gebhart/patrepeval huggingface dataset:
Glutamine and cancer: cell biology, physiology, and clinical opportunities (2013)

Glutamine is an abundant and versatile nutrient that participates in energy formation, redox homeostasis, macromolecular synthesis, and signaling in cancer cells. These characteristics make glutamine metabolism an appealing target for new clinical strategies to detect, monitor, and treat cancer. Here we review the metabolic functions of glutamine as a super nutrient and the surprising roles of glutamine in supporting the biological hallmarks of malignancy. We also review recent efforts in imaging and therapeutics to exploit tumor cell glutamine dependence, discuss some of the challenges in this arena, and suggest a disease-focused paradigm to deploy these emerging approaches.
Nuclear Magnetic Relaxation in Blood (1975)

The nuclear magnetic relaxation time T <L xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</L> of protons in human blood has been measured as a function of frequency, pH, and hematocrit. For whole blood at 25°C, T <L xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</L> is approximately 0.1 s at 20 kHz, increasing to approximately 1 s at 50 MHz. T <L xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</L> of whole blood is analyzed in terms of the exchange of water molecules between plasma and erythrocyte cytoplasm. A cellular residence time of 19 ms provides the best fit to the data. The T <L xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</L> values for plasma and cytoplasm are explained in terms of their protein content, using the well-established theory of nuclear relaxation in macromolecular solutions. The plasma and cytoplasm data are compared with previous T <L xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</L> results for apotransferrin and hemoglobin solutions, respectively, and qualitative agreement is found. The T <L xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</L> values increased with decreasing pH, as is expected from existing data on hemoglobin solutions.
Comparative study on the ALA photodynamic effects of human glioma and meningioma cells (1999)

ALA-PDT was more effective in killing U-105MG glioma cells than CH-157MN meningioma cells. The differential susceptibility was likely due to differential accumulation of PpIX in these cells. EGF, bFGF, or PDGF-BB did not have stimulatory or inhibitory effect on the efficiency of ALA-PDT.
Clinical epidemiology and disease burden of nonalcoholic fatty liver disease (2017)

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.
The Enteric Nervous System (1996)

The enteric nervous system is a collection of neurons in the gastrointestinal tract1 that constitutes the “brain of the gut” and can function independently of the central nervous system.2 This system controls the motility,3,4 exocrine and endocrine secretions,5 and microcirculation6 of the gastrointestinal tract; it is also involved in regulating immune and inflammatory processes.7 In the past decade, major advances in the understanding of the enteric nervous system have led to a greater appreciation of its importance in clinical medicine. In this review we highlight some of these advances.Development of the Enteric Nervous SystemThe enteric nervous system . . .
Human Papillomavirus: Detection of Viral DNA Sequences and Evidence for Molecular Heterogeneity in Metaplasias and Dysplasias of the Uterine Cervix (1983)

Colposcopic-directed biopsies of the uterine cervix from 22 patients were analyzed for the presence of human papillomavirus (HPV) DNA and structural antigens. 11 of the biopsies were classified microscopically as mild dysplasia, 3 as moderate dysplasia, 1 as severe dysplasia, and 7 as squamous metaplasia. Nonstringent hybridization with a bovine papillomavirus type 1 DNA probe and immunocytochemical analysis with an antiserum against papillomavirus genus-specific structural antigens were performed on all specimens. Of the 11 mild dysplasias, both HPV DNA and structural antigens were detected in 5, only HPV antigens in 3, only HPV DNA in 1, and neither DNA nor structural antigens in 2. Both HPV DNA and structural antigens were present in the 3 cases of moderate dysplasia. Only HPV DNA sequences were detected in the single case of severe dysplasia. HPV DNA was detected in 2 cases of squamous metaplasia. The 5 remaining cervical biopsies showing squamous metaplasia, tissue from 3 placentas, and 6 cervical carcinomas were negative for HPV DNA and structural antigens. Restriction enzyme cleavage patterns of HPV DNA in the dysplasias suggested that there are multiple virus types or subtypes associated with cervical dysplasia. Stringent hybridization with a HPV type 11 (HPV-11) probe revealed that only 1 of 10 dysplasias contained sequences with homology to the probe. Of the remaining 9 dysplasias, 5 contained HPV sequences detected under nonstringent hybridization. 2 of 4 squamous metaplasias contained viral sequences which hybridized to the HPV-11 probe as well as 1 of 6 cervical carcinomas.
DNA fingerprinting survey of various human tumors and their metastases. (1992)

DNA fingerprinting with the minisatellite probes 33.6 and 33.15 was used to screen for genetic abnormalities in primary tumors of a variety of organs and, where appropriate, their metastases, obtained from 32 patients. The constitutional DNA of each host, obtained from blood leukocytes or normal tissue, was used to produce control, individual-specific fingerprints for comparison with those of their tumor. Fingerprints obtained with probe 33.6 showed differences between tumor and host fingerprints in 69% of patients and those produced with 33.15 in 55%. The most common change was loss or reduction in the intensity of one or more bands, but the appearance of new bands, not present in the fingerprint of the constitutional DNA, was also noted in several tumor DNA samples. The findings are interpreted as indicating loss or rearrangement of expressed sequences in the chromosomal regions adjacent to the hypervariable tandem repeat intron arrays which are detected by these probes. In three patients further differences were identified between primary tumors and their metastatic deposits. With this technique it is possible to perform simultaneous multilocus screening of the genome and the present results show that it has potential for identification of as yet unknown abnormalities in DNA constitution, which may be of pathogenetic significance.
Low-temperature growth of high-integrity silicon oxide films by oxygen radical generated in high-density krypton plasma (2003)

This paper focuses attention on the electrical properties of silicon oxide films grown by Kr-O/sub 2/ mixed high-density and low electron temperature microwave-excited plasma at 400/spl deg/C. They exhibit high growth rate, high dielectric strength, high charge-to-breakdown, and low interface traps and bulk charge enough to replace thermally grown silicon oxide.
Cartilage, SOX9 and Notch signals in chondrogenesis (2006)

Cartilage repair is an ongoing medical challenge. Tissue engineered solutions to this problem rely on the availability of appropriately differentiated cells in sufficient numbers. This review discusses the potential of primary human articular chondrocytes and mesenchymal stem cells to fulfil this role. Chondrocytes have been transduced with a retrovirus containing the transcription factor SOX9, which permits a greatly improved response of the cells to three-dimensional culture systems, growth factor stimulation and hypoxic culture conditions. Human mesenchymal stem cells have been differentiated into chondrocytes using well-established methods, and the Notch signalling pathway has been studied in detail to establish its role during this process. Both approaches offer insights into these in vitro systems that are invaluable to understanding and designing future cartilage regeneration strategies.
Plasma Kallikrein Mediates Retinal Vascular Dysfunction and Induces Retinal Thickening in Diabetic Rats (2011)

These results show that PK contributes to retinal vascular dysfunctions in diabetic rats and that the combination of diabetes and intravitreal injection of PK in rats induces retinal thickening.
Synthesis of Derivatives of Alkylated and Arylated Piperidones and Piperidinols (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Derivatives of Alkylated and Arylated Piperidones and PiperidinolsEVERETT A. MAILEY and ALLAN R. DAYCite this: J. Org. Chem. 1957, 22, 9, 1061–1065Publication Date (Print):September 1, 1957Publication History Published online1 May 2002Published inissue 1 September 1957https://doi.org/10.1021/jo01360a017RIGHTS & PERMISSIONSArticle Views311Altmetric-Citations13LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (604 KB) Get e-Alerts Get e-Alerts
Rheumatoid synovial fluid contains bioactive leukemia inhibitory factor with cartilage degrading activity--another target for chondroprotective intervention. (2000)

These findings are consistent with the concept that IL-1 stimulates cartilage proteoglycan resorption in RA. They also support the hypothesis that LIF, too, contributes to cartilage proteoglycan resorption in RA. The residual stimulation not accounted for by IL-1 or LIF suggests other cytokines may contribute. The role of LIF and related or unrelated cytokines may need to be taken into account to optimize chondroprotection in RA and other rheumatic diseases.
Inhibition of Release of Neurotransmitters from Rat Dorsal Root Ganglia by a Novel Conjugate of a Clostridium botulinumToxin A Endopeptidase Fragment and Erythrina cristagalliLectin (2002)

Clostridial neurotoxins potently and specifically inhibit neurotransmitter release in defined cell types. Here we report that a catalytically active derivative (termed LH(N)/A) of the type A neurotoxin from Clostridium botulinum has been coupled to a lectin obtained from Erythrina cristagalli to form a novel conjugate. This conjugate exhibits an in vitro selectivity for nociceptive afferents compared with the anatomically adjacent spinal neurons, as assessed using in vitro primary neuronal culture systems to measure inhibition of release of neurotransmitters. Chemical conjugates prepared between E. cristagalli lectin and either natively sourced LH(N)/A or recombinant LH(N)/A purified from Escherichia coli are assessed, and equivalence of the recombinant material are demonstrated. Furthermore, the dependence of inhibition of neurotransmitter release on the cleavage of SNAP-25 is demonstrated through the use of an endopeptidase-deficient LH(N)/A conjugate variant. The duration of action of inhibition of neurotransmitter released by the conjugate in vitro is assessed and is comparable with that observed with Clostridium botulinum neurotoxin. Finally, in vivo electrophysiology shows that these in vitro actions have biological relevance in that sensory transmission from nociceptive afferents through the spinal cord is significantly attenuated. These data demonstrate that the potent endopeptidase activity of clostridial neurotoxins can be selectively retargeted to cells of interest and that inhibition of release of neurotransmitters from a neuronal population of therapeutic relevance to the treatment of pain can be achieved.
Influenza Virus PB1-F2 Protein Induces Cell Death through Mitochondrial ANT3 and VDAC1 (2005)

The influenza virus PB1-F2 is an 87-amino acid mitochondrial protein that previously has been shown to induce cell death, although the mechanism of apoptosis induction has remained unclear. In the process of characterizing its mechanism of action we found that the viral PB1-F2 protein sensitizes cells to apoptotic stimuli such as tumor necrosis factor alpha, as demonstrated by increased cleavage of caspase 3 substrates in PB1-F2-expressing cells. Moreover, treatment of purified mouse liver mitochondria with recombinant PB1-F2 protein resulted in cytochrome c release, loss of the mitochondrial membrane potential, and enhancement of tBid-induced mitochondrial permeabilization, suggesting a possible mechanism for the observed cellular sensitization to apoptosis. Using glutathione-S-transferase pulldowns with subsequent mass spectrometric analysis, we identified the mitochondrial interactors of the PB1-F2 protein and showed that the viral protein uniquely interacts with the inner mitochondrial membrane adenine nucleotide translocator 3 and the outer mitochondrial membrane voltage-dependent anion channel 1, both of which are implicated in the mitochondrial permeability transition during apoptosis. Consistent with this interaction, blockers of the permeability transition pore complex (PTPC) inhibited PB1-F2-induced mitochondrial permeabilization. Based on our findings, we propose a model whereby the proapoptotic PB1-F2 protein acts through the mitochondrial PTPC and may play a role in the down-regulation of the host immune response to infection.
Direct C–H arylation: a “Greener” approach towards facile synthesis of organic semiconducting molecules and polymers (2017)

Direct C–H arylation enables “greener” synthesis of π-conjugated small molecules and polymers without tedious preactivation of C–H bonds.
Two‐chain high molecular weight kininogen induces endothelial cell apoptosis and inhibits angiogenesis: partial activity within domain 5 (2000)

We previously reported that the binding of two-chain high molecular weight kininogen (HKa) to endothelial cells may occur through interactions with endothelial urokinase receptors. Since the binding of urokinase to urokinase receptors activates signaling responses and may stimulate mitogenesis, we assessed the effect of HKa binding on endothelial cell proliferation. Unexpectedly, HKa inhibited proliferation in response to several growth factors, with 50% inhibition caused by approximately 10 nM HKa. This activity was Zn(2+) dependent and not shared by either single-chain high molecular weight kininogen (HK) or low molecular weight kininogen. HKa selectively inhibited the proliferation of human umbilical vein and dermal microvascular endothelial cells, but did not affect that of umbilical vein or human aortic smooth muscle cells, trophoblasts, fibroblasts, or carcinoma cells. Inhibition of endothelial proliferation by HKa was associated with endothelial cell apoptosis and unaffected by antibodies that block the binding of HK or HKa to any of their known endothelial receptors. Recombinant HK domain 5 displayed activity similar to that of HKa. In vivo, HKa inhibited neovascularization of subcutaneously implanted Matrigel plugs, as well as rat corneal angiogenesis. These results demonstrate that HKa is a novel inhibitor of angiogenesis, whose activity is dependent on the unique conformation of the two-chain molecule.
Mechanical behavior of materials (1990)

This text serves to cover in more detail solid mechanics concepts and specifically the material response to stress and strain. This text spans solid mechanics concepts from stress and strain at an atomistic length scale, to linear elasticity, anisotropy, linear viscoelasticity, plasticity, dislocation generation and interactions, and fracture.
Reaction Kinetics of the Catalytic Esterification of Citric Acid with Ethanol (2006)

Reaction kinetics are presented for the reversible esterification reaction of citric acid with ethanol to form tri-ethyl citrate via mono-ethyl and di-ethyl citrates. The reaction was studied in batch isothermal experiments, self-catalyzed homogeneously by citric acid and the formed mono- and di-ethyl citrates, and heterogeneously catalyzed by macroporous Amberlyst-15 ion-exchange resin catalyst. Experimental data were obtained between 78 and 120 °C at different mole ratios of ethanol to citric acid and catalyst concentrations up to 5 wt % ion-exchange resin. The kinetics of ethanol etherification to form di-ethyl ether were included in the investigation. Kinetic modeling was performed using a pseudo-homogeneous UNIQUAC-based activity model, taking into consideration the rate of self-catalyzed esterification and the side reaction to form diethyl ether. The activity coefficients for the tri-ethyl citrate−ethanol and tri-ethyl citrate−water binary pairs were obtained from experimental vapor−liquid equilibrium data. Kinetics of the di-ethyl citrate to tri-ethyl citrate reaction limit the overall tri-ethyl citrate formation rate, as citric acid and mono-ethyl citrate are esterified rapidly to their equilibrium compositions. Higher temperatures lead to faster reaction kinetics but significantly increase the production of the undesired byproduct di-ethyl ether. The kinetic model developed is useful for the design and simulation of processes such as reactive distillation for tri-ethyl citrate formation.
Overexpression of cyclin D1 enhances gene amplification. (1996)

Defects in cell cycle control and increased genomic instability, including gene amplification, often occur during cancer development. Cyclin D1 plays a pivotal role in G1, and this gene is frequently amplified and overexpressed in several types of human cancer. This study demonstrates that ectopic overexpression of cyclin D1 in a rat liver epithelial cell line markedly increased the yield of cells containing amplified copies of the CAD gene. This effect was associated with a loss of G1-S checkpoint control, although the cyclin D1-overexpressing cells had a normal p53 gene. The capacity of cyclin D1 to enhance gene amplification may contribute to the process of genomic instability during tumor development.
Current Challenges of Cancer Anti-angiogenic Therapy and the Promise of Nanotherapeutics (2017)

With growing interest in cancer therapeutics, anti-angiogenic therapy has received considerable attention and is widely administered in several types of human cancers. Nonetheless, this type of therapy may induce multiple signaling pathways compared with cytotoxics and lead to worse outcomes in terms of resistance, invasion, metastasis, and overall survival (OS). Moreover, there are important challenges that limit the translation of promising biomarkers into clinical practice to monitor the efficiency of anti-angiogenic therapy. These pitfalls emphasize the urgent need for discovering alternative angiogenic inhibitors that target multiple angiogenic factors or developing a new drug delivery system for the current inhibitors. The great advantages of nanoparticles are their ability to offer effective routes that target the biological system and regulate different vital processes based on their unique features. Limited studies so far have addressed the effectiveness of nanoparticles in the normalization of the delicate balance between stimulating (pro-angiogenic) and inhibiting (anti-angiogenic) factors. In this review, we shed light on tumor vessels and their microenvironment and consider the current directions of anti-angiogenic and nanotherapeutic treatments. To the best of our knowledge, we consider an important effort in the understanding of anti-angiogenic agents (often a small volume of metals, nonmetallic molecules, or polymers) that can control the growth of new vessels.
Comparison of peptide enzyme-linked immunosorbent assay and radioimmunoprecipitation assay with in vitro-translated proteins for detection of serum antibodies to human papillomavirus type 16 E6 and E7 proteins (1994)

Antibodies to human papilloma virus (HPV) type 16 (HPV-16) E6 and E7 proteins in serum are markers for HPV-associated invasive cervical carcinoma. We compared two assays, a radioimmunoprecipitation assay with in vitro-translated HPV-16 E6 and E7 proteins and an enzyme-linked immunosorbent assay (ELISA) with E6 and E7 synthetic peptides, for their abilities to discriminate serologically between patients with invasive cervical cancer and controls. Among the patients, antibody prevalences were higher by the E6 radioimmunoprecipitation assay (55.7%) than by the E6 peptide ELISA (15.5%), but among the controls, they were lower by the radioimmunoprecipitation assay (1.7%) than by the E6 peptide ELISA (5%). For E7, antibody prevalences among the patients were comparable by the radioimmunoprecipitation assay (43%) and the peptide ELISA (41%), but among the controls they were higher by the E7 peptide ELISA (17.4%) than by the radioimmunoprecipitation assay (4.1%). There was good agreement between the E7 radioimmunoprecipitation assay and the E7 peptide ELISA among patients but not among controls. In tests with representative sera, heat denaturation of the translated proteins resulted in a complete loss of reactivity to the E6 protein and a marked decrease in reactivity to the E7 protein. Our study showed that the radioimmunoprecipitation assay discriminates better than the peptide ELISA between patients with invasive cervical cancer and controls and that this is related to the ability of the radioimmunoprecipitation assay to detect conformational epitopes.