Miracle-dz/UniFAR-FTUs huggingface dataset:
Interindividual variation in olanzapine concentration influenced by UGT1A4 L48V polymorphism in serum and upstream FMO polymorphisms in cerebrospinal fluid.

Pharmacogenetics is the study of variability in drug response attributed to genetic variation. Olanzapine (OLA) is a widely used antipsychotic drug for schizophrenia treatment. The pharmacokinetics of OLA display large inter-individual variation leading to multiple-fold differences in drug exposure between patients at a given dose. This variation in turn gives rise to the need of individualized dosing in order to avoid concentration-dependent adverse effects and therapeutic failure. The observed variability has been partially explained by environmental and physiological factors. Genetically determined differences in drug metabolism represent a less studied source of variability. Precluded contribution by cytochrome P450 (CYP) 2D6 calls for evaluation of the other major OLA metabolizing enzymes. The objective of this thesis was to study pharmacogenetic influence of flavin-containing monooxygenase (FMO) 1 and 3, CYP1A2 and uridine diphosphate-glucuronosyltransferase (UGT) 1A4 on therapeutic OLA exposure. We conducted genetic association studies applying gene re-sequencing and genotyping of candidate and tagging SNPs.Patients carrying the FMO1*6 allele displayed increased dose-adjusted concentrations (C/Ds) of OLA, in serum as well as cerebrospinal fluid. Patients who were homozygous for the FMO3 K158-G308 compound variant showed reduced C/Ds of OLA N-oxide metabolite, but no alteration in OLA exposure. This compound variant is expected to have clinical relevance primarily for non-African populations, since low frequencies were detected among native Africans. Deviation in OLA exposure was observed in carrier of a rare FMO3 mutation, predicted in silico to affect gene splicing. Reduced OLA exposure was observed in UGT1A4*3 carriers. The CYP1A2 -163(A) (CYP1A2*1F) variant was not associated with increase in CYP1A2-catalyzed OLA metabolism or reduction in OLA exposure. Correlations were detected for two cis-acting variants within the inter-genetic region of the CYP1A cluster and a trans-acting variant located upstream the locus encoding aryl hydrocarbon receptor. The inconsistent data reported for CYP1A2*1F could be explained by presence of ethnic specific haplotype structures incorporating the -163(A) variant.A continuously improved understanding of the wide range of factors that can influence pharmacokinetics and pharmacodynamics will increase the likelihood of achieving optimal treatment response for individual patients.
Elastin accumulation is regulated at the level of degradation by macrophage metalloelastase (MMP‐12) during experimental liver fibrosis

Elastin has been linked to maturity of liver fibrosis. To date, the regulation of elastin secretion and its degradation in liver fibrosis has not been characterized. The aim of this work was to define elastin accumulation and the role of the paradigm elastase macrophage metalloelastase (MMP‐12) in its turnover during fibrosis. Liver fibrosis was induced by either intraperitoneal injections of carbon tetrachloride (CCl4) for up to 12 weeks (rat and mouse) or oral administration of thioacetamide (TAA) for 1 year (mouse). Elastin synthesis, deposition, and degradation were investigated by immunohistochemistry, quantitative polymerase chain reaction (qPCR), western blotting, and casein zymography. The regulation of MMP‐12 elastin degradation was defined mechanistically using CD11b‐DTR and MMP‐12 knockout mice. In a CCl4 model of fibrosis in rat, elastin deposition was significantly increased only in advanced fibrosis. Tropoelastin expression increased with duration of injury. MMP‐12 protein levels were only modestly changed and in coimmunoprecipitation experiments MMP‐12 was bound in greater quantities to its inhibitor TIMP‐1 in advanced versus early fibrosis. Immunohistochemistry and macrophage depletion experiments indicated that macrophages were the sole source of MMP‐12. Exposure of CCl4 in MMP‐12−/− mice led to a similar degree of overall fibrosis compared to wildtype (WT) but increased perisinusoidal elastin. Conversely, oral administration of TAA caused both higher elastin accumulation and higher fibrosis in MMP‐12−/− mice compared with WT. Conclusion: Elastin is regulated at the level of degradation during liver fibrosis. Macrophage‐derived MMP‐12 regulates elastin degradation even in progressive experimental liver fibrosis. These observations have important implications for the design of antifibrotic therapies. (HEPATOLOGY 2012;55:1965–1975)
Mass spectrometric characterization of the Campylobacter jejuni adherence factor CadF reveals post‐translational processing that removes immunogenicity while retaining fibronectin binding

Campylobacter jejuni is a major gastrointestinal pathogen that colonizes host mucosa via interactions with extracellular matrix proteins, such as fibronectin (Fn). Fn‐binding is mediated by a 37 kDa outer membrane protein termed Campylobacter adherence Factor (CadF). The outer membrane protein profile of a recent gastrointestinal C. jejuni clinical isolate (JHH1) was analysed using 2‐DE and MS. Several spots were identified as products of the cadF gene. These included mass and pI variants of 34 and 30 kDa, as well as 24 kDa (CadF24) and 22 kDa (CadF22) mass variants. CadF variants were fully characterized by MALDI‐TOF MS and MALDI‐MS/MS. These data confirmed that CadF forms re‐folding variants resulting in spots with lower mass and varying pI that are identical at the amino acid sequence level and are not modified post‐translationally. CadF22 and CadF24, however, were characterized as N‐terminal, membrane‐associated polypeptides resulting from cleavage between serine195 and leucine196, and glycine201 and phenylalanine202, respectively. These variants were more abundant in the virulent (O) isolate of C. jejuni NCTC11168 when compared with the avirulent (genome sequenced) isolate. Hexahistidine fusion constructs of full‐length CadF (34 kDa), CadF24, and the deleted C‐terminal OmpA domain (14 kDa; CadF14) were created in Escherichia coli. Recombinant CadF variants were probed against patient sera and revealed that only full‐length CadF retained reactivity. Binding assays showed that CadF24 retained Fn‐binding capability, while CadF14 did not bind Fn. These data suggest that the immunogenic epitope of CadF is cleaved to generate smaller Fn‐binding polypeptides, which are not recognized by the host humoral response. CadF cleavage therefore may be associated with virulence in C. jejuni.
RESOLVING THE STRUCTURE AND KINEMATICS OF THE BN OBJECT AT 0.″2 RESOLUTION

We present sensitive 7 mm observations of the H53α recombination line and adjacent continuum, made toward the Orion BN/KL region. In the continuum we detect the BN object, the radio source I (GMR I) and the radio counterpart of the infrared (IR) source n (Orion-n). Comparing with observations made at similar angular resolutions but lower frequency, we discuss the spectral indices and angular sizes of these sources. In the H53α line, we only detect the BN object. This is the first time that radio recombination lines have been detected from this source. The LSR radial velocity of BN from the H53α line, vLSR = 20.1 ± 2.1 km s−1, is consistent with that found from previous studies in near-IR lines. While the continuum emission is expected to have considerable optical depth at 7 mm, the observed H53α line emission is consistent with an optically thin nature and we discuss possible explanations for this apparent discrepancy. There is evidence of a velocity gradient, with the NE part of BN being redshifted by ∼10 km s−1 with respect to the SW part. This is consistent with the suggestion of Jiang et al. that BN may be driving an ionized outflow along that direction.
Gender determination using cheiloscopy

Background: Although lip prints have been used as an evidence for human identification in forensic science, there exists a doubt about its role in gender determination. Aims: The present study was designed for documenting common patterns, as well as their variation in the study population, with objective of evaluating uniqueness of the lip print pattern among the study population, as well as to evaluate the possibility of gender determination. Study Design: Two hundred and thirty five lip prints were collected from volunteers among out patients of Darshan Dental College and Hospital, as well as community dental care camps of rural areas around Udaipur. Materials and Methods: Lip prints were recorded with transparent overlay and transferred on to a bond paper. It was then photographed using a Canon EOS 55OD 16 mega pixel digital camera. Software Picasa 3.6 and Microsoft Picture Manager were used to digitally enhance the quality and magnify the image bearing the groove pattern. Lip prints were later analyzed. Statistical Analysis: Pearson chi square test was adopted for statistical analysis and probability (P value) was calculated. Conclusion: In our study, none of the lip prints were identical, thus confirming the role of lip prints in individual identification. Dots, reticular and complex patterns were significant in gender determination.
Traffic modeling and prediction using sensor networks

We propose a probabilistic framework for modeling and predicting traffic patterns using information obtained from wireless sensor networks. For concreteness, we apply the proposed framework to a smart building application in which traffic patterns of humans are modeled and predicted through human detection and matching of their images taken from cameras at different locations. Experiments with more than 100,000 images of over 40 subjects demonstrate promising results in traffic pattern prediction using the proposed algorithm. The algorithm can also be applied to other applications, including surveillance, traffic monitoring, abnormality detection, and location-based services. In addition, the long-term deployment of the network can be used for security, energy conservation, and utilization improvement of smart buildings.
Differential and sequential delivery of fluorescent lysosomal probes into phagosomes in mouse peritoneal macrophages

It has previously been inferred that the fusion of a macrophage secondary lysosome with a phagosome delivers the entire lysosomal contents uniformly to the phagosome. We found, however, that different fluorescent lysosomal probes can enter phagosomes at remarkably different rates, even though they are initially sequestered together in the same organelles. Thus, sulforhodamine is almost exclusively delivered to yeast-containing phagosomes within 2 h of phagocytosis. But fluoresceinated, high molecular weight dextran accumulates in the same phagosomes only over a period of approximately 24 h. We postulate that the delivery of lysosomal contents may involve an intermittent and incremental process in which individual components can be selectively and sequentially transferred.
Neural correlates of exemplar novelty processing under different spatial attention conditions

The detection of novel events and their identification is a basic prerequisite in a rapidly changing environment. Recently, the processing of novelty has been shown to rely on the hippocampus and to be associated with activity in reward‐related areas. The present study investigated the influence of spatial attention on neural processing of novel relative to frequently presented standard and target stimuli. Never‐before‐seen Mandelbrot‐fractals absent of semantic content were employed as stimulus material. Consistent with current theories, novelty activated a widespread network of brain areas including the hippocampus. No activity, however, could be observed in reward‐related areas with the novel stimuli absent of a semantic meaning employed here. In the perceptual part of the novelty‐processing network a region in the lingual gyrus was found to specifically process novel events when they occurred outside the focus of spatial attention. These findings indicate that the initial detection of unexpected novel events generally occurs in specialized perceptual areas within the ventral visual stream, whereas activation of reward‐related areas appears to be restricted to events that do possess a semantic content indicative of the biological relevance of the stimulus. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Metabolic risk factors and long‐term graft function after paediatric renal transplantation

The aim of this study was to evaluate metabolic risk factors and their impact on long‐term allograft function in paediatric renal transplant (RTx) patients. We reviewed the medical records of 210 RTx patients who underwent transplantation at a median age of 4.5 years (range 0.7–18.2) and a median follow‐up of 7.0 years (range 1.5–18.0). Data on lipid and glucose metabolism, uric acid levels, weight and blood pressure were collected up to 13 years post‐RTx, and the findings were correlated with the measured glomerular filtration rate (GFR). Beyond the first year, GFR showed gradual deterioration with a mean decline of 2.4 ml/min/1.73 m2/year. Metabolic syndrome, overweight, hypertension and type 2 diabetes were diagnosed in 14–19%, 20–23%, 62–87% and 3–5% of the patients, respectively. These entities showed only mild association with the concomitant or long‐term GFR values. Dyslipidaemia was common and hypertriglyceridaemia associated with a lower GFR at 1.5 and 5 years post‐RTx (P = 0.008 and P = 0.017, respectively). Similarly, hyperuricaemia was frequent and associated significantly with GFR (P < 0.001). Except for hyperuricaemia and hypertriglyceridaemia, metabolic risk factors beyond the first postoperative year associated modestly with the long‐term kidney graft function in paediatric RTx patients.
On Measurement Bias in Causal Inference

This paper addresses the problem of measurement errors in causal inference and highlights several algebraic and graphical methods for eliminating systematic bias induced by such errors. In particulars, the paper discusses the control of partially observable confounders in parametric and non parametric models and the computational problem of obtaining bias-free effect estimates in such models.
Evaluation of two ELISA assay kits against RT-PCR for diagnosis of dengue virus infection in a hospital setting in Karachi, Pakistan.

OBJECTIVE To evaluate two commercially available ELISA-based kits against RT-PCR for the diagnosis of dengue virus infection in a Tertiary Care center in Karachi. METHODS During the 2006 Dengue outbreak, sera were collected from patients clinically classified as dengue fever and graded according to WHO grading. Out of these, 83 samples were selected randomly and analyzed using two different commercial kits (PanBio versus Calbiotech) and were compared with RT-PCR. Clinical charts of the inpatients were also reviewed. Statistical significance was considered at P < or = 0.05. RESULTS Clinically, a total of 29 (69%) in-patients were diagnosed with dengue haemorrhagic fever, the remaining 13 (30.9%) were diagnosed as dengue fever. Diagnostic PCR was positive in 73 (87.9%) of the total 83 patients. PanBio capture ELISA had a sensitivity of 83.5%. Calbiotech on the other hand, had a sensitivity of 50.7%. The association of PanBio assay with PCR was found to be statistically significant (p<0.001). CONCLUSION Although RT-PCR is considered as gold standard for diagnosis of dengue virus infection, serological methods play important role in diagnosis as they are cost effective and easily available, especially in dengue endemic countries. Sensitivity and specificity of commercial kits can be variable; therefore evaluation of commercial ELISA kits is important in local setting.
Molecular Characterization of Hemorrhagic Enteritis Viruses (HEV) Detected in HEV-Vaccinated Commercial Turkey Flocks in Germany

SUMMARY Despite the application of live hemorrhagic enteritis virus (HEV) vaccines, HEV field outbreaks are suspected to still occur in turkey flocks in Germany. Increasing secondary bacterial infections in HEV-vaccinated flocks suggest that vaccines may be losing efficacy or, possibly, that vaccine strains are causing disease. Thus, the goal of the current study was to investigate the diversity of HEV isolates from fattening turkey flocks between 2008 and 2012 by characterizing the open reading frame (ORF)1 gene at its 5′ and 3′ ends. Analyses of ORF1 sequences of field isolates and comparison with sequences present in databases revealed that in many cases (13 out of 16 samples), vaccine (avirulent) strains were present. In addition, data indicated the circulation of suspected virulent field isolates and these isolates (3 out of 16) cluster with an early isolate from Germany in the 1980s, but show some mutations in the predicted amino acid (aa) sequences of ORF1 compared to the early isolate. These virulent isolates clearly differ from the spleen-derived avirulent Domermuth vaccine strain used in Germany. In this study, a unique isolate was identified and showed unusual nucleotide mutations that resulted in aa exchanges at the 5′ end of ORF1 between aa positions 34 and 174. This genetic drift suggests evolution of HEV including virulent and vaccine-derived strains in the field. This may lead to evasion of vaccinal immunity by drifted viruses and/or an increase in the virulence of field strains.
Flow through and over model porous media with or without inertial effects

An experimental research program was designed to study laminar flows through and over models of porous media with or without inertial effects. The models used were made up of circular or square rods arranged to cover solid volume fraction  ranging from 0.03 to 0.49, and filling fraction h / H ranging from 0.34 to 1 of the test channel. In this way, the ratios of the depth of the test section to the porous medium pore H / l ranged from 5.75 to 18.25. Three types of model porous media were tested: (1) two-dimensional ‘horizontal’ models, having rod axes aligned along the span of the channel in a staggered or non-staggered fashion; (2) three-dimensional ‘vertical’ models with rod axes aligned in the transverse direction; and (3) three-dimensional ‘mesh’ models with rod axes aligned along both transverse and spanwise directions. Using a pressure-driven viscous fluid, the bulk Reynolds number Rebulk was varied from 0.1 to 10.3. Velocity measurements were obtained using particle image velocimetry at various streamwise-transverse planes of the test section. Differential pressure measurements were also obtained using electronic transducers. These measurements were used to determine relevant governing equations for the flow through the porous media; to characterize the effects of  rod shape and arrangement, h / H, H / l, porous media dimensionality, and Rebulk on the flow; and to predict the flow at the porous medium-free flow interface. The Izbash and quadratic Forchheimer equations were respectively found to describe well the flow through twoand three-dimensional porous media. Penetration of the free flow into the porous medium varied with φ and rod arrangement, but was nearly independent of the rod shape. At the interface between the porous medium and the free flow, h / H and H / l effects were found to be counteractive. Penetration was highest for the vertical models compared with the mesh and horizontal models. Inertial dependence of interfacial flow was weak when porous medium conditions were considered. The interfacial flow was found to follow a dose response formulation with a predictable slip coefficient.
The Fascial Elevation and Tendon Origin Resection Technique for the Treatment of Chronic Recalcitrant Medial Epicondylitis

Background: Medial epicondylitis is a tendinopathy of the common flexor-pronator origin, and surgical treatment is required when this condition fails to respond to nonoperative methods. This study details the development of a new technique, termed fascial elevation and tendon origin resection (FETOR), which facilitates the complete visualization and resection of the CFPO with limited soft tissue dissection. Purpose: To evaluate the outcomes of FETOR for the treatment of chronic recalcitrant medial epicondylitis. Study Design: Case series; Level of evidence, 4. Methods: The electronic medical records of patients who underwent FETOR from January 2008 to July 2011 were retrospectively reviewed. Outcome assessments included the visual analog scale (VAS) for average pain, pain at rest, and pain experienced during hard work or heavy lifting; the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire; and pain-free grip strength. Preoperative and postoperative data were compared. Results: A total of 22 elbows in 20 patients with a mean age of 48.8 years (range, 29-58 years) were included. At a mean follow-up of 35.6 months (range, 16-77 months), the VAS score decreased by 93% for average pain, 94% for pain at rest, and 83% for pain during hard work or heavy lifting (P < .001). The patients’ perception of arm function as assessed using the DASH recovered to the level of the healthy population (from a mean of 51.6 ± 18.0 to 8.0 ± 11.1; P < .001). The mean pain-free grip strength improved significantly from 53.7% ± 30.3% to 97.3% ± 19.8% of the uninvolved arm (P < .001). Eighteen (90%) patients were satisfied with the surgical outcomes, while 2 patients changed their jobs because of decreased elbow function. No major complications occurred. Conclusion: The FETOR technique is an effective and safe method for the treatment of chronic recalcitrant medial epicondylitis.
Developments in Plasma Arc Cutting (PAC) of Steel Alloys: A Review

The Plasma Arc Cutting (PAC) process was developed for difficult-to-machine materials in order to overcome the inefficiency and ineffectiveness of conventional machining methods when it comes to complex shapes and tool wear due to the contact between the tool and the workpiece. PAC consumes ionized gas, known as the heat source, and a high energy stream, known as the plasma. Many researchers have examined the PAC of steel alloys by considering the cutting power, scanning speed, cutting height and plasma gas pressure as the process parameters, and analysing the effects on the edge roughness, the kerf taper angle (conicity), burr formation, Heat Affected Zone (HAZ), Material Removal Rate (MRR), surface quality after cutting, and the metallurgical effects of the cut. A comprehensive review was carried out on developments in the analysis and optimization of PAC for steel alloys. It is observed that, the feed rate and edge roughness have a significant effect on the machining characteristics; however, less consideration was given by the researcher to these parameters. In addition, a critical comparison was made of the process parameters involved and the methods of analysis used, with the aim of providing the status of current research and guidance for future research.
Pulmonary Infection Caused by an Unusual, Slowly Growing Nontuberculous Mycobacterium

ABSTRACT Mycobacterium triplex, a recently described slowly growing nontuberculous mycobacterium, was isolated from a Finnish patient with pulmonary mycobacteriosis. The disease was successfully treated with antimycobacterial drugs. The strain isolated, which was similar to the type strain but differed slightly from the species description, was regarded as a variant of M. triplex sensu stricto. According to present knowledge this variant of the species has never been isolated before.