Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal structure of ovine interferon-tau at 2.1 A resolution.

Ovine interferon-tau (ovIFN-tau) is a pregnancy recognition hormone required for normal embryonic development in sheep. In addition to its novel role in reproductive physiology, ovIFN-tau displays antiviral and antiproliferative activities similar to the IFN-alpha subtypes. To probe the structural basis for its unique activity profile, the crystal structure of ovIFN-tau has been determined at 2.1 A resolution. The fold of ovIFN-tau is similar to the previously determined crystal structures of human IFN-alpha2b and human and murine IFN-beta, which each contain five alpha-helices. Comparison of ovIFN-tau with huIFN-alpha2b, huIFN-beta, and muIFN-beta reveals unexpected structural differences that occur in regions of considerable sequence identity. Specifically, main-chain differences up to 11 A occur for residues in helix A, the AB loop, helix B, and the BC loop. Furthermore, these regions are known to be important for receptor binding and biological activity. Of particular interest, a buried ion pair is observed in ovIFN-tau between Glu71 and Arg145 which displaces a conserved tryptophan residue (Trp77) from the helical bundle core. This ion pair represents a major change in the core of ovIFN-tau compared to huIFN-alpha2b. Based on amino acid sequence comparisons, these ovIFN-tau structural features may be conserved in several human IFN-alpha subtypes and IFN-omega. The structure identifies potential problems in interpreting site-directed mutagenesis data on the human IFN-alpha family that consists of 12 proteins.
A Randomized, Controlled, Double-Blind Crossover Study on the Effects of 2-L Infusions of 0.9% Saline and Plasma-Lyte® 148 on Renal Blood Flow Velocity and Renal Cortical Tissue Perfusion in Healthy Volunteers

Objective: We compared the effects of intravenous infusions of 0.9% saline ([Cl−] 154 mmol/L) and Plasma-Lyte 148 ([Cl−] 98 mmol/L, Baxter Healthcare) on renal blood flow velocity and perfusion in humans using magnetic resonance imaging (MRI). Background: Animal experiments suggest that hyperchloremia resulting from 0.9% saline infusion may affect renal hemodynamics adversely, a phenomenon not studied in humans. Methods: Twelve healthy adult male subjects received 2-L intravenous infusions over 1 hour of 0.9% saline or Plasma-Lyte 148 in a randomized, double-blind manner. Crossover studies were performed 7 to 10 days apart. MRI scanning proceeded for 90 minutes after commencement of infusion to measure renal artery blood flow velocity and renal cortical perfusion. Blood was sampled and weight recorded hourly for 4 hours. Results: Sustained hyperchloremia was seen with saline but not with Plasma-Lyte 148 (P < 0.0001), and fall in strong ion difference was greater with the former (P = 0.025). Blood volume changes were identical (P = 0.867), but there was greater expansion of the extravascular fluid volume after saline (P = 0.029). There was a significant reduction in mean renal artery flow velocity (P = 0.045) and renal cortical tissue perfusion (P = 0.008) from baseline after saline, but not after Plasma-Lyte 148. There was no difference in concentrations of urinary neutrophil gelatinase–associated lipocalin after the 2 infusions (P = 0.917). Conclusions: This is the first human study to demonstrate that intravenous infusion of 0.9% saline results in reductions in renal blood flow velocity and renal cortical tissue perfusion. This has implications for intravenous fluid therapy in perioperative and critically ill patients. NCT01087853
On implementing Chordal ring structures using Genetic Algorithm and Simulated Annealing

The paper presents an implementation analysis of Chordal ring structures using two modern heuristics namely Simulated Annealing and Genetic Algorithm. In recent years Chordal rings gained a lot of interest for physical topology of the next generation large-scale network infrastructure. Degree 3 Chordal ring structures possess small diameters, low average distances and easy routing schemes. For the implementation a case study of North Jutland has been considered as a test subject. When comparing the performance among the two employed heuristics, in our case, simulated annealing algorithm performs much better in an approximately equal run time. But if the run time is little more allowed then genetic algorithms tends to performs better.
High frequency modeling method of EMI filters

This paper deals with a high frequency modeling method of the common and differential mode inductors used in EMI filters. These filters are intended to reduce conducted emissions generated by power static converters towards power network. To model the EMI filters, it is necessary to identify the various parameters of the passive elements: inductors and capacitors. Because of their major impact on filter efficiency, these elements must be identified with accuracy. In this study, high frequency model of common mode coupled inductors is proposed. Simulation results of the proposed model are compared to the experimental data obtained using the specific experimental setup. These results made it possible to validate the proposed filter model and its robustness in a frequency range varying from 9 kHz to 30 MHz. The proposed high frequency inductor models will be very helpful for design optimization of EMI filters, since the high frequency behaviour of the filter mainly depends on magnetic materials used and on the geometrical characteristics of winding.
The cost-efficient, full ZVS range hybrid full-bridge-half-bridge family with shared lagging leg: Topology derivation, optimization design and experimental results

This paper focuses on a new dc-dc family, in which the lagging leg of a phase-shifted full bridge (PSFB) converter is also used to structure a new half bridge (HB) branch. Such a shared-lagging-leg (SLL) concept not only extends the ZVS range of lagging leg, but also provides another energy path for possible function extension, such as efficiency improvement and dynamical enhancement. In this paper, the existent SLL converters are reviewed and the general derivation of the SLL family is given, the ZVS feature in the SLL is analyzed and the possible improvements are presented. Finally, a new SLL converter integrating a current-driven PSFB and a LC resonant half bridge structures are proposed. The proposed SLL converter preserves all the advantages of its PSFB and HB counterparts, but eliminates their drawbacks, i.e., it has the minimal component amount, achieves the full ZVS range in the legs, eliminates the circle current and gets fully regulation in the output. The aforementioned analysis and design are also verified by the experimental results.
The collateral liquidity problem in contemporary finance and the resurrection of quantity theory

Since the 2008 crisis, the liquidity of collateral has become a serious concern for financial market institutions and regulators due to its increased importance in risk and cash flow management. Surprisingly, market participants mobilize old-fashioned economic theory, such as Irving Fisher’s quantity theory of money in their discussions of how to deal with the new problems of collateral liquidity. Today, ‘collateral is the new cash’, as one sector report claims, marking a shift from a quantity theory of money to one of collateral. Liquidity, I argue, poses not only practical problems to market participants and regulators, but also epistemic ones. Accordingly, practitioners not only produce practical but also theoretical responses to it, mobilizing classical economic theory in so doing. The problem of liquidity is shown to relate closely to a problem of ‘sovereignty’ in the narrow sense of guaranteeing the safe value of collateral. Contrary to established conceptions, sovereignty in this sense is not limited to states, but can also occur with monopolistic agents in the market such as global custodians. Thus, following the recent decade of crisis, general epistemic problems of liquidity and sovereignty in contemporary finance become visible through the practical problems and solutions in relation to collateral – specifically in the practical problems of buttressing liquidity in its double nature of collateral velocity and quality or safety.
COMPETITIVE BALANCE IN FOOTBALL: A COMPARATIVE STUDY BETWEEN BRAZIL AND THE MAIN EUROPEAN LEAGUES (2003-2016)

The present study compared the competitive balance (CB) of Brazilian professional football with those of Germany, Spain, France, England, Italy and Portugal first division leagues, between the period from 2003/2004 to 2016/2017. In addition, a trend line of the period and the overall effect was analysed. The CB was measured by the concentration of points by the first four teams placed in the final standings (C4ICB). Descriptive values showed that the competitions were not fully balanced (i.e. C4ICB> 100). (Md= 145, 148, 148, 152 and 155, respectively, p<0.05), with no differences for France (Md= 140), compared to Germany, Spain, Italy, England and Portugal (Md= 140, p> 0.05). The CB trend lines for Spain, Portugal and the overall effect were significant and showed a decline in the period (p <0.05). There was more stable behavior for Brazil and Italy, observing tendencies to significant models for the increments in the German and French leagues and a reduction in the CB in the English league. It is concluded that the Brazilian league was the most balanced in this period. Globally, there has been a growing inequality in these leagues, which may implicate in the success and attractiveness of the leagues in the future.
An NMR magnetic field meter for measuring high fields at liquid-helium temperatures

A nuclear-magnetic-resonance (NMR) magnetic field meter suitable for measuring high fields at liquid-helium temperatures is described. A continuous measurement range from 1 to 11 T with a probe rod of 1.7 m in length is obtained without changing the sample coil in the cryostat by means of a novel approach called the suppression method. The ratio of NMR signal to noise is increased by biasing the marginal oscillator into the hard state.
Evidence for a Holin-Like Protein Gene Fully Embedded Out of Frame in the Endolysin Gene of Staphylococcus aureusBacteriophage 187

ABSTRACT We have cloned, sequenced, and characterized the genes encoding the lytic system of the unique Staphylococcus aureus phage 187. The endolysin gene ply187 encodes a large cell wall-lytic enzyme (71.6 kDa). The catalytic site, responsible for the hydrolysis of staphylococcal peptidoglycan, was mapped to the N-terminal domain of the protein by the expression of defined ply187 domains. This enzymatically active N terminus showed convincing amino acid sequence homology to anN-acetylmuramoyl-l-alanine amidase, whereas the C-terminal part, whose function is unknown, revealed striking relatedness to major staphylococcal autolysins. An additional reading frame was identified entirely embedded out of frame (+1) within the 5′ region of ply187 and was shown to encode a small, hydrophobic protein of holin-like function. The hol187 gene features a dual-start motif, possibly enabling the synthesis of two products of different lengths (57 and 55 amino acids, respectively). Overproduction of Hol187 in Escherichia coli resulted in growth retardation, leakiness of the cytoplasmic membrane, and loss of de novo ATP synthesis. Compared to other holins identified to date, Hol187 completely lacks the highly charged C terminus. The secondary structure of the polypeptide is predicted to consist of two small, antiparallel, hydrophobic, transmembrane helices. These are supposed to be essential for integration into the membrane, since site-specific introduction of negatively charged amino acids into the first transmembrane domain (V7D G8D) completely abolished the function of the Hol187 polypeptide. With antibodies raised against a synthetic 18-mer peptide representing a central part of the protein, it was possible to detect Hol187 in the cytoplasmic membrane of phage-infected S. aureus cells. An important indication that the protein actually functions as a holin in vivo was that the gene (but not the V7D G8D mutation) was able to complement a phage λ Sam mutation in a nonsuppressing E. coli HB101 background. Plaque formation by λgt11::hol187 indicated that both phage genes have analogous functions. The data presented here indicate that a putative holin is encoded on a different reading frame within the enzymatically active domain of ply187 and that the holin is synthesized during the late stage of phage infection and found in the cytoplasmic membrane, where it causes membrane lesions which are thought to enable access of Ply187 to the peptidoglycan of phage-infected Staphylococcus cells.
Influence of Nanoencapsulation on Human Skin Transport of Flufenamic Acid

The effect of the inclusion of flufenamic acid in poly(lactide-co-glycolide) nanoparticles on the transport of flufenamic acid into excised human skin was investigated. Penetration and permeation data were acquired using two different in vitro test systems: the Saarbrücken penetration model, where the skin acts as its own receptor medium, and the Franz diffusion cell, where the receptor medium is a buffer solution. For the stratum corneum, no differences were found between nanoencapsulated and free drug. Drug accumulation in the deeper skin layers and drug transport across human epidermis were slightly delayed for the nanoencapsulated drug compared to the free drug after shorter incubation times (<12 h). In contrast, after longer incubation times (>12 h), the nanoencapsulated drug showed a statistically significantly enhanced transport and accumulation (p < 0.05). Additionally, nanoencapsulated flufenamic acid was visualized by multiphoton fluorescence microscopy. Particles were found homogeneously distributed on the skin surface and within the dermatoglyphs, but no nanoparticles were detected within or between the corneocytes.
Topology prediction of membrane proteins

A new method is described for prediction of protein membrane topology (intra‐ and extracellular sidedness) from multiply aligned amino acid sequences after determination of the membrane‐spanning segments. The prediction technique relies on residue compositional differences in the protein segments exposed at each side of the membrane. Intra/extracellular ratios are calculated for the residue types Asn, Asp, Gly, Phe, Pro, Trp, Tyr, and Val, preferably found on the extracellular side, and for Ala, Arg, Cys, and Lys, mostly occurring on the intracellular side. The consensus over these 12 residue distributions is used for sidedness prediction. The method was developed with a test set of 42 protein families, for which all but one were correctly predicted with the new algorithm. This represents an improvement over predictions based on the widely used “positive‐inside rule” and other techniques, where at least six mispredictions were observed for the same data set. Further, application of this and other methods to 12 protein families not in the test set still showed the better performance of the present technique, which was subsequently applied to another set of membrane protein families where the topology has yet to be determined.
Cancer risk assessment by rural and Appalachian family medicine physicians.

CONTEXT Challenges to the identification of hereditary cancer in primary care may be more pronounced in rural Appalachia, a medically underserved region. PURPOSE To examine primary care physicians' identification of hereditary cancers. METHODS A cross-sectional survey was mailed to family physicians in the midwestern and southeastern United States, stratified by rural/non-rural and Appalachian/non-Appalachian practice location (n = 176). Identification of hereditary breast-ovarian cancer (BRCA1/2), hereditary non-polyposis colon cancer (HNPCC), and other hereditary cancers was assessed. FINDINGS Less than half of physicians (45%) reported having patients with cancer genetic testing. Most (70%) correctly identified the BRCA1/2-relevant scenario; 49% correctly identified the HNPCC-relevant scenario. Factor analysis of psychosocial variables revealed 2 factors: Confidence (knowledge, comfort, confidence) and importance (responsible, important, effective, need) of identifying hereditary cancer. Greater confidence was associated with use of 3 generation pedigree in taking family history. Greater knowledge and access to genetic services were associated with use of genetic testing. More recent graduation year, greater knowledge, and greater confidence were associated with identifying the BRCA1/2-relevant scenario. Greater knowledge and confidence were associated with identifying the HNPCC-relevant scenario. CONCLUSIONS Though rural Appalachian physicians do not differ in ability to identify high risk individuals, access barriers may exist for genetic testing. Interventions are needed to boost physician confidence in identifying hereditary cancer and to improve availability and awareness of availability of genetic services.
Type 2 diabetes risk variants and colorectal cancer risk: the Multiethnic Cohort and PAGE studies

Background Diabetes has been positively associated with the risk of colorectal cancer. This study investigated whether recently established risk variants for diabetes also have effects on colorectal cancer. Methods 19 single nucleotide repeats (SNPs) associated with type 2 diabetes in genome-wide association studies were tested in a case–control study of 2011 colorectal cancer cases and 6049 controls nested in the Multiethnic Cohort study as part of the Population Architecture using Genomics and Epidemiology (PAGE) initiative. ORs and 95% CIs were estimated by unconditional logistic regression to evaluate the association between SNPs and colorectal cancer risk, adjusting for age, sex and race/ethnicity. Permutation testing was conducted to correct for multiple hypothesis testing. Results Four type 2 diabetes SNPs were associated with colorectal cancer risk: rs7578597 (THADA), rs864745 (JAZF1), rs5219 (KCNJ11) and rs7961581 (TSPAN8, LGR5). The strongest association was for the rs7578597 (THADA) Thr1187Ala missense polymorphism (Ptrend=0.004 adjusted for multiple testing), with the high risk allele for colorectal cancer being the low risk allele for diabetes. Similar patterns of associations were seen with further adjustment for diabetes status and body mass index. The association of diabetes status with colorectal cancer risk was somewhat weakened after adjustment for these SNPs. Conclusion The findings suggest that diabetes risk variants also influence colorectal cancer susceptibility, possibly through mechanisms different from those for diabetes.
High Amounts of S100-Alarmins Confer Antimicrobial Activity on Human Breast Milk Targeting Pathogens Relevant in Neonatal Sepsis

Sepsis is a leading cause of perinatal mortality worldwide. Breast milk (BM) feeding is protective against neonatal sepsis, but the molecular mechanisms remain unexplained. Despite various supplementations with potential bioactive components from BM formula feeding cannot protect from sepsis. S100-alarmins are important immunoregulators in newborns preventing excessive inflammation. At high concentrations, the S100A8/A9 protein complex also has antimicrobial properties due to its metal ion chelation capacity. To assess whether BM contains S100-alarmins that might mediate the sepsis-protective effect of BM 97 human BM samples stratified for gestational age, mode of delivery and sampling after birth were collected and analyzed. S100A8/A9 levels were massively elevated after birth (p < 0.0005). They slowly decreased during the first month of life, then reaching levels comparable to normal values in adult serum. The concentration of S100A8/A9 in BM was significantly higher after term compared with preterm birth (extremely preterm, p < 0.005; moderate preterm, p < 0.05) and after vaginal delivery compared with cesarean section (p < 0.0005). In newborn s100a9−/− mice, enterally supplied S100-alarmins could be retrieved systemically in the plasma. To explore the antimicrobial activity against common causal pathogens of neonatal sepsis, purified S100-alarmins and unmodified as well as S100A8/A9-depleted BM were used in growth inhibition tests. The high amount of S100A8/A9 proved to be an important mediator of the antimicrobial activity of BM, especially inhibiting the growth of manganese (Mn) sensitive bacteria such as Staphylococcus aureus (p < 0.00005) and group B streptococci (p < 0.005). Depletion of S100A8/A9 significantly reduced this effect (p < 0.05, respectively). The growth of Escherichia coli was also inhibited by BM (p < 0.00005) as well as by S100A8/A9 in culture assays (p < 0.05). But its growth in BM remained unaffected by the removal of S100A8/A9 and was neither dependent on Mn suggesting that the antimicrobial effects of S100A8/A9 in BM are primarily mediated by its Mn chelating capacity. In summary, the enteral supply of bioavailable, antimicrobially active amounts of S100-alarmins might be a promising option to protect newborns at high risk from infections and sepsis.
IS6110-Mediated Deletion Polymorphism in Isogenic Strains of Mycobacterium tuberculosis

ABSTRACT Previous studies have described IS6110-mediated polymorphism as an important driving force in Mycobacterium tuberculosis genome evolution and have provided indirect evidence for IS6110-driven deletion events. This study provides the first description of an IS6110-mediated deletion event in truly isogenic strains. We also provide further support for the hypothesis that the region from Rv1754 to Rv1765 is a hot spot for IS6110 insertion and deletion events.
LTV Limits and Borrower Risk

This paper explores the effects of the hard loan-to-value (LTV) limit implemented in Israel in 2012, which had three different cutoffs according to the borrower type: first-time home buyer, upgrader, or investor. The paper tries to overcome identification challenges where the treatment status is not observed. I find that this macroprudential policy measure succeeded in achieving its main goal, which was to reduce borrowers' leverage. I also find that constrained borrowers bought assets farther from the center of Israel, in neighborhoods with lower socioeconomic rankings; and a much stronger response than the impact of the 2010 soft LTV limit. Investors were found to be the borrower type most affected by the LTV limit. In terms of the credit market, the effect of the LTV limit on mortgage terms is counterintuitive: the limit increased the interest rate and the term to maturity. Plausible explanations for those results are discussed. ​
Towards Teaching Maternal Healthcare and Nutrition in Rural Ethiopia through a Serious Game

Ethiopia has one of the highest maternal and child mortality rates in the world, partly due to the low accessibility of educational content regarding nutrition and healthcare in the rural regions. This paper presents the first step for tackling this problem by means of a serious game, Easycare, designed for teaching illiterate users, with almost no previous experience with digital games, good practices for healthcare and nutrition. Promising results from a field study conducted in Ethiopia are also presented, showing the potential of the tool for education in developing countries.