gebhart/patrepeval huggingface dataset:
Measurement of vitellogenin protein in invertebrates : relevance and usefulness of mass spectrometry (LC-MS/MS) to propose a specific and transferable method across species (2011)

Reproductive success of organisms is related to the quantity and quality of eggs produced by females. Vitellogenin (Vg), precursor molecule of vitellin that is the energy available for embryonic development in oviparous organisms, is proposed as a relevant exposure and effect bio-chemical marker of endocrine disruptors in aquatic vertebrate species (e.g. fish, amphibian). Numerous strategies, such as enzyme-linked immunosorbent assays have been developed to characterise and quantify this protein in vertebrates. On the contrary, in invertebrates few methods are available. This gap mainly results from the low transferability of available antibodies in relation to phylogenetic distance and molecular divergence accumulated by proteins through animal evolution. Recently, our laboratory developed a quantitative assay of Vg in a widespread amphipod, Gammarus fossarum, using liquid chromatography tandem mass spectrometry (LC-MS/MS). This method offers the possibility to identify and quantify Vg, based only on the quantification of proteotypic peptides containing from 5 to 15 amino-acids. Despite a high molecular divergence observed for this type of protein throughout animal evolution, comparative and evolutive genomics revealed that partial conservation between homologous proteins can persist due to high functional constraints acting on residues clustered in the proteic structure forming conserved peptides within phylogenetical groups. In this context, the aim of this study was to assess the possibility to take advantage of peptidic motifs conservation to propose a transferable method across species. For this, our study focused on three model species for which sequence of egg yolk protein is well known, an amphipod, Gammarus fossarum, a cladocerean Daphnia magna and an insect Drosophila melanogaster. In first step, proteotypic peptides of Vg were identified for each species. In the second step, we tried to find these proteotypic peptides in closely related species, such as G. pulex, G. wautierii, D. pulex. This study showed the high relevance of mass spectrometry to propose a specific methodology for Vg measurement. Moreover, methodology proposed to Vg measurement is transferable from a species to another one from the same genus.
Microfabrication of an analog of the basal lamina: biocompatible membranes with complex topographies (2000)

A microfabrication approach was used to produce novel analogs of the basal lamina with complex topographic features. A test pattern of ridges and channels with length scales (40 to 310 micrometer) similar to the invaginations found in a native basal lamina was laser machined into the surface of a polyimide master chip. Negative replicates of the chip were produced using polydimethylsiloxane silicone elastomer and these replicates were used as templates for the production of thin ( approximately 21 micrometer) membranes of collagen or gelatin. The resulting membranes had a complex topography of ridges and channels that recapitulated the features of the master chip. To demonstrate their utility, these complex membranes were laminated to type I collagen sponges and their surfaces were seeded with cultured human epidermal keratinocytes to form a skin equivalent. The keratinocytes formed a differentiated and stratified epidermis that conformed to the features of the microfabricated membrane. The topography of the membrane influenced the differentiation of the keratinocytes because stratification was enhanced in the deeper channels. Membrane topography also controlled the gross surface features of the skin equivalent; infolds of the epidermis increased as channel depth increased. These novel microfabricated analogs of the basal lamina will help to elucidate the influence of topography on epithelial cell proliferation and differentiation and should have applications in the tissue engineering of skin equivalents as well as other basal lamina-containing tissues.
478. Highly Efficient Targeted Gene Addition in CD34+ Hematopoietic Stem/Progenitor Cells by Combining ZFN mRNA and AAV6 Donor Delivery (2015)

Zinc-finger nucleases (ZFNs) drive highly efficient genome editing by generating a site-specific DNA double-strand break (DSB) at a predetermined site in the genome. Subsequent repair of this break via the non-homologous end-joining (NHEJ) or homology-directed repair (HDR) pathways results in targeted gene disruption or gene correction/addition, respectively. Hematopoietic stem/progenitor cells (HSPC) are an important clinical target for gene therapy. These cells can be readily harvested from the subject, engineered using viral vectors, and re-introduced back into the patient where they give rise to all of the mature cells of the blood and immune system. Thus the ability to edit the genome of HSPCs could provide a corrective therapy for a number of monogenic diseases. However, achieving high levels of editing by HDR may be significantly more challenging than gene knockout by NHEJ. Here we report that the combination of delivering the ZFNs as mRNA and corrective donor DNA via a rAAV6 vector can induce highly efficient targeted gene addition in CD34+ HSPCs. Using CCR5-specific ZFNs and donor DNA templates as a model system we show that targeted addition of a novel restriction fragment length polymorphism (RFLP) was consistently achieved at >15%, while insertion of an eGFP expression cassette was achieved at >10% of the CCR5 loci in mobilized CD34+ cells. Furthermore, targeting the AAVS1 “safe harbor” locus with a pair of AAVS1-specific ZFNs (mRNA) and a RFLP donor (rAAV6) resulted in >30% of AAVS1 alleles specifically being edited to include the RFLP, suggesting this genome editing approach to achieve highly efficient targeted gene addition in CD34+ cells can be applied to different genetic loci. Edited HSPC undergo normal hematopoiesis in both in vitro differentiation assays and during engraftment of NSG mice. Using fetal liver derived cells, editing of primitive and more committed CD34+ HSPC subsets was observed at similar levels in HSPC CFU cultures, and by analysis of sorted populations of treated HSPC, including LT-HSC, and through the secondary transplantation of NSG mice. The use of ZFNs in combination with rAAV6 delivery of the donor DNA provides a significant advance in genome editing that has great potential for targeted correction of human disease-causing mutations and permanent transgene addition in human CD34+ HSPC.
Function and Structure of MalA/MalA′, Iterative Halogenases for Late-Stage C–H Functionalization of Indole Alkaloids (2017)

Malbrancheamide is a dichlorinated fungal indole alkaloid isolated from both Malbranchea aurantiaca and Malbranchea graminicola that belongs to a family of natural products containing a characteristic bicyclo[2.2.2]diazaoctane core. The introduction of chlorine atoms on the indole ring of malbrancheamide differentiates it from other members of this family and contributes significantly to its biological activity. In this study, we characterized the two flavin-dependent halogenases involved in the late-stage halogenation of malbrancheamide in two different fungal strains. MalA and MalA' catalyze the iterative dichlorination and monobromination of the free substrate premalbrancheamide as the final steps in the malbrancheamide biosynthetic pathway. Two unnatural bromo-chloro-malbrancheamide analogues were generated through MalA-mediated chemoenzymatic synthesis. Structural analysis and computational studies of MalA' in complex with three substrates revealed that the enzyme represents a new class of zinc-binding flavin-dependent halogenases and provides new insights into a potentially unique reaction mechanism.
Comprehensive Immunophenotypic Characterization of Adult and Fetal Testes, the Excretory Duct System, and Testicular and Epididymal Appendages (2016)

The immunophenotype of a normal testis and the excretory duct system has not been studied comprehensively in fetal and adult patients without testicular disease or hormonal manipulation so far. In addition, testicular (TA) and epididymal (EA) appendages are frequent paratesticular structures without previously reported comprehensive immunophenotypic studies. Immunohistochemistry for multiple markers, including the androgen receptor (AR), the estrogen receptor (ER), the progesterone receptor (PR), the prostate-specific antigen, the prostate-specific membrane antigen, PAX8, WT1, calretinin, CK7, CK20, OCT4, SALL4, and CD117, was performed on full sections of testicular/paratesticular tissue from a large cohort of adult and fetal autopsy patients. In contrast to adult germ cells (GC), fetal GC strongly express OCT4 and CD117, although the expression of these proteins is lost in the early postnatal period; SALL4, in contrast, is expressed in both fetal and adult GC, with only weak and focal expression in adult patients. Fetal Sertoli cells (SC) express WT1 and calretinin strongly and diffusely, in contrast to adult SC. Both fetal and adult excretory duct systems express CK7 and PAX8 with frequent AR coexpression, and all 3 main segments of the excretory duct system (ductuli efferentes, epididymis, and vas deferens) have unique immunophenotypes. The rete testis also has a unique immunohistochemical expression pattern, which includes strong expression of CK7, PAX8, WT1, calretinin, and AR. Finally, of the adult autopsy patients examined, 80% had a TA, and 60% had an EA; these paratesticular structures occurred at stereotypical locations, demonstrated reproducible morphologic features, and had a unique immunophenotype relative to other studied structures, with strong CK7, PAX8, WT1, AR, ER, and PR coexpression. The testis and the paratestis may be involved by diverse neoplastic and non-neoplastic processes, and knowledge of the immunophenotypic expression spectrum of these tissues may aid in clinical diagnosis and advance our understanding of the pathogenesis of both oncologic and nononcologic disease processes.
Effect of cancer vaccine formulation on synergy with anti-CTLA-4 and anti-PD-L1 checkpoint blockade therapy of cancer. (2016)

3094 Background: A promising avenue to increase the efficacy of anti-CTLA-4 and anti-PD-(L)1 checkpoint blockade therapies is to enhance T cell induction through vaccination. Surprisingly, concurrent gp100 peptide vaccination decreased clinical efficacy of anti-CTLA-4 in patients with melanoma. As a result, it is currently unclear how to effectively combine checkpoint blockade therapy with vaccination. We used an animal model of gp100 peptide vaccination and CTLA-4/PD-L1 checkpoint blockade to understand this phenomenon and define parameters for successful combination of checkpoint blockade and vaccination. Methods: We treated established B16 melanoma tumors with anti-CTLA-4 therapy and concurrent vaccination with gp100/IFA and studied T cell expansion, trafficking and therapeutic effector function. Results: Anti-CTLA-4 monotherapy significantly increased intratumoral levels of TRP-2 melanoma antigen-specific Teffs, as well as total CD44hiCD11ahiCD8lo Teffs at the tumor site. Conversely, gp100/IFA vaccination-induced, gp100-specific CD8+ T cells accumulated at the inflamed vaccination site. Surprisingly, combination of gp100/IFA vaccination and anti-CTLA-4 therapy caused non-gp100-specific Teff, induced by anti-CTLA-4 therapy, to also accumulate at the vaccination site and not at the tumor site. This Teff sequestration at the vaccination site was dependent on IFN-g, CXCR3 and ICAM-1. Replacing the gp100/IFA formulation with a gp100-encoding viral vector or a non-persistent, water-based formulation potently synergized with anti-CTLA-4 or anti-PD-L1 resulting in a high proportion of complete cure. Conclusions: Persistent vaccine formulations can fail to synergize, or even diminish the efficacy of, CTLA-4/PD-(L)1 checkpoint–based cancer immune therapy through the induction of aberrant T cell trafficking to the vaccination site. A non-persistent vaccine formulation can reverse these undesirable effects and potently synergize with anti-CTLA-4 and/or anti-PD-(L)1 checkpoint blockade, resulting in significantly improved anti-tumor activity.
<title>Bayesian matching technique for detecting simple objects in heavily noisy environment</title> (1991)

The template matching problem, for binary images corrupted with spatially white, binary, symmetric noise, is studied. Matching is compared based directly on the pixel-valued image data as well as on data coded by two simple schemes: a modification of the Hadamard basis and direct coarsening of resolution. Bayesian matching rules based on M-ary hypothesis tests are developed. The performance evaluation of these rules is provided. A study of the trade-off between the quantization level and the ability of detecting an object in the image is presented. This trade-off depends on the (external) noise generated at the moment the uncoded image is received. The sum-of-pixels and the histogram statistics are introduced in order to reduce the computational load inherent in the correlation statistic, with the resulting penalty of a higher probability of false alarm rate. The present work demonstrates by examples that it is beneficial for recognition to combine an image coding technique with the algorithm extracting some `basic' information from the image. In other words, coding (for compression) helps recognition. Numerical results illustrate this claim.
Some Issues in Design of Data Warehousing Systems (2011)

Information is one of the most valuable assets of an organization, and when used properly can assist intelligent decision-making that can significantly improve the functioning of an organization. Data warehousing is a recent technology that allows information to be easily and efficiently accessed for decision-making activities. On-line analytical processing (OLAP) tools are well studied for complex data analysis. A data warehouse is a set of subject-oriented, integrated, time varying and non-volatile databases used to support the decision-making activities (Inmon, 1992).Request access from your librarian to read this chapter's full text.
Apratylenchus vietnamensis gen. n., sp. n. and A. binhi gen. n., sp. n., sedentary Pratylenchidae (Nematoda: Tylenchida) from coffee in Vietnam, with proposal of Apratylenchinae subfam. n. (2009)

Abstract Apratylenchinae subfam. n. is proposed within the Pratylenchidae to include Apratylenchus gen. n. and two new species, A. vietnamensis gen. n., sp. n. and A. binhi gen. n., sp. n., from coffee plantations in Vietnam. Apratylenchus gen. n. is distinguished by the presence of transverse rows of cuticular tubercles on the annuli and by sexual dimorphism in which the males are stout and cylindrical, but mature sedentary females are club-shaped. The sedentary females are broadest in the posterior third although narrowing posterior to the vulva (V ≥ 85%). The female cephalic region is low and dome-shaped with all labial sectors fused to one another and the oral disc and the pharyngeal glands overlap the intestine ventrally. Males have a weak stylet with reduced knobs and a conical tail with a blunt terminus, arcuate spicules and a non-protrusible gubernaculum. Apratylenchus vietnamensis gen. n., sp. n. is characterised by a sedentary mature female with a 368-515 μm long club-shaped body, cephalic region low, dome shaped with three annuli, body annuli bearing a single or double row of refractive tubercles, stylet 17.0-19.9 μm long, V = ca 88-92, spermatheca filled with sperm and males known, if rarely found, in the type population. Males have a weak, 15 μm long stylet with reduced knobs, 16 μm spicules, a non-protrusible gubernaculum and low bursa. It differs from A. binhi gen. n., sp. n., the only other nominal species of the new genus, by longer female body (368-515 vs 326-364 μm), longer distance from anterior end to anus (353-512 vs 310-348 μm) and longer stylet (17.0-19.9 vs 14.7-16.9 μm). In addition, the spermatheca is filled with round sperm vs empty in A. binhi gen. n., sp. n. and the cuticle has less densely spaced and less pronounced tubercles. D2/D3 sequences of the 28 rDNA gene clearly support the separation of Apratylenchus gen. n. from other Pratylenchidae and further distinguish the two new species from each other.
Combinatorial and artificial intelligence methods in materials science II : symposium held December 1-4, Boston, Massachusetts, U.S.A (2004)

Over the past two years, combinatorial and artificial intelligence methods in materials science have become more accepted as a means to synthesize, test, characterize, and predict promising candidate materials. These methods open up the exploration of multidimensional chemical composition and process parameter space at a previously unavailable level of detail and can rapidly optimize molecular properties and process conditions that are difficult to predict using existing knowledge. Scientists from academic, industrial and governmental laboratories worldwide come together here with interdisciplinary presentations that: identify gaps in cross-discipline knowledge that hinder further research; outline emerging development areas; and stimulate nontraditional solutions to difficult multidisciplinary problems in high-throughput materials research. Topics include: combinatorial approaches to electronics materials, polymers and coatings, and nanomaterials and catalysts; instrumentation and methods for high-throughput analysis; and library design, data management and informatics. In particular, the book demonstrates that combinatorial methods have matured in catalyst research. Several remarkable scale-up reports are presented signifying the power of this new scientific methodology.
Determination of Equivalence Ratio and Oscillatory Heat Release Distributions in Non-Premixed Bluff Body-Stabilized Flames Using Chemiluminescence Imaging (2011)

In an effort to elucidate the fundamental processes controlling bluff body flame stabilization, the dependence of the spatial distribution of the local equivalence ratio and the heat release dynamics upon the mode of fuel injection was studied. Experiments were performed in a single flame holder combustion channel which was supplied with a high-temperature air stream. Jet-A fuel was injected across the incoming air stream from one of two locations: a cylindrical fuel bar installed 0.25 m upstream of the bluff body, or from fuel injectors integrated within the bluff body 2.5 cm upstream of the trailing edge (i.e., close-coupled injection). The time-averaged spatial distributions of the combustion heat release were characterized by CH* and C2* chemiluminescence imaging of the flame, and ratios of the C2* to CH* light emission were used to characterize the local equivalence ratio. The spatial average of the C2*/CH* value in the flame was found to increase linearly with increasing global equivalence ratio for fuel injection upstream of the bluff body, whereas this value was relatively constant for close-coupled injection. This constant value equaled the same average C2*/CH* value obtained for upstream fuel injection at globally stoichiometric conditions, suggesting that combustion resulting from close-coupled fuel injection took place, on average, in stoichiometric flamelets throughout the combustor. The heat release dynamics due to asymmetric (von Ka´rma´n) vortex shedding were also investigated for each operating condition by recording high-speed movies of the flame at 24 kHz. Upon processing of these movies, the amplitudes of heat release fluctuations due to von Ka´rma´n vortex shedding were found to be significantly higher for close-coupled injection than for injection well upstream of the flame holder for all operating conditions. This is attributed to an increase in span-wise fuel-air mixing and near-wake heat release for upstream fuel injection, resulting in a hotter recirculation zone which suppressed the von Ka´rma´n instability more than the close-coupled case.
Prediction of disability-free survival in healthy older people (2022)

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6-77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people.Trial registration Clinicaltrials.gov (NCT01038583).
Adaptive dropout rates for learning with corrupted features (2015)

Feature noising is an effective mechanism on reducing the risk of overfitting. To avoid an explosive searching space, existing work typically assumes that all features share a single noise level, which is often cross-validated. In this paper, we present a Bayesian feature noising model that flexibly allows for dimension-specific or group-specific noise levels, and we derive a learning algorithm that adaptively updates these noise levels. Our adaptive rule is simple and interpretable, by drawing a direct connection to the fitness of each individual feature or feature group. Empirical results on various datasets demonstrate the effectiveness on avoiding extensive tuning and sometimes improving the performance due to its flexibility.
Congestion management: The system operators challenge to balance transmission transfer capacity with an acceptable security level (2006)

The paper discusses the challenges and possible solutions to balance the increasing need of transfer capacity with an acceptable security level. The liberalised market system calls for flexibility in power exchanges to enhance the competition at the same time as there is an increasing need for someone to supervise the overall system operation. Operating the power system closer to technical limits makes it necessary to have efficient methods to deal with cases with insufficient transfer capacity. Major techniques discussed in this paper to handle this are the market splitting, locational marginal pricing and the recently proposed flow-based market coupling. Basic principles, possibilities and limitations of these techniques as well as suitable instruments to mitigate the limitations are addressed. A discussion of which market models these techniques are suitable for, is included. The paper further discusses the aspects related to defining appropriate transfer levels under different security criteria and the possibility to make corrective actions during emergencies. Moving from a preventively secure system operation to a correctable secure operation will significantly increase the transfer capacities and give the market some of the requested capacity, but at some risk for disconnection of loads and components