gebhart/patrepeval huggingface dataset:
An introduction to interactive television (1994)

The author discusses the following aspects: analogue versus digital systems, program content, compression capabilities, storage hierarchy and control system, transmission system, return path, set top box, remote control and navigation system, subscriber management, legal issues and the information superhighway.
Crest factor considerations in MC-CDMA with carrier interferometry codes (2002)

Carrier interferometry codes, applied to N-carrier MC-CDMA systems, enable 2N users to simultaneously share the system bandwidth with minimal degradation in performance (relative to the N orthogonal user case). This paper presents an analysis of crest factor considerations in MC-CDMA systems employing carrier interferometry codes. First, it is shown that the crest factor in downlink transmission demonstrates the desirable properties of low mean and low variance. Next, the poor crest factor observed in the uplink is characterized and it is shown how this can be effectively combated by use of Schroeder's (1970) analytical crest factor reduction techniques.
Follistatin and Activin: A Potential Intrinsic Regulatory System within Diverse Tissues (1991)

Until the 1920s, it was assumed that the sole gonadal hormones modulating anterior pituitary glandular secretions were lipid-soluble entities called steroids. Experimental evidence then surfaced during the ensuing decade that demonstrated that the testis also contained a hydrophilic material that might also influence pituitary secretory activity (1, 2). The name “inhibin” was given to this novel substance in view of its ability to inhibit hypertrophy of pituitary cells in castrated rats (2). Work in later years evoked the concept that inhibin could be an important regulator of follicle-stimulating hormone (FSH) secretion (3, 4). Thus, as a consequence of these landmark studies, investigators began a search to elucidate the chemical nature of the inhibins. Although inhibin was discovered as a potential secretory product of the testis, it was almost 45 years later that a nonsteroidal FSH suppressor was demonstrated in the ovarian follicular fluid of cows (5). Ironically, it was the ovarian follicular fluid from which chemists eventually isolated what was most likely the putative inhibin molecule described in the 1920s and 30s (6–9). Chemical characterization of the purified FSH-suppressing material revealed that inhibin is a 31-to 32-kDa heterodimer consisting of two distinct polypeptide chains, α and β. In pig follicular fluid, two inhibin heterodimers, A and B, were isolated and found to consist of a common α-subunit chain linked by disulphide bridges to a βA- or βB-subunit chain, respectively. Both inhibins were essentially equipotent in suppressing FSH secretion in the dispersed anterior pituitary cell bioassay system (6). At long last, the elusive inhibin had been proven a true chemical entity—a major breakthrough in reproductive endocrinology. However, little did anyone know that the gonads produced other FSH-regulatory polypeptide factors besides inhibin, and that the ability of these other factors to modulate FSH secretion could be only the tip of the iceberg with regard to the multi-functional properties of these factors, thereby extending their importance to other areas of biology.
Sensitive nested reverse transcription polymerase chain reaction detection of circulating prostatic tumor cells: comparison of prostate-specific membrane antigen and prostate-specific antigen-based assays. (1994)

A highly sensitive nested reverse transcriptase-PCR assay, with primers derived from the prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) cDNA sequences, has been used to detect occult hematogenous micrometastatic prostate cells. In 77 patients with prostate cancer, PSM and PSA primers detected circulating prostate cells in 48 (62.3%) and 7 (9.1%) patients, respectively. In treated stage D disease patients, PSM primers detected cells in 16 of 24 patients (66.7%), while PSA primers detected cells in 6 of 24 (25%). In post-radical prostectomy patients with negative serum PSA values, PSM primers detected metastases in 21 of 31 patients (67.7%), whereas PSA primers detected cells in only 1 of 33 (3.0%), indicating that micrometastatic spread may be a relatively early event in prostate cancer. The analysis of 40 individuals without known prostate cancer provides evidence that this assay is highly specific and suggests that PSM expression may predict the development of cancer in patients without clinically apparent prostate cancer. Using PSM primers, we detected micrometastases in 4 of 40 controls, 2 of whom had known benign prostatic hyperplasia and were later found to have previously undetected prostate cancer. The clinical significance of detection of hematogenous micrometastic prostate cells using PSM primers and potential applications of this molecular assay, as well as the assay for PSA, merit further study.
Ytterbium-169 Diethylenetriaminepentaacetic Acid Complex (1968)

RADIOACTIVE mercury-labeled chlormerodrin is the most widely used brain scanning agent today, but technetium-99m pertechnetate is continually gaining popularity and may soon replace it. Short-lived indium-113m chelate has also been employed successfully for brain (11) and kidney (9) scanning. These short-lived isotopes have greatly improved radionuclide imaging with decreased irradiation of the patient. We have developed a new radiopharmaceutical which depends on a short biological half-life to limit the radiation dose. This compound is prepared by chelating trivalent ytterbium 169, an isotope of one of the rare earth elements, with diethylenetriaminepentaacetic acid (DTPA). Ytterbium has several stable isotopes. The stable 168Yb has a natural abundance of only 0.135 per cent, but a very high thermal neutron capture cross-section (11,000 barns). It is available in enriched form, facilitating the production of 169Yb of high specific activity (greater than 100 mCi/mg). The product contains less than 1 per cent of 175Yb, which emits beta and gamma rays and decays with four and two-tenths days physical half-life. Ytterbium 169 has a physical half-life of thirty-two days and emits primarily gamma rays (8-308 keV). The predominant energies of the gamma rays are 63 and 198 keV, which are suitable for external radiation detection such as scanning. Ytterbium, like other lanthanons, is largely accumulated in the bones and the liver (3), but, when chelated with DTPA, it is excreted in the urine. Preparation of Radiopharmaceutical Ytterbium 169 was obtained as YbCl3 in HC1 from the 3M Company, St. Paul, Minn. The specific activity ranged from 20 to 100 mCi/mg. Ten mCi of 169Yb was diluted to 5 ml with 0.05 N HC1; then 10 mg of DTPA in 5 ml of pyrogen-free water was added, after which the pH was adjusted to between 6.5 and 7 with 0.5 N and 0.05 N NaOH solutions. Sodium chloride (60 mg) was added to make the solution isotonic. It was then sterilized by autoclaving at 15 psi for twenty minutes. The whole-body retention of the radioactivity (excluding the tail) was measured forty-eight hours after an intravenous injection of 169Yb-DTPA complex into the tail vein of white mice. The effects of storage, pH, excess DTPA, and carrier elements were studied to develop a preparation which would have minimum retention in the body. The final product was stable after repeated autoclaving and after storage for several months. There was no significant difference in the whole-body retention of the complex when the final pH was varied between 5 and 8. Studies with varying amounts of DTPA indicated that the molar excess of DTPA for maximum chelation depended on the amount of ytterbium. With higher amounts of 169Yb, a 3–10 molar excess of DTPA was sufficient to achieve maximum binding.
Aberrant Methylation of RASSF1A in Plasma DNA Before Breast Cancer Diagnosis in the Breast Cancer Family Registry (2009)

Abstract In addition to classic genetic mechanisms such as deletions and mutations, growth regulatory genes can be inactivated via methylation of cytosine-residues in their promoter regions. Hypermethylation of promoter CpG islands is now recognized as an important and early event in carcinogenesis. Detection of methylated DNA in serum or plasma has been suggested to be a marker for early cancer development. We examined methylation changes in RASSF1A, a growth regulatory gene in plasma DNA from blood collected before diagnosis from women with breast cancer and from controls. Samples were from two sets of subjects, 28 women with breast cancer and 10 of their unaffected siblings, and 33 women with breast cancer and 29 age- and ethnicity-matched population-based controls. Using methylation specific PCR, we found 11 of 61 (18%) cases were positive for methylation of RASSF1A in their plasma DNA collected before diagnosis. Two of 10 healthy high-risk sibling controls (20%) had plasma DNA positive for RASSF1A methylation in their plasma DNA compared with 0 of 29 (0%) population-based controls. Tumor tissue was available for 12 cases and all were positive for RASSF1A methylation. These results, if replicated, suggest that aberrant promoter hypermethylation in serum/plasma DNA may be common among high-risk women and may be present years before cancer diagnosis. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2723–5)
Bacterial lacZ gene as a highly sensitive marker to detect micrometastasis formation during tumor progression. (1990)

During tumor progression, micrometastases at their earliest stages have been difficult to analyze qualitatively or quantitatively because of a lack of suitably sensitive markers to discriminate small numbers of tumor cells from normal tissue cell populations. To overcome this problem, the Escherichia coli beta-galactosidase (lacZ) gene was introduced into human EJ Ha-ras oncogene-transfected BALB/c 3T3 cells with subsequent injection of transfected cells into athymic nude mice. Using a chromogenic substrate (5-bromo-4-chloro-3-indoyl-beta-D-galactopyranoside), the lacZ-bearing tumor cells at primary tumor sites as well as at secondary organs stain intensely blue and can be easily distinguished from the host tissue cells hours, days, or weeks postinjection. Staining of lacZ-bearing tumor cells is specific and extremely sensitive in detecting micrometastatic foci in lungs and other organs, including brain and kidney for the first time. Stable integration of the lacZ and ras genes into cultured cells and subsequent tumor cells was verified by Southern blot analyses. The lacZ gene appears to be a stable marker during tumor progression in vivo based both on phenotypic (5-bromo-4-chloro-3-indoyl-beta-D-galactopyranoside staining) and on genotypic (Southern blot analysis) evidence. Furthermore, 5-bromo-4-chloro-3-indoyl-beta-D-galactopyranoside staining of tumor cells can also be used together with alkaline phosphatase staining relatively specific for endothelial cells to relate the topographies of metastatic cells and host blood vessels in embedded sections. By using the lacZ gene as a sensitive quantitative marker, analyses of micrometastasis development in the lung indicate that the ras oncogene contributes to the metastatic phenotype in this EJ Ha-ras model system, although further genetic and/or phenotypic alterations appear to be necessary for long-term growth and development into overt metastases. These findings demonstrate the effectiveness and sensitivity of the bacterial lacZ gene as a phenotypic marker in tumor progression studies, providing both a qualitative and a quantitative tool in virtually any tumor system for examining micrometastasis formation in target organs and the relationship of tumor cells to host organ microenvironments.
Distinguishing Lung Adenocarcinoma from Lung Squamous Cell Carcinoma by Two Hypomethylated and Three Hypermethylated Genes: A Meta-Analysis (2016)

Significant differences in the aberrant methylation of genes exist among various histological types of non-small cell lung cancer (NSCLC), which includes adenocarcinoma (AC) and squamous cell carcinoma (SCC). Different chemotherapeutic regimens should be administered to the two NSCLC subtypes due to their unique genetic and epigenetic profiles. The purpose of this meta-analysis was to generate a list of differentially methylated genes between AC and SCC. Our meta-analysis encompassed 151 studies on 108 genes among 12946 AC and 10243 SCC patients. Our results showed two hypomethylated genes (CDKN2A and MGMT) and three hypermethylated genes (CDH13, RUNX3 and APC) in ACs compared with SCCs. In addition, our results showed that the pooled specificity and sensitivity values of CDH13 and APC were higher than those of CDKN2A, MGMT and RUNX3. Our findings might provide an alternative method to distinguish between the two NSCLC subtypes.
In Eukaryotic Flap Endonuclease 1, the C Terminus Is Essential for Substrate Binding (2001)

Flap endonuclease 1 (Fen1) is a structure-specific metallonuclease with important functions in DNA replication and DNA repair. It interacts like many other proteins involved in DNA metabolic events with proliferating cell nuclear antigen (PCNA), and its enzymatic activity is stimulated by PCNA in vitro. The PCNA interaction site is located close to the C terminus of Fen1 and is flanked by a conserved basic region of 35-38 amino acids in eukaryotic species but not in archaea. We have constructed two deletion mutants of human Fen1 that lack either the PCNA interaction motif or a part of its adjacent C-terminal region and analyzed them in a variety of assays. Remarkably, deletion of the basic C-terminal region did not affect PCNA interaction but resulted in a protein with significantly reduced enzymatic activity. Electrophoretic mobility shift analysis revealed that this mutant displayed a severe defect in substrate binding. Our results suggest that the C terminus of eukaryotic Fen1 consists of two functionally distinct regions that together might form an important regulatory domain.
A region of the 85-kilodalton (kDa) subunit of phosphatidylinositol 3-kinase binds the 110-kDa catalytic subunit in vivo. (1993)

Phosphatidylinositol (PI) 3-kinase is a heterodimer consisting of an 85-kDa subunit (p85) and 110-kDa subunit (p110). The 85-kDa noncatalytic subunit, which contains two Src homology 2 (SH2) domains, one SH3 domain, and a domain homologous to the carboxy terminus of the breakpoint cluster region gene product, is known to mediate the association of the PI 3-kinase complex with activated growth factor receptors. We previously demonstrated that the C-terminal SH2 domain of p85 is responsible for the interaction of PI 3-kinase with phosphorylated platelet-derived growth factor receptor. To define the region in p85 that directs the complex formation with the PI 3-kinase catalytic subunit, a series of truncated p85 mutants was analyzed for association with p110 in vivo. We found that a fragment of p85 containing the region between the two SH2 domains was sufficient to promote the interaction with p110 in vivo. The complex between the fragment of p85 and p110 had PI 3-kinase activity that was comparable in magnitude to the activity of p110 associated with full-length p85. The binding with p110 was abolished when this domain in p85 was disrupted. These results identify a novel structural and functional element that is responsible for localizing the catalytic subunit of PI 3-kinase.
Nearest-Neighbor Thermodynamics of Internal A·C Mismatches in DNA:  Sequence Dependence and pH Effects (1998)

Thermodynamics of 27 oligonucleotides with internal A.C mismatches at two different pHs were determined from UV absorbance versus temperature melting profiles. The data were combined with four literature values and used to derive nearest-neighbor parameters for all 16 trimer sequences with internal A.C mismatches at pH 7.0 and 5. 0. The results indicate that the contribution of single A.C mismatches to duplex stability is strongly dependent on the solution pH and the nearest-neighbor context. On average, the protonation of an internal A.C mismatch stabilizes the duplex by 1.39 kcal/mol for DeltaG degrees37 and 7.0 degreesC for the TM. The nearest-neighbor parameters predict DeltaG degrees37, DeltaH degrees, DeltaS degrees, and TM of oligonucleotides presented in this study with average deviations of 6.3%, 11.0%, 12.2%, and 1.8 degreesC, respectively, at pH 7.0 and 4.7%, 5.9%, 6.1%, and 1.3 degreesC, respectively, at pH 5. 0. At pH 7.0, the contribution of single A.C mismatches to helix stability ranges from 2.25 kcal/mol for TCA/AAT to 1.22 kcal/mol for GCG/CAC. At pH 5.0, however, the contribution of A+.C mismatches ranges from 1.09 kcal/mol for TCT/AAA to -0.43 kcal/mol for GCC/CAG. Implications of the results for replication fidelity and mismatch repair are discussed.
Non-invasive measurement of mechanical properties of arteries in health and disease (1999)

Major conduit arteries should, by their elastic nature, be able to store blood volume temporarily during systole and release it during diastole. This reduces the systolic blood pressure required for the flow of a given volume quantity and gradually suppresses the pulsatile flow pattern. The haemodynamic characteristics of arteries have consequences for the load of the heart but also for the mechanical load of the arterial wall. The repetitive stretching of the wall (strains of up to 10 per cent) may cause fragmentation of the elastic fibres in the wall, modifying wall elasticity. To maintain wall stress the elastic arteries respond with a diameter increase in combination with an increase of arterial wall thickness. A larger diameter for a smaller distension (change in artery diameter from diastole to systole) will restrict the reduction in storage capacity. Alternatively, pulse pressure may go up increasing the mechanical load on the wall. In recent years various methods have been developed to assess and monitor the above interaction. Most of these methods are based on ultrasound techniques because of its wide availability and its non-invasive and non-traumatic nature. Presently these techniques enable the assessment of wall thickness, diastolic diameter, distension waveform, i.e., the tie-dependent change in diameter, the relative pulsatile increase in diameter, and pulse wave velocity, for elastic and muscular arteries in humans but also in small animals such as rats and mice. The present paper discusses the techniques in more detail.
Evaluation of the premier EHEC assay for detection of Shiga toxin-producing Escherichia coli (1997)

An enzyme-linked immunosorbent assay for the detection of Shiga toxins (Premier EHEC assay; Meridian Diagnostics, Inc.) was compared to conventional sorbitol-MacConkey culture for the recovery of enterohemorrhagic Escherichia coli. A total of 74 enteric pathogens, including 8 E. coli O157:H7 isolates, were recovered from 974 stool specimens. Two of these specimens were not tested by Premier assaying due to insufficient sample and are not considered in the data analysis. The Premier EHEC assay detected the 6 evaluable specimens which were culture positive for E. coli O157:H7 and identified an additional 10 specimens as containing Shiga toxin. Seven isolates were recovered from these 10 specimens by an immunoblot assay and were confirmed as toxin producers by a cytotoxin assay. Of these seven, four isolates were serotype O157:H7, one was O26:NM, one was O6:H-, and one was O untypeable:H untypeable. Three specimens contained Shiga toxin by both EHEC immunoassaying and cytotoxin testing; however, no cytotoxin-producing E. coli could be recovered. The sorbitol-MacConkey method had a sensitivity and a specificity of 60 and 100%, respectively, while the Premier EHEC assay had a sensitivity and a specificity of 100 and 99.7%, respectively, for E. coli O157:H7 only. The Premier EHEC assay also detected an additional 20% Shiga toxin-producing E. coli (STEC) that were non-O157:H7. Thus, the Premier EHEC assay is a sensitive and specific method for the detection of all STEC isolates. Routine use would improve the detection of E. coli O157:H7 and allow for determination of the true incidence of STEC other than O157:H7. The presence of blood in the stool and/or the ages of the patients were poor predictors of the presence of STEC. Criteria need to be determined which would allow for the cost-effective incorporation of this assay into the routine screen for enteric pathogens in high-risk individuals, especially children.
A prioritized grid long short-term memory RNN for speech recognition (2016)

Recurrent neural networks (RNNs) are naturally suitable for speech recognition because of their ability of utilizing dynamically changing temporal information. Deep RNNs have been argued to be able to model temporal relationships at different time granularities, but suffer vanishing gradient problems. In this paper, we extend stacked long short-term memory (LSTM) RNNs by using grid LSTM blocks that formulate computation along not only the temporal dimension, but also the depth dimension, in order to alleviate this issue. Moreover, we prioritize the depth dimension over the temporal one to provide the depth dimension more updated information, since the output from it will be used for classification. We call this model the prioritized Grid LSTM (pGLSTM). Extensive experiments on four large datasets (AMI, HKUST, GALE, and MGB) indicate that the pGLSTM outperforms alternative deep LSTM models, beating stacked LSTMs with 4% to 7% relative improvement, and achieve new benchmarks among uni-directional models on all datasets.
New therapeutic approaches (1992)

New therapeutic approaches to asthma involve either improvements in existing classes of drug, or the development of novel drugs. Over the last 20 years there have been no new types of drug introduced, although several new classes of compound are now under development. Improvements in existing bronchodilators include long-acting inhaled beta 2-agonists, methyl xanthines with a reduced side effect profile and M3-selective anticholinergics. New bronchodilators include K+ channel activators and selective phosphodiesterase inhibitors. Corticosteroids are the most effective anti-inflammatory drugs and there are attempts to develop inhaled steroids with greater topical potency or increased systemic metabolism, or to develop drugs which retain the anti-inflammatory effects of steroids without side effects. Steroids are probably effective in asthma by inhibiting the synthesis of cytokines and drugs which inhibit cytokine synthesis or receptors are now being sought. Inhibitors of mediator synthesis and receptors currently under development and leukotriene D4-antagonists are promising. Immunomodulatory drugs such as methotrexate, cyclosporin A and gold may be useful in more severe asthma, but drugs which modulate the immune abberation of asthma more specifically may be of more widespread use in the future. There is no immediate prospect of a cure for asthma and a drug which may be taken orally once daily and has no side effects would be ideal.