Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards a definition of aspirin resistance: a typological approach

'Aspirin resistance' is a poorly defined term to describe the inability of aspirin to protect individuals from thrombotic complications and there are conflicting reports on incidence rates and clinical relevance of this phenomenon. Using collagen (1 w g/ml)-induced platelet aggregation and thromboxane formation (measured as thromboxane B 2 ) in citrated platelet-rich plasma, this study demonstrates that aspirin resistance can be classified into three distinct types. In aspirin responders, both, collagen-induced platelet aggregation and thromboxane formation was completely (>95%) inhibited by oral aspirin treatment (100 mg/day). In type I resistance (pharmacokinetic type), oral treatment with aspirin was ineffective but addition of aspirin (100 w M) in vitro resulted in a complete inhibition of collagen-induced platelet aggregation and thromboxane formation. In type II resistance (pharmacodynamic type), neither oral treatment with aspirin nor addition of aspirin in vitro inhibited collagen-induced platelet aggregation and thromboxane formation. In type III resistance (pseudo-resistance), platelet aggregation was induced by a low concentration of collagen (1 w g/ml) despite of a complete inhibition of thromboxane formation by oral aspirin treatment. This typology of aspirin resistance should help to clarify the mechanisms, the actual rate, and the possible clinical consequences of this phenomenon.
De novo exonic deletion of KDM6A in a Chinese girl with Kabuki syndrome: A case report and brief literature review

Kabuki syndrome (KS) is a rare condition with multiple congenital anomalies and mental retardation. Exonic deletions, disrupting the lysine (K)‐specific demethylase 6A (KDM6A) gene have been demonstrated as rare cause of KS. Here, we report a de novo 227‐kb deletion in chromosome Xp11.3 of a 7‐year‐old Chinese girl with KS. Besides the symptoms of KS, the patient also presented with skin allergic manifestations, which were considered to be a new, rare feature of the phenotypic spectrum. The deletion includes the upstream region and exons 1–2 of KDM6A and potentially causes haploinsuffiency of the gene. We also discuss the mutation spectrum of KDM6A and clinical variability of patients with KDM6A deletion through a literature review. © 2016 Wiley Periodicals, Inc.
Polyarteritis nodosa presenting as peripheral vascular disease and acute limb ischemia

The workshops were evaluated by asking attending trainees to complete a questionnaire after attending. The average group size was ten trainees. Of 29 trainees (out of 34 invited) who have taken part to date, 86% have completed questionnaires. All trainees either agreed (16%) or strongly agreed (84%) that the learning was “excellent. ” All agreed (20%) or strongly agreed (80%) with the statement that the workshops “will improve my practice and quality of care I provide. ” Comments included “the focus on GMP has produced something to make real changes” and “GMP vignettes were excellent in identifying real-life issues and solutions. ” Trainees required more time in exploring real-life vignettes and learning how to engage with management and governance systems, and so future recommendations would be to use less time on the first two sections of the workshop.
Propagation of Seizure-like Activity in a Model of Neocortex

Summary: Seizures in pediatric epilepsy are often associated with spreading, repetitive bursting activity in neocortex. The authors examined onset and propagation of seizure-like activity using a computational model of cortical circuitry. The model includes two pyramidal cell types and four types of inhibitory interneurons. Each neuron is represented by a multicompartmental model with biophysically realistic ion channels. The authors determined the role of bursting neurons and found that their capability of driving network oscillations is most prominent in networks with either weak or relatively strong excitatory synaptic coupling. Synaptic coupling strength was varied in a separate set of simulations to examine its role in network bursting. Oscillations both between cortical layers (vertical oscillations) and between cortical areas (horizontal oscillations) emerge at moderate excitatory coupling strengths. For horizontal propagation, existence of a fast-conducting fiber system and its properties are critical. Seizure-like oscillatory activity may originate from single neurons or small networks, and that activity may propagate in two principal fashions: one that can be represented by a unidirectional (pacemaker)-type process and the other as multi- or bidirectional propagating waves. The frequency of the bursting patterns relates to underlying propagating activity that can either sustain or disrupt the ongoing oscillation.
The Uncertainty-of-Outcome Hypothesis and the Industrial Organization of Sports Leagues

The uncertainty-of-outcome hypothesis (UOH) posits that sports fans value competitive contests, implying that competitive imbalance within a league will motivate stronger teams to leave. Testable hypotheses can be formulated utilizing the many college football conference realignments over the last century. The results support the UOH. For example, schools leaving an existing conference to form a new major conference, or join a preexisting one, were on average stronger than their former associates in the years before their departure. Also, the number of seed conference championships won by departing schools generally exceeded their “fair share” under an equal-likelihood assumption.
Discovery of Mycobacterium tuberculosis α-1,4-Glucan Branching Enzyme (GlgB) Inhibitors by Structure- and Ligand-based Virtual Screening*

Background: M. tuberculosis GlgB is essential for the biosynthesis of branched glucan and modulates pathogenesis and survival. Results: Two novel small molecules demonstrated significant inhibition of M. tuberculosis GlgB enzyme activity, growth and survival. Conclusion: Small molecules with diverse scaffolds but similar three-dimensional-structures show a similar biological effect. Significance: Deriving scaffolds from docking and similarity search is a successful design strategy for difficult targets. GlgB (α-1,4-glucan branching enzyme) is the key enzyme involved in the biosynthesis of α-glucan, which plays a significant role in the virulence and pathogenesis of Mycobacterium tuberculosis. Because α-glucans are implicated in the survival of both replicating and non-replicating bacteria, there exists an exigent need for the identification and development of novel inhibitors for targeting enzymes, such as GlgB, involved in this pathway. We have used the existing structural information of M. tuberculosis GlgB for high throughput virtual screening and molecular docking. A diverse database of 330,000 molecules was used for identifying novel and efficacious therapeutic agents for targeting GlgB. We also used three-dimensional shape as well as two-dimensional similarity matrix methods to identify diverse molecular scaffolds that inhibit M. tuberculosis GlgB activity. Virtual hits were generated after structure and ligand-based screening followed by filters based on interaction with human GlgB and in silico pharmacokinetic parameters. These hits were experimentally evaluated and resulted in the discovery of a number of structurally diverse chemical scaffolds that target M. tuberculosis GlgB. Although a number of inhibitors demonstrated in vitro enzyme inhibition, two compounds in particular showed excellent inhibition of in vivo M. tuberculosis survival and its ability to get phagocytosed. This work shows that in silico docking and three-dimensional chemical similarity could be an important therapeutic approach for developing inhibitors to specifically target the M. tuberculosis GlgB enzyme.
A Hypergiant ’ s View of the Internet Timm Böttger

The importance of IXPs to interconnect di↵erent networks and exchange tra c locally has been well studied over the last few years. However, far less is known about the role IXPs play as a platform to enable large-scale content delivery and to reach a world-wide customer base. In this paper, we study the infrastructure deployment of a content hypergiant, Netflix, and show that the combined worldwide IXP substrate is the major corner stone of its Content Delivery Network. This highlights the additional role that IXPs play in the Internet ecosystem, not just in terms of interconnection, but also allowing players such as Netflix to deliver significant amounts of tra c.
Chile's experience with stabilization, revisited

This paper evaluates Chile's stabilization policies since the early 1970s. Four episodes are examined: (a) the high inflation at the beginning of the military regime when inflation was close to 1000 percent per year; (b) the orthodox stabilization program of 1975; (c) the exchange rate-based stabilization of February 1978-June 1982; and (d) the post-1984 adjustment period with a large real devaluation and low inflation. Finally an overall evaluation of the post-1973 experience with stabilization is provided.
Renal denervation normalizes pressure and baroreceptor reflex in high renin hypertension in conscious rats.

High renin hypertension is usually accompanied by impairment of the baroreceptor reflexes. This feature has been mostly ascribed to overactivity of the renin-angiotensin system. However, renal nerves could also modulate the baroreceptor reflexes. In the present experiments, the effect of renal denervation on the depressed baroreceptor reflexes was studied in rats subjected to aortic ligation between the renal arteries. Renal denervation of the ischemic kidney was performed at the same time as aortic ligation. The resulting effects on arterial pressure, heart rate, plasma renin activity, and baroreceptor reflex control of heart rate were studied 10-12 days after ligation and denervation. Aortic ligation induced high levels of mean arterial pressure (166 +/- 6 versus 110 +/- 3 mm Hg in controls), heart rate (380 +/- 9 versus 352 +/- 8 beats per minute in controls), and plasma renin activity (44 +/- 5 versus 6 +/- 1.2 ng angiotensin I/ml/hr). The baroreceptor reflex sensitivity for bradycardia and tachycardia was significantly reduced (-0.18 +/- 0.04 and -0.18 +/- 0.05, respectively, versus -2.3 +/- 0.01 and -2.4 +2- 0.1 beats per minute per mm Hg in controls). Denervation of the ischemic kidney attenuated the development of hypertension in aortic-ligated rats (122 +/- 3 mm Hg), lowering heart rate (319 +/- 8 beats per minute) and normalizing baroreceptor reflex sensitivity to bradycardia (-2.0 +/- 0.2 beats per minute per mm Hg) and to tachycardia (-4.0 +/- 0.1 beats per minute per mm Hg). Plasma renin activity was also normalized (4.3 +/- 2.4 ng angiotensin I/ml/hr). (ABSTRACT TRUNCATED AT 250 WORDS)
On defining geographic markets

A number of different approaches for empirically defining a geograhic market are explored in this paper. It is demonstrated that the rest proposed by Horowitz, and even a generalization of it,provide conflicting and inconsistent results. Correlation analysis, while appealing in its simplicity, has the potential for providing misleading results. Finally, the notion of causality as applied here, seems to be a promising approach to the issue.
Women with breast cancer: perception of family functioning and adjustment to illness.

&NA; Fifty‐seven women with breast cancer completed measures of family adaptability and cohesion, marital adjustment, and psychosocial adjustment to illness. Using a circumplex model of family systems, we examined whether subjects who perceived their families at moderate levels of cohesion and adaptability reported better psychosocial adjustment than subjects from families with extreme levels of cohesion and adaptability. The results indicated that the patients who reported the best adjustment to breast cancer and in their marriages, also reported the highest levels of family cohesion. There was not a significant relationship between adjustment to illness and adaptability. The implications for the treatment of women with breast cancer and for the families of these patients were discussed.
Functional Topography of the Myelin‐associated Glycoprotein. I. Mapping of Domains by Electron Microscopy

The functional topography of the myelin‐associated glycoprotein (MAG) was investigated by electron microscopic analysis of rotary‐shadowed molecules of a MAG fragment (MAG 90) comprising the five immunoglobulin‐like domains of the extracellular part of the molecule. MAG 90 molecules appeared as rod‐like structures (18.5±1.2 nm long and 4.0±0.8 nm wide) with a globular domain at one end. Antibodies directed against the amino‐ and carboxy‐terminus of MAG 90 interacted with the non‐globular terminal region, indicating that the molecule is bent in the globular region with the amino‐ and carboxy‐terminal arms in close apposition to each other. An antibody which interferes with the binding of MAG to neurons interacted predominantly with the globular domain of MAG 90. The fibril‐forming collagen types I, III and V bound mainly to the non‐globular terminal region of MAG 90, whereas the majority of heparin molecules interacted with the globular region of the molecule. The L2/HNK‐1 carbohydrate structure was localized at the non‐globular region in the protein fragment comprising the fourth and fifth immunoglobulin‐like domains.
Arthur Burns and Inflation

Arthur Burns, Chairman of the Federal Open Market Committee of the Federal Reserve System from February 1970 until December 1977, was fiercely opposed to inflation. Yet, over his eight-year tenure, prices increased at an annualized rate of 6.5 percent. Why? One reason was Burns's belief that inflation arose from a variety of special factors, each of which was largely out of the control of the Federal Reserve.
Isolation and Characterization of Pepper Genes Interacting with the CMV-P1 Helicase Domain

Cucumber mosaic virus (CMV) is a destructive pathogen affecting Capsicum annuum (pepper) production. The pepper Cmr1 gene confers resistance to most CMV strains, but is overcome by CMV-P1 in a process dependent on the CMV-P1 RNA1 helicase domain (P1 helicase). Here, to identify host factors involved in CMV-P1 infection in pepper, a yeast two-hybrid library derived from a C. annuum ‘Bukang’ cDNA library was screened, producing a total of 76 potential clones interacting with the P1 helicase. Beta-galactosidase filter lift assay, PCR screening, and sequencing analysis narrowed the candidates to 10 genes putatively involved in virus infection. The candidate host genes were silenced in Nicotiana benthamiana plants that were then inoculated with CMV-P1 tagged with the green fluorescent protein (GFP). Plants silenced for seven of the genes showed development comparable to N. benthamiana wild type, whereas plants silenced for the other three genes showed developmental defects including stunting and severe distortion. Silencing formate dehydrogenase and calreticulin-3 precursor led to reduced virus accumulation. Formate dehydrogenase-silenced plants showed local infection in inoculated leaves, but not in upper (systemic) leaves. In the calreticulin-3 precursor-silenced plants, infection was not observed in either the inoculated or the upper leaves. Our results demonstrate that formate dehydrogenase and calreticulin-3 precursor are required for CMV-P1 infection.
The Reform of the UK's Auditor Independence Framework after the Enron Collapse: An Example of Evidence-based Policy Making

Following the collapse of Enron, the UK government set up a high level group of regulators and ministers to co-ordinate a review of the UK regulatory framework, including the key area of auditor independence. The Accountancy Foundation Review Board (Review Board), which was at the time responsible for the independent oversight of the UK accountancy professional bodies, took the leading role in the auditor independence review. A programme of research was set up by the Review Board and studies were provided by other bodies. The results of the research were compiled into a paper which underpinned the Review Board's recommendations for change. This was fed into the government review process. In this paper, the research is summarised and the Review Board's evidence-based recommendations are presented and compared with the government's final position. Few differences are found. Insights are provided into the nature of the regulatory reform process and the quality of the evidence which underpinned it.
From Lab Bench to Wall Street

In addition to publishing traditional Book Reviews, the FASEB Journal will publish, under our “Milestones” rubric, book-notes and/or memoirs written by the authors themselves. We invite our readers who are authors of books for the general reader to write about their work in the form of informal essays, memoirs, etc. Our first booknote/memoir is by Tamas Bartfai, Ph.D., who is the director of the Harold L. Dorris Neurological Research Center at The Scripps Research Institute La Jolla, California. Professor Bartfai is former head of central nervous system research at Hoffman-La Roche, Basel, Switzerland, and spent most of his professional career at Stockholm University. His essay explains the genesis of his new book, Drug Discovery: From Bedside to Wall Street, co-authored with Graham V. Lees (2005, Academic Press/Elsevier).
Optimal Adjustment of the Composition of Public Expenditure in Developing Countries

This paper analyses how the composition of public expenditure should be adjusted to maximize the economic growth rate in developing countries. We first apply a theoretical framework to empirical data from 50 countries. We then demonstrate how each country should adjust public expenditure for the purpose of maximizing growth. Results show that developing countries in Asia, the Middle East and Eastern Europe have generally misallocated public expenditures in favour of defence, at the expense of public services. Other region-specific results suggest that Asian developing countries should increase expenditure on education, and that Middle Eastern countries should decrease expenditure on education in favour of health.
New insights into the pathophysiology of the small airways in asthma

Asthma is a lung disease characterized by inflammation and remodeling of the airways, which leads to airflow obstruction and symptoms of wheeze, chest tightness, cough and dyspnea. It is now widely accepted that airway inflammation and remodeling occur not only in the central airways but also in the small airways and even in the lung parenchyma. Inflammation of the distal lung can be observed even in mild asthmatics with normal or noncompromised lung function. Moreover, the small airways and the lung parenchyma can produce many Th2 cytokines and chemokines involved in initiation and perpetuation of the inflammatory process. In addition, the distal parts of the lung have been recognized as a predominant site of airflow obstruction in asthmatics. In fact, the inflammation at this distal site has been described as more severe when compared to the large airway inflammation, and evidence of remodeling in the lung periphery is emerging. Recognition of asthma as a disease of the entire respiratory tract has an important clinical significance, highlighting the need to also consider the distal lung as a target in any therapeutic strategy for effective treatment of this disease.
Sub-national level of participation in international environmental cooperation: the role of Shiga Prefecture for Lake Biwa environment in Japan

From a state-centric view, sub-national level of participation at the international level can be only feasible if it is an active part of national policy. In the case of Shiga prefectural government's initiative for international lake-environmental cooperation, however, sub-national actors came to see themselves as direct players in the absence of national policy. This study examines under what conditions and in what ways such sub-national level of participation takes place by conducting a case study of Shiga's collaboration with the United Nations Environmental Programme (UNEP) over lake-environment risk reduction. The article finds that the process of Shiga's participation in transnational governance will have less chance of being duplicated effectively in other Japanese sub-national governments. Shiga's cooperation with the UNEP was primarily driven by the ad hoc bottom-up political mobilisation of the sub-national actors. In general, without institutionalised channels for sub-national governments to participate in the regional/international level, sub-national governments need to mobilise resources on such an ad hoc basis and only pioneering sub-national actors are capable of effectively engaged on unfamiliar territory with the formation process of transnational governance.
Temporal trends in outcomes of older patients with pneumonia.

BACKGROUND It is unclear how outcomes of care for patients hospitalized for pneumonia have changed as patterns of health care delivery have changed during the 1990s. This study was performed to determine trends in outcomes of care for older patients hospitalized for pneumonia. METHODS This retrospective analysis was based on Medicare claims and included most patients with pneumonia who were older than 65 years and admitted to acute care hospitals in Connecticut between October 1, 1991, and September 30, 1997 (fiscal years 1992-1997). We assessed the trends in hospital costs, discharge destination, hospital mortality rates, mortality rates within 30 days of discharge, and 30-day readmission rates for pneumonia. Multivariate logistic regression analyses were used to adjust for differences in patient characteristics. RESULTS The mean (+/- SD) length of stay declined from 11.9 + 11.4 days to 7.7 + 7.2 days between 1992 and 1997. During this period, adjusted in-hospital mortality rates declined (P =.02), while the adjusted risk of discharge to a nursing facility increased (P<.001) and the adjusted risk of hospital readmission for pneumonia within 30 days of discharge increased (P =.05). The adjusted risk of death 30 days after discharge increased, although the difference was not statistically significant (P =.09). CONCLUSIONS Between 1992 and 1997, the adjusted risks of mortality after discharge, placement in a nursing facility, and hospital readmission for pneumonia increased among older patients hospitalized for pneumonia, in association with a decline in mean hospital length of stay. These findings raise the question of whether the declining hospital length of stay has negatively affected patient outcomes. Arch Intern Med. 2000;160:3385-3391.
Expression of cell-associated and secreted forms of herpes simplex virus type 1 glycoprotein gB in mammalian cells

The gene for glycoprotein gB1 of herpes simplex virus type 1 strain Patton was expressed in stable Chinese hamster ovary cell lines. Expression vectors containing the dihydrofolate reductase (dhfr) cDNA plus the complete gB1 gene or a truncated gene lacking the 194 carboxyl-terminal amino acids of gB1 were transfected into CHO DHFR-deficient cells. Radioimmunoprecipitation demonstrated that the complete gB1 protein expressed in CHO cell lines was cell associated, whereas the truncated protein was secreted from the cells due to deletion of the transmembrane and C-terminal domains of gB1. Cells expressing the truncated gB1 protein were subjected to stepwise methotrexate selection, and a cell line was isolated in which the gB1 gene copy number had been amplified 10-fold and the level of expression of gB1 had increased over 60-fold. The truncated gB1 protein was purified from medium conditioned by the amplified cell line. N-terminal amino acid sequence analysis of this purified protein identified the signal peptide cleavage site and predicted the cleavage of a 30-amino-acid signal sequence from the primary protein. The immunogenicity of the truncated gB1 protein was also tested in mice, and high levels of antibody and protection from virus challenge were observed.