gebhart/patrepeval huggingface dataset:
Small Molecule Inhibitors of STAT3 for Cancer Therapy (2011)

Aberrant activation of the signal transducer and activator of transcription (STAT) 3 occurs in many human tumors. Constitutive STAT3 activity induces specific target genes that stimulate cell proliferation, prevent apoptosis, promote angiogenesis and facilitate tumor immune evasion. Thus, STAT3 is an attractive molecular target for the development of novel cancer therapeutics. Targeting and disruption of oncogenic STAT3 signaling may theoretically be accomplished through various approaches, involving direct and indirect strategies. Small molecular weight compounds have been used for this purpose. This review is intended to be full coverage of the small molecular inhibitors to develop direct STAT3 as a target for cancer therapy and will provide a discussion on the inhibitory modalities developed to date. At present, we retrieved related small molecular inhibitors experimental research papers about STAT3 as a cancer therapy target, the rationale to pursue the protein for the discovery and development of novel anticancer strategies and agents.
Phase II Study of the Antiangiogenic Agent SU5416 in Patients with Advanced Soft Tissue Sarcomas (2004)

SU5416 was relatively well tolerated but did not demonstrate significant antitumor activity against advanced soft tissue sarcoma. Correlative studies suggest that VEGF receptor or KIT inhibition was incomplete in at least some cases, providing a possible explanation for the observed lack of activity.
News on the treatment of women with Hypoactive Sexual Desire Disorder (HSDD) (2008)

A significant proportion of women reporting female sexual dysfunction (FSD) suffer from hypoactive sexual desire disorder (HSDD) which is characterized by a loss of sexual desire leading to distress. HSDD is highly prevalent in women of any age, but only in the recent years some research has been conducted to uncover the potential causes and to find therapeutic strategies. A complex interplay of biological, psychological and socio-relational factors is related to women's sexual health during the entire reproductive life span. Menopause is a time of vulnerability to sexual symptoms as a result of sex hormonal changes inducing climacteric syndrome. Vaginal dryness is a common feature significantly affecting genital arousal and, consequently, desire, orgasm and satisfaction. Recently, HSDD has been well described especially in surgical menopause, a clinical condition clearly characterized by the loss of both estrogens and androgens. Therefore, the major focus is on hormonal treatments, in particular the testosterone (T) patch which is able to restore T levels to premenopausal stage with a significant improvement of sexual activity, desire and satisfaction, reducing women’distress both in surgical and natural menopause. However, there is a medical need to develop novel therapies that can be used even in younger women. A great hope comes from drugs acting on central nervous dopaminergic, serotoninergic and noradrenergic pathways involved in mental drive, arousal and satisfaction. In any case, hormonal and non hormonal treatments and/or psychosexual strategies should be individualized and tailored on women's history and current needs to counteract the distress associated with HSDD.
Serologic Diagnosis of Lyme Disease (1988)

Indirect fluorescent antibody tests and enzyme-linked immunosorbent assays are being used as laboratory aids for the diagnosis of Lyme disease and related disorders. Depending on the needs, polyvalent or class-specific reagents can be used to detect total immunoglobulins (Ig) or IgM and IgG antibodies. The sensitivities of these assays are relatively low when serum samples are obtained from patients within 3 weeks after onset of erythema migrans and are tested by either the IFA method or ELISA. During neuritis or arthritis, IgG antibody levels are usually elevated, and serologic verification is more easily achieved. Cross-reactivity occurs when sera from patients with Lyme disease, relapsing fever, or treponemal infections are screened against heterologous antigens, but these diseases can usually be separated clinically or by further seroanalyses. Although IFA tests and ELISA are both suitable for confirming Lyme disease, the objective results and the ability to perform many more analyses make ELISA the preferred method.
Copper(I) salt-mediated arylation of phosphinyl-stabilized carbanions and synthetic application to heterocyclic compounds (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCopper(I) salt-mediated arylation of phosphinyl-stabilized carbanions and synthetic application to heterocyclic compoundsToru Minami, Takeshi Isonaka, Yoshiharu Okada, and Junji IchikawaCite this: J. Org. Chem. 1993, 58, 25, 7009–7015Publication Date (Print):December 1, 1993Publication History Published online1 May 2002Published inissue 1 December 1993https://doi.org/10.1021/jo00077a018RIGHTS & PERMISSIONSArticle Views1064Altmetric-Citations37LEARN 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 (882 KB) Get e-Alerts Get e-Alerts
Influence of different diets on development of DMH‐induced aberrant crypt foci and colon tumor incidence in Wistar rats (1995)

The present study was undertaken to investigate certain dietary factors known to affect the development of colon cancer for their ability to modulate aberrant crypt foci (ACF). Male Wistar rats were initiated with oral doses of dimethylhydrazine dihydrochloride (DMH-2HCl, 20 mg/kg body wt) once a week for 10 or 20 weeks. Throughout the study the animals were fed 1) semisynthetic casein-based control diet, 2) control diet with 20% lard, 3) control diet with 20% lard and 20% dietary fiber, or 4) control diet where most of the carbohydrate pool was substituted with sucrose and dextrin. The composition of the different diets was designed to achieve equivalent intakes of essential nutrients. Animals were killed after 10, 20 and 31 weeks. The study showed a pronounced effect of dietary composition on the development of DMH-induced ACF. The diet high in sucrose and dextrin caused a statistically significant increase (p < or = 0.05) in the total number of ACF and number of small and medium ACF. Adding lard to the standard diet did not cause an increase in ACF, but if the dietary fiber was added to the high-fat diet, a statistically significant reduction (p < or = 0.05) in the total number of ACF and number of small and medium ACF was observed. The values of large and extra-large foci reflected the same effect of diets on ACF. The results indicate that tumors in the group fed the diet high in refined carbohydrates were more prominent and occurred with a higher incidence. However, the difference is based on few tumors and is not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Molecular characterization of human brain N-acetylated alpha-linked acidic dipeptidase (NAALADase). (1998)

N-Acetylated alpha-linked acidic dipeptidase (NAALADase) is a neuropeptidase that may modulate glutamatergic neurotransmission. Independent of its characterization in the nervous system, one form of NAALADase was shown to be expressed at high levels in human prostatic adenocarcinomas, and it was designated the prostate-specific membrane antigen (PSMA). The NAALADase/PSMA gene is known to produce multiple mRNA splice forms, and based on previous immunohistochemical evidence, it had been assumed that the human brain and prostate expressed different isoforms of the enzyme. Because PSMA is being actively pursued as a target for autoimmune and cytotoxic targeting strategies to treat prostate cancer, the rigorous comparison of the two forms of the enzyme remained an important but untested question. To assess similarities and/or differences between human brain NAALADase and PSMA, we compared the two molecules using criteria of activity, immunoreactivity and sequences of the corresponding mRNAs. NAALADase from human cerebellar isolates displayed a kinetic profile and pharmacological sensitivities similar to PSMA. Also, Northern hybridization to PSMA cDNA detected indistinguishable sets of 2.8-, 4.0- and 6.0-kb RNA species in human brain and the LNCaP prostatic tumor cell line. In addition, the monoclonal antibody 7E11-C5 directed against the prostatic form of the enzyme immunoprecipitated 82% of human cerebellar NAALADase activity. Moreover, reverse transcription-polymerase chain reaction cloning of cerebellar cDNAs indicated that the human brain and prostate express a common mRNA splice form. Therefore, we conclude that the form of NAALADase also known as PSMA is expressed in brain and comprises a significant fraction of brain NAALADase activity.
Expression and Functional Characterization of aDrosophila Neuropeptide Precursor with Homology to Mammalian Preprotachykinin A (2000)

Peptides structurally related to mammalian tachykinins have recently been isolated from the brain and intestine of several insect species, where they are believed to function as both neuromodulators and hormones. Further evidence for the signaling role of insect tachykinin-related peptides was provided by the cloning and characterization of cDNAs for two tachykinin receptors from Drosophila melanogaster. However, no endogenous ligand has been isolated for the Drosophila tachykinin receptors to date. Analysis of the Drosophila genome allowed us to identify a putative tachykinin-related peptide prohormone (prepro-DTK) gene. A 1.5-kilobase pair cDNA amplified from a Drosophila head cDNA library contained an 870-base pair open reading frame, which encodes five novel Drosophila tachykinin-related peptides (called DTK peptides) with conserved C-terminal FXGXR-amide motifs common to other insect tachykinin-related peptides. The tachykinin-related peptide prohormone gene (Dtk) is both expressed and post-translationally processed in larval and adult midgut endocrine cells and in the central nervous system, with midgut expression starting at stage 17 of embryogenesis. The predicted Drosophila tachykinin peptides have potent stimulatory effects on the contractions of insect gut. These data provide additional evidence for the conservation of both the structure and function of the tachykinin peptides in the brain and gut during the course of evolution.
Identifying fake Amazon reviews as learning from crowds (2014)

Customers who buy products such as books online often rely on other customers reviews more than on reviews found on specialist magazines. Unfortunately the confidence in such reviews is often misplaced due to the explosion of so-called sock puppetry-Authors writing glowing reviews of their own books. Identifying such deceptive reviews is not easy. The first contribution of our work is the creation of a collection including a number of genuinely deceptive Amazon book reviews in collaboration with crime writer Jeremy Duns, who has devoted a great deal of effort in unmasking sock puppeting among his colleagues. But there can be no certainty concerning the other reviews in the collection: All we have is a number of cues, also developed in collaboration with Duns, suggesting that a review may be genuine or deceptive. Thus this corpus is an example of a collection where it is not possible to acquire the actual label for all instances, and where clues of deception were treated as annotators who assign them heuristic labels. A number of approaches have been proposed for such cases; we adopt here the 'learning from crowds' approach proposed by Raykar et al. (2010). Thanks to Duns' certainly fake reviews, the second contribution of this work consists in the evaluation of the effectiveness of different methods of annotation, according to the performance of models trained to detect deceptive reviews. © 2014 Association for Computational Linguistics.
TCDD-inducible poly-ADP-ribose polymerase (TIPARP/PARP7) mono-ADP-ribosylates and co-activates liver X receptors (2016)

Members of the poly-ADP-ribose polymerase (PARP) family catalyse the ADP-ribosylation of target proteins and are known to play important roles in many cellular processes, including DNA repair, differentiation and transcription. The majority of PARPs exhibit mono-ADP-ribosyltransferase activity rather than PARP activity; however, little is known about their biological activity. In the present study, we report that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-ADP-ribose polymerase (TIPARP), mono-ADP-ribosylates and positively regulates liver X receptor α (LXRα) and LXRβ activity. Overexpression of TIPARP enhanced LXR-reporter gene activity. TIPARP knockdown or deletion reduced LXR regulated target gene expression levels in HepG2 cells and in Tiparp(-/-)mouse embryonic fibroblasts (MEFs) respectively. Deletion and mutagenesis studies showed that TIPARP's zinc-finger and catalytic domains were required to enhance LXR activity. Protein interaction studies using TIPARP and LXRα/β peptide arrays revealed that LXRs interacted with an N-terminal sequence (a.a. 209-236) of TIPARP, which also overlapped with a putative co-activator domain of TIPARP (a.a. 200-225). Immunofluorescence studies showed that TIPARP and LXRα or LXRβ co-localized in the nucleus.In vitroribosylation assays provided evidence that TIPARP mono-ADP-ribosylated both LXRα and LXRβ. Co-immunoprecipitation (co-IP) studies revealed that ADP-ribosylase macrodomain 1 (MACROD1), but not MACROD2, interacted with LXRs in a TIPARP-dependent manner. This was complemented by reporter gene studies showing that MACROD1, but not MACROD2, prevented the TIPARP-dependent increase in LXR activity. GW3965-dependent increases in hepatic Srebp1 mRNA and protein expression levels were reduced in Tiparp(-/-)mice compared with Tiparp(+/+)mice. Taken together, these data identify a new mechanism of LXR regulation that involves TIPARP, ADP-ribosylation and MACROD1.
Increased expression of Fas antigen on bone marrow CD34+ cells of patients with aplastic anaemia (1995)

Fas antigen, a receptor molecule that mediates signals for programmed cell death, is involved in T-cell-mediated killing of malignant, virus-infected or allogeneic target cells. Interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), potent inhibitors of haemopoiesis, enhance Fas receptor expression on bone marrow (BM) CD34+ cells, and both cytokines render haemopoietic progenitor cells susceptible to Fas-mediated inhibition of colony formation due to the induction of apoptosis. Haemopoietic suppression in aplastic anaemia (AA) has been associated with aberrant IFN-gamma, increased TNF-beta expression, and elevated numbers of activated cytotoxic T-cells in marrow. We have now examined Fas antigen expression in fresh AA BM samples. In normal individuals few CD34+ cells expressed Fas antigen and normal marrow cells had low sensitivity to Fas-mediated inhibition of colony formation. In contrast, in early AA, BM CD34+ cells showed markedly increased percentages of Fas receptor-expressing CD34+ cells, which correlated with increased sensitivity of AA marrow cells to anti-Fas antibody-mediated inhibition of colony formation. The proportion of Fas antigen-bearing cells was lower in recovered patients' BM. Fas antigen was also detected in the marrow of some patients with myelodysplasia, especially the hypocellular variant. These results are consistent with the hypothesis that AA CD34+ cells, probably including haemopoietic progenitor cells, express high levels of Fas receptor due to in vivo exposure to IFN-gamma and/or TNF-alpha and are suitable targets for T-cell-mediated killing. Our results suggest that the Fas receptor/Fas ligand system are involved in the pathophysiology of BM failure.
The Retinoic Acid and cAMP-dependent Up-regulation of 3-O-Sulfotransferase-1 Leads to a Dramatic Augmentation of Anticoagulantly Active Heparan Sulfate Biosynthesis in F9 Embryonal Carcinoma Cells (1998)

Retinoic acid (RA) and dibutyryl cAMP plus theophilline (CT) trigger F9 cells to differentiate into parietal endoderm. The differentiation induces a 9-fold increase in total heparan sulfate (HStotal) biosynthesis and a 170-fold increase in anticoagulantly active HS (HSact) biosynthesis. Measurement of 3-O-sulfotransferase-1 mRNA and enzymatic activity demonstrated an increase of over 100-fold whereas determination of N-, 2-O, and 6-O-sulfotransferase enzymatic activities showed elevations of 2-, 3. 5-, and 3.7-fold, respectively. HSact precursor pool measurements reveal that 30% of control F9 HStotal can be converted into HSact while only an additional 10% of RACT F9 HStotal can be transformed into HSact. Disaccharide analysis of metabolic labeled HS indicated that 32% 3-O-sulfate containing disaccharides, i.e. GlcA-anManR3S and GlcA-anManR3S6S, are present in HSact and 68% GlcA-anManR3S and GlcA-anManR3S6S are found in anticoagulantly inactive HS (HSinact). By using adenosine 3'-phosphate 5'-phosphosulfate and purified 3-O-sulfotransferase-1, 30% of 3-O-sulfation occurs in HSact and 70% of 3-O-sulfation occurs in HSinact. The similar ratio of 3-O-sulfate distribution in HSact versus HSinact suggests that HSact production in the F9 system is determined by the abundance of 3-O-sulfotransferase-1 as well as the size of the HSact precursor pool. Extensively 3-O-sulfated HSinact may play an important functional role under in vivo conditions within the murine placenta.
[Micro-RNA and oncogenesis]. (2005)

MicroRNA are endogenous molecules which negatively regulate the expression of a variety of genes. These tiny non coding RNA molecules--18 to 25 nucleotides in length--repress, with efficiency and specificity- translation of target mRNA into protein, according to a process akin to RNA interference. MiRNA are critical in the development of plants and mammals since they play a key role on proteins which regulate the strict spatiotemporal control of each tissue. Very recent reports published during 2005 summer show miRNA as also involved in oncogenesis. Specific miRNA elicit oncogenic and antiapoptotic properties in lymphoma models and glioblastoma, respectively. The expression profile of the two hundred miARN, so far identified, reflects the tumor tissue lineage, leading to a potential tool for diagnosis. The occurrence of miRNA in solid tumors and haematological neoplasia opens new avenues for understanding of oncogenesis and, likely, for management of cancer diseases.
Design of a MEMS Ejector for Printing Applications (2002)

Applications for drop ejectors range from ink jet printing to drug delivery systems. MEMS (Micro-Electro-Mechanical Systems) fabrication techniques, particularly surface micromachining, allow production of small monolithic structures that can be adapted to many applications. We report on the design, fabrication, and testing of a surface micromachined MEMS liquid ejection system for printing applications. The ejectors were fabricated using the SUMMiT&#x2122; process,1 a surface micromachining technique. The only assembly required is electrical connection and attachment of a fluid reservoir. The process features three, four or five layers of structural polysilicon, separated by layers of sacrificial silicon dioxide. The final step of the fabrication process is the removal of the oxide to release the &#x201C;machined&#x201D; structure. The ejector produces small volume (2 &#x2013; 4 picoliters), satellite-free drops traveling at 5 &#x2013; 10 m/s. To eject a drop a piston is drawn rapidly towards a plate containing a nozzle through which the drop is ejected. The piston is electrostatically actuated. Since the electric field acts across the liquid bath, device operation is sensitive to the dielectric strength, breakdown voltage and conductivity of the fluid.
A wearable &#x201C;electronic patch&#x201D; for wireless continuous monitoring of chronically diseased patients (2008)

We present a wearable health system (WHS) for non-invasive and wireless monitoring of physiological signals. The system is made as an electronic patch where sensors, low power electronics, and radio communication are integrated in an adhesive material of hydrocolloid polymer making it a sticking patch. The patch is made with a reusable part and a disposable part which contains the adhesive material and the battery. This part is changed once every week. The patch has a size of 88 mm by 60 mm and a thickness of 5 mm. It is made for attachment on truncus or the greater muscle groups. The patch is demonstrated in two applications: Monitoring of electromyography (EMG) and arterial oxygen saturation by pulse oximetry (SpO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ). The pulse oximetry sensor is made of a concentric backside Silicon photodiode with a hole in the middle for the two light sources. This makes it suitable for reflectance pulse oximetry. For the EMG application three standard dry silver electrodes are used separated by 10 mm.