gebhart/patrepeval huggingface dataset:
The role of cholesterol metabolism and cholesterol transport in carcinogenesis: a review of scientific findings, relevant to future cancer therapeutics (2013)

While the unique metabolic activities of malignant tissues as potential targets for cancer therapeutics has been the subject of several recent reviews, the role of cholesterol metabolism in this context is yet to be fully explored. Cholesterol is an essential component of mammalian cell membranes as well as a precursor of bile acids and steroid hormones. The hypothesis that cancer cells need excess cholesterol and intermediates of the cholesterol biosynthesis pathway to maintain a high level of proliferation is well accepted, however the mechanisms by which malignant cells and tissues reprogram cholesterol synthesis, uptake and efflux are yet to be fully elucidated as potential therapeutic targets. High and low density plasma lipoproteins are the likely major suppliers of cholesterol to cancer cells and tumors, potentially via receptor mediated mechanisms. This review is primarily focused on the role(s) of lipoproteins in carcinogenesis, and their future roles as drug delivery vehicles for targeted cancer chemotherapy.
Characterization of E coli Hfq structure and its RNA binding properties (2005)

Hfq is a bacterial RNA-binding protein recently shown to contain the Sm motif, a characteristic of Sm proteins that function in RNA processing in archaea and eukaryotes. Hfq plays a major role in RNA-RNA interactions regulating translation. Comparative structural modeling and amino acid sequence alignment were used to predict the 3-D structure of Hfq and the model was in excellent agreement with the crystal structure which determined for S. aureus Hfq. The evolution of Hfq was explored by a BLAST search of microbial genomes followed by phyletic analysis. About half of the genomes examined contain at least one gene coding for Hfq. The presence and absence of Hfq closely followed major bacterial clades. The potential RNA binding residues on the two surfaces of the Hfq hexamer were proposed based on the bioinformatics studies and the mutant Hfq proteins with either single or double mutations on the two surfaces of the Hfq hexamer were generated. Their RNA binding properties was biophysically studied by gel-shift assay, fluorescence anisotropy and fluorescence quenching techniques. Results indicated that 1) point mutations on the distal surface of the Hfq hexamer, Y25A and K31A, have a major effect on A18 binding. Both reduce binding by about 1000 fold. Mutations on the proximal surface have a small or no influence on A18 binding. 2) Two mutations, F39A and R16A, on the proximal surface of the Hfq structure reduce binding to the DsrA domain II by 10 fold. Other mutations reduce binding by less than 2 fold. 3) An amino acid covariance was observed in L12 and F39. Mutation L12F can partially restore F39A in DsrA RNA binding. 4) It appears that two Hfq hexamers cooperatively bind one RNA for both DsrADII and A18.
Historical Conceptions of Dissociation and Psychosis: Nineteenth and Early Twentieth Century Perspectives on Severe Psychopathology (2008)

This chapter contains sections titled: Dissociation: Mesmerism, multiple personalities and hysteria Psychosis: Insanity, dementia praecox and schizophrenia Dissociation, psychosis and schizophrenia: The merging of constructs Conclusion References
Subcutaneous self-administration of highly purified follicle stimulating hormone and human chorionic gonadotrophin for the treatment of male hypogonadotrophic hypogonadism. Spanish Collaborative Group on Male Hypogonadotropic Hypogonadism (1997)

The efficacy and safety of highly purified follicle stimulating hormone (FSH) associated with human chorionic gonadotrophin (HCG) was studied in 60 men with hypogonadotrophic hypogonadism. Of these men, 16 suffered from Kallmann's syndrome, 19 from idiopathic hypogonadotrophic hypogonadism and 25 from hypopituitarism. Basal testosterone concentrations were found to be far below the normal range. At baseline, 26 patients were able to ejaculate and all of them showed azoospermia, while the remaining patients were aspermic. All patients self-administered s.c. injections of FSH (150 IU x three/week) and HCG (2500 IU x two/week) for at least 6 months and underwent periodic assessments of testicular function. Testosterone concentrations increased rapidly during treatment and all but one patient reached normal values. Testicular volume showed a sustained increase reaching almost 3-fold its baseline value. At the end of treatment, 48 patients (80.0%) had achieved a positive sperm count. The maximum sperm concentration during treatment was 24.5 +/- 8.1 x 10(6)/ml (mean +/- SEM). The median time to induce spermatogenesis was 5 months. Eleven patients reported adverse events, generally not related to treatment. Three patients experienced gynaecomastia. No local reactions at injection site were observed. In conclusion, the s.c. self-administration of highly purified FSH + HCG was well tolerated and effective in stimulating spermatogenesis and steroidogenesis in these patients.
Macromolecular Engineering by Atom Transfer Radical Polymerization (2014)

This Perspective presents recent advances in macromolecular engineering enabled by ATRP. They include the fundamental mechanistic and synthetic features of ATRP with emphasis on various catalytic/initiation systems that use parts-per-million concentrations of Cu catalysts and can be run in environmentally friendly media, e.g., water. The roles of the major components of ATRP--monomers, initiators, catalysts, and various additives--are explained, and their reactivity and structure are correlated. The effects of media and external stimuli on polymerization rates and control are presented. Some examples of precisely controlled elements of macromolecular architecture, such as chain uniformity, composition, topology, and functionality, are discussed. Syntheses of polymers with complex architecture, various hybrids, and bioconjugates are illustrated. Examples of current and forthcoming applications of ATRP are covered. Future challenges and perspectives for macromolecular engineering by ATRP are discussed.
ChemInform Abstract: VERDAZYLS, 24. TETRAKIS(4‐(3‐TERT‐BUTYL‐5‐PHENYLVERDAZYL‐1‐YL)PHENYL)METHANE, A TETRARADICAL (1976)

Abstract Tetraphenylmethan (I) wird mit rauchender Salpetersäure zu dem Derivat (IIa) nitriert, dessen katalytische Hydrierung das Tetramin (IIb) liefert.
FDA approves new kind of lymphoma treatment. Food and Drug Administration. (1997)

The Food and Drug Administration (FDA) approved rituximab (Rituxan) for treating patients with relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkin's lymphoma. The November 26 action was the first approval of a monoclonal antibody to treat cancers. The drug has not yet been tested in persons with HIV, although trials are now being organized. Rituximab, given in four doses over a 22-day period, works by killing B-cells, and appears to work well in combination with standard chemotherapy. Rituximab may be toxic if used as initial chemotherapy; its use follows other treatments that reduce the tumor burden. The cost of the treatment is about $11,000, and may be covered by some insurance policies. The drug was discovered by IDEC Pharmaceuticals and Genetech, Inc. Genetech has established programs to help patients with reimbursement problems and drug accessibility.
Evolving Treatment Paradigms for Chemotherapy-Induced Nausea and Vomiting (2012)

Background Chemotherapy-induced nausea and vomiting (CINV) is one of the most debilitating toxicities associated with cancer treatment. Although effective antiemetic agents are available, their use in practice often is suboptimal. Methods The author reviews the pathophysiology of CINV as well as the drug classes and cost considerations that should be incorporated into treatment planning. Results Several drug classes, including 5-hydroxytryptamine-3 receptor antagonists, neurokinin-1 receptor antagonists, and corticosteroids, are effective, especially when used in combination. Older antiemetic agents, such as prochlorperazine and metoclopramide, as well as olanzapine may provide reasonable alternatives in certain settings. Conclusions Interventions for CINV should include standard-of-care antiemetics combined with corticosteroids. The cost of using older, less expensive antiemetics may be outweighed by the expenditures to rescue patients after suboptimal prophylaxis, as well as the indirect costs of missed work and lost productivity.
Isolation and partial characterisation of ACV synthetase from Cephalosporium acremonium and Streptomyces clavuligerus. Evidence for the presence of phosphopantothenate in ACV synthetase. (1991)

delta-(L-alpha-Aminoadipoyl)-L-cysteinyl-D-valine (ACV) synthetase was isolated and partially characterised from Cephalosporium acremonium CO728 and Streptomyces clavuligerus. The purification procedure resulted in a 745- and 277-fold increase in specific enzyme activity, respectively. Both enzymes had similar apparent molecular masses of ca. 300 kdaltons by SDS-polyacrylamide electrophoresis, under reducing and denaturing conditions, and in excess of 600 kdaltons in the native state by gel filtration. Attempts to obtain an N-terminal amino acid sequence of ACV synthetase from C. acremonium were unsuccessful, hence internal amino acid sequence data were obtained after tryptic digestion of the protein. Phosphopantothenic acid was shown to be associated with the enzyme from both sources, which suggests the possible involvement of pantothenate as a 'swinging arm' in the formation of the tripeptide ACV.
New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. (1998)

Increasing knowledge about the biology of the non-Hodgkin's lymphomas has led to new approaches in classification. Rather than grouping lymphomas simply based on cell size, cell shape, and growth pattern, it is now possible to identify distinctive clinicopathologic entities. In many cases, the existence of specific immunologic and/or genetic features has confirmed the existence of these distinctive types of lymphoma. Since patients will be given these diagnoses by pathologists, it is important that clinicians be knowledgeable with regard to their clinical characteristics. The findings for the 13 most common lymphoma types that will be encountered in clinical practice are presented here.
Progestogens in hormonal replacement therapy: new molecules, risks, and benefits (2002)

While the benefits of progestogen use in hormone replacement therapy (HRT) are well recognized as far as endometrial protection is concerned, their risks and drawbacks have generated controversial articles. Several risks are attributed to progestogens as a class-effect; however, the progestogens used in HRT have varying pharmacological properties and do not induce the same side effects. Natural progesterone (P) and some of its derivatives, such as the 19-norprogesterones (Nestorone, nomegestrol acetate, trimegestone), do not bind to the androgen receptor and, hence, do not exert androgenic side effects. Newly synthesized molecules such as drospirenone or dienogest have no androgenic effect but do have a partial antiandrogenic effect. Drospirenone derives from spironolactone and binds to the mineralocorticoid receptor. When the cardiovascular risk factors are considered, some molecules with a higher androgenic potency than others attenuate the beneficial effects of estrogens on the lipid profile as well as the vasomotion. On the other hand, other progestogens devoid of androgenic properties do not exert these deleterious effects. The epidemiological data do not suggest any negative effect of the progestogens administered together with estrogens on cardiovascular morbidity or mortality. However, recent results suggest that in women with established coronary heart disease, HRT may not protect against further heart attacks when the progestogen selected possesses androgenic properties. The data related to the progestogen effect on breast tissue has been interpreted differently from country to country. However, it has been admitted that, according to the type of progestogen used and the dose and duration of its application, a predominant antiproliferative effect is observed in the human breast cells. As far as breast cancer risk is concerned, most epidemiological studies do not suggest any significant difference between the estrogens given alone or combined with progestogens in HRT. Complying with the classic contraindications of HRT and selecting molecules devoid of estrogenic, androgenic, or glucocorticoid effect should allow a larger use of the progestins without any major drawback.
A Linear Programming Based Tone Injection Algorithm for PAPR Reduction of OFDM and Linearly Precoded Systems (2013)

This work investigates the improvement of power amplifier efficiency through the reduction of peak-to-average power ratio (PAPR) of linearly precoded QAM data signals. In particular, we focus on the special cases of linear precoded modulation including the practical OFDM, OFDMA, and SC-FDMA signals that have been widely adopted in W-LAN and W-MAN. We apply the method of tone injection optimization for PAPR reduction. To reduce numerical complexity, we propose a linear programming algorithm which closely approximates the original tone injection optimization problem. Our comprehensive numerical results demonstrate substantial PAPR reduction and superior BER performance using several practical examples.
DCU-Symantec Submission for the WMT 2012 Quality Estimation Task (2012)

This paper describes the features and the machine learning methods used by Dublin City University (DCU) and SYMANTEC for the WMT 2012 quality estimation task. Two sets of features are proposed: one constrained, i.e. respecting the data limitation suggested by the workshop organisers, and one unconstrained, i.e. using data or tools trained on data that was not provided by the workshop organisers. In total, more than 300 features were extracted and used to train classifiers in order to predict the translation quality of unseen data. In this paper, we focus on a subset of our feature set that we consider to be relatively novel: features based on a topic model built using the Latent Dirichlet Allocation approach, and features based on source and target language syntax extracted using part-of-speech (POS) taggers and parsers. We evaluate nine feature combinations using four classification-based and four regression-based machine learning techniques. 1
Time-referenced single-path multi-bit ΔΣ ADC using a VCO based quantizer (2003)

In this paper, we present a novel single-path multi-bit delta-sigma analog-to-digital converter (/spl Delta//spl Sigma/ ADC) architecture that uses time as a reference for performing multi-bit digital-to analog conversion in the feedback path. The architecture uses a voltage-controlled oscillator (VCO) as a multi-bit quantizer. In the feedback path of the /spl Delta//spl Sigma/ ADC, the errors due to component mismatch are avoided by using a single-path for all the levels in a multi bit digital to-analog converter (DAC). The technique eliminates the need for feedback DAC architectures with static and dynamic component matching.
Improved red blood cell preservation correlates with decreased loss of bands 3, 4.1, acetylcholinestrase, and lipids in microvesicles (1996)

In earlier studies we have shown that a final concentration of 0.69% glycerol in blood mixed with an experimental additive solution, EAS 25, improves the in vitro quality and in vivo survival of red blood cells (RBCs). The objective of this study was to determine if the better preservation of RBCs in EAS 25 is correlated with the improved maintenance of membrane lipids and proteins and decreased vesiculation. Split units of RBCs were stored in Adsol or EAS 25 (mmol/L: adenine 2/2, dextrose 122/110, mannitol 42/55, glycerol 0/150, NaCl 154/50). After 12 weeks storage, RBC and microvesicle membranes were analyzed for cholesterol, phospholipid, diphenyl hexatriene fluorescence anisotropy, and acetylcholinesterase (AchE) activity. Bands 3 and 4.1 were identified in the microvesicle membranes by immunoblotting. The RBC membrane cholesterol, phospholipids, and AchE remained higher in EAS 25 than in Adsol (P < .001). Vesicle membrane lipids and AchE in EAS 25 were significantly less than in Adsol (P < .001). The fluidity of stored cells in both the solutions was greater than the prestorage samples. Immunoblotting analyses showed that bands 3 and 4.1 were greatly reduced in the microvesicle membranes shed by the RBCs stored in EAS 25 compared with those formed in Adsol.
Hematopoietic Stem Cell Emergence in Embryonic Life: Developmental Hematology Revisited (1996)

In utero, hematopoiesis takes place initially in the extraembryonic yolk sac, then switches to the liver, thymus, and, finally, bone marrow. This chronologic sequence and the fact that all blood-forming tissues but the yolk sac sustain hematopoiesis after colonization by stem cells of external origin have led to the hypothesis that the whole prenatal and postnatal blood system is founded by yolk sac-derived stem cells. Experimental data recently obtained from bird and mouse embryo models strongly suggest, however, that definitive hematopoiesis is established from an intraembryonic source of stem cells arising in the vicinity of the developing aorta. In agreement, an abundant population of CD34+ primitive hematopoietic cells has been identified in the equivalent area of the human embryo. These novel findings will contribute to our understanding of blood cell homeostasis and may help to further develop therapeutic protocols making use of fetal hematopoietic cells transplanted in utero or in postnatal life.
Utilization of Endoscopic Inoculation in a Mouse Model of Intrauterine Infection-Induced Preterm Birth: Role of Interleukin 1β1 (1999)

A novel murine model of intrauterine infection/inflammation-induced preterm birth based on direct endoscopic intracervical inoculation is described. Using this model, we investigated infection-induced premature pregnancy loss in normal and interleukin (IL) 1beta-deficient mice. Seventy-four CD-1, HS, C57BL/6J wild type (IL-1beta+/+), and C57BL/6J IL-1beta-deficient (IL-1beta-/-) mice were inoculated intracervically using a micro-endoscope, at a time corresponding to 70% of average gestation. Intracervical injection of lipopolysaccharide (LPS) or Escherichia coli reliably induced premature birth: 100% of mice intracervically injected with LPS and 92% of mice with a positive endometrial E. coli culture delivered prematurely within 36 h after inoculation. No losses were observed in mice inoculated with saline. Pregnancy loss was associated with increased uterine tissue cyclooxygenase-2 gene expression and uterine content of IL-1beta, tumor necrosis factor alpha, macrophage inflammatory protein-1alpha, and IL-6, as well as elevation of nuclear factor-kappaB activity in uterine tissues. Although IL-1beta-/- mice exhibited decreased uterine cytokine production in response to bacteria and LPS, IL-1beta deficiency did not affect the rate of pregnancy loss. This model using direct intracervical bacterial or LPS inoculation is useful for studying preterm pregnancy loss in genetically altered mice in order to develop novel interventions for infection-associated preterm labor.
Intracellular calcium regulates basolateral potassium channels in a chloride-secreting epithelium. (1985)

The two individual cell membranes of epithelia are functionally coupled, so that changes in apical membrane conductance are paralleled by changes in basolateral K+ conductance. However, the signal that regulates basolateral K+ conductance, thereby coupling the two membranes, is unknown. We tested the hypothesis that the cellular calcium concentration, [Ca2+]c, may regulate basolateral K+ conductance in canine tracheal epithelium, a Cl- -secreting epithelium that shows marked membrane coupling. Three findings support the hypothesis. First, the intracellular Ca2+ antagonist 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) attenuated the secretory response. Second, the secretagogue epinephrine increased [Ca2+]c, as measured with quin-2. Third, we found a K+ channel that was activated by Ca2+ on the cytosolic side of the membrane. Thus, cytosolic Ca2+ regulates the basolateral K+ conductance and may be the signal responsible for functional coupling of the two cell membranes.
The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies (2007)

Recombinant versions of the seven equine IgG subclasses were expressed in CHO cells. All assembled into intact immunoglobulins stabilised by disulphide bridges, although, reminiscent of human IgG4, a small proportion of equine IgG4 and IgG7 were held together by non-covalent bonds alone. All seven IgGs were N-glycosylated. In addition IgG3 appeared to be O-glycosylated and could bind the lectin jacalin. Staphylococcal protein A displayed weak binding for the equine IgGs in the order: IgG1>IgG3>IgG4>IgG7>IgG2=IgG5>IgG6. Streptococcal protein G bound strongly to IgG1, IgG4 and IgG7, moderately to IgG3, weakly to IgG2 and IgG6, and not at all to IgG5. Analysis of antibody effector functions revealed that IgG1, IgG3, IgG4, IgG5 and IgG7, but not IgG2 and IgG6, were able to elicit a strong respiratory burst from equine peripheral blood leukocytes, predicting that the former five IgG subclasses are able to interact with Fc receptors on effector cells. IgG1, IgG3, IgG4 and IgG7, but not IgG2, IgG5 and IgG6, were able to bind complement C1q and activate complement via the classical pathway. The differential effector function capabilities of the subclasses suggest that, for maximum efficacy, equine vaccine strategies should seek to elicit antibody responses of the IgG1, IgG3, IgG4, and IgG7 subclasses.
Systematic pan-cancer analysis of tumour purity (2015)

The tumour microenvironment is the non-cancerous cells present in and around a tumour, including mainly immune cells, but also fibroblasts and cells that comprise supporting blood vessels. These non-cancerous components of the tumour may play an important role in cancer biology. They also have a strong influence on the genomic analysis of tumour samples, and may alter the biological interpretation of results. Here we present a systematic analysis using different measurement modalities of tumour purity in >10,000 samples across 21 cancer types from the Cancer Genome Atlas. Patients are stratified according to clinical features in an attempt to detect clinical differences driven by purity levels. We demonstrate the confounding effect of tumour purity on correlating and clustering tumours with transcriptomics data. Finally, using a differential expression method that accounts for tumour purity, we find an immunotherapy gene signature in several cancer types that is not detected by traditional differential expression analyses.
IntracellularStaphylococcus aureus (2003)

Staphylococcus aureus is the bacterial pathogen which is responsible for approximately 80% of all cases of human osteomyelitis. It can invade and remain within osteoblasts. The fate of intracellular Staph. aureus after the death of the osteoblast has not been documented. We exposed human osteoblasts to Staph. aureus. After infection, the osteoblasts were either lysed with Triton X-100 or trypsinised. The bacteria released from both the trypsinised and lysed osteoblasts were cultured and counted. Colonies of the recovered bacteria were then introduced to additional cultures of human osteoblasts. The number of intracellular Staph. aureus recovered from the two techniques was equivalent. Staph. aureus recovered from time zero and 24 hours after infection, followed by lysis/trypsinisation, were capable of invading a second culture of human osteoblasts. Our findings indicate that dead or dying osteoblasts are capable of releasing viable Staph. aureus and that Staph. aureus released from dying or dead osteoblasts is capable of reinfecting human osteoblasts in culture.