Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling

4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 4-1BB also can bind to the tandem repeat–type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)–deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. Here, using sulfur-SAD phasing, we determined the crystal structure of m4-1BB to 2.2-Å resolution. We found that similar to other TNFRSFs, m4-1BB has four cysteine-rich domains (CRDs). However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. Moreover, we mapped two Asn residues within CRD4 that are N-linked glycosylated and mediate m4-1BB binding to Gal-9. Kinetics studies of m4-1BB disclosed a very tight nanomolar binding affinity to m4-1BBL with an unexpectedly strong avidity effect. Both N- and C-terminal domains of Gal-9 bound m4-1BB, but with lower affinity compared with m4-1BBL. Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. As multimerization and clustering is a prerequisite for TNFR intracellular signaling, and as m4-1BBL can only recruit two m4-1BB monomers, we hypothesize that m4-1BBL and Gal-9 act together to aid aggregation of m4-1BB monomers to efficiently initiate m4-1BB signaling.
Defects in d-Alanyl-Lipoteichoic Acid Synthesis in Streptococcus mutans Results in Acid Sensitivity

ABSTRACT In the cariogenic organism, Streptococcus mutans, low pH induces an acid tolerance response (ATR). To identify acid-regulated proteins comprising the ATR, transposon mutagenesis with the thermosensitive plasmid pGh9:ISS1 was used to produce clones that were able to grow at neutral pH, but not in medium at pH 5.0. Sequence analysis of one mutant (IS1A) indicated that transposition had created a 6.3-kb deletion, one end of which was indltB of the dlt operon encoding four proteins (DltA-DltD) involved in the synthesis ofd-alanyl-lipoteichoic acid. Inactivation of thedltC gene, encoding the d-alanyl carrier protein (Dcp), resulted in the generation of the acid-sensitive mutant, BH97LC. Compared to the wild-type strain, LT11, the mutant exhibited a threefold-longer doubling time and a 33% lower growth yield. In addition, it was unable to initiate growth below pH 6.5 and unadapted cells were unable to survive a 3-h exposure in medium buffered at pH 3.5, while a pH of 3.0 was required to kill the wild type in the same time period. Also, induction of the ATR in BH97LC, as measured by the number of survivors at a pH killing unadapted cells, was 3 to 4 orders of magnitude lower than that exhibited by the wild type. While the LTA of both strains contained a similar average number of glycerolphosphate residues, permeabilized cells of BH97LC did not incorporated-[14C]alanine into this amphiphile. This defect was correlated with the deficiency of Dcp. Chemical analysis of the LTA purified from the mutant confirmed the absence ofd-alanine-esters. Electron micrographs showed that BH97LC is characterized by unequal polar caps and is devoid of a fibrous extracellular matrix present on the surface of the wild-type cells. Proton permeability assays revealed that the mutant was more permeable to protons than the wild type. This observation suggests a mechanism for the loss of the characteristic acid tolerance response in S. mutans.
An Interdisciplinary Approach to Sports Concussion Evaluation and Management: The Role of a Neuropsychologist

Sports neuropsychology is a rapidly emerging field that affords neuropsychologists, the opportunity to work with a diverse group of individuals in terms of age, gender, sports, ethnicity, and language and sports has a way of bringing diverse communities together. Although working with athletes can be associated with unique challenges, neuropsychological assessment with this population and being part of an interdisciplinary sports medicine team is both exciting and rewarding and can merge a passion for sports with professional interests. This paper is intended to highlight the contribution of neuropsychology to the evaluation and management of sport-related concussion as well as describe the neuropsychologist's role as an integral member of interdisciplinary sports medicine teams. Clinical model, special considerations, assessment strategy, and administrative aspects of practice are discussed.
Gestational Diabetes May Represent Discovery of Preexisting Glucose Intolerance

A representative sample of 817 American women aged 20–44 yr who were not pregnant and had no medical history of diabetes were given 75-g 2-h oral glucose tolerance tests (OGTTs). Although these conditions are somewhat different from those recommended for pregnant women (100 g glucose, 3-h OGTT), 3.8% of the women might have been considered to have met O'Sullivan and Mahan criteria for gestational diabetes mellitus (GDM) had they been pregnant. Prevalence was 2–3% below age 35 yr, similar to that found in studies of pregnant women, and rose to 8% at age 40–44 yr. Rates of women meeting World Health Organization criteria for gestational impaired glucose tolerance (G-IGT) rose steadily from 5% at age 20–24 yr to 11% at age 40–44 yr. Risk factors for non-insulin-dependent diabetes mellitus (NIDDM) including parental history and obesity were more prevalent among women meeting these criteria than among women in the entire group; the same risk factors are also more prevalent among pregnant women with GDM. The similarity of rates in this study to rates of GDM and G-IGT, together with their association with risk factors for NIDDM, indicate that these entities are compatible with undiagnosed glucose intolerance occurring before pregnancy and discovered during the metabolic testing that generally accompanies prenatal care rather than conditions that have an etiologic relationship to pregnancy.
The relationship between initiation, barriers, product quality and internationalization

This study addresses the issue of how small and medium sized companies seek information about potential international partners for cooperation. In particular, we focus on two information sources; direct personal information and indirect personal information. We argue that the use of these information sources is related to how closely related the planned alliance is to the strategic core of the company, the degree of dissimilarity among potential partners, the degree of expected opportunism from potential partners and prior experience with cooperation. Our hypotheses were tested on a sample of small and medium sized companies. The results indicate that the planned alliance’s closeness to the strategic core of the company and partner dissimilarity are important predictors for how managers seek information about potential partners. 2 Co-authored with Magne Supphellen and Svein Haugland. This article was published in Journal of Business Research, 2002, Vol. 55, No. 9, 785-795.
Exploiting the ambiguity domain for non-stationary biomedical signal classification

Research in time-frequency distributions (TFDs) is limited in terms of their use of the available spatial domains and in their target applications. Most of the work up till now has been concentrated mainly on the t-ƒ domain space. This work presents a detailed study about the ambiguity domain (AD), their resemblance in the t-ƒ space and the significance of using such a representation. Further, a novel approach for the analysis and classification between normal and pathological speech signals is also provided. The quantitative measures obtained show comparable performance scores with the existing schemes. Evidently, gait from 51-normal and 161-abnormal subjects were studied and classified in this analysis. Results obtained from the quantitative analysis illustrate comparable performance characteristics with some of the recent schemes and a maximum classification accuracy of 97.5% is obtained.
, Mortality : The Ohasama Study Ambulatory Blood Pressure and 10-Year Risk of Cardiovascular and Noncardiovascular

The objective of this study was to elucidate the long-term prognostic significance of ambulatory blood pressure. Ambulatory and casual blood pressure values were obtained from 1332 subjects (872 women and 460 men) aged 40 years from the general population of a rural Japanese community. Survival was then followed for 14 370 patient years and analyzed by a Cox hazard model adjusted for possible confounding factors. There were 72 cardiovascular deaths during the 10.8-year follow-up. The relationship between 24-hour systolic blood pressure and the cardiovascular mortality risk was U-shaped in the first 5 years, then changed to J-shaped over the rest of the 10.8-year follow-up. After censoring the first 2 years of data, the risk flattened until it again increased for the fifth quintile of 24-hour systolic blood pressure for the 10.8-year follow-up period. For 24-hour diastolic blood pressure, the J-shaped relationship remained unchanged, regardless of follow-up duration and censoring. Ambulatory systolic blood pressure values consistently showed stronger predictive power for cardiovascular mortality risk than did casual systolic blood pressure in the 10.8-year follow-up data, whereas such relationships became more marked after censoring the first 2 years. When nighttime and daytime systolic blood pressure values were simultaneously included in the same Cox model, only nighttime blood pressure significantly predicted the cardiovascular mortality risk for the 10.8-year follow-up data. We conclude that the relationship between ambulatory systolic blood pressure and cardiovascular mortality is not U-shaped or J-shaped, and that nighttime blood pressure has better prognostic value than daytime blood pressure. (Hypertension. 2005;45:240-245.)
A Novel Transform Demodulation Algorithm for Motor Incipient Fault Detection

Faults, such as broken rotor bars, in induction motors may be detected by estimating the spectral signature of the stator currents, particularly the sidebands around the supply line frequency. However, the amplitude of the fundamental frequency (50 Hz) is considerably greater than the sideband amplitude. How to demodulate the signature frequency components under the heavy background of fundamental frequency, or how to remove the fundamental frequency, is becoming a key problem in motor current signature analysis. This paper puts forward a novel transform demodulation algorithm to solve the problem. The three-phase currents are transformed to a magnetic-torque (M-T) coordinate using this algorithm. It is found that the signature frequency components are demodulated in the magnetizing and torque-producing currents obtained by the transformation. Thus, the two demodulated M-T currents can be used to extract the enhanced signature frequency components of faults, and the incipient fault detection of induction motors is easy to realize. With both simulated and experimental data of broken rotor bars, it shows that the proposed algorithm can extract more detailed fault signature frequency components and realize the incipient fault detection of induction motors.
Optimization of the cryopreservation and thawing protocol for human hepatocytes for use in cell transplantation

Cryopreservation of human hepatocytes is important for their use in hepatocyte transplantation. On thawing, cryopreserved hepatocytes often have reduced viability and metabolic function in comparison with fresh cells. The aim of this study was to modify the different steps in the standard cryopreservation procedure in an attempt to improve the overall outcome. Human hepatocytes with a viability of 69% ± SD 16% were isolated from donor livers with a collagenase perfusion technique. Different cell densities, concentrations, rates, and methods of addition of dimethyl sulfoxide were tested for the freezing solution. Modified controlled‐rate freezer programs were tested to obtain a linear decrease in the temperature. Once they were frozen, the storage time and thawing method for hepatocytes were investigated. The effects on thawed cell viability and attachment, lactate dehydrogenase release, cytochrome P450 1A1/2 activity, and albumin synthesis were determined. The results were used to produce an improved cryopreservation protocol suitable for good manufacturing practice conditions. With a cell density of 107 cells/mL in University of Wisconsin solution containing 300 mM glucose, 10% (vol/vol) dimethyl sulfoxide was added dropwise over 5 minutes, and was immediately frozen. Thawing was done rapidly at 37°C, and dilution was performed with Eagle's minimum essential medium containing 300 mM glucose and 4% human serum albumin. Hepatocytes could be stored at −140°C without significant further loss of function for up to 3 years. With this protocol, hepatocytes had a viability of 52% ± 9%, an attachment efficiency of 48% ± 8%, and lactate dehydrogenase leakage of 17% ± 4%. This protocol is currently in use to cryopreserve hepatocytes for use in cell transplantation at our center. Liver Transpl 16:229–237, 2010. © 2010 AASLD.
Transmission of International Prices to Domestic Markets in Kenya: The Case of Food and Crude-oil Markets During the 2007-8 Global Crisis

This study looks at the transmission of international prices to the Kenyan economy in 2007-2008 with a focus on food and oil prices. The degree of price transmission between spatial markets signifies the level of integration of such markets. The information on magnitudes of the price elasticities of demand for imports, and the extent of price transmissions is very important in the design of policies to deal with external price shocks. The paper uses the imperfect substitute demand model and the Kenya CGE model to estimate the import elasticities that are then employed to simulate domestic price effects of external shocks. The findings show that aggregate import demand elasticities for food and crude oil in Kenya are fairly elastic, with coefficients being slightly greater than unity. This implies that when international prices fall, the demand for imported products rises by more than a proportionate quantity. Thus changes in international prices for oil and food are likely to have substantial effects on the country's trade balance. In addition, the results indicate that in the year 2007-2008, there was less than full transmission of external crude oil price shocks to domestic market prices, and the crisis had low or negligible effects on domestic prices for other goods and services. Similarly, transmissions of world market food prices to the domestic market were negligible. The results suggest very low integration between domestic and world markets, especially for agricultural products. The study recommends re-alignment of Kenya’s food production and supply strategies with international initiatives in order to meet food security requirements and stabilize domestic prices. Keywords : Price shocks, import elasticities, price transmission, market integration.
TRPV1 controls acid‐ and heat‐induced calcitonin gene‐related peptide release and sensitization by bradykinin in the isolated mouse trachea

Chronic cough derives from inflammatory hypersensitivity of tracheobronchial nerve endings, most of which express the polymodal capsaicin receptor‐channel transient receptor potential vanilloid (TRPV) type 1 and the secretory neuropeptide calcitonin gene‐related peptide (CGRP). An isolated mouse trachea preparation was established to measure chemically and thermally stimulated CGRP release as an index for sensory transduction of potential cough‐inducing stimuli. TRPV1 knockout mice were employed to assess the TRPV1 contribution to tracheal responsiveness and sensitization. Graded heat‐induced CGRP release depended entirely on extracellular calcium and partly on TRPV1; knockout mice showed 60% less CGRP release at 45°C (for 5 min) than wild‐types. This heat response was facilitated by the TRPV1 agonist ethanol and the TRPV1–3 agonist 2‐aminoethoxydiphenyl borate, effects that were reduced or absent in TRPV1−/−, respectively. The TRPV1 antagonists ruthenium red and N‐(4‐t‐butylphenyl)‐4‐(3‐chloropyridin‐2‐yl) tetrahydropyrazine‐1(2H)‐carboxamide were ineffective on the basal heat response. A step increase of temperature from 22 to 40°C caused a TRPV1‐independent CGRP release that was doubled by bradykinin in wild‐types but not TRPV1−/−. Proton stimulation resulted in a bell‐shaped concentration–response curve with threshold at pH 6.7 and a maximum at pH 5.7; responses were greatly reduced but not abolished in TRPV1−/−. Coadministration of amiloride (30 μm), the blocker of acid‐sensing ion channels, was ineffective in both TRPV1 genotypes. The data suggest that tracheal acid sensing mainly involves TRPV1 but not acid‐sensing ion channels, whereas noxious heat responsiveness partly depends and (inflammatory) sensitization to heat largely depends on the capsaicin receptor in tracheal nerve endings. Lowering of their heat threshold to near body temperature may sustain hypersensitivity and neurogenic inflammation of the upper airways.
Comparison of surgical and endovascular approach in management of spinal dural arteriovenous fistulas: A single center experience of 27 patients

Background: Spinal dural arteriovenous fistula (SDAVF) is a rare spinal vascular malformation with an annual incidence of 5-10 cases per million. The data on efficacy, recurrence rates and complications of endovascular versus surgical treatment of SDAVF is limited. Methods: We conducted a retrospective chart review of 27 adult patients with a diagnosis of SDAVF and who underwent treatment at Duke University Hospital between January 1, 1993 and December 31, 2012. We compared the outcome measures by Aminoff–Logue score (ALS) in patients who underwent treatment with endovascular embolization versus surgical ligation of fistula. We compared complication rates, recurrence rates as well as data on long-term follow up in these patients. Results: Out of 27 patients in the study, 10 patients underwent endovascular embolization (Onyx was used in 5 patients and NBCA in 5 patients) as the first line therapy. Seventeen patients underwent surgical ligation as initial therapeutic modality. Patients in both groups showed significant improvement in clinical status (ALS) after treatment. One patient in endovascular group developed spinal infarction due to accidental embolization of medullary artery. Three patients in embolization group had recurrence of fistula during the course of follow up requiring surgical ligation. Two patients in surgical group developed local wound infection. None of the patients in surgical group had recurrence of fistula during the course of follow up. Conclusions: Endovascular embolization and surgical ligation are effective treatment strategies for SDAVF. Our observations show that surgical ligation may offer permanent cure without any recurrence. Endovascular approach is associated with higher incidence of recurrence, especially with use of onyx.
Delivery of Macromolecules Using Arginine-Rich Cell-Penetrating Peptides: Ways to Overcome Endosomal Entrapment

Arginine-rich cell-penetrating peptides (AR-CPPs) are very promising tools for the delivery of therapeutic macromolecules such as peptides, proteins, and nucleic acids. These peptides allow efficient internalization of the linked cargos intracellularly through the endocytic pathway. However, when linked to bulky cargos, entrapment in the endocytic vesicles is a major limitation to the application of these peptides in cytosolic delivery. Attachment of a compatible endosomal escape device is, therefore, necessary to allow cytosolic delivery of the peptide-attached cargo. This review presents different endosomal escape devices currently in application in combination with AR-CPPs. Applications of fusogenic lipids, membrane-disruptive peptides, membrane-disruptive polymers, lysosomotropic agents, and photochemical internalization to enhance the cytosolic delivery of AR-CPPs-attached cargos are presented. The properties of each system and its mechanism of action for the enhancement of endosomal escape are discussed, together with its applications for the delivery of different macromolecules in vitro and, if applicable, in vivo.
Welfare, labour market deregulation and households’ poverty risks: An analysis of the risk of entering poverty at childbirth in different European welfare clusters

This article deals with families’ risk of entering poverty as a consequence of childbirth in four European Union (EU) welfare clusters. Poverty risks around childbirth are institutionally stratified according to specific characteristics of national welfare systems and the value they assign to family policies as well as the kind of labour market deregulation. While southern European countries are known for having welfare systems that make few provisions for ‘the future generations of citizens’, conservative and social-democratic countries differ significantly in the amount of their investments in family policies. We compare households’ risks of entering poverty at childbirth between Southern Europe and the rest of Europe using pooled longitudinal European Union Statistics on Income and Living Conditions (EU-SILC) data and applying panel models and propensity score matching. We show that childbirth is very poverty inducing only in southern Europe, especially for the less ‘labour market–attached’ households (precarious worker families, the unemployed) and traditional single-earner families, thereby pointing out the under-protectiveness of the Southern European systems of family and social policies. This situation is exacerbating additional inequality as families’ well-being largely depends on the previous unequal social stratification of resources.
Children's Food Allergies: Development of the Food Allergy Management and Adaptation Scale.

OBJECTIVE Develop a measure that evaluates effective pediatric food allergy (FA) management, child and parent FA anxiety, and integration of FA into family life. METHODS A semistructured family interview was developed to evaluate FA management using a pilot sample (n = 27). Rating scales evaluated eight dimensions of FA management (FAMComposite), child anxiety, parent anxiety, and overall balanced integration (BI). Families of children with IgE-mediated food allergies (n = 60, child age: 6-12) were recruited for interview and rating scale validation. RESULTS FAMComposite was correlated with physician ratings for families' food avoidance and reaction response readiness. FA anxiety was correlated with general anxiety measures for children, but not parents. Parents' FA anxiety was correlated with expectations of negative outcomes from FA. Low BI was associated with poor quality of life and negative impact on family functioning. CONCLUSIONS Preliminary analyses support Food Allergy Management and Adaptation Scale validity as a measure of family adaptation to pediatric FA.
A heuristic homotetic approach to the dimensioning of induction motors from specification data

Induction motors are presently the most widespread kind of electric machinery used in industrial and vehicle applications. In the engineering practice, it frequently happens that designers or final users have to roughly estimate the size, weight and some basic performance data of an induction motor based on few specification requirements such as its rated speed and power. This paper describes a heuristic approach which can help make a first-attempt dimensioning in an approximate but reliable way. The method uses homothety as the theoretical basis and derives practical laws by identifying homothetic law parameters through the statistical analysis of a set of sample built machines. The results obtained are compared to those derived from classical books showing significant discrepancies which fully justify the adoption of more sophisticated heuristic models as those being presented.