gebhart/patrepeval huggingface dataset:
A MAGE-A4 peptide presented by HLA-A2 is recognized by cytolytic T lymphocytes (1999)

The MAGE-encoded antigens that are recognized by cytolytic T lymphocytes (CTL) are shared by many tumors and are strictly tumor specific. Clinical trials involving therapeutic vaccination of cancer patients with MAGE antigenic peptides or proteins are in progress. To increase the range of patients eligible for therapy with peptides, it is important to identify additional MAGE epitopes. We have used a method to identify CTL epitopes, which selects naturally processed peptides. CD8(+) T cells, obtained from individuals without cancer, were stimulated with autologous dendritic cells infected with a recombinant adenovirus containing the MAGE-A4 coding sequence. Responder cell microcultures that specifically lysed autologous EBV-transformed B cells infected with vaccinia-MAGE-A4 were cloned using autologous stimulator cells infected with a Yersinia enterocolitica carrying the MAGE-A4 sequence. An anti-MAGE-A4 CTL clone was obtained and the epitope was found to be decapeptide GVYDGREHTV (amino acids 230-239) presented by HLA-A2 molecules. The CTL clone lysed HLA-A2 tumor cells expressing MAGE-A4. This is the first reported antigenic peptide encoded by MAGE-A4. It may be valuable for cancer immunotherapy because MAGE-A4 is expressed in 51% of lung carcinomas and 63% of esophageal carcinomas, whereas about 50% of Caucasians and Asians express HLA-A2.
The role of BRAF V600 mutation in melanoma (2012)

BRAF is a serine/threonine protein kinase activating the MAP kinase/ERK-signaling pathway. About 50 % of melanomas harbors activating BRAF mutations (over 90 % V600E). BRAFV600E has been implicated in different mechanisms underlying melanomagenesis, most of which due to the deregulated activation of the downstream MEK/ERK effectors. The first selective inhibitor of mutant BRAF, vemurafenib, after highly encouraging results of the phase I and II trial, was compared to dacarbazine in a phase III trial in treatment-naïve patients (BRIM-3). The study results showed a relative reduction of 63 % in risk of death and 74 % in risk of tumor progression. Considering all trials so far completed, median overall survival reached approximately 16 months for vemurafenib compared to less than 10 months for dacarbazine treatment. Vemurafenib has been extensively tested on melanoma patients expressing the BRAFV600E mutated form; it has been demonstrated to be also effective in inhibiting melanomas carrying the V600K mutation. In 2011, both FDA and EMA therefore approved vemurafenib for metastatic melanoma carrying BRAFV600 mutations. Some findings suggest that continuation of vemurafenib treatment is potentially beneficial after local therapy in a subset of patients with disease progression (PD). Among who continued vemurafenib >30 days after local therapy of PD lesion(s), a median overall survival was not reached, with a median follow-up of 15.5 months from initiation of BRAF inhibitor therapy. For patients who did not continue treatment, median overall survival from the time of disease progression was 1.4 months. A clinical phase I/II trial is evaluating the safety, tolerability and efficacy of vemurafenib in combination with the CTLA-4 inhibitor mAb ipilimumab. In the BRIM-7 trial vemurafenib is tested in association with GDC-0973, a potent and highly selective inhibitor of MEK1/2. Preliminary data seem to indicate that an additional inhibitor of mutated BRAF, GSK2118436, might be also active on a wider range of BRAF mutations (V600E-K-D-R); actually, treatment with such a compound is under evaluation in a phase III study among stage III-IV melanoma patients positive for BRAF mutations. Overall, BRAF inhibitors were well tolerated; common adverse events are arthralgia, rash, fatigue, alopecia, keratoacanthoma or cutaneous squamous-cell carcinoma, photosensitivity, nausea, and diarrhea, with some variants between different inhibitors.
Penetration of Hydrogen Peroxide from Contact Lenses or Tear-Side Solutions into the Aqueous Humor (1991)

Contact lenses were soaked in hydrogen peroxide (H2O2) solutions of 1 to 20 mM (34 to 680 ppm) and placed on isolated rabbit corneas to determine whether H2O2 could penetrate across the tissue into the artificial aqueous humor used to perfuse the endothelial surface. Corneas with intact epithelium allowed no H2O2 to cross into the perfusing fluid even with the lenses containing the highest (20 mM) concentration of peroxide. If the epithelium was removed a transient pulse of H2O2 appeared in the perfusing fluid only from lenses with 10 or 20 mM H2O2. The cornea metabolized H2O2 rapidly (the rate varying with the concentration) and thus the small quantities of H2O2 in the contact lenses (less than 400 nmol at 20 mM) are destroyed before diffusing across the entire thickness of the cornea. When the contact lens was replaced by a 0.8 ml saline containing H2O2, and renewed every 15 min, H2O2 crossed the intact cornea to the perfusing fluid when its concentration at the epithelium was between 3 and 4 mM. Should such larger quantities be presented to the epithelium (for example, in eye drops) the concentration, volume, and duration of exposure will determine whether H2O2 enters the anterior chamber. It is concluded that in the clinical situation of typical contact lens use in an eye with intact epithelium neither the corneal endothelium nor other intraocular tissues will be damaged by residual concentrations of H2O2 up to 680 ppm, whether in single or daily events.
New Valve and Bonding Designs for Microfluidic Biochips Containing Proteins (2006)

Two major concerns in the design and fabrication of microfluidic biochips are protein binding on the channel surface and protein denaturing during device assembly. In this paper, we describe new methods to solve these problems. A "fishbone" microvalve design based on the concept of superhydrophobicity was developed to replace the capillary valve in applications where the chip surface requires protein blocking to prevent nonspecific binding. Our experimental results show that the valve functions well in a CD-like ELISA device. The packaging of biochips containing pre-loaded proteins is also a challenging task since conventional sealing methods often require the use of high temperatures, electric voltages, or organic solvents that are detrimental to the protein activity. Using CO2 gas to enhance the diffusion of polymer molecules near the device surface can result in good bonding at low temperatures and low pressure. This bonding method has little influence on the activity of the pre-loaded proteins after bonding.
Efficient production of recombinant human factor VIII by co-expression of the heavy and light chains (1993)

We have developed a high-level expression system for human blood coagulation factor VIII (FVIII) consisting of a 90 kDa heavy (H-)chain and an 80 kDa light (L-)chain. Two expression plasmids were prepared, one expressing the H-chain and the other expressing the L-chain. These recombinant plasmids were designed to produce each chain linked to short additional amino acid residues derived from the FVIII precursor sequence. Furthermore, Kozak's translation initiation consensus sequence was introduced into the start codon for the H-chain. These modifications have dramatically increased the levels of expression of these chains. Chinese hamster ovary (CHO) cells co-transfected with these two recombinant plasmids were subjected to gene amplification and cloning. The final cell line, designated CTC-CF8, secretes 15 IU/day/10(6) cells of active FVIII which is indistinguishable from plasma-derived FVIII in its structure and biochemical properties. This system is suitable for large-scale production of pathogen-free recombinant human FVIII which can be used for the treatment of haemophilia A patients.
Calcium Transport in Perfused Duodena from Normal Chicks: Enhancement within Fourteen Minutes of Exposure to 1,25-Dihydroxyvitamin D3* (1984)

The effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3) on calcium transport was studied in vascularly perfused duodena of normal, vitamin D-replete chicks. Addition of 130 pM 1,25(OH)2D3 to the perfusate resulted in a significant increase in 45Ca transport from the lumen to the vascular effluent within 14 min; the transport rate rose to 140% of levels in comparable preparations exposed for 40 min to vehicle. No effects of 1,25(OH)2D3 were noted on the back flux or transfer of 45Ca from the vascular effluent to the lumen. Vascular perfusion with 100 microM colchicine, an antimicrotubular agent, abolished the rapid lumen-to-vascular effluent effect of 1,25(OH)2D3 on 45Ca transport, relative to preparations exposed to the secosteroid and 100 microM lumicolchicine, (a light inactivated analog of colchicine). Colchicine did not, however, alter basal 45Ca transport rates. Addition of 130 pM 1,25(OH)2D3 to the lumenal compartment of normal chicks or vascular perfusion of duodena from vitamin D-deficient birds failed to increase 45Ca transport above control levels. Perfusion of duodena from normal chicks with 650 pM 1,25(OH)2D3 further increased calcium transport to 170% of levels observed in preparations treated with 130 pM steroid, and 210% of levels in controls. Although 15 nM vitamin D3 had no effect, in one series of experiments 125 nM 25-hydroxyvitamin D3 elicited vascular calcium levels that were 185% of controls at 40 min. These results suggest that 1,25(OH)2D3 can act in vitamin D-replete animals to produce rapid unidirectional calcium transport responses (through unknown mechanisms), as well as by interaction with intestinal nuclear receptors in D-deficient animals to promote induction of protein(s) that support long acting calcium transport responses.
Visualization of Three Phases in Porous Media using Micro Computed Tomography (2004)

Three-phase flow in porous media is a common phenomenon in hydrocarbon reservoirs. This study presents quantitative maps of fluid distribution in a granular porous medium using micro computed tomography (MCT). The study was done in an effort to determine the position, distribution and saturation of each phase at the pore-scale level. Quartz sand was used as the porous media. The fluids used were water (doped with NaI), benzyl alcohol (BA) and decane (doped with iodo-dodecane). The three fluids and the solid phase were mapped in images that were acquired at a single energy setting. Single-phase, two-phase and three-phase saturation distributions were developed. The intermediate phase was detected by direct observation of the phase distribution in the porous medium thus confirming calculations using interfacial tensions and the spreading coefficient. The results obtained from this research showed that micro computed tomography (MCT) is a useful technique to study multi-phase flow mechanisms in porous media. This work provided three-dimensional maps of fluid saturations at the pore level and should allow the reconsideration and adjustment of pore-scale modeling. This method provides the possibility to obtain three-dimensional saturation data that can be used for simulator development and calibration of models.
Granular Diverting Agents Selection, Design, and Performance (1989)

ABSTRACT One of the main problems in chemical treatments concerns the proper placement of the treatment fluids. Specifically, a very distorted inflow pattern may result after stimulation by matrix acidising treatments carried out without a means to distribute the injected fluids over the entire zone to be produced. A theoretical and experimental study is reported aimed at developing a better understanding of the diversion process. This has resulted in practical guidelines for the application of chemical diverters in general and, in particular, for the use of benzoic acid and its derivatives. The results of the current study also indicated some areas of uncertainties requiring further investigation. It is concluded that benzoic acid can successfully be applied in matrix acid treatments in water injectors and gas wells.
Signaling through protein kinase C (1998)

Protein kinase C (PKC) comprises a large family of serine/threonine kinases which are activated by many extracellular signals. Inside the cell, PKCs are regulated by a variety of lipid second messengers, including the ubiquitous diacylglycerol and phosphatidylserine. Phosphorylation has also emerged as an important mechanism of regulation of all PKCs. Work in the last 20 years has provided evidence that these enzymes are involved in a multitude of physiological processes. Similarly, a number of proteins which are phosphorylated by PKCs have also been discovered and their role in cell biology has been investigated. More recently, there has been considerable interest in a number of specific PKC isoforms and their role in signaling pathways in the cell. This review will focus on recent findings on the mechanism of regulation of PKCepsilon, PKCmu and PKCzeta, and how these enzymes regulate cell growth, the actin cytoskeleton, apoptosis and other biological functions.
A new triphasic solid-solid-liquid catalytic system for the inexpensive and selective oxidation of secondary alcohols by calcium hypochlorite (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA new triphasic solid-solid-liquid catalytic system for the inexpensive and selective oxidation of secondary alcohols by calcium hypochloriteMichel Schneider, Jean Victor Weber, and Pierre P. FallerCite this: J. Org. Chem. 1982, 47, 2, 364–365Publication Date (Print):January 1, 1982Publication History Published online1 May 2002Published inissue 1 January 1982https://pubs.acs.org/doi/10.1021/jo00341a039https://doi.org/10.1021/jo00341a039research-articleACS PublicationsRequest reuse permissionsArticle Views306Altmetric-Citations31LEARN 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
Protein stitchery: design of a protein for selective binding to a specific DNA sequence. (1992)

We present a general strategy for designing proteins to recognize DNA sequences and illustrate this with an example based on the "Y-shaped scissors grip" model for leucine-zipper gene-regulatory proteins. The designed protein is formed from two copies, in tandem, of the basic (DNA binding) region of v-Jun. These copies are coupled through a tripeptide to yield a "dimer" expected to recognize the sequence TCATCGATGA (the v-Jun-v-Jun homodimer recognizes ATGACTCAT). We synthesized the protein and oligonucleotides containing the proposed binding sites and used gel-retardation assays and DNase I footprinting to establish that the dimer binds specifically to the DNA sequence TCATCGATGA but does not bind to the wild-type DNA sequences, nor to oligonucleotides in which the recognition half-site is modified by single-base changes. These results also provide strong support for the Y-shaped scissors grip model for binding of leucine-zipper proteins.
Photomodulation of conformational states. Synthesis of cyclic peptides with backbone-azobenzene moieties (1999)

The search for photoresponsive conformational transitions accompanied by changes in physicochemical and biological properties led us to the design of small cyclic peptides containing azobenzene moieties in the backbone. For this purpose, (4-aminomethyl)phenylazobenzoic acid (H-AMPB-OH) and (4-amino)phenylazobenzoic acid (H-APB-OH) were synthesized and used to cyclize a bis-cysteinyl-octapeptide giving monocyclic derivatives in which additional conformational restriction could be introduced by conversion to bicyclic structures with a disulphide bridge. While synthesis with H-AMPB-OH proceeded smoothly on a chlorotrityl-resin with Fmoc/tBu chemistry, the poor nucleophilicity of the arylamino group of H-APB-OH required special chemistry for satisfactory incorporation into the peptide chain. Additional difficulties were encountered in the reductive cleavage of the S-tert-butylthio group from the cysteine residues since concomitant reduction of the azobenzene moiety took place at competing rates. This difficulty was eventually bypassed by using the S-trityl protection. Side-chain cyclization of the APB-peptide proved to be difficult, suggesting that restricted conformational freedom was already present in the monocyclic form, a fact that was fully confirmed by NMR structural analysis. Conversely, the methylene spacer in the AMPB moiety introduced sufficient flexibility for facile and quantitative side-chain cyclization to the bicyclic form. Both of the monocyclic peptides and both of the bicyclic peptides are photoresponsive molecules which undergo cis/trans isomerization reversibly.
Roadmap for Developing and Validating Therapeutically Relevant Genomic Classifiers (2005)

Oncologists need improved tools for selecting treatments for individual patients. The development of therapeutically relevant prognostic markers has traditionally been slowed by poor study design, inconsistent findings, and lack of proper validation studies. Microarray expression profiling provides an exciting new technology for relating tumor gene expression to patient outcome, but it also provides increased challenges for translating initial research findings into robust diagnostics that benefit patients and physicians in therapeutic decision making. This article attempts to clarify some of the misconceptions about the development and validation of multigene expression signature classifiers and highlights the steps needed to move genomic signatures into clinical application as therapeutically relevant and robust diagnostics.
Estrogen Receptor β Inhibits Human Breast Cancer Cell Proliferation and Tumor Formation by Causing a G2 Cell Cycle Arrest (2004)

Studies indicate that estrogen receptor (ER) alpha mediates breast cancer-promoting effects of estrogens. The role of ERbeta in breast cancer is unknown. Elucidating the role of ERbeta in the pathogenesis of breast cancer is important because many human breast tumors express both ERalpha and ERbeta. We show that adenovirus-mediated expression of ERbeta changes the phenotype of ERalpha-positive MCF-7 cells. Estradiol increases cell proliferation and causes tumor formation of MCF-7 cells expressing only ERalpha. In contrast, introducing ERbeta into MCF-7 cells causes an inhibition of proliferation in vitro and prevents tumor formation in a mouse xenograft model in response to estradiol. ERbeta inhibits proliferation by repressing c-myc, cyclin D1, and cyclin A gene transcription, and increasing the expression of p21(Cip1) and p27(Kip1), which leads to a G(2) cell cycle arrest. These results demonstrate that ERalpha and ERbeta produce opposite effects in MCF-7 cells on cell proliferation and tumor formation. Natural or synthetic ERbeta-selective estrogens may lack breast cancer promoting properties exhibited by estrogens in hormone replacement regimens and may be useful for chemoprevention of breast cancer.
Enhancement of the dissolution rate of a poorly water-soluble drug (tolbutamide) by a spray-drying solvent deposition method and disintegrants (1987)

The dissolution rate of a poorly water-soluble drug, tolbutamide, was improved by spray-drying a diluted ammonia solution of the drug containing either a low-substituted hydroxypropylcellulose (L-HPC) or partly pregelatinized corn starch (PCS) as disintegrants. With L-HPC the resultant particles were agglomerates of disintegrant with drug on the surface and within the particles, while particles formed with PCS were composed of a single core of PCS on which the drug was deposited. The deposited drug crystals were very fine because the rapid solvent evaporation restricted crystal growth. The spray-dried particles prepared with PCS had a structure similar to that of an ordered mix. The drug dissolution rate from the spray-dried particles was more rapid than that of the powdered drug alone or with disintegrant and could be attributed to separation of the layer of fine drug crystals from the surface of the particles by swelling of disintegrant. PCS enhanced the drug dissolution rate compared with systems using corn starch. The dissolution rate also depended on the drug content of the particles which was higher than that in ordered mixtures or conventional solvent deposition systems. This system described also had the advantage of avoiding the use of organic solvents.
[Correlation between retinal nerve fiber layer defect, neuroretinal rim area and visual impairment in primary open angle glaucoma]. (1991)

120 eyes of normal subjects, 150 eyes of ocular hypertension, and 132 eyes of primary open angle glaucoma (POAG) were examined the retinal nerve fiber layer (RNFL), neuroretinal rim area (NRA), visual field, dark adaptation and pattern reversal visual evoked potential (PVEP), revealing that RNFL defect and NRA correlated with visual field defect, threshold of dark adaptation and latency of PVEP. RNFL examination using red free photographic technique yielded 96% sensitivity in glaucoma detection and 95% specificity in identifying normal eyes. Modified semiquantitative criterion for assessing RNFL defect had a good reproducibility. The mean NRA in normal eyes was 2.22 +/- 0.35 mm2. Therefore, 95% of the normal subjects had rim areas greater than 1.64 mm2; 82% of patients with POAG had NRA less than 1.64 mm2. 20.1% of the eyes of ocular hypertension had RNFL defect and 37.6% had NRA below the 95% lower point, suggesting that some patients with increased intraocular pressure could have structural abnormalities. The authors proposed that ocular hypertension without visual field defect but with significant RNFL defect and/or NRA decrease should be regarded as in a preliminary stage of POAG.
Resistance to Qol fungicides: implications for cereal disease management in Europe (2003)

John Lucas from Rothamsted Research discusses the spread of resistance to strobilurins (or Qol fungicides) in Europe and its implications for cereal disease management.