Miracle-dz/UniFAR-FTUs huggingface dataset:
Synthetic inhibitor of matrix metalloproteases decreases tumor growth and metastases in a syngeneic model of rat prostate cancer in vivo

Members of the matrix metalloprotease (MMP) family are implicated in the progression of several malignancies including prostate cancer due to their ability to break down extracellular matrix (ECM) components. In this study, we have evaluated the ability of a synthetic MMP inhibitor (A‐177430) to block tumor growth and metastases in a syngeneic model of rat prostate cancer. In an in vitro substrate assay, A‐177430 exhibited nanomolar potency (IC50 2–6 nM) against the enzymatic activity of several MMPs. For in vivo studies, male Copenhagen rats were injected s.c. with Mat Ly Lu rat prostate cancer cells (1 × 106 cells ) into the right flank and animals were administered i.p.with different doses (10–100 mg/kg per day) of A‐177430 for 16 days. Administration of A‐177430 resulted in a dose‐dependent decrease in tumor volume as compared to a control group of animals receiving vehicle alone. The maximum dose (100 mg/kg per day) of A‐177430 exhibited complete arrest in tumor growth and prevented the development of macroscopic tumor metastases to lungs without exhibiting any noticeable side effects. Histologic examination of primary tumors from experimental animals showed extensive tumor necrosis and decreased tumor angiogenesis as determined by factor VIII staining of primary tumors following A‐177430 treatment. These primary tumors from experimental animals also exhibited a significant increase in tumor cell DNA fragmentation as determined by TUNEL assay. Collectively, these results demonstrate the ability of MMP inhibitors to block tumor growth and metastases by blocking ECM degradation and by inhibiting tumor angiogenesis and promotion of prostate cancer cell apoptosis in vivo. Int. J. Cancer 87:276–282, 2000. © 2000 Wiley‐Liss, Inc.
Visual ContextRank for web image re-ranking

Previous web image re-ranking approaches usually construct similarity measure on image level. Considering the diversity of large scale web image database, these approaches ignore the difference of importance between target area and background area in images, thus are not robust to background clutter and may bring some false similarity contribution among images, especially for object query images. We propose ContextRank, re-ranking images by building Markov random process of a surfer jumping across visual words within and among images. For intra-image context, links of visual words are constructed if they are close enough within an image. For inter-image context, links of visual words between image pairs are constructed by incorporating both feature similarity and spatial consistency. Equally speaking, we build a random walk model on visual word level where spatial information is taken into account. The stationary distribution of visual words in each image is derived by calculating the principle eigenvector of link matrix. The score of images are the sum of scores of visual words in each image. Evaluation on object images collected from the Google search engine shows that our approach outperforms VisualRank, and is comparable with the state-of-art. Compared to VisualRank, our method reaches better performance without significant extra computation cost, which is suitable for potential requirement of large scale web image retrieval.
Inactivation of individual Ca(2+)-binding sites in the paired EF-hand sites of parvalbumin reveals asymmetrical metal-binding properties.

Previously a rat parvalbumin mutant protein PVF102W was constructed with a reporter Trp at position 102 in the middle of the hydrophobic center [Pauls, T. L. , et al. (1993) J. Biol. Chem. 268, 20897-20903]. In the present study three new parvalbumin mutant proteins, derived from PVF102W and containing alterations at positions essential for Ca2+ binding in either one of the two Ca(2+)-binding sites (PV-CD and PV-EF) or in both (PV-CD/-EF), were expressed and purified. With the flow dialysis method it was established that both PV-CD and PV-EF bind 1 Ca2+ with affinity constants KCa of 1.1 x 10(7) and 3.2 x 10(6) M-1, respectively. Mg2+ binding, monitored by equilibrium gel filtration in the absence of Ca2+, showed that both mutants bind 1 Mg2+ with KMg = 8 10(4) for PV-CD and 3 x 10(3) M-1 for PV-EF. Compared to the parameters of the parent mutant PVF102W (two sites with equal affinities of 2.7 x 10(7) and 3 x 10(4) M-1 for Ca2+ and Mg2+, respectively), these data indicate that inactivation of the EF site, much more than of the CD site, impairs divalent cation binding. The binding of Ca2+ and Mg2+ is mutually exclusive, indicative of a Ca2+/Mg2+ mixed site. However, as for PVF102W, the KMg values obtained from the competition equation are approximately 40-fold lower than the affinities measured by direct binding. PV-CD/-EF binds neither Ca2+ nor Mg2+. Trp fluorimetry revealed that in the three mutant PVs the residue Trp-102 is deeply buried in the hydrophobic core. (ABSTRACT TRUNCATED AT 250 WORDS)
Teaching Personal and Social Responsibility: Past, Present and Future

During the past decade the field of youth development has grown by leaps and bounds. With this growth have emerged numerous initiatives addressing challenges that many youth face in their community — especially youth living in underserved communities. These initiatives have been guided by a number of various curricular models. This article provides an overview of how the teaching for personal and social responsibility (TPSR) model has evolved. Its birthplace — a gym — is described where things were tried out, ideas tested, and learning about what worked and what did not work took place. Secondly, the present-day applications of the TPSR are examined — its use by a variety of professionals who work with kids in numerous settings (and ways). Finally, the article concludes with an assessment of the TPSR model and its future role in youth development programming. This will include a portrayal of school and community-based programs: their future missions, support and ideological underpinnings. Problems that face society, especially in segments of the underserved, will not go away. Preparing for the future challenges facing youth will require practitioners who view youth as contributors to their community instead of as problems. Such a commitment will interface well with the spirit of TPSR and will certainly be a response to the question: “What is worth doing and what is possible? ”
Cytochromes b561: ascorbate-mediated trans-membrane electron transport.

SIGNIFICANCE Cytochromes b561 (CYB561s) constitute a family of trans-membrane (TM), di-heme proteins, occurring in a variety of organs and cell types, in plants and animals, and using ascorbate (ASC) as an electron donor. CYB561s function as monodehydroascorbate reductase, regenerating ASC, and as Fe³⁺-reductases, providing reduced iron for TM transport. A CYB561-core domain is also associated with dopamine β-monooxygenase redox domains (DOMON) in ubiquitous CYBDOM proteins. In plants, CYBDOMs form large protein families. Physiological functions supported by CYB561s and CYBDOMs include stress defense, cell wall modifications, iron metabolism, tumor suppression, and various neurological processes, including memory retention. CYB561s, therefore, significantly broaden our view on the physiological roles of ASC. RECENT ADVANCES The ubiquitous nature of CYB561s is only recently being recognized. Significant advances have been made through the study of recombinant CYB561s, revealing structural and functional properties of a unique "two-heme four-helix" protein configuration. In addition, the DOMON domains of CYBDOMs are suggested to contain another heme b. CRITICAL ISSUES New CYB561 proteins are still being identified, and there is a need to provide an insight and overview on the various roles of these proteins and their structural properties. FUTURE DIRECTIONS Mutant studies will reveal in greater detail the mechanisms by which CYB561s and CYBDOMs participate in cell metabolism in plants and animals. Moreover, the availability of efficient heterologous expression systems should allow protein crystallization, more detailed (atomic-level) structural information, and insights into the intra-molecular mechanism of electron transport.
The role of high‐field magnetic resonance imaging in parkinsonian disorders: Pushing the boundaries forward

Historically, magnetic resonance imaging (MRI) has contributed little to the study of Parkinson's disease (PD), but modern MRI approaches have unveiled several complementary markers that are useful for research and clinical applications. Iron‐ and neuromelanin‐sensitive MRI detect qualitative changes in the substantia nigra. Quantitative MRI markers can be derived from diffusion weighted and iron‐sensitive imaging or volumetry. Functional brain alterations at rest or during task performance have been captured with functional and arterial spin labeling perfusion MRI. These markers are useful for the diagnosis of PD and atypical parkinsonism, to track disease progression from the premotor stages of these diseases and to better understand the neurobiological basis of clinical deficits. A current research goal using MRI is to generate time‐dependent models of the evolution of PD biomarkers that can help understand neurodegeneration and provide reliable markers for therapeutic trials. This article reviews recent advances in MRI biomarker research at high‐field (3T) and ultra high field‐imaging (7T) in PD and atypical parkinsonism. © 2017 International Parkinson and Movement Disorder Society.
A Holistic Landscape Description Reveals That Landscape Configuration Changes More over Time than Composition: Implications for Landscape Ecology Studies

Background Space-for-time substitution—that is, the assumption that spatial variations of a system can explain and predict the effect of temporal variations—is widely used in ecology. However, it is questionable whether it can validly be used to explain changes in biodiversity over time in response to land-cover changes. Hypothesis Here, we hypothesize that different temporal vs spatial trajectories of landscape composition and configuration may limit space-for-time substitution in landscape ecology. Land-cover conversion changes not just the surface areas given over to particular types of land cover, but also affects isolation, patch size and heterogeneity. This means that a small change in land cover over time may have only minor repercussions on landscape composition but potentially major consequences for landscape configuration. Methods Using land-cover maps of the Paris region for 1982 and 2003, we made a holistic description of the landscape disentangling landscape composition from configuration. After controlling for spatial variations, we analyzed and compared the amplitudes of changes in landscape composition and configuration over time. Results For comparable spatial variations, landscape configuration varied more than twice as much as composition over time. Temporal changes in composition and configuration were not always spatially matched. Significance The fact that landscape composition and configuration do not vary equally in space and time calls into question the use of space-for-time substitution in landscape ecology studies. The instability of landscapes over time appears to be attributable to configurational changes in the main. This may go some way to explaining why the landscape variables that account for changes over time in biodiversity are not the same ones that account for the spatial distribution of biodiversity.
Evaluating the Sources and Functions of Gradiency in Phoneme Categorization: An Individual Differences Approach

During spoken language comprehension listeners transform continuous acoustic cues into categories (e.g., /b/ and /p/). While long-standing research suggests that phonetic categories are activated in a gradient way, there are also clear individual differences in that more gradient categorization has been linked to various communication impairments such as dyslexia and specific language impairments (Joanisse, Manis, Keating, & Seidenberg, 2000; López-Zamora, Luque, Álvarez, & Cobos, 2012; Serniclaes, Van Heghe, Mousty, Carré, & Sprenger-Charolles, 2004; Werker & Tees, 1987). Crucially, most studies have used 2-alternative forced choice (2AFC) tasks to measure the sharpness of between-category boundaries. Here we propose an alternative paradigm that allows us to measure categorization gradiency in a more direct way. Furthermore, we follow an individual differences approach to (a) link this measure of gradiency to multiple cue integration, (b) explore its relationship to a set of other cognitive processes, and (c) evaluate its role in individuals’ ability to perceive speech in noise. Our results provide validation for this new method of assessing phoneme categorization gradiency and offer preliminary insights into how different aspects of speech perception may be linked to each other and to more general cognitive processes.
Endothelial nitric oxide synthase gene variation associated with chronic kidney disease after liver transplant.

OBJECTIVE To identify single nucleotide polymorphisms (SNPs) associated with risk of developing chronic kidney disease (CKD), a prevalent comorbidity, after liver transplant (LT). PATIENTS AND METHODS This study consists of a cohort of adult (> or =18 years) primary-LT recipients who had normal renal function before LT and who survived 1 year or more after LT at a high-volume US LT program between January 1, 1990, and December 31, 2000. Patients with adequate renal function (estimated glomerular filtration rate, > or =40 mL/min per 1.73 m(2) during follow-up; n=308) and patients with incident CKD (estimated glomerular filtration rate, <40 mL/min per 1.73 m(2) after LT; n=92) were identified. To investigate the association of 6 candidate genes with post-LT CKD, we selected SNPs that have been associated with renal function in the literature. Hazard ratios were estimated using Cox regression, adjusted for potential confounding variables. RESULTS The variant allele (298Asp) of the Glu298Asp SNP in the endothelial nitric oxide synthase gene (NOS3) was significantly associated with CKD after LT (P=.05; adjusted for multiple comparisons). The 5-year incidence of CKD was 70% among patients homozygous for the NOS3 variant allele (298Asp) compared with 42% among those not homozygous for the NOS3 variant allele. Specifically, homozygosity for the NOS3 variant allele conferred a 2.5-fold increased risk of developing CKD after LT (P=.005, adjusted for confounding variables). CONCLUSION Homozygosity for the variant allele of NOS3 (298Asp) is associated with CKD after LT and may be useful for identifying recipients at higher risk of post-LT CKD.
microRNA-34a regulates neurite outgrowth, spinal morphology, and function

The p53 family member TAp73 is a transcription factor that plays a key role in many biological processes, including neuronal development. In particular, we have shown that p73 drives the expression of miR-34a, but not miR-34b and c, in mouse cortical neurons. miR-34a in turn modulates the expression of synaptic targets including synaptotagmin-1 and syntaxin-1A. Here we show that this axis is retained in mouse ES cells committed to differentiate toward a neurological phenotype. Moreover, overexpression of miR-34a alters hippocampal spinal morphology, and results in electrophysiological changes consistent with a reduction in spinal function. Therefore, the TAp73/miR-34a axis has functional relevance in primary neurons. These data reinforce a role for miR-34a in neuronal development.
Vastus Medialis Obliquus Atrophy

Background: Quadriceps atrophy and in particular atrophy of the vastus medialis obliquus (VMO) muscle have been frequently related with patellofemoral pain syndrome (PFPS), despite very little objective evidence. Hypothesis: Patients with PFPS exhibit atrophy of the VMO in comparison with healthy controls. Study Design: Case-control study; Level of evidence, 3. Methods: Forty-six patients with PFPS and 30 healthy control persons with similar age, gender, body mass index, and activity index distributions underwent magnetic resonance imaging (MRI) of the quadriceps. The muscle size was determined by calculating the cross-sectional area of the total quadriceps and its components. Results: The cross-sectional area (CSA) of the VMO was significantly smaller in the PFPS group than in the control group (16.67 ± 4.97 cm2 vs 18.36 ± 5.25 cm2) (P = .040). A tendency was noted for a smaller total quadriceps CSA for the PFPS patients at midthigh level (66.99 ± 15.06 cm2 vs 70.83 ± 15.30 cm2) (P = .074). Conclusion: This is the first study to examine VMO size in PFPS patients by MRI. Patients with patellofemoral problems exhibited atrophy of the VMO. Although it is not clear whether this atrophy is a result or a cause of PFPS, the results of this study do show that atrophy of the VMO is a contributing factor in PFPS. Longitudinal, prospective studies are needed to establish the cause-effect relation of VMO atrophy and PFPS.
Description and analysis of the Brno276 system for LRE2011

This paper contains a description of data, systems and fusions developed by the joint team of Brno University of Technology (BUT), Politecnico di Torino (PoliTo) and AGNITIO for the NIST 2011 Language Recognition Evaluation. The primary submission was a fusion of one acoustic and three phonotactic systems, with extensive use of sub-space projections for both approaches. The results are analysed from the view-point of the new NIST measure involving theN = 24 worst language pairs. Some of the results are compared to the MIT-LL submission. As in our previous work, we conclude that having lots of carefully processed data is as important as having good algorithms.
Interpretation of serum antibody response to Anoplocephala perfoliata in relation to parasite burden and faecal egg count.

REASON FOR PERFORMING STUDY Increased knowledge is needed to assist in the interpretation of presently available diagnostic techniques for infection by the tapeworm Anoplocephala perfoliata in horses. HYPOTHESIS The suggested cut-off level of an A. perfoliata specific ELISA may not adequately reflect the actual infection level. Hence, faecal egg counts may be a more useful diagnostic test for individual horses than previously reported. METHODS Eighty-four horses admitted for slaughter at a Danish abattoir were examined for the presence of A. perfoliata. The number of tapeworms, their stage of development and gross pathological mucosal lesions were recorded and compared with serum antibody responses and faecal egg counts. Faecal egg counts were determined in samples from A. perfoliata infected horses using a semi quantitative centrifugation/flotation technique. Blood samples collected at slaughter were analysed by ELISA to determine serum antibody levels against A. perfoliata 12/13 kDa excretory/secretory antigens. RESULTS Macroscopically visible tapeworms were detected in 24 (29%) of the horses. The overall sensitivity of the faecal egg count was found to be 0.46; however, if the detection limit was increased to above 20 tapeworms, sensitivity increased to 0.89. There was a correlation of 0.71 between worm burden and egg count. The antibody levels correlated significantly with infection intensity despite a wide variation among horses with similar levels of infection. The optimal cut-off value was determined using receiver operating characteristic analysis. If cut-off was chosen at optical density (OD) = 0.7, sensitivity was 0.68 and specificity 0.71. CONCLUSIONS Both diagnostic methods were capable of revealing potentially pathogenic infections, with the faecal egg count being more applicable on the individual horse level. POTENTIAL RELEVANCE In the population of Danish horses investigated the serum ELISA test should be interpreted such that horses in need of anti-Anoplocephala treatment have an OD = 0.7 or above.
Neural relevance-aware query modeling for spoken document retrieval

Spoken document retrieval (SDR) is becoming a much-needed application due to that unprecedented volumes of audio-visual media have been made available in our daily life. As far as we are aware, most of the wide variety of SDR methods mainly focus on exploring robust indexing and effective retrieval methods to quantify the relevance degree between a pair of query and document. However, similar to information retrieval (IR), a fundamental challenge facing SDR is that a query is usually too short to convey a user's information need, such that a retrieval system cannot always achieve prospective efficacy when with the existing retrieval methods. In order to further boost retrieval performance, several studies turn their attention to reformulating the original query by leveraging an online pseudo-relevance feedback (PRF) process, which often comes at the price of taking significant time. Motivated by these observations, this paper presents a novel extension of the general line of SDR research and its contribution is at least two-fold. First, building on neural network-based techniques, we put forward a neural relevance-aware query modeling (NRM) framework, which is designed to not only infer a discriminative query language model automatically for a given query, but also get around the time-consuming PRF process. Second, the utility of the methods instantiated from our proposed framework and several widely-used retrieval methods are extensively analyzed and compared on a standard SDR task, which suggests the superiority of our methods.
The Interactive Influence of Cannabis-Related Negative Expectancies and Coping Motives on Cannabis Use Behavior and Problems

ABSTRACT Objectives: The present study tested whether coping motives for cannabis use moderate the effect of negative expectancies on cannabis use. Methods: Participants were 149 (36.2% female, 61.59% non-Hispanic Caucasian) current cannabis users aged 18-36 (M = 21.01, SD = 3.09) who completed measures of cannabis-related expectancies and motives for use. Hierarchical multiple regressions were employed to investigate the predictive value of the interaction between negative expectancies and coping motives on cannabis use outcomes. Results: Results revealed interactions between negative expectancies and coping motives with respect to past 90 day cannabis use frequency and cannabis problems. Global negative effects expectancies were associated with less frequent cannabis use, particularly among those with fewer coping motives. However, negative expectancies were related to more cannabis problems, particularly among those with higher coping motives. Conclusions: These results suggest it may be advisable to take coping motives into account when addressing expectancies among cannabis users.