Miracle-dz/UniFAR-FTUs huggingface dataset:
Ubiquitin plays an atypical role in GPCR-induced p38 MAP kinase activation on endosomes

Protease‐activated receptor 1 (PAR1) is a G protein–coupled receptor (GPCR) for thrombin and promotes inflammatory responses through multiple pathways including p38 mitogen‐activated protein kinase signaling. The mechanisms that govern PAR1‐induced p38 activation remain unclear. Here, we define an atypical ubiquitin‐dependent pathway for p38 activation used by PAR1 that regulates endothelial barrier permeability. Activated PAR1 K63‐linked ubiquitination is mediated by the NEDD4‐2 E3 ubiquitin ligase and initiated recruitment of transforming growth factor‐β–activated protein kinase‐1 binding protein‐2 (TAB2). The ubiquitin‐binding domain of TAB2 was essential for recruitment to PAR1‐containing endosomes. TAB2 associated with TAB1, which induced p38 activation independent of MKK3 and MKK6. The P2Y1 purinergic GPCR also stimulated p38 activation via NEDD4‐2–mediated ubiquitination and TAB1–TAB2. TAB1–TAB2‐dependent p38 activation was critical for PAR1‐promoted endothelial barrier permeability in vitro, and p38 signaling was required for PAR1‐induced vascular leakage in vivo. These studies define an atypical ubiquitin mediated signaling pathway used by a subset of GPCRs that regulates endosomal p38 signaling and endothelial barrier disruption.
Deep convolutional neural networks for pedestrian detection with skip pooling

With the big success of deep convolutional neural networks (CNN) in image classification task, many proposal based networks are proposed to detect given objects in an image. Faster R-CNN is such a network that uses a region proposal network (RPN) to generate nearly cost-free region proposals, which has shown excellent performance in ILSVRC and MS COCO datasets. However, Faster R-CNN does not behave so well for the task of pedestrian detection since the images in popular pedestrian detection datasets have more complicated background and contain a lot of small foreground objects. In this work, we leverage the RPN architecture of Faster R-CNN and extend it to a multi-layer version combined with skip pooling to tackle the pedestrian detection problem. Skip pooling is a kind of network connection that combines multiple ROI pooling results from lower layers to form a single input to a higher layer while bypassing intermediate layers. We comprehensively evaluate our network, referred to as SP-CNN, on the Caltech pedestrian detection benchmark and KITTI object detection benchmark. Our method achieves state-of-the-art accuracy on Caltech dataset and presents a comparable result on KITTI dataset while maintaining a good speed.
Balance control based on Capture Point error compensation for biped walking on uneven terrain

This paper tries to improve a balance control based on the Capture Point (CP) control. First the characteristics of the conventional balance controller are shown to be essentially the same as the CP controller. Then we analyze the transfer function of the balance controller. We introduce a new state variable with the CP integration to the CP and the ZMP (Zero-Moment Point) in order to trim a long term offset of the CP and the ZMP. Verification of the proposed balance controller is conducted through both simulation and experiments with a humanoid robot HRP-2[11].
Identification and characterization of three members of the human SR family of pre‐mRNA splicing factors.

SR proteins have a characteristic C‐terminal Ser/Arg‐rich repeat (RS domain) of variable length and constitute a family of highly conserved nuclear phosphoproteins that can function as both essential and alternative pre‐mRNA splicing factors. We have cloned a cDNA encoding a novel human SR protein designated SRp30c, which has an unusually short RS domain. We also cloned cDNAs encoding the human homologues of Drosophila SRp55/B52 and rat SRp40/HRS. Recombinant proteins expressed from these cDNAs are active in constitutive splicing, as shown by their ability to complement a HeLa cell S100 extract deficient in SR proteins. Additional cDNA clones reflect extensive alternative splicing of SRp40 and SRp55 pre‐mRNAs. The predicted protein isoforms lack the C‐terminal RS domain and might be involved in feedback regulatory loops. The ability of human SRp30c, SRp40 and SRp55 to modulate alternative splicing in vivo was compared with that of other SR proteins using a transient contransfection assay. The overexpression of individual SR proteins in HeLa cells affected the choice of alternative 5′ splice sites of adenovirus E1A and/or human beta‐thalassemia reporters. The resulting splicing patterns were characteristic for each SR protein. Consistent with the postulated importance of SR proteins in alternative splicing in vivo, we demonstrate complex changes in the levels of mRNAs encoding the above SR proteins upon T cell activation, concomitant with changes in the expression of alternatively spliced isoforms of CD44 and CD45.
Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive–compulsive disorder as an example of overlapping clinical and genetic heterogeneity

Individuals with obsessive–compulsive disorder (OCD) have also been shown to have comorbid lifetime diagnoses of major depressive disorder (MDD; rates greater than 70%), bipolar disorder (rates greater than 10%) and other anxiety disorders (e.g. panic disorder, post-traumatic stress disorder (PTSD)). In addition, overlap exists in some common genetic variants (e.g. the serotonin transporter gene (SLC6A4), the brain-derived neurotrophic factor (BDNF) gene), and rare variants in genes/chromosomal abnormalities (e.g. the 22q11 microdeletion syndrome) found across the affective/anxiety disorder spectrums. OCD has been proposed as a possible independent entity for DSM-5, but by others thought best retained as an anxiety disorder subtype (its current designation in DSM-IV), and yet by others considered best in the affective disorder spectrum. This review focuses on OCD, a well-studied but still puzzling heterogeneous disorder, regarding alterations in serotonergic, dopaminergic and glutamatergic neurotransmission in addition to other systems involved, and how related genes may be involved in the comorbidity of anxiety and affective disorders. OCD resembles disorders such as depression, in which gene × gene interactions, gene × environment interactions and stress elements coalesce to yield OC symptoms and, in some individuals, full-blown OCD with multiple comorbid disorders.
Tumor necrosis factor-alpha antibody for induction of remission in Crohn's disease.

BACKGROUND Crohn's disease may be refractory to conventional treatments such as corticosteroids, enteral nutrition and immuno-suppressive agents. A number of patients with the disease may also become steroid-dependent leading to increased risk of developing steroid-related adverse effects. Recent studies suggest that TNF-a blocking agents may be effective in inducing remission in Crohn's disease. OBJECTIVES To conduct a systematic review to evaluate the effectiveness of TNF-a blocking agents in inducing remission in patients with active Crohn's disease. SEARCH STRATEGY We searched MEDLINE (1966-June 2003), EMBASE (1984-June 2003), the Cochrane Central Register of Controlled Trials from the Cochrane Library (Issue 2, 2003) and the IBD Review Group Specialized Trials Register. We hand-searched the articles cited in each publication obtained. SELECTION CRITERIA We included only randomised controlled trials in which patients with active Crohn's disease (defined by a validated Crohn's disease activity index) were randomly allocated to receive a TNF-a blocking agent in the treatment arm, or to receive placebo or another treatment in the comparison arm. DATA COLLECTION AND ANALYSIS Data extraction and assessment of the methodological quality of each trial were independently performed by two reviewers. Any disagreement among reviewers was resolved by consensus. Outcome measures reported in the primary studies included clinical remission, clinical response and changes in disease activity index. MAIN RESULTS Ten studies were identified of which 4 met the inclusion criteria. The included studies either differed in the type of TNF-a blocking agent used or in the way outcomes were assessed to such an extent that we considered it inappropriate to combine the data statistically. There is evidence from one randomised controlled trial that suggests that a single intravenous infusion of the monoclonal antibody cA2, infliximab, may be effective for induction of remission in Crohn's disease. There was no difference in response rates among infliximab doses of 5, 10 or 20 mg/kg. The results of two other trials suggested that CDP571, the genetically engineered human TNF monoclonal antibody, may also be effective in reducing disease activity index at 2 weeks after an infusion. We did not find any evidence to support the use of etanercept in Crohn's disease. REVIEWER'S CONCLUSIONS Evidence from one randomized controlled trial suggests that a single infusion of infliximab may be effective for induction of remission in Crohn's disease. Based on this study, we can recommend a dose of 5 mg/kg. There is also some evidence that CDP571 may be effective in inducing remission in Crohn's disease. We did not find any evidence that supports the use of etanercept in Crohn's disease. The period of follow up for the patients in these studies was probably too short to allow adequate assessment of recently reported serious adverse effects such as tuberculosis and lymphoma.
Query Recommendation for Optimizing the Search Engine Results

Search engine query have been paying awareness in current days. Since web contents develop, the importance of search engines became more essential and at the same instance user performance reduces. Query recommendation is a method to improve search results in web. This paper presents a method for mining search engine query logs to obtain fast query recommendation on a large scale. Search engines generally return long list of ranked pages, finding the important information related to a particular topic is becoming increasingly difficult and therefore, optimized search engines become one of the most popular solution available. In this work, an algorithm has been applied to recommend related queries to a query submitted by user. For this, the technology used for allowing query recommendations is query log which contains attributes like query name, clicked URL, rank, time. Then, the similarity based on keywords as well as clicked URL’s is calculated. Additionally, clusters have been obtained by combining the similarities of both keywords and clicked URL’s to perform query clustering and further the sequential order of clicked URLs in each cluster has been discovered using the modified version of an existing sequential pattern mining technique. The final by product is further optimized by re-ranking the pages using the discovered sequential patterns. The proposed system here, is based on learning from query logs that predicts user information requirements and reduces the seek time of the user within the search result list.
Statistical NLOS Identification Based on AOA, TOA, and Signal Strength

Nonline-of-sight (NLOS) propagation is one of the challenges in radio positioning. Significant attention has been drawn to the mitigation of the NLOS effect in recent years. This paper focuses on the identification of NLOS conditions by employing the statistical decision theory. A Neyman-Pearson (NP) test method is first derived for scenarios where either 1-D or 2-D angular measurements are provided. A time-of-arrival (TOA) based method is then developed under idealized conditions to provide a performance reference. In the presence of both TOA and received signal strength (RSS) measurements, a joint identification method is derived to efficiently exploit the TOA and RSS measurements. Analytical expressions of the probability of detection (POD) and the probability of false alarm (PFA) are derived for all the scenarios considered. Two theorems and one corollary regarding the line-of-sight (LOS) conditions based on the angle of arrival (AOA) are also presented, and the proofs are provided. Simulation results demonstrate that the proposed methods perform well, and the joint TOA- and RSS-based method considerably outperforms the TOA-based methods. The proposed methods are robust to the model errors, as demonstrated through simulations. It is also shown that the analytical results agree well with the simulated ones.
Learning Visualizations by Analogy: Promoting Visual Literacy through Visualization Morphing

We propose the concept of teaching (and learning) unfamiliar visualizations by analogy, that is, demonstrating an unfamiliar visualization method by linking it to another more familiar one, where the in-betweens are designed to bridge the gap of these two visualizations and explain the difference in a gradual manner. As opposed to a textual description, our morphing explains an unfamiliar visualization through purely visual means. We demonstrate our idea by ways of four visualization pair examples: data table and parallel coordinates, scatterplot matrix and hyperbox, linear chart and spiral chart, and hierarchical pie chart and treemap. The analogy is commutative i.e. any member of the pair can be the unfamiliar visualization. A series of studies showed that this new paradigm can be an effective teaching tool. The participants could understand the unfamiliar visualization methods in all of the four pairs either fully or at least significantly better after they observed or interacted with the transitions from the familiar counterpart. The four examples suggest how helpful visualization pairings be identified and they will hopefully inspire other visualization morphings and associated transition strategies to be identified.
Down Syndrome: Interaction between Culture, Demography, and Biology in Determining the Prevalence of a Genetic Trait

The incidence of Down syndrome (DS) at conception is highly dependent upon the maternal age distribution and age-specific pregnancy rates. Live-birth prevalence of DS reflects these factors and fetal deaths. Since the introduction of prenatal diagnosis in the early 1970s, the role of fetal deaths in the equation has increased. Between 1920 and the early 1980s, DS live-birth prevalence decreased in many populations due to declining fertility rates, particularly among older women. In the late-1970s the trend reversed, as the median age of populations and birth rates among older women steadily increased. This paper illustrates these interactions using data we have analyzed for New York State (NYS) and comparative data obtained from the literature. Between 1983 and 1997 DS live-birth prevalence in NYS remained stable at about 9.9 per 10,000 live births. The number of prenatal tests performed increased by 158%, and the number of DS fetuses detected prenatally more than quadrupled. Fertility rates of women aged 35-49 continued to increase. The proportion of DS cases born to these older mothers increased from 23% in 1985 to 43% in 1997. We estimated that without prenatal diagnosis, DS live-birth prevalence would have been 17.0 per 10,000 live births by 1995. Cultural factors influence demographic trends, birthing technologies, physician practices, and women's decision-making regarding prenatal screening and diagnosis for DS.
A ~6000 yr diatom record of mid- to late Holocene fluctuations in the level of Lago Wiñaymarca, Lake Titicaca (Peru/Bolivia)

Abstract A multidecadal-scale lake-level reconstruction for Lago Wiñaymarca, the southern basin of Lake Titicaca, has been generated from diatom species abundance data. These data suggest that ~6500 cal yr BP Lago Wiñaymarca was dry, as indicated by a sediment unconformity. At ~4400 cal yr BP, the basin began to fill, as indicated by the dominance of shallow epiphytic species. It remained somewhat saline with extensive wetlands and abundant aquatic plants until ~3800 cal yr BP, when epiphytic species were replaced by planktic saline-indifferent species, suggesting a saline shallow lake. Wiñaymarca remained a relatively shallow lake that fluctuated on a multidecadal scale until ~1250 cal yr BP, when freshwater planktic species increased, suggesting a rise in lake level with a concomitant decrease in salinity. The lake became gradually fresher, dominated by deep, freshwater species from ~850 cal yr BP. By ~80 cal yr BP, saline-tolerant species were rare, and the lake was dominated by freshwater planktic diatoms, resembling the fresh and deep lake of today. These results reveal a more dynamic and chronologically specific record of lake-level fluctuations and associated ecological conditions that provide important new data for paleoclimatologists and archaeologists, to better understand human-environmental dynamics during the mid- to late Holocene.
The structure of DNA overstretched from the 5′5′ ends differs from the structure of DNA overstretched from the 3′3′ ends

It has been suggested that the structure that results when double-stranded DNA (dsDNA) is pulled from the 3′3′ ends differs from that which results when it is pulled from the 5′5′ ends. In this work, we demonstrate, using λ phage dsDNA, that the overstretched states do indeed show different properties, suggesting that they correspond to different structures. For 3′3′ pulling versus 5′5′ pulling, the following differences are observed: (i) the forces at which half of the molecules in the ensemble have made a complete force-induced transition to single stranded DNA are 141 ± 3 pN and 122 ± 4 pN, respectively; (ii) the extension vs. force curve for overstretched DNA has a marked change in slope at 127 ± 3 pN for 3′3′ and 110 ± 3 pN for 5′5′; (iii) the hysteresis (H) in the extension vs. force curves at 150 mM NaCl is 0.3 ± 0.8 pN μm for 3′3′ versus 13 ± 8 pN for 5′5′; and (iv) 3′3′ and 5′5′ molecules show different changes in hysteresis due to interactions with β-cyclodextrin, a molecule that is known to form stable host-guest complexes with rotated base pairs, and glyoxal that is known to bind stably to unpaired bases. These differences and additional findings are well-accommodated by the corresponding structures predicted on theoretical grounds.
The Boeing 777: no Chainsaw Massacres, please!

Iterative life cycle models have become popular in software engineering, e.g. in agile development. In contrast, the waterfall model appears to prevail in manufacturing engineering disciplines. This includes aircraft engineering and Boeing's project for developing its most recent passenger aircraft, the 777. The paper walks through the phases of the 777's development and compares this process to iterative development. The comparison suggests two observations: Firstly, the over-all waterfall approach in the 777 project appears to be well-motivated by the physical, manufactured nature of aircraft components such as wings, in addition to safety concerns. Secondly, several iterative elements in the development of the 777 can also be identified. A major source of these is digitalization of development, in particular the use of CAD tools for a process called digital preassembly.
c‐fos down‐regulation inhibits testosterone‐dependent male sexual behavior and the associated learning

Environmental stimulation results in an increased expression of transcription factors called immediate early genes (IEGs) in specific neuronal populations. In male Japanese quail, copulation with a female increases the expression of the IEGs zenk and c‐fos in the medial pre‐optic nucleus (POM), a key nucleus controlling male sexual behavior. The functional significance of this increased IEG expression that follows performance of copulatory behavior is unknown. We addressed this question by repeatedly quantifying the performance of appetitive (learned social proximity response) and consummatory (actual copulation) sexual behavior in castrated, testosterone‐treated males that received daily intra‐cerebroventricular injection of an antisense oligodeoxynucleotide targeting c‐fos or control vehicle. Daily antisense injections significantly inhibited the expression of copulatory behavior as well as the acquisition of the learned social proximity response. A strong reduction of the proximity response was still observed in antisense‐treated birds that copulated with a female, ruling out the indirect effect of the absence of interactions with females on the learning process. After a 2‐day interruption of behavioral testing but not of antisense injections, birds were submitted to a final copulatory test that confirmed the behavioral inhibition in antisense‐injected birds. Brains were collected at 90 min after the behavioral testing for quantification of c‐fos‐immunoreactive cells. A significant reduction of the number of c‐fos‐positive cells in the POM but not in other brain regions was observed following antisense injection. Taken together, the data suggest that c‐fos expression in the POM modulates copulatory behavior and sexual learning in male quail.
Mobility adaptive self-parameterization of routing protocols for mobile ad hoc networks

In the recent years, several routing protocol for mobile ad hoc networks (MANETs) have been developed. The performance of these protocols in a special scenario highly depends on the selection of "good" parameter values, e.g. update intervals. In MANETs, there does not exist any administrator or any infrastructure which could parameterize the routing protocols and static predefined parameters might not be suitable for the current scenario. So the mobile nodes have to self-parameterize. This paper presents a novel approach which enables mobile nodes to do a mobility-adaptive self-parameterization of their routing protocol. To measure the mobility in the MANET, we developed the MANET relative velocity indicator (MARVIN). Based on the continuously measurement of MARVIN the parameters of the routing protocol are adapted to the current scenario
Block-Orthogonal Space–Time Code Structure and Its Impact on QRDM Decoding Complexity Reduction

Full-rate space time codes (STCs) with rate number of transmit antennas have high multiplexing gain, but high decoding complexity even when decoded using reduced-complexity decoders such as sphere or QRDM decoders. In this paper, we introduce a new code property of STC called block-orthogonal property, which can be exploited by QR-decomposition-based decoders to achieve significant decoding complexity reduction without performance loss. We show that such complexity reduction principle can benefit the existing algebraic codes such as Perfect and DjABBA codes due to their inherent (but previously undiscovered) block-orthogonal property. In addition, we construct and optimize new full-rate block-orthogonal STC (BOSTC) that further maximize the QRDM complexity reduction potential. Simulation results of bit error rate (BER) performance against decoding complexity show that the new BOSTC outperforms all previously known codes as long as the QRDM decoder operates in reduced-complexity mode, and the code exhibits a desirable complexity saturation property.
Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors.

There are many potential barriers to the effective delivery of a drug in its active form to solid tumors. Most small-molecule chemotherapeutic agents have a large volume of distribution on i.v. administration ([Speth et al., 1988][1]; [Chabner and Longo, 1996][2]). The result of this is often a