gebhart/patrepeval huggingface dataset:
The keratinocyte in epidermal renewal and defence (2009)

Traditionally, keratinocytes have been considered inert constituents of the multilayered epidermis. Today's understanding has fundamentally changed. The keratinocyte is now recognized as an active player in epidermal renewal with key functions in the skin's immune defence. Under homeostatic conditions, keratinocyte progenitor cells are believed to divide symmetrically or asymmetrically, that is they continue to proliferate or go on to terminally differentiate and build up the overlaying epidermis. The fine-tuned process of epidermal renewal relies on an extraordinary network of signalling cascades which are governed by keratinocyte-receptor interactions with the environment through paracrine and autocrine circuits. Opposing this coordinated homeostatic process are signals of wounding and inflammation. They alter the fate of the keratinocyte and its response to the environment through changes in adhesion molecules and surface receptors, in addition to triggering an immediate inflammatory keratinocyte response in terms of secretion of cytokines, chemokines and antimicrobial peptides. If uncontrolled, the fundamental changes imposed by wounding and inflammation upon the homeostatic programme can lead to severe skin lesions including chronic inflammatory disorders. This review will describe the current knowledge of the regulatory signalling network which allows the keratinocyte to actively impact both epidermal homeostasis and the inflammatory response.
The Synthesis of C-Methyl Branched-Chain Deoxy Sugar Nucleosides by the Deoxygenative Methylation of O-Tosylated Adenosines with Grignard Reagents (1988)

Abstract The reaction of appropriately protected 2′-O-tosyladenosines with methylmagnesium bromide (or iodide) gave 9-(2-deoxy-3-C-methyl-β-d-threo-pentofuranosyl)adenine after deprotection. The same reaction on 3′-O-tosyladenosine derivatives afforded an epimeric pair of 2′-C-methyl-3′-deoxy sugar nucleosides. The modified structures of the sugar moieties were determined unambiguously.
The ferroptosis inducer erastin irreversibly inhibits system xc− and synergizes with cisplatin to increase cisplatin’s cytotoxicity in cancer cells (2018)

System x<sub>c</sub><sup>-</sup> was recently described as the most upstream node in a novel form of regulated necrotic cell death, called ferroptosis. In this context, the small molecule erastin was reported to target and inhibit system x<sub>c</sub><sup>-</sup>, leading to cysteine starvation, glutathione depletion and consequently ferroptotic cell death. Although the inhibitory effect of erastin towards system x<sub>c</sub><sup>-</sup> is well-documented, nothing is known about its mechanism of action. Therefore, we sought to interrogate in more detail the underlying mechanism of erastin's pro-ferroptotic effects. When comparing with some well-known inhibitors of system x<sub>c</sub><sup>-</sup>, erastin was the most efficient inhibitor acting at low micromolar concentrations. Notably, only a very short exposure of cells with low erastin concentrations was sufficient to cause a strong and persistent inhibition of system x<sub>c</sub><sup>-</sup>, causing glutathione depletion. These inhibitory effects towards system x<sub>c</sub><sup>-</sup> did not involve cysteine modifications of the transporter. More importantly, short exposure of tumor cells with erastin strongly potentiated the cytotoxic effects of cisplatin to efficiently eradicate tumor cells. Hence, our data suggests that only a very short pre-treatment of erastin suffices to synergize with cisplatin to efficiently induce cancer cell death, findings that might guide us in the design of novel cancer treatment paradigms.
LiveSynth: Towards an interactive synthesis flow (2016)

The incremental step of LiveSynth reduces synthesis time by about 95% for incremental changes. LiveSynth shifts the paradigm to small, incremental changes and more iterations per day. We advocate for an interactive synthesis flow as a way to boost design productivity.
Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy (2009)

Frameshift MYBPC3 mutations cause haploinsufficiency, deranged phosphorylation of contractile proteins, and reduced maximal force-generating capacity of cardiomyocytes. The enhanced Ca(2+) sensitivity in MYBPC3(mut) is due to hypophosphorylation of troponin I secondary to mutation-induced dysfunction.
A TECHNICAL, ECONOMIC AND ENVIRONMENTAL ASSESSMENT OF AMINE-BASED CO2 CAPTURE TECHNOLOGY FOR POWER PLANT GREENHOUSE GAS CONTROL (2002)

Capture and sequestration of CO{sub 2} from fossil fuel power plants is gaining widespread interest as a potential method of controlling greenhouse gas emissions. Performance and cost models of an amine (MEA)-based CO{sub 2} absorption system for post-combustion flue gas applications have been developed, and integrated with an existing power plant modeling framework that includes multi-pollutant control technologies for other regulated emissions. The integrated model has been applied to study the feasibility and cost of carbon capture and sequestration at both new and existing coal-burning power plants. The cost of carbon avoidance was shown to depend strongly on assumptions about the reference plant design, details of the CO{sub 2} capture system design, interactions with other pollution control systems, and method of CO{sub 2} storage. The CO{sub 2} avoidance cost for retrofit systems was found to be generally higher than for new plants, mainly because of the higher energy penalty resulting from less efficient heat integration, as well as site-specific difficulties typically encountered in retrofit applications. For all cases, a small reduction in CO{sub 2} capture cost was afforded by the SO{sub 2} emission trading credits generated by amine-based capture systems. Efforts are underway to model a broader suite of carbon capture and sequestration technologies for more comprehensive assessments in the context of multi-pollutant environmental management.
A Four Component Coupling Strategy for the Synthesis of D‐Phenylglycinamide‐Derived Non‐Covalent Factor Xa Inhibitors. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
A new panel-integratable inverter concept for grid-connected photovoltaic systems (2002)

This paper describes the problems of conventional inverter concepts for photovoltaic power systems and presents a new, panel-integratable inverter concept as a solution. This concept is advantageous regarding safety (no DC-lines), flexibility (modular concept), converted energy per year (no mismatch losses due to individual MPP tracking of each panel) and costs (no reinforced isolation due to AC distribution). Furthermore a 250 W DC to AC inverter is developed, which consists of a series resonant DC-DC power converter and a line inverter. The inverter has a high efficiency and consumes little power itself. Meeting international standards, sinusoidal line current with low distortion is achieved. The inverter has a built-in controller to operate the panel in the maximum power point. Above this, the concept allows the flexible use with many different combinations of solar panels. To realize an inexpensive system, the controller is built up using standard low-cost components.
Effects of tocopherol (vitamin E) acid succinate on morphological alterations and growth inhibition in melanoma cells in culture. (1982)

The effects of various forms of tocopherol (vitamin E) on the growth and differentiation of mouse melanoma (B-16) and mouse fibroblast (L-cells) cells in culture were studied. D-alpha-tocopherol acid succinate induced morphological alterations and growth inhibition in melanoma cells. When vitamin E acid succinate was removed 4 days after treatment, the above changes remained irreversible for a period of 24 hr, after which resistant cells and partially affected cells renewed cell division and eventually reached confluency. The relative efficacy of D and DL forms of vitamin E acid succinate remains to be evaluated. However, other forms of vitamin E such as DL-alpha-tocopherol free alcohol, Aquasol DL-alpha-tocopherol acetate, DL-alpha-tocopherol nicotinate, or sodium succinate with an equivalent volume of ethanol, at similar concentrations, were ineffective. Vitamin E acid succinate at similar concentrations did not induce morphological changes in fibroblasts. Melanoma cells were about 2-fold more sensitive to vitamin E acid succinate than were fibroblasts for the criterion of growth inhibition. Vitamin E acid succinate-induced morphological changes and growth inhibition in melanoma cells were expressed in hormone-supplemented serum-free medium, but the concentration requirement was about 5 times less than that needed in serum-supplemented medium. Although cyclic adenosine 3': 5'-monophosphate-stimulating agents are known to cause growth inhibition and morphological changes in melanoma cells in culture, vitamin E acid succinate-induced morphological alterations in melanoma cells are no mediated by a rise in cellular cyclic adenosine 3':5'-monophosphate. Ethanol was sufficient to increase the melanin content in melanoma cells. These data show that vitamin E acid succinate may be a potentially useful tumor therapeutic agent.
A hospital based study on the prevalence of conjunctivitis due to Chlamydia trachomatis. (2003)

A significant decrease in the prevalence of adult chlamydial conjunctivitis has occurred in the 10-year period among patients reporting to the ophthalmic hospitals in Chennai. PCR using cryptic plasmid primers was found to be the most sensitive method to detect C. trachomatis in patients with conjunctivitis.
In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma (2009)

The potent activity, together with the exclusive mechanistic profile, provides the rationale for the clinical evaluation of these drug combinations in multiple myeloma.
A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion. (1989)

Molecular level studies on platelets deficient in collagen-induced aggregation provide evidence for identifying possible platelet collagen receptors. We investigated platelets from a patient with mild bleeding time prolongation, but otherwise normal coagulation data. Her platelets lacked collagen-induced aggregation and adhesion, but retained normal aggregation and release by other agonists. Labeling her platelets with 125I or 3H and analysis by SDS-PAGE/autoradiography showed normal levels of glycoproteins Ia, Ib, IIa, IIb, IIIa, and IV. However, there were significantly decreased incorporations of both radioactivities into a 61-kD membrane glycoprotein (GP), which was identified as GPVI from its mobility on unreduced-reduced, two-dimensional SDS-PAGE. Sugiyama et al. (1987. Blood. 69: 1712) reported that the serum from an idiopathic thrombocytopenic purpura (ITP) patient contained an antibody against a 62-kD platelet protein. Our patient's platelets lacked the antigen for the ITP patient's antibody, demonstrating that the ITP serum contains a specific antibody against GPVI. The patient's parents' platelets contained approximately 50% the normal amount of GPVI, but still had normal collagen-induced aggregation and adhesion. The patient's platelets did not bind to types I and III collagen fibrils. Our results suggest that GPVI functions as a collagen receptor.
Model-based morphological segmentation and labeling of coronary angiograms (1999)

A method for extraction and labeling of the coronary arterial tree (CAT) using minimal user supervision in single-view angiograms is proposed. The CAT structural description (skeleton and borders) is produced, along with quantitative information for the artery dimensions and assignment of coded labels, based on a given coronary artery model represented by a graph. The stages of the method are: 1) CAT tracking and detection; 2) artery skeleton and border estimation; 3) feature graph creation; and iv) artery labeling by graph matching. The approximate CAT centerline and borders are extracted by recursive tracking based on circular template analysis. The accurate skeleton and borders of each CAT segment are computed, based on morphological homotopy modification and watershed transform. The approximate centerline and borders are used for constructing the artery segment enclosing area (ASEA), where the defined skeleton and border curves are considered as markers. Using the marked ASEA, an artery gradient image is constructed where all the ASEA pixels (except the skeleton ones) are assigned the gradient magnitude of the original image. The artery gradient image markers are imposed as its unique regional minima by the homotopy modification method, the watershed transform is used for extracting the artery segment borders, and the feature graph is updated. Finally, given the created feature graph and the known model graph, a graph matching algorithm assigns the appropriate labels to the extracted CAT using weighted maximal cliques on the association graph corresponding to the two given graphs. Experimental results using clinical digitized coronary angiograms are presented.
MUC1 Oncoprotein Promotes Refractoriness to Chemotherapy in Thyroid Cancer Cells (2007)

Overexpression of MUC1 oncoprotein is frequently observed in cancer and contributes to confer resistance to genotoxic agents. Papillary, follicular, and anaplastic thyroid carcinomas are the three forms of thyroid epithelial cancer. Anaplastic tumors are less differentiated and extremely aggressive, characterized by a poor prognosis. Little is known about the role of MUC1 in thyroid cancer. We recently showed that autocrine production of interleukin (IL)-4 and IL-10 controls thyroid cancer cell survival, growth, and resistance to chemotherapy through activation of Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) and phosphatidylinositide 3'-OH kinase (PI3K)/Akt pathways. In the present study, we showed that MUC1 COOH-terminal subunit (MUC1-C) is overexpressed in all the histologic variants of thyroid cancer cells and localizes to mitochondria where it interferes with the release of mitochondrial proapoptotic proteins. Moreover, IL-4 and IL-10 promote the increase of MUC1-C expression levels in normal thyroid cells, whereas blockage of both cytokines or neutralization of JAK/STAT and PI3K/Akt pathways through the exogenous expression of SOCS-1 and Akt(K179M) leads to a significant decrease of MUC1-C in primary thyroid cancer cells. Interestingly, down-regulation of MUC1 expression by direct targeting with RNA interference sensitizes anaplastic thyroid cancer cells to chemotherapy-induced apoptosis in vitro. Thus, MUC1 is a main component of the survival network acting in thyroid cancer and could be considered a key molecular target for sensitizing cancer cells to conventional or novel treatments.
Interplant communication: airborne methyl jasmonate induces synthesis of proteinase inhibitors in plant leaves. (1990)

Inducible defensive responses in plants are known to be activated locally and systemically by signaling molecules that are produced at sites of pathogen or insect attacks, but only one chemical signal, ethylene, is known to travel through the atmosphere to activate plant defensive genes. Methyl jasmonate, a common plant secondary compound, when applied to surfaces of tomato plants, induces the synthesis of defensive proteinase inhibitor proteins in the treated plants and in nearby plants as well. The presence of methyl jasmonate in the atmosphere of chambers containing plants from three species of two families, Solanaceae and Fabaceae, results in the accumulation of proteinase inhibitors in leaves of all three species. When sagebrush, Artemisia tridentata, a plant shown to possess methyl jasmonate in leaf surface structures, is incubated in chambers with tomato plants, proteinase inhibitor accumulation is induced in the tomato leaves, demonstrating that interplant communication can occur from leaves of one species of plant to leaves of another species to activate the expression of defensive genes.
Two Related Regulatory Sequences Are Required for Maximal Induction of Saccharomyces cerevisiae his3 Transcription (1987)

In Saccharomyces cerevisiae, the coordinate induction of his3 and other amino acid biosynthesis genes is mediated by the binding of GCN4 activator protein to specific promoter sequences. The his3 regulatory region contains the sequence TGACTC, which with some variation is repeated six times upstream of the mRNA initiation site. The requirements for maximal his3 induction were examined with a series of sequential 5' deletion mutations as well as a set of small internal deletions. Deletions encroaching as far downstream as position -142 behave indistinguishably from the wild-type gene, thus indicating that the two proximal copies of the regulatory sequence are sufficient for maximal induction. Deletions with breakpoints between -137 and -99 confer inducibility, but not to the normal wild-type level. A deletion ending immediately upstream of the proximal TGACTC sequence (position -99) shows some constitutive expression that is independent of the gcn4 gene product. Deletions extending to -94 or beyond do not produce detectable levels of his3 mRNA. Small internal deletions that only remove the proximal regulatory sequence and a 1-base-pair deletion of the thymine residue at -99 abolish induction, but do not affect the basal level of transcription. These results indicate that the proximal copy between -99 and -94 is absolutely required for his3 induction, whereas the copy between -142 and -137 is required only for the maximal level of induction and is inactive by itself. From these and other observations, we suggest the possibility that these related regulatory sequences may be targets for two distinct proteins.
In vitro and in vivo antifungal activities of DU-6859a, a fluoroquinolone, in combination with amphotericin B and fluconazole against pathogenic fungi (1995)

DU-6859a is an investigational fluoroquinolone agent with potent bactericidal activity, but by itself it has no antifungal activity. When combined with amphotericin B (AmB), however, DU-6859a clearly enhanced the in vitro antifungal activity of AmB against Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, and Cryptococcus neoformans in microdilution checkerboard studies. Positive interactions of DU-6859a with AmB against Aspergillus fumigatus were dependent on the medium used; yeast nitrogen base supplemented with amino acids, ammonium sulfate, and 1% glucose was better for demonstrating synergism, while in RPMI 1640 medium, unexpected antagonism between the drugs occurred against three of the strains tested. In combination with fluconazole (Flu), DU-6859a increased the activity of Flu against C. albicans both in synthetic amino acid medium fungal and in supplemented yeast nitrogen base. An in vitro time-kill study revealed that DU-6859a combined with AmB significantly suppressed the regrowth of C. albicans compared with the suppression brought about by AmB used alone in a concentration-dependent fashion. Furthermore, in a model of C. albicans infection in mice, the fungal load in infected kidneys was significantly less in mice given the combination treatment of DU-6859a plus either AmB or Flu, and thus, the combination treatment resulted in prolonged survival of infected mice compared with treatment with either antifungal alone. The prolonged survival in mice given the combined treatment was also observed in mice with A. fumigatus infection, indicating that DU-6859a potentiated the actions of the antifungal agents in vivo as well as in vitro.
Role and regulation of coordinately expressedde novopurine biosynthetic enzymesPPATandPAICSin lung cancer (2015)

Cancer cells exhibit altered metabolism including aerobic glycolysis that channels several glycolytic intermediates into de novo purine biosynthetic pathway. We discovered increased expression of phosphoribosyl amidotransferase (PPAT) and phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) enzymes of de novo purine biosynthetic pathway in lung adenocarcinomas. Transcript analyses from next-generation RNA sequencing and gene expression profiling studies suggested that PPAT and PAICS can serve as prognostic biomarkers for aggressive lung adenocarcinoma. Immunohistochemical analysis of PAICS performed on tissue microarrays showed increased expression with disease progression and was significantly associated with poor prognosis. Through gene knockdown and over-expression studies we demonstrate that altering PPAT and PAICS expression modulates pyruvate kinase activity, cell proliferation and invasion. Furthermore we identified genomic amplification and aneuploidy of the divergently transcribed PPAT-PAICS genomic region in a subset of lung cancers. We also present evidence for regulation of both PPAT and PAICS and pyruvate kinase activity by L-glutamine, a co-substrate for PPAT. A glutamine antagonist, 6-Diazo-5-oxo-L-norleucine (DON) blocked glutamine mediated induction of PPAT and PAICS as well as reduced pyruvate kinase activity. In summary, this study reveals the regulatory mechanisms by which purine biosynthetic pathway enzymes PPAT and PAICS, and pyruvate kinase activity is increased and exposes an existing metabolic vulnerability in lung cancer cells that can be explored for pharmacological intervention.
Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker (2008)

Modified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients. The 6-bp deletion in TS-3'UTR might be a candidate to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial.
Monitoring viral RNA in infected cells with LNA flow-FISH (2010)

We previously showed the feasibility of using locked nucleic acid (LNA) for flow cytometric-fluorescence in situ hybridization (LNA flow-FISH) detection of a target cellular mRNA. Here we demonstrate how the method can be used to monitor viral RNA in infected cells. We compared the results of the LNA flow-FISH with other methods of quantifying virus replication, including the use of an enhanced green fluorescent protein (EGFP) viral construct and quantitative reverse-transcription polymerase chain reaction. We found that an LNA probe complementary to Sindbis virus RNA is able to track the increase in viral RNA over time in early infection. In addition, this method is comparable to the EGFP construct in sensitivity, with both peaking around 3 h and at the same level of infected cells. Finally, we observed that the LNA flow-FISH method responds to the decrease in levels of viral RNA caused by antiviral medication. This technique represents a straightforward way to monitor viral infection in cells and is easily applicable to any virus.