Miracle-dz/UniFAR-FTUs huggingface dataset:
A dynamic hydrophobic core orchestrates allostery in protein kinases

The synchronized motions of inner core residues allosterically modulate the activity of the protein kinase A catalytic subunit. Eukaryotic protein kinases (EPKs) constitute a class of allosteric switches that mediate a myriad of signaling events. It has been postulated that EPKs’ active and inactive states depend on the structural architecture of their hydrophobic cores, organized around two highly conserved spines: C-spine and R-spine. How the spines orchestrate the transition of the enzyme between catalytically uncommitted and committed states remains elusive. Using relaxation dispersion nuclear magnetic resonance spectroscopy, we found that the hydrophobic core of the catalytic subunit of protein kinase A, a prototypical and ubiquitous EPK, moves synchronously to poise the C subunit for catalysis in response to binding adenosine 5′-triphosphate. In addition to completing the C-spine, the adenine ring fuses the β structures of the N-lobe and the C-lobe. Additional residues that bridge the two spines (I150 and V104) are revealed as part of the correlated hydrophobic network; their importance was validated by mutagenesis, which led to inactivation. Because the hydrophobic architecture of the catalytic core is conserved throughout the EPK superfamily, the present study suggests a universal mechanism for dynamically driven allosteric activation of kinases mediated by coordinated signal transmission through ordered motifs in their hydrophobic cores.
Automating statistics management for query optimizers

Statistics play a key role in influencing the quality of plans chosen by a database query optimizer. We identify the statistics that are essential for an optimizer. We introduce novel techniques that help significantly reduce the set of statistics that need to be created without sacrificing the quality of query plans generated. We discuss how these techniques can be leveraged to automate statistics management in databases. We have implemented and experimentally evaluated our approach on Microsoft SQL Server 7.0.
Renal resistive index in addition to low-grade albuminuria complements screening for target organ damage in therapy-resistant hypertension

Objective We examined the value of renal resistive index (RRI) for prevalence of cardiovascular target organ damage in therapy-resistant hypertension in comparison to low-grade albuminuria. Methods Eighty-four patients with therapy-resistant hypertension (age 59.7 ± 8.1 years) were screened for cardiovascular target organ damage with coronary computed tomography, cardiac magnetic resonance imaging (MRI), Doppler sonography for the assessment of carotid intima media thickness and, RRI, pulse wave velocity and for low-grade albuminuria of at least 10 mg/day in men and 15 mg/day in women, respectively. Results In patients with RRI greater than 0.7 pulse wave velocity (11.6 ± 3.7 vs. 9.8 ± 2.2 m/s; P = 0.02) intima media thickness (0.85 ± 0.09 vs. 0.76 ± 0.1 mm; P = 0.007) and Agatston score of coronary calcification (640 ± 915 vs. 129 ± 256; P = 0.05) were increased, whereas left ventricular mass (127 ± 24.5 vs. 125 ± 15.0 g; P = 0.70) was similar between the two groups. When patients were categorized according to low-grade albuminuria left ventricular mass was significantly higher in those with low-grade albuminuria (123 ± 25.8 vs. 135 ± 15.7 g; P = 0.01), whereas vascular parameters (intima media thickness, Agatston score, pulse wave velocity) did not differ between the two groups. Conclusion In patients with therapy-resistant hypertension RRI reflects functional and structural vascular parameters, whereas low-grade albuminuria is related to cardiac structural changes. Thus, measurement of RRI in addition to low-grade albuminuria complements screening for target organ damage in therapy-resistant hypertension.
Interest in Rhinoplasty and Awareness about its Postoperative Complications Among Female high School Students

Introduction: Rhinoplasty is a popular cosmetic surgical procedure. Informal statistics show that Iran has one of the highest rates of rhinoplasty in the world. However, rhinoplasty like any other surgery can have complications. Materials and Methods: In this cross-sectional study, 320 female students were selected by multistage cluster-stratified sampling from high schools in Kerman, Iran and each completed a questionnaire. Results: More than half of the students said they would like to undergo rhinoplasty. The main reasons for wanting rhinoplasty were beauty and because it is fashionable. However, more than half of the interested students did not know about the possible postoperative complications of rhinoplasty. There was no relation between interest in having rhinoplasty and parents’ education, city of birth or economic status. Conclusion: Many teenagers are interested in having rhinoplasty in Iran. As the number of teenagers and young adults who choose to have cosmetic surgery increases, surgeons should consider their expectations, motivations and awareness of postoperative complications before surgery.
Human T Lymphotropic Virus Type 1 Increases T Lymphocyte Migration by Recruiting the Cytoskeleton Organizer CRMP2

Recruitment of virus-infected T lymphocytes into the CNS is an essential step in the development of virus-associated neuroinflammatory diseases, notably myelopathy induced by retrovirus human T leukemia virus-1 (HTLV-1). We have recently shown the key role of collapsin response mediator protein 2 (CRMP2), a phosphoprotein involved in cytoskeleton rearrangement, in the control of human lymphocyte migration and in brain targeting in animal models of virus-induced neuroinflammation. Using lymphocytes cloned from infected patients and chronically infected T cells, we found that HTLV-1 affects CRMP2 activity, resulting in an increased migratory potential. Elevated CRMP2 expression accompanies a higher phosphorylation level of CRMP2 and its more pronounced adhesion to tubulin and actin. CRMP2 forms, a full length and a shorter, cleaved one, are also affected. Tax transfection and extinction strategies show the involvement of this viral protein in enhanced full-length and active CRMP2, resulting in prominent migratory rate. A role for other viral proteins in CRMP2 phosphorylation is suspected. Full-length CRMP2 confers a migratory advantage possibly by preempting the negative effect of short CRMP2 we observe on T lymphocyte migration. In addition, HTLV-1–induced migration seems, in part, supported by the ability of infected cell to increase the proteosomal degradation of short CRMP2. Finally, gene expression in CD69+ cells selected from patients suggests that HTLV-1 has the capacity to influence the CRMP2/PI3K/Akt axis thus to positively control cytoskeleton organization and lymphocyte migration. Our data provide an additional clue to understanding the infiltration of HTLV-1–infected lymphocytes into various tissues and suggest that the regulation of CRMP2 activity by virus infection is a novel aspect of neuroinflammation.
Tetra- and Penta-Acylated Lipid A Structures of Porphyromonas gingivalis LPS Differentially Activate TLR4-Mediated NF-κB Signal Transduction Cascade and Immuno-Inflammatory Response in Human Gingival Fibroblasts

Background Porphyromonas gingivalis is a major pathogen of periodontal disease that affects a majority of adults worldwide. Increasing evidence shows that periodontal disease is linked to various systemic diseases like diabetes and cardiovascular disease, by contributing to increased systemic levels of inflammation. Lipopolysaccharides (LPS), as a key virulent attribute of P. gingivalis, possesses significant amount of lipid A heterogeneity containing tetra- (LPS1435/1449) and penta-acylated (LPS1690) structures. Hitherto, the exact molecular mechanism of P. gingivalis LPS involved in periodontal pathogenesis remains unclear, due to limited understanding of the specific receptors and signaling pathways involved in LPS-host cell interactions. Methodology/Principal Findings This study systematically investigated the effects of P. gingivalis LPS1435/1449 and LPS1690 on the expression of TLR2 and TLR4 signal transduction and the activation of pro-inflammatory cytokines IL-6 and IL-8 in human gingival fibroblasts (HGFs). We found that LPS1435/1449 and LPS1690 differentially modulated TLR2 and TLR4 expression. NF-κB pathway was significantly activated by LPS1690 but not by LPS1435/1449. In addition, LPS1690 induced significant expression of NF-κB and p38 MPAK pathways-related genes, such as NFKBIA, NFKB1, IKBKB, MAP2K4 and MAPK8. Notably, the pro-inflammatory genes including GM-CSF, CXCL10, G-CSF, IL-6, IL-8 and CCL2 were significantly upregulated by LPS1690 while down-regulated by LPS1435/1449. Blocking assays confirmed that TLR4-mediated NF-κB signaling was vital in LPS1690-induced expression of IL-6 and IL-8 in HGFs. Conclusions/Significance The present study suggests that the tetra- and penta-acylated lipid A structures of P. gingivalis LPS differentially activate TLR4-mediated NF-κB signaling pathway, and significantly modulate the expression of IL-6 and IL-8 in HGFs. The ability to alter the lipid A structure of LPS could be one of the strategies carried-out by P. gingivalis to evade innate host defense in gingival tissues, thereby contributing to periodontal pathogenesis.
HSP-HMMER: a tool for protein domain identification on a large scale

HMMER is arguably the best tool for protein domain identification, which is essential for biological function prediction. There are many software and hardware enhancements of HMMER; however, most of them are not scalable to a large number of processors. The exponential growth of the number of protein sequences in public databases, which is currently set at more than 13 million, demands the use of HMMER on a very large scale. We have developed a highly scalable parallel (HSP) HMMER approach that enables identification of conserved functional domains in millions of proteins in less than a day using thousands of processing nodes on a supercomputer.
AXIN 2 Polymorphisms , the β-Catenin Destruction Complex Expression Profile and Breast Cancer Susceptibility

Breast cancer is one of the most common diseases suffered by women around the world, with an estimated 990,000 new cases and 375,000 deaths each year (Brito et al., 2009). In the last report of IARC (International Agency for Research on Cancer), for 2030 there will be 27 million new cases of cancer diagnosed in the world, 75 million people will have the disease and 17 million will die each year. In Brazil, breast cancer is among the most important cause of death since 1979 (Brito et al., 2009). In 2014, new cases were 49,400, with an estimated risk of 50.1 cases for every 100,000 women. Breast cancer is considered the most common cancer on the population, accounting for 28% of new cancer patients, furthermore, is the seventh leading cause of death in Brazil after vascular disease and diabetes, overcoming the other cancers, and it is responsible of 2.3% of deaths in the country (INCA, 2014), considered as a public health problem and classified as an epidemic. High mortality is caused by its capacity to generate metastasis, being the main targets lung, liver and bone (Teixeira et al., 2009; Santos et al., 2010). Breast
Antiviral effect of cationic compounds on bacteriophages

The antiviral activity of several cationic compounds – cetyltrimethylammonium bromide (CTAB), chitosan, nisin, and lysozyme – was investigated on the bacteriophage c2 (DNA head and non-contractile tail) infecting Lactococcus strains and the bacteriophage MS2 (F-specific RNA) infecting E. coli. Firstly, these activities were evaluated in a phosphate buffer pH 7 – 10 mM. The CTAB had a virucidal effect on the Lactococcus bacteriophages, but not on the MS2. After 1 min of contact with 0.125 mM CTAB, the c2 population was reduced from 6 to 1.5 log(pfu)/mL and completely deactivated at 1 mM. On the contrary, chitosan inhibited the MS2 more than it did the bacteriophages c2. No antiviral effect was observed for the nisin or the lysozyme on bacteriophages after 1 min of treatment. A 1 and 2.5 log reduction was respectively observed for nisin and lysozyme when the treatment time increased (5 or 10 min). These results showed that the antiviral effect depended both on the virus and structure of the antimicrobial compounds. The antiviral activity of these compounds was also evaluated in different physico-chemical conditions and in complex matrices. The antiviral activity of CTAB was impaired in acid pH and with an increase of the ionic strength. These results might be explained by the electrostatic interactions between cationic compounds and negatively charged particles such as bacteriophages or other compounds in a matrix. Milk proved to be protective suggesting the components of food could interfere with antimicrobial compounds.
An Evaluation of Dose Equivalence between Synchrotron Microbeam Radiation Therapy and Conventional Broadbeam Radiation Using Clonogenic and Cell Impedance Assays

Background High-dose synchrotron microbeam radiation therapy (MRT) has shown the potential to deliver improved outcomes over conventional broadbeam (BB) radiation therapy. To implement synchrotron MRT clinically for cancer treatment, it is necessary to undertake dose equivalence studies to identify MRT doses that give similar outcomes to BB treatments. Aim To develop an in vitro approach to determine biological dose equivalence between MRT and BB using two different cell-based assays. Methods The acute response of tumour and normal cell lines (EMT6.5, 4T1.2, NMuMG, EMT6.5ch, 4T1ch5, SaOS-2) to MRT (50–560 Gy) and BB (1.5–10 Gy) irradiation was investigated using clonogenic and real time cell impedance sensing (RT-CIS)/xCELLigence assays. MRT was performed using a lattice of 25 or 50 µm-wide planar, polychromatic kilovoltage X-ray microbeams with 200 µm peak separation. BB irradiations were performed using a Co60 teletherapy unit or a synchrotron radiation source. BB doses that would generate biological responses similar to MRT were calculated by data interpolation and verified by clonogenic and RT-CIS assays. Results For a given cell line, MRT equivalent BB doses identified by RT-CIS/xCELLigence were similar to those identified by clonogenic assays. Dose equivalence between MRT and BB were verified in vitro in two cell lines; EMT6.5ch and SaOS-2 by clonogenic assays and RT-CIS/xCELLigence. We found for example, that BB doses of 3.4±0.1 Gy and 4.40±0.04 Gy were radiobiologically equivalent to a peak, microbeam dose of 112 Gy using clonogenic and RT-CIS assays respectively on EMT6.5ch cells. Conclusion Our data provides the first determination of biological dose equivalence between BB and MRT modalities for different cell lines and identifies RT-CIS/xCELLigence assays as a suitable substitute for clonogenic assays. These results will be useful for the safe selection of MRT doses for future veterinary and clinical trials.
Efficient Fault Diagnosis Schemes for Reliable Lightweight Cryptographic ISO/IEC Standard CLEFIA Benchmarked on ASIC and FPGA

Lightweight block ciphers are essential for providing low-cost confidentiality to sensitive constrained applications. Nonetheless, this confidentiality does not guarantee their reliability in the presence of natural and malicious faults. In this paper, fault diagnosis schemes for the lightweight internationally standardized block cipher CLEFIA are proposed. This symmetric-key cipher is compatible with yet lighter in hardware than the Advanced Encryption Standard and enables the implementation of cryptographic functionality with low complexity and power consumption. To the best of the authors' knowledge, there has been no fault diagnosis scheme presented in the literature for the CLEFIA to date. In addition to providing fault diagnosis approaches for the linear blocks in the encryption and the decryption of the CLEFIA, error detection approaches are presented for the nonlinear S-boxes, applicable to their composite-field implementations as well as their lookup table realizations. Through fault-injection simulations, the proposed schemes are benchmarked, and it is shown that they achieve error coverage of close to 100%. Finally, both application-specific integrated circuit and field-programmable gate array implementations of the proposed error detection structures are presented to assess their efficiency and overhead. The proposed fault diagnosis architectures make the implementations of the International Organization for Standardization/International Electrotechnical Commission-standardized CLEFIA more reliable.
Characterization and Expression of Netrin-1 and Its Receptors UNC5B and DCC in Human Placenta

Netrins are a family of proteins that mediate axonal guidance in the central nervous system (CNS). In addition to the CNS, netrins are involved in cell adhesion, motility, proliferation, differentiation, and survival. Because these processes occur in the placenta, we raised the question of whether netrin-1 is expressed by placental cells during development. In the present study, we analyzed the spatial and temporal distribution of netrin-1 and its two receptors, DCC (deleted in colorectal cancer) and UNC5B (uncoordinated-5 homolog) in human placenta using RT-PCR, Western blotting, and immunohistochemistry analysis. We demonstrated the presence of the proteins and transcripts of netrin-1 and its receptors in placenta and cytotrophoblasts. Furthermore, using immunohistochemistry, we localized endogenous netrin-1 protein staining to villous and extravillous cytotrophoblasts, and secreted netrin-1 outside the syncytiotrophoblasts. The DCC receptor was localized to syncytiotrophoblasts and invasive extravillous cytotrophoblasts during the first trimester and at term. On the other hand, the UNC5B receptor was localized to villous and extravillous cytotrophoblasts proximal to anchoring areas during the first trimester. At term, UNC5B was observed in decidual cells and weakly in extravillous cells. The discrete pattern of netrin-1 and netrin-1 receptor distribution suggested that netrin-1 protein functions might vary with its localization in the placenta and probably with time of gestation.
Nutritive value of some improved varieties of legumes.

The nutritional quality of some improved varieties of chick peas (Cicer arietinum), mash beans (Phaseolus mungo), mung beans (Phaseolus aureus) and cow peas (Vigna sinensis), grown in Pakistan, was measured chemically (including amino acid analyses) and biologically in N-balance experiments with growing rats. Lysine and total sulphur amino acids were lowered in varieties with a higher content of protein. The true protein digestibility (TD), biological value (BV) and net protein utilisation (NPU) of different varieties of chick peas, mung beans and cow peas varied between 85–89, 83–85 and 87–92%, 62–69, 54–56 and 55–59% and 55–60, 45–48 and 50–51%, respectively. The TD of protein was highest (89%) in chick peas, 6560 having a higher protein content (29.4%) while its BV was lowest (62%) as compared to the other varieties of chick peas. There was a significant correlation (r=0.97) between BV and the total sulphur containing amino acids and BV could be predicted from the regression equation; BV (%)= 33.03 + 10.56x methionine+cystine (g per 16 g N). This indicates that methionine+cystine are the first limiting amino acids in these varieties. Tannin content does not seem to affect the TD of mash and mung beans.
Population structuring of the tsetse Glossina tachinoides resulting from landscape fragmentation in the Mouhoun River basin, Burkina Faso

The impact of landscape fragmentation resulting from human‐ and climate‐mediated factors on the structure of a population of Glossina tachinoides Westwood (Diptera: Glossinidae) in the Mouhoun River basin, Burkina Faso, was investigated. Allele frequencies at five microsatellite loci were compared in four populations. The average distance between samples was 72 km. The sampling points traversed an ecological cline in terms of rainfall and riverine forest ecotype, along a river loop that enlarged from upstream to downstream. Microsatellite DNA demonstrated no structuring among the groups studied (FST = 0.015, P = 0.07), which is contrary to findings pertaining to Glossina palpalis gambiensis Vanderplank in the same geographical area. The populations of G. tachinoides showed complete panmixia (FIS = 0, P = 0.5 for the whole sample) and no genetic differentiation among populations or global positioning system trap locations. This is in line with the results of dispersal studies which indicated higher diffusion coefficients for G. tachinoides than for G. p. gambiensis. The impact of these findings is discussed within the framework of control campaigns currently promoted by the Pan African Tsetse and Trypanosomosis Eradication Campaign.
Experimental evaluation of lifetime bounds for wireless sensor networks

In this paper we present a method for experimental lifetime measurements of sensor networks. Despite the importance of experimental validation, none of the lifetime models proposed so far has been validated experimentally. One of the reasons for the absence of practical validations might be the long lifetime of batteries which make the validation of the proposed models non-trivial and time consuming. Our solution enables validation of lifetime models within a reasonable amount of time. We also use our method to validate a simple mathematical model that provides bounds on the lifetime of sensor networks.
Recovery Trends in Marine Mammal Populations

Marine mammals have greatly benefitted from a shift from resource exploitation towards conservation. Often lauded as symbols of conservation success, some marine mammal populations have shown remarkable recoveries after severe depletions. Others have remained at low abundance levels, continued to decline, or become extinct or extirpated. Here we provide a quantitative assessment of (1) publicly available population-level abundance data for marine mammals worldwide, (2) abundance trends and recovery status, and (3) historic population decline and recent recovery. We compiled 182 population abundance time series for 47 species and identified major data gaps. In order to compare across the largest possible set of time series with varying data quality, quantity and frequency, we considered an increase in population abundance as evidence of recovery. Using robust log-linear regression over three generations, we were able to classify abundance trends for 92 spatially non-overlapping populations as Significantly Increasing (42%), Significantly Decreasing (10%), Non-Significant Change (28%) and Unknown (20%). Our results were comparable to IUCN classifications for equivalent species. Among different groupings, pinnipeds and other marine mammals (sirenians, polar bears and otters) showed the highest proportion of recovering populations, likely benefiting from relatively fast life histories and nearshore habitats that provided visibility and protective management measures. Recovery was less frequent among cetaceans, but more common in coastal than offshore populations. For marine mammals with available historical abundance estimates (n = 47), larger historical population declines were associated with low or variable recent recoveries so far. Overall, our results show that many formerly depleted marine mammal populations are recovering. However, data-deficient populations and those with decreasing and non-significant trends require attention. In particular, increased study of populations with major data gaps, including offshore small cetaceans, cryptic species, and marine mammals in low latitudes and developing nations, is needed to better understand the status of marine mammal populations worldwide.