Miracle-dz/UniFAR-FTUs huggingface dataset:
Cognitive stimulation with the Wisconsin Card Sorting Test: functional MR imaging at 1.5 T.

PURPOSE To determine whether functional magnetic resonance (MR) imaging can demonstrate a specific pattern of cerebral activation during cognitive stimulation by using a high-level cognitive task such as the Wisconsin Card Sorting Test. MATERIALS AND METHODS Thirty-one healthy volunteers underwent functional MR imaging with a 1.5-T MR imager with a standard head coil (100/50 [repetition time msec/echo time msec], 230-mm field of view, 40 degrees flip angle, 256 x 256 matrix). For stimulation, a personal computer version of the Wisconsin Card Sorting Test was used. Image analysis was done off-line, and cross-correlation coefficients between the stimulus function and the signal intensity response were calculated on a pixel-by-pixel basis and overlaid onto the corresponding anatomic MR image for each volunteer. RESULTS Stimulation resulted in strongly frontal activation, which included the mesial and the dorsolateral prefrontal cortexes, interconnected with Brodmann areas 44, 45, and 46. While activation was often bilateral, the largest area of activation was in the right hemisphere. Activation also was found in the basal ganglia and the mesial thalamic nuclei. CONCLUSION Functional MR imaging can demonstrate a specific pattern during activation with a cognitive task. Functional MR imaging has promise for more precise anatomic and functional imaging studies of brain interaction than have other imaging modalities.
Multiplex Approach for Screening Genetic Markers of Microbial Indicators

Genetic markers are expected to provide better specificity in epidemiological studies and potentially serve as better indicators of waterborne pathogens. Methods used to assess genetic markers of emerging microbial indicators include pulsed field gel electrophoresis, polymerase chain reaction (PCR), and microarrays. This paper outlines a high‐throughput approach to screen for such genetic markers using a set of theoretical and experimental screening tools. The theoretical screening involves evaluating genes related to the ribosomal RNA and specific functions from emerging indicator groups, followed by experimental validation with appropriate sampling schemes and high‐throughput and economical screening methods, such as microarrays, real time PCR, and on‐chip PCR. Analysis of a wide range of samples covering temporal variability in location, host, and waterborne disease outbreaks is essential. The proposed approach is expected to shorten the time and cost associated with searching for new genetic markers of emerging indicators by at least 10‐fold.
C CHILD POVERTY AND CHANGES IN CHILD POVERTY *

This article offers a cross-country overview of child poverty, changes in child poverty, and the impact of public policy in North America and Europe. Levels and changes in child poverty rates in 12 Organisation for Economic Co-operation and Development (OECD) countries during the 1990s are documented using data from the Luxembourg Income Study project, and a decomposition analysis is used to uncover the relative role of demographic factors, labor markets, and income transfers from the state in determining the magnitude and direction of the changes. Child poverty rates fell noticeably in only three countries and rose in three others. In no country were demographic factors a force for higher child poverty rates, but these factors were also limited in their ability to cushion children from adverse shocks originating in the labor market or the government sector. Increases in the labor market engagement of mothers consistently lowered child poverty rates, while decreases in the employment rates and earnings of fathers were a force for higher rates. Finally, there is no single road to lower child poverty rates. Reforms to income transfers intended to increase labor supply may or may not end up lowering the child poverty rate.
Development and Evaluation of Novel Real-Time Reverse Transcription-PCR Assays with Locked Nucleic Acid Probes Targeting Leader Sequences of Human-Pathogenic Coronaviruses

ABSTRACT Based on findings in small RNA-sequencing (Seq) data analysis, we developed highly sensitive and specific real-time reverse transcription (RT)-PCR assays with locked nucleic acid probes targeting the abundantly expressed leader sequences of Middle East respiratory syndrome coronavirus (MERS-CoV) and other human coronaviruses. Analytical and clinical evaluations showed their noninferiority to a commercial multiplex PCR test for the detection of these coronaviruses.
Lipopolysaccharide modulates p300 and Sirt1 to promote PRMT1 stability via an SCFFbxl17-recognized acetyldegron

ABSTRACT E3 ubiquitin ligase recognizes its protein substrates via specific molecular signatures for ubiquitin proteasomal degradation. However, the role of acetylation/deacetylation in the process of E3 ubiquitin ligase recognizing its protein substrates is not fully studied. Here, we report that a tandem IK motif in protein arginine methyltransferase 1 (PRMT1) forms an acetyldegron to recruit the F-box/LRR-repeat protein 17 (FBXL17), a component of the SKP1–CUL1–F-box protein (SCF)-type E3 ubiquitin ligase complex. PRMT1 is polyubiquitylated for proteasome degradation with a half-life of approximately 4 h in lung epithelial cells. SCFFbxl17 mediates PRMT1 polyubiquitylation at K117. SCFFbxl17 specifically binds PRMT1 via a unique motif IKxxxIK. Strikingly, the acetylation/deacetylation status of the lysine residues within the motif determines Fbxl17 binding. Deacetylation on both K200 and K205 by Sirtuin 1 (Sirt1) and acetylation of p300 (EP300) on K205 collaboratively prepare the motif for SCFFbxl17 binding thereby triggering PRMT1 protein degradation. Pathogen-derived lipopolysaccharide (LPS) downregulates Sirt1 and p300 to protect PRMT1 from degradation. This study demonstrates that LPS promotes PRMT1 stability by blockade of PRMT1 and SCFFbxl17 binding via an acetylation/deacetylation-modified acetyldegron; and LPS-elevated levels of PRMT1 lead to bronchial epithelial cell overgrowth in pulmonary inflammatory diseases. Summary: Bacteria-derived endotoxin LPS downregulates both the acetyltransferase p300 and the deacetylase Sirt1 to promote PRMT1 protein stability via an SCFFbxl17 E3 ligase-recognized acetydegron that augments bronchial epithelial cell overgrowth.
Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999.

I. Purpose and Scope II. Methacholine Challenge Testing A. Indications B. Contraindications C. Technician Training/Qualifications D. Safety E. Patient Preparation F. Choice and Preparation of Methacholine G. Dosing Protocols 1. Two-Minute Tidal Breathing Dosing Protocol 2. Five-Breath Dosimeter Protocol H. Nebulizers and Dosimeters I. Spirometry and Other End-point Measures J. Data Presentation K. Interpretation III. Exercise Challenge A. Indications B. Contraindications and Patient Preparation C. Exercise Challenge Testing D. Assessing the Response References Appendix A: Sample Methacholine Challenge Test Consent Form Appendix B: Sample Methacholine Challenge Pretest Questionnaire Appendix C: Sample Report Format Appendix D: Equipment Sources
Impact of Biocontrol Pseudomonas fluorescens CHA0 and a Genetically Modified Derivative on the Diversity of Culturable Fungi in the Cucumber Rhizosphere

ABSTRACT Little is known about the effects of Pseudomonasbiocontrol inoculants on nontarget rhizosphere fungi. This issue was addressed using the biocontrol agent Pseudomonas fluorescens CHA0-Rif, which produces the antimicrobial polyketides 2,4-diacetylphloroglucinol (Phl) and pyoluteorin (Plt) and protects cucumber from several fungal pathogens, includingPythium spp. , as well as the genetically modified derivative CHA0-Rif(pME3424). Strain CHA0-Rif(pME3424) overproduces Phl and Plt and displays improved biocontrol efficacy compared with CHA0-Rif. Cucumber was grown repeatedly in the same soil, which was left uninoculated, was inoculated with CHA0-Rif or CHA0-Rif(pME3424), or was treated with the fungicide metalaxyl (Ridomil). Treatments were applied to soil at the start of each 32-day-long cucumber growth cycle, and their effects on the diversity of the rhizosphere populations of culturable fungi were assessed at the end of the first and fifth cycles. Over 11,000 colonies were studied and assigned to 105 fungal species (plus several sterile morphotypes). The most frequently isolated fungal species (mainly belonging to the generaPaecilomyces, Phialocephala, Fusarium, Gliocladium, Penicillium, Mortierella, Verticillium, Trichoderma, Staphylotrichum, Coniothyrium, Cylindrocarpon, Myrothecium, and Monocillium) were common in the four treatments, and no fungal species was totally suppressed or found exclusively following one particular treatment. However, in each of the two growth cycles studied, significant differences were found between treatments (e.g., between the control and the other treatments and/or between the two inoculation treatments) using discriminant analysis. Despite these differences in the composition and/or relative abundance of species in the fungal community, treatments had no effect on species diversity indices, and species abundance distributions fit the truncated lognormal function in most cases. In addition, the impact of treatments at the 32-day mark of either growth cycle was smaller than the effect of growing cucumber repeatedly in the same soil.
Microvillus Inclusion Disease: Loss of Myosin Vb Disrupts Intracellular Traffic and Cell Polarity

Microvillus inclusion disease (MVID) is a congenital enteropathy characterized by loss of apical microvilli and formation of cytoplasmic inclusions lined by microvilli in enterocytes. MVID is caused by mutations in the MYO5B gene, coding for the myosin Vb motor protein. Although myosin Vb is implicated in the organization of intracellular transport and cell surface polarity in epithelial cells, its precise role in the pathogenesis of MVID is unknown. We performed correlative immunohistochemistry analyses of sections from duodenal biopsies of a MVID patient, compound heterozygous for two novel MYO5B mutations, predicting loss of function of myosin Vb in duodenal enterocytes together with a stable MYO5B CaCo2 RNAi cell system. Our findings show that myosin Vb‐deficient enterocytes display disruption of cell polarity as reflected by mislocalized apical and basolateral transporter proteins, altered distribution of certain endosomal/lysosomal constituents including Rab GTPases. Together, this severe disturbance of epithelial cell function could shed light on the pathology and symptoms of MVID.
Cohort mortality study of Swedish pulp and paper mill workers-nonmalignant diseases.

OBJECTIVES The aim of this study was to determine mortality among pulp and paper mill workers according to the main mill pulping process, department, and gender, particular reference being given to diseases of the circulatory and respiratory systems. METHODS The cohort of 18 163 men and 2 291 women employed between 1939 and 1999 and with >1 year of employment was followed for mortality from 1952 to 2001 (acute myocardial infarction from 1969). Standardized mortality ratios (SMR) with 95% confidence intervals (95% CI) were estimated by comparing the observed number of deaths with the expected number for the entire Swedish population. Exposure was assessed from personnel files in the mills. Data from an exposure measurement database are also presented. RESULTS There were 5898 deaths in the cohort. Total mortality had an SMR of 1.02 (95% CI 0.98-1.06) for the men in the sulfate mills and an SMR of 0.93 (95% CI 0.90-0.97) for the men in the sulfite mills. Mortality from acute myocardial infarction was increased among the men in both the sulfate and sulfite mills [SMR 1.22 (95% CI 1.12-1.32) and SMR 1.11 (95% CI 1.02-1.21), respectively] and by department in sulfate pulping (SMR 1.29, 95% CI 1.07-1.54), paper production (SMR 1.26, 95% CI 1.06-1.49), and maintenance (SMR 1.16, 95% CI 1.02-1.30). Mortality from cerebrovascular disease, diabetes mellitus, and nonmalignant respiratory diseases was not increased. CONCLUSIONS Death from acute myocardial infarction, but not cerebrovascular diseases, was increased in this cohort and was probably related to a combination of different occupational exposures (eg, dust, sulfur compounds, shift work, and noise).
Present state of the surgical treatment of chronic frontal sinusitis.

PREFACE Chronic frontal sinusitis has been the subject of deep concern among physicians, so much so that a French professor has called it "the nightmare of the specialists. " Notwithstanding the antibiotics, surgery still plays an important part in the treatment of the infections of the paranasal cavities, and this is due to the fact that when acute inflammation has become chronic antibiotics are not effective. The most important reason why an acute sinusitis becomes chronic is retention. Retention can be caused by something outside the sinus region, such as a deviation of the nasal septum, hypertrophy of the middle turbinate, nasal polyposis, and constriction of the nasofrontal duct. It can also be caused by something within the sinus, and among the latter causes one of the most important is the size of the sinus. Large sinuses very frequently show deep diverticula, partial partition, and retention cells. The surgeon can act
Interaction Between Vitamin K-Dependent Protein S and the Complement Protein, C4b-Binding Protein

In 1977, Di Scipio et al reported the isolation of a previously unknown human vitamin Independent plasma protein, which was given the name protein S. The protein was also subsequently purified from bovine plasma. Human and bovine protein S are single chain molecules with molecular weights of 69,000 and 64,000 daltons (d), respectively. Like the other vitamin K-dependent plasma proteins, protein S contains approximately 10 Gla residues localized to the NH2 terminal portion of the molecule. The reported NH2 terminal amino acid sequence is highly homologous to corresponding regions of the vitamin K-dependent coagulation proteins, and in the presence of Ca protein S has a high affinity for negatively charged phospholipids. So far, no experimental data indicate that protein S is a zymogen to a serine protease, and no clearly defined function has yet been assigned to it. A proteolytic modification of protein S occurs during blood coagulation and is presumably mediated by the thrombin then formed. In a purified system, protein S is very sensitive to proteolysis by thrombin, and the susceptible peptide bond is located in the NH2-terminal part of the molecule. The resulting 8000 molecular weight fragment, containing the whole gamma-carboxyglutamic acid residue (Gla) containing region, is still linked to the rest of the molecule by disulfide bridges. Although no mass is lost, the thrombin modified protein S appears to bind Ca, and thus presumably phospholipids as well, much less effectively than does intact protein S. Recently, Walker reported that bovine protein S could function as a nonenzymatic cofactor to protein Ca in the degradation of phospholipid bound coagulation Factor Va. This observation suggests that protein S may be involved in regulating the coagulation cascade. Protein S may even have a regulatory function in another important cascade system, the complement system, a suggestion based on the recent observation that protein S forms a noncovalent complex with one of the regulatory proteins in this system. It is this complex formation, and its potential physiologic significance, that is the subject of this review.
Statistical Applications in Genetics and Molecular Biology Case-Control Inference of Interaction between Genetic and Nongenetic Risk Factors under Assumptions on Their Distribution

In genetic association studies, there is increasing interest in understanding the joint effects of genetic and nongenetic factors. For rare diseases, the case-control study is a practical design, and logistic regression is the standard method of inference. However, the power to detect statistical interaction is a concern, even with relatively large samples. Under independence of genetic and nongenetic covariates, improved precision of interaction estimators is possible, but logistic regression does not make use of this assumption and consequently is not statistically efficient. In recent work to improve efficiency, profile likelihood methods have been used to develop semiparametric inference that incorporates the independence assumption. We describe an alternate derivation of these estimators for rare diseases that is based on classic arguments from casecontrol inference. These arguments lead to a simplification in the variance estimator. We also describe a strategy for relaxing the independence assumption. Under either independence or the proposed dependence model, inference for association parameters is conveniently obtained by fitting a conditional logistic regression. The statistical properties of the proposed methodology are investigated by simulation.
Role of Left Ventricular Assist Devices in Assessment of Patients for Combined Heart–Kidney Transplantation

We read with interest the recent manuscript by Schaffer et al (1) and the accompanying editorial by Kumar and Tallaj (2) regarding combined heart–kidney transplantation (HKT) in patients with end-stage heart failure and chronic renal insufficiency. We agree that the option of HKT in patients with nondialysis-dependent renal insufficiency (NDDRI) requires further exploration. It is possible that some patients may experience an improvement in renal function with heart transplantation alone, which can be difficult to predict prior to transplantation. Both articles discuss the potential utilization of left ventricular assist devices (LVADs), which we would like to elaborate on further.
Mental imagery for relearning of people after brain injury

Objective: This paper reported on the application of mental imagery to the relearning of daily task performance in people with brain injury. Method: The changes in two subjects who had suffered from cerebral infarction shown throughout a 3-week mental imagery programme were described. The subjects’ improvement in task performance and other clinical outcomes illustrated the programme's therapeutic effects on skill relearning, maintenance and generalization. Results: After completing the programme, the subjects showed improvements in performance at both the trained and untrained tasks. Feedback from the patients also suggested its ability to enhance their day-to-day functioning. Clinical assessment results indicated that the subjects experienced an increase in the attention and sequential processing functions but not in the motor and other cognitive functions. Conclusion: Mental imagery appears to be effective at enhancing the task relearning of subjects after brain injury. The skills acquired under this treatment regime can be retained and then generalized to other tasks. Its therapeutic effect is probably mediated by the improved attention and planning and execution functions associated with the rehearsal. Further research should conduct clinical controlled trials to gather evidence on its efficacy at promoting functional regain in people suffering from neurological disorders.
Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis

We previously reported that Parkinson’s disease (PD) kinase LRRK2 phosphorylates a subset of Rab GTPases on a conserved residue in their switch-II domains (Steger et al., 2016) (PMID: 26824392). Here, we systematically analyzed the Rab protein family and found 14 of them (Rab3A/B/C/D, Rab5A/B/C, Rab8A/B, Rab10, Rab12, Rab29, Rab35 and Rab43) to be specifically phosphorylated by LRRK2, with evidence for endogenous phosphorylation for ten of them (Rab3A/B/C/D, Rab8A/B, Rab10, Rab12, Rab35 and Rab43). Affinity enrichment mass spectrometry revealed that the primary ciliogenesis regulator, RILPL1 specifically interacts with the LRRK2-phosphorylated forms of Rab8A and Rab10, whereas RILPL2 binds to phosphorylated Rab8A, Rab10, and Rab12. Induction of primary cilia formation by serum starvation led to a two-fold reduction in ciliogenesis in fibroblasts derived from pathogenic LRRK2-R1441G knock-in mice. These results implicate LRRK2 in primary ciliogenesis and suggest that Rab-mediated protein transport and/or signaling defects at cilia may contribute to LRRK2-dependent pathologies.
Establishing a protein expression profile database for the normal human pituitary gland using two-dimensional high-performance liquid chromatography combined with LTQ-Orbitrap mass spectrometry

In this study, we selected adult normal pituitary gland tissues from six patients during operations for pituitary microadenomas via the transsphenoidal approach for extended normal pituitary tissue resection around the tumor, and analyzed the protein expression of human normal pituitary using two-dimensional high-performance liquid chromatography combined with LTQ-Orbitrap mass spectrometry proteomics technology. The ten most highly expressed proteins in normal human pituitary were: alpha 3 type VI collagen isoform 5 precursor (abundance among tall pituitary proteins, 1.30%), fibrinogen beta chain preproprotein (0.99%), vimentin (0.73%), prolactin (0.69%), ATP synthase, H+ transporting and mitochondrial F1 complex beta subunit precursor (0.52%), keratin I (0.49%), growth hormone (0.45%), carbonic anhydrase I (0.40%), heat shock protein 90 kDa I (0.31%), and annexin V (0.30%). Based on the biological function classifications of these proteins, the top three categories by content were neuroendocrine proteins (abundance among all pituitary proteins, 40.1%), catalytic and metabolic proteins (28.3%), and cell signal transduction proteins (9.8%). Based on cell positioning classification, the top three categories were cell organelle (24.5%), membrane (20.8%), and cytoplasm (13.0%). Based on biological process classification, the top three categories of proteins are involved in physiological processes (42.9%), cellular processes (40.4%), and regulation of biological processes (9.1%). Our experimental findings indicate that a protein expression profile database of normal human pituitary can be precisely and efficiently established by proteomics technology.
Reduced-order models for damped geometrically non-linear vibrations of thin shells via real normal form

Reduced-order models for a general class of non-linear oscillators with viscous damping, quadratic and cubic non-linearities, are derived thanks to a real normal form procedure. A special emphasis is put on the treatment of the damping terms, and its effect on the normal dynamics. In particular, it is demonstrated that the type of non-linearity (hardening/softening behaviour) depends on damping. The methodology is then applied for reducing the non-linear dynamics exhibited by a circular cylindrical shell, hamonically excited in the spectral neighbourhood of the natural frequency of an asymmetric mode. The approximation, which consists in using time-invariant manifold instead of computing an accurate time-dependent one, is discussed. The results show that the method is efficient for producing accurate reduced-order models without a special need for intensive numerical computations. Validity limits of the approximation is then assessed by using the amplitude of the forcing as bifurcation parameter. Finally, the method is compared to the Proper Orthogonal Decomposition method (POD).