gebhart/patrepeval huggingface dataset:
Optimum Weighted PCM for Speech Signals (1978)

Weighted digital modulation schemes which provide bit error probabilities matched to the PCM bits with respect to their sensitivity to digital errors are analyzed. The channel is additive, white Gaussian. The PCM system has arbitrary code, companding law and input signal density function. Especially optimum weighted PSK/PCM and QAM/PCM are given for speech signals. The average channel signal to noise ratio is kept constant when schemes are compared. We obtain a channel signal to noise ratio gain in threshold extension of 2 dB for standard 8 bit PCM. The performance of suboptimum schemes, where the number of different bit error probability levels are smaller than the number of PCM bits are also studied. Two levels per 8 bit PCM word yield more than half of the achievable gain (in dB) and 4 levels is almost equal to optimum.
Helicobacter-induced inflammatory bowel disease in IL-10- and T cell-deficient mice (2001)

Inflammatory bowel disease (IBD) is thought to result from a dysregulated mucosal immune response to luminal microbial antigens, with T lymphocytes mediating the colonic pathology. Infection with Helicobacter spp has been reported to cause IBD in immunodeficient mice, some of which lack T lymphocytes. To further understand the role of T cells and microbial antigens in triggering IBD, we infected interleukin (IL)-10(-/-), recombinase-activating gene (Rag)1(-/-), T-cell receptor (TCR)-alpha(-/-), TCR-beta(-/-), and wild-type mice with Helicobacter hepaticus or Helicobacter bilis and compared the histopathological IBD phenotype. IL-10(-/-) mice developed severe diffuse IBD with either H. bilis or H. hepaticus, whereas Rag1(-/-), TCR-alpha(-/-), TCR-beta(-/-), and wild-type mice showed different susceptibilities to Helicobacter spp infection. Proinflammatory cytokine mRNA expression was increased in the colons of Helicobacter-infected IL-10(-/-) and TCR-alpha(-/-) mice with IBD. These results confirm and extend the role of Helicobacter as a useful tool for investigating microbial-induced IBD and show the importance, but not strict dependence, of T cells in the development of bacterial-induced IBD.
PCR : essential techniques (1996)

GENERAL INTRODUCTION: History of PCR Legal Aspects of Performing PCR Choice of Method Conditions Equipment Solutions and Chemicals PCR PROTOCOLS: Enzymology Gene Expression and Cloning Quantitative PCR DNA Sequencing In Vitro Mutagenesis Genetics and Systematics Diagnostics Forensics Detection of PCR Primers Environmental PCR Molecular Archaeology.
Sirt1 Involvement in rd10 Mouse Retinal Degeneration (2009)

The results suggest a link between Sirt1 production and retinal degeneration in rd10 mice. The anti-apoptotic, neuroprotective role of Sirt1 in the mouse retina is based on the involvement of Sirt1 in double DNA strand-break repair mechanisms and in maintaining energy homeostasis in photoreceptor cells. The results suggest that the neuroprotective properties of Sirt1 may gradually weaken in rd10 mouse photoreceptor cells.
New software for lens retro‐illumination digital image analysis (1999)

The RIA software significantly improves the accuracy of cataract measurement in lens images with uneven pupil illumination or confounding opacities. Automation of (i) image loading, (ii) pupil detection and (iii) defining of the opacity area increases the efficiency of digital eye photography, eliminates human errors and speeds assessment.
TNF alpha and IL-1 beta are separate targets in chronic arthritis. (2000)

Chronic arthritis is characterized by persistent joint inflammation and concomitant joint destruction. Using murine arthritis models and neutralizing antibodies as well as cytokine-specific knockout conditions, it was found that tumor necrosis factor alpha (TNF alpha) is important in joint swelling, whereas a direct role in tissue destruction is unlikely. Interleukin-1 (IL-1) is not a dominant cytokine in early joint swelling, but has a pivotal role in sustained cell infiltration and erosive cartilage damage. TNF alpha-independent IL-1 production is a prominent feature in murine arthritis models, implying that IL-1 as well as TNF alpha are appropriate targets for therapy. These observations provide evidence for the potential uncoupling of joint inflammation and erosive changes and underline the need for TNF alpha/IL-1 directed combination-therapy approaches.
Maintenance of Androgen Responsiveness by Glucocorticoids in Shionogi Mammary Carcinoma Cells in Culture1 (1988)

The possibility that glucocorticoids can delay or prevent loss of responsiveness to androgens in androgen-deprived cells was investigated. While a complete loss of responsiveness to dihydrotestosterone (DHT) was observed within 60 days of androgen deprivation, addition of the synthetic glucocorticoid dexamethasone (DEX) delayed both the loss of growth responsiveness to DHT and the increase in spontaneous growth rate by approximately equal to 60 days. When the growth response to DEX was studied, the changes found were similar to those described above for DHT, namely loss of response following steroid deprivation and preservation of response in cells preincubated with DHT or DEX. In addition, long-term incubation in the presence of DEX was accompanied by low-amplitude stimulation of cell growth at extremely low concentrations of DHT and DEX, suggesting that androgen- and glucocorticoid-hypersensitive cell clones developed during androgen deprivation. The present data show that long-term incubation of androgen-sensitive Shionogi cells leads not only to an increase in the spontaneous growth rate, but also to the appearance of androgen- and glucocorticoid-hypersensitive cells, which may well play an important role in the development of resistance to endocrine therapy in human hormone-sensitive cancers. Although it is not as efficient as DHT, the glucocorticoid DEX can delay the loss of androgen sensitivity in this cell line.
Magnetocardiography: current status and perspectives. Part II: Clinical applications. (2002)

Magnetocardiography (MCG) is a non-invasive and risk-free technique allowing body surface recording of the magnetic fields generated by the electrical activity of the heart. The MCG recording system allows spatially and temporally accurate measurements of the very weak magnetic fields produced by currents flowing within myocardial fibers during cardiac activity. MCG has now been around for over 30 years, but only recently has progress in instrumentation put the technique on the verge of clinical applicability. This review summarizes the physical principles, instrumentation, main clinical applications and perspectives for the clinical use of MCG. This second part is devoted to the description of the main current clinical applications and perspectives.
Probes for Detection of Specific DNA Sequences at the Single-Molecule Level (2000)

A method has been developed for highly sensitive detection of specific DNA sequences in a homogeneous assay using labeled oligonucleotide molecules in combination with single-molecule photon burst counting and identification. The fluorescently labeled oligonucleotides are called smart probes because they report the presence of complementary target sequences by a strong increase in fluorescence intensity. The smart probes consist of a fluorescent dye attached at the terminus of a hairpin oligonucleotide. The presented technique takes advantage of the fact that the used oxazine dye JA242 is efficiently quenched by complementary guanosine residues. Upon specific hybridization to the target DNA, the smart probe undergoes a conformational change that forces the fluorescent dye and the guanosine residues apart, thereby increasing the fluorescence intensity about six fold in ensemble measurements. To increase the detection sensitivity below the nanomolar range, a confocal fluorescence microscope was used to observe the fluorescence bursts from individual smart probes in the presence and absence of target DNA as they passed through the focused laser beam. Smart probes were excited by a pulsed diode laser emitting at 635 nm with a repetition rate of 64 MHz. Each fluorescence burst was identified by three independent parameters: (a) the burst size, (b) the burst duration, and (c) the fluorescence lifetime. Through the use of this multiparameter analysis, higher discrimination accuracies between smart probes and hybridized probe-target duplexes were achieved. The presented multiparameter detection technique permits the identification of picomolar target DNA concentrations in a homogeneous assay, i.e., the detection of specific DNA sequences in a 200-fold excess of labeled probe molecules.
Dynamic Contrast-Enhanced Magnetic Resonance Imaging of Vascular Changes Induced by Sunitinib in Papillary Renal Cell Carcinoma Xenograft Tumors (2009)

To investigate further the antiangiogenic potential of sunitinib for renal cell carcinoma (RCC) treatment, its effects on tumor vasculature were monitored by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using an orthotopic KCI-18 model of human RCC xenografts in nude mice. Tumor-bearing mice were treated with various doses of sunitinib, and vascular changes were assessed by DCE-MRI and histologic studies. Sunitinib induced dose-dependent vascular changes, which were observed both in kidney tumors and in normal kidneys by DCE-MRI. A dosage of 10 mg/kg per day caused mild changes in Gd uptake and clearance kinetics in kidney tumors. A dosage of 40 mg/kg per day induced increased vascular tumor permeability with Gd retention, probably resulting from the destruction of tumor vasculature, and also caused vascular alterations of normal vessels. However, sunitinib at 20 mg/kg per day caused increased tumor perfusion and decreased vascular permeability associated with thinning and regularization of tumor vessels while mildly affecting normal vessels as confirmed by histologic diagnosis. Alterations in tumor vasculature resulted in a significant inhibition of KCI-18 RCC tumor growth at sunitinib dosages of 20 and 40 mg/kg per day. Sunitinib also exerted a direct cytotoxic effect in KCI-18 cells in vitro. KCI-18 cells and tumors expressed vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor beta molecular targets of sunitinib that were modulated by the drug treatment. These data suggest that a sunitinib dosage of 20 mg/kg per day, which inhibits RCC tumor growth and regularizes tumor vessels with milder effects on normal vessels, could be used to improve blood flow for combination with chemotherapy. These studies emphasize the clinical potential of DCE-MRI in selecting the dose and schedule of antiangiogenic compounds.
SEROLOGICAL REACTIONS IN PNEUMONIA WITH A NON-PROTEIN SOMATIC FRACTION OF PNEUMOCOCCUS (1930)

1. Sera from individuals acutely ill with lobar pneumonia possess the capacity to precipitate in high titre a non-protein somatic fraction derived from pneumococci (Fraction C). Following crisis the reaction is no longer demonstrable. 2. Sera obtained from cases of pneumococcus pneumonia during illness and convalescence have been tested for antibodies specifically reactive with three chemically distinct constituents of Pneumococcus. The results, when correlated with the course of disease, demonstrate differences in the occurrence of each qualitatively distinct antibody. 3. The precipitation of pneumococcus Fraction C is not limited to the sera of individuals ill with pneumococcus infection. But in the few other cases available for comparative tests, definite reactions have been obtained only in streptococcus and staphylococcus infections and in acute rheumatic fever.
Prasugrel: A Critical Comparison with Clopidogrel (2009)

Thienopyridine antiplatelet drugs have been used for 15 years for the prevention of coronary stent thrombosis in patients undergoing percutaneous coronary intervention with stent placement. Ticlopidine, the first approved thienopyridine, has in large part been replaced by clopidogrel, a more potent and better tolerated thienopyridine. Now, prasugrel, the newest agent, is currently available for use in the United States. Although prasugrel is similar to clopidogrel, it is about 10 times more potent and has a quicker onset of action. Data from the largest trial comparing clopidogrel and prasugrel indicate that this increased potency and quicker onset of prasugrel equate to a reduction in major adverse cardiovascular events, although higher rates of major bleeding were reported. Prasugrel also differs from clopidogrel in that it may be less prone to drug-drug interactions and patient nonresponsiveness, although further research is needed in both of these areas. Given the totality of data available, prasugrel appears to be a promising treatment option for patients with acute coronary syndromes who are undergoing percutaneous coronary interventions.
Advances in Monoclonal Antibody Technology: Genetic Engineering of Mice, Cells, and Immunoglobulins (2005)

The ability to produce antibodies that are directed against specific antigens has played a crucial role in advancing scientific discoveries. Recombinant technologies have extended the application of antibodies beyond the research laboratory and into the clinic for the treatment of cancer and other diseases. Creative approaches using these technologies have been used to reduce the antibody to its minimal functional size, and/or make them bifunctional (immunotoxins), bispecific, or less immunoreactive (humanized). Additionally, mice that are engineered to generate antibodies of human genomic origin have been used to produce therapeutic antibodies and are being further developed. As the research and clinical demands for antibodies continue to increase, the development of improved resources (cell lines and animals) to improve production efficiency, generate larger repertoires, and deliver greater yields of antibodies is being explored, and advances in this area are discussed further in this review.
Transplantation of Cartilagenous Tissue Generated in Vitro Into Articular Joint Defects (1995)

The purpose of this pilot study was to determine whether isolated rabbit chondrocytes will form cartilagenous tissue in culture and whether this tissue can be used as a cartilage transplant in order to resurface damaged joints. Chondrocytes were isolated from rabbit articular cartilage, plated as a monolayer on Millicell-CMR filters and maintained in cell culture. The cells formed cartilagenous tissue that could be removed from the filter support by two weeks in culture. The chondrocytes synthesize type II collagen indicating that they maintained their phenotype under these conditions. For the transplant studies, two types of articular surface defects, either full thickness into subchondral bone or intra-chondral, were created in rabbits. The cartilagenous tissue was placed in the defect either without fixation or with the topical application of an adhesive agent (Cell-Tak or Nexaband Avian). The joints were examined within two weeks following the surgery. No transplants remained in the defects in those animals in which tissue fixation had been attempted with Cell-Tak. Those grafts fixed into the cartilage defect with Nexaband Avian remained in place but consisted of a condensed layer of acellular tissue. However, cartilagenous tissue was present and intact in five of the six animals in which the transplant had been placed, in the absence of adhesive, into a full thickness defect. In conclusion, cartilagenous tissue generated in vitro can survive transplantation but an appropriate method to fix grafts into intra-chondral defects is required.
Interstitial Fluid Pressure in Tumors: Therapeutic Barrier and Biomarker of Angiogenesis (2008)

Interstitial fluid pressure is elevated in virtually all solid malignant tumors as a result of abnormalities of the vasculature and interstitium. High interstitial fluid pressure is an independent predictor of disease recurrence in cervical cancer patients treated with radiotherapy, has been implicated as an important factor that impairs the delivery of chemotherapy to tumors and may influence the regulation and distribution of cytokines and growth factors. Targeted molecular treatments that inhibit angiogenesis or alter interstitial fluid dynamics also produce early reductions in interstitial fluid pressure. Reductions in interstitial fluid pressure due to anti-angiogenic treatment have been associated with improved therapeutic outcome in preclinical studies when these agents are combined with radiotherapy or conventional cytotoxic chemotherapy. Pretreatment interstitial fluid pressure and the change in pressure during treatment may provide important predictive information that in the future will be used to optimize therapy in individual patients.
Erfahrungen mit D2E7 (2000)

D2E7 is a fully human antibody against TNFα the sequence of which is entirely derived from the genome of human lymphocytes. Therefore, it should be less immunogenic for the recipient than chimaeric and "humanised" antibodies and soluble receptor constructs currently in use. In a clinical phase-1 study (DE001/003) in 120 patients with long-lasting "refractory" active rheumatoid arthritis (disease duration 11.5 years, disease activity score [DAS] 5.32) D2E7 was given in doses of 0.5-10 mg/kg D2E7 i.v. over 3-5 minutes every two weeks over a time period of now 1œ years and resulted in an impressive statistically significant and long-lasting reduction of disease activity (moderate DAS response in 80%, decrease in the number of swollen and tender joints and the ESR >50%) with all doses > 1 (3) mg/kg body weight. The tolerability was good. In a further phase-1 study (DE004) in 24 patients with long-lasting (10.1 years) "refractory" (3.4 DMARDs) RA 0.5 mg/kg body weight D2E7 s.c. over 12 weeks resulted in a moderate DAS response in 78% of patients but in no patients on placebo. 283 patients (disease duration 8 years, CRP 51 mg/l, 4 previous DMARDs) were treated with weekly 20, 40, 80 mg D2E7 s.c. or placebo in a 4-arm randomised phase-2 study. After 12 weeks an improvement of the CRP and the number of swollen joints > 60 % was reached, significantly (p < 0.001) superior to placebo. In patients with incomplete response to methotrexate (median 15 mg/week) 18 patients each received 1 mg/kg D2E7 i.v. or 1mg/kg D2E7 s.c. or placebo. Within the first 4 weeks 28 % of patients on placebo, 45 % (s.c.) and 72% (i.v.), respectively, reached a DAS response. 66 patients of the study DE003 with a complete set of X-rays at baseline, after 6 and 12 months showed no progression in the Ratingen score and the Sharp score when scored blinded as to patient identity and chronological sequence of the films. 22 of these patients from Ratingen had X-rays a mean of 18 months before baseline. They showed a significant radiographic progression during this pre-treatment period. Without doubt D2E7 has improved the options in the treatment of severe rheumatoid arthritis.
Increased Insulin Sensitivity and Obesity Resistance in Mice Lacking the Protein Tyrosine Phosphatase-1B Gene (1999)

Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity.
Effect of cerebral extracellular fluid acidity on total and regional cerebral blood flow (1979)

Total and regional cerebral blood flow (CBF), and cerebrospinal fluid (CSF), and arterial blood acid-base status were measured in 26 chloralose-urethan-anesthetized dogs before and after 30 and 60 min of ventriculocisternal perfusion with artificial CSF equilibrated with 7% CO2 and containing either low (8.7 or 9.1 meq/l), normal (19.6 meq/l), or high (34.7 meq/l) bicarbonate ion concentration ([HCO3-]). An inverse linear relationship was observed between the CSF pH and total CBF. Regional blood flow changes were greater in structures that were closest to the ventricular system. In addition, regional blood flow changes were greater in all tissues studied after 60 min of perfusion than after 30. Perfusion with the control [HCO3-] caused no significant changes in either acid-base status or CBF. We believe that the regional cerebral blood flow changes are the result of changes in the H+ concentration gradient across the cerebral extracellular fluid (ECF) space due to the diffusional exchange of HCO3- between CSF and ECF. It is concluded that cerebral ECF acidity is important in the local regulation of cerebral blood flow.
Polyphyletic origins of Brassica napus: new evidence based on organelle and nuclear RFLP analyses (1992)

Accessions representing a range of diversity in Brassica napus and their potential diploid progenitor species were analyzed using nuclear, chloroplast (ct), and mitochondrial (mt) RFLPs. Based on RFLPs of ctDNA and mtDNA, cytoplasmic genomes of the diploid species examined could be classified into four major types, represented by almost all B. rapa, Broccoletto (a specialized form of B. rapa), B. oleracea, and B. montana. Results from phylogenetic analyses of these data suggest that B. montana might be closely related to the prototype that gave rise to both cytoplasms of B. rapa and B. oleracea. The four major types of cytoplasms found in the diploid species were also observed in B. napus accessions. A majority of the cultivated B. napus examined contained a cytoplasm different from those of either B. rapa and B. oleracea. These B. napus accessions (designated M/N cytoplasm type) had the same chloroplast genome as that of B. montana and a unique mitochondrial genome that was somewhat intermediate between those of B. montana and B. rapa. These results strongly support the concept of multiple origins of B. napus and provide the first evidence that most cultivated forms of B. napus were derived from a cross in which a closely related ancestral species of B. rapa and B. oleracea was the maternal donor. Phylogenetic relationships based on nuclear RFLPs clearly separated B. napus accessions having different cytoplasm types, providing further evidence for multiple origins of B. napus. Brassica napus accessions having M/N type cytoplasm were clustered together as three subgroups: one contained oilseed cultivars from Canada, a second contained oilseed cultivars from Europe, and a third contained accessions of rutabaga.Key words: Brassica napus, molecular taxonomy, RFLP, chloroplast, mitochondrion.