gebhart/patrepeval huggingface dataset:
In utero transfer of adult bone marrow cells into recipients with severe combined immunodeficiency disorder yields lymphoid progeny with T- and B-cell functional capabilities (1995)

To determine if in utero transplantation could restore the immune system of mice with a severe combined immunodeficiency (SCID) disorder, C57BL/6Sz-scid/scid fetuses were injected on day 14/15 of gestation with adult congenic donor bone marrow (BM) cells. Congenic BM engrafted in one of eight (13%) recipients. Reconstitution of both lymphoid and nonlymphoid lineages was observed. In vitro and in vivo T-cell function was documented. Stem cells were shown to have engrafted by secondary transfer studies. When fully allogeneic C57BL/6 (H-2b) or B10.BR (H-2k) adult. BM cells were given to C.B-17-scid/scid (H-2d) fetal recipients, 15 of 54 (28%) recipients had evidence of engraftment, with up to 76% of peripheral blood (PB) being of in utero donor BM origin on day 131 postnatally. In all mice with persistent leukocyte engraftment, T- and B-lymphoid cells were entirely of donor origin. Donor T cells were tolerant to host but not third party alloantigens as measured in vitro. In vivo, T-cell function appeared intact. Although most mice had lower levels of B-cell engraftment than T-cell engraftment, mice with > or = 10% B cells were able to produce normal levels of IgM. Despite transplantation of fully allogeneic BM cells, stem cell engraftment could be demonstrated by secondary transfer of BM cells into lethally irradiated recipients that were congenic to the original in utero donor BM source. These data indicate that adult BM cells, even those fully allogeneic with the fetal recipient, can give rise to progeny with multilineage potential, which leads to restoration of T-cell and B-cell function.
Experimental Analysis of a Spatialised Audio Interface for People with Visual Impairments (2020)

Sound perception is a fundamental skill for many people with severe sight impairments. The research presented in this article is part of an ongoing project with the aim to create a mobile guidance aid to help people with vision impairments find objects within an unknown indoor environment. This system requires an effective non-visual interface and uses bone-conduction headphones to transmit audio instructions to the user. It has been implemented and tested with spatialised audio cues, which convey the direction of a predefined target in 3D space. We present an in-depth evaluation of the audio interface with several experiments that involve a large number of participants, both blindfolded and with actual visual impairments, and analyse the pros and cons of our design choices. In addition to producing results comparable to the state-of-the-art, we found that Fitts’s Law (a predictive model for human movement) provides a suitable metric that can be used to improve and refine the quality of the audio interface in future mobile navigation aids.
Inhibition of tumor necrosis factor prevents myocardial dysfunction during burn shock (1994)

Tumor necrosis factor-alpha (TNF) is a pluripotent cytokine that mediates many of the hemodynamic manifestations of endotoxic shock. To determine whether TNF is responsible for postburn myocardial dysfunction, we compared cardiac function (Langendorff preparation) in 49 guinea pigs 18 h after thermal injury. Group 1 (n = 15) was sham burned; all remaining animals received a 43% surface area burn under anesthesia. Group 2 (n = 15) received lactated Ringer solution (LR, 4 ml.kg-1.%burn-1). Group 3 (n = 9) received LR and drug vehicle. Group 4 (n = 10) received LR plus 1 mg of TNF inhibitor consisting of the human p80 TNF receptor linked to the Fc portion of human immunoglobulin G1, which was shown to specifically bind and neutralize TNF secreted by guinea pig peritoneal macrophages in vitro. Burn injury caused a significant fall in left ventricular pressure (LVP, from 86 +/- 2 to 62 +/- 3 mmHg, P < 0.05) and maximal rate of LVP rise (+) and fall (-) (+/- dP/dtmax) [from 1,365 +/- 42 to 1,109 +/- 44 mmHg/s (P < 0.05) and from 1,184 +/- 31 to 881 +/- 40 mmHg/s (P < 0.05), respectively], a decrease in time to peak systolic LVP (from 111 +/- 2 to 102 +/- 2 ms, P < 0.05), and a decrease in time to +dP/dtmax (from 57 +/- 1 to 48 +/- 1 ms, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies (2017)

Extending the success of chimeric antigen receptor (CAR) T cells to T-cell malignancies is problematic because most target antigens are shared between normal and malignant cells, leading to CAR T-cell fratricide. CD7 is a transmembrane protein highly expressed in acute T-cell leukemia (T-ALL) and in a subset of peripheral T-cell lymphomas. Normal expression of CD7 is largely confined to T cells and natural killer (NK) cells, reducing the risk of off-target-organ toxicity. Here, we show that the expression of a CD7-specific CAR impaired expansion of transduced T cells because of residual CD7 expression and the ensuing fratricide. We demonstrate that targeted genomic disruption of the CD7 gene prevented this fratricide and enabled expansion of CD7 CAR T cells without compromising their cytotoxic function. CD7 CAR T cells produced robust cytotoxicity against malignant T-cell lines and primary tumors and were protective in a mouse xenograft model of T-ALL. Although CD7 CAR T cells were also toxic against unedited (CD7<sup>+</sup>) T and NK lymphocytes, we show that the CD7-edited T cells themselves can respond to viral peptides and therefore could be protective against pathogens. Hence, genomic disruption of a target antigen overcomes fratricide of CAR T cells and establishes the feasibility of using CD7 CAR T cells for the targeted therapy of T-cell malignancies.
Serum neurofilament heavy chains as early marker of motor neuron degeneration (2019)

Abstract Objective To determine whether serum phosphorylated neurofilament heavy chain (pNfH) levels are elevated before patients were diagnosed with sporadic or familial ALS, and what the prognostic value of these prediagnostic pNfH levels is. Methods pNfH was measured via ELISA in leftovers of serum drawn for routine purposes before the time of diagnosis. These prediagnostic samples were retrieved from the biobank of the University Hospitals Leuven for 95 patients who in follow‐up received a diagnosis of ALS. Additionally, 35 patients with mild cognitive impairment (MCI) and 85 healthy controls (HC) were included in this retrospective study. Results The median disease duration (range) from onset to prediagnostic sampling and from onset to diagnosis was 6.5 (−71.9–36.1) and 9.9 (2.0–40.7) months, respectively. Fifty‐eight percent of the prediagnostic samples had serum pNfH levels above the 95th percentile of pNfH levels measured in HC. Serum pNfH levels (median (range)) were elevated up to 18 months before the diagnosis of ALS (91 pg/mL (6–342 pg/mL)) in comparison with HC (30 pg/mL (6–146 pg/mL); P = 0.05), and increased during the prediagnostic stage, which was not observed in patients with MCI. Furthermore, prediagnostic pNfH levels were a univariate predictor of survival in ALS (hazard ratio (95% CI): 2.16 (1.20–3.87); P = 0.01). Interpretation Our findings demonstrate that serum pNfH is elevated well before the time of diagnosis in mainly sporadic ALS patients. These results encourage to prospectively explore if pNfH has an added value to shorten the diagnostic delay in ALS.
Soluble Monomeric IgG1 Fc (2012)

Antibody fragments are emerging as promising biopharmaceuticals because of their relatively small size and other unique properties. However, compared with full-size antibodies, these antibody fragments lack the ability to bind the neonatal Fc receptor (FcRn) and have reduced half-lives. Fc engineered to bind antigens but preserve interactions with FcRn and Fc fused with monomeric proteins currently are being developed as candidate therapeutics with prolonged half-lives; in these and other cases, Fc is a dimer of two CH2-CH3 chains. To further reduce the size of Fc but preserve FcRn binding, we generated three human soluble monomeric IgG1 Fcs (mFcs) by using a combination of structure-based rational protein design combined with multiple screening strategies. These mFcs were highly soluble and retained binding to human FcRn comparable with that of Fc. These results provide direct experimental evidence that efficient binding to human FcRn does not require human Fc dimerization. The newly identified mFcs are promising for the development of mFc fusion proteins and for novel types of mFc-based therapeutic antibodies of small size and long half-lives.
TAFI, or Plasma Procarboxypeptidase B, Couples the Coagulation and Fibrinolytic Cascades through the Thrombin-Thrombomodulin Complex (1996)

TAFI (thrombin-activatable fibrinolysis inhibitor) is a recently discovered plasma protein that can be activated by thrombin-catalyzed proteolysis to a carboxypeptidase B-like enzyme that inhibits fibrinolysis. This work shows that the thrombin-thrombomodulin complex, rather than free thrombin, is the most likely physiologic activator. Thrombomodulin increases the catalytic efficiency of the reaction by a factor of 1250, an effect expressed almost exclusively through an increase in kcat. The kinetics of the reaction conform to a model whereby thrombin can interact with either TAFI (Km = 1.0 microM) or thrombomodulin (Kd = 8.6 nM), and either binary complex so formed can then interact with the third component to form the ternary thrombin-thrombomodulin-TAFI complex from which activated TAFI is produced with kcat = 1.2 s-1. This work also shows that activated TAFI down-regulates tPA-induced fibrinolysis half-maximally at a concentration of 1.0 nM in a system of purified components. This concentration of TAFI is about 2% of the level of the zymogen in plasma, which indicates that ample activated TAFI could be generated to very significantly modulate fibrinolysis in vivo. Therefore, TAFI in vitro and possibly in vivo defines an explicit molecular connection between the coagulation and fibrinolytic cascades, such that expression of activity in the former down-regulates the activity of the latter.
Interleukin 1 suppresses expression of cartilage-specific types II and IX collagens and increases types I and III collagens in human chondrocytes. (1988)

In inflammatory diseases such as rheumatoid arthritis, functions of chondrocytes including synthesis of matrix proteins and proteinases are altered through interactions with cells of the infiltrating pannus. One of the major secreted products of mononuclear inflammatory cells is IL-1. In this study we found that recombinant human IL-1 beta suppressed synthesis of cartilage-specific type II collagen by cultured human costal chondrocytes associated with decreased steady state levels of alpha 1 (II) and alpha 1(IX) procollagen mRNAs. In contrast, IL-1 increased synthesis of types I and III collagens and levels of alpha 1(I), alpha 2(I), and alpha 1(III) procollagen mRNAs, as we described previously using human articular chondrocytes and synovial fibroblasts. This stimulatory effect of IL-1 was observed only when IL-1-stimulated PGE2 synthesis was blocked by the cyclooxygenase inhibitor indomethacin. The suppression of type II collagen mRNA levels by IL-1 alone was not due to IL-1-stimulated PGE2, since addition of indomethacin did not reverse, but actually potentiated, this inhibition. Continuous exposure of freshly isolated chondrocytes from day 2 of culture to approximately half-maximal concentrations of IL-1 (2.5 pM) completely suppressed levels of type II collagen mRNA and increased levels of types I and III collagen mRNAs, thereby reversing the ratio of alpha 1(II)/alpha 1(I) procollagen mRNAs from greater than 6.0 to less than 1.0 by day 7. IL-1, therefore, can modify, at a pretranslational level, the relative amounts of the different types of collagen synthesized in cartilage and thereby could be responsible for the inappropriate repair of cartilage matrix in inflammatory conditions.
Existence of a “Hot” Atom Mechanism for the Dissociation ofO2on Pt(111) (1996)

The dissociation of ${\mathrm{O}}_{2}$ on a Pt(111) surface was studied by variable temperature scanning tunneling microscopy at 150--106 K. The two oxygen atoms created by the dissociation appear in pairs, with average distances of two lattice constants. Since thermal random walk sets in only at around 200 K, with a diffusion barrier of 0.43 eV and a preexponential factor of ${10}^{\ensuremath{-}6.3}{\mathrm{cm}}^{2}{\mathrm{s}}^{\ensuremath{-}1}$, the distribution of distances at around 160 K evidences nonthermal processes during the dissociation. It is concluded that transient ballistic motion exists, where the short range traveled is in agreement with recent molecular dynamics studies.
Characterization of a new type of human papillomavirus found in a lesion of Bowen's disease of the skin (1986)

The genome of a human papillomavirus (HPV) found in a patient with Bowen's disease of the skin was molecularly cloned. Blot hybridization experiments, performed under stringent conditions, revealed no cross-hybridization between this HPV DNA and the other known HPV DNAs, showing that this HPV represents a new type, tentatively named HPV34. In relaxed hybridization conditions, the highest cross-hybridization was observed with HPV16 DNA. The physical map of HPV34 DNA was aligned with the genetic map of HPV16 DNA by heteroduplex mapping. HPV34 was not detected in 12 additional patients with Bowen's disease of the skin, but a closely related HPV DNA was found in one patient with penile Bowenoid papulosis.
Cyclin-dependent kinase 2 is an ideal target for ovary tumors with elevated cyclin E1 expression (2015)

CCNE1 gene amplification is present in 15-20% ovary tumor specimens. Here, we showed that Cyclin E1 (CCNE1) was overexpressed in 30% of established ovarian cancer cell lines. We also showed that CCNE1 was stained positive in over 40% of primary ovary tumor specimens regardless of their histological types while CCNE1 staining was either negative or low in normal ovary and benign ovary tumor tissues. However, the status of CCNE1 overexpression was not associated with the tumorigenic potential of ovarian cancer cell lines and also did not correlate with pathological grades of ovary tumor specimens. Subsequent experiments with CCNE1 siRNAs showed that knockdown of CCNE1 reduced cell growth only in cells with inherent CCNE1 overexpression, indicating that these cells may have developed an addiction to CCNE1 for growth/survival. As CCNE1 is a regulatory factor of cyclin-dependent kinase 2 (Cdk2), we investigated the effect of Cdk2 inhibitor on ovary tumorigenecity. Ovarian cancer cells with elevated CCNE1 expression were 40 times more sensitive to Cdk2 inhibitorSNS-032 than those without inherent CCNE1 overexpression. Moreover, SNS-032 greatly prolonged the survival of mice bearing ovary tumors with inherent CCNE1 overexpression. This study suggests that ovary tumors with elevated CCNE1 expression may be staged for Cdk2-targeted therapy.
Biocompatibility and drug delivery systems (2010)

Drug delivery technology has emerged as an important focus of biotechnological research and commercial enterprise. While much attention is justifiably focused on the design and effectiveness of drug delivery devices, the nature of their interaction with surrounding tissues – their biocompatibility – is crucial. Here we discuss biocompatibility, specifically as it relates to drug delivery systems, which differ from other biomaterial-based devices by possibly containing large quantities of drugs with their own effects on tissues.
Physics and chemistry of plasma pollution control technology (2008)

Gaseous pollution control technologies for acid gases (NOx, SOx, etc), volatile organic compounds, greenhouse gases, ozone layer depleting substances, etc have been commercialized based on catalysis, incineration and adsorption methods. However, non-thermal plasma techniques based on electron beams and corona discharges are becoming significant due to advantages such as lower costs, higher removal efficiency and smaller space volume. In order to commercialize this new technology, the pollution gas removal rate, energy efficiency of removal, pressure drop of reactors and useable by-product production rates must be improved and identification of major fundamental processes and optimizations of reactor and power supply for an integrated system must be investigated. In this work, the chemistry and physics of plasma pollution control are discussed and the limitation of this type of plasma is outlined based on the plasma parameters.
Global mapping of transcription start sites and promoter motifs in the symbiotic α-proteobacterium Sinorhizobium meliloti1021 (2013)

By identifying TSS and promoters on a global scale, our work provides a firm foundation for the continued study of S. meliloti gene expression with relation to gene organization, σ factors and other transcription factors, and regulatory RNAs.
Inference Attacks on Property-Preserving Encrypted Databases (2015)

Many encrypted database (EDB) systems have been proposed in the last few years as cloud computing has grown in popularity and data breaches have increased. The state-of-the-art EDB systems for relational databases can handle SQL queries over encrypted data and are competitive with commercial database systems. These systems, most of which are based on the design of CryptDB (SOSP 2011), achieve these properties by making use of property-preserving encryption schemes such as deterministic (DTE) and order- preserving encryption (OPE). In this paper, we study the concrete security provided by such systems. We present a series of attacks that recover the plaintext from DTE- and OPE-encrypted database columns using only the encrypted column and publicly-available auxiliary information. We consider well-known attacks, including frequency analysis and sorting, as well as new attacks based on combinatorial optimization.
Arachidonic acid metabolism of the murine eosinophil. II. Involvement of the lipoxygenase pathway in the response to the lymphokine eosinophil stimulation promoter. (1982)

Eosinophil stimulation promoter (ESP) is a murine lymphokine that enhances the migration of eosinophils. Exogenous arachidonic acid between 0.5 and 2 micrograms/ml potentiated the activity of ESP on murine eosinophil migration, whereas such concentrations did not affect migration in the absence of ESP. Among the lipoxygenase products identified from an enriched population of murine eosinophils, leukotriene B4 (optimal activity at 100 ng/ml) and 12-HETE (optimal activity at 2 micrograms/ml) stimulated migration of these cells. Another lipoxygenase product from these cells 15-HETE inhibited ESP-induced migration; between 5 and 10 micrograms/ml 15-HETE decreased by one-half both stimulated migration and 12-HETE biosynthesis. Structurally diverse drugs at concentrations that inhibited HETE biosynthesis inhibited ESP-induced migration. The concentrations that decreased migration activity by one-half were 5 microM NDGA, 10 microM ETYA, and 150 microM BW755C. Aspirin and indomethacin at concentrations reported to inhibit prostaglandin biosynthesis did not substantially inhibit ESP activity, but concentrations of indomethacin above 20 microM caused concentration-dependent inhibition of migration. The selective lipoxygenases inhibitor 134,7,10,13-eicosatetraynoic acid was more potent than ETYA in inhibition of ESP-induced migration, and the selective cyclooxygenase inhibitor 6,9,12-octadecatriynoic acid did not effect inhibition. These results are consistent with the hypothesis that stimulation of eosinophils by the lymphokine ESP involves the generation of lipoxygenase products from arachidonic acid, which positively and negatively regulate the migratory activities of these cells.
Squalene Emulsions for Parenteral Vaccine and Drug Delivery (2009)

Squalene is a linear triterpene that is extensively utilized as a principal component of parenteral emulsions for drug and vaccine delivery. In this review, the chemical structure and sources of squalene are presented. Moreover, the physicochemical and biological properties of squalene-containing emulsions are evaluated in the context of parenteral formulations. Historical and current parenteral emulsion products containing squalene or squalane are discussed. The safety of squalene-based products is also addressed. Finally, analytical techniques for characterization of squalene emulsions are examined.
Marketing of Fresh Vegetables and Fruits by Small Farmers in Tennessee (1994)

Direct market alternatives have been advocated as important mechanisms by which the small producer can gain entry into high priced fresh produce markets by cutting short the channels in the traditional market system. The paper examines the traditional marketing system, problems faced by small farmers in this system and various direct marketing alternatives. The study estimates the determinants of the number of various direct marketing outlets in Tennessee, using county lend data. The estimated model provides "good fit" for pick-your-own operations and its combination with roadside stands. THe co-efficient for per capita income was significant for all outlets except peddlers.
Deep Clustering for Unsupervised Learning of Visual Features (2018)

Clustering is a class of unsupervised learning methods that has been extensively applied and studied in computer vision. Little work has been done to adapt it to the end-to-end training of visual features on large scale datasets. In this work, we present DeepCluster, a clustering method that jointly learns the parameters of a neural network and the cluster assignments of the resulting features. DeepCluster iteratively groups the features with a standard clustering algorithm, k-means, and uses the subsequent assignments as supervision to update the weights of the network. We apply DeepCluster to the unsupervised training of convolutional neural networks on large datasets like ImageNet and YFCC100M. The resulting model outperforms the current state of the art by a significant margin on all the standard benchmarks.
A system for compiling and debugging structured data processing controllers (1996)

This paper describes a system for designing and implementing controllers for structured data processing. A graphical input style describes the format of the data to be processed along with the necessary control actions. Advantages over FSM approaches include: (1) ease of design changes, (2) ease of debugging, and (3) a shorter design cycle.
Silencing of genes at nontelomeric sites in yeast is controlled by sequestration of silencing factors at telomeres by Rap 1 protein. (1996)

Rap1p binds to silencer elements and telomeric repeats in yeast, where it appears to initiate silencing by recruiting Sir3p and Sir4p to the chromosome through interactions with its carboxy-terminal domain. Sir3p and Sir4p interact in vitro with histones H3 and H4 and are likely to be structural components of silent chromatin. We show that targeting of these Sir proteins to the chromosome is sufficient to initiate stable silencing either at a silent mating-type locus lacking a functional silencer element or at a telomere in a strain in which the Rap1p carboxy-terminal silencing domain has been deleted. Silencing by Sir protein targeting can also be initiated at a telomere-proximal site (ADH4), but is much weaker at an internal chromosomal locus (LYS2). Strikingly, deletion of the Rap1p silencing domain, which abolishes telomeric silencing, improves targeted silencing at LYS2 by both Sir3p and Sir4p, while weakening the silencing activity of these proteins at or near a telomere. This effect may result from the release of Sir proteins from the telomeres, thus increasing their effective concentration at other chromosomal sites. We suggest that telomeres and Rap1p serve a regulatory role in sequestering Sir proteins at telomeres, controlling silencing at other loci in trans and preventing indiscriminate gene silencing throughout the genome.