Miracle-dz/UniFAR-FTUs huggingface dataset:
Fibroblasts Derive from Hepatocytes in Liver Fibrosis via Epithelial to Mesenchymal Transition*

Activated fibroblasts are key contributors to the fibrotic extracellular matrix accumulation during liver fibrosis. The origin of such fibroblasts is still debated, although several studies point to stellate cells as the principal source. The role of adult hepatocytes as contributors to the accumulation of fibroblasts in the fibrotic liver is yet undetermined. Here, we provide evidence that the pro-fibrotic growth factor, TGF-β1, induces adult mouse hepatocytes to undergo phenotypic and functional changes typical of epithelial to mesenchymal transition (EMT). We perform lineage-tracing experiments using AlbCre. R26RstoplacZ double transgenic mice to demonstrate that hepatocytes which undergo EMT contribute substantially to the population of FSP1-positive fibroblasts in CCL4-induced liver fibrosis. Furthermore, we demonstrate that bone morphogenic protein-7 (BMP7), a member of the TGFβ superfamily, which is known to antagonize TGFβ signaling, significantly inhibits progression of liver fibrosis in these mice. BMP7 treatment abolishes EMT-derived fibroblasts, suggesting that the therapeutic effect of BMP7 was at least partially due to the inhibition of EMT. These results provide direct evidence for the functional involvement of adult hepatocytes in the accumulation of activated fibroblasts in the fibrotic liver. Furthermore, our findings suggest that EMT is a promising therapeutic target for the attenuation of liver fibrosis.
Cloning and sequence analysis of the gene for a carbapenem-hydrolyzing class A beta-lactamase, Sme-1, from Serratia marcescens S6

Serratia marcescens S6 produces a pI 9.7 carbapenem-hydrolyzing beta-lactamase that is probably encoded by the chromosome (Y. Yang, P. Wu, and D. M. Livermore, Antimicrob. Agents Chemother. 34:755-758, 1990). A total of 11.3 kb of genomic DNA from this strain was cloned into plasmid pACYC184 in Escherichia coli. After further subclonings, the carbapenem-hydrolyzing beta-lactamase gene (blaSme-1) was sequenced (EMBL accession number Z28968). The gene corresponded to an 882-bp open reading frame which encoded a 294-amino-acid polypeptide. This open reading frame was preceded by a -10 and a -35 region consistent with a putative promoter sequence of members of the family Enterobacteriaceae. This promoter was active in E. coli and S. marcescens, as demonstrated by primer extension analysis. N-terminal sequencing showed that the Sme-1 enzyme had a 27-amino-acid leader peptide and enabled calculation of the molecular mass of the mature protein (29.3 kDa). Sequence alignment revealed that Sme-1 is a class A serine beta-lactamase and not a class B metalloenzyme. The earlier view that the enzyme was zinc dependent was discounted. Among class A beta-lactamases, Sme-1 had the greatest amino acid identity (70%) with the pI 6.9 carbapenem-hydrolyzing beta-lactamase, NMC-A, from Enterobacter cloacae NOR-1. Comparison of these two protein sequences suggested a role for specific residues in carbapenem hydrolysis. The relatedness of Sme-1 to other class A beta-lactamases such as the TEM and SHV types was remote. This work details the sequence of the second carbapenem-hydrolyzing class A beta-lactamase from an enterobacterial species and the first in the genus Serratia.
The Integration of ERM and Strategy: Implications for Corporate Governance

SYNOPSIS: Since the early 2000s, expectations have increased for organizations to strengthen corporate governance with enterprise risk management (ERM) processes, with the accounting profession playing a major role in these efforts. The ultimate goal of an effective ERM process is to help boards and senior executives to manage risks in the context of strategy so that the organization is more likely to achieve its key objectives. We conduct semi-structured interviews of 15 ERM champions to provide insights about whether the ERM process is integrated with the strategic-planning and execution processes of the firm. We find that while the decision to launch ERM often is based on a desire for ERM to provide strategic value, the integration of ERM with strategy typically is limited. We then examine the ERM implementation process to identify possible ERM implementation practices limiting ERM's integration with strategy. We find that organizations' (1) culture and approach to preparing for ERM's launch, (2) ERM l.
Granulocyte colony‐stimulating factor administration modulates the surface expression of effector cell molecules on human monocytes

Granulocyte colony‐stimulating factor (G‐CSF) has been shown to stimulate human neutrophil functions, both in vitro and in vivo. We examined the effects of G‐CSF administration on the surface expression of effector cell molecules on human neutrophils and monocytes. G‐CSF (50 μg/m2/d) was administered subcutaneously to five healthy volunteers once a day for 7 d. Venous blood was obtained immediately before and after the completion of G‐CSF administration and 1 week after the last G‐CSF administration. The surface expression of complement receptors (CR), Fc receptors for IgG (FcR) and cellular adhesion molecules on human neutrophils and monocytes were determined by indirect immunofluorescence using flow cytometry and monoclonal antibodies. The expression of CR1, CR3, FcRI and FcRII on neutrophils increased significantly after G‐CSF administration and then decreased after the last G‐CSF administration. The expression of human leucocyte adhesion molecule‐1 (LAM‐1) on neutrophils reflected the above expression. On the other hand, the administration of G‐CSF increased the expression of CR1, CR3, FcRI and FcRIII on monocytes. The expression of CR1, CR3 and FcRI on monocytes then decreased after the last G‐CSF administration, whereas the expression of FcRIII remained at an increased level. These findings indicate that G‐CSF administration modulates the expression of effector cell molecules on circulating monocytes as well as on neutrophils, resulting in enhanced defence against selected infections or in potentiation of the tumouricidal capacity of phagocytes in cancer patients.
A PRELIMINARY REPORT UPON SOME HALOPHILIC BACTERIA

While studying the micro6rganisms concerned in the fermentation of cucumber pickles a group of bacteria were isolated and studied which appear sufficiently interesting to deserve special comment. These organisms were isolated from the scum which grows on the surface of the brine after active fermentation (respiration) has ceased. The interesting fact about these organisms is that certain members of the group demand an appreciable concentration of sodium chloride for development.
Taking Stock of Assisted Voluntary Return from Europe: Decision Making, Reintegration and Sustainable Return – Time for a Paradigm Shift

Assisted Voluntary Return (AVR) is a central component of European Union (EU) member states migration management policies and has grown in popularity over the past two decades. At present, all EU member states have active AVR programmes, however, despite the growing prevalence of these programmes there has been a dearth of research and evaluation on AVR. In addition, a common goal of these AVR programmes is to achieve a sustainable return, but this term lacks a commonly used definition, making sustainable return an ambiguous policy objective. This paper takes stock of the most recent research on AVR focusing on decision making in the uptake of AVR, reintegration, and sustainable return. It is argued that it is time for a fundamental shift in our underlying assumptions regarding sustainable return in the field of AVR policy and practice. The working paper addresses key research gaps in the field and poses recommendations on how to move the agenda forward on AVR.
Investigation of copper-tin transient liquid phase bonding reliability for 3D integration

Copper tin transient liquid phase bonding reliability was investigated with different setups including CuSn to Cu and CuSn to CuSn bonding. Additionally, a thermal treatment just after CuSn electrodeposition (ECD) was compared to the classical configuration. Thermal cycling test (TCT) was achieved with electrical and mechanical tests carried out before and after TCT to discriminate the setups. Before TCT, each configuration has very good electrical properties in terms of yield (>90%) and Kelvin resistance. Shear tests show good mechanical properties in all tested cases as well. However, SEM images reveal different kinds and densities of voids. Kirkendall voids are localized at the Cu/Cu3Sn interface. Smaller voids are visible at the initial bonding interface in the case of CuSn to Cu bonding. After TCT, configurations are well discriminated. CuSn to Cu configuration exhibits the worst properties: electrical yield drops at nearly 30% and shear strength loses 80% of its initial value. On the other hand, CuSn to CuSn configuration and configuration including the post ECD thermal treatment keep correct electrical yield above 80%, and has shear strength loss in the range of 30 to 50%. SEM images after TCT reveals crack localization mainly through Kirkendall voids planes either on top side or on bottom side. Hypotheses regarding these results are discussed.
Health Effects of Subchronic Exposure to Environmental Levels of Diesel Exhaust

Diesel exhaust is a public health concern and contributor to both ambient and occupational air pollution. As part of a general health assessment of multiple anthropogenic source emissions conducted by the National Environmental Respiratory Center (NERC), a series of health assays was conducted on rats and mice exposed to environmentally relevant levels of diesel exhaust. This article summarizes the study design and exposures, and reports findings on several general indicators of toxicity and carcinogenic potential. Diesel exhaust was generated from a commonly used 2000 model 5.9-L, 6-cylinder turbo diesel engine operated on a variable-load heavy-duty test cycle burning national average certification fuel. Animals were exposed to clean air (control) or four dilutions of whole emissions based on particulate matter concentration (30, 100, 300, and 1000 μg/m3). Male and female F344 rats and A/J mice were exposed by whole-body inhalation 6 h/day, 7 days/wk, for either 1 wk or 6 mo. Exposures were characterized in detail. Effects of exposure on clinical observations, body and organ weights, serum chemistry, hematology, histopathology, bronchoalveolar lavage, and serum clotting factors were mild. Significant exposure-related effects occurring in both male and female rats included decreases in serum cholesterol and clotting Factor VII and slight increases in serum gamma-glutamyl transferase. Several other responses met screening criteria for significant exposure effects but were not consistent between genders or exposure times and were not corroborated by related parameters. Carcinogenic potential as determined by micronucleated reticulocyte counts and proliferation of adenomas in A/J mice were unaffected by 6 mo of exposure. Parallel studies demonstrated effects on cardiac function and resistance to viral infection; however, the results reported here show few and only modest health hazards from subchronic or shorter exposures to realistic concentrations of contemporary diesel emissions.
Defined Sequence Modules and an Architectural Element Cooperate To Promote Initiation at an Ectopic Mammalian Chromosomal Replication Origin

ABSTRACT A small DNA fragment containing the high-frequency initiation region (IR) ori-β from the hamster dihydrofolate reductase locus functions as an independent replicator in ectopic locations in both hamster and human cells. Conversely, a fragment of the human lamin B2 locus containing the previously mapped IR serves as an independent replicator at ectopic chromosomal sites in hamster cells. At least four defined sequence elements are specifically required for full activity of ectopic ori-β in hamster cells. These include an AT-rich element, a 4-bp sequence located within the mapped IR, a region of intrinsically bent DNA located between these two elements, and a RIP60 protein binding site adjacent to the bent region. The ori-β AT-rich element is critical for initiation activity in human, as well as hamster, cells and can be functionally substituted for by an AT-rich region from the human lamin B2 IR that differs in nucleotide sequence and length. Taken together, the results demonstrate that two mammalian replicators can be activated at ectopic sites in chromosomes of another mammal and lead us to speculate that they may share functionally related elements.
Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1

Nucleotide sequences in three hypervariable regions of the human immunodeficiency virus type 1 (HIV-1) env gene were obtained by sequencing provirus present in peripheral blood mononuclear cells of HIV-infected individuals. Single molecules of target sequences were isolated by limiting dilution and amplified in two stages by the polymerase chain reaction, using nested primers. The product was directly sequenced to avoid errors introduced by Taq polymerase during the amplification process. There was extensive variation between sequences from the same individual as well as between sequences from different individuals. Interpatient variability was markedly less in individuals infected from a common source. A high proportion of amino acid substitutions in the hypervariable regions altered the number and positions of potential N-linked glycosylation sites. Sequences in two hypervariable regions frequently contained short (3- to 15-bp) duplications or deletions, and by amplifying peripheral blood mononuclear cell DNA containing 10(2) or 10(3) proviral molecules and analyzing the product by high-resolution electrophoresis, the total number and abundance of distinct length variants within an individual could be estimated, providing a more comprehensive analysis of the variants present than would be obtained by sequencing alone. Sequences from many individuals showed frequent amino acid substitutions at certain key positions for neutralizing-antibody and cytotoxic T-cell recognition in the immunodominant loop. The rates of synonymous and nonsynonymous nucleotide substitution in the region of this and flanking regions indicate that strong positive selection for amino acid change is operating in the generation of antigenic diversity.
Protective effect of grape by-product-fortified breads against cholesterol/cholic acid diet-induced hypercholesterolaemia in rats.

BACKGROUND New breads fortified with two different forms of grape by-products, namely dried powdered skins (PGP) and freeze-dried extract therefrom (EGP), were characterised and their protective effect against hypercholesterolaemia in rats was studied. RESULTS The phenolic compound profiles of supplemented breads were dominated by epicatechin and catechin together with appreciable amounts of dimeric procyanidins. Sensory evaluation of enhanced breads revealed that a maximum of 6% PGP or 1.4% EGP could be incorporated to prepare acceptable products. Intake of high-cholesterol/cholic acid diet containing 6% PGP- or 1.4% EGP-fortified bread increased fresh stool weight and significantly reduced protein and fat digestion but did not negatively affect animal growth. PGP- and EGP-fortified breads diminished the negative impact of high-cholesterol/cholic acid diet, lowering total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), lipid peroxidation, glucose and leptin levels, preventing visceral fat accumulation and increasing high-density lipoprotein cholesterol and plasma ferric-reducing antioxidant power levels. Since control bread feeding significantly lowered TC, LDL-C and lipid peroxidation compared with high-fat diet, it may suggested that not only grape by-products but also another components in bread were related to lipid metabolism. CONCLUSION These results demonstrate that intake of both PGP- and EGP-fortified sourdough mixed rye breads might contribute to a reduction of cardiovascular risk.
Soarian™ – Workflow Management Applied for Health Care

Summary Objectives: To describe and comment on functionality and architecture of the software product Soarian™ developed by Siemens, to identify key differentiators to related products, and to comment on predecessor systems and beta versions. This has been done in the framework of a conference on health information systems of the IMIA. Methods: Analyzing existing literature. Site visit of a predecessor system at Haukeland Sykehus, Bergen. Pilot of a beta version at the Erlangen University Medical Center, elaborating on major characteristics in discussion rounds. Results: Soarian is a functional comprehensive, clinically oriented software product to support health care processes and to be used for health care professional workstations. It is a software product, designed and written completely new. Three major key differentiators were identified in comparison to related software products: Soarian’s workflow engine, its embedded analytics, and its ‘smart’ user interface. The targeted reduced installation time is stated to be 12 months or less. Conclusions: Soarian has good chances to become one of the major software products for health care professional workstations in the international market to support patient-centered, shared care. Its global design may help to better support and maintain national or language specific versions. The first installations of Soarian will be critical, as they will show how the system will be accepted. To use such software products efficiently, organizational aspects within hospitals as well as between health care institutions have to be considered, e.g. strategic IT planning.
Acquisition of cell migration defines NK cell differentiation from hematopoietic stem cell precursors

Human natural killer (NK) cells are generated from CD34+ precursors and can be differentiated in vitro by co-culture with developmentally supportive stromal cells. Despite the requirement for stromal cell contact in this process, the nature of these contacts has been poorly defined. We have previously identified a requirement for NK cell signaling receptors associated with terminal maturation in NK cell migration. However, the relationship between NK cell migration and differentiation is still unclear. Here, we perform continuous long-term imaging and tracking of NK cell progenitors undergoing in vitro differentiation. We demonstrate that NK cell precursors can be tracked over long time periods on the order of weeks by utilizing phase-contrast microscopy, and show that these cells acquire increasing motility as they mature. Additionally, we observe that NK cells display a more heterogeneous range of migratory behaviors at later stages of development, with the acquisition of complex modes of migration that are associated with terminal maturation. Together these data demonstrate previously unknown migratory behaviors of innate lymphocytes undergoing lineage differentiation revealed by long-term imaging and analysis workflows.
Subsidizing Fuel Efficient Cars: Evidence from China's Automobile Industry

This paper examines the response of vehicle purchase behavior to China’s largest national subsidy program for fuel-efficient vehicles during 2010 and 2011. Using variation from the program’s eligibility cutoffs and the rollout of the subsidy program, the program is found to boost sales for subsidized vehicle models, but also to create a substitution effect within highly fuel-efficient vehicles. Estimates imply that ignoring the substitution effect would lead one to conclude that the program is welfare enhancing, whereas in fact the marginal cost of the program exceeds the marginal benefit by as much as 300 percent. (JEL D12, H25, L25, L62, O14, P23, P36)
Estimating Heterogeneity in Random Effects Models for Longitudinal Data

In this paper, we are interested in estimating parameters entering nonlinear mixed effects models using a likelihood maximization approach. As the accuracy of the likelihood approximation is likely to govern the quality of the derived estimates of both the distribution of the random effects and the fixed parameters, we propose a methodological approach based on the adaptive Gauss Hermite quadrature to better approximate the likelihood function. This work presents improvements of this quadrature that render it accurate and computationally efficient in the problem of likelihood approximation with, an application to mixture models, models which allow the description of coexistence of several different homogeneous subpopulations specifying the distribution of random effects as a mixture of Gaussian distributions. These improvements are based on a new choice of the scaling matrix followed by its optimisation. An application to a phase III clinical trial of an anticoagulant molecule is proposed and estimation results are compared to those obtained with the most frequently used method in population pharmacokinetic analysis. Moreover, in order to evaluate the accuracy of the estimations, an analysis of simulated pharmacokinetic data derived from the model and the a priori values of population parameters of the previous study are presented. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Essential tremor course and disability

Objective: To correlate autopsy findings with the clinical course and disability profile in clinically diagnosed longitudinally followed autopsied essential tremor (ET) patients. Methods: All ET patients followed by one neurologist between 1970 and 2001 who came to autopsy were included. Clinical features and disability were recorded prospectively. Autopsy studies were performed by a qualified neuropathologist. Results: Twenty cases (10 men and 10 women) had ET onset between childhood and age 68 (median 46.5 years). Six cases had additional features of Parkinson syndrome (PS), with presence of bradykinesia, rigidity, and rest tremor (RT). These included progressive supranuclear palsy (PSP; n = 2), drug-induced parkinsonism (n = 2), idiopathic Parkinson disease (PD; n = 1), and basal ganglia status cribrosus (n = 1). Of the remaining 14 ET cases, 6 had additional RT but no bradykinesia or rigidity. Ten of these 14 (71%) reported physical disability. Eleven of the 14 (79%) had only upper limb (UL) tremor at onset, and 8 of these 11 (73%) had subsequent cranial extension of tremor. Two patients clinically had mild cerebellar ataxia but no cerebellar histologic abnormality. There was no consistent brain pathology in the ET or ET + RT cases. Conclusions: UL tremor was the most common onset, which often progressed to the cranial musculature. Functional disability and psychological distress were common in these patients. Functional disability was related to the UL tremor. Six of 20 (30%) had additional features of PS. Six of the remaining 14 (43%) had ET and RT; there was no identifiable pathology in these cases. The risk of PD in ET cases was comparable with that in the general population. PSP in two cases was incidental comorbidity.
Bonuszahlungen an Manager : Gerechtigkeitsurteile und betriebliche Folgewirkungen

Gut 50% der Beschäftigten beurteilen Bonuszahlungen an Geschäftsführer in ihrem Unternehmen als ungerecht. Dies zeigt eine neue repräsentative Befragung, die diesem Aufsatz zugrunde liegt. Ziel der Befragung ist es zu ermitteln, welches die Ursachen dafür sind, dass Bonuszahlungen als gerecht oder als ungerecht beurteilt werden. Zudem wurde gefragt, ob und unter welchen Bedingungen Bonuszahlungen zu (negativen) innerbetrieblichen Folgewirkungen, wie etwa Kooperationsverweigerung mit der Geschäftsführung oder Verringerung der Arbeitsmotivation, führt? Verdeutlicht wird, insbesondere Verteilungskriterien wie die Höhe der Bonuszahlungen und Kriterien der Beitragsgerechtigkeit beeinflussen die Gerechtigkeitsurteile und die innerbetrieblich beobachteten Folgewirkungen, nicht jedoch Merkmale der sogenannten Verfahrensgerechtigkeit wie Informiertheit oder Mitwirkungsmöglichkeiten.