Miracle-dz/UniFAR-FTUs huggingface dataset:
BRAF mutations in hairy-cell leukemia.

BACKGROUND Hairy-cell leukemia (HCL) is a well-defined clinicopathological entity whose underlying genetic lesion is still obscure. METHODS We searched for HCL-associated mutations by performing massively parallel sequencing of the whole exome of leukemic and matched normal cells purified from the peripheral blood of an index patient with HCL. Findings were validated by Sanger sequencing in 47 additional patients with HCL. RESULTS Whole-exome sequencing identified five missense somatic clonal mutations that were confirmed on Sanger sequencing, including a heterozygous mutation in BRAF that results in the BRAF V600E variant protein. Since BRAF V600E is oncogenic in other tumors, further analyses were focused on this genetic lesion. The same BRAF mutation was noted in all the other 47 patients with HCL who were evaluated by means of Sanger sequencing. None of the 195 patients with other peripheral B-cell lymphomas or leukemias who were evaluated carried the BRAF V600E variant, including 38 patients with splenic marginal-zone lymphomas or unclassifiable splenic lymphomas or leukemias. In immunohistologic and Western blot studies, HCL cells expressed phosphorylated MEK and ERK (the downstream targets of the BRAF kinase), indicating a constitutive activation of the RAF-MEK-ERK mitogen-activated protein kinase pathway in HCL. In vitro incubation of BRAF-mutated primary leukemic hairy cells from 5 patients with PLX-4720, a specific inhibitor of active BRAF, led to a marked decrease in phosphorylated ERK and MEK. CONCLUSIONS; The BRAF V600E mutation was present in all patients with HCL who were evaluated. This finding may have implications for the pathogenesis, diagnosis, and targeted therapy of HCL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others.).
Role of the Renin‐Angiotensin System In the Pathogenesis of Severe Hypertension in Rats

Plasma renin levels are elevated in accelerated or malignant hypertension. To see if this increase of renin is a concurrent phenomenon or a pathogenetic factor in the increase of blood pressure, severe hypertension was produced in rats by occluding the aorta between the origins of the renal arteries. Eight days later, these animals had developed severe hypertension (mean blood pressure = 201 ± 3 mm Hg) and markedly elevated plasma renin levels (151 ± 35 ng angiotensin II/ml hr−1; normal range = 11 ± 0.6). When the kidney distal to the ligature was excised at the time of the coarctation, the animals developed only a moderate increase in blood pressure (mean = 120 ± 1.3 mm Hg) and their plasma renin levels remained in the normal range. When the nonnephrectomized animals with severe hypertension were injected with antibodies against angiotensin II, blood pressure decreased, reaching its lowest point (126 ± 12 mm Hg) 2 days later. This work demonstrates that the severe increase in blood pressure is not due to the mechanical increase in resistance caused by complete coarctation of the aorta; rather, it is due to a humoral factor produced by the kidney, and this factor is renin.
Economic Transition in Southeast Europe

The article examines some of the main features of the transition to a market economy in Southeast Europe (SEE). Since the early 1990s, a number of politically determined processes have had very negative economic implications for the whole SEE region, since many important economic reforms have been substantially delayed. Although the overall prospects have improved over the past few years, the SEE economies are still facing a number of internal constraints on growth and development, which in some countries are aggravated by externally-imposed reform agendas, aid-dependency and inappropriate international assistance policies. The article analyses macroeconomic performance of individual SEE countries in the 1990s, progress with institutional reforms, their development prospects, the role of FDI and European Union policies. Today, a key challenge for these countries is to carry forward the transition to a market economy and create sound conditions for self-sustainable economic growth, while at the same time preparing for future EU membership.
Exact Superreplication Strategies for a Class of Derivative Assets

A superreplicating hedging strategy is commonly used when delta hedging is infeasible or is too expensive. This article provides an exact analytical solution to the superreplication problem for a class of derivative asset payoffs. The class contains common payoffs that are neither uniformly convex nor concave. A digital option, a bull spread, a bear spread, and some portfolios of bull spreads or bear spreads, are all included as special cases. The problem is approached by first solving for the transition density of a process that has a two‐valued volatility. Using this process to model the underlying asset and identifying the two volatility values as σmin and σmax, the value function for any derivative asset in the class is shown to solve the Black–Scholes–Barenblatt equation. The subreplication problem and several related extensions, such as option pricing with transaction costs, calculating superreplicating bounds, and superreplication with multiple risky assets, are also addressed.
Genetic organization and regulation of a meta cleavage pathway for catechols produced from catabolism of toluene, benzene, phenol, and cresols by Pseudomonas pickettii PKO1

Plasmid pRO1957 contains a 26.5-kb BamHI restriction endonuclease-cleaved DNA fragment cloned from the chromosome of Pseudomonas pickettii PKO1 that allows P. aeruginosa PAO1c to grow on toluene, benzene, phenol, or m-cresol as the sole carbon source. The genes encoding enzymes for meta cleavage of catechol or 3-methylcatechol, derived from catabolism of these substrates, were subcloned from pRO1957 and were shown to be organized into a single operon with the promoter proximal to tbuE. Deletion and analysis of subclones demonstrated that the order of genes in the meta cleavage operon was tbuEFGKIHJ, which encoded catechol 2,3-dioxygenase, 2-hydroxymuconate semialdehyde hydrolase, 2-hydroxymuconate semialdehyde dehydrogenase, 4-hydroxy-2-oxovalerate aldolase, 4-oxalocrotonate decarboxylase, 4-oxalocrotonate isomerase, and 2-hydroxypent-2,4-dienoate hydratase, respectively. The regulatory gene for the tbuEFGKIHJ operon, designated tbuS, was subcloned into vector plasmid pRO2317 from pRO1957 as a 1.3-kb PstI fragment, designated pRO2345. When tbuS was not present, meta pathway enzyme expression was partially derepressed, but these activity levels could not be fully induced. However, when tbuS was present in trans with tbuEFGKIHJ, meta pathway enzymes were repressed in the absence of an effector and were fully induced when an effector was present. This behavior suggests that the gene product of tbuS acts as both a repressor and an activator. Phenol and m-cresol were inducers of meta pathway enzymatic activity. Catechol, 3-methylcatechol, 4-methylcatechol, o-cresol, and p-cresol were not inducers but could be metabolized by cells previously induced by phenol or m-cresol.
Flexible HARQ: A high throughput hybrid-ARQ protocol

Hybrid ARQ (HARQ) and link adaptation (LA) are two powerful techniques to improve the data throughput in wireless communication systems. However, when integrated with LA, conventional HARQ does not provide much gain over LA without significantly increasing the number of retransmissions and initial coding rate. In this paper, we explore the feasibility of achieving high throughput by combining HARQ and LA in a more efficient manner. We first introduce an analytical model to provide some insight to LA and HARQ. Then we propose a HARQ protocol, called Flexible HARQ, which allows flexible bandwidth allocation of retransmission data and new transmission data based on imperfect channel state information (CSI) and soft decoding information sent along with ACK/NACK feedback. Several schemes for bandwidth allocation are proposed. Both simulation results and analytical results show significant throughput improvement over LA and conventional HARQ.
Inter-Carrier Interference Suppression in No-Guard-Interval Orthogonal Frequency-Division-Multiplexing System

The inter-carrier interference (ICI) in the no-guard-interval orthogonal frequency-division-multiplexing (NGI-OFDM) system causes severe performance degradation when 2-samples/symbol (Sa/sym) digital signal processing (DSP) is used at the receiver. To enable narrow bandwidth devices and low sampling rate DSP, a novel ICI suppression (ICIS) method is proposed and experimentally demonstrated in this letter. The proposed method improves the performance of the 4-Gbaud 25-carrier NGI-OFDM system by up to 4 dB, and 2-Sa/sym DSP with ICIS achieves comparable performance as the conventional 8-Sa/sym DSP without ICIS, with moderately increased complexity.
INVESTMENT TRENDS OF FOREIGN INSTITUTIONAL INVESTORS IN INDIA: AN ANALYTICAL OVERVIEW

The permission to Foreign Institutional Investors (FIIs) in 1992, to invest in Indian stock market was the first major step of government towards the implication of the globalization policies regarding Indian financial system. Since then, FIIs have been contributing significantly and emerged as one of the main sources of equity capital flows to Indian stock markets. Present paper provides a glimpse of the latest investment trends of FIIs during year 2008-09 and 2009-10 (so far). The paper also provides an overview of FIIs related regulatory environment and recent policy changes to attract outgoing FIIs capital from Indian stock markets after global financial crisis.
Stability analysis and internal dynamics of MIMO GMAW process

Abstract In this paper, stability and internal dynamics for a gas metal arc welding (GMAW) process will be studied. GMAW process is considered as a nonlinear MIMO system and input-output feedback linearization method will be applied for control purposes. Internal dynamics is the unobservable part of the system dynamics; its stability analysis is a vital step in the investigation of the system stability as a whole. Also, drop detachment dynamics, will be considered here by tracking a saw-toothed arc length voltage Simulations results are presented to illustrate the system performance.
Economic Costs of Population Aging

In just over three decades all those born during the post-war baby boom will be 65 and older, and the fraction of the population 'old' will be far greater than previously experienced in Canada, or indeed in any modern industrial nation. That prospect has given rise to major concerns about our ability as a society to meet the large anticipated additions to health care, pension, and other costs associated with the increase in the older population. However, a balanced view requires that attention be given to all publicly provided services, not only to those services used in large measure by the elderly, and also to privately provided goods and services, since the costs must be charged against the same national income in both cases. Beyond that, it is important to recognize that population change affects not only the demand side of the economy, but also the supply side, the nation's productive capacity. This paper reviews the literature to assess the magnitude of the prospective cost increases associated with the aging of the Canadian population and considers the practical implications for government programs and policies.
Utilizing the media to help increase organ donation in the Hispanic American population

Salim A, Berry C, Ley EJ, Schulman D, Navarro S, Chan LS. Utilizing the media to help increase organ donation in the Hispanic American population. Clin Transplant 2011: 25: E622–E628. © 2011 John Wiley & Sons A/S.
What are the roles of the many different types of potassium channel expressed in cerebellar granule cells?

Potassium (K) channels have a key role in the regulation of neuronal excitability. Over a hundred different subunits encoding distinct K channel subtypes have been identified so far. A major challenge is to relate these many different channel subunits to the functional K currents observed in native neurons. In this review, we have concentrated on cerebellar granule neurons (CGNs). We have considered each of the three principal super families of K channels in turn, namely, the six transmembrane domain, voltage-gated super family, the two transmembrane domain, inward-rectifier super family and the four transmembrane domain, leak channel super family. For each super family, we have identified the subunits that are expressed in CGNs and related the properties of these expressed channel subunits to the functional currents seen in electrophysiological recordings from these neurons. In some cases, there are strong molecular candidates for proteins underlying observed currents. In other cases the correlation is less clear. We show that at least 26 potassium channel a subunits are moderately or strongly expressed in CGNs. Nevertheless, a good empirical model of CGN function has been obtained with just six distinct K conductances. The transient K current in CGNs, seems due to expression of Kv4.2 channels or Kv4.2/4.3 heteromers, while the Kca current is due to expression of large-conductance slo channels. The G-protein activated KIR current is probably due to heteromeric expression of KiR3.1 and KiR3.2. Perhaps KiR2.2 subunits underlie the KiR current when it is constitutively active. The leak conductance can be attributed to TASK-1 and or TASK-3 channels. With less certainty, the IK-slow current may be due to expression of one or more members of the KCNQ or EAG family. Lastly, the delayed-rectifier Kv current has as many as six different potential contributors from the extensive Kv family of α subunits. Since many of these subunits are highly regulated by neurotransmitters, physiological regulators and, often, auxiliary subunits, the resulting electrical properties of CGNs may be highly dynamic and subject to constant fine-tuning.
The internationalization strategies of rapidly internationalizing high-tech UK SMEs: Planned and unplanned activities

Purpose – The purpose of this paper is to investigate aspects of causation and effectuation decision-making in respect of the planned and unplanned nature of the internationalization strategies of a small sample of rapidly internationalizing, high-tech UK small and medium enterprises (SMEs). These exhibit four different rates of scale of international intensity (percentage of overseas sales to total sales) and market scope (geographical coverage and commitment). Design/methodology/approach – Interviews with managers of 16 independently owned high-technology-oriented manufacturing SMEs were undertaken in this investigation to reduce the potential effect of bias from parental decision-making and firm size, also trade sectoral conditions. These were drawn from an existing database. Findings – Aspects of both causation and effectuation logic were evident in planned and unplanned aspects of decision-making. Moreover, industry factors were seen to affect internationalization strategies in various ways and not l.
ISOLATION AND CHARACTERIZATION OF ANTIBIOTIC PRODUCING THERMOPHILIC BACILLUS IN SELECTED HOTSPRINGS ALONG LAKE BOGORIA , KENYA

Extreme habitats are increasingly being recognized as sources of secondary metabolites which provide an encouraging source for development of novel natural pharmaceuticals. Saline and hot water lakes are now becoming appreciated as rich and untapped reservoirs of extremophilic microorganisms with previously uncharacterized functions. Bacilli, a large homogeneous group of bacteria that survive in a wide range of environmental conditions, is one such microorganism. Formation of resistant spores allows it to survive in high temperatures zones where other organisms cannot. The objective of this study was to isolate, identify, and characterize Bacillus organisms with the potential to produce secondary metabolites with antibacterial properties from the hot springs of Lake Bogoria. Eighty samples were collected from surface and sediment waters of selected hot springs and inoculated directly into nutrient broth in universal bottles. Samples were initially incubated at 45 o C for 48 hours and growth was examined by checking for turbidity. Out of the 80 bottles inoculated with sample, thirty three exhibited growth. Subsequent streaking on nutrient agar and Gram staining showed that nine of the isolated organisms were Gram-positive rods, twenty were Gram-negative rods, and four were Gram-positive cocci. Only Gram-positive rods were processed further. Biochemical characterization revealed that all nine processed isolates were catalase-positive and non produced gas upon sugar fermentation. They however had varying results for indole, motility, lactose fermentation, glucose fermentation and H2S production. Antibacterial profiling was performed using ATCC organisms: Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Escherichia coli 35218, and Pseudomonas aeruginosa ATCC 27853. Isolates D1, D5, D8, D22 and S15 inhibited growth of Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 which was shown by clear zones of inhibition around the discs. No inhibition was noted against S. aureus ATCC 29213 and E. coli 35218. Phylogenetic analysis of amplified 16S rDNA gene showed that D1, D5, D8, D22 and S15 formed close phylogenetic clusters with known members of Bacillus organisms with a (88-99%) sequence identity. The current study shows the presence of thermophilic Bacillus species, which are producers of biomolecules with antibacterial properties within the hot springs of Lake Bogoria. Characterization of the antibacterial compounds produced will be useful for the discovery of novel antimicrobial substances that are effective against wide range of pathogens.
Extracting debate graphs from parliamentary transcripts: a study directed at UK house of commons debates

The paper proposes a framework---the Debate Graph Extraction (DGE) framework---for extracting debate graphs from transcripts of political debates. The idea is to represent the structure of a debate as a graph with speakers as nodes and "exchanges" as links. Links between nodes are established according to the semantic similarity between the speeches and indicate an alignment of content between them. Nodes are labelled according to the "attitude" (sentiment) of the speakers, positive or negative, using a lexicon based technique founded on SentiWordNet. The attitude of the speakers is then used to label the graph links as being either "supporting" or "opposing". If both speakers have the same attitude (both negative or both positive) the link is labelled as being supporting; otherwise the link is labelled as being opposing. The resulting graphs capture the abstract representation of a debate as two opposing fractions exchanging arguments on related content.
Peroxisome Proliferator-Activated Receptor-α Contributes to the Anti-Inflammatory Activity of Glucocorticoids

Glucocorticoids (GCs) are effective anti-inflammatory agents widely used in the therapeutic approach to treatment of acute and chronic inflammatory diseases. Previous results suggest that peroxisome proliferator-activated receptor-α (PPAR-α), an intracellular transcription factor activated by fatty acids, plays a role in the control of inflammation. With the aim of characterizing the role of PPAR-α in GC-mediated anti-inflammatory activity, we tested the efficacy of dexamethasone (DEX), a synthetic GC specific for glucocorticoid receptor, in an experimental model of lung inflammation, carrageenan-induced pleurisy, comparing mice lacking PPAR-α (PPAR-αKO) with wild-type (WT) mice. We also tested the possible synergism of combined treatment with DEX and clofibrate, a PPAR-α agonist. Results indicate that DEX-mediated anti-inflammatory activity is weakened in PPAR-αKO mice compared with WT controls, and that is increased in WT mice when combined with PPAR-α agonist treatment. In particular, DEX was less effective in PPAR-αKO, compared with WT mice, as evaluated by inhibition of NF-κB, of TNF-α production, of cell migration, of cycloxygenase-2 (COX-2) and inducible nitric-oxide synthase activation. Interestingly enough, macrophages from PPAR-αKO were less susceptible to DEX-induced COX-2 inhibition in vitro compared with WT mice. However, PPAR-α transfection in PPAR-αKO macrophages, with consequent receptor expression, resulted in reconstitution of susceptibility to DEX-induced COX-2 inhibition to levels comparable with that obtained in WT macrophages. It is noteworthy that the DEX effect on macrophages in vitro was significantly increased in WT cells when combined with PPAR-α agonist treatment. These results indicate that PPAR-α can contribute to the anti-inflammatory activity of GCs.
Valuation effects of international joint venture formation: Hong Kong listed companies

The study tests the abnormal returns of announcements of joint-venturing in Mainland China by Hong Kong-based companies. As the Hong Kong stock market is one of the most mature stock markets in the world, the response of the stock price should be among the best quality. Thus the positive response suggests that international joint ventures provide potential profits to the parent firms, which is predicted by the nowadays standard eclectic theory. The result supports the hypothesis of abnormal returns.
Quantification of Qualitative Firm-Level Survey Data

Survey data are widely used to provide indicators of economic activity ahead of the publication of official data. This paper proposes an indicator based on a theoretically consistent procedure for quantifying firm-level survey responses that are ordered and categorical. Firms' survey responses are assumed to be triggered by a latent continuous random variable as it crosses thresholds. Breaking tradition these thresholds are not assumed time invariant. An application to firm-level survey data from the Confederation of British Industry shows that the proposed indicator of manufacturing output growth outperforms traditional indicators that assume time-invariant thresholds.
Structural Requirements for the Ectodomain Cleavage of Human Cell Surface Macrophage Colony-stimulating Factor*

One form of human macrophage colony-stimulating factor (CSF-1256, M-CSFα) is a member of a restricted set of cell surface transmembrane proteins, which is selected to undergo proteolytic ectodomain cleavage. To determine the substrate requirements for this cleavage, we have constructed a series of mutations in the cytoplasmic tail, transmembrane domain, and juxtamembrane region of CSF-1256 and stably expressed the mutated genes in NIH 3T3 cells. Our results demonstrate that membrane association of the CSF-1 precursor is required for cleavage of its growth factor ectodomain and furthermore that the juxtamembrane region Pro161-Gln162-Leu163-Gln164-Glu165 (PQLQE) (residues 161–165 of the ectodomain) is an essential determinant of cell surface CSF-1256 cleavage and that the cleavage site is partially sequence-specific. Furthermore, a mechanism of steric hindrance, which likely involves interference with protease accessibility, is postulated to explain the observed decreases in the cleavage efficiency in certain CSF-1 mutants. Finally, our results strongly suggest that the CSF-1 ectodomain is cleaved at or very near the cell surface by a membrane-associated proteolytic system.