gebhart/patrepeval huggingface dataset:
Lupus risk variants in the PXK locus alter B-cell receptor internalization (2015)

Genome wide association studies have identified variants in PXK that confer risk for humoral autoimmune diseases, including systemic lupus erythematosus (SLE or lupus), rheumatoid arthritis and more recently systemic sclerosis. While PXK is involved in trafficking of epidermal growth factor Receptor (EGFR) in COS-7 cells, mechanisms linking PXK to lupus pathophysiology have remained undefined. In an effort to uncover the mechanism at this locus that increases lupus-risk, we undertook a fine-mapping analysis in a large multi-ancestral study of lupus patients and controls. We define a large (257kb) common haplotype marking a single causal variant that confers lupus risk detected only in European ancestral populations and spans the promoter through the 3' UTR of PXK. The strongest association was found at rs6445972 with P < 4.62 × 10(-10), OR 0.81 (0.75-0.86). Using stepwise logistic regression analysis, we demonstrate that one signal drives the genetic association in the region. Bayesian analysis confirms our results, identifying a 95% credible set consisting of 172 variants spanning 202 kb. Functionally, we found that PXK operates on the B-cell antigen receptor (BCR); we confirmed that PXK influenced the rate of BCR internalization. Furthermore, we demonstrate that individuals carrying the risk haplotype exhibited a decreased rate of BCR internalization, a process known to impact B cell survival and cell fate. Taken together, these data define a new candidate mechanism for the genetic association of variants around PXK with lupus risk and highlight the regulation of intracellular trafficking as a genetically regulated pathway mediating human autoimmunity.
Musculoskeletal tissues-on-a-chip: role of natural polymers in reproducing tissue-specific microenvironments (2022)

Over the past years, 3D<i>in vitro</i>models have been widely employed in the regenerative medicine field. Among them, organ-on-a-chip technology has the potential to elucidate cellular mechanism exploiting multichannel microfluidic devices to establish 3D co-culture systems that offer control over the cellular, physico-chemical and biochemical microenvironments. To deliver the most relevant cues to cells, it is of paramount importance to select the most appropriate matrix for mimicking the extracellular matrix of the native tissue. Natural polymers-based hydrogels are the elected candidates for reproducing tissue-specific microenvironments in musculoskeletal tissue-on-a-chip models owning to their interesting and peculiar physico-chemical, mechanical and biological properties. Despite these advantages, there is still a gap between the biomaterials complexity in conventional tissue engineering and the application of these biomaterials in 3D<i>in vitro</i>microfluidic models. In this review, the aim is to suggest the adoption of more suitable biomaterials, alternative crosslinking strategies and tissue engineered-inspired approaches in organ-on-a-chip to better mimic the complexity of physiological musculoskeletal tissues. Accordingly, after giving an overview of the musculoskeletal tissue compositions, the properties of the main natural polymers employed in microfluidic systems are investigated, together with the main musculoskeletal tissues-on-a-chip devices.
Covalent Surface Modification of Oxide Surfaces (2014)

The modification of surfaces by the deposition of a robust overlayer provides an excellent handle with which to tune the properties of a bulk substrate to those of interest. Such control over the surface properties becomes increasingly important with the continuing efforts at down-sizing the active components in optoelectronic devices, and the corresponding increase in the surface area/volume ratio. Relevant properties to tune include the degree to which a surface is wetted by water or oil. Analogously, for biosensing applications there is an increasing interest in so-called "romantic surfaces": surfaces that repel all biological entities, apart from one, to which it binds strongly. Such systems require both long lasting and highly specific tuning of the surface properties. This Review presents one approach to obtain robust surface modifications of the surface of oxides, namely the covalent attachment of monolayers.
Direct epicardial mapping predicts the recovery of left ventricular dysfunction in chronic ischaemic myocardium (2004)

Direct epicardial mapping is able to predict the recovery of chronically ischaemic dysfunctional myocardium and thereby proves the presence of myocardial viability.
Income Maximization using Prices and QoS for a Multi-Class Telecommunications System (2007)

In this letter we develop a novel method of controlling a multi-class, QoS-enabled telecommunications system, using pricing and resource allocation for income maximization. We propose a solution using the limiting regime approximation, which reduces the associated computational burden
Optoelektronische Meßverfahren mit Doppeldioden / Opto-electronic measuring methods with twin diodes (1979)

Article Optoelektronische Meßverfahren mit Doppeldioden / Opto-electronic measuring methods with twin diodes was published on December 1, 1979 in the journal tm - Technisches Messen (volume 514-524, issue JG).
Recursive least squares with forgetting for online estimation of vehicle mass and road grade: theory and experiments (2005)

Good estimates of vehicle mass and road grade are important in automation of heavy duty vehicles, vehicle following manoeuvres or traditional powertrain control schemes. Recursive least square (RLS) with multiple forgetting factors accounts for different rates of change for different parameters and thus, enables simultaneous estimation of the time-varying grade and the piece-wise constant mass. An ad hoc modification of the update law for the gain in the RLS scheme is proposed and used in simulation and experiments. We demonstrate that the proposed scheme estimates mass within 5% of its actual value and tracks grade with good accuracy provided that inputs are persistently exciting. The experimental setups, signals, their source and their accuracy are discussed. Issues like lack of persistent excitations in certain parts of the run or difficulties of parameter tracking during gear shift are explained and suggestions to bypass these problems are made.
Athymic mouse model of a human T-cell tumor. (1985)

Because of the large number of different immunoconjugates which can be produced from monoclonal antibody-directed anti-cancer therapy, it would be useful to have in vivo tumor models to compare such preparations. Although historically human leukemias-lymphomas have been difficult to establish in athymic mice we have succeeded in establishing human T-cell tumors from primary MOLT-4 cultures in 290 of 353 animals and have successfully transferred tumors in 42 of 45 animals during ten serial passages. The potential utility of this model for testing immunoconjugates of murine monoclonal antibody T101 have been confirmed by: (a) in all 148 tumors sampled including all passaged tumors the human T-cell antigen, T65, was expressed in a manner identical to that of cultured cells; (b) 111In-T101 was concentrated preferentially in the tumor; and (c) T101 injected by both the i.p. and i.v. routes bound to tumor and induced antigenic modulation to the same extent as that observed previously in vitro and in human studies.
Reliable B Cell Epitope Predictions: Impacts of Method Development and Improved Benchmarking (2012)

The interaction between antibodies and antigens is one of the most important immune system mechanisms for clearing infectious organisms from the host. Antibodies bind to antigens at sites referred to as B-cell epitopes. Identification of the exact location of B-cell epitopes is essential in several biomedical applications such as; rational vaccine design, development of disease diagnostics and immunotherapeutics. However, experimental mapping of epitopes is resource intensive making in silico methods an appealing complementary approach. To date, the reported performance of methods for in silico mapping of B-cell epitopes has been moderate. Several issues regarding the evaluation data sets may however have led to the performance values being underestimated: Rarely, all potential epitopes have been mapped on an antigen, and antibodies are generally raised against the antigen in a given biological context not against the antigen monomer. Improper dealing with these aspects leads to many artificial false positive predictions and hence to incorrect low performance values. To demonstrate the impact of proper benchmark definitions, we here present an updated version of the DiscoTope method incorporating a novel spatial neighborhood definition and half-sphere exposure as surface measure. Compared to other state-of-the-art prediction methods, Discotope-2.0 displayed improved performance both in cross-validation and in independent evaluations. Using DiscoTope-2.0, we assessed the impact on performance when using proper benchmark definitions. For 13 proteins in the training data set where sufficient biological information was available to make a proper benchmark redefinition, the average AUC performance was improved from 0.791 to 0.824. Similarly, the average AUC performance on an independent evaluation data set improved from 0.712 to 0.727. Our results thus demonstrate that given proper benchmark definitions, B-cell epitope prediction methods achieve highly significant predictive performances suggesting these tools to be a powerful asset in rational epitope discovery. The updated version of DiscoTope is available at www.cbs.dtu.dk/services/DiscoTope-2.0.
“Direct” 13C Hyperpolarization of 13C‐Acetate by MicroTesla NMR Signal Amplification by Reversible Exchange (SABRE) (2019)

Abstract Herein, we demonstrate “direct” 13 C hyperpolarization of 13 C‐acetate via signal amplification by reversible exchange (SABRE). The standard SABRE homogeneous catalyst [Ir‐IMes; [IrCl(COD)(IMes)], (IMes=1,3‐bis(2,4,6‐trimethylphenyl), imidazole‐2‐ylidene; COD=cyclooctadiene)] was first activated in the presence of an auxiliary substrate (pyridine) in alcohol. Following addition of sodium 1‐ 13 C‐acetate, parahydrogen bubbling within a microtesla magnetic field (i.e. under conditions of SABRE in shield enables alignment transfer to heteronuclei, SABRE‐SHEATH) resulted in positive enhancements of up to ≈100‐fold in the 13 C NMR signal compared to thermal equilibrium at 9.4 T. The present results are consistent with a mechanism of “direct” transfer of spin order from parahydrogen to 13 C spins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the 13 C acetate resonance, but we find that relaxation dynamics at microtesla fields alter the optimal matching from the traditional SABRE‐SHEATH picture. Further development of this approach could lead to new ways to rapidly, cheaply, and simply hyperpolarize a broad range of substrates (e.g. metabolites with carboxyl groups) for various applications, including biomedical NMR and MRI of cellular and in vivo metabolism.
Natural Language Processing Technologies in Radiology Research and Clinical Applications (2016)

The migration of imaging reports to electronic medical record systems holds great potential in terms of advancing radiology research and practice by leveraging the large volume of data continuously being updated, integrated, and shared. However, there are significant challenges as well, largely due to the heterogeneity of how these data are formatted. Indeed, although there is movement toward structured reporting in radiology (ie, hierarchically itemized reporting with use of standardized terminology), the majority of radiology reports remain unstructured and use free-form language. To effectively "mine" these large datasets for hypothesis testing, a robust strategy for extracting the necessary information is needed. Manual extraction of information is a time-consuming and often unmanageable task. "Intelligent" search engines that instead rely on natural language processing (NLP), a computer-based approach to analyzing free-form text or speech, can be used to automate this data mining task. The overall goal of NLP is to translate natural human language into a structured format (ie, a fixed collection of elements), each with a standardized set of choices for its value, that is easily manipulated by computer programs to (among other things) order into subcategories or query for the presence or absence of a finding. The authors review the fundamentals of NLP and describe various techniques that constitute NLP in radiology, along with some key applications.
Reward Optimizing Recommendation using Deep Learning and Fast Maximum Inner Product Search (2022)

How can we build and optimize a recommender system that must rapidly fill slates (i.e. banners) of personalized recommendations? The combination of deep learning stacks with fast maximum inner product search (MIPS) algorithms have shown it is possible to deploy flexible models in production that can rapidly deliver personalized recommendations to users. Albeit promising, this methodology is unfortunately not sufficient to build a recommender system which maximizes the reward, e.g. the probability of click. Usually instead a proxy loss is optimized and A/B testing is used to test if the system actually improved performance. This tutorial takes participants through the necessary steps to model the reward and directly optimize the reward of recommendation engines built upon fast search algorithms to produce high-performance reward-optimizing recommender systems.
Improvements in Receiver Intermodulation Rejection Tests (1972)

This paper introduces some of the efforts recently inaugurated at the Army Electronics Command to develop the next generation of receiver susceptibility limits. These new limits will be based on a statistical scoring technique and therefore, require that a receiver's susceptibility characteristics be completely described. To insure that the level of test effort is contained within a reasonable scope, associated test methods will emphasize integration of engineering analysis with collection of measured data. In the process of developing applicable analysis models for receiver intermodulation rejection requirements, it was determined that most present test specifications and procedures are based on inadequate rule of thumb guidelines rather than fundamental engineering laws. Additionally, it was established that all test data has been derived by sampling only a very few (usually three) test frequencies with no consideration to how the total number and relative amplitudes of intermodulation responses varied with receiver dial frequency. To eliminate the above shortcomings, a detailed frequency analysis model has been derived which establishes the interrelationships between receiver dial frequency IF, local oscillator frequency, IM response order and total number of probable IM responses. The paper presents the above derivation, illustrates its application to common EMI receivers and summarizes' measured data in support of stated conclusions. The objective is to show that application of engineering analysis can produce more informative data in terms of worst case and typical performance characteristics while simultaneously removing existing redundancy in data collection' The. information content is directly applicable to preparation of (l) EMI Control and Test. Plans as rèquired by MIL-STD's 461, 462 and 469; (2) interference prediction analysis as specified in MIL-E-6051D; (3) collection of spectrum signature under MIL-STD-469; (4) frequency assignments for.cosite installations, and (5) inputs for receiver design tradeoff studies.
The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice (2010)

Pramipexole (PRA) is a preferential D3R agonist that, in rats and humans, modifies prepulse inhibition (PPI) of the acoustic startle reflex, an operational measure of sensorimotor gating. The ability to use similar PPI measures across species, and the relative ease of genetic manipulations in mice, suggests that molecular studies of the D3R regulation of sensorimotor gating might be best pursued in mice. Here, we evaluate the effects of PRA on PPI and locomotion in C57BL/6J mice, the background strain for many gene knockout mouse models. Male C57BL/6J mice were tested for PPI and locomotor activity after injection of PRA. No significant effects of PRA on PPI were observed at any dose (0.1-10.0 mg/kg), but a significant reduction in startle magnitude was observed after 10 mg/kg PRA. In contrast, the D1/2 agonist, apomorphine (5 mg/kg) significantly reduced PPI in these mice. At doses of PRA that did not alter startle magnitude (0.3, 1, 3 mg/kg), significant decreases in the amount of locomotor and investigatory behavior were observed. Distinct from findings in rats and humans, it seems that either: (i) PRA does not activate D3Rs in C57BL/6J mice, or (ii) D3R agonists are not sufficient to alter PPI in this mouse strain.
Impaired expression of protein phosphatase 2A subunits enhances metastatic potential of human prostate cancer cells through activation of AKT pathway (2013)

We conclude that loss of expression of scaffold and regulatory subunits of PP2A is responsible for its altered function during PCa pathogenesis.
The real zeros of a random polynomial with dependent coefficients (2009)

Abstract. Mark Kac gave one of the first results analyzing random polynomial zeros. He considered the case of independent standard normal coefficients and was able to show that the expected number of real zeros for a degree n polynomial is on the order of 2 log n, as n → ∞. Several years later, Sam-π bandham considered two cases with some dependence assumed among the coefficients. The first case looked at coefficients with an exponentially decaying covariance function, while the second assumed a constant covariance. He showed that the expectation of the number of real zeros for an exponentially decaying covariance matches the independent case, while having a constant covariance reduces the expected number of zeros in half. In this paper we will apply techniques similar to Sambandham’s and extend his results to a wider class of covariance functions. Under certain restrictions on the spectral density, we will show that the order of the expected number of real zeros remains the same as in the independent case. 1. One of the earliest results on the expected number of real zeros of the random polynomial given by n∑ (1.1) Pn(x) = Xkx k k=0 came from Mark Kac [6]. Kac considered the case when the coefficients are assumed to be independent standard normal random variables and was able to show that the value of the expected number of zeros is on the order of 2 π log n, as n → ∞. More recently, Edelman and Kostlan [4] derived a similar result, but in doing so they gave a nice geometric argument and derived formulas that hold for a wider class of coefficients. A natural generalization of this problem is to assume some dependence among the coefficients. Let X0, X1,... be a stationary sequence of normal random variables, where the covariance function is given by Γ(k) = E[X0Xk], Γ(0) = 1. Under these assumptions, two important results came from Sambandham. The first assumes that Γ(k) = ρk, where ρ ∈ (0, 1 2) [8]. In this case, it was shown that the expected number of zeros is on the same order as when the coefficients are independent. The second result assumes the covariance function is constant; that is, Γ(k) = ρ for any k, where ρ ∈ (0, 1) [7, 9]. Here, it was shown that the order of the
Localized surface plasmon resonance sensor based on Ag-PVA nanocomposite thin films (2009)

In this work we demonstrate the use of nanocomposite thin films of poly(vinyl alcohol) with embedded silver NPs for chemosensing purposes. Silver NPs are in situ synthesized inside polyvinyl alcohol during the bake step of the formation of a nanocomposite thin film. The polymer in the nanocomposite provides an appropriate chemical and electromagnetic environment for metal NPs in order to interact with and hence detect the chemical species. A limit of detection below 20 nM is found when detecting 2-mercaptoethanol as the analyte, when measuring spectral changes (peak wavelength, linewidth and intensity) in the Localized Surface Plasmon Resonance. Potential qualitative and semi-quantitative sensors based on such nanocomposites would be easy-to-prepare, easy-to-use and low-cost, which are the basis of a fully disposable sensing platform technology.
Clostridium perfringens phospholipase C-induced platelet/leukocyte interactions impede neutrophil diapedesis (2006)

Clostridium perfringens gas gangrene is a fulminant necrotizing infection in which inflammatory cells are notably absent from infected tissues but are often massed within adjacent vessels. It has been shown that C. perfringens phospholipase C (PLC) stimulates formation of large intravascular platelet/leukocyte complexes and that PLC-induced activation of platelet gpIIbIIIa plays a major role. In vivo, such aggregates contribute to microvascular thrombosis and ischaemic necrosis of tissue. However, the effects of adherent platelets on neutrophil diapedesis have not been established. The present work investigated (1) the contribution of platelet P-selectin (CD62P) to PLC-induced cellular complex formation and (2) the effects of platelet adhesion on neutrophil diapedesis. The effects of anti-gpIIbIIIa and anti-CD62P strategies on PLC-induced complex formation were measured by flow cytometry and followed by light microscopy. Both platelet gpIIbIIIa and CD62P contributed to the formation of platelet/leukocyte complexes. Specifically, gpIIbIIIa mediated the formation of large platelet/platelet aggregates that were tethered to the leukocyte principally via CD62P. Neutrophil diapedesis, quantified by a transendothelial cell migration assay and visualized by electron microscopy, was significantly reduced (>60%) by the adherence of large platelet aggregates. It was concluded that the absence of a tissue inflammatory response in C. perfringens gas gangrene is due, in part, to impaired neutrophil mobility caused by large aggregates of adherent platelets induced by PLC. Further, an adjunctive immunotherapeutic strategy targeting both gpIIbIIIa and CD62P may improve the tissue inflammatory response, prevent vascular occlusion, maintain tissue viability, and reduce the need for radical amputation in patients with clostridial gas gangrene.
The Model for Optimizing Replenishment Point with Service Level Constraints (2007)

An optimizing model for studying replenishment policy with service level constraints is proposed. To realize the integrative decision of service level and replenishment point, the service level in a supply chain is defined as the probability of satisfying product demand in each planning period. Inventory variation under stochastic demand is analyzed, and the average inventory in planning periods is invited into the decision model. The planning output in every period is stochastic variables having the same distributions with the product demands. A numerical analysis is given to validate the approach.
Preparation of Alkyl-Substituted Indoles in the Benzene Portion. Part 12. Enantiospecific Synthesis of Hapalindole O. (1994)

An important chiral ketone derivative, (3S, 4R)-3-methyl-4-pivaloyloxy-3-vinylcyclohexan-1-one (16) was prepared from (R)-(-)-carvone (10) using a stereo-controlled conjugate addition of the vinyl group to (R)-3-methyl-6-(1-methylethylidene)-4-pivaloyloxy-2-cyclohexen-1-one (13). The first enantiospecific total synthesis of a terrestrial blue-green alga constituent, hapalindole O (1) was accomplished by condensation of this ketone 16 with α, α-dimethyl-1-(p-toluenesulfonyl)-1H-indole-4-methanol (6) to construct the fundamental carbon framework of the hapalindole 21, followed by introduction of the nitrogen function, stereoselective reduction of the tetra-substituted double bond with lithium aluminum hydride, and subsequent isothiocyanate formation.