gebhart/patrepeval huggingface dataset:
Ketones and lactate “fuel” tumor growth and metastasis (2010)

Previously, we proposed a new model for understanding the "Warburg effect" in tumor metabolism. In this scheme, cancer-associated fibroblasts undergo aerobic glycolysis and the resulting energy-rich metabolites are then transferred to epithelial cancer cells, where they enter the TCA cycle, resulting in high ATP production via oxidative phosphorylation. We have termed this new paradigm "The Reverse Warburg Effect." Here, we directly evaluate whether the end-products of aerobic glycolysis (3-hydroxy-butyrate and L-lactate) can stimulate tumor growth and metastasis, using MDA-MB-231 breast cancer xenografts as a model system. More specifically, we show that administration of 3-hydroxy-butyrate (a ketone body) increases tumor growth by ∼2.5-fold, without any measurable increases in tumor vascularization/angiogenesis. Both 3-hydroxy-butyrate and L-lactate functioned as chemo-attractants, stimulating the migration of epithelial cancer cells. Although L-lactate did not increase primary tumor growth, it stimulated the formation of lung metastases by ∼10-fold. Thus, we conclude that ketones and lactate fuel tumor growth and metastasis, providing functional evidence to support the "Reverse Warburg Effect". Moreover, we discuss the possibility that it may be unwise to use lactate-containing i.v. solutions (such as Lactated Ringer's or Hartmann's solution) in cancer patients, given the dramatic metastasis-promoting properties of L-lactate. Also, we provide evidence for the up-regulation of oxidative mitochondrial metabolism and the TCA cycle in human breast cancer cells in vivo, via an informatics analysis of the existing raw transcriptional profiles of epithelial breast cancer cells and adjacent stromal cells. Lastly, our findings may explain why diabetic patients have an increased incidence of cancer, due to increased ketone production, and a tendency towards autophagy/mitophagy in their adipose tissue.
Discovery of a gene cluster for the biosynthesis of novel cyclic peptide compound, KK-1, in Curvularia clavata (2023)

KK-1, a cyclic depsipeptide with 10 residues produced by a filamentous fungus <i>Curvularia clavata</i> BAUA-2787, is a promising pesticide active compound with high activity against many plant pathogens, especially <i>Botrytis cinerea</i>. As a first step toward the future mass production of KK-1 through synthetic biological approaches, we aimed to identify the genes responsible for the KK-1 biosynthesis. To achieve this, we conducted whole genome sequencing and transcriptome analysis of <i>C. clavata</i> BAUA-2787 to predict the KK-1 biosynthetic gene cluster. We then generated the overexpression and deletion mutants for each cluster gene using our originally developed transformation system for this fungus, and analyzed the KK-1 production and the cluster gene expression levels to confirm their involvement in KK-1 biosynthesis. As a result of these, a region of approximately 71 kb was found, containing 10 open reading frames, which were co-induced during KK-1 production, as a biosynthetic gene cluster. These include <i>kk1B</i>, which encodes nonribosomal peptide synthetase with a domain structure that is consistent with the structural features of KK-1, and <i>kk1F</i>, which encodes a transcription factor. The overexpression of <i>kk1F</i> increased the expression of the entire cluster genes and, consequently, improved KK-1 production, whereas its deletion decreased the expression of the entire cluster genes and almost eliminated KK-1 production, demonstrating that the protein encoded by <i>kk1F</i> regulates the expressions of the other nine cluster genes cooperatively as the pathway-specific transcription factor. Furthermore, the deletion of each cluster gene caused a reduction in KK-1 productivity, indicating that each gene is involved in KK-1 production. The genes <i>kk1A</i>, <i>kk1D</i>, <i>kk1H</i>, and <i>kk1I</i>, which showed a significant decrease in KK-1 productivity due to deletion, were presumed to be directly involved in KK-1 structure formation, including the biosynthesis of the constituent residues. <i>kk1C</i>, <i>kk1E</i>, <i>kk1G</i>, and <i>kk1J</i>, which maintained a certain level of KK-1 productivity despite deletion, were possibly involved in promoting or assisting KK-1 production, such as extracellular transportation and the removal of aberrant units incorporated into the peptide chain.
Prevention of postischemic tissue injury by controlled reperfusion: A preliminary study (2003)

Restoration of arterial blood flow to severely and acutely ischemic extremities results in tissue necrosis and systemic-metabolic complications associated with multiorgan failure and death. Surgical revascularization alone (SRA) was compared with revascularization and controlled reperfusion using standard cardiopulmonary bypass (R-CPB) in 41 patients with acute lower limb ischemia and ischemia-induced neurological dysfunction. The mean ischemia time was 17 ± 10 hours. Eighteen patients (44%) had unilateral femoral artery occlusion, 23 (56%) had distal aortic occlusion. Eleven patients (27%) presented ischemia-induced paraplegia. SRA was performed in 23 patients (56%), and R-CPB in 18 (44%). End-points were hospital mortality, lower limb amputation, the number of surgical fasciotomies, and the incidence of permanent neurological morbidity. Hospital mortality was 19.5%; it was 33% after SRA, and 5.5% with R-CPB (p = 0.007). R-CBP was superior to SRA in terms of amputation rate (0% vs. 21.7%, p = 0.056), number of fasciotomies performed (7% vs. 64%, p = 0.002), and neurological recovery (86% vs. 19%, p = 0.000). After acute lower limb ischemia controlled reperfusion using standard cardiopulmonary bypass techniques preserves skeletal muscle and nerve function and prevents local as well as systemic complications of postischemic restoration of bloodflow.
Outcomes of primary total hip arthroplasty following septic arthritis of the hip (2022)

There was a ten-fold increased risk of PJI in patients with a history of septic arthritis who underwent THA compared with those who underwent THA for OA with a ten-year cumulative incidence of 7%. The risk of any infection had a strong downward trend as the time interval between the diagnosis of septic arthritis and THA increased, highlighted by a 3.1-fold higher risk when THAs were performed within five years of the diagnosis being made. Cite this article: <i>Bone Joint J</i> 2022;104-B(2):227-234.
A Fully Differential 4-Bit Analog Compute-In-Memory Architecture for Inference Application (2023)

A robust, fully differential multiplication and accumulate (MAC) scheme for analog compute-in-memory (CIM) architecture is proposed in this article. The proposed method achieves a high signal margin for 4-bit CIM architecture due to fully differential voltage changes on read bit-lines (RBL/RBLBs). The signal margin achieved for 4-bit MAC operation is 32 mV, which is 1.14×, 5.82×, and 10.24× higher than the state-of-the-art. The proposed scheme is robust against the process, voltage, and temperature (PVT) variations and achieves a variability metric (σ/µ) of 3.64 %, which is 2.36× and 2.66× lower than the reported works. The architecture has achieved an energy-efficiency of 2.53 TOPS/W at 1 V supply voltage in 65 nm CMOS technology, that is 6.2× efficient than digital baseline HW [25]. Furthermore, the inference accuracy of the architecture is 97.6% on the MNIST data set with a LeNet-5 CNN model. The figure-of-merit (FoM) of the proposed design is 355, which is 3.28×, 3.58×, and 17.75× higher than state-of-the-art.
History of Sandia?s MicroChemLab: a path to reduced false alarms in handheld systems. (2021)

Abstract not provided.
Illuminating Mitochondrial Function and Dysfunction using Multiphoton Technology (2009)

Studying differential cell function or dysfunction within the kidney is made difficult by cellular heterogeneity, alterations in regional blood flow, oxygen tension, and interstitial tonicity, resulting in extremely complex anatomic and physiologic arrangements. Creative investigators have developed techniques to reduce this heterogeneity but often with loss or alteration of three-dimensional cellular associations, anatomic and physiologic cell-to-cell interactions, and harsh isolation and experimental conditions. These limitations have made “absolutes” difficult to determine, especially in relation to pathologic processes such as cell type involvement in renal ischemia. In this issue of JASN , Hall et al. 1 use multiphoton microscopy of kidney slices to compare mitochondrial parameters and differential cellular responses to stress. This approach allows them to quantify several key parameters of mitochondrial function and dysfunction in proximal tubular (PT) cells and directly compare different PT segments with each other and with distal tubular (DT) cells of the thick ascending limb (TAL). Because mitochondrial alterations play a central role in normal cell function and in response to injury, the article adds to our previous knowledge about an important area.

To understand the significance and limitations of their contribution, one must first understand what is known about differences between PT and TAL cells. Abundant mitochondria in cortical and outer medullary renal epithelial cells are necessary to meet the ATP demands of sodium transport by high-capacity aerobic metabolism. They compose 33% of the volume of proximal convoluted tubular S1 cells, 39% of the cells in the S2 segment, and 22% of the volume of cells in the proximal straight S3 segment; in the medullary and cortical TAL cells, mitochondria account for 30 to 44% of cell volume.2 Differential tubular cell metabolism is also notable for the absence of aerobic and anaerobic glycolysis in the proximal convoluted tubule (S1), …
Sulfated non-anticoagulant heparin derivative modifies intracellular hemoglobin, inhibits cell sickling in vitro, and prolongs survival of sickle cell mice under hypoxia (2021)

Sickle cell disease (SCD) is an autosomal recessive genetic disease caused by a single point mutation, resulting in abnormal sickle hemoglobin (HbS). During hypoxia or dehydration, HbS polymerizes to form insoluble aggregates and induces sickling of red blood cells, which increases the adhesiveness of the cells, thereby altering the rheological properties of the blood, and triggers inflammatory responses, leading to hemolysis and vaso-occlusive crises. Unfractionated heparin and low-molecular weight heparins have been suggested as treatments to relieve coagulation complications in SCD. However, they are associated with bleeding complications after repeated dosing. An alternative sulfated non-anticoagulant heparin derivative (S-NACH) was previously reported to have no to low systemic anticoagulant activity and no bleeding side effects, and it interfered with P-selectin-dependent binding of sickle cells to endothelial cells, with concomitant decrease in the levels of adhesion biomarkers in SCD mice. S-NACH has been further engineered and structurally enhanced to bind with and modify HbS to inhibit sickling directly, thus employing a multimodal approach. Here, we show that S-NACH can: (i) directly engage in Schiff-base reactions with HbS to decrease red blood cell sickling under both normoxia and hypoxia in vitro, (ii) prolong the survival of SCD mice under hypoxia, and (iii) regulate the altered steady state levels of pro- and anti-inflammatory cytokines. Thus, our proof-of-concept, in vitro and in vivo preclinical studies demonstrate that the multimodal S-NACH is a highly promising candidate for development into an improved and optimized alternative to low-molecular weight heparins for the treatment of patients with SCD.
Efficient Succinic Acid Production from Glucose through Overexpression of Pyruvate Carboxylase in an Escherichia coli Alcohol Dehydrogenase and Lactate Dehydrogenase Mutant (2005)

An adhE, ldhA double mutant Escherichia coli strain, SBS110MG, has been constructed to produce succinic acid in the presence of heterologous pyruvate carboxylase (PYC). The strategic design aims at diverting maximum quantities of NADH for succinate synthesis by inactivation of NADH competing pathways to increase succinate yield and productivity. Additionally an operational PFL enzyme allows formation of acetyl-CoA for biosynthesis and formate as a potential source of reducing equivalents. Furthermore, PYC diverts pyruvate toward OAA to favor succinate generation. SBS110MG harboring plasmid pHL413, which encodes the heterologous pyruvate carboxylase from Lactococcus lactis, produced 15.6 g/L (132 mM) of succinate from 18.7 g/L (104 mM) of glucose after 24 h of culture in an atmosphere of CO(2) yielding 1.3 mol of succinate per mole of glucose. This molar yield exceeded the maximum theoretical yield of succinate that can be achieved from glucose (1 mol/mol) under anaerobic conditions in terms of NADH balance. The current work further explores the importance of the presence of formate as a source of reducing equivalents in SBS110MG(pHL413). Inactivation of the native formate dehydrogenase pathway (FDH) in this strain significantly reduced succinate yield, suggesting that reducing power was lost in the form of formate. Additionally we investigated the effect of ptsG inactivation in SBS110MG(pHL413) to evaluate the possibility of a further increase in succinate yield. Elimination of the ptsG system increased the succinate yield to 1.4 mol/mol at the expense of a reduction in glucose consumption of 33%. In the presence of PYC and an efficient conversion of glucose to products, the ptsG mutation is not indispensable since PEP converted to pyruvate as a result of glucose phosphorylation by the glucose specific PTS permease EIICB(glu) can be rediverted toward OAA favoring succinate production.
Digital Droplet PCR and IDAA for the Detection of CRISPR Indel Edits in the Malaria Species Anopheles Stephensi (2020)

CRISPR/Cas9 technology is a powerful tool for the design of gene-drive systems to control and/or modify mosquito vector populations; however, CRISPR/Cas9-mediated nonhomologous end joining mutations can have an important impact on generating alleles resistant to the drive and thus on drive efficiency. We demonstrate and compare the insertions or deletions (indels) detection capabilities of two techniques in the malaria vector mosquito <i>Anopheles stephensi</i>: Indel Detection by Amplicon Analysis (IDAA™) and Droplet Digital™ PCR (ddPCR™). Both techniques showed accuracy and reproducibility for indel frequencies across mosquito samples containing different ratios of indels of various sizes. Moreover, these techniques have advantages that make them potentially better suited for high-throughput nonhomologous end joining analysis in cage trials and contained field testing of gene-drive mosquitoes.
PSA regulates androgen receptor expression in prostate cancer cells (2011)

PSA localizes to nuclei of androgen-stimulated PrCa cells, and controls AR mRNA and protein levels. This regulatory loop is specific for PSA, does not involve known AR activators such as Src and AKT, and may contribute to AR signaling under conditions of increasing PSA levels in patients.
Radiologist Compliance With California CT Dose Reporting Requirements: A Single-Center Review of Pediatric Chest CT (2015)

Our institutional processes, which primarily rely on correct human performance, do not ensure accurate dose reporting and are prone to variation in dose reporting format. In view of this finding, we are exploring higher-reliability processes, including better-defined standards and automated dose reporting systems, to improve compliance.
A stakeholder-centric software architecture analysis approach (1996)

Article A stakeholder-centric software architecture analysis approach Share on Authors: Sonia Bot Nortel Technology, P.O. Box 3711, Station C, Ottawa, Ontario, Canada K1Y 4H7 Nortel Technology, P.O. Box 3711, Station C, Ottawa, Ontario, Canada K1Y 4H7View Profile , Chung-Horng Lung Nortel Technology, P.O. Box 3711, Station C, Ottawa, Ontario, Canada K1Y 4H7 Nortel Technology, P.O. Box 3711, Station C, Ottawa, Ontario, Canada K1Y 4H7View Profile , Mark Farrell Nortel Technology, P.O. Box 3711, Station C, Ottawa, Ontario, Canada K1Y 4H7 Nortel Technology, P.O. Box 3711, Station C, Ottawa, Ontario, Canada K1Y 4H7View Profile Authors Info & Claims ISAW '96: Joint proceedings of the second international software architecture workshop (ISAW-2) and international workshop on multiple perspectives in software development (Viewpoints '96) on SIGSOFT '96 workshopsOctober 1996 Pages 152–154https://doi.org/10.1145/243327.243632Online:14 October 1996Publication History 8citation556DownloadsMetricsTotal Citations8Total Downloads556Last 12 Months8Last 6 weeks1 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 SiteGet Access
Multi sensor data fusion with flange mounted acoustic emission sensors in the monitoring of fluidised beds (2003)

Acoustic emission (AE) sensors screwed onto flanges of pipelines transporting particulate materials have been used in monitoring particle velocity. The sensor signals have been analysed in a data fusion scenario to give alarms in cases of particulate clotting, which often hinders the smooth transport of bulk materials in closed conduits. Furthermore the sensor signals were used in a correlation algorithm to estimate particulate velocity. The airflow is an established means of sustaining fluidised bed behaviour in bulk material transport. The sensors were integrated in a network using profibus technology. Independent airflow measurements and Computational Fluid Dynamic (CFD) simulations verified the particulate flow velocity. The sensor-networking scenario can be observed in a telematic set-up, which will be demonstrated during the presentation of this paper, if Internet access is available in the presentation room. This paper presents results from signal processing, sensor data fusion and some aspects of system integration. This is a collaboration between SIEMENS, Telemark, Te-Tek, Porsgrunn and Telemark University College. Part of the project was conducted within the context of a thematic network of the European Union, THEIERE. The Royal Norwegian Research Council supports Urmila Datta in this R&D effort.
Applications of a versatile technique for trace analysis: atmospheric pressure negative chemical ionization. (1980)

The ability to use ambient air as a carrier and reagent gas in an atmospheric pressure chemical ionization source allows instantaneous air analysis to be combined with hypersensitivity toward a wide variety of compounds. The TAGA (Trace Atmospheric Gas Analyser) is an instrument which is designed to use both positive and negative atmospheric pressure chemical ionization (APCI) for trace gas analysis; this paper describes several applications of negative APCI which demonstrates that the technique is not limited to environmental monitoring. Examples are described which suggest that the TAGA can be used for the detection of illicit drugs and explosives, and for the analysis of breath or skin emissions, as well as for air pollution measurements. The applications are not restricted by the use of ambient air as a reagent gas; addition to the air carrier of various gases allows specific reagent ions such as Cl- or Br- to be generated. Furthermore, in certain situations pure gas carriers can be used to provide even more flexibility in the ion chemistry, with a short term absorber-desorber system used to transfer the sample from the ambient air into the ion source region. The potential uses for APCI are expanding continuously as the understanding of the complex ion-molecule chemistry grows. This paper underlines the complementary relation between the development of new negative chemical ionization (NCI) techniques and practical applications using the TAGA system.
Evaluation of cyclophosphamide as an immune enhancer for the NY-ESO-1/ISCOMATRIX vaccine in patients with metastatic melanoma. (2013)

3093^ Background: We have previously demonstrated potent immunogenicity of the NY-ESO-1/ISCOMATRIX vaccine in patients with resected melanoma; however the same vaccine induced only a few vaccine antigen specific immune responses in patients with advanced disease. Therefore, we have enrolled a second cohort of patients with advanced melanoma in the clinical trial LUD2002-013 to investigate whether pre-treatment with the immune-modulator cyclophosphamide could improve the immunogenicity of the NY-ESO-1/ISCOMATRIX vaccine. Methods: LUD2002-013 was an open-label phase II study intended to evaluate the safety and immunogenicity of the NY-ESO-1/ISCOMATRIX vaccine in patients with advanced melanoma. The first cohort of patients received vaccine alone; a second cohort with 19 patients was added after evaluation of responses in Cohort 1 and received vaccine in combination with low-dose cyclophosphamide. Patients received 3 injections of NY-ESO-1 ISCOMATRIX preceded, in Cohort 2, by cyclophosphamide at a dose of 300 mg/m 2 every four weeks. Assessment of clinical and immunological responses was undertaken at week 11. Results: Fifteen patients of Cohort 2 completed at least one cycle of vaccination. No objective responses were observed with three patients having stable disease for more than three months. The inclusion of cyclophosphamide into the vaccination protocol did not lead to any significant toxicity. Seven of fourteen patients in Cohort 2 developed a vaccine induced NY-ESO-1 specific CD4 T cell response, a significant increase compared to cohort 1 (p=0.019). No differences were observed in the frequency of vaccine induced antibody or CD8 T cell responses. No change in the frequency of peripheral blood regulatory T cells or myeloid derived suppressor cells was detected. Conclusions: The administration of low dose cyclophosphamide has significantly increased the NY-ESO-1 specific CD4 T cell response of the NY-ESO-1/ISCOMATRIX vaccine in patients with metastatic melanoma. Given the emerging importance of CD4 T cells in tumour regression, the present findings warrant further clinical exploration of combining cyclophosphamide with vaccines and other immune-modulatory agents. Clinical trial information: NCT00518206.
Effect of a rapid thermal annealing process on the electrical properties of an aluminum‐doped indium zinc tin oxide thin film transistor (2016)

We report the effect of a rapid thermal annealing process (RTP) on the electrical properties of an aluminum‐doped indium zinc tin oxide (Al‐IZTO) thin film transistor (TFT) with a back‐channel etched (BCE) structure. First, the RTP temperatures were varied from 250 to 350 °C, and their effect on Al‐IZTO TFT was investigated. The 250 °C RTP produced the best transfer characteristics (subthreshold swing = 0.11 V/dec, hysteresis = −0.25 V, and mobility = 26.42 cm 2 V −1 s −1 ), and as the temperature increased, the TFTs showed slightly degraded properties in hysteresis and subthreshold swing. Through the transmission line method (TLM), the channel shortening effect and contact properties according to the annealing temperature were studied. The reliability against a negative gate bias stress under illumination (NBIS) was also analyzed. At high RTP temperature (&gt;300 °C), stability under NBIS was considerably improved, and the 350 °C RTP device showed turn‐on voltage shift of −1.7 V. The microwave photoconductivity decay (μ‐PCD) method revealed that the RTP effectively reduced shallow localized states, which enhanced the NBIS stability at high temperature. Finally, the RTP was compared with the conventional furnace process at the same temperature in terms of transfer characteristics and uniformity. Even with a much shorter process time for the RTP, Al‐IZTO TFTs exhibited similar or better transfer properties and uniformity to or than the furnace annealing.