Miracle-dz/UniFAR-FTUs huggingface dataset:
Does Greater Adiposity Increase Blood Pressure and Hypertension Risk?: Mendelian Randomization Using the FTO/MC4R Genotype

Elevated blood pressure increases the risk of experiencing cardiovascular events like myocardial infarction and stroke. Current observational data suggest that body mass index may have a causal role in the etiology of hypertension, but this may be influenced by confounding and reverse causation. Through the use of instrumental variable methods, we aim to estimate the strength of the unconfounded and unbiased association between body mass index/adiposity and blood pressure. We explore these issues in the Copenhagen General Population Study. We used instrumental variable methods to obtain estimates of the causal association between body mass index and blood pressure. This was performed using both rs9939609 (FTO) and rs17782313 (MC4R) genotypes as instruments for body mass index. Avoiding the epidemiological problems of confounding, bias, and reverse causation, we confirmed observational associations between body mass index and blood pressure. In analyses including those taking antihypertensive drugs, but for whom appropriate adjustment had been made, systolic blood pressure was seen to increase by 3.85 mm Hg (95% CI: 1.88 to 5.83 mm Hg) for each 10% increase in body mass index (P=0.0002), with diastolic blood pressure showing an increase of 1.79 mm Hg (95% CI: 0.68 to 2.90 mm Hg) for each 10% increase in body mass index (P=0.002). Observed associations are large and illustrate the considerable benefits in terms of reductions in blood pressure–related morbidity that could be achieved through a reduction in body mass index.
Discursive strategies and radical technological change: Multilevel discourse analysis of the early computer (1947–1958)

Research summary: This paper uses multilevel discourse analysis to advance strategic management research, focusing on the question of why firms fail in the face of radical technological change. Answering this question requires addressing how customers develop their interpretations and evaluation criteria of the new technology. This interpretive process occurs through discussions with other market participants. Firms can influence customers' interpretations through the use of language and visual images—what we call “discursive strategies. ” Firms can fail to navigate technological disruptions because their discursive strategies do not communicate effectively with customers. Yet, methodological limitations have restricted the study of discursive strategies. We draw on multilevel discourse analysis and apply this method to explain why IBM outperformed Remington Rand in the early insurance market for computers.
Target of Rapamycin Complex 2 Signals to Downstream Effector Yeast Protein Kinase 2 (Ypk2) through Adheres-Voraciously-to-Target-of-Rapamycin-2 Protein 1 (Avo1) in Saccharomyces cerevisiae*

Background: Molecular mechanisms underlying target of rapamycin complex 2 (TORC2) signaling are poorly understood. Results: The TORC2 component Avo1 directly interacts with a downstream substrate Ypk2. Conclusion: Avo1-Ypk2 interaction is essential for TORC2-Ypk2 coupling and activation of the downstream effector pathway(s) regulating cell integrity and actin organization. Significance: Physical associations between TORC2 components and specific downstream effectors provide the molecular basis for selective downstream signaling. The conserved Ser/Thr kinase target of rapamycin (TOR) serves as a central regulator in controlling cell growth-related functions. There exist two distinct TOR complexes, TORC1 and TORC2, each coupling to specific downstream effectors and signaling pathways. In Saccharomyces cerevisiae, TORC2 is involved in regulating actin organization and maintaining cell wall integrity. Ypk2 (yeast protein kinase 2), a member of the cAMP-dependent, cGMP-dependent, and PKC (AGC) kinase family, is a TORC2 substrate known to participate in actin and cell wall regulation. Employing avo3ts mutants with defects in TORC2 functions that are suppressible by active Ypk2, we investigated the molecular interactions involved in mediating TORC2 signaling to Ypk2. GST pulldown assays in yeast lysates demonstrated physical interactions between Ypk2 and components of TORC2. In vitro binding assays revealed that Avo1 directly binds to Ypk2. In avo3ts mutants, the TORC2-Ypk2 interaction was reduced and could be restored by AVO1 overexpression, highlighting the important role of Avo1 in coupling TORC2 to Ypk2. The interaction was mapped to an internal region (amino acids 600–840) of Avo1 and a C-terminal region of Ypk2. Ypk2334–677, a truncated form of Ypk2 containing the Avo1-interacting region, was able to interfere with Avo1-Ypk2 interaction in vitro. Overexpressing Ypk2334–677 in yeast cells resulted in a perturbation of TORC2 functions, causing defective cell wall integrity, aberrant actin organization, and diminished TORC2-dependent Ypk2 phosphorylation evidenced by the loss of an electrophoretic mobility shift. Together, our data support the conclusion that the direct Avo1-Ypk2 interaction is crucial for TORC2 signaling to the downstream Ypk2 pathway.
Fully dynamic planarity testing with applications

This paper introduces compressed certificates for planarity, biconnectivity and triconnectivity in planar graphs, and proves many structural properties of certificates in planar graphs. As an application of our compressed certificates, we develop efficient dynamic planar algorithms. In particular, we consider the following three operations on a planar graph <italic>G</italic>: (i) insert an edge if the resultant graph remains planar; (ii) delete an edge; and (iii) test whether an edge could be added to the graph without violating planarity. We show how to support each of the above operations in <italic>O</italic>(<italic>n</italic><supscrpt>2/3</supscrpt>) time, where <italic>n</italic> is the number of vertices in the graph. The bound for tests and deletions is worst-case, while the bound for insertions is amortized. This is the first algorithm for this problem with sub-linear running time, and it affirmatively answers a question posed in Epstein et al. [1992]. We use our compressed certificates for biconnectivity and triconnectivity to maintain the biconnected and triconnected components of a dynamic planar graph. The time bounds are the same: <italic>O</italic>(<italic>n</italic><supscrpt>2/3</supscrpt>) worst-case time per edge deletion, <italic>O</italic>(<italic>n</italic><supscrpt>2/3</supscrpt>) amortized time per edge insertion, and <italic>O</italic>(<italic>n</italic><supscrpt>2/3</supscrpt>) amortized time per edge insertion, and <italic>O</italic>(<italic>n</italic><supscrpt>2/3</supscrpt>)worst-case time to check whether two vertices are either biconnected or triconnected.
Growth , economic development and structural transition in small vulnerable states

This paper reviews the critical theoretical and policy issues relating to growth, economic development and structural transition in small states. The paper discusses alternative perspectives on small size and highlights the salient characteristics which give rise to their economic sub-optimality. The theoretical and empirical relationship between size and growth is reviewed, including recent inferences relating to structural transition and comparative advantage in small states. This discussion derives several insights from endogenous growth theory and highlights the critical role of available endogenous policy options, particularly with respect to trade and its implications for the process of growth and development. The discussion of vulnerability touches upon methodological and data issues relating to measurement, provides a critique of alternative indices and the impact of vulnerability in small states.
Tractable Reasoning in First-Order Knowledge Bases with Disjunctive Information

This work proposes a new methodology for establishing the tractability of a reasoning service that deals with expressive first-order knowledge bases. It consists of defining a logic that is weaker than classical logic and that has two properties: first, the entailment problem can be reduced to the model checking problem for a small number of characteristic models; and second, the model checking problem itself is tractable for formulas with a bounded number of variables. We show this methodology in action for the reasoning service previously proposed by Liu, Lakemeyer and Levesque for dealing with disjunctive information. They show that their reasoning is tractable in the propositional case and decidable in the first-order case. Here we apply the methodology and prove that the reasoning is also tractable in the first-order case if the knowledge base and the query both use a bounded number of variables.
Near-far effect mitigation for GNSS software receivers using subspace projection

This paper proposes an improved implementation of the subspace projection method aiming to minimize the near-far effect that occurs in Global Navigation Satellite System receivers. Our technique does not demand phase estimation of the strong signals, thus being suitable for non-coherent receivers. Simulation results demonstrate the effectiveness and the limitations of the proposed mitigation technique.
Semantic Labeling of Online Information Sources December 8 , 2006

Software agents need to combine information from a variety of heterogeneous sources in the course of automating a task, such as planning a trip. In order to be able to use a source, an agent must have a model of it, i.e., understand the semantics of the input and output data it uses, as well as its functionality. Currently, source modeling is done by the user, but as large numbers of sources come online, it is impractical to expect the user to manually model them. To address this problem, it has been proposed that service providers use common ontologies. However, it appears to be equally impractical to expect service providers to conform to a standard, as there is very little incentive for them to do so. Instead, we propose to automatically learn the semantics of information sources by labeling the input and output parameters used by the source with semantic types of the user’s domain model. We describe two machine learning techniques for semantic labeling: one that uses source’s metadata, such as that contained in a Web Service Definition file, and one that uses the source’s content to classify the semantic types it uses. We go beyond previous works by verifying the classifier’s predictions by invoking the source with some sample data of the predicted type. We provide performance results of both classification methods and validate our approach on several live Web source — both Web services and HTML-form based sources. We also describe application of the semantic mapping technology within the CALO project.
Evaluating the energy efficiency of software defined-based cloud radio access networks

Densifying the communications network and integrating innovative technologies leads to increased power consumption (PC), along with increased signalling and degraded scalability. The latter can be mitigated by using software defined networks, while cloud radio access network (C-RAN) reduces the PC. Since evaluating and improving the PC is an important key success factor for the upcoming fifth generations, a reliable power model (PM) is required. This study proposes a componentised, linear and parameterised PM, and explores the individual components relevant for PC analysis, particularly for software defined C-RAN (SDC-RAN) architecture. The model quantifies the energy efficiency (EE) by capturing the PC of individual components, and measures the amount of PC in the network. Cooling and total PC of C-RAN and SDC-RAN for different parameters such as varying numbers of antennas and different system's bandwidth share has also been considered. The results show that SDC-RAN increases the total PC by about 20% compared with C-RAN. Additionally, the study shows the results of modelling the participating core network's control plane unit's PC along with establishing the accuracy of the components and the parameterised models.
The C66W Mutation in the Deafness Dystonia Peptide 1 (DDP1) Affects the Formation of Functional DDP1·TIM13 Complexes in the Mitochondrial Intermembrane Space*

Mohr-Tranebjaerg syndrome is a progressive, neurodegenerative disorder caused by loss-of-function mutations in theDDP1/TIMM8A gene. DDP1 belongs to a family of evolutionary conserved proteins that are organized in hetero-oligomeric complexes in the mitochondrial intermembrane space. They mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane. All of them share a conserved Cys4 metal binding site proposed to be required for the formation of zinc fingers. So far, the only missense mutation known to cause a full-blown clinical phenotype is a C66W exchange directly affecting this Cys4motif. Here, we show that the mutant human protein is efficiently imported into mitochondria and sorted into the intermembrane space. In contrast to wild-type DDP1, it does not complement the function of its yeast homologue Tim8. The C66W mutation impairs binding of Zn2+ ions via the Cys4 motif. As a consequence, the mutated DDP1 is incorrectly folded and loses its ability to assemble into a hetero-hexameric 70-kDa complex with its cognate partner protein human Tim13. Thus, an assembly defect of DDP1 is the molecular basis of Mohr-Tranebjaerg syndrome in patients carrying the C66W mutation.
Mismatched codebooks and the role of entropy coding in lossy data compression

We introduce a universal quantization scheme based on random coding, and we analyze its performance. This scheme consists of a source-independent random codebook (typically mismatched to the source distribution), followed by optimal entropy coding that is matched to the quantized codeword distribution. A single-letter formula is derived for the rate achieved by this scheme at a given distortion, in the limit of large codebook dimension. The rate reduction due to entropy coding is quantified, and it is shown that it can be arbitrarily large. In the special case of "almost uniform" codebooks (e.g., an independent and identically distributed (i.i.d.) Gaussian codebook with large variance) and difference distortion measures, a novel connection is drawn between the compression achieved by the present scheme and the performance of "universal" entropy-coded dithered lattice quantizers. This connection generalizes the "half-a-bit" bound on the redundancy of dithered lattice quantizers. Moreover, it demonstrates a strong notion of universality where a single "almost uniform" codebook is near optimal for any source and any difference distortion measure. The proofs are based on the fact that the limiting empirical distribution of the first matching codeword in a random codebook can be precisely identified. This is done using elaborate large deviations techniques, that allow the derivation of a new "almost sure" version of the conditional limit theorem.
Do the effects of testosterone on muscle strength, physical function, body composition, and quality of life persist six months after treatment in intermediate-frail and frail elderly men?

CONTEXT Short-term testosterone (T) treatment in frail elderly men improves muscle mass and strength. It is unclear whether these effects can be maintained post treatment. OBJECTIVE To assess the durability of androgen effects in frail men. DESIGN AND SETTING Single center, randomized, double-blind, placebo-controlled trial to investigate the effects of 6 months T (25-75 mg daily) on muscle strength, body composition, physical function, and quality of life (QoL). Participants were assessed at the end of treatment (6 months) and 6 months after treatment cessation (12 months). PARTICIPANTS 274 intermediate-frail and frail elderly men aged 65-90 years with low T levels. RESULTS Mean T increased from 11.1 (3.1) nmol/liter at baseline to 18.4 (3.5) nmol/liter at 6 months, then declined to 10.5 (3.7) nmol/L at 12 months, in the T-treated group. Isometric knee extension peak torque increased in the T-treated group compared with placebo to give an adjusted mean difference (95% CI) between groups of 8.1 (-0.2 to 16.5) Nm at 6 months. Lean mass increased in the T-treated group giving a difference between groups of 1.2 (0.8 to 1.7) kg at 6 months. Somatic and sexual symptoms improved during treatment. None of these differences between groups remained at 12 months. Prostate specific antigen (PSA) levels and haematocrit increased slightly during treatment but returned to baseline by 12 months. CONCLUSION The effects of 6-month T treatment on muscle strength, lean mass, and QoL in frail men are not maintained at 6 months post treatment.
A Cross-Linguistic PET Study of Tone Perception in Mandarin Chinese and English Speakers

PET was used in a cross-linguistic study to determine whether neural mechanisms subserving pitch perception differ as a function of linguistic relevance. We compared tone perception in 12 native Mandarin speakers, who use tonal patterns to distinguish lexical meaning, with that of 12 native speakers of a nontone language, English. Subjects were scanned under two conditions: a silent resting baseline and a tonal task involving discrimination of pitch patterns in Mandarin words. Both groups showed common regions of CBF increase, but only Mandarin speakers showed additional activation in frontal, parietal, and parieto-occipital regions of the left hemisphere; this latter finding indicates that language experience may influence brain circuitry in the processing of auditory cues. In contrast, only the English group showed activity in the right inferior frontal cortex, consistent with a right-hemispheric role in pitch perception.
Evaluation of the Limulus Amebocyte Lysate and Recombinant Factor C Assays for Assessment of Airborne Endotoxin

ABSTRACT As a potent inflammatory agent, endotoxin is a key analyte of interest for studies of lung ailments in domestic environments and occupational settings with organic dust. A relatively unexplored advance in endotoxin exposure assessment is the use of recombinant factor C (rFC) from the Limulus pathway in a fluorometric assay. In this study, we compared airborne endotoxin concentrations in laboratory- and field-collected parallel air samples using the kinetic Limulus amebocyte lysate (LAL) assay and the rFC assay. Air sampling was performed using paired Institute of Occupational Medicine (IOM) samplers, Button samplers, closed-face cassettes, and cyclone samplers. Field sampling was performed in 10 livestock production facilities, including those housing swine, chicken, turkey, dairy cows, cattle, and horses. Laboratory sampling was performed in exposure chambers using resuspended airborne dust collected in five livestock facilities. Paired samples were extracted in pyrogen-free water with 0.05% Tween 20 and analyzed using LAL and rFC assays. In 402 field sample pairs there was excellent agreement between endotoxin concentrations determined by LAL and rFC (r = 0.93; P < 0.0001). In 510 laboratory sample pairs there was also excellent agreement between the two assays (r = 0.86; P < 0.0001). Correlations for subgroups of facility or dust type ranged from 0.65 to 0.96. Mixed-model analysis of variance (ANOVA) for the field studies showed significant interactions of facility-sampler and facility-assay. rFC/LAL ratios of the geometric means were 0.9 to 1.14 for the samplers (not significantly different from 1.0). The data from this study demonstrate that the LAL assay and the rFC assay return similar estimates of exposure in livestock facilities. Both methods provided suitable lower limits of detection such that all but 19 of 1,824 samples were quantifiable.
Pch2 Modulates Chromatid Partner Choice During Meiotic Double-Strand Break Repair in Saccharomyces cerevisiae

In most organisms, the segregation of chromosomes during the first meiotic division is dependent upon at least one crossover (CO) between each pair of homologous chromosomes. COs can result from chromosome double-strand breaks (DSBs) that are induced and preferentially repaired using the homologous chromosome as a template. The PCH2 gene of budding yeast is required to establish proper meiotic chromosome axis structure and to regulate meiotic interhomolog DSB repair outcomes. These roles appear conserved in the mouse ortholog of PCH2, Trip13, which is also involved in meiotic chromosome axis organization and the regulation of DSB repair. Using a combination of genetic and physical assays to monitor meiotic DSB repair, we present data consistent with pch2Δ mutants showing defects in suppressing intersister DSB repair. These defects appear most pronounced in dmc1Δ mutants, which are defective for interhomolog repair, and explain the previously reported observation that pch2Δ dmc1Δ cells can complete meiosis. Results from genetic epistasis analyses involving spo13Δ, rad54Δ, and mek1/MEK1 alleles and an intersister recombination reporter assay are also consistent with Pch2 acting to limit intersister repair. We propose a model in which Pch2 is required to promote full Mek1 activity and thereby promotes interhomolog repair.
Per-thread cycle accounting in SMT processors

This paper proposes a cycle accounting architecture for Simultaneous Multithreading (SMT) processors that estimates the execution times for each of the threads had they been executed alone, while they are running simultaneously on the SMT processor. This is done by accounting each cycle to either a base, miss event or waiting cycle component during multi-threaded execution. Single-threaded alone execution time is then estimated as the sum of the base and miss event components; the waiting cycle component represents the lost cycle count due to SMT execution. The cycle accounting architecture incurs reasonable hardware cost (around 1KB of storage) and estimates single-threaded performance with average prediction errors around 7.2% for two-program workloads and 11.7% for four-program workloads. The cycle accounting architecture has several important applications to system software and its interaction with SMT hardware. For one, the estimated single-thread alone execution time provides an accurate picture to system software of the actually consumed processor cycles per thread. The alone execution time instead of the total execution time (timeslice) may make system software scheduling policies more effective. Second, a new class of thread-progress aware SMT fetch policies based on per-thread progress indicators enable system software level priorities to be enforced at the hardware level.
Acetaldehyde alters Ca 2 (cid:1) -release channel gating and muscle contraction in a dose-dependent manner

Acetaldehyde alters Ca 2 (cid:1) -release channel gating and muscle contraction in a dose-depen-dent manner. Am J Physiol Cell Physiol 286: C1188–C1194, 2004. We studied whether acetaldehyde, which is produced by alcohol consumption, impacts ryanodine receptor (RyR) activity and muscle force. Exposure to (cid:2) 50–200 (cid:3) M acetaldehyde enhanced channel activity of frog RyR and rabbit RyR1 incorporated into lipid bilayers. An increase in acetaldehyde to 1 mM modiﬁed channel activity in a time-dependent manner, with a brief activation and then inhibition. Application of 200 (cid:3) M acetaldehyde to frog ﬁbers increased twitch tension. The maximum rate of rise of tetanus tension was accelerated to 1.5 and 1.74 times the control rate on exposure of ﬁbers to 50 and 200 (cid:3) M acetaldehyde, respectively. Fluorescence monitoring with ﬂuo 3 demonstrated that 200–400 (cid:3) M acetaldehyde induced Ca 2 (cid:1) release from the sarcoplasmic reticulum (SR) in frog muscles. Acetaldehyde at 1 mM inhibited twitch tension by (cid:2) 12%, with an increased relaxation time after a small, transient twitch potentiation. These results suggest that moderate concentrations of acetaldehyde can elicit Ca 2 (cid:1) release from the SR by increasing the open probability of the RyR channel, resulting in increased tension. However, the effects of acetaldehyde at clinical doses (1–30 (cid:3) M) are unlikely to mediate alcohol-induced acute muscle dysfunction.