Miracle-dz/UniFAR-FTUs huggingface dataset:
Stabilization of the E3 Ubiquitin Ligase Nrdp1 by the Deubiquitinating Enzyme USP8

ABSTRACT Nrdp1 is a RING finger-containing E3 ubiquitin ligase that physically interacts with and regulates steady-state cellular levels of the ErbB3 and ErbB4 receptor tyrosine kinases and has been implicated in the degradation of the inhibitor-of-apoptosis protein BRUCE. Here we demonstrate that the Nrdp1 protein undergoes efficient proteasome-dependent degradation and that mutations in its RING finger domain that disrupt ubiquitin ligase activity enhance stability. These observations suggest that Nrdp1 self-ubiquitination and stability could play an important role in regulating the activity of this protein. Using affinity chromatography, we identified the deubiquitinating enzyme USP8 (also called Ubpy) as a protein that physically interacts with Nrdp1. Nrdp1 and USP8 could be coimmunoprecipitated, and in transfected cells USP8 specifically bound to Nrdp1 but not cbl, a RING finger E3 ligase involved in ligand-stimulated epidermal growth factor receptor down-regulation. The USP8 rhodanese and catalytic domains mediated Nrdp1 binding. USP8 markedly enhanced the stability of Nrdp1, and a point mutant that disrupts USP8 catalytic activity destabilized endogenous Nrdp1. Our results indicate that Nrdp1 is a specific target for the USP8 deubiquitinating enzyme and are consistent with a model where USP8 augments Nrdp1 activity by mediating its stabilization.
An ALC Description Default Logic with Exceptions-First

Knowledge formalization and reasoning automation are central within Artificial Intelligence. Classical logic has been traditionally used for such purposes. However, it is better suited to deal with complete knowledge in ideal circumstances. In real situations, in which the knowledge is partial, classical logic is not sufficient since it is monotonic. No monotonic logics have been proposed to better cope with practical reasoning. A successful formalization of no monotonic reasoning is Reiter's default logic which extends classical logic with default rules. Unfortunately, default logic is undividable. One reason for that is the use of classical logic as its monotonic basis. In this work, we change the default logic monotonic basis and propose a new default logic based on the description logic ALC. This new default logic is decidable and useful to formalize practical reasoning on hierarchical ontology's with exceptions, specially the ones that deals with legal knowledge and reasoning. On the default counterpart, we add some restrictions to the application of defaults in order to obtain nice properties such as coherence and elimination of anomalous extensions. We present the main algorithms used to build the extensions for this logic with its complexity analysis.
Organisation and gel contraction by human colonic carcinoma (HCA‐7) sublines grown in 3‐dimensional collagen gel

The role of cell‐matrix interactions in controlling phenotypic heterogeneity in human colonic carcinoma sublines has been investigated. Four cell lines (colony 1, colony 3, colony 6 and colony 30) previously isolated from a single human colonic carcinoma cell line, HCA‐7, were grown in 3‐dimensional collagen gels. In collagen, the growth of the 4 sublines ranged from well‐organised glandular structures (colony 30) to elongated branching structures (colony 3). The capability of cells to organise into glandular structures in collagen correlated with the degree of differentiation observed in their xenografts. Certain sublines, most notably colony 3, were able to contract the collagen gel. Gel contraction could be partially inhibited by a function‐blocking antibody directed to the α2 integrin chain but not by an antibody directed to the α3 integrin chain demonstrating a role for α2 integrin in the contraction process. In addition, colony 3 cultures treated with the function‐blocking α2 antibody formed more compact structures with limited outgrowth, suggesting a role for α2 integrin in cell migration. Gel contraction and cell migration in collagen gel was largely restricted to 1 subline, colony 3. The subsequent demonstration that α2 integrin is involved in both of these processes suggests that integrin expression and function has a role in generating the phenotypic heterogeneity exhibited by these cell lines.
Racial variation in the distribution of Ha‐ras‐1 alleles

Restriction fragment length polymorphism analyses of the Ha‐ras‐1 proto‐oncogene were undertaken in white and black populations residing in the Baltimore‐Washington metropolitan area to address whether specific rare alleles of the Ha‐ras‐1 proto‐oncogene locus vary in their distribution among different racial groups. High‐molecular‐weight genomic DNA samples from the lungs of 80 lung cancer patients and 92 accident victims were digested with appropriate restriction enzymes and subjected to Southern analysis using the 6.6‐kb BamHl human Ha‐ras‐1 recombinant fragment from the plasmid pEC. Thirty allelomorphs of different sizes were detected among the 172 study subjects. An association was observed between race and specific alleles. Rare alleles were more frequent in black cancer patients and trauma victims than in whites. Within each racial category, lung cancer patients had an excess of rare alleles. These data indicate the importance of controlling for racial variation when designing studies to determine human cancer risk factors.
Perfect simulation for wavelet thresholding with correlated coefficients

We introduce a new method of Bayesian wavelet shrinkage for reconstructing a signal when we observe a noisy version. Rather than making the usual assumption that the wavelet coefficients of the signal are independent, we assume that they are locally correlated in both location (time) and scale (frequency). This leads us to prefer a novel prior structure to which is, unfortunately, analytically intractable. We demonstrate that it is possible to draw exact, independent samples from the posterior distribution using Coupling From The Past, making a simulation-based approach possible.
Deregulation of the TP53/p14ARF tumor suppressor pathway in low-grade diffuse astrocytomas and its influence on clinical course.

PURPOSE The chromosome 9p21 region harbors three tumor suppressor genes, p14(ARF), p15(INK4b), and p16(INK4a), all of which can be targets for hypermethylation-associated inactivation in low-grade gliomas. p16(INK4a) and p15(INK4b) are critically involved in the RB1 pathway, whereas p14(ARF) acts as an upstream regulator of the TP53 pathway. The role of each tumor suppressor pathway in low-grade diffuse astrocytomas and their relationships with clinical behavior remain to be elucidated. EXPERIMENTAL DESIGN We assessed the alterations of the RB1/CDK4/p16(INK4a)/p15(INK4b) and the TP53/MDM2/p14(ARF) pathways in 46 WHO grade II astrocytomas and analyzed their impact on prognosis. RESULTS The TP53/MDM2/p14(ARF) pathway was altered in 32 of 46 cases (70%) by either TP53 mutation (25 cases) or p14(ARF) methylation (9 cases). The RB1/CDK4/p16(INK4a)/p15(INK4b) pathway was disrupted in 6 of 46 cases (13%) by either RB1 methylation (1 case), p16(INK4a) methylation (3 cases), or p15(INK4b) methylation or homozygous deletion (3 cases). Generally speaking, individual tumors thus tended to display alteration of only one component from both pathways. Any independently analyzed genetic alteration failed to provide statistically prognostic information. The alternate or simultaneous presence of TP53 mutation and p14(ARF) methylation emerged as a univariate predictor of a shorter progression-free survival (P = 0.0456) but was not statistically significant when age and extent of surgery were included in the analysis. CONCLUSIONS Alternative disruption of the TP53/p14(ARF) pathway represents a frequent event in low-grade diffuse astrocytomas and correlates with an unfavorable clinical course. However, its value is unlikely to include prognostic utility that is independent of other conventional prognostic factors.
Changes in cellular energy budget as a measure of whole effluent toxicity in zebrafish (Danio rerio)

Organisms exposed to suboptimal conditions face an a priori cost of combating stress in terms of metabolic resources. The energy available for maintenance, growth, and reproduction, based on the biochemical analysis of the energy budget rather than on the direct measurement of those endpoints, may therefore provide a sensitive measure of stress in an organism. The aim of this study was to validate changes in energy budget as an ecologically relevant sublethal parameter by comparing these responses with physiological, growth, and reproductive endpoints. A toxicity test with zebrafish (Danio rerio) was conducted where fish were exposed to a control and 50, 75, and 100% effluent for 28 d under flow‐through conditions. Effects of effluent exposure were measured as changes in glycogen, lipid, and protein budgets. Furthermore, the observed effects were linked to different processes like growth, condition, respiration, and reproduction within the same populations. Our results indicate that changes in lipid budgets in exposed fish were the most sensitive endpoint. Excellent relations were found between cellular energy budgets, relative condition factor, and respiration (r2 = 0.795, p < 0.001; and r2 = 0.735, p < 0.001, respectively), but relations were poorer for reproductive output (r2 = 0.410, p < 0.034). As a whole, especially changes in lipid energy budgets provide a sensitive and fast indicator of altered condition in zebrafish under the given exposure regime and allow linking cellular effects to other endpoints within the same exposed populations.
Robust radial imaging with predetermined isotropic gradient delay correction

P. Speier, F. Trautwein Siemens AG MED, Erlangen, Germany Introduction There is continued interest in Non-Cartesian (NC) acquisition schemes due to their promise of higher SNR and PAT acceleration factors and better motion insensitivity than standard Cartesian schemes. However, in clinical routine Cartesian imaging is used virtually exclusively. The main reason for this lack of routine use, besides the increased complexity of reconstruction algorithms, is probably that NC imaging requires more precise realizations of k-space trajectories than Cartesian imaging, which in turn requires higher precision in scanner control. For example, timing delays between reference clock events (NCO) and receive events (ADC) have been shown [1] to be detrimental to the quality of radially acquired images but not to Cartesian images. The system imperfections that degrade NC image quality most are delays between played out gradient moments (MG) and ADCs. D. Peters et. al. [2] demonstrated that these gradient delays can be described by a model that assumes that each physical gradient axis has its own delay value. Measuring trajectories frequently before taking the actual image is adequate only in an academic setting, but quite impossible in a clinical routine setting. Therefore the goal of this paper is to parameterize the delays between MG and ADC with sufficient accuracy for clinical radial imaging applications.
Near field fluid coupling between internal motion of the organ of Corti and the basilar membrane

The pressure distribution in each of the fluid chambers of the cochlea can be decomposed into a 1D, or plane wave, component and a near field component, which decays rapidly away from the excitation point. The transverse motion of the basilar membrane, BM, for example, generates both a 1D pressure field, which couples into the slow wave, and a local near field pressure, proportional to the BM acceleration, that generates an added mass on the BM due to the fluid motion. When the organ of Corti, OC, undergoes internal motion, due for example to outer hair cell activity, this motion will not itself generate any 1D pressure if the OC is incompressible and the BM is constrained not to move volumetrically, and so will not directly couple into the slow wave. This motion will, however, generate a near field pressure, proportional to the OC acceleration, which will act on the OC and thus increases its effective mass. The near field pressure due to this OC motion will also act on the BM, generating a force on the BM proportional to the acceleration of the OC, and thus create a “coupling mass” effect. By reciprocity, this coupling mass is the same as that acting on the OC due to the motion of the BM. This near field fluid coupling is initially observed in a finite element model of a slice of the cochlea. These simulations suggest a simple analytical formulation for the fluid coupling, using higher order beam modes across the width of the cochlear partition. It is well known that the added mass due to the near field pressure dominates the overall mass of the BM, and thus significantly affects the micromechanical dynamics. This work not only quantifies the added mass of the OC due its own motion in the fluid, and shows that this is important, but also demonstrates that the coupling mass effect between the BM and OC significantly affects the dynamics of simple micromechanical models.
High prevalence of self-reported injuries and illnesses in talented female athletes

Background A thorough knowledge of the epidemiology and severity of injuries and illness in youth female elite sports is lacking due to the methodological challenges involved in recording them. In this study, the prevalence and incidence of injuries and illness are assessed among youth female elite athletes. Instead of solely focusing on time-loss injuries, our study included all substantial and non-substantial health problems (ie, injuries, mental problems and illnesses). Methods Sixty young elite Dutch female athletes (age: 16.6 years (SD: 2.3), weight: 58.3 kg (SD: 15.1), height: 154.1 cm (SD: 44.2)) participating in soccer (n=23), basketball (n=22) and gymnastic (n=15) talent development programmes were prospectively followed during one season (September 2014 to April 2015). To collect health problem data, all athletes completed the Oslo Sports Trauma Research Center Questionnaire on Health Problems every other week. Main outcome measures were average prevalence of injury and incidence density of injury. Results At any given time, 47.9% of the athletes reported an injury (95% CI 43.6% to 52.6%) and 9.1% reported an illness (95% CI 5.1 to 19.0). The average injury incidence density was 8.6 per 1000 hours of athlete exposure. The average number of self-reported injuries per athlete per season was significantly higher in soccer athletes (4.3±2.7) than in basketball athletes (2.6±2.0) (p=0.03) and not significantly higher than in the gymnastic squad. The knee and the ankle were two of the most common injury locations for all squads. Knee injuries in basketball and soccer and heel injuries in the gymnastic squad had the highest impact on sports participation. Conclusion High prevalence of self-reported injuries among talented female athletes suggests that future efforts towards their prevention are warranted.
Towards an Algorithmic Statistics

While Kolmogorov complexity is the accepted absolute measure of information content of an individual nite object, a similarly absolute notion is needed for the relation between an individual data sample and an individual model summarizing the information in the data, for example, a nite set where the data sample typically came from. The statistical theory based on such relations between individual objects can be called algorithmic statistics, in contrast to ordinary statistical theory that deals with relations between probabilistic ensembles. We develop a new algorithmic theory of typical statistic, suucient statistic, and minimal suucient statistic.
Human Th1 Cells That Express CD300a Are Polyfunctional and After Stimulation Up-Regulate the T-Box Transcription Factor Eomesodermin

Human naïve CD4 T cells express low levels of the immunomodulatory receptor CD300a, whereas effector/memory CD4 cells can be either CD300a+ or CD300a−. This suggested that CD300a expression could define a specific subset within the effector/memory CD4 T cell subpopulations. In fact, ex vivo analysis of the IFN-γ producing CD4 T cells showed that they are enriched in the CD300a+ subset. Moreover, stimulated CD4 T cells producing TNF-α and IL-2 besides IFN-γ (polyfunctional) are predominantly CD300a+. In addition to producing markedly higher levels of Th1-associated cytokines, the stimulated CD300a+ CD4 T cells are distinguished by a striking up-regulation of the T-box transcription factor eomesodermin (Eomes), whereas T-bet is up-regulated in both CD300a+ and CD300a− activated CD4 T cells to similar levels. The pleiotropic cytokine TGF-β1 has a determinant role in dictating the development of this Th1 subset, as its presence inhibits the expression of CD300a and down-regulates the expression of Eomes and IFN-γ. We conclude that CD300a+ human Th1 cells tend to be polyfunctional and after stimulation up-regulate Eomes.
Relationship between DNA ploidy,expression of ki-67 antigen and gastric cancer metastasis.

AIM:To evaluate the relationship between the expression of Ki-67 antigen and the pathobiological behaviours of gastric cancers especially their distant metastases.METHODS:Fifty-six specimens of gastric cancer routinely fixed in formalin and embedded in paraffin (FFEP) were studied by immunohistochemical method.RESULTS: Expression of Ki-67 antigen was significantly related to the distant metastases to liver, ovary and adrenal gland (P < 0.01), but not related to the histological type, growth pattern, depth of invasion, histological differentiation and the metastases to local lymph nodes (P > 0.05). Furthermore, the Ki-67 antigen expression was significantly related to the DNA aneuploidy pattern, which is closely related to poor prognosis (P < 0.05). CONCLUSION:Overexpression of Ki-67 can be used as an objectiv marker of the proliferative activity for predicting prognosis of gastric cancer and metastatic potential to distant organs.
Athermal arrayed-waveguide-grating wavelength division multiplexer and manufacturing method therefor

Disclosed are an athermal arrayed-waveguide-grating wavelength division multiplexer and a manufacturing method therefor. The athermal arrayed-waveguide-grating wavelength division multiplexer comprises an AWG chip (100), interlayers (200), a bottom plate (300) and a temperature compensating device (400). The interlayers (200) adopt a first interlayer and a second interlayer (203) with the expansion coefficients thereof being same or approximate to that of the AWG chip (100). The input waveguide, the input planar waveguide and the partial output planar waveguide of the AWG chip (100) are fixed on the first interlayer, and the output waveguide of the AWG chip (100) is fixed on the second interlayer (203). The input planar waveguide or the output planar waveguide of the AWG chip (100) are provided with a cutting seam (104) which divides the AWG chip (100) into a first chip (101) and a second chip (102). The first interlayer is divided into a first part (201) and a second part (202) along the direction of the face of the cutting seam (104). Thermally curing glue with a similar thermal expansion coefficient to that of the AWG chip (100) is arranged between the AWG chip (100) and the interlayers. The first part (201) of the first interlayer and the bottom plate are fixed by adopting bonding glue capable of realizing thermal expansion movement, and the second part (202) of the first interlayer and the second interlayer (203) are fixedly bonded to the upper surface of the bottom plate. Along the direction of the division plane, one end of the temperature compensating device (400) is fixed on the first chip (101) or the upper surface of the first part (201) of the first interlayer, and the other end of the temperature compensating device is fixed on the upper surface of the second interlayer (203).
Distributed Energy Aware MAC Layer Protocol for Wireless Sensor Networks

Due to the fact that sensor nodes are untethered and unattended, energy management is a critical issue in communication mechanism of a wireless sensor network. In this paper, we address this problem and propose a novel solution based on media access control technique. Our protocol DE-MAC exploits the inherent features of TDMA to avoid the main sources of energy wastage: collision and control packet overhead. It uses the concept of periodic listen and sleep in order to avoid idle listening and overhearing. However, unlike existing MAC-layer protocols, DE-MAC treats the critical nodes differently in a distributed manner. Motivated by the fact that a weaker node should be used less frequently in a routing in order to accomplish load balancing, DE-MAC performs a local election procedure and chooses the worstoff node/nodes as the winner/winners and makes them sleep more than the other neighboring nodes. Since the election procedure is fully integrated with the TDMA slot assignment, our protocol suffers no extra throughput loss. We evaluate DE-MAC and present the simulation results which explicitly show the gain in performance.
Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease.

CONTEXT Sickle cell disease is characterized by a state of nitric oxide resistance and limited bioavailability of l-arginine, the substrate for nitric oxide synthesis. We hypothesized that increased arginase activity and dysregulated arginine metabolism contribute to endothelial dysfunction, pulmonary hypertension, and patient outcomes. OBJECTIVE To explore the role of arginase in sickle cell disease pathogenesis, pulmonary hypertension, and mortality. DESIGN Plasma amino acid levels, plasma and erythrocyte arginase activities, and pulmonary hypertension status as measured by Doppler echocardiogram were prospectively obtained in outpatients with sickle cell disease. Patients were followed up for survival up to 49 months. SETTING Urban tertiary care center and community clinics in the United States between February 2001 and March 2005. PARTICIPANTS Two hundred twenty-eight patients with sickle cell disease, aged 18 to 74 years, and 36 control participants. MAIN OUTCOME MEASURES Plasma amino acid levels, plasma and erythrocyte arginase activities, diagnosis of pulmonary hypertension, and mortality. RESULTS Plasma arginase activity was significantly elevated in patients with sickle cell disease, with highest activity found in patients with secondary pulmonary hypertension. Arginase activity correlated with the arginine-ornithine ratio, and lower ratios were associated with greater severity of pulmonary hypertension and with mortality in this population (risk ratio, 2.5; 95% confidence interval [CI], 1.2-5.2; P = .006). Global arginine bioavailability, characterized by the ratio of arginine to ornithine plus citrulline, was also strongly associated with mortality (risk ratio, 3.6; 95% CI, 1.5-8.3; P<.001). Increased plasma arginase activity was correlated with increased intravascular hemolytic rate and, to a lesser extent, with markers of inflammation and soluble adhesion molecule levels. CONCLUSIONS These data support a novel mechanism of disease in which hemolysis contributes to reduced nitric oxide bioavailability and endothelial dysfunction via release of erythrocyte arginase, which limits arginine bioavailability, and release of erythrocyte hemoglobin, which scavenges nitric oxide. The ratios of arginine to ornithine and arginine to ornithine plus citrulline are independently associated with pulmonary hypertension and increased mortality in patients with sickle cell disease.
HCI and sports

Sport is an area in which the number of available computing devices is growing rapidly. However, HCI has so far devoted rather little attention to the sports domain. This workshop aims to form a community around sports by gathering existing activity in the HCI domain, thus starting a discussion on what HCI can contribute to the sports domain, as well as what HCI can gain from studying sports. Author