gebhart/patrepeval huggingface dataset:
Clinical investigation in duchenne dystrophy: 2. Determination of the “power” of therapeutic trials based on the natural history (1983)

A prospective study of 114 patients with DMD provided data for "power" calculations for future therapeutic trials. There was a decline in strength of 0.4 units per year (on a 0-10 scale). Contractures of the iliotibial bands, hip flexors, and heel cords developed before 6 years. Contractures of other joints accompanied the increased use of wheelchairs. All children walked until 8 years with functional "improvement" between 3-6 years. Children of the same age varied widely in their strength, degree of contracture, and functional abilities. Fifteen percent of the patients appear to have a milder variety of the disease and are termed "outliers." To test a drug which might slow the disease to 25% of its original rate of progression, two groups (placebo and treatment) of 40 patients each would have to be followed for one year.
Pro-apoptotic activity of α-bisabolol in preclinical models of primary human acute leukemia cells (2011)

Our study provides the first evidence that α-bisabolol is a pro-apoptotic agent for primary human acute leukemia cells.
A Common Role for Various Human Truncated Adenomatous Polyposis Coli Isoforms in the Control of Beta-Catenin Activity and Cell Proliferation (2012)

The tumour suppressor gene adenomatous polyposis coli (APC) is mutated in most colorectal cancer cases, leading to the synthesis of truncated APC products and the stabilization of β-catenin. Truncated APC is almost always retained in tumour cells, suggesting that it serves an essential function. Here, RNA interference has been used to down-regulate truncated APC in several colorectal cancer cell lines expressing truncated APCs of different lengths, thereby performing an analysis covering most of the mutation cluster region (MCR). The consequences on proliferation in vitro, tumour formation in vivo and the level and transcriptional activity of β-catenin have been investigated. Down-regulation of truncated APC results in an inhibition of tumour cell population expansion in vitro in 6 cell lines out of 6 and inhibition of tumour outgrowth in vivo as analysed in one of these cell lines, HT29. This provides a general rule explaining the retention of truncated APC in colorectal tumours and defines it as a suitable target for therapeutic intervention. Actually, we also show that it is possible to design a shRNA that targets a specific truncated isoform of APC without altering the expression of wild-type APC. Down-regulation of truncated APC is accompanied by an up-regulation of the transcriptional activity of β-catenin in 5 out of 6 cell lines. Surprisingly, the increased signalling is associated in most cases (4 out of 5) with an up-regulation of β-catenin levels, indicating that truncated APC can still modulate wnt signalling through controlling the level of β-catenin. This control can happen even when truncated APC lacks the β-catenin inhibiting domain (CiD) involved in targeting β-catenin for proteasomal degradation. Thus, truncated APC is an essential component of colorectal cancer cells, required for cell proliferation, possibly by adjusting β-catenin signalling to the "just right" level.
Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. (1986)

We have previously shown that a brief episode of ischemia slows the rate of ATP depletion during subsequent ischemic episodes. Additionally, intermittent reperfusion may be beneficial to the myocardium by washing out catabolites that have accumulated during ischemia. Thus, we proposed that multiple brief ischemic episodes might actually protect the heart from a subsequent sustained ischemic insult. To test this hypothesis, two sets of experiments were performed. In the first set, one group of dogs (n = 7) was preconditioned with four 5 min circumflex occlusions, each separated by 5 min of reperfusion, followed by a sustained 40 min occlusion. The control group (n = 5) received a single 40 min occlusion. In the second study, an identical preconditioning protocol was followed, and animals (n = 9) then received a sustained 3 hr occlusion. Control animals (n = 7) received a single 3 hr occlusion. Animals were allowed 4 days of reperfusion thereafter. Histologic infarct size then was measured and was related to the major baseline predictors of infarct size, including the anatomic area at risk and collateral blood flow. In the 40 min study, preconditioning with ischemia paradoxically limited infarct size to 25% of that seen in the control group (p less than .001). Collateral blood flows were not significantly different in the two groups. In the 3 hr study, there was no difference between infarct size in the preconditioned and control groups. The protective effect of preconditioning in the 40 min study may have been due to reduced ATP depletion and/or to reduced catabolite accumulation during the sustained occlusion. These results suggest that the multiple anginal episodes that often precede myocardial infarction in man may delay cell death after coronary occlusion, and thereby allow for greater salvage of myocardium through reperfusion therapy.
View-based Maps (2010)

Robotic systems that can create and use visual maps in real-time have obvious advantages in many applications, from automatic driving to mobile manipulation in the home. In this paper we describe a mapping system based on retaining stereo views of the environment that are collected as the robot moves. Connections among the views are formed by consistent geometric matching of their features. Out-of-sequence matching is the key problem: how to find connections from the current view to other corresponding views in the map. Our approach uses a vocabulary tree to propose candidate views, and a strong geometric filter to eliminate false positives: essentially, the robot continually re-recognizes where it is. We present experiments showing the utility of the approach on video data, including incremental map building in large indoor and outdoor environments, map building without localization, and re-localization when lost.
Radio Local Distribution System for High-Speed Digital Communications (1983)

The radio local distribution system (RLDS) has been proposed to transmit various business information signals. The proposed RLDS uses a 26 GHz band and time division multiple access (TDMA). The main features of the RLDS are the use of radio equipment containing the microwave integrated circuit (MIC) and the adoption of the demand-assigned TDMA (DA/TDMA) technique. The MIC is more suitable than conventional waveguide circuits for mass production because its components are miniaturized. The DA/TDMA system, operating in a fully variable demand-assignment mode, uses simple control systems with a low bit rate. As a result, the RLDS can serve a local distribution system of high-speed digital communications both expeditiously and economically.
Tumour Cytochrome P450 and Drug Activation (2002)

The expression of drug metabolising cytochrome P450s (CYPs) notably 1A, 1B, 2C, 3A, 2D subfamily members have been identified in a wide range of human cancers. Individual tumour types have distinct P450 profiles as studied by detection of P450 activity, identification of immunoreactive CYP protein and detection of CYP mRNA. Selected P450s, especially CYP1B1, are overexpressed in tumours including cancers of the lung, breast, liver, gastrointestinal tract, prostate, bladder. Several prodrug anti-tumour agents have retrospectively been identified as P450 substrates for which tumour CYP activation may hitherto have been underestimated. Those in clinical use include prodrug alkylating agents (cyclophosphamide, ifosphamide, dacarbazine, procarbazine), Tegafur, a prodrug fluoropyrimidine, methoxymorphylinodoxorubicin, a metabolically activated anthracycline, as well as flutamide and tamoxifen, two non-steroidal hormone receptor antagonists that are significantly more active following CYP-hydroxylation. More exciting is the prospect of developing new agents designed to be selectively dependent on tumour CYP activation. This can be illustrated with P450 activation of the 2-(4-aminophenyl)benzothiazoles exclusively in CYP1A1 inducible tumours. Also of interest is the bioreductive antitumour prodrug AQ4N, a CYP3A substrate that is activated to a cytotoxic metabolite specifically in hypoxic tumour regions.
Enzyme replacement therapy in a murine model of Morquio A syndrome (2007)

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to accumulation of keratan sulfate (KS) and chrondroitin-6-sulfate. The pharmacokinetics and biodistributions were determined for two recombinant human GALNSs produced in CHO cell lines: native GALNS and sulfatase-modifier-factor 1 (SUMF1) modified GALNS. Preclinical studies of enzyme replacement therapy (ERT) by using two GALNS enzymes were performed on MPS IVA mice. The half-lives in blood circulation of two phosphorylated GALNS enzymes were similar (native, 2.4 min; SUMF1, 3.3 min). After intravenous doses of 250 units/g body weight were administered, each enzyme was primarily recovered in liver and spleen, with detectable activity in other tissues including bone and bone marrow. At 4 h post-injection, enzyme activity was retained in the liver, spleen, bone and bone marrow at levels that were 20-850% of enzyme activity in the wild-type mice. After intravenous doses of 250 units/g of native GALNS, and 250, 600 or 1000 units/g of SUMF1-GALNS were administered weekly for 12 weeks, MPS IVA mice showed marked reduction of storage in visceral organs, sinus lining cells in bone marrow, heart valves, ligaments and connective tissues. A dose-dependent clearance of storage material was observed in brain. The blood KS level assayed by tandem mass spectrometry was reduced nearly to normal level. These preclinical studies demonstrate the clearance of tissue and blood KS by administered GALNS, providing the in vivo rationale for the design of ERT trials in MPS IVA.
Nowcasting US inflation using a MIDAS augmented Phillips curve (2016)

We present a mixed-frequency model for real-time monitoring of US inflation. Our approach relies on a mixed-data sampling (MIDAS) augmented Phillips curve with daily oil prices for nowcasting inflation. In line with the literature we find that performances of inflation nowcasting models rely on two key elements: the inclusion of high-frequency oil prices and a rolling-window framework. Our approach succeeds in providing a policy-oriented tool for monitoring inflation in real-time.
A biological system producing a self-assembling cholesteric protein liquid crystal (1971)

ABSTRACT The protein in the oothecal glands of praying mantids (Sphodromantis tenuidentata, Mio mantis monacha) exists in the form of lamellar liquid crystalline spherulites, which coalesce asthey flow out of a punctured gland tubule. Electron micrographs of sections of these spherulites after fixation show parabolic patterns of an electron-light component, set in a continuous matrix of protein. Such patterns arisein helicoidal systems (e.g. arthropod cuticle) and microdensito metric scans of the matrix show a rhythmical electron-density variation consistent with helicoidal structure. Double spiral patterns identical to those seen in liquid crystal spherulites are illustrated. These properties resemble those of cholesteric liquid crystals. The constructional units appear to be molecular rather than fibrillar as described by previous authors. The helicoidal architecture arises by self-assembly in the gland lumen. Lamellar surface structures self-assembled spontaneously on glass coverslips when the protein was left to stand for several days. When heated to 55 °C, the birefringent liquid crystalline protein abruptly changes to an isotropic gel, with associated loss of parabolic patterning in electron micrographs and of the rhythmical electron-density variation on microdensitometric scans. This behaviour is compared to the formation of gelatin from collagen, in terms of the randomization of an originally ordered secondary structure.
Old Mice Demonstrate Organ Dysfunction as well as Prolonged Inflammation, Immunosuppression, and Weight Loss in a Modified Surgical Sepsis Model* (2019)

The results indicate that this murine cecal ligation and puncture + daily chronic stress model of surgical sepsis in old mice adhered to current Minimum Quality Threshold in Pre-Clinical Sepsis Studies guidelines and met Sepsis-3 criteria. In addition, it effectively created a state of persistent inflammation, immunosuppression, and weight loss, thought to be a key aspect of chronic sepsis pathobiology and increasingly more prevalent after human sepsis.
Constrained via minimization with practical considerations for multi-layer VLSI/PCB routing problems (1991)

Article Free Access Share on Constrained via minimization with practical considerations for multi-layer VLSI/PCB routing problems Authors: Sung-Chuan Fang Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, R.O.C. Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, R.O.C.View Profile , Kuo-En Chang Department of Information and Computer Education, National Taiwan Normal University, Taipei, Taiwan, R.O.C. Department of Information and Computer Education, National Taiwan Normal University, Taipei, Taiwan, R.O.C.View Profile , Wu-Shiung Feng Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, R.O.C. Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, R.O.C.View Profile , Sao-Jie Chen Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, R.O.C. Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, R.O.C.View Profile Authors Info & Claims DAC '91: Proceedings of the 28th ACM/IEEE Design Automation ConferenceJune 1991 Pages 60–65https://doi.org/10.1145/127601.127629Published:01 June 1991Publication History 15citation536DownloadsMetricsTotal Citations15Total Downloads536Last 12 Months43Last 6 weeks6 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Cloned Erwinia chrysanthemi out genes enable Escherichia coli to selectively secrete a diverse family of heterologous proteins to its milieu. (1991)

The out genes of the enterobacterial plant pathogen Erwinia chrysanthemi are responsible for the efficient extracellular secretion of multiple plant cell wall-degrading enzymes, including four isozymes of pectate lyase, exo-poly-alpha-D-galacturonosidase, pectin methylesterase, and cellulase. Out- mutants of Er. chrysanthemi are unable to export any of these proteins beyond the periplasm and are severely reduced in virulence. We have cloned out genes from Er. chrysanthemi in the stable, low-copy-number cosmid pCPP19 by complementing several transposon-induced mutations. The cloned out genes were clustered in a 12-kilobase chromosomal DNA region, complemented all existing out mutations in Er. chrysanthemi EC16, and enabled Escherichia coli strains to efficiently secrete the extracellular pectic enzymes produced from cloned Er. chrysanthemi genes, while retaining the periplasmic marker protein beta-lactamase. DNA sequencing of a 2.4-kilobase EcoRI fragment within the out cluster revealed four genes arranged colinearly and sharing substantial similarity with the Klebsiella pneumoniae genes pulH, pulI, pulJ, and pulK, which are necessary for pullulanase secretion. However, K. pneumoniae cells harboring the cloned Er. chrysanthemi pelE gene were unable to secrete the Erwinia pectate lyase. Furthermore, the Er. chrysanthemi Out system was unable to secrete an extracellular pectate lyase encoded by a gene from a closely related plant pathogen. Erwinia carotovora ssp. carotovora. The results suggest that these enterobacteria secrete polysaccharidases by a conserved mechanism whose protein-recognition capacities have diverged.
Effective gene therapy in an authentic model of Tay-Sachs-related diseases (2006)

Tay-Sachs disease is a prototypic neurodegenerative disease. Lysosomal storage of GM2 ganglioside in Tay-Sachs and the related disorder, Sandhoff disease, is caused by deficiency of beta-hexosaminidase A, a heterodimeric protein. Tay-Sachs-related diseases (GM2 gangliosidoses) are incurable, but gene therapy has the potential for widespread correction of the underlying lysosomal defect by means of the secretion-recapture cellular pathway for enzymatic complementation. Sandhoff mice, lacking the beta-subunit of hexosaminidase, manifest many signs of classical human Tay-Sachs disease and, with an acute course, die before 20 weeks of age. We treated Sandhoff mice by stereotaxic intracranial inoculation of recombinant adeno-associated viral vectors encoding the complementing human beta-hexosaminidase alpha and beta subunit genes and elements, including an HIV tat sequence, to enhance protein expression and distribution. Animals survived for >1 year with sustained, widespread, and abundant enzyme delivery in the nervous system. Onset of the disease was delayed with preservation of motor function; inflammation and GM2 ganglioside storage in the brain and spinal cord was reduced. Gene delivery of beta-hexosaminidase A by using adeno-associated viral vectors has realistic potential for treating the human Tay-Sachs-related diseases.
Telomerase as a universal tumor antigen for cancer vaccines (2008)

T-cell immunotherapy relies on the fundamental concept that tumor antigens exist and are presented in the context of MHC molecules for recognition by specific T cells capable of cytolysis. However, heterogeneous expression of most characterized tumor antigens limits the broad applicability of cancer vaccines that target such antigens. Telomerase, on the other hand, represents a prototype of a universal tumor antigen due to both its expression by the vast majority of tumors and its inherent functional involvement in oncogenic transformation. Given these attractive features, the identification of epitopes within human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, has led to the investigation of this tumor antigen as a broadly applicable immunological target. Basic immunological analyses have revealed that hTERT is immunogenic, and initial clinical trials of multiple vaccine formulations have demonstrated that hTERT-specific immune responses can be safely induced in patients and impact on clinical outcomes. Second-generation vaccines are now addressing strategies to enhance cellular immunity against hTERT without toxicity. Findings obtained from these trials will inform the possibility of broad-spectrum cancer immunotherapy or even immunoprevention.
Epigallocatechin-3-gallate Inhibits Epidermal Growth Factor Receptor Signaling Pathway (2004)

Epidermal growth factor receptor (EGFR) activation is absolutely required for cervical cell proliferation. This suggests that EGFR-inhibitory agents may be of therapeutic value. In the present study, we investigated the effects of epigallocatechin-3-gallate (EGCG), a bioactive green tea polyphenol, on EGFR signaling in cervical cells. EGCG inhibits epidermal growth factor-dependent activation of EGFR, and EGFR-dependent activation of the mitogen-activated protein kinases ERK1/2. EGCG also inhibits EGFR-dependent AKT activity. The EGCG-dependent reduction in ERK and AKT activity is associated with reduced phosphorylation of downstream substrates, including p90RSK, FKHR, and BAD. These changes are associated with increased p53, p21(WAF-1), and p27(KIP-1) levels, reduced cyclin E level, and reduced CDK2 kinase activity. Consistent with these findings, flow cytometry and TUNEL (terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling) staining revealed EGCG-dependent G(1) arrest. Moreover, sustained EGCG treatment caused apoptotic cell death. In addition to inhibiting EGFR, cell-free studies demonstrated that EGCG directly inhibits ERK1/2 and AKT, suggesting that EGCG acts simultaneously at multiple levels to inhibit EGF-dependent signaling. Importantly, the EGCG inhibition is selective, as EGCG does not effect the EGFR-dependent activation of JNK. These results suggest that EGCG acts to selectively inhibit multiple EGF-dependent kinases to inhibit cell proliferation.
Dermal microvascular endothelial cells express CD32 receptors in vivo and in vitro (1996)

Immune complexes are thought to be the major cause of cutaneous necrotizing vasculitis, but the mechanism of immune complex targeting to specific vessels is largely unknown. In myelomonocytic cells, immune complex binding and receptor-mediated endocytosis are mediated by Fc gamma R. We asked whether dermal microvascular endothelial cells (DMEC) express Fc gamma Rs. In cryostat sections of normal human skin, mAb IV.3 or AT10, both recognizing CD32 (Fc gamma RII), localizes to the luminal surface of DMEC of the superficial but not of the deep vascular plexus. All DMEC do not express CD16 (Fc gamma RIII) or CD64 (Fc gamma RI) molecules. Adult skin-derived DMEC in culture express CD32 (Fc gamma RII) molecules, as measured by FACS, but are negative for CD16 or CD64. HUVEC, tested for comparison, do not express CD16, 32, or 64 proteins. By reverse-transcriptase PCR and subsequent Southern blot analysis, the isoform of the CD32 molecule expressed on DMEC is determined as Fc gamma RIIa. HUVEC do not contain Fc gamma RIIa or Fc gamma RIIb mRNA. In DMEC, Fc gamma RIIa cross-linking results in immediate intracellular free Ca2+ ([Ca2+]i) concentration fluxes and in rapid internalization of the occupied receptors. We conclude that DMEC are equipped with fully functional Fc gamma RIIa molecules.
Partial purification and characterization of the major species-specific protein antigens of Rickettsia typhi and Rickettsia prowazekii identified by rocket immunoelectrophoresis (1981)

Species-specific antigens from Rickettsia typhi and Rickettsia prowazekii were readily solubilized by French pressure cell extraction or sonication of Renografin density gradient-purified rickettsiae and were identified by rocket immunoelectrophoresis. As measured by quantitative rocket immunoelectrophoresis, the species-specific typhus rocket antigens (STRAs) appeared to be proteins; they were denatured by heating at 56 degrees C for 30 min but not by 50 degrees C treatment, and they were sensitive to pronase and trypsin but were not affected by periodate oxidation, glycosidases of various specificities, phospholipase A, or lipase. STRAs from both R. typhi and R. prowazekii were separated from common antigens by DE52 column chromatography of 100,000-X-g supernatant fractions of rickettsial extracts. The purified STRAs were characterized by crossed immunoelectrophoresis, by polyacrylamide gel electrophoresis on Davis and sodium dodecyl sulfate gels, and by an enzyme-linked immunosorbent assay. The two purified STRAs were proteins with similar native electrophoretic mobilities in agarose and polyacrylamide gels, and these proteins had similar polypeptide patterns on sodium dodecyl sulfate gels. Most of the STRA activity migrated as a single protein band on sodium dodecyl sulfate-polyacrylamide and Davis polyacrylamide gels, although minor protein bands with STRA activity were also detected. The major STRA proteins constituted 10 to 15% of the total cellular protein of R. typhi and R. prowazekii. According to sensitive enzyme-linked immunosorbent assay titrations, the STRA of R. prowazekii had substantial cross-reactivity with rabbit antiserum prepared against R. typhi, as shown also by rocket immunoelectrophoresis, whereas the STRA of R. typhi reacted only very weakly with antiserum prepared against R. prowazekii according to the enzyme-linked immunosorbent assay and not at all according to rocket immunoelectrophoresis.