gebhart/patrepeval huggingface dataset:
Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma (2016)

High-dose interleukin-2 (HD IL-2) was approved for treatment of metastatic renal cell carcinoma (mRCC) in 1992 and for metastatic melanoma (mM) in 1998, in an era predating targeted therapies and immune checkpoint inhibitors. The PROCLAIM<sup>SM</sup> registry was established to collect and analyze data for patients treated with HD IL-2 in the current era. This analysis includes 170 patients with mM and 192 patients with mRCC treated between 2005 and 2012 with survival data current as of July 27, 2015. For patients with mM, complete response (CR) was observed in 5 %, partial response (PR) in 10 %, stable disease (SD) in 22 %, and 63 % had progressive disease (PD). The median overall survival (mOS) for these patients was 19.6 months, with a median follow-up of 43.1 months. The mOS was not reached for patients achieving CR or PR, and was 33.4 months for patients with SD. For patients with mRCC, 6 % achieved CR, 9 % had PR, 22 % had SD, and 62 % had PD. The mOS was 41 months, with a median follow-up of 46.6 months. The mOS for patients who had CR and PR was not reached and was 49.6 months for patients with SD. There were no treatment-related deaths among 362 patients. The duration of mOS for patients with mM and mRCC is longer than historically reported. These data support a continued role for IL-2 in the treatment of eligible patients with mM or mRCC and warrant further evaluation of HD IL-2 in combination or sequence with other therapeutic agents.
Synthesis and luminescence properties of new red-shifted absorption lanthanide(iii) chelates suitable for peptide and protein labelling (2010)

The synthesis and photo-physical properties of an original bis-pyridinylpyrazine chromophore efficiently sensitising europium(III) and samarium(III) are described. The corresponding lanthanide(III) complexes display in aqueous solutions a maximum excitation wavelength which is significantly red-shifted compared to the usual terpyridine-based chelates, and a valuable luminescence brightness above 2,000 dm(3) mol(-1) cm(-1) at 345 nm was obtained with a europium(III) derivative. Further functionalisation with three different bioconjugatable handles was also investigated and their ability to efficiently label a model hexapeptide was evaluated and compared. Finally, the best bioconjugatable europium(III) chelate was used in representative labelling experiments involving monoclonal antibodies and the luminescence features of the corresponding bioconjugates remained satisfactory.
RNA binding proteins and the pathological cascade in ALS/FTD neurodegeneration (2017)

Advanced genetic approaches have accelerated the identification of causative genes linked to the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the disease-related proteins encoded by these genes form aggregates in the cellular machineries that regulate RNA and protein quality control in cells. Cross-talk among the signaling pathways governing these machineries leads to pathological cascades mediated by the accumulation of mutant RNA binding proteins. We outline the molecular basis of ALS and FTD pathogenesis and discuss the prospects for therapeutic strategies to treat these diseases.
Name-ethnicity classification from open sources (2009)

The problem of ethnicity identification from names has a variety of important applications, including biomedical research, demographic studies, and marketing. Here we report on the development of an ethnicity classifier where all training data is extracted from public, non-confidential (and hence somewhat unreliable) sources. Our classifier uses hidden Markov models (HMMs) and decision trees to classify names into 13 cultural/ethnic groups with individual group accuracy comparable accuracy to earlier binary (e.g., Spanish/non-Spanish) classifiers. We have applied this classifier to over 20 million names from a large-scale news corpus, identifying interesting temporal and spatial trends on the representation of particular cultural/ethnic groups.
Initial Management of Glycemia in Type 2 Diabetes Mellitus (2002)

An asymptomatic 45-year-old Hispanic man has a fasting plasma glucose level of 142 mg per deciliter (7.9 mmol per liter) on initial evaluation and 139 mg per deciliter (7.7 mmol per liter) on reevaluation. Other than a steady gain in weight since college and borderline hypertension, his medical history is unremarkable. He is 175 cm (5 ft 9 in.) tall and weighs 95 kg (209 lb; body-mass index, 31.2), and his blood pressure is 138/88 mm Hg. Physical examination is notable only for abdominal obesity and absent ankle reflexes. How should this patient be treated?
Alleles from chromosomes 1 and 3 of NOD mice combine to influence Sjögren's syndrome-like autoimmune exocrinopathy. (2000)

Alleles on chromosomes 1 (Idd5) and 3 (Idd3) in combination appear to greatly influence susceptibility and resistance to development of autoimmune exocrinopathy. The association with certain Idd, but not other Idd loci, indicate that genetic overlap is present but probably not inclusive.
Four of the seven zinc fingers of the Evi-1 myeloid-transforming gene are required for sequence-specific binding to GA(C/T)AAGA(T/C)AAGATAA. (1993)

Expression of the Evi-1 gene is activated in murine myeloid leukemias by retroviral insertions and in human acute myelogenous leukemia by translocations and inversions involving chromosome band 3q26 where the gene resides. Aberrant expression of the Evi-1 gene has been shown to interfere with myeloid differentiation, which is proposed to be the basis for its role in leukemias. The Evi-1 gene encodes a 145-kDa DNA-binding protein containing two domains of seven and three Cys2-His2 zinc fingers. Previous studies identified a portion of the consensus DNA-binding sequence for the first domain of zinc fingers. The experiments presented here extend these studies and demonstrate that the first domain recognizes a consensus of 15 nucleotides consisting of GA(C/T)AAGA(T/C)AAGATAA. The first three fingers of the first domain do not detectably bind DNA but contribute to the binding by conferring a relative specificity for GACAA verses GATAA in the first position. The first three fingers also contribute to optimal binding of the 15-nucleotide consensus sequence.
Cellular senescence drives age-dependent hepatic steatosis (2017)

The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state of irreversible cell-cycle arrest combined with the secretion of proinflammatory cytokines and mitochondrial dysfunction. Senescent cells contribute to age-related tissue degeneration. Here we show that the accumulation of senescent cells promotes hepatic fat accumulation and steatosis. We report a close correlation between hepatic fat accumulation and markers of hepatocyte senescence. The elimination of senescent cells by suicide gene-meditated ablation of p16<sup>Ink4a</sup>-expressing senescent cells in INK-ATTAC mice or by treatment with a combination of the senolytic drugs dasatinib and quercetin (D+Q) reduces overall hepatic steatosis. Conversely, inducing hepatocyte senescence promotes fat accumulation in vitro and in vivo. Mechanistically, we show that mitochondria in senescent cells lose the ability to metabolize fatty acids efficiently. Our study demonstrates that cellular senescence drives hepatic steatosis and elimination of senescent cells may be a novel therapeutic strategy to reduce steatosis.
Directed osteogenic differentiation of human mesenchymal stem/precursor cells on silicate substituted calcium phosphate (2012)

Insufficient, underactive, or inappropriate osteoblast function results in serious clinical conditions such as osteoporosis, osteogenesis imperfecta and fracture nonunion and therefore the control of osteogenesis is a medical priority. In vitro mesenchymal stem cells (MSCs) can be directed to form osteoblasts through the addition of soluble factors such as β-glycerophosphate, ascorbic acid, and dexamethasone; however this is unlikely to be practical in the clinical setting. An alternative approach would be to use a scaffold or matrix engineered to provide cues for differentiation without the need for soluble factors. Here we describe studies using Silicate-substituted calcium phosphate (Si-CaP) and unmodified hydroxyapatite (HA) to test whether these materials are capable of promoting osteogenic differentiation of MSCs in the absence of soluble factors. Si-CaP supported attachment and proliferation of MSCs and induced osteogenesis to a greater extent than HA, as evidenced through upregulation of the osteoblast-related genes: Runx2 (1.2 fold), Col1a1 (2 fold), Pth1r (1.5 fold), and Bglap (1.7 fold) Dmp1 (1.1 fold), respectively. Osteogenic-associated proteins, alkaline phosphatase (1.4 fold), RUNX2, COL1A1, and BGLAP, were also upregulated and there was an increased production of mineralized bone matrix (1.75 fold), as detected by the Von Kossa Assay. These data indicate that inorganic substrates are capable of directing the differentiation programme of stem cells in the absence of known chemical drivers and therefore may provide the basis for bone repair in the clinical setting.
Monophosphoric acid diesters of 7.beta.-hydroxycholesterol and of pyrimidine nucleosides as potential antitumor agents: synthesis and preliminary evaluation of antitumor activity (1990)

7 beta-Hydroxycholesterol, which has been shown to be selectively cytotoxic toward tumor cells cultured in vitro, was converted into the corresponding water-soluble phosphoric acid ester and linked to a pyrimidine nucleoside such as 5-fluoro-2'-deoxyuridine or 2'-deoxyuridine. 2-Chlorophenyl phosphorodichloridate (3), without activation, was used directly to phosphorylate the protected oxygenated sterol. The intermediate phosphorylated the 5'-OH group of nucleoside selectively, leading to compounds 1a and 1b after deprotection. These compounds were screened for their antiproliferative activity toward EL-4 murine leukemia cells in vitro and for their antitumor activity against the mice bearing Krebs II ascitic carcinoma in vivo.
Using invariants to recognize airplanes in inverse synthetic aperture radar images (2003)

We propose a novel method for recognizing airplanes in an inverse synthetic aperture radar (ISAR) image. The method utilizes the conspicuous scatterers at fixed positions in a 2-D ISAR image, and a point-scatterer model is used to model the airplane. The geometric relationships of the scatterers can be used to generate a set of cross-ratio vectors and a database for recognition can thus be built. A pair of stable cross-ratios is applied to the database as a search key to reduce the cost of the search. Furthermore, ordered geometric invariants and the circular matching technique are employed to alleviate the computational complexity. The experimental results show that the proposed method is both robust and effective in recognizing airplanes in ISAR images.
Rates of addition of styrene to 9-substituted acridizinium ions (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRates of addition of styrene to 9-substituted acridizinium ionsJohn Westerman and Charles K. BradsherCite this: J. Org. Chem. 1971, 36, 7, 969–970Publication Date (Print):April 1, 1971Publication History Published online1 May 2002Published inissue 1 April 1971https://doi.org/10.1021/jo00806a024RIGHTS & PERMISSIONSArticle Views49Altmetric-Citations15LEARN 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 (239 KB) Get e-Alerts Get e-Alerts
Molecular Targets for Human Papillomaviruses: Prospects for Antiviral Therapy (1998)

A substantial medical need exists for the development of antiviral medicines for the treatment of diseases associated with infection by human papillomaviruses (HPVs). HPVs are associated with various benign and malignant lesions including benign genital condyloma, common skin warts, laryngeal papillomas and anogenital cancer. Since treatment options are limited and typically not very satisfactory, the development of safe and effective antiviral drugs for HPV could have substantial clinical impact. In the last few years, exciting advances have been made in our understanding of papillomavirus replication and the effects that the virus has on growth of the host cell. Although still somewhat rudimentary, techniques have been developed for limited virion production in vitro offering the promise of more rapid advances in the dissection and understanding of the virus life cycle. Of the 8-10 HPV gene products that are made during infection, only one encodes enzymatic activities, the E1 helicase. Successful antiviral therapies have traditionally targeted viral enzymes such as polymerases, kinases and proteases. In contrast, macromolecular interactions which mediate the functions of E6, E7 and E2 are thought to be more difficult targets for small molecule therapy.
The generation and chemistry of dianions derived from furancarboxylic acids (1981)

Methods for the generation of the dianionic species lithium 5-lithiofuran-2-carboxylate (5) and lithium 2-lithiofuran-3-carboxylate (21) from furan-2-and furan-3-carboxylic acids respectively are described. The reactions of (5) and (21) with a range of electrophiles have been examined; in general these are very efficient with aldehydes and ketones but not as satisfactory with alkyl halides and epoxides. The dianions do not couple with allylic or benzylic halides, nor with nitriles or orthoesters. The generation of lithium-5-lithio-3-methylfuran-2-carboxylate (15) from 3-methylfuran-2-carboxylic acid is also described; the chemistry of (15) is very similar to (5) derived from furan-2-carboxylic acid.
Janus kinase-3 (JAK3) inhibition: a novel immunosuppressive option for allogeneic transplantation (2004)

Abstract Current immunosuppressive therapy in clinical organ transplantation is based on drugs that suppress various functions of immunocompetent cells but still affect cells and organ compartments other than the immune system. Hence, these drugs have considerable side effects which lead to increased morbidity and reduced life-quality of transplant recipients. A major step forward in the rationale design of clinical immunosuppression resides in the elucidation of molecular targets that play a critical role specifically within the immune system. Recently, Janus kinase 3 (JAK3) has been identified as such a molecule. Genetic absence or ablation of this tyrosine kinase is associated with defective T-cell immunity that results in severe combined immunodeficiency (SCID) without apparent changes in other organ systems. Furthermore, pharmacological inhibition has significantly prolonged allograft survival in several experimental models of organ transplantation. The present review provides an overview of the emerging role of JAK3 in the immune system and the development of JAK3-inhibiting drugs. The potential clinical application of JAK3 inhibitors in organ transplantations is discussed in the light of a recent series of successful kidney transplantations in non-human primates immunosuppressed solely with a novel JAK3 inhibitor.
The Algase wandering scale: Initial psychometrics of a new caregiver reporting tool (2001)

This paper reports on the Algase wandering scale (AWS), a 28-item questionnaire, based on five dimensions of wandering. With factor analysis, an eight-factor solution explained nearly 70 percent of the variance in ratings for 151 long-term care subjects and confirmed three of the structuring dimensions. Reliability of the AWS was examined for internal consistency and for inter-rater reliability. The AWS had an alpha of .86; subscale alphas ranged between .88 (persistent walking) and .57 (routinized walking). Inter-rater reliabilities, estimated through cross-rater comparisons of the AWS and subscales with a four-point judgement of wandering status, were moderately strong and no significant differences existed between two sets of raters. Validity of the AWS and its subscales was supported by examining their ability to differentiate wanderers and nonwanderers, by positive correlation with measures of cognitive impairment and with multiple parameters of observed wandering, and by negative or no correlations with nonwandering locomotion. Although the AWS may be a useful measure of wandering in long-term care settings, validation of its factor structure and evaluation in cross-cultural samples is needed.
Individual CD34+CD38lowCD19−CD10− Progenitor Cells From Human Cord Blood Generate B Lymphocytes and Granulocytes (1997)

Identification of human hematopoietic stem cells and analysis of molecular mechanisms regulating their function require biological assays that permit differentiation in all hematopoietic lineages simultaneously. In this study, we established conditions that permit the joint expression of the B-lymphoid and myeloid potential from cord blood-derived CD34+CD38lowCD19−/CD10− primitive progenitors that lack B-specific markers and transcripts. When cocultured during 6 weeks with the murine stromal cells MS-5 in the absence of exogenous human cytokines, CD34+CD38lowCD19−CD10− cells generated a high number of CD19+ B cells. Virtually all of these cells expressed a CD34−CD10+CD19+cIgM− phenotype of late pro-B cells and transcripts of Pax-5, λ-like, and μ chain were detected. We further show that 7% of CD34+CD38lowCD19− cells from cord blood, when grown individually with MS-5 cells, generated both CD19+ and CD11b+ cells after 6 weeks. Efficient B-cell differentiation was also observed in vivo after transplantation of human cord blood-derived unfractionated mononuclear cells or CD34+CD19+CD10− cells into immune-deficient mice. In contrast to the in vitro situation, all stages of B-cell differentiation were observed in vivo, including pro-B, pre-B, and sIgM+ B cells. Interestingly, human progenitors with the ability to differentiate along both B-lymphoid and granulocytic pathways were also detected among human CD34+CD38low cells in the marrow of chimeric mice 6 to 7 weeks after transplantation. Both in vitro and in vivo systems will offer an invaluable tool to further identify the lymphoid and myeloid potentialities of primitive progenitor cells isolated from fetal as well as adult human hematopoietic tissues and characterize stromal-derived signals that regulate their function.
Salutary effects of adiponectin on colon cancer: in vivo and in vitro studies in mice (2012)

These new mechanistic and pathophysiology studies provide evidence for an important role of adiponectin in colon cancer. The data indicate that adiponectin or analogues might be useful agents in the management or chemoprevention of colon cancer.
Expression of high-mobility group box protein 1 in diabetic foot atherogenesis (2015)

The role of high mobility group box 1 (HMGB1) has been demonstrated in stroke and coronary artery disease but not in peripheral arterial occlusive disease (PAOD). The pathogenesis of HMGB1 in acute and chronic vascular injury is also not well understood. We hypothesized that HMGB1 induces inflammatory markers in diabetic PAOD patients. We studied 36 diabetic patients, including 29 patients with PAOD, who had undergone amputation for diabetic foot and 7 nondiabetic patients who had undergone amputation after traumatic injury. Expression of HMGB1 and inflammatory markers were quantified using immunohistochemical staining. Mitochondrial DNA copy number was quantified using real-time polymerase chain reaction. Compared with that in the traumatic amputation group, HMGB1 expression in vessels was significantly higher in the diabetes and diabetic PAOD groups. In all subjects, arterial stenosis grade was positively correlated with the expression levels of HMGB1, 8-hydroxyguanosine, malondialdehyde, vascular cell adhesion molecule 1, and inflammatory markers CD3, and CD68 in both the intima and the media of vessels. Furthermore, HMGB1 expression level was positively correlated with 8-hydroxyguanosine, vascular cell adhesion molecule 1, nuclear factor-kB, CD3, and CD68 expression. Within the PAOD subgroup, subjects with HMGB1 expression had higher expression of the autophagy marker LC3A/B and higher mitochondrial DNA copy number. HMGB1 may be an inflammatory mediator with roles in oxidative damage and proinflammatory and inflammatory processes in diabetic atherogenesis. Moreover, it may have dual effects by compensating for increased mitochondrial DNA copy number and increased autophagy marker expression.
Web usage mining (2000)

Web usage mining is the application of data mining techniques to discover usage patterns from Web data, in order to understand and better serve the needs of Web-based applications. Web usage mining consists of three phases, namely preprocessing, pattern discovery , and pattern analysis . This paper describes each of these phases in detail. Given its application potential, Web usage mining has seen a rapid increase in interest, from both the research and practice communities. This paper provides a detailed taxonomy of the work in this area, including research efforts as well as commercial offerings. An up-to-date survey of the existing work is also provided. Finally, a brief overview of the WebSIFT system as an example of a prototypical Web usage mining system is given.