Miracle-dz/UniFAR-FTUs huggingface dataset:
Assembly of influenza hemagglutinin trimers and its role in intracellular transport

The hemagglutinin (HA) of influenza virus is a homotrimeric integral membrane glycoprotein. It is cotranslationally inserted into the endoplasmic reticulum as a precursor called HA0 and transported to the cell surface via the Golgi complex. We have, in this study, investigated the kinetics and cellular location of the assembly reaction that results in HA0 trimerization. Three independent criteria were used for determining the formation of quaternary structure: the appearance of an epitope recognized by trimer-specific monoclonal antibodies; the acquisition of trypsin resistance, a characteristic of trimers; and the formation of stable complexes which cosedimented with the mature HA0 trimer (9S20,w) in sucrose gradients containing Triton X- 100. The results showed that oligomer formation is a posttranslational event, occurring with a half time of approximately 7.5 min after completion of synthesis. Assembly occurs in the endoplasmic reticulum, followed almost immediately by transport to the Golgi complex. A stabilization event in trimer structure occurs when HA0 leaves the Golgi complex or reaches the plasma membrane. Approximately 10% of the newly synthesized HA0 formed aberrant trimers which were not transported from the endoplasmic reticulum to the Golgi complex or the plasma membrane. Taken together the results suggested that formation of correctly folded quaternary structure constitutes a key event regulating the transport of the protein out of the endoplasmic reticulum. Further changes in subunit interactions occur as the trimers move along the secretory pathway.
AAC(6′)-Iaf, a Novel Aminoglycoside 6′-N-Acetyltransferase from Multidrug-Resistant Pseudomonas aeruginosa Clinical Isolates

ABSTRACT We report here the characterization of a novel aminoglycoside resistance gene, aac(6′)-Iaf, present in two multidrug-resistant (MDR) Pseudomonas aeruginosa clinical isolates. These isolates, IMCJ798 and IMCJ799, were independently obtained from two patients, one with a urinary tract infection and the other with a decubitus ulcer, in a hospital located in the western part of Japan. Although the antibiotic resistance profiles of IMCJ798 and IMCJ799 were similar to that of MDR P. aeruginosa IMCJ2.S1, which caused outbreaks in the eastern part of Japan, the pulsed-field gel electrophoresis patterns for these isolates were different from that for IMCJ2.S1. Both IMCJ798 and IMCJ799 were found to contain a novel chromosomal class 1 integron, In123, which included aac(6′)-Iaf as the first cassette gene. The encoded protein, AAC(6′)-Iaf, was found to consist of 183 amino acids, with 91 and 87% identity to AAC(6′)-Iq and AAC(6′)-Im, respectively. IMCJ798, IMCJ799, and Escherichia coli transformants carrying a plasmid containing the aac(6′)-Iaf gene and its upstream region were highly resistant to amikacin, dibekacin, and kanamycin but not to gentamicin. The production of AAC(6′)-Iaf in these strains was confirmed by Western blot analysis. Thin-layer chromatography indicated that AAC(6′)-Iaf is a functional acetyltransferase that specifically modifies the amino groups at the 6′ positions of aminoglycosides. Collectively, these findings indicate that AAC(6′)-Iaf contributes to aminoglycoside resistance.
Autoreactive T-Cell Clones from the Nonobese Diabetic Mouse

The availability of cloned lines of T cells reactive with islet antigens has provided investigators with new tools to study how T cells contribute to autoimmune disease. T-cell clones isolated from the diabetes-prone nonobese diabetic (NOD) mouse are proving to be particularly valuable for analyzing pathogenesis and hold great promise for determining which T-cell subsets are involved in β-cell destruction versus immunoregulation of the inflammatory process. Diabetogenic T-cell clones have been mostly of the CD4+, Th1 phenotype, but CD8+ T cell clones are also capable of transferring disease. In some cases, T-cell lines and clones (CD4+ and CD8+) have been found to have protective properties. In general T-cell antigen specificities have not been defined, as islet cells or lysates were used as the selecting antigen. However, there is an increasing number of reports of T cells specific for defined islet proteins, such as insulin and GAD, and some of these lines can induce disease. The variety of T-cell clones that have been produced indicate that there may a variety of conditions that lead to or protect against β-cell destruction and provide further evidence that autoantigens are generated during development of disease.
Preparing for the New Economy: Advertising Strategies and Change in Destination Marketing Organizations

Information technology, especially the World Wide Web, has had a tremendous impact on the tourism industry over the past years. It is difficult for most destination marketing organizations, however, to keep pace with the evolution of new technologies, the emergence of innovative advertising strategies, the changes in the consumer market, and the growing competition due to increasing globalization. The National Laboratory for Tourism and eCommerce organized a workshop in an effort to identify effective strategies for tourism advertising on the Internet. The results indicated that information technology has led to a number of profound changes in the assumptions underlying communication strategies. It was concluded that the change occurring in the new economy involves a rethinking of who partners and competitors are and how networks with other organizations can increase organizational capacity to learn. Thus, it is argued that success of destination marketing organizations in the new economy is more about change in approach than technology itself.
Bipolar disorder in children and adolescents: international perspective on epidemiology and phenomenology.

OBJECTIVE There is considerable skepticism outside the US over the prevalence of pediatric bipolar disorder (BD). We wished to evaluate the epidemiology of BD in children and adolescents in non-US samples. METHOD We reviewed studies on the prevalence of BD in children and adolescents in international samples. We also describe our sample of 27 children with BD at the University of Navarra. RESULTS There are important and frequently overlooked differences in the definition of BD between the International Classification of Diseases 10th edition (ICD-10) and DSM-IV and methodological differences in epidemiological studies that may partially explain international differences in prevalence of pediatric BD. The prevalence of bipolar spectrum disorder in young adults in Switzerland is 11%. In Holland the 6-month prevalence of mania in adolescents was 1.9% and of hypomania 0.9%. Only 1.2% of hospitalized youth (<15 years) in Denmark and 1.7% of adolescents in Finland had BD. In our clinic, the prevalence of DSM-IV BD in children 5-18 years old is 4%, and of any mood disorders 27%. There are also data from Brazil, India and Turkey with varying results. CONCLUSION Relative lack of data, ICD-10 and DSM-IV differences in diagnostic criteria, different levels of recognition of Child and Adolescent Psychiatry as a true specialty in Europe, clinician bias against BD, an overdiagnosis of the disorder in USA and/or a true higher prevalence of pediatric BD in USA may explain these results. US-International differences may be a methodological artifact and research is needed in this field.
Intracellular Localization of Hyaluronan in Proliferating Cells

Hyaluronan is a high molecular weight glycosaminoglycan found in the extracellular matrix of many tissues, where it is believed to promote cell migration and proliferation. It was recently shown that hyaluronan-dependent pericellular matrix formation is a rapid process that occurs as cells detach during mitosis. Growing evidence for intracellular hyaluronan in tissues in vivo, together with evidence of intracellular hyaluronan binding molecules, prompted us to examine hyaluronan distribution and uptake as well as hyaluronan binding sites in cells and their relationship to cell proliferation in vitro, using a biotinylated hyaluronan binding protein and fluorescein-labeled hyaluronan. In permeabilized smooth muscle cells and fibroblasts, hyaluronan staining was seen in the cytoplasm in a diffuse, network-like pattern and in vesicles. Nuclear hyaluronan staining was observed and confirmed by confocal microscopy and was often associated with nucleoli and nuclear clefts. After serum stimulation of 3T3 cells, there was a dramatic increase in cytoplasmic hyaluronan staining, especially during late prophase/early prometaphase of mitosis. In contrast, unstimulated cells were negative. There was a pronounced alteration in the amount and distribution of hyaluronan binding sites, from a mostly nucleolar distribution in unstimulated cells to one throughout the cytoplasm and nucleus after stimulation. Exogenous fluorescein-labeled hyaluronan was taken up avidly into vesicles in growing cells but was localized distinctly compared to endogenous hyaluronan, suggesting that hyaluronan in cells may be derived from an intracellular source. These data indicate that intracellular hyaluronan may be involved in nucleolar function, chromosomal rearrangement, or other events in proliferating cells.
Compilation of a Functional Language for the Multithreaded Architecture: DAVRID

Multithreading has been much focused on as one of the strongest parallel instruction execution paradigms for massively parallel processing. In this paper, we describe the compilation processes of parallel programming language Id- for a multithreaded architecture DAVRID(DAtaflow Von Neumann RISC hybrlD). Two fundamental issues in parallel processing, tolerance to communication latency and inexpensive synchronization, are solved by a compiler-controlled multithreading. Our compiler features a simple mechanism for handling closures, and a loop unfolding technique for handling parallel and sequential loops in separate, which can greatly contribute to parallel execution of loops.
Surgical treatment of vertebral artery insufficiency caused by cervical spondylosis.

C ERVICAL spondylosis accompanied by arthritic bony spurs that compress the vertebral artery is not uncommon in older people, ~,21,23,2~ and is often most severe during rotation and hyperextension of the neck. The most common site of formation of these osteophytes is on the uncinate portion of the vertebrae, which in embryonic stages is the junction of the centrum and lateral masses, called the "neurocentral," "uncovertebral," or "Luschka's" joint. There is disagreement on whether this is a true joint or not. 3,m1,18 It has been suggested that compression and displacement of one or both vertebral arteries may interfere with circulation in the vertebrobasilar arterial system. To date, few attempts have been made to correct this condition by surgical measures. The surgical procedure presented here evolved from observations of cadavers with displaced vertebral arteries due to severe osteophytes on the uncinate portion of the vertebrae. The ease with which those lateral osteophytes could be exposed and removed through the anterior approach with excision of the longus colli muscle led us to develop a simple method of removing the hypertrophied uncovertebral joint (uncectomy) without making a burr hole or performing an interbody fusion as described by Bakay and Leslie? Even after the spurs and fibrocartilaginous masses had been removed, the verterbral artery was still kinked due to marked perivascular fibrosis; a crease remained in the adventitia, with evidence of chronic irritation of the vertebral nerve. I therefore advocate excision of the fibrosis including the adventitia and periarterial vertebral nerve, following unroofing of the transverse fora-
Estimating the Hidden Costs of Environmental Regulation

This paper examines whether accounting systems identify all the costs of environmental regulation. We estimate the relation between the “visible” cost of regulatory compliance, i.e., costs that are correctly classified in firms’ accounting systems, and “hidden” costs i.e., costs that are embedded in other accounts. We use plant-level data from 55 steel mills to estimate hidden costs, and we follow up with structured interviews of corporate-level managers and plant-level accountants. Empirical results show that a $1 increase in the visible cost of environmental regulation is associated with an increase in total cost (at the margin) of $10-11, of which $9-10 are hidden in other accounts. The findings suggest that inappropriate identification and accumulation of the costs of environmental compliance are likely to lead to distorted costs in firms subject to environmental regulation.
Vandetanib for the treatment of lung cancer

Introduction: VEGF and EGFR are validated pathways for targeted therapy in non-small cell lung cancer (NSCLC). Once considered to be separate targets, VEGF and EGFR are now shown to have interconnected downstream pathways, potentiating the effectiveness of their dual signaling inhibition in cancer therapy. Molecules such as vandetanib that inhibit VEGFR and EGFR have also been reported to inhibit other receptors, including RET and additional kinases, and may be beneficial in treating patients with solid tumors. Areas covered: This review covers the significance of targeting VEGF and EGFR in the treatment of NSCLC and the rationale behind their dual inhibition. Clinical trials that evaluate the use of vandetanib in the setting of refractory NSCLC are also explored. Expert opinion: Vandetanib is currently not approved in the setting of NSCLC. However, its approval for medullary thyroid cancer makes it promising for identifying markers and potentially a NSCLC patient population who will benefit from the treatment.
Inflammatory bowel disease: re-evaluation of the diagnosis in a prospective population based study in south eastern Norway.

BACKGROUND: The incidence figures for ulcerative colitis (UC) and Crohn's disease (CD) have been difficult to interpret, and geographical variations may be due to differences in classification criteria and study design. Few studies have based the incidence on prospective systematic follow up to confirm the initial diagnosis. METHODS: Between 1990 and 1993, in a prospective incidence study of inflammatory bowel disease (IBD) in south eastern Norway, 527 cases of UC, 228 cases of CD, 36 cases of indeterminate colitis (IND), and 55 cases of possible IBD were identified, yielding an annual incidence of 13.6, 5.9, 0.9, and 1.4 per 10(5) respectively. The diagnosis and all clinical data were reviewed by two gastroenterologists independently of each other. One to two years after diagnosis, all patients were offered a clinical follow up in which the initial diagnosis was assessed. RESULTS: Between the time of diagnosis and the follow up, 16 patients had died, four of complications related to IBD. Of the remaining 830 patients, 98% (814/830) were available for follow up, 93% (772/830) attended a clinical examination which included a colonoscopy in 77% (637/830), and the remainder had had a telephone interview, or reassessment based on hospital records, or both. Twenty seven patients were reclassified as not having IBD (3%), and 65 patients were characterised as possible IBD (8%). Of the patients initially classified as UC, 88% had their diagnosis confirmed, compared with 91% with an initial diagnosis of CD. In patients with indeterminate colitis, 33% were classified as definite UC and 17% as CD. This reclassification of patients yielded a corrected annual incidence of 12.8 for UC and 6.0 for CD. CONCLUSION: At follow up one to two years after the diagnosis of IBD, the initial incidence was only marginally altered. This is probably due to uniform inclusion criteria and careful diagnostic methods. The study also illustrates the importance of the re-evaluation of the initial diagnosis as close to 10%, both among patients with UC and CD, were reclassified at follow up.
A Theory of Trade Secrets in Firms

This article provides a simple theoretical model of trade secrets in hierarchical firms. A crucial assumption is that each manager has access to trade secrets pertaining to his own hierarchical level as well as to all lower levels. The article explores some implications of this assumption for optimal degree of trade secrets accumulation and protection as well as for the wage structure in firms. In addition, the model implies that managers may have an incentive to overpay their subordinates and protect their firms' trade secrets too much. Copyright Economics Department of the University of Pennsylvania and the Osaka University Institute of Social and Economic Research Association
Age of Onset of Streptozocin Diabetes Determines the Renal Structural Response in the Rat

Prepubertal years of insulin-dependent diabetes mellitus are protected from the nephropathic effects of this disease, yet this effect of immaturity has not been investigated in an animal model. Male Munich-Wistar rats were made diabetic with streptozocin at two ages: weanling (≈4 wk) and pubescent(≈10 wk). After 5 wk of untreated diabetes, weanling diabetic animals showed relatively greater growth of the medulla, whereas relative proportions of these areas were constant in the older animals. Glomerular volume increased by ≈35% in older diabetic animals, but no glomerular enlargement was demonstrated in weanling rats with diabetes. Glomerular ultrastructure was not significantly altered during the short course of this study. The renal structural response to diabetes is age-dependent in the rat, with prepubertal animals protected from glomerular hypertrophy. Longer studies are needed to see if these differences will eventually parallel those demonstrated in patients with onset of diabetes before and after puberty. This model may ultimately prove to be valuable in determining the mechanism via which prepubertal kidneys are protected from the nephropathic effects of insulin-dependent diabetes mellitus.
Primary and secondary experience in developing adaptive information systems supporting knowledge transfer

One can evidence an increased and complex dynamic in the today's society in terms of technology that is being used, amounts of data that are being collected and processed by computers, and the resulting information overloads. The main challenge is how to address such a change with regard to the design of information systems and how those information systems are aligned with the change in human behaviour. This paper aims to address the issue of designing information systems that support Science 2.0 - a new phenomenon of interrelated sociotechnical interactions in which communication is the heart of science and the environment that enables critiquing, suggesting and sharing ideas and data in real time with almost no costs. This paper underlines problems related to the institutionalisation of knowledge transfer and its weaknesses. It also pinpoints John Dewey's primary and secondary experience as a point of departure which provides theories, theoretical frameworks and models such as information behaviour, documents and communities of action, the quadruple Helix model, activity theory, evolutionary learning and knowledge sharing communities. All these can be utilised for designing adaptive information systems that support better knowledge transfer.
Detection of in situ activation of transglutaminase during apoptosis: correlation with the cell cycle phase by multiparameter flow and laser scanning cytometry.

BACKGROUND One of the hallmarks of apoptosis is activation of tissue transglutaminase (Tgase; also called transglutaminase type 2 [TGase 2]). Its activation causes cross-linking of cytoplasmic proteins, making them insoluble and presumably less immunogenic. Several biochemical and cytochemical methods to detect activity of TGase 2 exist, but none has been adapted for multiparameter flow or image cytometry. METHODS Apoptosis of HL-60 or U-937 leukemic cells was induced by camptothecin, tumor necrosis factor alpha, hyperthermia, or the cytotoxic RNase onconase. Two different approaches to detect TGase 2 activation were developed: (a) the unfixed cells were treated with 4',6'-diamidino-2-phenylindole, and sulforhodamine 101 in solutions of nonionic detergents; (b) the TGase 2 substrate fluoresceinated polyamine cadaverine (F-CDV) was administered into the cultures for several hours before cell harvesting. The cells were then fixed and their DNA counterstained with propidium. Cellular fluorescence was measured by flow or laser scanning cytometry. RESULTS (a) Exposure of nonapoptotic cells to detergents caused their full lysis, resulting in preparation of isolated nuclei devoid of cytoplasm. Conversely, the cross-linking of cytoplasmic protein by activated TGase 2 in apoptotic cells provided resistance to detergents: the nuclei or nuclear (chromatin) fragments of apoptotic cells remained attached to the cytoplasmic protein, embedded within the proteinaceous "shell. " Such cells were identified by their high protein content: intensity of fluorescence after staining with the protein fluorochrome sulforhodamine 101 was markedly higher than that of isolated nuclei. (b) Activation of TGase 2 was also detected by virtue of intense cell labeling with fluoresceinated polyamine cadaverine. Interestingly, in many cells apoptosis progressed without evidence of activation of TGase 2, suggesting that this event may not be a prerequisite for completion of apoptosis. CONCLUSIONS Activation of TGase 2 can be detected simply by cell resistance to detergents or in situ reactivity with F-CDV. Both methods allow one to correlate activation of TGase 2 with the cell cycle position. However, because activation of TGase 2 is not always detected during apoptosis, the lack of the activation cannot be considered a marker of nonapoptotic cells. Hence, an apoptotic index based solely on TGase 2 activation may underestimate incidence of apoptosis.
Equilibrium in the Pricing of Capital Assets, Risk-Bearing Debt Instruments, and the Question of Optimal Capital structure: A Comment

In a recent article in this Journal, Haugen and Pappas (H-P, hereafter) [1] attempted to prove, within the framework of the capital asset pricing model, the already proven proposition that the cost of capital is invariant with respect to leverage even with risky debt. The H-P proof contains a serious error which we would like to point out in this note.
Effects of ECB balance sheet policy announcements on inflation expectations

We investigate whether ECB balance sheet policy announcements in the wake of the global financial crisis have affected the ECB’s monetary policy credibility as measured by long-term inflation expectations, by looking at their effects on euro area inflation swap rates of maturities up to 10 years. We consider asset purchase programmes and long-term refinancing operations with maturities above 6 months. We find that these announcements only led to a slight increase in long-term inflation expectations. We therefore find no strong evidence to suggest that ECB balance sheet policy announcements have led to much higher long-term inflation expectations, suggesting that the monetary policy credibility of the ECB has not been harmed by these policies.