Miracle-dz/UniFAR-FTUs huggingface dataset:
Which dressings reduce inflammation and improve venous leg ulcer healing

Chronic venous leg ulcers (VLU) affect around 1% of the adult population in the Western world. The impact of VLU is both social and economic, with significant expenditures on active venous ulcers to provide medical treatment and eventual healing. At the core of VLU is venous hypertension which affects the venous macrocirculation. The changes incurred in venous hemodynamics leads to microcirculatory changes affecting the postcapillary venule and surrounding tissues. Inflammation by leukocytes affecting the venous endothelium, promotes a complex cascade and activation of adhesion molecules expression, chemokines and cytokines released, altered growth factor responses, and activation of protease (e.g. tPA) and proteinase (e.g. MMPs) activity that causes dysregulation and compromise of tissue integrity with eventual dermal damage and ulcer development. A critical component to treating VLU is correcting the abnormal venous hemodynamics and compression therapy. Unfortunately, VLU recurrence ranges between 30–70%, and other modalities in therapy along with compression are required. The goal for adjuvant products is to restore the balance from an inflammatory chronic wound to that of a reparative wound that will promote provisional matrix and epithelialization. There are many products on the market that can be used as adjuvant to compression therapy, but it must be recognized that there is a paucity of clinical trials that have evaluated the clinical effectiveness of specific products with clearly defined end points, and most importantly a healed VLU with a low recurrence rate. This review will discuss the fundamentals of VLU inflammation, and evaluate the available literature that may have benefit in reducing inflammation and lead to effective VLU healing.
Combination Bidding in Multi-Unit Auctions

This paper considers the problem of identification and estimation in the first-price multi-unit auction. It is motivated by the auctions of bus routes held in London where bidders submit bids on combinations of routes as well as on individual routes. We show that submitting a combination bid lower than the sum of the bids on the constituent routes does not require cost synergies and can instead serve as a tool to leverage market power across the different routes. As a result, the welfare consequences of allowing combination bidding in the first price auction are ambiguous, and depend on the importance of the cost synergies. We provide conditions for non-parametric identification of the multidimensional private information in the multi-unit first price auction and derive partial identification results when they are not satisfied. We propose an estimation method consisting of two stages: In the first stage, the distribution of bids is estimated parametrically. In the second stage, the (set of) costs and distribution(s) of costs consistent with the observed behavior are inferred based on the first order conditions for optimally chosen bids. We apply the estimation method to data from the London bus routes market. We quantify the magnitude of cost synergies and assess possible efficiency losses arising in this market.
The Perceptual Interaction of Simple and Complex Point Symbol Shapes and Background Textures in Visual Search on Tourist Maps

This study investigated visual search for simple and complex geometric and pictorial point symbols displayed on light and dark smooth and textured map backgrounds. Groupadministered tests asked subjects to count occurrences of target symbols. Efficiency of visual search was determined by analyzing subjects’ self-recorded counts and times for accuracy and speed. Results for symbols indicate that simple geometric and pictorial symbols are easier to search, especially when their shapes differ considerably. In contrast, complex geometric and pictorial symbols differing only in minor details of shape or orientation are harder to search. Results for backgrounds show that high value contrast between symbol and background (e.g. black symbol on white ground) facilitates search, while low contrast (e.g. black symbol on dark gray ground) yields poorer results. Since subjects also found it harder to identify symbols displayed on textured backgrounds (e.g. aerial photograph, satellite image, or relief shading), visual noise is another background factor.
Microseismicity and permeability enhancement of hydrogeologic structures during massive fluid injections into granite at 3 km depth at the Soultz HDR site

SUMMARY A high-rate injection of 20 000 m3 of water into granite between 2.8 and 3.4 km depth at the Soultz hot dry rock (HDR) test site in France in 1993 September led to a 200-fold increase in borehole transmissivity and produced a subvertical cloud of microseismicity of dimensions 0.5 km wide, 1.2 km long, 1.5 km high and oriented 25°NW. The resulting data set is unusually complete and well suited to studying permeability creation/enhancement processes in crystalline rock and the utility of microseismic data for revealing them. Although the microseismic cloud defined using joint hypocentre determination (JHD) locations was diffuse and showed little structure, application of the collapsing method showed it to be composed largely of discrete tubes and planes that propagated coherently. One prominent structure that extended 350 m downwards from the vicinity of a flow inlet early in the injection and that appears to contain a major flow path was subjected to detailed investigation to establish its hydrogeologic nature and the mechanisms underpinning its inferred permeability enhancement. High-resolution microseismic mapping techniques (i.e. multiplets and clustering) showed it to be a subvertical, NNW–SSE striking, fracture zone of width 10–20 m. The strike and scale of the structure identifies it as a member of a family of hydrothermally altered, cataclastic shear structures that constitute the primary permeable paths for fluid migration within the rock mass, both under ambient and forced fluid flow conditions. The microseismicity occurred on subvertical, small-scale fractures within the cataclastic shear zone whose azimuths scatter within 22° of parallel to the parent structure. Although the structure is likely to have been naturally permeable to some degree, its permeability appears to have been significantly enhanced as a consequence of the injection. The most likely mechanism of permeability enhancement, which is in accord with the strong preference for the microseismicity to grow downwards, involves strike-slip shearing, which produced the opening of vertical tubes at along-strike jogs in the fault (the so-called Hill mesh). Seismic moment release averaged over the structure suggests shear displacements of at least 0.3 mm occurred, which are sufficient to generate aperture changes that are hydraulically significant. The preponderance of discrete structures within the microseismic cloud after collapsing suggests that significant flow and permeability enhancement (i.e. stimulation) within the rock mass is largely confined to the interiors of shear zones that appear to have a spacing of approximately 100 m.
Occult HCV Infection (OCI) Diagnosis in Cirrhotic and Non-cirrhotic Naïve Patients by Intra-PBMC Nested Viral RNA PCR

Abstract Background and Aims: Occult HCV infections (OCIs) include IgG antibody seronegative cryptogenic (COCIs), as well as seropositive secondary naïve (SNOCIs) and experienced (SEOCIs) cases. We used peripheral-blood-mononuclear-cell (PBMC)-PCR to evaluate COCIs and SNOCIs prevalence, serum HCV spontaneous disappearance (SCSD) in naïve cirrhotics and non-cirrhotics, intra-PBMC HCV-RNA strands in relation to cirrhosis density in naïve non-viremia cases, and HCV-RNA seroconversion after 1 year of solitary naïve intra-PBMC infection. Methods: The anti-HCV IgG antibody-positive naïve-patients (n = 785) were classified into viremic (n = 673) and non-viremic [n = 112, including non-cirrhotics (n = 55) and cirrhotics (n = 57)], and 62 controls without evidence of HCV-infection. Controls and post-HCV non-viremia cases (n = 62+112 = 174) were submitted to hepatic Fibroscan-Elastography evaluation. All subjects (n = 847) were screened for intra-PBMC HCV-RNA sense and antisense strands by nested-PCR. Results: Naïve-OCI cases (4.84%) that were diagnosed by PBMC-PCR significantly raised the total numbers of HCV-infection to 714 (p = 0.01). The percent positivity of SNOCIs (34.82%) was significantly higher than for asymptomatic-COCIs (3.125%, p = 0.0001). Comparing PBMC-PCR with single-step-reverse-transcription (SRT)-PCR for identification of SCSD in naïve IgG antibody-positive non-viremia patients (n = 112) revealed a decline in SCSD prevalence by PBMC-PCR (from 14.27% to 9.3%), regardless of presence of hepatic cirrhosis (p = 0.03). SCSD was found to be higher by PBMC-PCR in non-cirrhotics compared to cirrhotics (p = 0.0001), with an insignificant difference when using SRT-PCR (p = 0.45). Intra-PBMC HCV-RNA infection was significantly more frequent in cirrhotics compared to both non-cirrhotics and controls (p < 0.0005). An increased hepatic fibrosis density was recognized in intra-PBMC HCV-RNA infection with sense (p = 0.0001) or antisense strand (p = 0.003). HCV-RNA seroconversion was associated with intra-PBMC infection when both sense and antisense strands were detected (p = 0.047). Conclusions: Intracellular HCV-RNA evaluation is crucial for diagnosing OCIs and addressing relapse probability.
Theoretical considerations of electrical conductivity in a partially molten mantle and implications for geothermometry

Relationships between bulk effective electrical conductivity, melt fraction, and liquid path connectivity are derived for a partially melted material. Hashin-Shtrikman bounds are determined for the conductivity on the basis of entropy production and compared with results obtained for exact geometrical models for the limiting cases of isolated melt pockets and complete grain boundary wetting. Models used are (1) a spherical particle assemblage of an infinite number of different-sized composite spheres, each containing an inner core of one phase, surrounded by an outer shell of a second phase, and (2) a three-dimensional periodic array of identical-sized cubes of one phase, surrounded by a second phase that extends continuously throughout the body. Both models yield the same expressions as those of the upper Hashin-Shtrikman bound for the bulk conductivity dependence on melt fraction for small melt fractions with complete liquid bridging. A small dependence on grain size and shape is inferred. Partial melting in the form of isolated melt pockets is found to be ineffective in raising bulk conductivity significantly over that of the solid phase material. Quasi-continuous grain boundary wetting is considered in terms of analog modeling. Melt fraction and liquid path connectivity are found to be main determining factors for electrical conductivity. It is concluded that grain boundary and/or edge wetting is necessary for partial melting to raise bulk conduction in the mantle appreciably over that of its solid phase material. Such wetting is therefore inferred to be a highly probable mechanism responsible for high conductivity anomalies observed in deep geomagnetic soundings. Implications for geothermometry are considered.
Directions of anhysteretic and rotational remanent magnetizations in rotating samples

Summary. These experiments support Stephenson’s predictions that partial anhysteretic remanent magnetizations produced in rotating samples deviate from the steady field direction, which is collinear with the rotation axis, by amounts depending on the angle, 7, between the alternating magnetic field axis and the rotation axis. A similar effect was observed for partial rotational remanent magnetizations. Possible differences between the two remanence types were noted.
Migratory and adhesive cues controlling innate-like lymphocyte surveillance of the pathogen-exposed surface of the lymph node

Lymph nodes (LNs) contain innate-like lymphocytes that survey the subcapsular sinus (SCS) and associated macrophages for pathogen entry. The factors promoting this surveillance behavior have not been defined. Here, we report that IL7RhiCcr6+ lymphocytes in mouse LNs rapidly produce IL17 upon bacterial and fungal challenge. We show that these innate-like lymphocytes are mostly LN resident. Ccr6 is required for their accumulation near the SCS and for efficient IL17 induction. Migration into the SCS intrinsically requires S1pr1, whereas movement from the sinus into the parenchyma involves the integrin LFA1 and its ligand ICAM1. CD169, a sialic acid-binding lectin, helps retain the cells within the sinus, preventing their loss in lymph flow. These findings establish a role for Ccr6 in augmenting innate-like lymphocyte responses to lymph-borne pathogens, and they define requirements for cell movement between parenchyma and SCS in what we speculate is a program of immune surveillance that helps achieve LN barrier immunity. DOI: http://dx.doi. org/10.7554/eLife.18156. 001
Observations of ridge‐hotspot interactions in the Southern Ocean

The evolution of ridge-hotspot systems is not well understood. In this investigation, satellite-derived marine gravity data are used in conjunction with underway bathymetric and magnetic anomaly profiles to investigate the nature of ridge-hotspot interaction at four sparsely explored systems in the Southern Ocean. These systems illustrate three different stages of ridge-hotspot interaction in which a migrating spreading center approaches a hotspot (Pacific-Antarctic/Louisville), passes over or is captured by the hotspot (Mid-Atlantic/Shona-Discovery), and ultimately migrates away from the hotspot (Southeast Indian/Kerguelen). All of these systems show some evidence of discrete ridge jumps in the direction of the hotspot as the spreading center attempts to relocate toward the hotspot by asymmetric spreading. Interestingly, these ridge jumps show no evidence of propagating offsets as have been seen on many other ridge-hotspot systems. A simple model predicts that typical plume excess temperatures can weaken the lithosphere sufficiently to promote asymmetric spreading and possibly allow a discrete ridge jump. The presence of previously uncharted, obliquely oriented aseismic ridges and gravity lineations between the ridge and the hotspot supports the notion of asthenospheric flux from the plume to the spreading center both before and after the time when the hotspot is ridge centered. The azimuths of the aseismic ridges cannot be explained by plate kinematics alone; they consistently extend from the ends toward the centers of the adjacent spreading segments suggesting some interaction between plume derived asthenospheric flux and local lithospheric structure. The features discussed here also indicate that the transfer of asthenospheric material from the plume to the spreading center is influenced by the local plate boundary configuration and interaction with transform offsets.
Capital Budgeting vs. Market Timing: An Evaluation Using Demographics

An ongoing debate sets capital budgeting against market timing. The primary difficulty in evaluating these theories is finding distinct exogenous proxies for investment opportunities and mispricing. We use demand shifts induced by demographics to address this problem, and hence, provide a more definitive analysis of the theories. According to capital budgeting, industries anticipating positive demand shifts in the near future should issue more equity (and debt) to finance additional capacity. To the extent that demographic shifts in the more distant future are not incorporated into equity prices, market timing implies that industries anticipating positive demand shifts in the distant future should issue less equity due to undervaluation. We find evidence supporting both capital budgeting and market timing: new listings and equity issuance by existing listings respond positively to demand shifts up to 5 years ahead, and negatively to demand shifts 5 to 10 years ahead.
GASSST: global alignment short sequence search tool

Motivation: The rapid development of next-generation sequencing technologies able to produce huge amounts of sequence data is leading to a wide range of new applications. This triggers the need for fast and accurate alignment software. Common techniques often restrict indels in the alignment to improve speed, whereas more flexible aligners are too slow for large-scale applications. Moreover, many current aligners are becoming inefficient as generated reads grow ever larger. Our goal with our new aligner GASSST (Global Alignment Short Sequence Search Tool) is thus 2-fold—achieving high performance with no restrictions on the number of indels with a design that is still effective on long reads. Results: We propose a new efficient filtering step that discards most alignments coming from the seed phase before they are checked by the costly dynamic programming algorithm. We use a carefully designed series of filters of increasing complexity and efficiency to quickly eliminate most candidate alignments in a wide range of configurations. The main filter uses a precomputed table containing the alignment score of short four base words aligned against each other. This table is reused several times by a new algorithm designed to approximate the score of the full dynamic programming algorithm. We compare the performance of GASSST against BWA, BFAST, SSAHA2 and PASS. We found that GASSST achieves high sensitivity in a wide range of configurations and faster overall execution time than other state-of-the-art aligners. Availability: GASSST is distributed under the CeCILL software license at http://www.irisa.fr/symbiose/projects/gassst/ Contact: guillaume.rizk@irisa.fr; dominique.lavenier@irisa.fr Supplementary information: Supplementary data are available at Bioinformatics online.
Mast cells and the power of local RAS activation.

More than 100 years ago, mast cells were discovered and named by Paul Ehrlich who was the first to recognize this well-fed appearing cell loaded with huge cytoplasmic granules in various tissues [1]. Mast cells derive from CD34þ multipotent bone marrow progenitor cells which circulate in small numbers in the blood as basophilic leucocytes, and enter the mucosal surfaces and connective tissue compartments of multiple organs [2]. This distinct cell type is today best known for its key role in immunoglobulinE-mediated allergic reactions such as bronchial asthma and anaphylactic reactions. More recently, however, mast cells have been found to be important modulators and mediators of innate immunity, chronic inflammation, tissue remodelling and organ fibrosis [3–5].
Hypoxic epithelial necrosis triggers neutrophilic inflammation via IL-1 receptor signaling in cystic fibrosis lung disease.

RATIONALE In many organs, hypoxic cell death triggers sterile neutrophilic inflammation via IL-1R signaling. Although hypoxia is common in airways from patients with cystic fibrosis (CF), its role in neutrophilic inflammation remains unknown. We recently demonstrated that hypoxic epithelial necrosis caused by airway mucus obstruction precedes neutrophilic inflammation in Scnn1b-transgenic (Scnn1b-Tg) mice with CF-like lung disease. OBJECTIVES To determine the role of epithelial necrosis and IL-1R signaling in the development of neutrophilic airway inflammation, mucus obstruction, and structural lung damage in CF lung disease. METHODS We used genetic deletion and pharmacologic inhibition of IL-1R in Scnn1b-Tg mice and determined effects on airway epithelial necrosis; levels of IL-1α, keratinocyte chemoattractant, and neutrophils in bronchoalveolar lavage; and mortality, mucus obstruction, and structural lung damage. Furthermore, we analyzed lung tissues from 21 patients with CF and chronic obstructive pulmonary disease and 19 control subjects for the presence of epithelial necrosis. MEASUREMENTS AND MAIN RESULTS Lack of IL-1R had no effect on epithelial necrosis and elevated IL-1α, but abrogated airway neutrophilia and reduced mortality, mucus obstruction, and emphysema in Scnn1b-Tg mice. Treatment of adult Scnn1b-Tg mice with the IL-1R antagonist anakinra had protective effects on neutrophilic inflammation and emphysema. Numbers of necrotic airway epithelial cells were elevated and correlated with mucus obstruction in patients with CF and chronic obstructive pulmonary disease. CONCLUSIONS Our results support an important role of hypoxic epithelial necrosis in the pathogenesis of neutrophilic inflammation independent of bacterial infection and suggest IL-1R as a novel target for antiinflammatory therapy in CF and potentially other mucoobstructive airway diseases.
Long Serial Analysis of Gene Expression for Gene Discovery and Transcriptome Profiling in the Widespread Marine Coccolithophore Emiliania huxleyi

ABSTRACT The abundant and widespread coccolithophore Emiliania huxleyi plays an important role in mediating CO2 exchange between the ocean and the atmosphere through its impact on marine photosynthesis and calcification. Here, we use long serial analysis of gene expression (SAGE) to identify E. huxleyi genes responsive to nitrogen (N) or phosphorus (P) starvation. Long SAGE is an elegant approach for examining quantitative and comprehensive gene expression patterns without a priori knowledge of gene sequences via the detection of 21-bp nucleotide sequence tags. E. huxleyi appears to have a robust transcriptional-level response to macronutrient deficiency, with 42 tags uniquely present or up-regulated twofold or greater in the N-starved library and 128 tags uniquely present or up-regulated twofold or greater in the P-starved library. The expression patterns of several tags were validated with reverse transcriptase PCR. Roughly 48% of these differentially expressed tags could be mapped to publicly available genomic or expressed sequence tag (EST) sequence data. For example, in the P-starved library a number of the tags mapped to genes with a role in P scavenging, including a putative phosphate-repressible permease and a putative polyphosphate synthetase. In short, the long SAGE analyses have (i) identified many new differentially regulated gene sequences, (ii) assigned regulation data to EST sequences with no database homology and unknown function, and (iii) highlighted previously uncharacterized aspects of E. huxleyi N and P physiology. To this end, our long SAGE libraries provide a new public resource for gene discovery and transcriptional analysis in this biogeochemically important marine organism.
Quantitative Metabolomics Reveals an Epigenetic Blueprint for Iron Acquisition in Uropathogenic Escherichia coli

Bacterial pathogens are frequently distinguished by the presence of acquired genes associated with iron acquisition. The presence of specific siderophore receptor genes, however, does not reliably predict activity of the complex protein assemblies involved in synthesis and transport of these secondary metabolites. Here, we have developed a novel quantitative metabolomic approach based on stable isotope dilution to compare the complement of siderophores produced by Escherichia coli strains associated with intestinal colonization or urinary tract disease. Because uropathogenic E. coli are believed to reside in the gut microbiome prior to infection, we compared siderophore production between urinary and rectal isolates within individual patients with recurrent UTI. While all strains produced enterobactin, strong preferential expression of the siderophores yersiniabactin and salmochelin was observed among urinary strains. Conventional PCR genotyping of siderophore receptors was often insensitive to these differences. A linearized enterobactin siderophore was also identified as a product of strains with an active salmochelin gene cluster. These findings argue that qualitative and quantitative epi-genetic optimization occurs in the E. coli secondary metabolome among human uropathogens. Because the virulence-associated biosynthetic pathways are distinct from those associated with rectal colonization, these results suggest strategies for virulence-targeted therapies.