gebhart/patrepeval huggingface dataset:
Speech analysis/Synthesis based on a sinusoidal representation (1986)

A sinusoidal model for the speech waveform is used to develop a new analysis/synthesis technique that is characterized by the amplitudes, frequencies, and phases of the component sine waves. These parameters are estimated from the short-time Fourier transform using a simple peak-picking algorithm. Rapid changes in the highly resolved spectral components are tracked using the concept of "birth" and "death" of the underlying sine waves. For a given frequency track a cubic function is used to unwrap and interpolate the phase such that the phase track is maximally smooth. This phase function is applied to a sine-wave generator, which is amplitude modulated and added to the other sine waves to give the final speech output. The resulting synthetic waveform preserves the general waveform shape and is essentially perceptually indistinguishable from the original speech. Furthermore, in the presence of noise the perceptual characteristics of the speech as well as the noise are maintained. In addition, it was found that the representation was sufficiently general that high-quality reproduction was obtained for a larger class of inputs including: two overlapping, superposed speech waveforms; music waveforms; speech in musical backgrounds; and certain marine biologic sounds. Finally, the analysis/synthesis system forms the basis for new approaches to the problems of speech transformations including time-scale and pitch-scale modification, and midrate speech coding [8], [9].
Heat pipe turbine vane cooling (2009)

The applicability of using heat pipe principles to cool gas turbine vanes is addressed in this beginning program. This innovative concept involves fitting out the vane interior as a heat pipe and extending the vane into an adjacent heat sink, thus transferring the vane incident heat transfer through the heat pipe to heat sink. This design provides an extremely high heat transfer rate and an uniform temperature along the vane due to the internal change of phase of the heat pipe working fluid. Furthermore, this technology can also eliminate hot spots at the vane leading and trailing edges and increase the vane life by preventing thermal fatigue cracking. There is also the possibility of requiring no bleed air from the compressor, and therefore eliminating engine performance losses resulting from the diversion of compressor discharge air. Significant improvement in gas turbine performance can be achieved by using heat pipe technology in place of conventional air cooled vanes. A detailed numerical analysis of a heat pipe vane will be made and an experimental model will be designed in the first year of this new program.
Advanced glycation endproducts and cigarette smoking. (1998)

The incidence of certain ageing sequelae such as lung and cardiovascular disease and cataract are higher in smokers than in non-smokers. We recently proposed that certain components of mainstream cigarette smoke can react with plasma and extracellular matrix proteins to form covalent adducts with many of the properties of advanced glycation endproducts (AGE). AGEs have been implicated previously in the pathogenesis of the end-organ complications of diabetes and ageing, including cataract, atherosclerosis and renal insufficiency. In these circumstances, AGEs arise in vivo from the non-enzymatic reaction of reducing sugars with amino groups. Over time the initial Schiff base and Amadori products that form gradually undergo dehydration and rearrangement to produce reactive, carbonyl containing compounds with characteristic fluorescence and covalent crosslinking properties. Recent studies indicate that in smokers, tobacco-derived AGEs accumulate on plasma low density lipoprotein (LDL), structural proteins present within the vascular wall, and the lens proteins of the eye. These data point to a new and significant source of Maillard products in the human environment, significantly broaden the role of Maillard chemistry in pathological processes, and provide new insight into the pathogenesis of atherosclerosis and other diseases associated with tobacco usage.
Potentiation of calcium- and caffeine-induced calcium release by cyclic ADP-ribose. (1993)

Cyclic ADP-ribose (cADPR) is a naturally occurring metabolite of NAD+ that is as potent as inositol 1,4,5-trisphosphate (IP3) in mobilizing Ca2+ in sea urchin eggs. Previous pharmacological evidence suggests that cADPR acts through a system similar to the Ca(2+)-induced Ca2+ release (CICR). Here I showed that in the presence of low concentrations of cADPR addition of Ca2+ to egg homogenates stimulated further release of Ca2+ in a concentration-dependent manner. In the absence of cADPR, no induced release was seen, and the added Ca2+ was, instead, sequestered by a thapsigargin-sensitive transport system. High concentrations of strontium (> 50 microM) could also induce Ca2+ release. The effective concentrations of Sr2+, however, were reduced 10-20-fold in the presence of low concentrations of cADPR. Barium, at up to 0.4 mM, did not stimulate Ca2+ release with or without cADPR. The potentiation between divalent cations and cADPR was mutual since the Ca2+ releasing activity of cADPR was also increased in the presence of strontium. Ionomycin and thapsigargin both released Ca2+ but neither potentiated Ca2+ release induced by divalent cations. Caffeine also released Ca2+ in a concentration-dependent manner, and its potency was greatly increased by low concentrations of cADPR, while no such simulation was seen with IP3. Conversely, low concentrations of caffeine that were not sufficient to release Ca2+ increased the effectiveness of cADPR 10-fold. Isocaffeine, an isomer of caffeine, was four to five times less effective, demonstrating the specificity of the caffeine effect. These results suggest that cADPR can function as an endogenous regulator of CICR in eggs.
Clinical consequences of defects in peroxisomal β-oxidation (2001)

The disorders of peroxisomal β-oxidation, which have been well characterised at the molecular level, include defects of acyl-CoA oxidase, defects of the D-bifunctional protein (D-BP) (including specific defects of its enoyl-CoA hydratase and D-3-hydroxyacyl-CoA dehydrogenase components), defects of the very-long-chain fatty acid (VLCFA)-CoA importer [X-linked adrenoleukodystrophy (ALD)] and α-methylacyl-CoA racemase deficiency. A survey of the clinical consequences of these defects indicates that defects in the acyl-CoA oxidase and D-BP can produce neonatal hypotonia, seizures in early infancy, retinopathy and progressive neurological dysfunction with leukodystrophy on imaging. Defects in the VLCFA-CoA importer and in the racemase do not produce disease until a long time after the neonatal period. However, again the clinical picture is dominated by neurological disease: impaired cognitive function with leukodystrophy in childhood X-linked ALD and retinopathy and neuropathy in racemase deficiency. It is difficult to escape the conclusion that defective peroxisomal β-oxidation has effects (such as impaired neuronal migration in the developing brain), which are more serious than those produced by the accumulation of substrates (VLCFAs, pristanic acid) alone.
Hydrolysis of phosphonate esters catalyzed by 5'-nucleotide phosphodiesterase (1975)

4-Nitrophenyl and 2-napthyl monoesters of phenylphosphonic acid have been synthesized, and an enzyme catalyzing their hydrolysis was resolved from alkaline phosphatase of a commerical calf intestinal alkaline phosphatase preparation by extensive ion-exchange chromatography, chromatography on L-phenylalanyl-Sepharose with a decreasing gradient of (NH4) 2SO4, and gel filtration. Detergent-solubilized enzyme from fresh bovine intestine was purified after (NH4)2SO4 fractionation by the same technique. The purified enzyme is homogeneous by polyacrylamide gel electrophoresis and sedimentation equilibrium centrifugation. It has a molecular weight of 108,000, contains approximately 21% carbohydrate, and has an amino acid composition considerably different from that reported from alkaline phosphatase from the same tissue. The homogeneous intestinal enzyme, an efficient catalyst of phosphonate ester hydoolysis but not of phosphate monoester hydrolysis, was identified as a 5'-nucleotide phosphodiesterase by its ability to hydrolyze 4-nitrophenyl esters of 5'-TMP but not of 3'-TMP. Also consistent with this identification was the ability of the enzyme to hydrolyze 5'-ATP to 5'-AMP and PPi, NAD+ to 5'-AMP and NMN, TpT to 5'-TMP and thymidine, pApApApA to 5'-AMP, and only the single-stranded portion of tRNA from the 3'-OH end. Snake venom 5'-nucleotide phosphodiesterase also hydrolyzes phosphonate esters, but 3'-nucleotide phosphodiesterase of spleen and cyclic 3',5'-AMP phosphodiesterase do not. Thus, types of phosphodiesterases can be conveniently distinguished by their ability to hydrolyze phosphonate esters. As substrates for 5'-nucleotide phosphodiesterases, phosphonate esters are preferable to the more conventional esters of nucleotides and bis(4-nitrophenyl) phosphate because of their superior stability and ease of synthesis. Furthermore, the rate of hydrolysis of phosphonate esters under saturating conditions is greater than that of the conventional substrates. At substrate concentrations of 1 mM the rates of hydrolysis of phosphonate esters and of nucleotide esters are comparable and both superior to that of bis(4-nitrophenyl) phosphate.
Caps on Eukaryotic mRNAs (2014)

Abstract A 5′‐terminal cap is added to most eukaryotic cellular and viral messenger ribonucleic acids (mRNAs) at an early stage of transcription. Capping is essential and modulates several subsequent events in gene expression including pre‐mRNA splicing, 3′‐poly(A) addition, overall stability, nuclear exit to cytoplasm, protein synthesis, and mRNA turnover initiated by decapping. These and other effects involve cap‐binding proteins that recognise the m7GpppN cap structure. Capping proceeds by a similar series of enzymatic steps in a wide range of systems, but differences exist between metazoans and unicellular eukaryotes and viruses, pointing to capping enzymes as potential targets for the development of selective drugs against some fungal, viral and parasitic infections. Moreover, the unique structural features of caps enable us to define the initiation sites and promoter regions of gene transcription, and provide a basis for advanced sequencer‐mediated high‐throughput genome‐wide profiling of gene expression in a wide range of cell types. Key Concepts: mRNA caps are now known to be essential components of gene expression in eukaryotic organisms. The history of the discovery of the presence of 5′ caps on messenger RNA and its subsequent scientific flowering is a good example of how a seemingly small biochemical observation can lead to the deeper understanding of a wide range of fundamental molecular biological phenomena. Evolution has resulted in wide variations in capping structure and function among organisms ranging from viruses to humans; the selective forces underlying such variation requires more research. Research that has documented viral‐specific capping reactions in viruses should prove to be a fertile source of research leading to new and novel anti‐viral agents. The ‘cap‐snatching’ strategies of influenza viruses is a remarkable example of an apparent adaptation to enhance infectivity and is a particularly compelling target for therapeutic intervention. The NMD mRNA surveillance pathway, which includes a pioneer round of translation with cap‐binding proteins, results in a striking decrease of defective mRNA in cells of patients with genetic diseases containing premature termination codons. Methylation of genomic DNA and mRNA is now widely accepted as a major pathway of the regulation of both transcription and translation in eukaryotes. Protein synthesis is a major field of gene expression where many players work for mRNA capping, decapping, decoding, quality control of gene transcripts and peptide elongation. Micro RNAs are now widely accepted as major players in the translational control of protein synthesis. The analysis of cap‐trapped sequences by high‐throughput sequencers enables one to carry out a genome‐wide identification of promoters together with quantification of their expression, thus elucidating a promoter‐based network of transcriptional regulation.
Ratiometric dosing of irinotecan (IRI) and floxuridine (FLOX) in a phase I trial: A new approach for enhancing the activity of combination chemotherapy (2007)

2549 Background: Like many pairs of chemotherapy agents, the combination of IRI and FLOX displays ratio-dependent activity in vitro. CPX-1, a liposome formulation of IRI:FLOX, was developed to maintain a synergistic 1:1 molar ratio in vivo, was highly active in preclinical models, and was evaluated in a phase 1 trial (CLTR0104–101). Methods: Doses were escalated from 30U/m 2 (1U= 1 mg IRI + 0.36 mg FLOX) to 270 U/m 2 given on day 1 and 15 of each 28 day cycle. Adult patients (pts) with advanced solid tumors, ECOG PS&lt;2, adequate bone marrow, liver, and renal function were eligible; 4 pts per cohort. After defining the MTD, additional pts with CRC were enrolled (extension phase). IRI completed greater than 12 months prior to this trial was allowed in the absence of resistance to IRI. PK was done on day 1 and 15 of the 1 st cycle. Results: Safety: The dose escalation phase enrolled 24 pts in 6 cohorts and added 2 pts in the 5 th cohort (210U/m 2 ; the MTD) after noting dose limiting diarrhea (3 pts) and neutropenia (1 pt) including one death from dehydration and renal failure due to prolonged diarrhea (gr3) &amp; vomiting (gr2) at 270U/m 2 . An additional 7 pts with CRC received 210U/m 2 in the extension phase. Grade 3/4 adverse events included diarrhea, nausea, vomiting, neutropenia and thrombocytopenia with most occurring at 270U/m 2 . No new toxicities were observed for this combination. Response: 30/33 pts were evaluable with 2 confirmed PRs (NSCLC and CRC), 21 SD and 7 PD. Median PFS was 5.4 mos. (0.3–11.8 mos.) in 15 pts w/CRC. PK: All pts maintained synergistic plasma IRI:FLOX ratios for 24h. IRI and FLOX AUCs (0-inf) were greater for CPX-1 than expected for conventional drugs. AUCs for SN-38 and 5FU at 210U/m 2 were 0.8 ± 0.1 and 10 ± 8.7 μg-hr/mL, respectively, indicating bioavailability for both drugs. Conclusion: CPX-1 was well tolerated in the outpatient setting and evidence of anti-tumor activity was obtained. This is the first clinical evaluation of ratiometric dosing in which a synergistic drug ratio, pre-selected in vitro based on optimal anti-tumor activity, was maintained systemically to enhance therapeutic benefit. [Table: see text]
National hospital discharge survey: annual summary, 1998. (2000)

An estimated 31.8 million inpatients were discharged from non-Federal short-stay hospitals in 1998. These patients used an estimated 160.9 million days of care. Patients 65 years of age and over accounted for 39 percent of discharges and used 48 percent of days of care. Heart disease and deliveries made up 26 percent of first-listed diagnoses. One or more procedures were reported for 63 percent of discharges. The cesarean rate per 100 deliveries increased from 20.8 in 1995 to 22.5 in 1998. An estimated 3.8 million newborn infants were discharged from short-stay hospitals after average stays of 3.2 days.
State-Based Modeling and Object Extraction From Echocardiogram Video (2008)

In this paper, we propose a hierarchical state-based model for representing an echocardiogram video. It captures the semantics of video segments from dynamic characteristics of objects present in each segment. Our objective is to provide an effective method for segmenting an echo video into view, state, and substate levels. This is motivated by the need for building efficient indexing tools to support better content management. The modeling is done using four different views, namely, short axis, long axis, apical four chamber, and apical two chamber. For view classification, an artificial neural network is trained with the histogram of a region of interest of each video frame. Object states are detected with the help of synthetic M-mode images. In contrast to traditional single M-mode, we present a novel approach named sweep M-mode for state detection. We also introduce radial M-mode for substate identification from color flow Doppler 2-D imaging. The video model described here represents the semantics of video segments using first-order predicates. Suitable operators have been defined for querying the segments. We have carried out experiments on 20 echo videos and compared the results with manual annotation done by two experts. View classification accuracy is 97.19%. Misclassification error of the state detection stage is less than 13%, which is within acceptable range since only frames at the state boundaries are found to be misclassified.
Phase shifting and optical proximity corrections to improve CD control on logic devices in manufacturing for sub-0.35-μm i-line (1997)

The use of I-Line exposure wavelength for manufacturing at and beyond 0.35 micrometers presents many challenges in manufacturing. The lack of resolution, depth of focus, exposure latitude, and iso/dense offsets have caused some to switch from I-Line to DUV. With our installed I-Line base we felt it necessary to implement techniques to extend our tool life, reduce manufacturing costs while improving manufacturing margins. The results of the differential modification techniques were used to reduce the effects of topography, density, and low k lens issues. The differences seen between the binary and phase shift plates show the advantage of phase shifting below 0.35 (mu) manufacturing. We have been able to demonstrate between critical dimension (CD) control using phase shift mask with dense iso compensation over a standard binary reticle. The data shows improved CD control across the stepper field, wafer, and overall lot distribution. The impact of this work was improved speed performance. It also allowed us to move the CD's to smaller dimension because of the better control without increasing fallout due to electrical parametric roll-off.
Translation of the cell adhesion molecule ALCAM in axonal growth cones – regulation and functional importance (2012)

ALCAM is a cell adhesion molecule that is present on extending axons and has been shown to be crucial for elongation and navigation of retinal ganglion cell (RGC) axons. In the present study, we show that ALCAM mRNA is present in axonal growth cones of RGCs in vivo and in vitro, and that translation of ALCAM occurs in RGC growth cones separated from their soma. This growth cone translation is regulated by the 3'-untranslated region (3'-UTR) of ALCAM and depends on the activity of the kinases ERK and TOR (target of rapamycin). We also investigated the impact of the growth cone translation of ALCAM on axonal functions. Growth cone translation of ALCAM is crucial for the enhanced elongation of axons extending in contact with ALCAM protein. The local translation of ALCAM in the growth cone is able to rapidly counterbalance experimentally induced ALCAM internalization, thereby contributing to the maintenance of constant ALCAM levels in the plasma membrane. Assays where RGC axons have the choice to grow on laminin or both ALCAM and laminin - as is the case in the developing retina - reveal that the axonal preference for ALCAM-containing lanes depends on translation of ALCAM in growth cones. Taken together, these results show for the first time that translation of a cell adhesion molecule in growth cones, as well as the impact of this local translation on the behavior of axon and growth cone.
Equipotentiality of thalamo-amygdala and thalamo-cortico-amygdala circuits in auditory fear conditioning (1992)

The goal of the present study was to examine the contribution of thalamo-amygdala and thalamo-cortico-amygdala projections to fear conditioning. Lesions were used to destroy either the thalamo-cortico- amygdala projection, the thalamo-amygdala projection, or both projections, and the effects of such lesions on the acquisition of conditioned fear responses (changes in arterial pressure and freezing behavior) to a tone paired with footshock were measured. In each group of animals examined, a large lesion of the acoustic thalamus, including all nuclei of the medial geniculate body and adjacent portions of the posterior thalamus, was made on one side of the brain to block auditory transmission to the forebrain at the level of the thalamus on that side. In this way, experimental lesions could be made on the contralateral side of the brain. Thus, animals with thalamo-amygdala pathway lesions received a large lesion of the acoustic thalamus on one side. Contralaterally, only the nuclei that project to the amygdala (the medial division of the medial geniculate body, the posterior intralaminar nucleus, and the suprageniculate nucleus) were selectively destroyed, leaving much of the thalamo-cortico-amygdala projection intact. For thalamo-cortico-amygdala pathway lesions, the acoustic thalamus was destroyed on one side and temporal and perirhinal cortices were ablated contralaterally. In these animals, thalamo-amygdala projections were intact on the side of the cortical lesion. Destruction of either pathway alone had no effect on auditory fear conditioning. However, combined lesions of the two sensory pathways disrupted conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)
c-myc oncogene alterations in human thyroid carcinomas. (1987)

A possible role of the c-myc oncogene in the neoplastic transformation of the human thyroid has been investigated. The structure, the methylation status, and the copy number of this oncogene have been analyzed in normal and in tumor thyroid DNAs by Southern blotting technique and dot blot hybridization. Among six carcinomas, four presented abnormal c-myc DNA structure: Three cases showed a mutation in the 5' flanking region of the gene, originating a new EcoRI site; the other case showed a deletion of 5 kb involving the first exon of the gene. This deletion was also observed in the white blood cells of the same individual. In addition, in three carcinomas a double dose of the oncogene has been demonstrated. In all the carcinomas examined, undermethylation of the c-myc oncogene has been observed. These findings suggest that c-myc oncogene alterations might be involved in the malignant transformation of the human thyroids and can be considered as tumor markers.