB-LT and LB-HT cold thermoreceptors appear to be responsible for basal and irritation-evoked tearing and blinking, respectively.
Primary Motor Cortex Tuning to Intended Movement Kinematics in Humans with Tetraplegia

The relationship between spiking activities in motor cortex and movement kinematics has been well studied in neurologically intact nonhuman primates. We examined the relationship between spiking activities in primary motor cortex (M1) and intended movement kinematics (position and velocity) using 96-microelectrode arrays chronically implanted in two humans with tetraplegia. Study participants were asked to perform two different tasks: imagined pursuit tracking of a cursor moving on a computer screen and a “neural cursor center-out” task in which cursor position was controlled by the participant's neural activity. In the pursuit tracking task, the majority of neurons were significantly tuned: 90% were tuned to velocity and 86% were tuned to position in one participant; 95% and 84%, respectively, in the other. Additionally, velocity and position of the tracked cursor could be decoded from the ensemble of neurons. In the neural cursor center-out task, tuning to direction of the intended target was well captured by a log-linear cosine function. Neural spiking soon after target appearance could be used to classify the intended target with an accuracy of 95% in one participant, and 80% in the other. It was also possible to extract information about the direction of the difference vector between the target position and the instantaneous neural cursor position. Our results indicate that correlations between spiking activity and intended movement velocity and position are present in human M1 after the loss of descending motor pathways, and that M1 spiking activities share many kinematic tuning features whether movement is imagined by humans with tetraplegia, or is performed as shown previously in able-bodied nonhuman primates.
Effect of Footwear Modifications on Oscillations at the Achilles Tendon during Running on a Treadmill and Over Ground: A Cross-Sectional Study

Background Achilles tendon injuries are known to commonly occur in runners. During running repeated impacts are transferred in axial direction along the lower leg, therefore possibly affecting the oscillation behavior of the Achilles tendon. The purpose of the present study was to explore the effects of different footwear modifications and different ground conditions (over ground versus treadmill) on oscillations at the Achilles tendon. Methods Oscillations were measured in 20 male runners using two tri-axial accelerometers. Participants ran in three different shoe types on a treadmill and over ground. Data analysis was limited to stance phase and performed in time and frequency space. Statistical comparison was conducted between oscillations in vertical and horizontal direction, between running shoes and between ground conditions (treadmill versus over ground running). Results Differences in the oscillation behavior could be detected between measurement directions with peak accelerations in the vertical being lower than those in the horizontal direction, p < 0.01. Peak accelerations occurred earlier at the distal accelerometer than at the proximal one, p < 0.01. Average normalized power differed between running shoes (p < 0.01) with harder damping material resulting in higher power values. Little to no power attenuation was found between the two accelerometers. Oscillation behavior of the Achilles tendon is not influenced by ground condition. Conclusion Differences in shoe configurations may lead to variations in running technique and impact forces and therefore result in alterations of the vibration behavior at the Achilles tendon. The absence of power attenuation may have been caused by either a short distance between the two accelerometers or high stiffness of the tendon. High stiffness of the tendon will lead to complete transmission of the signal along the Achilles tendon and therefore no attenuation occurs.
Toward a knockout for every gene : Caenorhabditis elegans Efficient target-selected mutagenesis in Material Supplemental

License Commons Creative . http://creativecommons.org/licenses/by-nc/3.0/ described at as a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), ). After six months, it is available under http://genome.cshlp. org/site/misc/terms.xhtml for the first six months after the full-issue publication date (see This article is distributed exclusively by Cold Spring Harbor Laboratory Press
Corporate Social Responsibility and Information Asymmetry

This research investigates the connection between Corporate Social Responsibility (CSR) and the issue of information asymmetry. Our CSR sample comes from the DJSI (Dow Jones Sustainability North America Index), and the sample consists from 764 firm-year observations during 2002 to 2010. Our empirical work find there is a significantly negative relationship between CSR and information asymmetry proxy, which means that market responds CSR with smaller gap between bid-ask spreads. CSR also reduces the excess returns when higher degree of information asymmetry exists, which compensate less excess returns to investor than non-CSR firms. Furthermore, CSR firms have less degree of overreaction than matching firms when the book-to-market effect and intangible information are considered.
Estimation of Cerebral Venous Saturation in Newborn Infants by Near Infrared Spectroscopy

ABSTRACT: The purpose of the study was to evaluate the near infrared spectroscopy technique for determination of the cerebral venous oxygen saturation. By tilting the patient's head down 15°, changes in OD may be caused by changes in cerebral blood volume. On the assumption that increases in cerebral blood volume consist of venous blood only, cerebral venous oxygen saturation can be calculated as the measured change in oxygenated Hb divided by the change in total Hb. Two groups of mechanically ventilated, newborn infants were investigated: 10 asphyxiated, term infants and another 22 preterm infants with respiratory distress syndrome. All were monitored by near infrared spectroscopy during tilting, and cerebral blood flow was estimated by the 133Xe clearance technique immediately before tilting. Cerebral venous oxygen saturation could not be calculated in 13 preterm infants, as the blood volume remained constant during tilting. In the remaining 19, cerebral venous oxygen saturation averaged 0.67 (SD = 0.09) in asphyxiated infants and 0.53 (SD = 0.15) in preterm infants (p = 0.03). The corresponding values of cerebral blood flow were closely and inversely related to oxygen extraction calculated from cerebral venous saturation as estimated by near infrared spectroscopy.
The Nature and Importance of the Father-Infant Relationship.

The authors discuss several studies which invalidate the common presumption that fathers play an insignificant role in the sociopersonality development of their infant children. It is shown that fathers are extremely salient individuals in the lives of their children, particularly their sons. Fathers may play an important role in the adoption of cultural mores and sex-typed behavior. The social and practical implications of these findings, and their relevance to family practitioners, are stressed.
Evaluation of PrediXcan for prioritizing GWAS associations and predicting gene expression1*

Genome-wide association studies (GWAS) have been successful in facilitating the understanding of genetic architecture behind human diseases, but this approach faces many challenges. To identify disease-related loci with modest to weak effect size, GWAS requires very large sample sizes, which can be computational burdensome. In addition, the interpretation of discovered associations remains difficult. PrediXcan was developed to help address these issues. With built in SNP-expression models, PrediXcan is able to predict the expression of genes that are regulated by putative expression quantitative trait loci (eQTLs), and these predicted expression levels can then be used to perform gene-based association studies. This approach reduces the multiple testing burden from millions of variants down to several thousand genes. But most importantly, the identified associations can reveal the genes that are under regulation of eQTLs and consequently involved in disease pathogenesis. In this study, two of the most practical functions of PrediXcan were tested: 1) predicting gene expression, and 2) prioritizing GWAS results. We tested the prediction accuracy of PrediXcan by comparing the predicted and observed gene expression levels, and also looked into some potential influential factors and a filter criterion with the aim of improving PrediXcan performance. As for GWAS prioritization, predicted gene expression levels were used to obtain gene-trait associations, and background regions of significant associations were examined to decrease the likelihood of false positives. Our results showed that 1) PrediXcan predicted gene expression levels accurately for some but not all genes; 2) including more putative eQTLs into prediction did not improve the prediction accuracy; and 3) integrating predicted gene expression levels from the two PrediXcan whole blood models did not eliminate false positives. Still, PrediXcan was able to prioritize GWAS associations that were below the genome-wide significance threshold in GWAS, while retaining GWAS significant results. This study suggests several ways to consider PrediXcan’s performance that will be of value to eQTL and complex human disease research.
Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation

Tank-binding kinase (TBK)1 plays a central role in innate immunity: it serves as an integrator of multiple signals induced by receptor-mediated pathogen detection and as a modulator of IFN levels. Efforts to better understand the biology of this key immunological factor have intensified recently as growing evidence implicates aberrant TBK1 activity in a variety of autoimmune diseases and cancers. Nevertheless, key molecular details of TBK1 regulation and substrate selection remain unanswered. Here, structures of phosphorylated and unphosphorylated human TBK1 kinase and ubiquitin-like domains, combined with biochemical studies, indicate a molecular mechanism of activation via transautophosphorylation. These TBK1 structures are consistent with the tripartite architecture observed recently for the related kinase IKKβ, but domain contributions toward target recognition appear to differ for the two enzymes. In particular, both TBK1 autoactivation and substrate specificity are likely driven by signal-dependent colocalization events.