Miracle-dz/UniFAR-FTUs huggingface dataset:
Haplotypes at LBX1 Have Distinct Inheritance Patterns with Opposite Effects in Adolescent Idiopathic Scoliosis

Adolescent idiopathic scoliosis (AIS) is a clinically significant disorder with high heritability that affects 2–4% of the population. Genome-wide association studies have identified LBX1 as a strong susceptibility locus for AIS in Asian and Caucasian populations. Here we further dissect the genetic association with AIS in a Caucasian population. To identify genetic markers associated with AIS we employed a genome-wide association study (GWAS) design comparing 620 female Caucasian patients who developed idiopathic scoliosis during adolescence with 1,287 ethnically matched females who had normal spinal curves by skeletal maturity. The genomic region around LBX1 was imputed and haplotypes investigated for genetic signals under different inheritance models. The strongest signal was identified upstream of LBX1 (rs11190878, Ptrend = 4.18×10-9, OR = 0.63[0.54–0.74]). None of the remaining SNPs pass the genome-wide significance threshold. We found rs11190870, downstream of LBX1 and previously associated with AIS in Asian populations, to be in modest linkage disequilibrium (LD) with rs11190878 (r2 = 0.40, D' = 0.81). Haplotype analysis shows that rs11190870 and rs11190878 track a single risk factor that resides on the ancestral haplotype and is shared across ethnic groups. We identify six haplotypes at the LBX1 locus including two strongly associated haplotypes; a recessive risk haplotype (TTA, Controlfreq = 0.52, P = 1.25×10-9, OR = 1.56), and a co-dominant protective haplotype (CCG, Controlfreq = 0.28, P = 2.75×10-7, OR = 0.65). Together the association signals from LBX1 explain 1.4% of phenotypic variance. Our results identify two clinically relevant haplotypes in the LBX1-region with opposite effects on AIS risk. The study demonstrates the utility of haplotypes over un-phased SNPs for individualized risk assessment by more strongly delineating individuals at risk for AIS without compromising the effect size.
Efficacy of the levonorgestrel intrauterine system in treating menorrhagia: Actualities and ambiguities

Objective To review the literature on usage of the levonorgestrel intrauterine system (LNG IUS) in women with fibroids or adenomyosis in an attempt to develop a pragmatic approach when faced with enlarged uteri. Data sources Computerised searches of MEDLINE and EMBASE up to December 2000. Some of the information was obtained from references listed in the primary sources and references already known to the authors. Study selection Studies and case reports were excluded if they did not specifically provide information about LNG IUS usage in women with fibroids and adenomyosis. Data extraction and synthesis After perusal, each relevant publication was summarised and appraised in terms of whether it contained information relevant to the stated objective. Discussion This area is sparsely researched, as there were no randomised-controlled studies. One large contraceptive study suggests the LNG IUS has a protective effect from the complications of uterine fibroids and smaller case studies suggest it is also useful in women with symptomatic fibroids. However, there is also evidence of an increased risk of expulsion and there may be a place for initial adjunctive medical treatment to minimise this risk. An observational study and isolated reports of women with adenomyosis report significant symptomatic relief in these women. Conclusion Available data refute the notion that uterine enlargement is a contraindication to insertion of the LNG IUS, but there appear to be reasons for a cautious approach when dealing with pathological uteri.
Performance, Firm Size, and the 'Basicness' of Research

Using novel firm-level panel data this paper investigates the relationship between performance, firm size, and the composition of innovative activity. We distinguish between firm-level indicators of applied research using patents and indicators of basic research using scientific publications in 'hard science' journals. We look at total factor productivity and growth as measures of firm performance. Our results indicate that the relation of performance with patents is stronger for small firms than for large firms. By contrast, the relation of performance with scientific publications is stronger for large firms than for small firms. Patenting is beneficial especially to small firms, while publications are by far the strongest indicator of success for large firms. Many small firms appear to publish for non-pecuniary reasons (e.g., a 'taste' for open science). Important differences across technology fields are found.
FREIGHT TRANSPORT SUPPLY AND DEMAND CONDITIONS IN THE NORDIC COUNTRIES: RECENT EVIDENCE

This paper summarizes the outcomes of research performed under the Scandinet project, which the European Commission awarded in 1996 to a consortium of 7 European research institutions under the 4th Framework program. The overall objective of the project was to identify the means for enhancing the use of intermodal freight supply solutions within the Nordic region of Europe. Findings are presented from 3 research tasks which accomplished the following: 1) identified the structure of supply and demand for single-mode and intermodal freight transit in Europe's northernmost region; 2) explored the contents of market demand from small and large industrial users; and 3) assessed the quality of market performance of operators, and the relationship between transport service quality as supplied by carriers and required by shippers.
Counting Pairs of Lattice Paths by Intersections

We count the pairs of walks between diagonally opposite corners of a given lattice rectangle by the number of points in which they intersect. We note that the number of such pairs with one intersection is twice the number with no intersection and we give a bijective proof of that fact. Some probabilistic variants of the problem are also investigated.
Innovation in manufacturing from product variety and labor productivity growth to economic development in Chile

In recent decades the expansion of the Chilean economy has been closely related to the Copper Industry, currently representing over fifty percent of Chilean exports. For the economy to grow sustainably in the long term, knowledge needs to be accumulated in the production process, export needs to be diversified and market competitiveness must be promoted. This work offers an analysis of the Chilean economy focusing on some opportunities and challenges that need to be considered to achieve growth for the following decades. It then contributes to our understanding of the innovative process in the Chilean economy with studies of the relation of knowledge flows and RD product diversification with total output and productivity; and labor productivity with the competitiveness of markets.
Protecting Gorgonian Corals off Alaska from Fishing Impacts

Large deep sea corals of the Order Gorgonacea are found in the North Pacific Ocean off Alaska, USA. The North Pacific Fishery Management Council has identified these corals as essential fish habitat of particular concern, so management measures to reduce the fishery impacts are being considered. These corals have been shown to be 1) important shelter for rockfish and other fish species; 2) very long lived; 3) easily damaged by fishing gear; and 4) slow to recover from damage. Coral conservation measures previously implemented include trawl closure areas and a prohibition on commercial harvests. Because other fishing gears (e.g., longlines and pots) also impact corals, a prohibition of all gear types in areas of high coral concentration was proposed and evaluated. The proposal was tabled because available scientific data on coral distribution was at too large of a scale to define discrete locations of coral colonies. Additionally, many fishermen using longline and pot gear were concerned about being displaced from areas they had previously fished, and many felt that their gear caused less damage to corals than trawl gear. Involvement of stakeholders at the local level will allow for better information exchange, including information on coral distribution, fishing gear impacts, and development of appropriate management measures.
What are the effects of input subsidy programs on equilibrium maize prices? Evidence from Malawi and Zambia

An important hypothesized benefit of large-scale input subsidy programs in Africa is that by raising maize production, the subsidies should put downward pressure on retail maize prices to the benefit of urban consumers and the rural poor who tend to be net food buyers. To inform debates related to this rationale for input subsidies, this study estimates the effects of fertilizer subsidies on retail maize prices in Malawi and Zambia using market or district-level panel data covering the 2000/01 to 2011/12 maize marketing years. Results indicate that roughly doubling the size of Malawi’s subsidy program (i.e., increasing the amount of subsidized fertilizer distributed to each district by 4,000 metric tons per year) reduces maize prices by 1.2% to 1.6% on average. In Zambia, roughly doubling the scale of the country’s subsidy program (i.e., increasing the amount of subsidized fertilizer distributed to each district by 1,000 metric tons per year) reduces maize prices by 1.8% to 2.4% on average. The results are robust across countries and model specifications, and indicate that the fertilizer subsidy programs in Malawi and Zambia have had a minimal effect on reducing retail maize prices.
Comparison of Neurologic and Radiographic Outcomes with Solitaire versus Merci/Penumbra Systems for Acute Stroke Intervention

Background and Purpose. The Solitaire Flow Restoration was approved by the FDA in 2012 for mechanical thrombolysis of proximal occlusion of intracranial arteries. To compare the Solitaire FR device and the Merci/Penumbra (previously FDA approved) systems in terms of safety, clinical outcomes, and efficacy including radiographic brain parenchymal salvage. Methods. Thirty-one consecutive patients treated with the Solitaire and 20 patients with comparable baseline characteristics treated with Merci or Penumbra systems were included in the study. Primary outcome measures included recanalization rate and modified Rankin Scale score at followup. Secondary outcomes included length of procedure, incidence of symptomatic intracranial hemorrhage, 90-day mortality, and radiographic analysis of percentage area salvage. Results. Compared with the Merci/Penumbra group, the Solitaire group showed a statistically significant improvement in favorable outcomes (mRS ≤ 2) (69% versus 35%, P = 0.03) and symptomatic ICH rate (0 versus 15%, P = 0.05) with a trend towards higher recanalization rates (93.5% versus 75%, P = 0.096) and shorter length of procedure (58.5 min versus 70.8 min, P = 0.08). Radiographic comparison also showed a significantly larger area of salvage in the Solitaire group (81.9% versus 71.9%, P = 0.05). Conclusion. Our study suggests that the Solitaire system allows faster, safer, and more efficient thrombectomy than Merci or Penumbra systems.
Effects of Defined Mutations in the 5′ Nontranslated Region of Rubella Virus Genomic RNA on Virus Viability and Macromolecule Synthesis

ABSTRACT The 5′ end of the genomic RNA of rubella virus (RUB) contains a 14-nucleotide (nt) single-stranded leader (ss-leader) followed by a stem-and-loop structure [5′(+)SL] (nt 15 to 65), the complement of which at the 3′ end of the minus-strand RNA [3′(−)SL] has been proposed to function as a promoter for synthesis of genomic plus strands. A second intriguing feature of the 5′ end of the RUB genomic RNA is the presence of a short (17 codons) open reading frame (ORF) located between nt 3 and 54; the ORF encoding the viral nonstructural proteins (NSPs) initiates at nt 41 in an alternate translational frame. To address the functional significance of these features, we compared the 5′-terminal sequences of six different strains of RUB, with the result that the short ORF is preserved (although the coding sequence is not conserved) as is the stem part of both the 5′(+)SL and 3′(−)SL, while the upper loop part of both structures varies. Next, using Robo302, an infectious cDNA clone of RUB, we introduced 31 different mutations into the 5′-terminal noncoding region, and their effects on virus replication and macromolecular synthesis were examined. This mutagenesis revealed that the short ORF is not essential for virus replication. The AA dinucleotide at nt 2 and 3 is of critical importance since point mutations and deletions that altered or removed both of these nucleotides were lethal. None of the other mutations within either the ss-leader or the 5′(+)SL [and accordingly within the 3′(−)SL], including deletions of up to 15 nt from the 5′(+)SL and three different multiple-point mutations that lead to destabilization of the 5′(+)SL, were lethal. Some of the mutations within both ss-leader and the 5′(+)SL resulted in viruses that grew to lower titers than the wild-type virus and formed opaque and/or small plaques; in general mutations within the stem had a more profound effect on viral phenotype than did mutations in either the ss-leader or upper loop. Mutations in the 5′(+)SL, but not in the ss-leader, resulted in a significant reduction in NSP synthesis, indicating that this structure is important for efficient translation of the NSP ORF. In contrast, viral plus-strand RNA synthesis was unaffected by the 5′(+)SL mutations as well as the ss-leader mutations, which argues against the proposed function of the 3′(−)SL as a promoter for initiation of the genomic plus-strand RNA.
A New Mechanism for Recurrent Adaptive Radiations

Models of adaptive radiation through intraspecific competition have attracted mounting attention. Here we show how extending such models in a simple manner, by including a quantitative trait under weak directional selection, naturally leads to rich macroevolutionary patterns involving recurrent adaptive radiations and extinctions. Extensive tests demonstrate the robustness of this finding to a wide range of variations in model assumptions. In particular, recurrent adaptive radiations and extinctions readily unfold both for asexual and for sexual populations. Since the mechanisms driving the investigated processes of endogenous diversification result from generic geometric features of the underlying fitness landscapes—frequency‐dependent disruptive selection in one trait and weak directional selection in another—the reported phenomena can be expected to occur in a wide variety of eco‐evolutionary settings.
Intergroup Conflict: Individual, Group, and Collective Interests

Intergroup conflicts generally involve conflicts of interests within the competing groups as well. This article outlines a taxonomy of games, called team games, which incorporates the intragroup and intergroup levels of conflict. Its aims are to provide a coherent framework for analyzing the prototypical problems of cooperation and competition that arise within and between groups, and to review an extensive research program that has used this framework to study individual and group behavior in the laboratory. Depending on the game's payoff structure, contradictions or conflicts are created among the rational choices at the individual, group, and collective levels—a generalization of the contradiction between individual and collective rationality occurring in the traditional mixed-motive games. These contradictions are studied so as to identify the theoretical and behavioral conditions that determine which level of rationality prevails.
Neutralino dark matter in the MSSM with CP violation

In the MSSM, the presence of CP phases can have a significant impact on the neutralino relic abundance. These phase effects are on the one hand due to shifts in the masses, on the other hand due to modifications of the couplings. Typical variations in Ωh2 solely from modifications in the couplings are O(10%–100%).
Stirring the Embers: High-Sensitivity VLBI Observations of GRB 030329

We present high-sensitivity Very Long Baseline Interferometry (VLBI) observations 806 days after the γ-ray burst of 2003 March 29 (GRB 030329). The angular diameter of the radio afterglow is measured to be 0.347 ± 0.09 mas, corresponding to 0.99 ± 0.26 pc at the redshift of GRB 030329 (z = 0.1685). The evolution of the image size favors a uniform external density over an R-2 windlike density profile (at distances of R ≳ 1018 cm from the source), although the latter cannot be ruled out yet. The current apparent expansion velocity of the image size is only mildly relativistic, suggesting a nonrelativistic transition time of tNR ~ 1 yr. A rebrightening, or at least a significant flattening in the flux decay, is expected within the next several years as the counterjet becomes visible (this has not yet been observed). An upper limit of <1.9c is set on the proper motion of the flux centroid.
Variability of excitatory currents due to single-channel noise, receptor number and morphological heterogeneity.

Patch clamp recordings of excitatory postsynaptic currents (EPSCs) in central neurons reveal large fluctuations in amplitudes and decay times of AMPA-receptor-mediated EPSCs. By using Monte Carlo simulations of synaptic transmission in brainstem interneurons, we tested several hypothesis that could account for the observed variability. The coefficient of variation (CV) of 0.5 for miniature amplitudes cannot be explained by fluctuations in vesicle content or receptor distribution, but is traced to variations in receptor number, which is estimated as 77+/-39 receptors per bouton. As the variability of rise times reflects fluctuations in size of the post-synaptic density and heterogeneity of the receptor distribution, the relatively small CV=0.37 of experimentally determined values points to a homogeneous arrangement of receptors. Within our model the large variability of decay times (CV=0.49) can only be explained by fluctuations in the transmitter time course (mean residence times of 0.4+/-0.13 ms), presumably resulting from heterogeneities in synaptic morphology. Hence, our simulations indicate that different noise sources control the variability of amplitudes, rise and decay times. In particular, the distribution of decay times yields information about the synaptic transmission process, which cannot be obtained from other observables.
Safety of Resuming Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis Patients Concomitant with the Treatment of Active Tuberculosis: A Retrospective Nationwide Registry of the Korean Society of Spondyloarthritis Research

Backgrounds Patients who develop an active tuberculosis infection during tumor necrosis factor (TNF) inhibitor treatment typically discontinue TNF inhibitor and receive standard anti-tuberculosis treatment. However, there is currently insufficient information on patient outcomes following resumption of TNF inhibitor treatment during ongoing anti- tuberculosis treatment. Our study was designed to investigate the safety of resuming TNF inhibitors in ankylosing spondylitis (AS) patients who developed tuberculosis as a complication of the use of TNF inhibitors. Methods Through the nationwide registry of the Korean Society of Spondyloarthritis Research, 3929 AS patients who were prescribed TNF inhibitors were recruited between June 2003 and June 2014 at fourteen referral hospitals. Clinical information was analyzed about the patients who experienced tuberculosis after exposure to TNF inhibitors. The clinical features of resumers and non-resumers of TNF inhibitors were compared and the outcomes of tuberculosis were surveyed individually. Findings Fifty-six AS patients were treated for tuberculosis associated with TNF inhibitors. Among them, 23 patients resumed TNF inhibitors, and these patients were found to be exposed to TNF inhibitors for a longer period of time and experienced more frequent disease flare-up after discontinuation of TNF inhibitors compared with those who did not resume. Fifteen patients resumed TNF inhibitors during anti-tuberculosis treatment (early resumers) and 8 after completion of anti-tuberculosis treatment (late resumers). Median time to resuming TNF inhibitor from tuberculosis was 3.3 and 9.0 months in the early and late resumers, respectively. Tuberculosis was treated successfully in all resumers and did not relapse in any of them during follow-up (median 33.8 [IQR; 20.8–66.7] months). Conclusions Instances of tuberculosis were treated successfully in our AS patients, even when given concomitantly with TNF inhibitors. We suggest that early resumption of TNF inhibitors in AS patients could be safe under effective coverage of tuberculosis.
Fiscal policy in the Great Recession

This thesis investigates three questions on fiscal policy that have gained importance in the recent turbulent times of general economic decline, labelled as the Great Recession. The first chapter examines how government spending multipliers can vary depending on the location of the debt holder. Empirically, we find that fiscal multipliers are larger when government purchases are financed by issuing debt to non-resident foreign investors, than to resident home investors. Using a theoretical model we then show how the location of the government debt holder produces these di↵erential responses through the extent that investment is crowded out in each case. Increasing international capital mobility of the resident private sector can attenuate the di↵erence between the two types of financing. The second chapter contributes to the current debate on fiscal sustainability and fiscal coordination in currency unions. It does so using a large-scale New-Keynesian DSGE model calibrated to the EA South and EA North, and fed with a particular fiscal policy scenario identified using the guidelines of the Stability and Growth Pact. The results suggest that when monetary policy is constrained by the zero-lower bound an expansion in the EA North o↵sets a consolidation in the EA South leading to a union-wide increase in output. The third chapter studies the e↵ects of fiscal policy in a setting where crisis shocks propagate through the real exchange rate to generate distortions in labour and financial markets. The joint presence of labour market and financial frictions, modelled as downward nominal rigid wages and a collateral constraint on private borrowing, endogenously generate unemployment and persistently high debt levels. Fiscal policies aiming to stimulate or consolidate the economy a↵ect the movement of the real exchange rate in such a way so as to generate it toothless in the face of a ’debt-unemployment’ trade-o↵. iii
The Role of Bioreactors in Tissue Engineering for Musculoskeletal Applications

Tissue engineering involves using the principles of biology, chemistry and engineering to design a ‘neotissue’ that augments a malfunctioning in vivo tissue. The main requirements for functional engineered tissue include reparative cellular components that proliferate on a biocompatible scaffold grown within a bioreactor that provides specific biochemical and physical signals to regulate cell differentiation and tissue assembly. We discuss the role of bioreactors in tissue engineering and evaluate the principles of bioreactor design. We evaluate the methods of cell stimulation and review the bioreactors in common use today.