gebhart/patrepeval huggingface dataset:
Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response (2006)

In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.
Growth inhibition of hormone-responsive and -resistant human breast cancer cells in culture by N1, N12-bis(ethyl)spermine. (1993)

Previous studies have documented differential sensitivity of human lung cancer and melanoma cell lines to the cytotoxic effects of N1, N12-bis(ethyl)spermine (BESpm). We show here that BESpm can significantly inhibit the growth of six human breast cancer cell lines with 50% inhibitory concentration in the microM range. The degree of inhibition does not correlate with estrogen receptor status. Detailed studies with estrogen receptor-positive MCF-7 and estrogen receptor- negative Hs578t cells show a similar dose-response curve with concentrations of 1-10 microM resulting in maximal growth inhibition. Growth inhibition in both lines is associated with an 8-12-fold induction of the polyamine catabolic enzyme, spermidine/spermine N1-acetyltransferase, and a progressive decrease in intracellular polyamine levels over 6 days even though steady-state levels of BESpm are achieved within 24 h. Similar studies on WTMCF7 and AdrRMCF7 cells show that the acquisition of resistance to hormonal or doxorubicin therapy is not associated with resistance to the growth-inhibitory effects of BESpm. These results suggest that BESpm exerts similar growth-inhibitory effects against both hormone-responsive and -unresponsive human breast cancer cells, a finding which has significance for the potential use of polyamine analogues in treating human breast cancer.
The influence of ATM on operating systems (2002)

The features of ATM offered many attractions to the application community, such as fine-grained multiplexing and high-throughput links. These created considerable challenges for the O.S. designer, since a small protocol data unit size (the 48 byte "cell") and link bandwidths within a (binary) order of magnitude of memory bandwidths demanded considerable rethinking of operating system structure.Using an historical and personal perspective, this paper describes two aspects of that rethinking which I participated in directly, namely, those of new event signalling and memory buffering schemes. Ideas and techniques stemming from ATM network research influenced first research operating systems and then commercial operating systems. The positive results of ATM networking, although indirect, have benefitted applications and systems far beyond the original design goals.
Expression of Wnt pathway mediators in metaplasic tissue in animal model and clinical samples of tendinopathy (2013)

Activation of the Wnt signalling pathway and its effect on TDSCs might contribute to tissue metaplasia and failed healing in some cases of tendinopathy.
Formulation and Acoustic Studies of a New Phase-Shift Agent for Diagnostic and Therapeutic Ultrasound (2011)

Recent efforts in the area of acoustic droplet vaporization with the objective of designing extravascular ultrasound contrast agents has led to the development of stabilized, lipid-encapsulated nanodroplets of the highly volatile compound decafluorobutane (DFB). We developed two methods of generating DFB droplets, the first of which involves condensing DFB gas (boiling point from -1.1 to -2 °C) followed by extrusion with a lipid formulation in HEPES buffer. Acoustic droplet vaporization of micrometer-sized lipid-coated droplets at diagnostic ultrasound frequencies and mechanical indices were confirmed optically. In our second formulation methodology, we demonstrate the formulation of submicrometer-sized lipid-coated nanodroplets based upon condensation of preformed microbubbles containing DFB. The droplets are routinely in the 200-300 nm range and yield microbubbles on the order of 1-5 μm once vaporized, consistent with ideal gas law expansion predictions. The simple and effective nature of this methodology allows for the development of a variety of different formulations that can be used for imaging, drug and gene delivery, and therapy. This study is the first to our knowledge to demonstrate both a method of generating ADV agents by microbubble condensation and formulation of primarily submicrometer droplets of decafluorobutane that remain stable at physiological temperatures. Finally, activation of DFB nanodroplets is demonstrated using pressures within the FDA guidelines for diagnostic imaging, which may minimize the potential for bioeffects in humans. This methodology offers a new means of developing extravascular contrast agents for diagnostic and therapeutic applications.
A second branched-chain alpha-keto acid dehydrogenase gene cluster (bkdFGH) from Streptomyces avermitilis: its relationship to avermectin biosynthesis and the construction of a bkdF mutant suitable for the production of novel antiparasitic avermectins (1995)

A second cluster of genes encoding the E1 alpha, E1 beta, and E2 subunits of branched-chain alpha-keto acid dehydrogenase (BCDH), bkdFGH, has been cloned and characterized from Streptomyces avermitilis, the soil microorganism which produces anthelmintic avermectins. Open reading frame 1 (ORF1) (bkdF, encoding E1 alpha), would encode a polypeptide of 44,394 Da (406 amino acids). The putative start codon of the incompletely sequenced ORF2 (bkdG, encoding E1 beta) is located 83 bp downstream from the end of ORF1. The deduced amino acid sequence of bkdF resembled the corresponding E1 alpha subunit of several prokaryotic and eukaryotic BCDH complexes. An S. avermitilis bkd mutant constructed by deletion of a genomic region comprising the 5' end of bkdF is also described. The mutant exhibited a typical Bkd- phenotype: it lacked E1 BCDH activity and had lost the ability to grow on solid minimal medium containing isoleucine, leucine, and valine as sole carbon sources. Since BCDH provides an alpha-branched-chain fatty acid starter unit, either S(+)-alpha-methylbutyryl coenzyme A or isobutyryl coenzyme A, which is essential to initiate the synthesis of the avermectin polyketide backbone in S. avermitilis, the disrupted mutant cannot make the natural avermectins in a medium lacking both S(+)-alpha-methylbutyrate and isobutyrate. Supplementation with either one of these compounds restores production of the corresponding natural avermectins, while supplementation of the medium with alternative fatty acids results in the formation of novel avermectins. These results verify that the BCDH-catalyzed reaction of branched-chain amino acid catabolism constitutes a crucial step to provide fatty acid precursors for antibiotic biosynthesis in S. avermitilis.
The Preclinical Research Progress of Stem Cells Therapy in Parkinson’s Disease (2016)

Parkinson's disease (PD) is a type of degenerative disorder of the basal ganglia, causing tremor at rest, muscle rigidity hypokinesia, and dementia. The effectiveness of drug treatments gradually diminishes because the conversion to dopamine within the brain is increasingly disrupted by the progressive degeneration of the dopaminergic terminals. After long-term treatment, most patients with PD suffer from disability that cannot be satisfactorily controlled. To solve these issues, stem cells have recently been used for cell therapy of PD. In this review, the characteristics of different stem cells and their therapeutic effects on PD treatment will be discussed.
Spectral Dependence Of The Diffuse Attenuation Coefficient Of Light In Ocean Waters (1986)

A study of the spectral nature of the diffuse attenuation coefficient of light, K(X), for various types of oceanic waters has been performed. These attenuation spectra were computed from downwelling spectral irradiance data Ed(X) obtained by U.S., French, and Japanese in-vestigators working in widely separated oceanic regions and using different measuring techniques and equipment. Attenuation properties were calculated over the spectral region from 365 to 700 nm and for depths from near-surface to in excess of 100 m. Examining the K(X) data, we find that strong, simple, and useful relationships exist between the value of K at some selected reference wavelength, Xo, and the value of K at some other wavelength such that K(X) = M(X) [K(X0)-Kw(X0)] + Kw(X), where Kw is the attenuation coefficient for pure sea water. For oceanic waters (for example, Jerlov types I through III), the relationships are linear. These relationships appear to be useful throughout the entire spectral range examined and are particularly good between 420 and, say, 580 nm. The significance of the existence of such relationships is that they allow the inference of the spectral attenuation coefficient at all wavelengths from the attenuation value at a single wavelength and also provide analytical expressions for modeling the spectral nature of the attenuation in ocean and clear coastal water.
AL-FEC for Improved Mobile Reception of MPEG-2 DVB-T Transport Streams (2009)

We investigate the use of application layer FEC protection in DVB-T (Digital Video Broadcasting-Terrestrial) networks for the provision of mobile services. Mobile reception is characterized by variations of the received signal caused by fast fading and shadowing. DVB-T was originally designed for fixed and portable reception, and generally does not provide enough quality in mobile environments. The link layer protection mechanism MPE-FEC (Multi Protocol Encapsulation-Forward Error Correction) was standardized in DVB-H (Digital Video Broadcasting-Handheld) for the protection of mobile TV services. Although DVB-T itself does not incorporate any link or application layer protection mechanism, AL-FEC (Application layer Forward Error Correction) protection can be introduced in DVB-T in a backwards compatible way. By means of AL-FEC, it is possible to improve the robustness of DVB-T services for the provision of mobile TV. In this paper, we explain the concept of AL-FEC protection in DVB-T and evaluate its performance by means of laboratory measurements and dynamic simulations with shadowing. We study different configurations of AL-FEC and compare its performance with MPE-FEC. In this paper, we discuss some implementation aspects of AL-FEC in real scenarios and propose an implementation based on Raptor codes and hash sequences. We also present results obtained by a first AL-FEC prototype for DVB-T that demonstrates the feasibility of the approach.
Cytokines in pancreatic carcinoma (2004)

Circulating levels of several cytokines were high in patients with pancreatic carcinoma, and their association with weight loss and poor performance status suggested that they may be involved in these disease manifestations. Furthermore, serum cytokine levels, in particular IL-6, may be a useful prognostic marker.
On the data model and access method of summary data management (1989)

A data model and an access method for summary data management are presented. Summary data, represented as a trinary tuple (statistical function, category, summary), are metaknowledge summarized by a statistical function of a category of individual information typically stored in a conventional database. For instance, (average-income, female engineer with 10 years' experience and master's degree, $45000) is a summary datum. The computational complexity of the derivability problem has been found intractable in general, and the proposed summary data model, enforcing the disjointness constraint, alleviates the intractable problem without loss of information. In order to store, manage, and access summary data, a multidimensional access method called summary data (SD) tree is proposed. By preserving the category hierarchy, the SD tree provides for efficient operations, including summary data search, derivation, insertion, and deletion.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effect of Lung-Volume–Reduction Surgery in Patients with Severe Emphysema (2000)

In selected patients with severe emphysema, lung-volume-reduction surgery can improve FEV1, walking distance, and quality of life. Whether it reduces mortality is uncertain.
Microcarriers Designed for Cell Culture and Tissue Engineering of Bone (2012)

Microspherical particulates have been an attractive form of biomaterials that find usefulness in cell delivery and tissue engineering. A variety of compositions, including bioactive ceramics, degradable polymers, and their composites, have been developed into a microsphere form and have demonstrated the potential to fill defective bone and to populate tissue cells on curved matrices. To enhance the capacity of cell delivery, the conventional solid form of spheres is engineered to have either a porous structure to hold cells or a thin shell to in-situ encapsulate cells within the structure. Microcarriers can also be a potential reservoir system of bioactive molecules that have therapeutic effects in regulating cell behaviors. Due to their specific form, advanced technologies to culture cell-loaded microcarriers are required, such as simple agitation or shaking, spinner flask, and rotating chamber system. Here, we review systematically, from material design to culture technology, the microspherical carriers used for the delivery of cells and tissue engineering, particularly of bone.
Unified single-cell analysis of testis gene regulation and pathology in 5 mouse strains (2018)

Abstract By removing the confounding factor of cellular heterogeneity, single cell genomics can revolutionize the study of development and disease, but methods are needed to simplify comparison among individuals. To develop such a framework, we assayed the transcriptome in 62,600 single cells from the testes of wildtype mice, and mice with gonadal defects due to disruption of the genes Mlh3 , Hormad1 , Cul4a or Cnp . The resulting expression atlas of distinct cell clusters revealed novel markers and new insights into testis gene regulation. By jointly analysing mutant and wildtype cells using a model-based factor analysis method, SDA, we decomposed our data into 46 components that identify novel meiotic gene regulatory programmes, mutant-specific pathological processes, and technical effects. Moreover, we identify, de novo , DNA sequence motifs associated with each component, and show that SDA can be used to impute expression values from single cell data. Analysis of SDA components also led us to identify a rare population of macrophages within the seminiferous tubules of Mlh3-/- and Hormad1-/- testes, an area typically associated with immune privilege. We provide a web application to enable interactive exploration of testis gene expression and components at http://www.stats.ox.ac.uk/~wells/testisAtlas.html
Specific immunosuppressive effects of constant infusion of 2'-deoxycoformycin. (1981)

The effect of continuous infusion into C57BL/6J mice of 2'-deoxycoformycin (DCF), a tight-binding inhibitor of adenosine deaminase, on the biological function of bone marrow stem cells and T- and B-lymphocytes was evaluated. Greater than 85% inhibition of adenosine deaminase in erythrocytes, thymus, and bone marrow was noted after DCF infusion at 0.4 mg per kg body weight per day, while lesser extents of inhibition were characteristic of spleen and lymph nodes. The reconstitution of lethally irradiated C57BL/6J mice with bone marrow cells from DCF- and 0.9% NaCl infused mice of the same strain was compared. The two groups of animals were virtually identical with respect to (a) the number of spleen colony-forming units, (b) the response of splenic lymphocytes to both B- and T-cell mitogens, (c) hematological analysis of peripheral blood elements, and (d) survival time, thus strongly supporting the lack of effect of DCF infusion on the capacity of stem cells to differentiate. In contradistinction, DCF infusion was highly lymphocytotoxic as noted by the severe necrosis in both B- and T-cell regions in lymph nodes and spleen and by the dramatic weight reduction in spleen and thymus. Histopathology of other tissues including bone marrow was normal except for the occurrence of hepatitis. A striking decrease in blastogenesis induced by the mitogens concanavalin A, phytohemagglutinin, and Escherichia coli lipopolysaccharides was also observed after DCF infusion. Consistent with these data, in vitro incubation of bone marrow cells with DCF did not impair the number of spleen colony-forming units produced in lethally irradiated mice. These data suggest a potential use for adenosine deaminase inhibitors in the prevention of graft-versus-host disease in hematopoietic transplantation.
Chemoprevention of carcinogen-induced mammary tumorigenesis by the hybrid polar cytodifferentiation agent, suberanilohydroxamic acid (SAHA). (2000)

Hybrid Polar Cytodifferentiation (HPC) agents represent a novel class of anticancer compounds which act by inducing terminal differentiation and/or apoptosis rather than by cytotoxic action. Among these are HPC agents such as hexamethylenebisacetamide (HMBA) and more potent 2nd generation hybrid/polar compounds such as suberanilohydroxamic acid (SAHA). As of the present, most studies on HPC agents have focused on cancers of the hematopoietic system rather than solid epithelial tumors. The objective of the present study therefore was to assess the chemopreventive action of these two related compounds in the N-methylnitrosourea (NMU)-induced rat mammary tumor model. Female Sprague-Dawley rats were fed diets containing 450 and 900 ppm, SAHA and 1000 and 2000 ppm HMBA, starting one week prior to NMU administration and continued for a period of 18 weeks. Mammary tumor development was monitored by palpation throughout the study, and at termination tumor incidence, number, multiplicity, latency and volume were determined. Weight gain was measured biweekly throughout the study. The salient results were as follows: SAHA at 900 ppm reduced NMU-induced mammary tumor incidence by 40%, total tumors by 66%, mean tumor multiplicity by 43% and mean tumor volume by 78%, with no detectable toxic side effects. HMBA exerted no tumor inhibiting effects at either concentration. This study represents the first demonstration that an HPC agent, namely SAHA, can inhibit the development of a chemically-induced, solid, epithelial tumor, at a relatively low dose (approximately 13 mgs/rat/day) without untoward side effects.
A platform for scalable one-pass analytics using MapReduce (2011)

Today's one-pass analytics applications tend to be data-intensive in nature and require the ability to process high volumes of data efficiently. MapReduce is a popular programming model for processing large datasets using a cluster of machines. However, the traditional MapReduce model is not well-suited for one-pass analytics, since it is geared towards batch processing and requires the data set to be fully loaded into the cluster before running analytical queries. This paper examines, from a systems standpoint, what architectural design changes are necessary to bring the benefits of the MapReduce model to incremental one-pass analytics. Our empirical and theoretical analyses of Hadoop-based MapReduce systems show that the widely-used sort-merge implementation for partitioning and parallel processing poses a fundamental barrier to incremental one-pass analytics, despite various optimizations. To address these limitations, we propose a new data analysis platform that employs hash techniques to enable fast in-memory processing, and a new frequent key based technique to extend such processing to workloads that require a large key-state space. Evaluation of our Hadoop-based prototype using real-world workloads shows that our new platform significantly improves the progress of map tasks, allows the reduce progress to keep up with the map progress, with up to 3 orders of magnitude reduction of internal data spills, and enables results to be returned continuously during the job.
Three-dimensional models of four mouse mast cell chymases. Identification of proteoglycan binding regions and protease-specific antigenic epitopes. (1993)

Mouse mast cell protease (mMCP) 1, mMCP-2, mMCP-4, and mMCP-5 are serine proteases which are predicted to have chymotryptic specificity (chymases). They are bound to negatively charged heparin or chondroitin sulfate proteoglycans and are stored in secretory granules. Three-dimensional (3D) models of these four proteases were constructed with a comparative molecular modeling technique based on satisfaction of spatial constraints. The models were used to predict immunogenic epitopes and surface regions that are likely to interact with proteoglycans. Nine potential antigenic segments in the four chymases were identified on the basis of solvent accessibility, protrusion, flexibility, and sequence variability. These segments are suitable epitopes for preparation of protease-specific antipeptide immunoglobulin. Two regions with net charges ranging from +6 to +10 at neutral pH were found on the surfaces of mMCP-4 and mMCP-5. The two regions are located far from the substrate binding cleft at diametrically opposite ends of the folded proteases. A strong positive electrostatic potential surrounds the two regions. Thus, they are good candidates for binding sites that interact with heparin proteoglycan in the granules of serosal mast cells. In contrast, mMCP-1 and mMCP-2, which are present in granules of mucosal mast cells that contain chondroitin sulfate, lack one of these regions and have a lower charge density in the other. The differences between the 3D models provide a structural basis for the selective localization of specific chymases within mouse mast cells that contain different proteoglycans.