gebhart/patrepeval huggingface dataset:
Enforced P-glycoprotein pump function in murine bone marrow cells results in expansion of side population stem cells in vitro and repopulating cells in vivo (2000)

The human multidrug resistance-1 (MDR1) gene product, P-glycoprotein (P-gp), is well known for its ability to confer drug resistance; however, recent evidence suggests that P-gp expression can have more general effects on cellular development. In support of this idea, it was previously shown that retroviral-mediated MDR1 expression in murine bone marrow cells resulted in the expansion of stem cells in culture and in the development of a myeloproliferative syndrome in transplanted mice. It is now reported that MDR1-mediated stem cell expansion is associated with an increase in side population (SP) stem cells, defined by Hoechst dye staining. Transduction of murine bone marrow cells with an MDR1 retroviral vector resulted in an almost 2 log increase in SP cell numbers over 12 days in culture, whereas there was a rapid loss of SP cells from control cultures. Stem cell amplification was not limited to ex vivo expansion cultures but was also evident when MDR1-transduced cells were directly transplanted into irradiated mice. In these cases, stem cell expansion was associated with relatively high vector copy numbers in stem cell clones. As previously reported, some cases were associated with a characteristic myeloproliferative syndrome. A functionally inactive MDR1 mutant cDNA was used to show that P-gp pump function was required both for amplification of phenotypically defined SP cells and functionally defined repopulating cells. These studies further support the concept that ABC transporter function can have important effects on hematopoietic stem cell development.
On the importance of initialization and momentum in deep learning (2013)

Deep and recurrent neural networks (DNNs and RNNs respectively) are powerful models that were considered to be almost impossible to train using stochastic gradient descent with momentum. In this paper, we show that when stochastic gradient descent with momentum uses a well-designed random initialization and a particular type of slowly increasing schedule for the momentum parameter, it can train both DNNs and RNNs (on datasets with long-term dependencies) to levels of performance that were previously achievable only with Hessian-Free optimization. We find that both the initialization and the momentum are crucial since poorly initialized networks cannot be trained with momentum and well-initialized networks perform markedly worse when the momentum is absent or poorly tuned. Our success training these models suggests that previous attempts to train deep and recurrent neural networks from random initializations have likely failed due to poor initialization schemes. Furthermore, carefully tuned momentum methods suffice for dealing with the curvature issues in deep and recurrent network training objectives without the need for sophisticated second-order methods. 1.
MRI in lung cancer: a pictorial essay (2011)

Imaging studies play a critical role in the diagnosis and staging of lung cancer. CT and 18-fluorodeoxyglucose positron emission tomography CT (PET/CT) are widely and routinely used for staging and assessment of treatment response. Many radiologists still use MRI only for the assessment of superior sulcus tumours, and in cases where invasion of the spinal cord canal is suspected. MRI can detect and stage lung cancer, and this method could be an excellent alternative to CT or PET/CT in the investigation of lung malignancies and other diseases. This pictorial essay discusses the use of MRI in the investigation of lung cancer.
Quantitative measurement of the reduction of platinum(iv) complexes using X-ray absorption near-edge spectroscopy (XANES) (2012)

The platinum(II) drugs cisplatin, carboplatin and oxaliplatin are usefully employed against a range of malignancies, but toxicities and resistance have spurred the search for improved analogs. This has included investigation of the platinum(IV) oxidation state, which provides greater kinetic inertness. It is generally accepted that Pt(IV) complexes must be reduced to Pt(II) for activation. As such, the ability to monitor reduction of Pt(IV) complexes is critical to guiding the design of candidates, and providing mechanistic understanding. Here we report in full that the white line height of X-ray absorption near-edge spectra (XANES) of Pt complexes, normalized to the post-edge minima, can be used to quantitatively determine the proportion of each oxidation state in a mixture. A series of Pt(IV) complexes based on the Pt(II) complexes cisplatin and transplatin were prepared with chlorido, acetato or hydroxido axial ligands, and studies into their reduction potential and cytotoxicity against A2780 human ovarian cancer cells were performed, demonstrating the relationship between reduction potential and cytotoxicity. Analysis of white line height demonstrated a clear and consistent difference between Pt(II) (1.52 ± 0.05) and Pt(IV) (2.43 ± 0.19) complexes. Reduction of Pt(IV) complexes over time in cell growth media and A2780 cells was observed by XANES, and shown to correspond with their reduction potentials and cytotoxicities. We propose that this method is useful for monitoring reduction of metal-based drug candidates in complex biological systems.
A High Q Cavity Stabilized Gunn Oscillator at 94 GHz (2005)

The set up and the performance of a 94 GHz second harmonic Gunn oscillator that is cavity stabilized at its fundamental frequency is described. The cavity has a quality factor of about 7000 and reduces the phase noise by nearly 40 dB. The oscillator generates an output power of 40 mW, sufficient to drive low noise balanced mixers, to synchronize Impatt oscillators or to operate as a reference source in coherent radar systems.
IL-31 a TH2 Cytokine Involved in Immunity and Inflammation (2010)

Cytokines are immunal regulatory proteins, however they also play a relevant role in inflammatory diseases. IL-31 is a newly discovered cytokine expressed primarily in TH2 cells, introduced by activated CD4+ T cells. IL-31 is capable of inducing chemokines and other cytokines in several inflammatory diseases via its surface receptor. This cytokine is also produced by mast cells and mast cell line, suggesting a role in allergic diseases. In this editorial we revisit the biological role of IL-31 in immunity and inflammation.
Estimation of deduplication ratios in large data sets (2012)

We study the problem of accurately estimating the data reduction ratio achieved by deduplication and compression on a specific data set. This turns out to be a challenging task - It has been shown both empirically and analytically that essentially all of the data at hand needs to be inspected in order to come up with a accurate estimation when deduplication is involved. Moreover, even when permitted to inspect all the data, there are challenges in devising an efficient, yet accurate, method. Efficiency in this case refers to the demanding CPU, memory and disk usage associated with deduplication and compression. Our study focuses on what can be done when scanning the entire data set. We present a novel two-phased framework for such estimations. Our techniques are provably accurate, yet run with very low memory requirements and avoid overheads associated with maintaining large deduplication tables. We give formal proofs of the correctness of our algorithm, compare it to existing techniques from the database and streaming literature and evaluate our technique on a number of real world workloads. For example, we estimate the data reduction ratio of a 7 TB data set with accuracy guarantees of at most a 1% relative error while using as little as 1 MB of RAM (and no additional disk access). In the interesting case of full-file deduplication, our framework readily accepts optimizations that allow estimation on a large data set without reading most of the actual data. For one of the workloads we used in this work we achieved accuracy guarantee of 2% relative error while reading only 27% of the data from disk. Our technique is practical, simple to implement, and useful for multiple scenarios, including estimating the number of disks to buy, choosing a deduplication technique, deciding whether to dedupe or not dedupe and conducting large-scale academic studies related to deduplication ratios.
Stimulation of arterial endothelial cell prostacyclin synthesis by high density lipoproteins. (1982)

Prostacyclin (PGI2) is a vasoactive prostaglandin synthesized by vascular endothelial and smooth muscle cells. In order to investigate whether plasma lipoproteins influence the biosynthesis and release of prostacyclin by vascular tissues, human high density lipoproteins (HDL) and low density lipoproteins (LDL) were incubated with porcine arterial endothelial cells grown in tissue culture. PGI2 production was measured by radioimmunoassay of its stable metabolite, 6-keto-PGF1 alpha. In incubations of HDL with endothelial cells for 24 h, levels of 6-keto-PGF1 alpha in the medium increased significantly in a dose-dependent fashion to values 5-fold above control. This effect was less pronounced in confluent than in subconfluent cultures and did not occur in the presence of an inhibitor of cyclooxygenase. No significant stimulation of 6-keto-PGF1 alpha was observed when the endothelial cells were incubated with LDL. In time course experiments with HDL, 6-keto-PGF1 alpha levels increased continuously over 24 h. Rat HDL, containing a high content of arachidonate in its cholesterol ester fatty acids, caused a 2-4-fold greater release of 6-keto-PGF1 alpha than human HDL. The delipidated apoprotein of both human and rat HDL caused similar stimulation of 6-keto-PGF1 alpha production, but much less than intact HDL. The data indicate that HDL stimulates PGI2 synthesis by cultured arterial endothelial cells, possibly by providing the cells with arachidonate.
Human aldehyde dehydrogenase gene family (1998)

Twelve aldehyde dehydrogenase (ALDH) genes have been identified in humans. These genes, located on different chromosomes, encode a group of enzymes which oxidizes varieties of aliphatic and aromatic aldehydes. Metabolic disorders and clinical problems associated with mutations of ALDH1, ALDH2, ALDH4, ALDH10 and succinic semialdehyde (SSDH) genes have been emerged. Comparison of the human ALDHs indicates a wide range of divergency (> 80 - < 15% identity at the protein sequence level) among them. However, several protein regions, some of which are implicated in functional activities, are conserved in the family members. The phylogenic tree constructed of 56 ALDH sequences of humans, animals, fungi, protozoa and eubacteria, suggests that the present-day human ALDH genes were derived from four ancestral genes that existed prior to the divergence of Eubacteria and Eukaryotes. The neighbor-joining tree derived from 12 human ALDHs and antiquitin indicates that diversification within the ALDH1/2/5/6 gene cluster occurred during the Neoproterozoic period (about 800 million years ago). Duplication in the ALDH 3/10/7/8 gene cluster occurred in Phanerozoic period (about 300 million years ago). Separations of ALDH3/ALDH10 and that of ALDH7/ALDH8 had occurred during the period of appearance and radiation of mammalian species.
Engineering the gut microbiota to treat hyperammonemia (2015)

Increasing evidence indicates that the gut microbiota can be altered to ameliorate or prevent disease states, and engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research. In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease. Here, we engineered murine gut microbiota to reduce urease activity. Animals were depleted of their preexisting gut microbiota and then inoculated with altered Schaedler flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility.
New Syntheses with Oils and Fats as Renewable Raw Materials for the Chemical Industry (2000)

Oils and fats are the most important renewable raw materials for the chemical industry. Hitherto, industrial oleochemistry has concentrated predominantly on the carboxy functionality of fatty acids but, more recently, modern synthetic methods have been applied extensively to fatty compounds for the selective functionalization of the alkyl chain. Radical, electrophilic, nucleophilic, and pericyclic as well as transition metal catalyzed additions to the C-C double bond of, for example, oleic acid as the prototype of a readily accessible, unsaturated fatty acid have led to a large number of novel fatty compounds from which interesting properties are expected. Functionalization of C-H bonds in the alkyl chain is also feasible with remarkable selectivity. Effective and highly versatile catalysts for the metathesis of esters of unsaturated fatty acids have been developed, which lead to new and interesting omega-unsaturated fatty acids. The epoxidation of unsaturated fatty acids has been developed extensively. Enzymatic reactions allow syntheses with high selectivity and yield of mono- and diglycerides and esters of carbohydrates with a variety of surfactant properties. Regio- and enantioselective microbial hydrations and hydroxylations widen the spectrum of selective reactions. Of considerable significance is that, with the use of gene technology, natural oils and fats have been improved significantly and will be improved still further, insofar as they show a more uniform and often unusual fatty acid spectrum. Numerous fatty acids are now available in a purity which makes them attractive for synthesis and as raw materials for the chemical industry.
Increased synovial fluid levels of interleukin-12, sCD25 and sTNF-RII/sTNF-RI ratio delineate a cytokine pattern characteristic of immune arthropathies. (2000)

The assessment of cytokines and their soluble receptors in the synovial fluid (SF) of inflammatory arthropathies may be useful in studying pathogenetic and immunoregulatory mechanisms underlying different diseases. The aim of this work was to study the cytokine network occurring in inflammatory arthropathies and to identify a cytokine profile which is characteristic of an immune-mediated synovitis. Levels of IL-12, as well as IL-4, IL-8, IL-10, IFN-gamma, sCD25, TNF-alpha and its soluble receptors were measured in the SF of various arthropathies, i.e. non-inflammatory arthropathies: "control" meniscus pathology (n = 21), osteoarthritis (n = 22) and chronic crystal arthritis (n = 9); a non-immune inflammatory arthropathy: acute crystal arthritis (n = 11); 2 immune inflammatory arthropathies: reactive arthritis (ReA) (n = 23) and rheumatoid arthritis (RA) (n = 44). SF levels of IL-10, TNF-alpha and sTNF-RII were found to be increased in the three inflammatory arthropathies compared to the "control" meniscus group. Within the inflammatory group, acute crystal arthritis was characterized by a significantly higher sTNF-RI/TNF-alpha ratio and ReA by a significantly lower sTNF-RII/TNF-alpha ratio compared to the two other diseases. The two immune arthropathies, RA and ReA, were characterized by increased SF levels of IL-12, sCD25 and of the sTNF-RII/sTNF-RI ratio. ReA differed however from RA by showing lower IL-8 and IL-4 levels, higher IFN-gamma levels and a higher IL-12/IL-10 ratio, suggesting a more prevalent Th1 profile in ReA SF. Our data indicate that the measurement of SF cytokines and soluble receptors may discriminate between each inflammatory arthropathy and might be useful in clinical practice.
Severely Impaired B Lymphocyte Proliferation, Survival, and Induction of the c-Myc:Cullin 1 Ubiquitin Ligase Pathway Resulting from CD22 Deficiency on the C57BL/6 Genetic Background (2004)

Understanding the molecular mechanisms through which CD22 regulates B lymphocyte homeostasis, signal transduction, and tolerance is critical to defining normal B cell function and understanding the role of CD22 in autoimmunity. Therefore, CD22 function was examined in vivo and in vitro using B cells from CD22-deficient (CD22(-/-)) mice. Backcrossing of founder CD22(-/-) mice onto the C57BL/6 (B6) genetic background from a B6/129 mixed background resulted in a dramatically reduced B cell proliferative response following IgM ligation, characterized by a paucity of lymphoblasts and augmented apoptosis. Also, the phenotype of splenic B6 CD22(-/-) B cells was uniquely HSA(high) and IgD(low)/CD21(low) with intermediate levels of CD5 expression, although the percentages of mature and transitional B cells were normal. That B6 CD22(-/-) B cells predominantly underwent apoptosis following IgM ligation correlated with this unique tolerant phenotype, as well as defective induction of the c-Myc:Cullin 1 (CUL1) ubiquitin ligase pathway that is necessary for progression to the S phase of cell cycle. CD40 ligation compensated for CD22 deficiency by restoring lymphoblast development, proliferation, c-Myc and CUL1 expression, and protein ubiquitination/degradation in IgM-stimulated B6 CD22(-/-) B cell cultures. Thereby, this study expands our current understanding of the complex role of CD22 during B cell homeostasis and Ag responsiveness, and reveals that the impact of CD22 deficiency is dictated by the genetic background on which it is rendered. Moreover, this study defines CD22 and CD40 as the first examples of lymphocyte coreceptors that influence induction of the c-Myc:CUL1 ubiquitin ligase pathway.
The role of conjunctival epithelial cell xanthine oxidoreductase/xanthine oxidase in oxidative reactions on the ocular surface of dry eye patients with Sjögren's syndrome. (2007)

Previous papers examined lipid peroxidase levels and myeloperoxidase activity as products of oxidative and inflammatory reactions in the tear fluid of patients suffering from dry eye. The aim of the present paper was to investigate whether the enzymes xanthine oxidoreductase/xanthine oxidase known to generate reactive oxygen species contribute to oxidative reactions on the ocular surface. Xanthine oxidoreductase/xanthine oxidase were examined immunohistochemically as well as histochemically in conjunctival epithelial cells of patients suffering from dry eye. Patients with verified autoimmune dry eye (Sjögren's syndrome) participated in our study; normal eyes served as controls. Conjunctival epithelial cells were obtained by the method of impression cytology using Millicell membranes. The results revealed a pronounced expression, as well as activity of xanthine oxidoreductase/xanthine oxidase in the conjunctival epithelium of dry eye. It is suggested that reactive oxygen species which are generated by this enzymatic system, contribute to oxidative reactions on the eye surface of patients with ocular manifestations of autoimmune disease (Sjögren's syndrome).
Human Fibroblasts Release Reactive Oxygen Species in Response to Treatment with Synovial Fluids from Patients Suffering from Arthritis (1990)

Human fibroblasts in primary culture released reactive oxygen species upon exposure to synovial fluid obtained by joint aspiration from twelve patients suffering from rheumatoid arthritis. The primary radical produced was O2- as determined by ESR spin trapping and cytochrome c reduction. In contrast to the oxidative burst in granulocytes and monocytes, radical formation proceeded continuously for at least four hours. Low-level chemiluminescence was increased upon exposure to inflammatory human synovial fluids. Spectral characteristics and effects of azide and 1,4-diazabicyclo-(2,2,2)-octane led to the conclusion that the photoemissive species were excited carbonyls. Radical production and light emission were not altered either by xanthine or allopurinol, nor by azide, cyanide or rotenone. The O2- production increased in the presence of NADH or NADPH, making an NAD(P)H oxidase a likely source. The liberation of reactive oxygen species correlated with the number of leukocytes present in the inflammatory joint fluids, but not with the concentrations of immunoglobulins and complement factor C3.
Support vector machines for spam categorization (1999)

We study the use of support vector machines (SVM's) in classifying e-mail as spam or nonspam by comparing it to three other classification algorithms: Ripper, Rocchio, and boosting decision trees. These four algorithms were tested on two different data sets: one data set where the number of features were constrained to the 1000 best features and another data set where the dimensionality was over 7000. SVM's performed best when using binary features. For both data sets, boosting trees and SVM's had acceptable test performance in terms of accuracy and speed. However, SVM's had significantly less training time.
Treatment of Idiopathic Pulmonary Fibrosis with a New Antifibrotic Agent, Pirfenidone: Results of a Prospective, Open-label Phase II Study (1999)

Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of unknown etiology and fatal outcome. Currently available therapies are ineffective and associated with significant adverse effects. Pirfenidone, a new, investigational antifibrotic agent, was evaluated for its tolerability and usefulness in terminally ill patients with advanced IPF. Consecutive patients with IPF and deterioration despite conventional therapy or who were unable to tolerate or unwilling to try conventional therapy were treated with oral pirfenidone. Treatment was administered on a compassionate basis (open-label). Fifty-four patients were followed for mortality, change in lung function, and adverse effects. Their mean age was 62, mean duration of symptoms 4.6 yr, and time since lung biopsy was 3.2 yr. Conventional therapy was discontinued in 38 of 46 patients; the other eight were able to decrease their prednisone dosage and eight had no previous conventional treatment. One- and 2-yr survival was 78% (95% CI 66%, 89%) and 63% (95% CI 50%, 76%), respectively. Patients whose lung functions had deteriorated prior to enrollment appeared to stabilize after beginning treatment. Adverse effects were relatively minor. The results of this study are encouraging. Pirfenidone is a promising new treatment for IPF that is well tolerated.
AP‐1 DNA‐binding activity is inhibited by selenite and selenodiglutathione (1995)

The binding of the transcription factor AP-1 to DNA has been shown to be modulated by redox control mechanisms. Selenite and selenodiglutathione (GS-Se-SG), inhibit mammalian cell growth and are efficient oxidants of reduced thioredoxin and reduced thioredoxin reductase. Here, we report that selenite and GS-Se-SG efficiently inhibited AP-1 DNA-binding in nuclear extracts from 3B6 lymphocytes. A GS-Se-SG concentration of 0.75 microM resulted in 50% inhibition of AP-1 DNA-binding, whereas the same effect was achieved with 7.5 microM selenite. Nuclear extracts prepared from human 3B6 lymphocytes exposed for 4 h to 10 microM selenite showed a 50% reduction of AP-1 binding. These data suggest that selenite and selenodiglutathione inactivate the AP-1 factor and provide a mechanism by which selenium compounds inhibit cell growth.