Miracle-dz/UniFAR-FTUs huggingface dataset:
Blood flow response of human calf muscles to static contractions at various percentages of MVC.

Six male subjects within the age range of 20-35 yr consented to perform static calf muscle contractions at 7.5, 15, and 30% of their maximum voluntary contractile strength (MVC) for a period of 2 min each. Isometric contractions were performed in a sitting position by pressing the knee against a solid support plate via plantar flexion. Calf muscle blood flow (BF) was measured periodically before, during, and after each contraction by a Whitney gauge. Average resting BF was 3.9 ml . min-1 . 100 ml-1 of calf volume. During the 7.5, 15, and 30% MVC contractions, BF increased to steady-state levels of 7.2, 7.9, and 5.3 ml . min-1 . 100 ml-1, respectively. The values for 7.5 and 15% MVC were significantly higher than resting BF (P less than or equal to 0.05). The postcontraction hyperemia, measured as the area under the postcontraction BF curve, averaged 4.4, 10.1, and 23.2 ml/100 ml, respectively, for the 7.5, 15, and 30% MVC efforts. Comparison of these values with corresponding hyperemic volumes during contraction showed that the portions of the total BF response that occurred in the postcontraction periods were 41, 57, and 88%, respectively, for the 7.5, 15, and 30% efforts. These results demonstrate that during static calf muscle contractions BF increases by only a modest amount, and at even small forces of contraction a sizable portion of the total flow response occurs in the postcontraction period.
PTH and phospholipase A2 in the aging process of intestinal cells

In this study we analyzed, for the first time, alterations in phospholipase A2 (PLA2) activity and response to parathyroid hormone (PTH) in rat enterocytes with aging. We found that PTH, rapidly stimulate arachidonic acid (AA) release in rat duodenal cells (+1‐ to 2‐fold), an effect that is greatly potentiated by aging (+4‐fold). We also found that hormone‐induced AA release in young animals is Ca2+‐dependent via cPLA2, while AA released by PTH in cells from aged rats is due to the activation of cPLA2 and the Ca2+‐independent PLA2 (iPLA2). In enterocytes from 3 months old rats, PTH induced, in a time and dose‐dependent fashion, the phosphorylation of cPLA2 on serine 505, with a maximun at 10 min (+7‐fold). Basal levels of cPLA2 serine‐phosphorylation were higher in old enterocytes, affecting the hormone response which was greatly diminished (+2‐fold at 10 min). cPLA2 phosphorylation impairment in old animals was not related to changes of cPLA2 protein expression and did not explain the substantial increase on PTH‐induced AA release with aging, further suggesting the involvement of a different PLA2 isoform. Intracellular Ca2+ chelation (BAPTA‐AM, 5 μM) suppressed the serine phosphorylation of cPLA2 in both, young and aged rats, demonstrating that intracellular Ca2+ is required for full activation of cPLA2 in enterocytes stimulated with PTH. Hormone effect on cPLA2 was suppressed to a great extent by the MAP kinases ERK 1 and ERK2 inhibitor, PD 98059 (20 μM), the cAMP antagonist, Rp‐cAMP, and the PKC inhibitor Ro31820 both, in young and aged animals. Enterocytes exposure to PTH also resulted in phospho‐cPLA2 translocation from cytosol to nuclei and membrane fractions, where phospholipase subtrates reside. Hormone‐induced enzyme translocation is also modified by aging where, in contrast to young animals, part of phospho‐cPLA2 remained cytosolic. Collectively, these data suggest that PTH activates in duodenal cells, a Ca2+‐dependent cytosolic PLA2 and attendant AA release and that this activation requires prior stimulation of intracellular ERK1/2, PKA, and PKC. cPLA2 is the major enzyme responsible for AA release in young enterocytes while cPLA2 and the Ca2+‐independent iPLA2, potentiate PTH‐induced AA release in aged cells. Impairment of PTH activation of PLA2 isoforms upon aging may result in abnormal hormone regulation of membrane fluidity and permeability and thereby affecting intestinal cell membrane function.
DNA Hypermethylation Profiles in Squamous Cell Carcinoma of the Vulva

Gene silencing through promoter hypermethylation is a growing concept in the development of human cancers. In this study, we examined the contribution of aberrant methylation of promoter regions in methylation-prone tumor suppressors to the pathogenesis of vulvar cancer. Thirteen cell lines from 12 patients with squamous cell carcinoma of the vulva were evaluated for aberrant methylation status and gene copy number alterations, concomitantly, using the methylation-specific multiplex ligation-dependent probe amplification assay. Of the 22 tumor suppressor genes examined, aberrant methylation was observed for 9 genes: tumor protein p73 (TP73), fragile histidine triad (FHIT), von Hippel-Lindau (VHL), adenomatosis polyposis coli (APC), estrogen receptor 1 (ESR1), cyclin-dependent kinase inhibitor 2B (CDKN2B), death-associated protein kinase 1 (DAPK1), glutathione S-transferase pi (GSTP1), and immunoglobin superfamily, member 4 (IGSF4). The most frequently methylated genes included TP73 in 9 of 13 cell lines, and IGSF4, DAPK1, and FHIT in 3 of 13 cell lines. Methylation-specific polymerase chain reaction was performed for TP73 and FHIT to confirm aberrant methylation by methylation-specific multiplex ligation-dependent probe amplification. In the context of gene copy number and methylation status, both copies of the TP73 gene were hypermethylated. Loss or decreased mRNA expression of TP73 and IGSF4 by reverse transcription polymerase chain reaction confirmed aberrant methylation. Frequent genetic alterations of loss and gain of gene copy number included gain of GSTP1 and multiple endocrine neoplasia type 1 (MEN1), and loss of malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) and IGSF4 in over 50% of the squamous cell carcinoma of the vulva cell lines. These findings underscore the contribution of both genetic and epigenetic events to the underlying pathogenesis of squamous cell carcinoma of the vulva.
Internally located cleavable signal sequences direct the formation of Semliki Forest virus membrane proteins from a polyprotein precursor

The proteolytic processes involved in the cotranslational production of the Semliki Forest virus proteins p62, 6K, and E1 from a common precursor polypeptide were analyzed by an in vitro translation-translocation assay. By studying the behavior of wild-type and mutant variants of the polyprotein, we show that the signal sequences responsible for membrane translocation of the 6K and E1 proteins reside in the C-terminal regions of p62 and 6K, respectively. We present evidence suggesting that the polyprotein is processed on the luminal side by signal peptidase at consensus cleavage sites immediately following the signal sequences. Our results also lead us to conclude that the 6K protein is a transmembrane polypeptide with its N terminus on the luminal side of the membrane (type I). Thus, the production of all three membrane proteins is directed by alternating signal and stop-transfer (anchor) sequences that function in translocation and cleavage of the virus precursor polyprotein. This also shows conclusively that internally located signal sequences can be cleaved by signal peptidase.
A Conserved Val to Ile Switch near the Heme Pocket of Animal and Bacterial Nitric-oxide Synthases Helps Determine Their Distinct Catalytic Profiles*

Nitric oxide (NO) release from nitric oxide synthases (NOSs) is largely dependent on the dissociation of an enzyme ferric heme-NO product complex (FeIIINO). Although the NOS-like protein from Bacillus subtilis (bsNOS) generates FeIIINO from the reaction intermediate N-hydroxy-l-arginine (NOHA), its NO dissociation is about 20-fold slower than in mammalian NOSs. Crystal structures suggest that a conserved Val to Ile switch near the heme pocket of bsNOS might determine its kinetic profile. To test this we generated complementary mutations in the mouse inducible NOS oxygenase domain (iNOSoxy, V346I) and in bsNOS (I224V) and characterized the kinetics and extent of their NO synthesis from NOHA and their NO-binding kinetics. The mutations did not greatly alter binding of Arg, (6R)-tetrahydrobiopterin, or alter the electronic properties of the heme or various heme-ligand complexes. Stopped-flow spectroscopy was used to study heme transitions during single turnover NOHA reactions. I224V bsNOS displayed three heme transitions involving four species as typically occurs in wild-type NOS, the beginning ferrous enzyme, a ferrous-dioxy (FeIIO2) intermediate, FeIIINO, and an ending ferric enzyme. The rate of each transition was increased relative to wild-type bsNOS, with FeIIINO dissociation being 3.6 times faster. In V346I iNOSoxy we consecutively observed the beginning ferrous, FeIIO2, a mixture of FeIIINO and ferric heme species, and ending ferric enzyme. The rate of each transition was decreased relative to wild-type iNOSoxy, with the FeIIINO dissociation being 3 times slower. An independent measure of NO binding kinetics confirmed that V346I iNOSoxy has slower NO binding and dissociation than wild-type. Citrulline production by both mutants was only slightly lower than wild-type enzymes, indicating good coupling. Our data suggest that a greater shielding of the heme pocket caused by the Val/Ile switch slows down NO synthesis and NO release in NOS, and thus identifies a structural basis for regulating these kinetic variables.
The Role of Potentially Retrievable Inferior Vena Cava Filters in High-Risk Patients Undergoing Joint Arthroplasty.

INTRODUCTION Some patients undergoing total joint arthroplasty are at increased risk for venous thromboembolism (VTE). The aim of the present study was to evaluate the safety and efficacy of prIVCF in preventing PE in patients undergoing joint replacement surgery who are at high-risk for VTE. MATERIALS AND METHODS In this prospective, IRB-approved study, prIVCF were placed in consecutive patients who met specific high-risk criteria (history of VTE or hypercoaguable state) prior to total joint arthroplasty. Patients were followed until the IVC filter was removed. Outcomes and complications were recorded per Society of Interventional Radiology guidelines. RESULTS One hundred and nine potentially retrievable IVC filters were placed in 105 patients, who all subsequently underwent joint arthroplasty. One hundred eight IVC filters (98.9%) were retrieved successfully in a mean time of 44.1 days (range 13-183 days). There was 1 failed IVC filter retrieval attempt (0.9%) at 46 days post implantation. Two patients (1.9%) presented with recurrent PE and were successfully treated with anticoagulation prior to IVC filter retrieval. There were no fatalities from perioperative PE. In 1 patient (0.9%), a fractured filter leg had embolized during retrieval. CONCLUSION Potentially retrievable IVC filters are safe and effective for prophylaxis against PE in patients at high-risk for VTE undergoing joint arthroplasty.
Memory T‐cell trafficking: new directions for busy commuters

The immune system is unique in representing a network of interacting cells of enormous complexity and yet being based on single cells travelling around the body. The development of effective and regulated immunity relies upon co‐ordinated migration of each cellular component, which is regulated by diverse signals provided by the tissue. Co‐ordinated migration is particularly relevant to the recirculation of primed T cells, which, while performing continuous immune surveillance, need to promptly localize to antigenic sites, reside for a time sufficient to carry out their effector function and then efficiently leave the tissue to avoid bystander damage. Recent advances that have helped to clarify a number of key molecular mechanisms underlying the complexity and efficiency of memory T‐cell trafficking, including antigen‐dependent T‐cell trafficking, the regulation of T‐cell motility by costimulatory molecules, T‐cell migration out of target tissue and fugetaxis, are reviewed in this article.
Characterization of a novel transgenic mouse line expressing Cre recombinase under the control of the Cdx2 neural specific enhancer

Several genetically modified mouse models have been generated in order to drive expression of the Cre recombinase in the neuroectoderm. However, none of them specifically targets the posterior neural plate during neurulation. To fill this gap, we have generated a new transgenic mouse line in which Cre expression is controlled by a neural specific enhancer (NSE) from the Caudal‐related homeobox 2 (Cdx2) locus. Analyses of Cre activity via breeding with R26R‐YFP reporter mice have indicated that the Cdx2NSE‐Cre mouse line allows for recombination of LoxP sites in most cells of the posterior neural plate as soon as from the head fold stage. Detailed examination of double‐transgenic embryos has revealed that this novel Cre‐driver line allows targeting the entire posterior neural tube with an anterior limit in the caudal hindbrain. Of note, the Cdx2NSE regulatory sequences direct Cre expression along the whole dorso‐ventral axis (including pre‐migratory neural crest cells) and, accordingly, YFP fluorescence has been also observed in multiple non‐cranial neural crest derivatives of double‐transgenic embryos. Therefore, we believe that the Cdx2NSE‐Cre mouse line represents an important novel genetic tool for the study of early events occurring in the caudal neuroectoderm during the formation of both the central and the peripheral nervous systems. genesis 51:777–784. © 2013 Wiley Periodicals, Inc.
Potential of Rhodobacter capsulatus Grown in Anaerobic-Light or Aerobic-Dark Conditions as Bioremediation Agent for Biological Wastewater Treatments

The use of microorganisms to clean up wastewater provides a cheaper alternative to the conventional treatment plant. The efficiency of this method can be improved by the choice of microorganism with the potential of removing contaminants. One such group is photosynthetic bacteria. Rhodobacter capsulatus is a purple non-sulfur bacterium (PNSB) found to be capable of different metabolic activities depending on the environmental conditions. Cell growth in different media and conditions was tested, obtaining a concentration of about 108 CFU/mL under aerobic-dark and 109 CFU/mL under anaerobic-light conditions. The biomass was then used as a bioremediation agent for denitrification and nitrification of municipal wastewater to evaluate the potential to be employed as an additive in biological wastewater treatment. Inoculating a sample of mixed liquor withdrawn from the municipal wastewater treatment plant with R. capsulatus grown in aerobic-dark and anaerobic-light conditions caused a significant decrease of N-NO3 (>95%), N-NH3 (70%) and SCOD (soluble chemical oxygen demand) (>69%), independent of the growth conditions. A preliminary evaluation of costs indicated that R. capsulatus grown in aerobic-dark conditions could be more convenient for industrial application.
A cascade voltage controller for three-phase islanded microgrids

This paper proposes a cascade or multiloop digital control strategy for the voltage regulation of a three-phase islanded single distributed generation (DG) unit microgrid and its dedicated load. The cascade control strategy consists of an inner dq-currents control loop and an outer dq-voltages control loop responsible for providing the set-points of the inner loop. To design the outer loop, a constrained optimization-based loop shaping method is adopted. It uses multi-input multi-output (MIMO) nonparametric or spectral models of the system for an arbitrary number of desired operating points along with a linearly parameterized MIMO controller to form a set of open-loop transfer function matrices. Minimizing the summation of the second norm of the errors between the open-loop transfer function matrices and a desired one, the coefficients of the controller are optimally determined. Taking several load change scenarios, the performance of the proposed controller is evaluated based on time-domain simulation studies in MATLAB/PLECS.
Acute Regulation of Na+/H+ Exchanger NHE3 by Parathyroid Hormone via NHE3 Phosphorylation and Dynamin-dependent Endocytosis*

Parathyroid hormone (PTH) is a potent inhibitor of mammalian renal proximal tubule Na+transport via its action on the apical membrane Na+/H+ exchanger NHE3. In the opossum kidney cell line, inhibition of NHE3 activity was detected from 5 to 45 min after PTH addition. Increase in NHE3 phosphorylation on multiple serines was evident after 5 min of PTH, but decrease in surface NHE3 antigen was not detectable until after 30 min of PTH. The decrease in surface NHE3 antigen was due to increased NHE3 endocytosis. When endocytic trafficking was arrested with a dominant negative dynamin mutant (K44A), the early inhibition (5 min) of NHE3 activity by PTH was not affected, whereas the late inhibition (30 min) and decreased surface NHE3 antigen induced by PTH were abrogated. We conclude that PTH acutely inhibits NHE3 activity in a biphasic fashion by NHE3 phosphorylation followed by dynamin-dependent endocytosis.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-1 and receptor-2 agonists for cancer therapy

Importance of the field: Agents that activate the TNF-related apoptosis-inducing ligand death receptors, TRAIL-R1 and TRAIL-R2, have attracted substantial attention and investment as potential anti-cancer therapies. Preclinical studies of TRAIL-R agonists indicate that they may be efficacious in a wide range of tumor types, especially when combined with chemotherapeutic agents. Areas covered in this review: The rationale for clinical development of TRAIL-R agonists is described, including the basis for combining these agents with other agents that modulate the ‘checks and balances’ of the apoptotic pathways. Accruing data that highlight differences between TRAIL-R1 and TRAIL-R2 that could affect the clinical significance of their specific agonists are described. The clinical experience to date with each of the agonists is summarized. What the reader will gain: The reader will gain an understanding of the rationale for the clinical development of TRAIL-R agonists, as well as the current status of clinical trials of these interesting new agents. Take home message: Ongoing clinical trials will provide important information regarding the future development of TRAIL-R agonists.
Food intake patterns among Australian adolescents.

OBJECTIVES This study aimed to evaluate the food intake patterns of adolescents with respect to the Australian Guide to Healthy Eating, and to examine variations in food intake patterns by age, gender and region of residence. DESIGN Cross-sectional online food survey administered through schools. PARTICIPANTS AND SETTING In 2004-2005, 3841 secondary students in years seven (12-13 years) and nine (14-15 years) drawn from 37 secondary schools in Victoria, Australia completed an online food intake patterns survey. OUTCOME MEASURES Food intake was measured by a Food Frequency Questionnaire (FFQ), and categorized according to the five basic food groups (fruit, vegetables, meat, dairy, cereal) and the 'extra' food group as defined by the Australian Guide to Healthy Eating (AGHE). The foods groups were examined in the study population and compared across age, gender and region. RESULTS Many adolescents in this sample reported food intakes that deviated substantially from recommendations of the AGHE. For example, two-thirds of participants failed to consume foods from the five recommended food groups daily; over a third reported eating fruit 'rarely or never'; and 22% reported eating fast foods every day. Food intakes were generally more in line with dietary guidelines among girls than boys. Regional differences were less consistent, and there were few differences by age. CONCLUSION A significant proportion of adolescents have food intakes that fall short of the recommendations outlined in the Australian Guide to Healthy Eating. This highlights the need for public health initiatives to promote healthier food intake patterns among adolescents.
Thymic microenvironmental abnormalities in MRL/MP-lpr/lpr, BXSB/MpJ Yaa and C3H HeJ-gld/gld mice.

Efforts to define the stromal architecture of thymic tissues of normal mice have used a panel of monoclonal antibodies (MTS series) to examine the localization of cell subtypes, including reagents that define thymic epithelial and stromal elements. Recent work with these MTS mAbs disclosed significant abnormalities in the thymic cortex of New Zealand mice including the appearance of medullary type epithelial cells in the cortical areas and the presence of epithelial free spaces or 'cortical holes'. To determine whether such abnormalities are unique to NZB mice or are found in other models of murine lupus, we examined the thymi of MRL/MP-lpr/lpr BXSB/MpJ Yaa, C3H/HeJ-gld/gld and C57BL/6 control mice. Thymi from all models of murine lupus showed dramatic alterations in the thymic microarchitecture. For example, staining with MTS10, a mAb which is specific for subcapsular and medullary epithelia, was decreased in the subcapsular and medullary regions. Moreover, there was increased staining in the thymic cortex, suggesting an abnormality in the localization of MTS10-reactive cells. Moreover, all three murine lupus strains demonstrated 'cortical holes' or cortical epithelial cell-free regions. By using MTS33, MTS35 and flow cytometry, both C3H/gld and BXSB/Yaa, but not MRL/lpr mice, showed decreased cortical thymocyte frequencies. Possible defects in the maturation of double-positive thymocytes to single-positive status in C3H/gld mice is implied by abnormally high levels of double-positive cells and low levels of single-positive cells. Finally, MRL/lpr thymocytes had lowered frequencies of CD3-4+8+ and increased levels of TCR-alpha/beta high cells. (ABSTRACT TRUNCATED AT 250 WORDS)
Using comparable corpora to track diachronic and synchronic changes in lexical density and lexical richness

This study from the area of language variation and change is based on exploitation of the comparable diachronic and synchronic corpora of 20th century British and American English language (the ‘Brown family’ of corpora). We investigate recent changes of lexical density and lexical richness in two consecutive thirty-year time gaps in British English (1931–1961 and 1961–1991) and in 1961–1992 in American English. Furthermore, we compare the diachronic changes between these two language varieties and discuss the results of the synchronic comparison of these two features between British and American parts of the corpora (in 1961 and in 1991/2). Additionally, we explore the possibilities of these comparable corpora by using two different approaches to their exploitation: using the fifteen fine-grained text genres, and using only the four main text categories. Finally, we discuss the impact of the chosen approaches in making hypotheses about the way language changes.
Human small‐cell lung‐cancer cells are cytokine‐resistant but NK/LAK‐sensitive

We have studied the effects of 8 cytokines and their combinations on the in vitro growth of 10 human small‐cell cancer lines (SCLC). Interferon‐α and γ (IFN‐α and γ) caused significant but slight growth inhibition over a 7‐day incubation period. However, none of the other 6 cytokines, tumor necrosis factor (TNF), lymphotoxin (LT), interleukin‐1β (IL‐1β), interleukin‐2 (IL‐2), transforming growth factor‐β1 (TGF‐β1), or granulocyte colony‐stimulating factor (G‐CSF), modified SCLC cell proliferation. In contrast, all 10 lines were sensitive to lysis by natural killer (NK) and lymphokine‐activated killer (LAK) cells. Sensitivity to LAK cells could be Increased by pretreatment of SCLC cells with IFN‐γ. As resistance to the cytostatic/cytotoxic activity of some cytokines has been associated with autocrine production of cytokines, we screened the SCLC lines for cytokine mRNAs. Within the limits of detection of the assay we found no expression of TNF, TGF‐β1, IL‐1β or IL‐6 mRNA in the 10 SCLC lines.