Miracle-dz/UniFAR-FTUs huggingface dataset:
Single and Combined Exposure to Zinc- and Copper-Containing Welding Fumes Lead to Asymptomatic Systemic Inflammation

Objective: Recently, it has been shown that exposure to welding fumes containing both zinc and copper leads to asymptomatic systemic inflammation in humans as shown by an increase of blood C-reactive protein. In the present study, it was investigated which metal is responsible for this effect. Methods: Fifteen healthy male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc. Results: For each exposure blood C-reactive protein increased. Conclusions: Copper- and zinc-containing welding fumes are able to induce systemic inflammation.
L-SR1: A SECOND ORDER OPTIMIZATION METHOD

We describe L-SR1, a new second order method to train deep neural networks. Second order methods hold great promise for distributed training of deep networks. Unfortunately, they have not proven practical. Two significant barriers to their success are inappropriate handling of saddle points, and poor conditioning of the Hessian. L-SR1 is a practical second order method that addresses these concerns. We provide experimental results showing that L-SR1 performs at least as well as Nesterov’s Accelerated Gradient Descent, on the MNIST and CIFAR10 datasets. For the CIFAR10 dataset, we see competitive performance on shallow networks like LeNet5, as well as on deeper networks like residual networks. Furthermore, we perform an experimental analysis of L-SR1 with respect to its hyperparameters to gain greater intuition. Finally, we outline the potential usefulness of L-SR1 in distributed training of deep neural networks.
IMPRINT OF A 2 MILLION YEAR OLD SOURCE ON THE COSMIC-RAY ANISOTROPY

We study numerically the anisotropy of the cosmic-ray (CR) flux emitted by a single source calculating the trajectories of individual CRs. We show that the contribution of a single source to the observed anisotropy is determined solely by the fraction the source contributes to the total CR intensity, its age, and its distance and does not depend on the CR energy at late times. Therefore, the observation of a constant dipole anisotropy indicates that a single source dominates the CR flux in the corresponding energy range. A natural explanation for the plateau between 2–20 TeV observed in the CR anisotropy is thus the presence of a single, nearby source. For the source age of 2 Myr, as suggested by the explanation of the antiproton and positron data from PAMELA and AMS-02 through a local source, we determine the source distance as ∼200 pc. Combined with the contribution of the global CR sea calculated in the escape model, we can explain qualitatively the data for the dipole anisotropy. Our results suggest that the assumption of a smooth CR source distribution should be abandoned between ≃200 GeV and 1 PeV.
Implementation of a Comprehensive Cancer Control Program at the Worksite: Year One Summary Report

The worksite is an ideal forum for cancer risk assessment. We describe here the baseline characteristics of a large cohort. Participants completed surveys that assessed a variety of risk factors and behavioral mediators. Personalized feedback letters identified cancer risks. A total of 4395 surveys were received. Cancer prevalence was 6.5% (range, 4.3% to 11.2%). The most common risk factors were lack of exercise (41%; 32% to 68%), obesity (28%; 24% to 39%), and smoking (14%; 13% to 32%). Cardiovascular risk was also common (25%; 15% to 48%). Screening was fair to good for all cancers except colon cancer. The perceived risk for cancer was less than that for cardiovascular disease (P < 0.0001). Most smokers were in the pre-contemplation phase, whereas action/maintenance phases predominated for breast and colon cancer screening. Modifiable cancer risk factors can be identified in the majority of workers. Inaccurate risk perception is an important target for future interventions.
A “Protease Activation Cascade” in the Pathogenesis of Alzheimer's Disease

Abstract: A pathway to Alzheimer's disease (AD) relevant to sporadic AD pathogenesis is described that involves the early and progressive activation of proteolytic systems including, but not limited to, the calpain‐calpastatin and endosomal‐lysosomal systems. Activation of these proteolytic systems is initiated by normal brain aging and is propelled by the genetic and environmental factors known to increase AD risk. Recent studies show how cathepsins and calpains, acting directly or indirectly through other proteolytic pathways and cellular signaling cascades, may promote β‐amyloidogenesis, neurofibrillary pathology, as well as mediate neurodegeneration in AD.
Safeners coordinately induce the expression of multiple proteins and MRP transcripts involved in herbicide metabolism and detoxification in Triticum tauschii seedling tissues

Chemicals called safeners protect cereal crops from herbicide toxicity. Proteomic methods (2‐D PAGE and LC‐MS/MS) were utilized to identify safener‐ and/or herbicide‐regulated proteins in three tissues (root, leaf, and coleoptile) of Triticum tauschii seedlings to better understand a safener's mechanism of action. Growth experiments showed that the safener cloquintocet‐mexyl protected seedlings from injury by the herbicide dimethenamid. In total, 29 safener‐induced and 10 herbicide‐regulated proteins were identified by LC‐MS/MS. These proteins were classified into two major categories based on their expression patterns, and were further classified into several functional groups. Surprisingly, mutually exclusive sets of proteins were identified following herbicide or safener treatment, suggesting that different signaling pathways may be recruited. Safener‐responsive proteins, mostly involved in xenobiotic detoxification, also included several new proteins that had not been previously identified as safener‐responsive, whereas herbicide‐regulated proteins belonged to several classes involved in general stress responses. Quantitative RT‐PCR revealed that multidrug resistance‐associated protein (MRP) transcripts were highly induced by safeners and two MRP genes were differentially expressed. Our results indicate that safeners protect T. tauschii seedlings from herbicide toxicity by coordinately inducing proteins involved in an entire herbicide detoxification pathway mainly in the coleoptile and root, thereby protecting new leaves from herbicide injury.
Defective Number Sense or Impaired Access? Differential Impairments in Different Subgroups of Children With Mathematics Difficulties

Developmental dyscalculia (DD) is a specific learning disability in mathematics that affects around 6% of the population. Currently, the core deficit of DD remains unknown. While the number sense deficit hypothesis suggests that the core deficit of DD lies in the inability to represent nonsymbolic numerosity, the access deficit hypothesis suggests that the origin of this disability lies in the inability to associate numbers with the underlying magnitude representation. The present study compared the performance of DDs with their low-achieving (LA) and normally achieving peers in nonsymbolic numerosity processing and number-magnitude mapping over 1 year (from kindergarten to 1st grade). The results demonstrated differential impairments in different subgroups of children with mathematics difficulties. While DDs showed deficits in both nonsymbolic numerosity processing and number-magnitude mapping, LAs showed deficit only in the number-magnitude mapping. Furthermore, the deficit in number-magnitude mapping among the DD group was partially explained by their number sense deficit. The number sense deficit hypothesis is supported. Theoretical and practical implications are discussed.
Approches combinatoires pour la reconstruction d'une voie de biosynthèse chez la levure : variation des niveaux d'expression et analyse fonctionnelle d'une étape clé de la voie

Afin d’optimiser la production d’un compose d’interet tout en evitant les consequences nefastes sur la viabilite cellulaire, un defi majeur de l’ingenierie metabolique est d’obtenir un equilibre entre les flux metaboliques endogenes de la cellule et le flux consomme par une nouvelle voie de biosynthese. Dans ce contexte d’optimisation, les strategies combinatoires generent une diversite de voies metaboliques et de modes de regulation rassemblant de precieuses informations quant aux choix d’orientations strategiques a faire. Notre etude s’inscrit dans un projet visant a produire les molecules responsables de l’arome, de la couleur et du parfum du safran (Crocus sativus) chez Saccharomyces cerevisiae. Une approche combinatoire a ete adoptee pour moduler les niveaux d’expression de trois genes menant a la synthese de leur precurseur commun : la zeaxanthine. Cette strategie nous a permis de decrire des biais inattendus dans la regulation des niveaux d’expression des genes exprimes sur plasmide. Nous avons detecte une forte interference transcriptionnelle entre les genes dans notre systeme, ainsi qu’une influence de la nature des sequences codantes. Ces elements, identifies comme critiques, imposent sur les niveaux d’expression des trois genes une regulation plus importante que la force des promoteurs qui les controlent. Afin de poursuivre le projet vers son objectif final, la reaction de clivage de la zeaxanthine menant a la synthese des composes d’interet du safran a fait l’objet d’une analyse fonctionnelle detaillee. Une absence d’activite de l’enzyme decrite dans la litterature comme responsable de cette reaction nous a conduits a proposer des perspectives d’ingenierie pour atteindre l’objectif final du projet
ENVIRONMENTALAND SOCIAL RISK

This study aimed to analyze the environmental and social risks in Bangladesh along with the attitude of Bangladeshi people towards foreign products offered by multinational companies. Analyses were mostly qualitative in nature. However, quantitative approach involving survey was used to explore the attitude of people and to compare their attitude in respect of gender and age. A structured, close-ended questionnaire having forty questions under eight variables (quality, price, promise, differentiation, trust and credibility, self expressive benefits, foreign culture attraction and satisfaction and loyalty) measured on Likert scale has been used. Convenience sampling method has been applied to collect data from 200 respondents. For data analysis purposes descriptive statistics, independent sample t-test, one-way ANOVA and internal correlation have been applied. Reliability of instrument has been judged by applying cronbach’s alpha. The study found that there are both positive and negative aspects in environmental and social components of Bangladesh and the people of this country have an overall favorable attitude towards foreign products.
Real‐time risk stratification of patients with acute pulmonary embolism by grading the reflux of contrast into the inferior vena cava on computerized tomographic pulmonary angiography

Summary. Objective: To investigate whether fast grading of reflux of contrast to the inferior vena cava (IVC) on computerized tomographic pulmonary angiography (CTPA) is a potential biomarker for real‐time risk stratification. Methods: We retrospectively identified 343 patients investigated for possible pulmonary embolism (PE) by CTPA at our medical center between September 2004 and March 2006. A total of 145 consecutive patients with PE (age 67 ± 19 years) and 168 consecutive ones with negative CTPAs (age 64 ± 20 years) fulfilled entry criteria. CTPAs were evaluated for retrograde reflux of contrast to the IVC by fast visual grading from 1 to 6 using the original axial images. Pulmonary obstruction index, the diameters of right and left ventricles and pulmonary artery, and patient survival data were recorded as well. Results: Twenty‐nine (20.0%) patients with positive CTs and 23 (13.7%) patients with negative CTs had substantial degrees (≥4) of reflux of contrast to the IVC (P = 0.14). The Kaplan–Meier 30‐day survival curves demonstrated significant reduction in survival in individuals with PE and grade ≥4 reflux of contrast to the IVC compared with lower grades (P = 0.008), but not in patients with grade ≥4 and no PE on CTPA (P = 0.26). The other cardiovascular parameters showed no significant correlation with survival in patients with and without PE. Conclusion: Substantial grades of reflux of contrast to the IVC during CTPA could predict early mortality in patients with acute PE. Rapid grading of reflux of contrast from the original axial CTPA images can be used for real‐time risk stratification in patients with acute PE.
Differential Involvement of Protein Kinase C and Protein Kinase A in Ghrelin‐Induced Growth Hormone and Gonadotrophin Release from Goldfish (Carassius auratus) Pituitary Cells

Ghrelin (GRLN) and its receptor have been identified and characterised in goldfish brain and the pituitary, and recent evidence shows that goldfish (g)GRLN19 induces both growth hormone (GH) and maturational gonadotrophin (LH) release through an extracellular Ca2+‐dependent mechanism in goldfish. To further understand the role of GRLN in hormone release, the present study examined the involvement of protein kinase C (PKC) and protein kinase A (PKA) in gGRLN19‐induced GH and LH release and corresponding Ca2+ signals in primary cultures of goldfish pituitary cells. Treatments with PKC inhibitors, Bis‐II and Gö 6976, significantly reduced gGRLN19‐induced GH and LH release and their corresponding intracellular Ca2+ signals in identified somatotrophs and gonadotrophs, respectively. gGRLN19 was unable to further stimulate hormone release or Ca2+ signals when cells were pretreated with the PKC agonist, DiC8. PKA inhibitors, H‐89 and KT 5720, inhibited gGRLN19‐induced LH release and Ca2+ signals in gonadotrophs but not GH release or Ca2+ signals in somatotrophs. Interestingly, pretreatment of pituitary cells with the adenylate cyclase activator forskolin potentiated gGRLN19‐induced GH, but not LH, release, although it had no effect on intracellular Ca2+ signals in either cell type. Taken together, the results suggest that PKC is an important intracellular component in gGRLN19‐induced GH and LH release, whereas PKA is involved in gGRLN19‐elicited LH release. Furthermore, the PKA pathway potentiates gGRLN19‐induced GH release via a Ca2+‐independent mechanism. Overall, the present study provides insight into the neuroendocrine regulation of GH and LH release by elucidating the mechanistic aspects of GRLN, a hormone involved in many critical physiological processes, including pituitary functions.
Reply to Schiffer

be able to recover a priori. Part of the significance of such a case may be described as follows. The case of Pierre shows that externalism may well lead to a situation in which certain inferences are valid, but don't a priori look to be so. The case of Peter, if it worked, would show something perhaps more surprising: that externalism may well lead to a situation in which certain inferences look valid, but aren't. Now, Stephen appears to agree with me on the first central claim -namely, that I have described a case in which Earthly and Twin Earthly contents cohabit. I quote from p. 31.
Pattern formation in the flow of thin films down an incline : Constant flux configuration

We present fully nonlinear time-dependent simulations of a thin liquid film flowing down an inclined plane. Within the lubrication approximation, and assuming complete wetting, we find that varying the inclination angle considerably modifies the shape of the emerging patterns: Finger-shaped patterns result for the flow down a vertical plane, while saw-tooth patterns develop for the flows down an inclined plane. However, in all of our simulations, the roots always move, indicating that the shape of the patterns is not necessarily related to the surface coverage, a technologically important feature of the flow. Furthermore, we find that triangular steady-state patterns may be produced for the flow down an incline, while the fingers typically grow in length for all explored times. We find quantitative agreement with reported experiments, and suggest new ones. © 2001 American Institute of Physics. @DOI: 10.1063/1.1409965 #
Identification of Two Rat Genes Orthologous to the Human Interleukin-8 Receptors*

The genes encoding two functional human interleukin-8 (IL-8) receptors have been identified by molecular cloning techniques and they are members of the rhodopsin G-protein coupled receptor (GCR) superfamily. We report the molecular cloning of two rat GCR genes (rat CXCR1-like and rat CXCR2) whose conceptualized amino acid sequences are approximately 70% identical to the human IL-8 A and B receptor subtypes. The murine GRO-like peptide, macrophage inflammatory peptide-2 (MIP-2), elevates intracellular calcium levels in HEK293 cells expressing the rat CXCR2 receptor. Southern blot analysis of restriction-digested rodent and human genomic DNAs indicate that rat CXCR1-like and CXCR2 are: 1) each single copy genes in the rat genome; 2) most closely related to the human IL-8 receptor genes; and 3) orthologous to two previously identified murine genes. CXCR2 mRNA is detected in adult rat lung, spleen, and neutrophils. CXCR1-like mRNA can be detected in adult rat lung, native rat macrophages, and a rat alveolar macrophage cell line (NR8383). These data identify the rat orthologs of the human IL-8 receptors, and describe cellular and tissue targets of rat C-X-C chemokine peptides.
Screening of Transforming Growth Factor Beta 3 and Jagged2 Genes in the Malay Population With Nonsyndromic Cleft Lip With or Without Cleft Palate.

OBJECTIVE To determine the prevalence of mutations in transforming growth factor beta 3 (TGFβ3) and Jagged2 genes and their association with nonsyndromic cleft lip with or without cleft palate (CL±P) patients. DESIGN Cross-sectional study on nonsyndromic CL±P and noncleft patients. SETTING Reconstructive clinic and outpatient dental clinic, Hospital Universiti Sains, Malaysia. PATIENTS Blood samples of 96 nonsyndromic CL±P and 96 noncleft subjects. MAIN OUTCOME MEASURE Prevalence and association of mutations in TGFβ3 and Jagged2 genes with nonsyndromic CL±P. RESULTS Most of the nonsyndromic CL±P patients (53.1%) had left unilateral CLP. There were slightly more females (56.6%) compared with males. The prevalence of the mutations in the TGFβ3 gene was 17.7 (95% confidence interval [CI]: 9.5, 24.5) and in the Jagged2 gene was 12.5% (95% CI: 5.5, 18.5), which was higher compared with the noncleft group. For the TGFβ3 gene, there was no mutation in the coding region in either of the groups. All variants were single nucleotide polymorphisms located within the intronic flanking region. Two variants were identified (g.15812T>G and g.15966A>G) in both nonsyndromic CL±P and noncleft patients. However, the association was not significant (P > .05). Three variants (g.19779C>T, g.19547G>A, and g.19712C>T) were identified in the Jagged2 gene among nonsyndromic CL±P and noncleft patients. Only g.19712C>T showed a significant association with nonsyndromic CL±P patients (P = .039). CONCLUSION g.19712C>T might play a crucial role in the development of cleft lip and palate. To the best of our knowledge, this is the first report of the mutation found within intron 13 of the Jagged2 gene among nonsyndromic CL±P Malay patients.
Ubiquinone redox cycle as a cellular antioxidant defense system

Ubiquinone (UQ) reductase responsible for reduction of non‐mitochondrial UQ was investigated in rats toward demonstrating an antioxidant role of UQ. In the liver, most of cellular UQ‐10 reductase activity was attributable to a novel NADPH‐UQ reductase in cytosol. The enzyme was not inhibited by dicumarol and rotenone, and had a Km of 19 μM for NADPH and 307 μM for NADH at the optimum pH 7.4. The enzyme was purified 300‐fold to apparent homogeneity from the liver cytosol by an affinity chromatographic method. The purified enzyme reduced UQ‐10 in lecithin liposomes, and protected the liposomes from lipid peroxidation. Furthermore, supplementation of rats with UQ‐10 was observed to increase the enzyme level in their livers without affecting levels of other antioxidant factors. The observations suggested that cytosolic NADPH‐UQ reductase is responsible for cellular UQ redox cycle as an endogenous antioxidant.
Emerging drugs for postmenopausal osteoporosis

Postmenopausal osteoporosis (PMO) is a common skeletal disease with serious consequences due to fractures, including increased risk of disability and death. The risk of fractures can be reduced with medications that are currently available; however, these drugs are frequently not prescribed due to failure to recognize that a patient is at high risk for fracture; fear of adverse drug effects; or, sometimes, high cost. When these drugs are prescribed, long-term adherence to therapy is poor. Efforts to improve the clinical effectiveness of pharmacological therapies have included lengthening the interval between doses, simplifying drug administration, and manipulating the molecular structure of drugs in existing therapeutic classes. Recent improvement in understanding the pathophysiology of PMO at the molecular level has fostered the development of new therapeutic agents with novel mechanisms of action. This is a review of the data on the efficacy and safety of emerging drugs for the treatment of PMO, including agents with novel mechanisms of action (denosumab, odanacatib, antibody to sclerostin), new estrogen agonists/antagonists (lasofoxifene, bazedoxifene, arzoxifene), new delivery systems for existing drugs (salmon calcitonin, teriparatide), and drug combinations given concurrently, sequentially, or cyclically. These new therapeutic agents, new delivery systems, and new methods of combining drugs may ultimately reduce the great personal and economic burden of osteoporotic fractures.
Mutations of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma

Backgrounds: The Raf/MEK/ERK (mitogen activated protein kinase—MAPK) signal transduction cascade is an important mediator of a number of cellular fates, including growth, proliferation, and survival. The BRAF gene, one of the human isoforms of RAF, is activated by oncogenic Ras, leading to cooperative effects in cells responding to growth factor signals. Aims: The aim of this study was to elucidate a possible function of BRAF in liver tumours. Methods: Mutations of BRAF and KRAS were evaluated in 25 hepatocellular carcinomas (HCC) and in 69 cholangiocarcinomas (CC) by direct DNA sequencing analyses after microdissection. The presence of active intermediates of the MAPK pathway was assessed immunohistochemically. The results obtained were correlated with histopathological variables and patient survival. Results: Activating BRAF missense mutations were identified in 15/69 CC (22%) and in one case of tumour surrounding liver. KRAS mutations were found in 31 of 69 (45%) CC examined and in two cases of tumour surrounding non-neoplastic liver tissue. In HCC, neither BRAF nor KRAS mutations were detected. All 31 CC with KRAS mutations had an intact BRAF gene. We failed to observe a correlation between BRAF or KRAS mutations and histopathological factors or prognosis of patients. Conclusions: Our data indicate that BRAF gene mutations are a relatively common event in CC but not in HCC. Disruption of the Raf/MEK/ERK (MAPK) kinase pathway, either by RAS or BRAF mutation, was detected in approximately 62% of all CC and is therefore one of the most frequent defects in cholangiocellular carcinogenesis.