Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficient algorithms on sets of permutations, dominance, and real-weighted APSP

Sets of permutations play an important role in the design of some efficient algorithms. In this paper we design two algorithms that manipulate sets of permutations. Both algorithms, each solving a different problem, use fast matrix multiplication techniques to achieve a significant improvement in the running time over the naive solutions. For a set of permutations P ⊂ Sn we say that i k-dominates j if the number of permutations π ∈ P for which π(i) < π(j) is k. The dominance matrix of P is the n x n matrix DP where DP(i, j) = k if and only if i k-dominates j. We give an efficient algorithm for computing DP using fast rectangular matrix multiplication. In particular, when |P| = n our algorithm runs in O(n2.684) time. Computing the dominance matrix of permutations is computationally equivalent to the dominance problem in computational geometry. Thus, our algorithm slightly improves upon a well-known O(n2.688) time algorithm of Matousek for the dominance problem. Permutation dominance is used, together with several other ingredients, to obtain a truly sub-cubic algorithm for the All Pairs Shortest Paths (APSP) problem in real-weighted directed graphs, where the number of distinct weights emanating from each vertex is O(n0.338). A special case of this algorithm implies an O(n2.842) time algorithm for real vertex-weighted APSP, which slightly improves a recent result of Chan [STOC-07]. A set of permutations P ⊂ Sn is fully expanding if the product of any two elements of P yields a distinct permutation. Stated otherwise, |P2| = |P|2 where P2 ⊂ Sn is the set of products of two elements of P. We present a randomized algorithm that computes |P2| and hence decides if P is fully expanding. The algorithm also produces a table that, for any σ1, σ2, σ3, σ4 ∈ P, answers the query σ1σ2 = σ3σ4 in O(1) time. The algorithm uses, among other ingredients, a combination of fast matrix multiplication and polynomial identity testing. In particular, for |P| = n our algorithm runs in O(nω) time where ω < 2.376 is the matrix multiplication exponent. We note that the naive deterministic solution for this problem requires Θ(n3) time.
Periodic limb movement disorder and restless legs syndrome in dialysis patients

Background: Sleep disturbances, in particular restless legs or limb movements, during the night are often reported by uremic patients. However, polysomnography (PSG) studies have never been carried out to confirm the actual occurrence of these disorders and the association with other objective and self‐reported sleep–wake data.
Flexural creep of all‐polypropylene composites: Model analysis

In this article, simple viscoelastic and empirical models are presented to predict and analyze the flexural creep behavior of all-poly(propylene) (all-PP) composites. Results of the successful application of these models to the actual creep behavior of unidirectional (UD) and cross-ply (CP) all-PP composites tested by short-term flexural creep measurements over a temperature range of 20–80°C are presented. Analysis of the momentary creep behavior of all-PP composites with different tape lay-ups are made to understand their deformation mechanism. Further to the main theme of the article, an interesting discrepancy while predicting the long-term creep behavior of these composites based on the time-temperature superposition (TTS) principle and Findley power law model is visualized which has also been illustrated here. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Salvicine Inactivates β1 Integrin and Inhibits Adhesion of MDA-MB-435 Cells to Fibronectin via Reactive Oxygen Species Signaling

Integrin-mediated adhesion to the extracellular matrix plays a fundamental role in tumor metastasis. Salvicine, a novel diterpenoid quinone compound identified as a nonintercalative topoisomerase II poison, possesses a broad range of antitumor and antimetastatic activity. Here, the mechanism underlying the antimetastatic capacity of salvicine was investigated by exploring the effect of salvicine on integrin-mediated cell adhesion. Salvicine inhibited the adhesion of human breast cancer MDA-MB-435 cells to fibronectin and collagen without affecting nonspecific adhesion to poly-l-lysine. The fibronectin-dependent formation of focal adhesions and actin stress fibers was also inhibited by salvicine, leading to a rounded cell morphology. Furthermore, salvicine down-regulated β1 integrin ligand affinity, clustering and signaling via dephosphorylation of focal adhesion kinase and paxillin. Conversely, salvicine induced extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. The effect of salvicine on β1 integrin function and cell adhesion was reversed by U0126 and SB203580, inhibitors of MAPK/ERK kinase 1/2 and p38 MAPK, respectively. Salvicine also induced the production of reactive oxygen species (ROS) that was reversed by ROS scavenger N-acetyl-l-cysteine. N-acetyl-l-cysteine additionally reversed the salvicine-induced activation of ERK and p38 MAPK, thereby maintaining functional β1 integrin activity and restoring cell adhesion and spreading. Together, this study reveals that salvicine activates ERK and p38 MAPK by triggering the generation of ROS, which in turn inhibits β1 integrin ligand affinity. These findings contribute to a better understanding of the antimetastatic activity of salvicine and shed new light on the complex roles of ROS and downstream signaling molecules, particularly p38 MAPK, in the regulation of integrin function and cell adhesion. (Mol Cancer Res 2008;6(2):194–204)
CD34+/CD105+ cells are enriched in primitive circulating progenitors residing in the G0 phase of the cell cycle and contain all bone marrow and cord blood CD34+/CD38low/− precursors

A subset of circulating CD34+ cells was found to express CD105 antigen. Sorting experiments showed that most granulocyte–macrophage colony‐forming units (GM‐CFU) and burst‐forming units — erythroid (BFU‐E) were retained in the CD34+/CD105− fraction, whereas rare GM‐CFU/BFU‐E were generated from CD34+/CD105+ cells. Megakaryocytic aggregates were entirely retained in the CD34+/CD105+ fraction. Neutralizing doses of an anti‐TGF‐β1 antibody demonstrated CD34+/CD105+ cells capable of colony‐forming activity without any significant effect on CD34+/CD105− cells. Cloning of secondary colonies revealed that CD34+/CD105+ cells had a significantly higher secondary cloning efficiency than CD34+/CD105− cells. CD34+/CD105+ cells had a significantly higher long‐term culture‐initiating cell (LTC‐IC) frequency than CD34+/CD105− cells. Kinetic analysis showed that 75% of CD34+/CD105+ cells consisted of DNA 2n G0Ki‐67− cells whereas 82% of CD34+/CD105− were DNA 2n G1Ki‐67+ cells, and this latter subset showed a RNA content consistently higher than CD34+/CD105+ cells. CD34+/CD105+ progenitors were CD25+, whereas CD34+/CD105− contained a small CD25+ subset. Three‐colour analysis of bone marrow and cord blood CD34+ cells demonstrated that all the CD34+/CD38low/− primitive precursors were contained in CD34+/CD105+ cells. Extensive characterization of these CD105+ precursors indicated that they have biological properties associated with primitive haematopoietic precursors.
Can Fortification be Implemented in Rural African Communities Where Micronutrient Deficiencies are Greatest? Lessons from Projects in Malawi, Tanzania, and Senegal

Background Fortifying common foods with micronutrients is an effective strategy for decreasing micronutrient deficiencies at a population level. National fortification initiatives often do not impact remote communities that are unreached by commercially produced food. The feasibility and sustainability of small-scale fortification as a mechanism to overcome this barrier are not well documented. Objective To document the process and assess the feasibility of implementation of community-based fortification of staple grains in rural communities in Malawi, Tanzania, and Senegal. Methods In the late 1990s, World Vision piloted community-level fortification within a large-scale, multicountry, integrated nutrition and health program. The exploratory approach focused on developing appropriate community-based methods and processes for flour fortification. An external review in 2012 documented the implementation process, identified barriers and enablers for sustainability and effectiveness, and evaluated the potential for replication and/or scale-up of the intervention. Results Strong advocacy influenced national policy and legislation for mandatory national-level fortification of staple grains. Piloting community-based fortification led to community acceptance of the consumption of fortified foods; however, lack of realistic funding mechanisms limited sustainability. Conclusions Despite the complexity and challenges of community-based fortification, it demonstrates great potential to address unmet needs for micronutrients in vulnerable populations. Further work is needed to determine contextually feasible and sustainable mechanisms for premix supply, quality control, and cost recovery. Incorporating community-based fortification into national fortification frameworks is recommended for countries where a significant proportion of the population may have very limited access to commercially fortified foods.
Sincell: an R/Bioconductor package for statistical assessment of cell-state hierarchies from single-cell RNA-seq

Summary: Cell differentiation processes are achieved through a continuum of hierarchical intermediate cell states that might be captured by single-cell RNA seq. Existing computational approaches for the assessment of cell-state hierarchies from single-cell data can be formalized under a general framework composed of (i) a metric to assess cell-to-cell similarities (with or without a dimensionality reduction step) and (ii) a graph-building algorithm (optionally making use of a cell clustering step). The Sincell R package implements a methodological toolbox allowing flexible workflows under such a framework. Furthermore, Sincell contributes new algorithms to provide cell-state hierarchies with statistical support while accounting for stochastic factors in single-cell RNA seq. Graphical representations and functional association tests are provided to interpret hierarchies. The functionalities of Sincell are illustrated in a real case study, which demonstrates its ability to discriminate noisy from stable cell-state hierarchies. Availability and implementation: Sincell is an open-source R/Bioconductor package available at http://bioconductor.org/packages/sincell. A detailed manual and a vignette are provided with the package. Contact: antonio.rausell@isb-sib.ch Supplementary information: Supplementary data are available at Bioinformatics online.
Distinct patterns of seasonal Greenland glacier velocity

Predicting Greenland Ice Sheet mass loss due to ice dynamics requires a complete understanding of spatiotemporal velocity fluctuations and related control mechanisms. We present a 5 year record of seasonal velocity measurements for 55 marine‐terminating glaciers distributed around the ice sheet margin, along with ice‐front position and runoff data sets for each glacier. Among glaciers with substantial speed variations, we find three distinct seasonal velocity patterns. One pattern indicates relatively high glacier sensitivity to ice‐front position. The other two patterns are more prevalent and appear to be meltwater controlled. These patterns reveal differences in which some subglacial systems likely transition seasonally from inefficient, distributed hydrologic networks to efficient, channelized drainage, while others do not. The difference may be determined by meltwater availability, which in some regions may be influenced by perennial firn aquifers. Our results highlight the need to understand subglacial meltwater availability on an ice sheet‐wide scale to predict future dynamic changes.
GNAT1 associated with autosomal recessive congenital stationary night blindness.

PURPOSE Congenital stationary night blindness is a nonprogressive retinal disorder manifesting as impaired night vision and is generally associated with other ocular symptoms, such as nystagmus, myopia, and strabismus. This study was conducted to further investigate the genetic basis of CSNB in a consanguineous Pakistani family. METHODS A consanguineous family with multiple individuals manifesting cardinal symptoms of congenital stationary night blindness was ascertained. All family members underwent detailed ophthalmic examination, including fundus photographic examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion and genome-wide linkage analyses were completed and two-point LOD scores were calculated. Bidirectional sequencing of GNAT1 was completed, and quantitative expression of Gnat1 transcript levels were investigated in ocular tissues at different postnatal intervals. RESULTS The results of ophthalmic examinations were suggestive of early-onset stationary night blindness with no extraocular anomalies. The genome-wide scan localized the critical interval to chromosome 3, region p22.1-p14.3, with maximum two-point LOD scores of 3.09 at θ = 0, flanked by markers D3S3522 and D3S1289. Subsequently, a missense mutation in GNAT1, p.D129G, was identified, which segregated within the family, consistent with an autosomal recessive mode of inheritance, and was not present in 192 ethnically matched control chromosomes. Expression analysis suggested that Gnat1 is expressed at approximately postnatal day (P)7 and is predominantly expressed in the retina. CONCLUSIONS These data suggest that a homozygous missense mutation in GNAT1 is associated with autosomal recessive stationary night blindness.
Lymphocyte lineage-specific and developmental stage specific mechanisms suppress cyclin D3 expression in response to DNA double strand breaks

ABSTRACT Mammalian cells are thought to protect themselves and their host organisms from DNA double strand breaks (DSBs) through universal mechanisms that restrain cellular proliferation until DNA is repaired. The Cyclin D3 protein drives G1-to-S cell cycle progression and is required for proliferation of immature T and B cells and of mature B cells during a T cell-dependent immune response. We demonstrate that mouse thymocytes and pre-B cells, but not mature B cells, repress Cyclin D3 protein levels in response to DSBs. This response requires the ATM protein kinase that is activated by DSBs. Cyclin D3 protein loss in thymocytes coincides with decreased association of Cyclin D3 mRNA with the HuR RNA binding protein that ATM regulates. HuR inactivation reduces basal Cyclin D3 protein levels without affecting Cyclin D3 mRNA levels, indicating that thymocytes repress Cyclin D3 expression via ATM-dependent inhibition of Cyclin D3 mRNA translation. In contrast, ATM-dependent transcriptional repression of the Cyclin D3 gene represses Cyclin D3 protein levels in pre-B cells. Retrovirus-driven Cyclin D3 expression is resistant to transcriptional repression by DSBs; this prevents pre-B cells from suppressing Cyclin D3 protein levels and from inhibiting DNA synthesis to the normal extent following DSBs. Our data indicate that immature B and T cells use lymphocyte lineage- and developmental stage-specific mechanisms to inhibit Cyclin D3 protein levels and thereby help prevent cellular proliferation in response to DSBs. We discuss the relevance of these cellular context-dependent DSB response mechanisms in restraining proliferation, maintaining genomic integrity, and suppressing malignant transformation of lymphocytes.
Effects of cooperation on the secrecy of multiple access channels with generalized feedback

We investigate the effects of user cooperation on the secrecy of multiple access channels with generalized feedback (MAC-GF). We show that cooperation can increase the achievable secrecy region. We propose achievable schemes which use compress-and-forward (CAF) based transmission strategies. CAF based strategies allow users to increase their rates up to levels which are not decodable by the cooperating partners, consequently improving the secrecy of the users. We also provide outer bounds on the achievable equivocation rates. The outer bounds we derive depend only on the channel inputs and outputs, and hence, are easily computable. Finally, we specialize our results to a Gaussian MAC-GF, and present numerical results which demonstrate the beneficial effects of cooperation on secrecy.
Production of a Highly Protease-Resistant Fungal α-Galactosidase in Transgenic Maize Seeds for Simplified Feed Processing

Raffinose-family oligosaccharide (RFO) in soybeans is one of the major anti-nutritional factors for poultry and livestocks. α-Galactosidase is commonly supplemented into the animal feed to hydrolyze α-1,6-galactosidic bonds on the RFOs. To simplify the feed processing, a protease-resistant α-galactosidase encoding gene from Gibberella sp. strain F75, aga-F75, was modified by codon optimization and heterologously expressed in the embryos of transgentic maize driven by the embryo-specific promoter ZM-leg1A. The progenies were produced by backcrossing with the commercial inbred variety Zheng58. PCR, southern blot and western blot analysis confirmed the stable integration and tissue specific expression of the modified gene, aga-F75m, in seeds over four generations. The expression level of Aga-F75M reached up to 10,000 units per kilogram of maize seeds. In comparison with its counterpart produced in Pichia pastoris strain GS115, maize seed-derived Aga-F75M showed a lower temperature optimum (50°C) and lower stability over alkaline pH range, but better thermal stability at 60°C to 70°C and resistance to feed pelleting inactivation (80°C). This is the first report of producing α-galactosidase in transgenic plant. The study offers an effective and economic approach for direct utilization of α-galactosidase-producing maize without any purification or supplementation procedures in the feed processing.
A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis.

BACKGROUND Ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and 2, has clinically significant activity in myelofibrosis. METHODS In this double-blind trial, we randomly assigned patients with intermediate-2 or high-risk myelofibrosis to twice-daily oral ruxolitinib (155 patients) or placebo (154 patients). The primary end point was the proportion of patients with a reduction in spleen volume of 35% or more at 24 weeks, assessed by means of magnetic resonance imaging. Secondary end points included the durability of response, changes in symptom burden (assessed by the total symptom score), and overall survival. RESULTS The primary end point was reached in 41.9% of patients in the ruxolitinib group as compared with 0.7% in the placebo group (P<0.001). A reduction in spleen volume was maintained in patients who received ruxolitinib; 67.0% of the patients with a response had the response for 48 weeks or more. There was an improvement of 50% or more in the total symptom score at 24 weeks in 45.9% of patients who received ruxolitinib as compared with 5.3% of patients who received placebo (P<0.001). Thirteen deaths occurred in the ruxolitinib group as compared with 24 deaths in the placebo group (hazard ratio, 0.50; 95% confidence interval, 0.25 to 0.98; P=0.04). The rate of discontinuation of the study drug because of adverse events was 11.0% in the ruxolitinib group and 10.6% in the placebo group. Among patients who received ruxolitinib, anemia and thrombocytopenia were the most common adverse events, but they rarely led to discontinuation of the drug (in one patient for each event). Two patients had transformation to acute myeloid leukemia; both were in the ruxolitinib group. CONCLUSIONS Ruxolitinib, as compared with placebo, provided significant clinical benefits in patients with myelofibrosis by reducing spleen size, ameliorating debilitating myelofibrosis-related symptoms, and improving overall survival. These benefits came at the cost of more frequent anemia and thrombocytopenia in the early part of the treatment period. (Funded by Incyte; COMFORT-I ClinicalTrials.gov number, NCT00952289.).
The Evolutionary History and Spatiotemporal Dynamics of the Fever, Thrombocytopenia and Leukocytopenia Syndrome Virus (FTLSV) in China

Background In 2007, a novel bunyavirus was found in Henan Province, China and named fever, thrombocytopenia and leukocytopenia syndrome virus (FTLSV); since then, FTLSV has been found in ticks and animals in many Chinese provinces. Human-to-human transmission has been documented, indicating that FTLSV should be considered a potential public health threat. Determining the historical spread of FTLSV could help curtail its spread and prevent future movement of this virus. Method/Principal Findings To examine the pattern of FTLSV evolution and the origin of outbreak strains, as well to examine the rate of evolution, the genome of 12 FTLSV strains were sequenced and a phylogenetic and Bayesian phylogeographic analysis of all available FTLSV sequences in China were performed. Analysis based on the FTLSV L segment suggests that the virus likely originated somewhere in Huaiyangshan circa 1790 (95% highest probability density interval: 1756–1817) and began spreading around 1806 (95% highest probability density interval: 1773–1834). Analysis also indicates that when FTLSV arrived in Jiangsu province from Huaiyangshan, Jiangsu Province became another source for the spread of the disease. Bayesian factor test analysis identified three major transmission routes: Huaiyangshan to Jiangsu, Jiangsu to Liaoning, and Jiangsu to Shandong. The speed of FTLSV movement has increased in recent decades, likely facilitated by modern human activity and ecosystem changes. In addition, evidence of RNA segment reassortment was found in FTLSV; purifying selection appears to have been the dominant force in the evolution of this virus. Conclusion Results presented in the manuscript suggest that the Huaiyangshan area is likely be the origin of FTLSV in China and identified probable viral migration routes. These results provide new insights into the origin and spread of FTLSV in China, and provide a foundation for future virological surveillance and control.
Sexual imprinting in human mate choice

Animal and human studies have shown that individuals choose mates partly on the basis of similarity, a tendency referred to as homogamy. Several authors have suggested that a specific innate recognition mechanism, phenotypic matching, allows the organism to detect similar others by their resemblance to itself. However, several objections have been raised to this theory on both empirical and theoretical grounds. Here, we report that homogamy in humans is attained partly by sexual imprinting on the opposite–sex parent during childhood. We hypothesized that children fashion a mental model of their opposite–sex parent's phenotype that is used as a template for acquiring mates. To disentangle the effects of phenotypic matching and sexual imprinting, adopted daughters and their rearing families were examined. Judges found significant resemblance on facial traits between daughter's husband and her adoptive father. Furthermore, this effect may be modified by the quality of the father–daughter relationship during childhood. Daughters who received more emotional support from their adoptive father were more likely to choose mates similar to the father than those whose father provided a less positive emotional atmosphere.