Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum from methimazole-treated patients induces activation of aryl hydrocarbon receptor, a transcription factor that binds to dioxin-response elements.

BACKGROUND The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by xenobiotic substances such as dioxin. After activation, it binds to dioxin response elements of DNA, thereby inducing transcription of a variety of xenobiotic metabolizing enzymes. To investigate whether AhR-activating substances accumulate in patients with endocrine disorders, we tested serum samples for AhR-stimulating activity. METHODS Serum AhR-stimulating activity was evaluated by exposing the HepG2 cells transiently transfected with an AhR-responsive reporter plasmid to serum samples. On the basis of preliminary findings that implicated methimazole (MMI), wild-type and AhR-null mice were treated with MMI, and their plasma AhR-stimulating activities and thyroxine levels were quantified. RESULTS In 28 randomly chosen patients, 7 out of 10 Graves' disease patients exhibited increased serum AhR-stimulating activity. The increased activity did not correlate with thyroid hormone status. However, we hypothesized that it might be caused by MMI. Subsequent analyses revealed that in 25 of 26 MMI-treated Graves' patients, serum samples collected after the MMI treatment had significantly higher AhR-stimulating activity compared to samples obtained when the same patients were not on MMI. By contrast, serum AhR-stimulating activity was unchanged in samples from the seven patients on propylthiouracil (PTU) compared to serum taken before the PTU treatment. In vitro experiments demonstrated that an MMI metabolite 3-methyl-2-thiohydantoin, but not MMI, activated AhR. MMI increased plasma AhR-stimulating activities and reduced plasma thyroxine concentrations, in both wild-type and AhR-deficient mice. CONCLUSIONS Graves' patients taking MMI have increased serum AhR-stimulating activity, which is unrelated to thyroid hormone status, but correlates with MMI treatment. The AhR activation is likely caused by 3-methyl-2-thiohydantoin. Further studies are required to determine the potency of 3-methyl-2-thiohydantoin as an AhR activator and the significance of the differences between MMI and PTU observed in this study.
Crystal structure of the phosphorolytic exoribonuclease RNase PH from Bacillus subtilis and implications for its quaternary structure and tRNA binding

RNase PH is a member of the family of phosphorolytic 3′ → 5′ exoribonucleases that also includes polynucleotide phosphorylase (PNPase). RNase PH is involved in the maturation of tRNA precursors and especially important for removal of nucleotide residues near the CCA acceptor end of the mature tRNAs. Wild‐type and triple mutant R68Q‐R73Q‐R76Q RNase PH from Bacillus subtilis have been crystallized and the structures determined by X‐ray diffraction to medium resolution. Wild‐type and triple mutant RNase PH crystallize as a hexamer and dimer, respectively. The structures contain a rare left‐handed βαβ‐motif in the N‐terminal portion of the protein. This motif has also been identified in other enzymes involved in RNA metabolism. The RNase PH structure and active site can, despite low sequence similarity, be overlayed with the N‐terminal core of the structure and active site of Streptomyces antibioticus PNPase. The surface of the RNase PH dimer fit the shape of a tRNA molecule.
An object-oriented simulation program for CMS

The CMS detector simulation package, OSCAR, is based on the Geant4 simulation toolkit and the CMS object-oriented framework for simulation and reconstruction. Geant4 provides a rich set of physics processes describing in detail electromagnetic and hadronic interactions. It also provides the tools for the implementation of the full CMS detector geometry and the interfaces required for recovering information from the particle tracking in the detectors. This functionality is interfaced to the CMS framework, which, via its "action on demand" mechanisms, allows the user to selectively load desired modules and to configure and tune the final application. The complete CMS detector is rather complex with more than 1 million geometrical volumes. OSCAR has been validated by comparing its results with test beam data and with results from simulation with a GEANT3-based program. It has been successfully deployed in the 2004 data challenge for CMS, where more than 35 million events for various LHC physics channels were simulated and analysed.
Three Adjacent Serines in the Extracellular Domains of the CaR Are Required for l-Amino Acid-mediated Potentiation of Receptor Function*

The extracellular calcium (Ca2+ o )-sensing receptor (CaR) is a key player in Ca2+ o homeostasis. The activity of CaR can be potentiated by various l-amino acids. In this study, we examined whether conserved amino acid residues involved in the binding of glutamate to metabotropic glutamate receptors (mGluRs) also participate in the potentiation of the activity of CaR byl-phenylalanine. Ser-170 corresponding to Thr-188 in rat mGluR1a appears to be important for the modulating actions of phenylalanine. In the presence of phenylalanine, a mutant CaR with a single mutation S170A showed no significant decrease in its EC50 for stimulation by Ca2+ o and a modest increase in its maximal activity. In addition, mutating Ser-169 and Ser-171 together with Ser-170 yielded a more complete block of the phenylalanine modulation than did the single mutation. The presence of the triple mutation, S169A/S170A/S171A, also eliminated phenylalanine potentiation of the activities of heterodimeric receptors in which one of the monomeric receptors had intact triple serines (A877Stop). The putative amino acid binding site of the CaR is probably close to or structurally dependent on the Ca2+ o binding sites of the receptor, because mutant CaRs with mutations in the putative amino acid binding site exhibited severely reduced responses to Ca2+ o .
Clinical correlation of gallstone disease in a Chinese population in Taiwan: experience at Cheng Hsin General Hospital.

AIM To explore the prevalence of gallstone disease (GSD) in Taiwan and condition-associated factors related to it. METHODS We studied a total of 2386 healthy adults (1235 males and 1151 females) voluntarily admitted to Cheng Hsin General Hospital for a paid physical check-up between January 2002 and December 2002. Blood samples and ultrasound sonography results were collected. RESULTS The overall prevalence of GSD among this study-population was 5.3%, including 1.7% (n=40) having a single stone, 2.3% (n=55) having multiple stones, and 1.3% (n=31) having cholecystectomy. The prevalence revealed a statistically significant increase with increasing age (P<0.0001). Females exhibited a greater prevalence of multiple stones than did males (3.0% vs 1.7%, P=0.04). Using multiple logistic regression analysis, the following appeared to be significantly related to the prevalence of GSD: older age (40-49 years vs < 40 years, OR=1.63 [95% CI: 0.76-3.48], 50-59 years vs < 40 years, OR=4.93 [95% CI: 2.43-9.99], 60-69 years vs < 40 years, OR=6.82 [95% CI: 3.19-14.60], > or = 70 years vs < 40 years, OR=10.65 [95% CI: 4.78-23.73]), higher BMI (> or = 27 kg/m2 vs < 24 kg/m2, adjusted OR=1.74 [95% CI: 1.04-2.88]), and higher FPG (> or = 126 mg/dL vs < 110 mg/dL, OR=1.71, 95%CI: 1.01-2.96). CONCLUSION Older age (> or = 50 years), obesity (BMI > or = 27 kg/m2), and type 2 diabetes (FPG > or = 126 mg/dL) are associated with the prevalence of GSD.
Impact of High Oil Prices on Pakistan ’ s Economic Growth

This paper discussed the impact of higher oil prices on the Pakistan’s economy during 1990 to 2008. Pakistan is not oil producing rather oil-importing country. An increase in oil price leads to inflation, increase budget deficit and puts downward pressure on exchange rate which makes imports more expensive. The rising oil prices are the major concern for all the developing economies and Pakistan is suffering from it too. The increase in oil price has further effect the daily consumption pattern of households badly. This study analyzes that, how change in real crude oil price effects the real GDP positively and many other factors differently. For example, a lower government spending, a higher real stock price and a lower interest rate would raise real output for Pakistan.
Use of a bioabsorbable implant for the repair of severed digital flexor tendons in four horses

A new bioabsorbable implant composed of poly-L-lactic acid was used to repair the severed digital flexor tendons of four horses. The limbs were immobilised with distal casts which were changed after six to eight weeks and removed after 12 to 16 weeks. The horses were followed clinically and ultrasonographically for from seven to 19 months after the surgery. The ultrasonographic examination after the cast had been removed showed that the implants had been well incorporated into scar tissue. Two of the horses were mildly lame at the trot seven months after the surgery, but had returned to work after 12 months. The other two horses are still lame. No complications were observed with the implant.
Diabetes prevalence and body mass index differ by ethnicity: the Multiethnic Cohort.

OBJECTIVE The high prevalence of diabetes in non-Caucasian populations is reported not only for Native Hawaiians who suffer from high rates of obesity, but also for Japanese with a relatively low body weight. The objectives of this study were to estimate the prevalence of diabetes among participants of the Multiethnic Cohort (MEC) and to examine the association of body mass index (BMI) with self-reported diabetes by ethnicity. DESIGN Cross-sectional analysis of baseline questionnaire at cohort entry. PARTICIPANTS 187,439 MEC subjects in Hawaii and California from five ethnic groups. MAIN OUTCOME MEASURES Participants completed a 26-page, self-administered survey with questions concerning anthropometrics, demographic, medical, lifestyle, and food consumption behavior. Age-adjusted prevalence of diabetes was calculated by sex and ethnicity and stratified by BMI. Prevalence ratios were determined using logistic regression while adjusting for variables that are known to be related to diabetes. The c statistic was computed to compare models with different confounders. RESULTS The prevalence of self-reported diabetes in the MEC was 11.6%. The age-adjusted diabetes prevalence ranged from 6.3% in Caucasians to 10.2% in Japanese, 16.1% in Native Hawaiians, 15.0% in African Americans, and 15.8% in Latinos. After adjustment for known risk factors, the prevalence ratio by ethnicity ranged between 2.1 (African American and Latino), 2.8 (Japanese), and 3.0 (Native Hawaiian) as compared to Caucasians. These differences were observed among all BMI categories. CONCLUSIONS Ethnic differences in the prevalence of diabetes persisted after stratification by BMI. The prevalence of diabetes was at least two-fold higher in all ethnic groups than among Caucasians.
Supervised learning with random labelling errors

Classical supervised learning from a training set of labelled examples assumes that the labels are correct. But in reality labelling errors may originate, for example, from human mistakes, diverging human opinions, or errors of the measuring instruments. In such cases the training set is misleading and in consequence the learning may suffer. In this thesis we consider probabilistic modelling of random label noise. The goal of this research is two-fold. First, to develop new improved algorithms and architectures from a principled footing which are able to detect and bypass the unwanted effects of mislabelling. Second, to study the performance of such methods both empirically and theoretically. We build upon two classical probabilistic classifiers, the normal discriminant analysis and the logistic regression and introduce the label-noise robust versions of these classifiers. We also develop useful extensions such as a sparse extension and a kernel extension in order to broaden applicability of the robust classifiers. Finally, we devise an ensemble of the robust classifiers in order to understand how the robust models perform collectively. Theoretical and empirical analysis of the proposed models show that the new robust models are superior to the traditional approaches in terms of parameter estimation and classification performance.
A positive feedback loop between RIP3 and JNK controls non-alcoholic steatohepatitis

Non‐alcoholic fatty liver disease (NAFLD) represents the most common liver disease in Western countries and often progresses to non‐alcoholic steatohepatitis (NASH) leading ultimately to liver fibrosis and liver cancer. The occurrence of hepatocyte cell death—so far characterized as hepatocyte apoptosis—represents a fundamental step from benign steatosis toward progressive steatohepatitis. In contrast, the function of RIP3‐dependent “necroptosis” in NASH and NASH‐induced fibrosis is currently unknown. We show that RIP3 is upregulated in human NASH and in a dietary mouse model of steatohepatitis. RIP3 mediates liver injury, inflammation, induction of hepatic progenitor cells/activated cholangiocytes, and liver fibrosis through a pathway suppressed by Caspase‐8. This function of RIP3 is mediated by a positive feedback loop involving activation of Jun‐(N)‐terminal Kinase (JNK). Furthermore, RIP3‐dependent JNK activation promotes the release of pro‐inflammatory mediators like MCP‐1, thereby attracting macrophages to the injured liver and further augmenting RIP3‐dependent signaling, cell death, and liver fibrosis. Thus, RIP3‐dependent necroptosis controls NASH‐induced liver fibrosis. This pathway might represent a novel and specific target for pharmacological strategies in patients with NASH.
L-NAME hypertension alters endothelial and smooth muscle function in rat aorta. Prevention by trandolapril and verapamil.

Nitric oxide is an important regulator of vascular function and blood pressure. Chronic administration of nitric oxide inhibitors provides a new model of hypertension with pronounced target organ damage. We investigated the effects of oral treatment with N omega-nitro-L-arginine methyl ester (L-NAME) for 6 weeks on vascular reactivity of the aorta in Wistar-Kyoto rats. Certain rats received verapamil or trandolapril in addition to L-NAME. Systolic blood pressure increased in the L-NAME group (by approximately or equal to 80 mm Hg systolic) but not in controls or rats treated with verapamil or trandolapril. Isometric tension changes of aortic rings were recorded. Endothelium-dependent relaxations to acetylcholine were reduced in the L-NAME group (58 +/- 6% versus 104 +/- 1% in placebo, P < .05) but were normalized by treatment with verapamil or trandolapril. In contrast, endothelium-independent relaxations to sodium nitroprusside were not significantly reduced in L-NAME hypertension but were slightly enhanced by trandolapril therapy (P < .05) in the L-NAME group only. In quiescent rings, acetylcholine caused endothelium-dependent contractions in particular after in vitro incubation with L-NAME. These contractions tended to be enhanced in L-NAME hypertension (23 +/- 4% versus 14 +/- 3% in the placebo group; P = NS) and were significantly reduced after treatment with verapamil or trandolapril (P < .05). Concentrations to norepinephrine and angiotensin I and II were unaffected by L-NAME hypertension, whereas those to endothelin-1 were reduced (P < .05). (ABSTRACT TRUNCATED AT 250 WORDS)
The economic impact of smoke-free legislation on sales turnover in restaurants and pubs in Tasmania

Tasmania has a population of approximately 473 400—about 4% of the population of Australia—and around 320 bars (known in Australia as “pubs”) and licensed clubs and 400 restaurants and cafes. Legislation came into force there on 1 September 2001 to mandate smoke-free enclosed work and public places, with exemptions for bar and gaming areas where meals are not served or consumed. Our study assessed the economic impact of introducing smoke-free polices in Tasmania on sales in bars, licensed clubs, restaurants, and cafes. We used seasonally adjusted monthly sales data from January 1990 to September 2002 and statistically controlled for trends and random fluctuations. Three distinct hypotheses about the nature of the economic impact are examined. Firstly, the impact was abrupt and permanent; it resulted in a …
Assessment of Influential Range and Characteristics of Fugitive Dust in Limestone Extraction Processes

Abstract Fugitive dust emission from limestone extraction areas is a significant pollution source. The cracking operation in limestone extraction areas easily causes high total suspended particulate (TSP) concentrations in the atmosphere, occasionally exceeding the 1-hr national emission standard of Taiwan (500 μg/m3). The concentration and size distribution were measured at different distances (0.05–15 km) in the extraction areas. The highest hourly concentrations of TSP, PM10 (suspended particulate matter [PM] smaller than 10 μm), and PM2.5 (suspended PM smaller than 2.5 μm) are 1111, 825, and 236 μg/m3, respectively, during the cracking process. Measurement results obtained from the Micro-Orifice Uniform Deposit Impactor indicated that the mass median aerodynamic diameter is ∼0.7 μm, with the geometric standard deviation exceeding 7. In addition, the emission factors are 0.143 and 0.211 kg/t for both vertical well and stair extraction operations, respectively. Experimental results demonstrate that the corresponding TSP control efficiencies for spraying water, planting grass, setting short walls, paving gravel roads, and establishing vertical well transportation are ∼55, 50, 44, 22, and 30%, respectively. Furthermore, the PM10 control efficiencies are ∼45, 41, 54, 35, and 30%, respectively, whereas the PM2.5 control efficiencies are roughly 23, 31, 15, 11, and 10%, individually.
Lower Incidence of Adjacent Segment Degeneration After Anterior Cervical Fusion Found With Those Fusing C5-6 and C6-7 Than Those Leaving C5-6 or C6-7 as an Adjacent Level

Study Design Retrospective analysis of adjacent disc degeneration (ADD) after anterior cervical decompression and fusion (ADF). Objectives To elucidate the influence of the number of levels fused in ADF on the incidence of ADD. Summary of Background Data ADD is known as a complication associated with ADF. However, how the number of levels fused affects the incidence of ADD is not well understood. Methods One hundred and two patients with cervical degenerative disease, who underwent ADF and were followed for more than 24 months, were retrospectively analyzed. They were classified into 2 groups, a long group (L group) consisting of 50 cases with ADF of 4 or more disc levels, and a short group (S group) consisting of 52 cases with ADF of 3 or fewer disc levels. Furthermore, the patients were also divided into 2 groups according to inclusion or exclusion of C5-6 and C6-7 (C group: including both, NC group: not including both). The incidence of ADD, and that of symptomatic ADD (sADD), was compared between the 2 classifications. Results In the L group, there were 13 cases of ADD (26.0%), including 1 case of sADD (2.0%), whereas in the S group, there were 22 cases of ADD (42.3%), including 11 cases of sADD (21.2%). The incidence of sADD was significantly lesser in the L group (P=0.024). Three cases with sADD in the S group required revision surgery, whereas no additional surgery related to ADD was performed on patients in the L group. In addition, in the C group, ADD occurred in 20 of 71 cases (28.2%) and sADD occurred in 4 of 71 cases (5.6%), whereas in the NC group, ADD occurred in 15 of 31 cases (48.4%) and sADD occurred in 8 of 31 cases (25.8%). The incidence of ADD and sADD were significantly lesser in the C group (P=0.048). Conclusions ADD occurs less frequently among patients in whom C5-6 and C6-7 are fused than among those in whom C5-6 or C6-7 is left at an adjacent level, irrespective of the length of the fusion.
Warm season precipitation signal in δ2 H values of wood lignin methoxyl groups from high elevation larch trees in Switzerland.

RATIONALE In this study, we tested stable hydrogen isotope ratios of wood lignin methoxyl groups (δ2 Hmethoxyl values) as a palaeoclimate proxy in dendrochronology. This is a quite new method in the field of dendrochronology and the sample preparation is much simpler than the methods used before to measure δ2 H values from wood. METHODS We measured δ2 Hmethoxyl values in high elevation larch trees (Larix decidua Mill.) from Simplon Valley (southern Switzerland). Thirty-seven larch trees were sampled and five individuals analysed for their δ2 Hmethoxyl values at annual (1971-2009) and pentadal resolution (1746-2009). The δ2 Hmethoxyl values were measured as CH3 I released upon treatment of the dried wood samples with hydroiodic acid. 10-90 μL from the head-space were injected into the gas chromatography/high-temperature conversion/isotope ratio mass spectrometry (GC/HTC-IRMS) system. RESULTS Testing the climate response of the δ2 Hmethoxyl values, the annually resolved series show a positive correlation of r = 0.60 with June/July precipitation. The pentadally resolved δ2 Hmethoxyl series do not show any significant correlation to climate parameters. CONCLUSIONS Increased precipitation during June and July, which are on average warm and relatively dry months, results in higher δ2 H values of the xylem water and, therefore, higher δ2 H values in the lignin methoxyl groups. Therefore, we suggest that δ2 Hmethoxyl values of high elevation larch trees might serve as a summer precipitation proxy.
The validity of the lactate minimum test for determination of the maximal lactate steady state.

PURPOSE The purpose of this study was to investigate the validity of the lactate minimum test ([Lac-]BMIN) in the determination of the velocity at the maximal lactate steady state (V-MLSS), and to identify those physiological factors most closely associated with 8-km running performance. METHODS Thirteen trained male runners (VO2max range 53-67 mL.kg-1.min-1) took part in an 8-km simulated race on flat roads and completed a comprehensive battery of laboratory tests. RESULTS Performance velocity was most strongly correlated with the estimated running velocity at VO2max (r = 0.93) and with V-MLSS (r = 0.92) and velocity at lactate threshold (V-Tlac) (r= 0.93). The running velocity at the ventilatory threshold (V-Tvent) (r = 0.81) and the [Lac-]BMIN (r = 0.83) also produced good correlations with performance velocity. Performance running velocity (mean +/- SEM 16.0 +/- 0.3 km.h-1) was not significantly different from V-MLSS (15.7 +/- 0.3 km.h-1). The running velocity at [Lac-]BMIN (14.9 +/- 0.2 km.h-1) was not significantly different from the V-Tlac (15.1 +/- 0.3 km.h-1) or V-Tvent (14.9 +/- 0.2 km.h-1) was not significantly different from the V-Tlac (15.1 +/- 0.3 km.h-1) or V-Tvent (14.9 +/- 0.3 km.h-1) but was significantly lower than the V-MLSS (P < 0.05). The [Lac-]BMIN provided the lowest correlation with V-MLSS (r = 0.61) and the worst estimate of V-MLSS (SEE = 0.75 km.h-1) compared with the other measures of lactate accumulation. The V-Tlac was not significantly different from V-MLSS and provided the highest correlation (r = 0.94) and a close estimate (SEE = 0.33 km.h-1) of the V-MLSS. CONCLUSIONS It is concluded that of the measures studied relating to blood lactate accumulation during submaximal exercise, V-Tlac provides the best estimate of the V-MLSS and the V-Tlac had equal predictive power for 8-km race performance.