gebhart/patrepeval huggingface dataset:
New directions in natural killer cell-based immunotherapy of human cancer (2003)

Efforts at harnessing the antitumour activity of natural killer (NK) cells have been investigated for the immunotherapy of human cancer for over two decades. Initial trials, focusing on the use of ex vivo-generated lymphokine activated killer (LAK) cells or activated NK cells, or in vivo cytokine therapy to expand and activate NK cells against autologous tumours, have yielded only modest success. Recent understanding of the means by which NK cells kill target cells through a complex set of activating and inhibitory receptors recognising corresponding ligands on tumour cells has paved the way for the design of improved strategies for NK cell-based immunotherapy. The net balance of activating and inhibitory signals through NK cell receptors determines whether an NK cell becomes activated or not. Successful therapeutic strategies should now focus on manipulating the balance in favour of activating receptor signalling. In the case of autologous cancers, such strategies may include the use of monoclonal antibodies with cytokines to better direct NK cells to their tumour targets through the process of antibody-dependent cellular cytotoxicity (ADCC) or the in vivo blocking of inhibitory interactions between NK receptors (NKRs) and ligands on tumour cells. Alternatively, allogeneic NK cells can be used whenever there is mismatching of inhibitory NK cell receptors and ligands. Finally, methods to modulate expression of NK cell receptors and their ligands on tumour cells by cytokines and other agents should be explored. In this review, the impact of NKR biology on the development of novel strategies for the use of NK cells in the treatment of human cancer is discussed.
Antiprogestins in Ovarian Cancer (2012)

The overall goal of this chapter is to provide evidence for the feasibility of repositioning antiprogestin compounds originally utilized for reproductive medicine toward ovarian cancer therapy. This disease is the most deadly of the female reproductive track; at the time of diagnosis, in the majority of cases abnormal growths have progressed outside the ovaries and into the nearby fallopian tubes, uterus, and peritoneal cavity. Thus, the majority of diagnosed patients require cytoreductive surgery followed by platinum-based chemotherapy The efficacy of this therapy, however, is limited by the elevated toxicity of the platinum derivatives The majority of relapsing patients are platinum-resistant, with very limited chemotherapeutic options, and a median survival time of about only two years The five-year survival for ovarian cancer patients is extremely disappointing, ranging from 37% to 45% Hence, new therapeutic interventions to overcome the limitations of platinum-based therapy for ovarian cancer patients are greatly needed.
Affymetrix Whole-Transcript Human Gene 1.0 ST Array is Highly Concordant with Standard 3′ Expression Arrays (2008)

The recently released Affymetrix Human Gene 1.0 ST array has two major differences compared with standard 3' based arrays: (i) it interrogates the entire mRNA transcript, and (ii) it uses DNA targets. To assess the impact of these differences on array performance, we performed a series of comparative hybridizations between the Human Gene 1.0 ST and the Affymetrix HG-U133 Plus 2.0 and the Illumina HumanRef-8 BeadChip arrays. Additionally, both RNA and DNA targets were hybridized on HG-U133 Plus 2.0 arrays. The results show that the overall reproducibility of the Gene 1.0 ST array is best. When looking only at the high intensity probes, the reproducibility of the Gene 1.0 ST array and the Illumina BeadChip array is equally good. Concordance of array results was assessed using different inter-platform mappings. Agreements are best between the two labeling protocols using HG-U133 Plus 2.0 array. The Gene 1.0 ST array is most concordant with the HG-U133 array hybridized with cDNA targets. This may reflect the impact of the target type. Overall, the high degree of correspondence provides strong evidence for the reliability of the Gene 1.0 ST array.
Predicting bioavailability of monoclonal antibodies after subcutaneous administration: Open innovation challenge (2020)

Despite the increasing trend towards subcutaneous delivery of monoclonal antibodies, factors influencing the subcutaneous bioavailability of these molecules remain poorly understood. To address critical knowledge gaps and issues during development of subcutaneous dosage forms for monoclonal antibodies, the Subcutaneous Drug Delivery and Development Consortium was convened in 2018 as a pre-competitive collaboration of recognized industry experts. One of the Consortium's eight problem statements highlights the challenges of predicting human bioavailability of subcutaneously administered monoclonal antibodies due to a lack of reliable in vitro and preclinical in vivo predictive models. In this paper, we assess the current landscape in subcutaneous bioavailability prediction for monoclonal antibodies and discuss the gaps and opportunities associated with bioavailability models for biotherapeutics. We also issue an open challenge to industry and academia, encouraging the development of reliable models to enable subcutaneous bioavailability prediction of therapeutic large molecules in humans and improve translation from preclinical species.
Epidemiology of glaucoma in Japan--a nationwide glaucoma survey. (1991)

A population-based, collaborative glaucoma survey was conducted in seven regions throughout Japan, during the years of 1988 and 1989. The total number of subjects examined was 8,126 out of 16,078 residents aged 40 years or older, representing a participation rate of 50.54%. There were no significant differences in background factors between participants and randomly sampled nonparticipants. A mainstay of the screening consisted of tonometry and fundus photography with nonmydriatic camera, followed by automatic perimetry as a recall examination. Overall prevalences obtained were primary open-angle glaucoma (POAG) 0.58%, low-tension glaucoma (LTG) 2.04%, primary angle closure glaucoma (PACG) 0.34%, other types of glaucomas 0.60%, and ocular hypertension (OH) 1.37% at the time of screening. The very high prevalence of LTG and extremely low prevalence of OH in the Japanese might reflect a racial peculiarity in the age-specific trend of the intraocular pressure. The prevalence of PACG was found much higher in Japanese than in Caucasians, with a predilection for women. Racial peculiarities as revealed in this study were discussed, with particular reference to the refractive status in the Japanese that showed progressive decrease in myopia with age.
Bonding of alkoxysilanes to dehydroxylated silica surfaces: a new adhesion mechanism (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBonding of alkoxysilanes to dehydroxylated silica surfaces: a new adhesion mechanismLawrence H. Dubois and Bernard R. ZegarskiCite this: J. Phys. Chem. 1993, 97, 8, 1665–1670Publication Date (Print):February 1, 1993Publication History Published online1 May 2002Published inissue 1 February 1993https://pubs.acs.org/doi/10.1021/j100110a032https://doi.org/10.1021/j100110a032research-articleACS PublicationsRequest reuse permissionsArticle Views470Altmetric-Citations44LEARN 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 InRedditEmail Other access options Get e-Alerts
Hypophosphatasia. (2013)

Hypophosphatasia (HPP) is a rare, inherited, potentially life-threatening metabolic disorder that arises from loss-of-function mutations in the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). As a result of these mutations (as many as 260 genetic mutations have been associated with HPP), patients have disordered bone mineralization leading to rickets, osteomalacia, fractures and other skeletal abnormalities as well as other systemic complications such as seizures, respiratory compromise, dental anomalies, nephrocalcinosis and/or weakness and chronic pain. HPP may appear across the age spectrum, from in utero, to infancy, childhood, adolescence and/or adulthood. More severe cases tend to be seen in utero and infancy, and in these instances, mortality may be as high as 50%. In surviving or older patients, disability and poor quality of life may be seen. Based on clinical presentation, HPP can be mistakenly diagnosed as other skeletal diseases, but a low alkaline phosphatase is an important, distinguishing sign of this condition. While patients with HPP may benefit from supportive measures, at the present time, there is no approved specific therapy for HPP.
Characterization of laterally deformable elastomer membranes for microfluidics (2007)

This work presents experimental characterization and numerical modeling of laterally deflecting polydimethylsiloxane (PDMS) membranes under pneumatic actuation. The device for this study is a membrane valve seat that partially closes a perpendicular fluid microchannel, fabricated using single-layer soft lithography. Membranes with thickness between 8 and 14 µm have been experimentally tested up to 207 kPa, and maximum lateral displacement beyond 20 µm has been demonstrated. Investigation of geometric parameters by factorial design shows that the height of the membrane is more dominant than the width and thickness, and this is attributed to the zero-displacement boundary condition at the foot of the membrane where it is bonded to a flat substrate. A numerical model that incorporates hyperelastic material testing data shows close agreement with the deflection behavior of experimental samples, accurately predicting that a membrane of 10 µm thick, 100 µm wide and 45 µm tall deflects approximately 13 µm at 207 kPa. Simulation further shows that sidewall effects from bulk compression of the elastomer material in the actuation cavity have a significant effect, reducing maximum displacement by as much as 15% over predictions based on deformation that is limited strictly to the membrane only. Experimental yield, SEM imaging and stress simulations emphasize that the membrane foot region requires the greatest attention in terms of process development.
Global analysis of antibody repertoires. II. Evidence for specificity, self‐selection and the immunological “homunculus” of antibodies in normal serum (1993)

The serum IgM repertoires of C57BL/6, DBA/2 and BALB/c mouse strains were analyzed using a recently developed global and quantitative assay that measures antibody reactivities to a very large number of antigens. A characteristic repertoire could be assigned to each strain. The different repertoires could be successfully classified with multivariate statistics. Many common reactivities were also observed among the different strains, which allows the definition of a mouse-specific repertoire. Analysis of human sera support this notion. To investigate the impact of minor genetic differences on the serum IgM repertoire, the congenic strains B10.D2/oSn and B10.D2/nSn, which differ in the expression of the C5 component of complement, were analyzed. The two strains could be separated based on the reactivity profiles obtained. The analysis of the results reveals that many antigenic proteins are not recognized at all by natural antibodies, while others are disproportionately reactive, the resulting patterns giving rise to what could be the definition of an "immunological homunculus". The relevance of this type of analysis for clinical applications is discussed.
Computerized Tomography and Transrectal Ultrasound in the Assessment of Local Extension of Prostatic Cancer Before Radical Retropubic Prostatectomy (1987)

The value of computerized tomography and transrectal ultrasound in the demonstration of local extension of prostatic cancer was evaluated in 38 patients undergoing radical retropubic prostatectomy. Transrectal ultrasound proved to be reliable for the demonstration of local extension of cancer beyond the prostatic capsule (sensitivity 86 per cent, specificity 94 per cent and accuracy 90 per cent). Invasion of the seminal vesicles was demonstrated by ultrasound, with a sensitivity of 29 per cent, specificity 100 per cent and accuracy 77 per cent. The addition of transrectal ultrasound scanning to clinical evaluation increased sensitivity in relation to detection of extraprostatic involvement from 15 to 92 per cent. When computerized tomography scanning was added to clinical examination, the sensitivity increased from 15 to only 46 per cent. Transrectal ultrasound is valuable for the preoperative evaluation of patients in whom radical prostatectomy is being considered as treatment for clinically localized prostatic cancer.
Biodiversity and systematics of basidiomycetous yeasts as determined by large-subunit rDNA D1/D2 domain sequence analysis. (2000)

The molecular systematics of 337 strains of basidiomycetous yeasts and yeast-like fungi, representing 230 species in 18 anamorphic and 24 teleomorphic genera, was determined by sequence analysis of the D1/D2 region of the large-subunit rDNA. The data were compared with published sequences of other basidiomycetous fungi. The results demonstrated that the yeast species and genera are phylogenetically distributed among the Microbotryum, Sporidiobolus, Agaricostilbum and Erythrobasidium clades of the Urediniomycetes; the Tremellales, Trichosporonales ord. nov., Filobasidiales and Cystofilobasidiales clades of the Hymenomycetes; and the Ustilaginales, Microstromatales and Malasseziales clades of the Ustilaginomycetes. Genera such as Bensingtonia, Cryptococcus, Rhodotorula and Sporobolomyces are polyphyletic, i.e. they occur in two or more clades. In contrast, other genera, e.g. Bullera, Cystofilobasidium, Fellomyces, Filobasidiella, Filobasidium, Kondoa, Kurtzmanomyces, Leucosporidium, Rhodosporidium, Sporidiobolus and Udeniomyces, are monophyletic. The majority of the species can be identified using D1/D2 analyses, although the internal transcribed spacer region is required to distinguish closely related species. The intergenic spacer region is recommended for additional differentiation of species and strains.
Caring for the whole patient. (1993)

Caring for the whole patient requires as much understanding and commitment from managers as it does from physicians and nurses.
Distinct mechanisms of axonal globule formation in mice expressing human wild type α-synuclein or dementia with Lewy bodies-linked P123H ß-synuclein (2012)

Lysosomal pathology was similarly observed for both αS- and P123H βS-globules, while oxidative stress was associated with the αS-globules, and to a lesser extent with the P123H βS-globules. Other pathologies, such as mitochondrial alteration and LRRK2 accumulation, were exclusively detected for αS-globules. Collectively, both αS- and P123H βS-globules were formed through similar but distinct pathogenic mechanisms. Our findings suggest that synuclein family members might contribute to diverse axonal pathologies.
Measurement and modeling of the transient difference between blood and subcutaneous glucose concentrations in the rat after injection of insulin (1998)

The kinetics of the fall in subcutaneous fluid glucose concentration in anesthetized rats (n = 7) after intravenous injection of insulin (0.5 units/kg) was studied by using 5 x 10(-4) cm2 active area, <150-sec 10-90% response time, amperometric glucose sensors. The onset of the decline in the subcutaneous glucose concentration was delayed and statistically different (P < 0.001) from that in blood (8.9 +/- 2.1 min vs. 3.3 +/- 0.5 min). Similarly, the rate of drop in glucose concentration between 6 and 20 min after the insulin injection was different for subcutaneous tissue (3.9 +/- 1.3 mg.dl-1. min-1) and blood (6.8 +/- 2.0 mg.dl-1.min-1) (P = 0.003). The hypoglycemic nadir in subcutaneous fluid occurred 24.5 +/- 6.8 min after that in the blood (P < 0.001). A "forward" mass-transfer model, predicting the subcutaneous glucose concentration from the blood glucose concentrations and an "inverse" model, predicting the blood glucose concentration from the subcutaneous glucose concentration were derived. By using an algorithm based on the latter, the average discrepancy between the measured blood glucose concentration and that estimated from the subcutaneous measurement through the entire 4-hr experiment was reduced from 22.9% to 11.1% (P = 0.025). The maximum discrepancy during the 40-min period after the injection of insulin was reduced from 84.1% to 29.3% (P = 0.006).
Tissue Disaggregation (1994)

The extracellular matrix of mammalian tissue is composed of a complex mix of constituitive proteins. This matrix must be broken down to recover single cells effectively for culture and/or staining (1). Tissue dissociation and its affiliated problems were described and defined over 80 years ago by Rous and Jones (2). More recent reviews (3, 4) have revealed newer methods for creating single-cell suspensions. Numerous procedures exist for dissociating solid tumors. They are usually multistep procedures involving one or a combination of mechanical, enzymatic, or chemical manipulations. Ideally, the dissociation protocol is individualized for the tissue of interest and evaluated relative to both optimal and representative cell yield.
In vitro RNA polymerase interaction with a restriction fragment containing the Escherichia coli origin of replication (1985)

The interaction of RNA polymerase with a restriction fragment containing the origin of Escherichia coli replication (oriC) was examined by methods used to investigate transcription promoter activities. Interactions of RNA polymerase with oriC were determined and characterized by agarose gel exclusion under conditions of polymerase binding and RNA synthesis initiation. These interactions were further demonstrated and defined by nitrocellulose retention experiments under various reaction conditions. The binding of RNA polymerase to the oriC fragment was compared to binding to the tetracycline promoter (tet), a known strong promoter of transcription. Specific localization of the RNA polymerase-oriC interaction was determined by restriction protection experiments. The binding of RNA polymerase was determined to be located near the HindIII site of oriC. These methods allowed the observation and characterization of a specific association of RNA polymerase with the origin of E. coli DNA replication.
Sequential Interactions of the TCR with Two Distinct Cytoplasmic Tyrosine Kinases (1994)

The T cell antigen receptor (TCR) initiates signals by interacting with cytoplasmic protein tyrosine kinases (PTKs) through a 17-residue sequence motif [called the antigen recognition activation motif (ARAM)] that is contained in the TCR zeta and CD3 chains. TCR stimulation induces the tyrosine phosphorylation of several cellular substrates, including the ARAMs. Lck kinase activity is required for phosphorylation of two conserved tyrosine residues in an ARAM. This phosphorylation leads to the recruitment of a second cytoplasmic PTK, ZAP-70, through both of the ZAP-70 Src homology 2 domains and its phosphorylation. Thus, TCR signal transduction is initiated by the sequential interaction of two PTKs with TCR ARAMs.
Cyclization of ylidenemalononitriles. 9. Rearrangement of 2-cyano-3-(1-methylcyclopentyl)indenone to 4a-methyl-9-oxo-10-cyano-1,2,3,4,4a,9-hexahydrophenanthrene (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyclization of ylidenemalononitriles. 9. Rearrangement of 2-cyano-3-(1-methylcyclopentyl)indenone to 4a-methyl-9-oxo-10-cyano-1,2,3,4,4a,9-hexahydrophenanthreneE. Campaigne and Ronald A. ForschCite this: J. Org. Chem. 1978, 43, 6, 1044–1050Publication Date (Print):March 1, 1978Publication History Published online1 May 2002Published inissue 1 March 1978https://pubs.acs.org/doi/10.1021/jo00400a005https://doi.org/10.1021/jo00400a005research-articleACS PublicationsRequest reuse permissionsArticle Views237Altmetric-Citations10LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Overexpression of ∊-Protein Kinase C Enhances Nerve Growth Factor-induced Phosphorylation of Mitogen-activated Protein Kinases and Neurite Outgrowth (1995)

Protein kinase C (PKC) activation enhances neurite outgrowth in several cell lines and primary neurons. The PKC isozymes that mediate this response are unknown. One clue to their identity has come from studies using PC12 cells treated with ethanol. In these cells, ethanol increases levels of delta-PKC and epsilon-PKC and markedly enhances nerve growth factor (NGF)-induced neurite outgrowth and activation of mitogen-activated protein (MAP) kinases by a PKC-dependent mechanism. Since these findings suggest that delta-PKC or epsilon-PKC can promote neural differentiation, we studied neurite outgrowth in stably transfected PC12 cell lines that overexpress these isozymes. Overexpression of epsilon-PKC markedly increased NGF-induced neurite outgrowth. This effect was blocked by down-regulating PKC or by treating cells with the PKC inhibitor GF 109203X. In addition, overexpression of epsilon-PKC enhanced NGF-induced phosphorylation of MAP kinases. In contrast, overexpression of delta-PKC did not alter responses to NGF. These results demonstrate that epsilon-PKC promotes NGF-induced neurite outgrowth by enhancing NGF signal transduction. These findings suggest a role for epsilon-PKC in neural differentiation and plasticity.
A Simple Parallel Algorithm for the Maximal Independent Set Problem (1986)

Two basic design strategies are used to develop a very simple and fast parallel algorithms for the maximal independent set (MIS) problem. The first strategy consists of assigning identical copies of a simple algorithm to small local portions of the problem input. The algorithm is designed so that when the copies are executed in parallel the correct problem output is produced very quickly. A very simple Monte Carlo algorithm for the MIS problem is presented which is based upon this strategy. The second strategy is a general and powerful technique for removing randomization from algorithms. This strategy is used to convert the Monte Carlo algorithm for this MIS problem into a simple deterministic algorithm with the same parallel running time.