Miracle-dz/UniFAR-FTUs huggingface dataset:
Thymic Stromal Lymphopoietin Amplifies the Differentiation of Alternatively Activated Macrophages

The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) has been associated with the promotion of type 2 inflammation and the induction of allergic disease. In humans TSLP is elevated in the lungs of asthma patients and in the lesional skin of individuals with atopic dermatitis, whereas mice lacking TSLP responses are refractory to models of Th2-driven allergic disease. Although several cell types, including dendritic cells, basophils, and CD4 T cells, have been shown to respond to TSLP, its role in macrophage differentiation has not been studied. Type 2 cytokines (i.e., IL-4 and IL-13) can drive the differentiation of macrophages into alternatively activated macrophages (aaMϕs, also referred to as M2 macrophages). This population of macrophages is associated with allergic inflammation. We therefore reasoned that TSLP/TSLPR signaling may be involved in the differentiation and activation of aaMϕs during allergic airway inflammation. In this study, we report that TSLP changes the quiescent phenotype of pulmonary macrophages toward an aaMϕ phenotype during TSLP-induced airway inflammation. This differentiation of airway macrophages was IL-13–, but not IL-4–, dependent. Taken together, we demonstrate in this study that TSLP/TSLPR plays a significant role in the amplification of aaMΦ polarization and chemokine production, thereby contributing to allergic inflammation.
Determination of piceatannol in rat serum and liver microsomes: pharmacokinetics and phase I and II biotransformation.

A method of analysis of piceatannol in biological fluids is necessary to study the kinetics of in vitro and in vivo metabolism and determine its concentration in foodstuffs. A novel and simple high-performance liquid chromatographic method was developed for simultaneous determination of piceatannol and products of its metabolism in rat serum and liver microsomes. Serum, or microsomes (0.1 mL), were precipitated with acetonitrile after addition of the internal standard, 4-methylumbelliferone. Separation was achieved on a phenomenex C(18) column (250 x 4.6 mm i.d., 5 microm) equipped with a phenomenex C(18) (4 x 3.0 mm i.d., 5 microm) guardcolumn with fluorescence excitation at 320 nm and emission at 420 nm. Separation was also possible with UV detection at 310 nm. The fluorescent calibration curves were linear ranging from 0.05 to 100 microg/mL. The mean extraction efficiency was >95%. Precision of the assay was <10% (coefficient of variation), and was within 10% at the limit of quantitation (0.05 ng/mL). Bias of the assay was lower than 7%. The limit of detection was 50 ng/mL for a 0.1 mL sample. The assay was applied successfully to the in vitro kinetic study of metabolism of piceatannol in rat liver microsomes and pharmacokinetics in rats. Three metabolites of piceatannol have been identified.
Volume Changes in the Menisci and Articular Cartilage of Runners

Background Articular cartilage contributes to transferring enormous loads as uniformly as possible from one skeletal segment to the next. Whether it manages this task when subjected to the high repetitive loading cycles occurring during long-distance running and can remain intact is still the topic of controversy. Purpose To investigate the changes in cartilaginous volumes of the tibia, patella, and medial and lateral menisci after extreme dynamic loading as occurs in long-distance runners. Study Design Controlled laboratory study. Methods Forty-eight knees of male athletes were studied (38 ± 14 years). The subjects ran around a predetermined and precisely measured course (5, 10, 20 km), the beginning and end of the run being in the magnetic resonance imaging investigation room. The scan protocol was 60-minute rest period, first measurement, run, 3-minute delay, and second measurement. Results Overall, there were significant reductions in volume (P < .05) for the patella, tibia, and menisci. There was evidence of significant change after a running distance of 5 km. A further statistical reduction of the volume could only be demonstrated for the medial meniscus after 10 and 20 km. Conclusion Tibial, patellar, and meniscal cartilaginous volumes show not only load-dependent volume changes but also an asymptotic curve. This is the first time that meniscal volume changes due to loading have been used as an indicator of the important mechanical contribution that the menisci make to sustaining the knee during repetitive loading. Clinical Relevance On the basis of the results of this study, the authors assume that the cartilage is able to adapt well to the loads caused by running.
Stimulation of insulin secretion by gastric inhibitory polypeptide in man.

ABSTRACT The effect of very highly purified gastric inhibitory polypeptide (GIP) on insulin secretion in man was tested in normal volunteers. Administration of physiological doses of GIP together with glucose by IV infusion resulted in potentiation of the rise in IRI in the blood and improvement in glucose tolerance. It is concluded that GIP is a potent insulinotropic hormone and probably takes part in physiological potentiation of insulin secretion in response to hyperglycemia during absorption of nutrients from the intestine.
Molecular characterization of OP354‐like P[8] (P[8]b subtype) human rotaviruses a species isolated in Japan

OP354‐like P[8] (P[8]b subtype) species A rotaviruses (RVAs) were isolated first time in Japan during a RVA survey in Okayama Prefecture between 2006 and 2009. Two of 236 RVA‐positive samples were identified as G1P[8]b by reverse transcription polymerase chain reaction. P[8]b strains (RVA/human‐wt/JPN/OH1998/2008/G1P[8]b and RVA/human‐wt/JPN/OH2024/2008/G1P[8]b) were isolated only in May, 2008 and both patients infected with P[8]b viruses lived in the same city, suggesting that the prevalence of P[8]b RVAs is limited considerably in Okayama Prefecture. Molecular analysis of four genes (VP4, VP6, VP7, and NSP4 genes) of Japanese P[8]b strains revealed that the VP4 genes of these strains were related closely to those of Southeast Asian and Indian P[8]b strains. In contrast, the VP6, VP7, and NSP4 genes of Japanese P[8]b strains were highly homologous to G1P[8]a strains prevalent in the same area. These results suggest that the Japanese P[8]b strain may be a result of reassortment events between Japanese G1P[8]a viruses and unidentified Asian viruses possessing the P[8]b VP4 gene. J. Med. Virol. 84:697–704, 2012. © 2011 Wiley Periodicals, Inc.
Simultaneous Articulatory and Acoustic Distortion in L1 and L2 Listening: Locally Time-Reversed "Fast" Speech

The current study explores how native and non-native speakers cope with simultaneous articulatory and acoustic distortion in speech perception. The articulatory distortion was generated by asking a speaker to articulate target speech as fast as possible (fast speech). The acoustic distortion was created by dividing speech signals into small segments with equal time duration (e.g., 50 ms) from the onset of speech, and flipping every segment on a temporal axis, and putting them back together (locally time-reversed speech). This study explored how “locally time-reversed fast speech” was intelligible as compared to “locally time-reversed normal speech” measured in Ishida, Samuel, and Arai (2016). Participants were native English speakers and native Japanese speakers who spoke English as a second language. They listened to English words and pseudowords that contained a lot of stop consonants. These items were spoken fast and locally time-reversed at every 10, 20, 30, 40, 50, or 60 ms. In general, “locally time-reversed fast speech” became gradually unintelligible as the length of reversed segments increased. Native speakers generally understood locally time-reversed fast spoken words well but not pseudowords, while non-native speakers hardly understood both words and pseudowords. Language proficiency strongly supported the perceptual restoration of locally time-reversed fast speech.
Effect of pregnancy on proteoglycan‐induced progressive polyarthritis in BALB/c mice: remission of disease activity

Proteoglycan‐induced arthritis is a murine autoimmune model displaying many similarities to human rheumatoid arthritis and ankylosing spondylitis, as has been documented by clinical, immunological and histopathological studies. Since the onset of arthritis correlates with the serum antibody level to mouse cartilage proteoglycan (PG), it is believed that these autoreactivc antibodies may play crucial roles in the pathological mechanisms of PG‐induced arthritis. We have found that fertility in these PG‐induced arthritic mice had been reduced but, unlike collagen‐induced arthritis, had not been completely lost. Moreover, pregnancy had a beneficial effect upon the clinical symptoms with very little or no influence on scrum antibody levels. Although fertility was retained and arthritic mothers delivered healthy offspring, the birth frequency was significantly less than in non‐arthritic age‐matched controls. Furthermore, the presence of anti‐PG autoantibodies (predominantly IgG1 subclass) transmitted from arthritic mothers to infants transplacentally and by milk during the lactation period did not render these offspring either resistant or more sensitive to subsequent induction of arthritis. Subsequent immunization of infants with ‘arthritogenic’ PG revealed an unaltered susceptibility to arthritis induction.
MODULATION OF THE EXPRESSION OF HLA CLASS II ANTIGENS BY GAMMA INTERFERON AND PHORBOL ESTER TPA ON MYELOID LEUKAEMIC CELL LINES

We investigated the effect of gamma interferon and phorbol ester (TPA), on the expression of HLA class II molecules of myeloid leukaemic cell lines K562, U937, KG‐1, HG60 and ML‐2. Gamma interferon induced the expression of HLA‐DR but not HLA‐DQ on HL‐60 and ML‐2, increased the expression of HLA‐DR and DQ on U937 and induced the expression of HLA‐DQ on KG‐1. TPA treatment did not affect the expression of HLA class II antigens on U937 and KG‐I and induced the expression of HLA‐DR and HLA‐DQ on HL‐60 and ML‐2. TPA treatment did not affect the HLA phenotype of K562 but gamma interferon did induce HLA class I molecules. Thus, gamma interferon cannot only increase the expression of HLA products already expressed on the cells but can also induce the de novo synthesis of these molecules on myeloid leukaemic cell lines.
Pharmacokinetic and Pharmacodynamic Interactions between Intravenous Ciprofloxacin and Oral Ferrous Sulfate

Abstract Changes in oral bioavailability and in vitro antimicrobial activity have been the focus of many previous interaction studies for metal cations and quinolones. This study is the first to examine the possibility of an interaction in the systemic circulation using ciprofloxacin and ferrous sulfate as representative interactants in a rat model, and to determine the changes, if any, in the pharmacokinetics and pharmacodynamics of the antibiotic. To minimize direct physical interaction in the gastrointestinal (GI) tract, the current study design required the male Sprague Dawley rats (220-240 g) to be dosed with 100 mg/kg of oral ferrous sulfate and 5 mg/kg of intravenous ciprofloxacin. Control animals received only intravenous ciprofloxacin. Blood and urine samples were collected over time for quantitation of ciprofloxacin independently by both HPLC (H) and microbiological (M) assays. Results showed that the disposition of ciprofloxacin in control animals was biexponential with a mean (±SD) terminal elimination half-life (t1/2,λz) of 0.93±0.30 h. A large apparent volume of distribution (Vd,λz: 6.96±1.56 L/kg) was observed. In addition, concentration vs. time profiles generated by both assays were similar. When the antibiotic was dosed with oral iron, parameter estimates generated by HPLC appeared to show a wider distribution and a longer elimination of ciprofloxacin; mean Vd,λzand t1/2,λz estimates increased by 2- and 4-fold, respectively. Relative to controls, antibiotic exposure (AUC0−∞) was also significantly higher (p<0.05) in the presence of iron (1.89±0.15 vs. 1.00±0.39 mg/h/L). A strong assay dependency was observed for ciprofloxacin concentrations observed post-distribution; the respective M/H ratios for AUC0−∞ and urinary recovery were 1.1 and 0.9 for controls and 0.7 and 0.5 for animals receiving oral iron. This iron related reduction in antimicrobial activity was in clear contrast to the higher exposure and longer t1/2,λz of the antibiotic. In conclusion, concomitant oral iron dosing induced significant changes in the pharmacokinetics/pharmacodynamics of intravenous ciprofloxacin.
Validating Arguments for Observational Instruments: Attending to Multiple Sources of Variation

Measurement scholars have recently constructed validity arguments in support of a variety of educational assessments, including classroom observation instruments. In this article, we note that users must examine the robustness of validity arguments to variation in the implementation of these instruments. We illustrate how such an analysis might be used to assess a validity argument constructed for the Mathematical Quality of Instruction instrument, focusing in particular on the effects of varying the rater pool, subject matter content, observation procedure, and district context. Variation in the subject matter content of lessons did not affect rater agreement with master scores, but the evaluation of other portions of the validity argument varied according to the composition of the rater pool, observation procedure, and district context. These results demonstrate the need for conducting such analyses, especially for classroom observation instruments that are subject to multiple sources of variation.
The Medial SuralMedial Gastrocnemius Perforator Local Flap

The medial suralmedial gastrocnemius perforator flap has previously been described as a free flap distinguished by the potential for a large yet thin cutaneous flap that incorporates the calf skin territory. Its medial sural vascular pedicle can be tailored to allow reach extending from the popliteal fossa to the suprapatellar area also as a local flap without any need for microsurgery. Two variations presented are possible as either a broad-based peninsular or island flap. Both are alternatives to the more traditional medial gastrocnemius muscle flap and, because this is a true muscle perforator flap, function is always preserved.
Following anterior resection for rectal cancer, defunctioning ileostomy closure may be significantly delayed by adjuvant chemotherapy: a retrospective study

Objective A temporary loop ileostomy is often created to minimize the impact of peritoneal sepsis from an anastomotic dehiscence following colo‐anal or low colorectal anastomosis. These stomas are not without complications. Clinicians tend to advise patients that their loop ileostomy will be reversed within 6–12 weeks of formation. However, factors such as adjuvant chemotherapy may affect the timing of closure. The aim of this study was to review the time between formation and closure of loop ileostomies following total mesorectal excision in patients with rectal cancer.
Author Clustering using Hierarchical Clustering Analysis

This paper presents our approach to the Author Clustering task at PAN 2017. We performed a hierarchical clustering analysis of different document features: typed and untyped character n-grams, and word n-grams. We experimented with two feature representation methods, log-entropy model, and tf-idf; while tuning minimum frequency threshold values to reduce the dimensionality. Our system was ranked 1 in both subtasks, author clustering and authorship-link ranking.
Pharmacological and signaling analysis of human chemokine receptor CCR-7 stably expressed in HEK-293 cells: high-affinity binding of recombinant ligands MIP-3beta and SLC stimulates multiple signaling cascades.

The chemokine receptor CCR-7 is expressed in T, NK, and dendritic cells in a time-ordered and stimulus-dependent manner. Thorough analyses of the pharmacological profiles of the recombinant ligands for CCR-7, MIP-3beta/ELC/CK-beta 11, and SLC/Exodus-2/TCA4/6C-kine, using CCR-7-expressing HEK-293E transfectants determine that ligands both bind with a K(d) in the 100 pM range-10- to 100-fold greater affinities than published K(d) values. High-affinity binding of each ligand is associated with rapid mobilization of intracellular calcium and cell migration as predicted for chemokine GPCRs, and in keeping with more recent evidence, robust activation of mitogen-activated protein kinase (MAPK).
A Comparison of Menu Configurations and Pointing Devices for Use with Wearable Computers while Mobile and Stationary

Wearable computing technology offers tremendous possibilities to support users in performing a variety of tasks that go beyond traditional desk-based computer interaction. Recent wearable systems share many capabilities with desk-based workstations, but often differ in the way user input is acquired and processed. This paper investigates four commercially available pointing devices and four on-screen menu configurations to assess which are most appropriate for performing menu selection tasks using a wearable computer system in a mobile and stationary scenario. We conducted a controlled user study to compare a trackball, touchpad, gyroscopic mouse and Twiddler2 in combination with pull-down, linear (fixed and pop-up) and pie pop-up menus. Our results indicate that pie pop-up menus are the most effective menu structure irrespective of the input device used, and that the trackball device outperforms the remaining devices in terms of speed and error rate.
Predominant α2/β2/γ3 AMPK activation during exercise in human skeletal muscle

5′AMP‐activated protein kinase (AMPK) is a key regulator of cellular metabolism and is regulated in muscle during exercise. We have previously established that only three of 12 possible AMPK α/β/γ‐heterotrimers are present in human skeletal muscle. Previous studies describe discrepancies between total AMPK activity and regulation of its target acetyl‐CoA‐carboxylase (ACC)β. Also, exercise training decreases expression of the regulatory γ3 AMPK subunit and attenuates α2 AMPK activity during exercise. We hypothesize that these observations reflect a differential regulation of the AMPK heterotrimers. We provide evidence here that only the α2/β2/γ3 subunit is phosphorylated and activated during high‐intensity exercise in vivo. The activity associated with the remaining two AMPK heterotrimers, α1/β2/γ1 and α2/β2/γ1, is either unchanged (20 min, 80% maximal oxygen uptake ) or decreased (30 or 120 s sprint‐exercise). The differential activity of the heterotrimers leads to a total α‐AMPK activity, that is decreased (30 s trial), unchanged (120 s trial) and increased (20 min trial). AMPK activity associated with the α2/β2/γ3 heterotrimer was strongly correlated to γ3‐associated α‐Thr‐172 AMPK phosphorylation (r2= 0.84, P < 0.001) and to ACCβ Ser‐221 phosphorylation (r2= 0.65, P < 0.001). These data single out the α2/β2/γ3 heterotrimer as an important actor in exercise‐regulated AMPK signalling in human skeletal muscle, probably mediating phosphorylation of ACCβ.
Differential Regulation of Transcription through Distinct Suppressor of Hairless DNA Binding Site Architectures during Notch Signaling in Proneural Clusters

ABSTRACT In Drosophila melanogaster, achaete (ac) and m8 are model basic helix-loop-helix activator (bHLH A) and repressor genes, respectively, that have the opposite cell expression pattern in proneural clusters during Notch signaling. Previous studies have shown that activation of m8 transcription in specific cells within proneural clusters by Notch signaling is programmed by a “combinatorial” and “architectural” DNA transcription code containing binding sites for the Su(H) and proneural bHLH A proteins. Here we show the novel result that the ac promoter contains a similar combinatorial code of Su(H) and bHLH A binding sites but contains a different Su(H) site architectural code that does not mediate activation during Notch signaling, thus programming a cell expression pattern opposite that of m8 in proneural clusters.
Keratin mutations of epidermolysis bullosa simplex alter the kinetics of stress response to osmotic shock

The intermediate filament cytoskeleton is thought to confer physical resilience on tissue cells, on the basis of extrapolations from the phenotype of cell fragility that results from mutations in skin keratins. There is a need for functional cell assays in which the impact of stress on intermediate filaments can be induced and analyzed. Using osmotic shock, we have induced cytoskeleton changes that suggest protective functions for actin and intermediate filament systems. Induction of the resulting stress response has been monitored in keratinocyte cells lines carrying K5 or K14 mutations, which are associated with varying severity of epidermolysis bullosa simplex. Cells with severe mutations were more sensitive to osmotic stress and took longer to recover from it. Their stress-activated response pathways were induced faster, as seen by early activation of JNK, ATF-2 and c-Jun. We demonstrate that the speed of a cell's response to hypotonic stress, by activation of the SAPK/JNK pathway, is correlated with the clinical severity of the mutation carried. The response to hypo-osmotic shock constitutes a discriminating stress assay to distinguish between the effects of different keratin mutations and is a potentially valuable tool in developing therapeutic strategies for keratin-based skin fragility disorders.
Effects of early abciximab administration before primary percutaneous coronary intervention on left ventricular function assessed by cardiac magnetic resonance.

BACKGROUND It has been shown that early abciximab administration before primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI) improves efficacy of treatment. However, there are no data on the impact of this strategy on left ventricular (LV) function during long-term follow-up. AIM To analyse the effects of early abciximab administration in patients with first anterior STEMI treated with pPCI on infarct size and LV function assessed by cardiac magnetic resonance. METHODS A total of 59 patients with STEMI, <12 hours from the chest pain onset, without cardiogenic shock, admitted to local hospitals without interventional facilities, with anticipated delay to pPCI <90 min were randomly assigned to two study groups: 27 patients received abciximab before transfer to the catheterisation laboratory (early abciximab group), and 32 patients received abciximab in the catheterisation laboratory just before pPCI (late abciximab group). All patients received aspirin and heparin (70 U/kg) before transfer to the cath lab. Clopidogrel loading dose was administered in the cath lab before angiography. RESULTS Cardiac magnetic resonance was performed in 14 patients from each study group 1 year after pPCI and revealed a significantly lower LV end-systolic volume index (p=0.003), end-diastolic volume index (p=0.009) and better ejection fraction (p <0.05) in patients who received abciximab early. CONCLUSIONS Early abciximab administration prior to transfer for pPCI in patients with first anterior STEMI results in a lower degree of LV remodelling and better LV ejection fraction at 1-year follow-up compared to late abciximab administration in the cath lab during pPCI.