gebhart/patrepeval huggingface dataset:
ecancermedicalscience (2016)

The vast genetic alterations characteristic of tumours produce a number of tumour antigens that enable the immune system to differentiate tumour cells from normal cells. Counter to this, tumour cells have developed mechanisms by which to evade host immunity in their constant quest for growth and survival. Tumour-associated antigens (TAAs) are one of the fundamental triggers of the immune response. They are important because they activate, via major histocompatibility complex (MHC), the T cell response, an important line of defense against tumourigenesis. However, the persistence of tumours despite host immunity implies that tumour cells develop immune avoidance. An example of this is the up-regulation of inhibitory immune checkpoint proteins, by tumours, which induces a form of self-tolerance. The majority of monoclonal antibodies in clinical practice have been developed to target tumour-specific antigens. More recently there has been research in the down-regulation of immune checkpoint proteins as a way of increasing anti-tumour immunity.
The mTOR Inhibitor Rapamycin Suppresses DNA Double-Strand Break Repair (2010)

mTOR (mammalian target of rapamycin) signaling plays a key role in the development of many tumor types. Therefore, mTOR is an attractive target for cancer therapeutics. Although mTOR inhibitors are thought to have radiosensitization activity, the molecular bases remain largely unknown. Here we show that treating MCF7 breast cancer cells with rapamycin (an mTOR inhibitor) results in significant suppression of homologous recombination (HR) and nonhomologous end joining (NHEJ), two major mechanisms required for repairing ionizing radiation-induced DNA DSBs. We observed that rapamycin impaired recruitment of BRCA1 and Rad51 to DNA repair foci, both essential for HR. Moreover, consistent with the suppressive role of rapamycin on both HR and NHEJ, persistent radiation-induced DSBs were detected in cells pretreated with rapamycin. Furthermore, the frequency of chromosome and chromatid breaks was increased in cells treated with rapamycin before and after irradiation. Thus our results show that radiosensitization by mTOR inhibitors occurs via disruption of the major two DNA DSB repair pathways.
A ferroelectric-piezoelectric random access memory (1971)

A two-dimensional ferroelectric memory array is combined with a piezoelectric interrogation technique to provide a memory device with nonvolatile storage, random access, non-destructive readout and compatibility with integrated circuits. Binary information is stored as either a positive or negative polarization state in ferroelectric ceramic material and is read out by sensing the polarity of the piezoelectric response of the material. Calculations and experimental results are presented for a 5 word × 5 bits per word prototype device for which a complete logic and driving circuit has been designed and used. Switching characteristics, disturb pulse sensitivity, and changes with temperature are presented. Calculations show that word-to-word capacitive coupling will affect the maximum size of the memory and will probably limit the number of words per chip to approximately 25. No such limit exists on the number of bits per word.
Atherosclerotic and Thrombophilic Risk Factors in Patients with Recurrent Central Retinal Vein Occlusion (2008)

Dyslipidemia and hyperhomocysteinemia are independent risk factors for the occurrence of recurrent CRVO. A complete assessment of atherosclerotic and thrombophilic risk factors in CRVO patients. In addition, the need for a specific treatment is suggested.
Synthesis and biological evaluation of substituted benzenesulfonamides as novel potent membrane-bound phospholipase A2 inhibitors (1991)

A novel series of 4-[N-methyl-N-[(E)-3-[4-(methylsulfonyl)phenyl]-2- propenoyl]amino]benzenesulfonamides has been prepared and evaluated as membrane-bound phospholipase A2 inhibitors. A structure-activity relationship study indicated that the optimum potency was realized with the N-(phenylalkyl)piperidine derivatives 3 and 4. These compounds inhibited the liberation of arachidonic acid from the rabbit heart membrane fraction with IC30 values of 0.028 and 0.009 microM, respectively. Several compounds (3, 4, and 28), which proved to be potent inhibitors in vitro, significantly reduced the size of myocardial infarction in coronary occluded rats by iv administrations prior to the ligation. N-(1-Benzyl-4-piperidinyl)-4-[N-methyl-N-[(E)-3-[ 4-(methylsulfonyl)phenyl]-2-propenoyl]amino]-benzenesulfonamide (3, ER-3826), which showed the protective in vivo effects at doses higher than 0.3 mg/kg iv, was finally chosen as a leading candidate.
Electrical Detection of DNA Hybridization with Single‐Base Specificity Using Transistors Based on CVD‐Grown Graphene Sheets (2010)

Large-sized chemical vapor deposited graphene films configured as solution-gated transistors can label-freely and electrically detect DNA hybridization with single-base specificity. The gate voltage which gives the minimum device conductance (Vg,min) is sensitive to the charge transfer between DNA molecules and graphene, and thus is used to detect the DNA hybridization. The DNA detection is attributed to the electronic n-doping from DNA to graphene rather than the electrostatic gating effect or impurity screening effect.
The Importance of RNA-Based Vaccines in the Fight against COVID-19: An Overview (2021)

In recent years, vaccine development using ribonucleic acid (RNA) has become the most promising and studied approach to produce safe and effective new vaccines, not only for prophylaxis but also as a treatment. The use of messenger RNA (mRNA) as an immunogenic has several advantages to vaccine development compared to other platforms, such as lower coast, the absence of cell cultures, and the possibility to combine different targets. During the COVID-19 pandemic, the use of mRNA as a vaccine became more relevant; two out of the four most widely applied vaccines against COVID-19 in the world are based on this platform. However, even though it presents advantages for vaccine application, mRNA technology faces several pivotal challenges to improve mRNA stability, delivery, and the potential to generate the related protein needed to induce a humoral- and T-cell-mediated immune response. The application of mRNA to vaccine development emerged as a powerful tool to fight against cancer and non-infectious and infectious diseases, for example, and represents a relevant research field for future decades. Based on these advantages, this review emphasizes mRNA and self-amplifying RNA (saRNA) for vaccine development, mainly to fight against COVID-19, together with the challenges related to this approach.
Perceptual optimization of DCT color quantization matrices (2002)

The JPEG baseline standard for image compression employs a block discrete cosine transform (DCT) and uniform quantization. For a monochrome image, a single quantization matrix is allowed, while for a color image, distinct matrices are allowed for each color channel. We describe a method, called DCTune, for the design of color quantization matrices that is based on a model of the visibility of quantization artifacts. The model describes the artifact visibility as a function of DCT frequency, color channel, and display resolution and brightness. The model also describes the summation of artifacts over space and frequency, and masking of artifacts by the image itself. The DCTune matrices are different from the de facto JPEG matrices, and appear to provide superior visual quality at equal bit-rates.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Primary Structure and Tissue-specific Expression of Human β-Hydroxyisobutyryl-coenzyme A Hydrolase (1996)

beta-Hydroxyisobutyryl-CoA (HIBYL-CoA) hydrolase is responsible for the specific hydrolysis of HIBYL-CoA, a saline catabolite, as well as the hydrolysis of beta-hydroxypropionyl-CoA, an intermediate in a minor pathway of propionate metabolism. We have obtained the amino acid sequences of several tryptic peptides derived from purified rat liver HIBYL-CoA hydrolase, and the NH2-terminal peptize sequence was matched to the translated sequence of a human expressed sequence tag present in the data base of the IMAGE Consortium (Lawrence Livermore National Laboratory, Livermore, CA). The complete nucleotide sequence and the deduced amino acid sequence showed no similarity to the sequences of well known thioesterases but showed significant homology to the enoyl-CoA hydratase/isomerase enzyme family. The cDNA fragment corresponding to the mature (processed) protein was expressed in Escherichia coli. The purified recombinant enzyme displayed substrate specificity very similar to that of the rat enzyme and was specifically bound by polyclonal antibodies raised against purified rat liver HIBYL-CoA hydrolase. Northern and Western blot analyses with various human tissues indicated predominant expression in liver, heart, and kidney, with discrepancies occurring in the amounts of HIBYL-CoA hydrolase mRNA compared to stably expressed protein in several tissues.
TAT-Mediated Neurogenin 3 Protein Transduction Stimulates Pancreatic Endocrine Differentiation In Vitro (2005)

Stem cell technologies hold great potential for the treatment of type 1 diabetes, provided that functional transplantable beta-cells can be selectively generated in an efficient manner. Such a process should recapitulate, at least to a certain extent, the embryonic development of beta-cells in vitro. However, progress at identifying the transcription factors involved in beta-cell development has not been accompanied by a parallel success at unraveling the pattern of their instructive extracellular signals. Here we present proof of principle of a novel approach to circumvent this problem, based on the use of the HIV/TAT protein transduction domain. Neurogenin 3 (ngn3), a factor whose expression is essential for pancreatic endocrine differentiation, was fused to the TAT domain. Administration of TAT/ngn3 to cultured pancreatic explants results in efficient uptake, nuclear translocation, and stimulation of downstream reporter and endogenous genes. Consistent with the predicted activity of the protein, e9.5 and e13.5 mouse pancreatic explants cultured in the presence of TAT/ngn3 show an increased level of endocrine differentiation compared with control samples. Our results raise the possibility of sequentially specifying stem/progenitor cells toward the beta-cell lineage, by using the appropriate sequence and combination of TAT-fused transcription factors.
The Role of HER2/neu Overexpression/Amplification in the Progression of Ductal Carcinoma In Situ to Invasive Carcinoma of the Breast (2002)

HER2/neu overexpression/amplification is seen more frequently in ductal carcinoma in situ, particularly high-grade ductal carcinoma in situ (50-60%), than in invasive ductal carcinoma of the breast (25-30%). To date, however, the role of HER2/neu in the progression of in situ to invasive disease has not been clarified. Two hundred fifty-one breast tumors were retrieved from the pathology files at Mount Sinai Hospital. These included 91 cases of ductal carcinoma in situ, 136 cases of invasive ductal carcinomas with associated ductal carcinoma in situ, and 24 cases of pure invasive carcinomas. All cases were reviewed and stained with two monoclonal antibodies to HER2/neu (CB11 and TAB250). Immunohistochemical staining was recorded using a semiquantitative scoring system (1). Representative cases were also investigated using fluorescence in situ hybridization. HER2/neu protein overexpression (defined as immunohistochemical staining with score of >or=5) was seen in 34% of cases of pure ductal carcinoma in situ, 17% of invasive carcinomas with associated ductal carcinoma in situ, and 12.5% of pure invasive carcinomas (P =.01). Sixty percent of cases of high-grade ductal carcinoma in situ showed HER2/neu protein overexpression, versus 29% of high-grade invasive carcinomas with associated ductal carcinoma in situ and 22% of high-grade pure invasive ductal carcinomas (P =.02). The concordance between the immunohistochemical staining in the in situ and invasive components of individual tumors was 90%. Thirty-three cases were also evaluated by fluorescence in situ hybridization and showed concordance between the immunohistochemical results and the degree of gene amplification in 91% of cases, whereas 3 of 33 cases showed HER2/neu gene amplification (HER2/CEP17 = 2.3-3.7) by fluorescence in situ hybridization in the absence of positive immunohistochemical staining. One case showed HER2/neu gene amplification in the associated ductal carcinoma in situ (HER2/CEP17 ratio = 6.5), with no evidence of gene amplification in the invasive tumor (HER2/CEP17 ratio = 1.14). Multiple genetic events are required for the development of an invasive phenotype. The findings from this study suggest that the genetic event of HER2/neu gene amplification/protein overexpression may not play a key role in the progression of ductal carcinoma in situ to invasive carcinoma and that other molecular alterations may be more important in the initiation of invasion in ductal carcinoma of the breast.
The springboard (2006)

Modes allow a few inputs to invoke many operations, yet if a user misclassifies or forgets the state of a system, modes can result in errors. Spring-loaded modes (quasimodes) maintain a mode while the user holds a control such as a button or key. The Springboard is an interaction technique for tablet computers that extends quasimodes to encompass multiple tool modes in a single spring-loaded control. The Springboard allows the user to continue holding down a nonpreferred-hand command button after selecting a tool from a menu as a way to repeatedly apply the same tool. We find the Springboard improves performance for both a local marking menu and for a non-local marking menu ("lagoon") at the lower left corner of the screen. Despite the round-trip costs incurred to move the pen to a tool lagoon, a keystroke-level analysis of the true cost of each technique reveals the local marking menu is not significantly faster.
Pharmacological analysis of neutrophil chemotactic factor production by leucocytes and roles of PAF in allergic inflammation in rats (1994)

1. The role of platelet activating factor (PAF) in neutrophil infiltration in air pouch type allergic inflammation in rats was investigated. 2. Neutrophil infiltration into the pouch fluid 8 h after injection of the antigen (azobenzenearsonate-conjugated acetyl bovine serum albumin) solution into the air pouch of immunized rats was inhibited dose-dependently by treatment with PAF antagonists (CV-3988, L-652,731 and Y-24,180) in parallel with the decrease in neutrophil chemotactic activity in the pouch fluid. 3. Four hours after injection of the antigen solution into the air pouch of immunized and non-immunized rats, there was no significant difference between the two groups in the number of total leucocytes, neutrophils, mononuclear cells and eosinophils in the pouch fluid. However, when the infiltrated leucocytes were incubated in medium, chemotactic factor production by leucocytes from immunized rats was greater than that from non-immunized rats. 4. When leucocytes from non-immunized rats were preincubated for various periods in the medium containing 10 or 50 nM of PAF, washed, and further incubated in the medium containing no PAF, chemotactic factor production was not stimulated. 5. The increase in the chemotactic activity in the conditioned medium was not suppressed by the 5-lipoxygenase inhibitor, AA861. In addition, the chemotactic activity in the conditioned medium was not inhibited by the PAF antagonists. 6. Incubation of the infiltrated leucocytes in the medium containing the protein synthesis inhibitor, cycloheximide, inhibited chemotactic factor production in a concentration-dependent manner in parallel with the decrease in uptake of [3H]-leucine into the acid-insoluble fraction of leucocytes. 7. Separation of the chemotactic activity in the conditioned medium by isoelectric focusing revealed that the leucocyte infiltrated into the pouch fluid produce two kinds of factors, viz. leucocyte-derived neutrophil chemotactic factor-i (LDNCF-1) and LDNCF-2 of which pI values are 4-5 and above 8,respectively.8. The results indicate that PAF has no significant role in leucocyte activation to produce chemotactic factors, and that neutrophil chemotactic factors produced by infiltrated leucocytes are not PAF or leukotriene B4 but are produced through a protein synthesis mechanism.9. The mechanism of action of PAF antagonists on neutrophil infiltration into the inflammatory locus is discussed.
Immunogenicity of multiple antigen peptides containing B and non-repeat T cell epitopes of the circumsporozoite protein of Plasmodium falciparum (1993)

We have characterized the immune response of mice to multiple Ag peptide systems (MAP) containing the immunodominant B cell epitope (NANP)3 and one of three distinct Th epitopes, Th2R, Th3R, and CS.T3, of the C terminal region of the circumsporozoite protein of Plasmodium falciparum, a human malaria parasite. Mice of three different MHC haplotypes (H-2k, H-2d, and H-2a) were immunized with the various MAP constructs. Mice of all three strains produced antibodies, but their anti-sporozoite titers were considerably lower than their anti-peptide titers as detected by ELISA. These antibodies reacted at high titers not only with the repeat polymer (NANP)50, but also with MAP that contained only the respective Th sequence. The antibody binding site within each of the Th sequences was mapped, using truncated peptides, in an inhibition assay. A primary antibody response, induced by a single i.v. inoculation of sporozoites, was greatly enhanced by the injection of MAP.
Synthesis of a Novel Pentagastrin‐Drug Conjugate for a Targeted Tumor Therapy (2008)

The synthesis of the novel pentagastrin seco-CBI conjugate 3, which is based on the highly cytotoxic antitumor antibiotic (+)-duocarmycin SA (1), is reported. A key step in the synthesis is the palladium-catalyzed carbonylation of aryl bromide 7 to give the benzyl ester 16, which is transformed into the new seco-CBI derivative 21 bearing a carboxylic acid ester moiety. Subsequent transformation of 21 into an activated ester followed by the introduction of beta-alanine and tetragastrin led to the new pentagastrin drug 3 that contains a peptide moiety for targeting cancer cells expressing CCK-B/gastrin receptors.
Bioactive Coatings of Endovascular Stents Based on Polyelectrolyte Multilayers (2003)

Layer-by-layer self-assembly of two polysaccharides, hyaluronan (HA) and chitosan (CH), was employed to engineer bioactive coatings for endovascular stents. A polyethyleneimine (PEI) primer layer was adsorbed on the metallic surface to initiate the sequential adsorption of the weak polyelectrolytes. The multilayer growth was monitored using a radiolabeled HA and shown to be linear as a function of the number of layers. The chemical structure, interfacial properties, and morphology of the self-assembled multilayer were investigated by time-of-flight secondary ions mass spectrometry (ToF-SIMS), contact angle measurements, and atomic force microscopy (AFM), respectively. Multilayer-coated NiTi disks presented enhanced antifouling properties, compared to unmodified NiTi disks, as demonstrated by a decrease of platelet adhesion in an in vitro assay (38% reduction; p = 0.036). An ex vivo assay on a porcine model indicated that the coating did not prevent fouling by neutrophils. To assess whether the multilayers may be exploited as in situ drug delivery systems, the nitric-oxide-donor sodium nitroprusside (SNP) was incorporated within the multilayer. SNP-doped multilayers were shown to further reduce platelet adhesion, compared to standard multilayers (40% reduction). When NiTi wires coated with a multilayer containing a fluorescently labeled HA were placed in intimate contact with the vascular wall, the polysaccharide translocated on the porcine aortic samples, as shown by confocal microscopy observation of a treated artery. The enhanced thromboresistance of the self-assembled multilayer together with the antiinflammatory and wound healing properties of hyaluronan and chitosan are expected to reduce the neointimal hyperplasia associated with stent implantation.
Inhibitory effects of acyclic nucleoside phosphonate analogs, including (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, on Epstein-Barr virus replication (1991)

(S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-2,6-diaminopurine [(S)-HPMPDAP], cyclic (S)-HPMPA [(S)-cHPMPA], 9-(2-phosphonylmethoxyethoxyethyl)-2,6-diaminopurine (PMEDAP), and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] were examined for their inhibitory effects on Epstein-Barr virus (EBV) replication. The 50% effective concentrations for inhibition of viral DNA replication were 0.16, 0.03, 2.0, 1.5, and 0.08 microM for PMEDAP, (S)-HPMPC, (S)-HPMPDAP, (S)-cHPMPA, and (S)-HPMPA, respectively. The relative efficacies based on the in vitro therapeutic index was (S)-HPMPC (5,000) greater than PMEDAP (1,000) = (S)-HPMPA (1,000) greater than (S)-cHPMPA (136) greater than (S)-HPMPDAP (78). Certain ratios of combinations of (S)-HPMPC with 3'-azido-3'-deoxythymidine produced a synergistic inhibitory effect on EBV genome replication, but others exhibited an antagonistic effect. These results indicate that this series of acyclic nucleoside phosphonate analogs, and in particular (S)-HPMPC, are potent and selective anti-EBV agents in vitro.
Nonlithographic fabrication of lateral superlattices for nanometric electromagnetic-optic applications (2002)

A nonlithographic technique that utilizes highly ordered anodized aluminum oxide (AAO) porous membrane as a template is employed as a general fabrication means for the formation of an array of vastly different two-dimensional lateral superlattice nanostructures. The fact that material systems as different as metals, semiconductors, and carbon nanotubes can be treated with the same ease attest to the generality of this nanofabrication approach. The original AAO membranes determine the uniformity, packing density, and size of the nanostructures. The flexibility of using a variety of materials, the accurate control over fabrication process, and the command over AAO template attributes, gives us the freedom of engineering various physical properties determined by the shape, size, composition, and doping of the nanostructures. The novel nanomaterial platform realized by this unique technique is powerfully enabling for a broad range of applications.
NMR solution structure of Cn12, a novel peptide from the Mexican scorpion Centruroides noxius with a typical β‐toxin sequence but with α‐like physiological activity (2004)

Cn12 isolated from the venom of the scorpion Centruroides noxius has 67 amino-acid residues, closely packed with four disulfide bridges. Its primary structure and disulfide bridges were determined. Cn12 is not lethal to mammals and arthropods in vivo at doses up to 100 microg per animal. Its 3D structure was determined by proton NMR using 850 distance constraints, 36 phi angles derived from 36 coupling constants obtained by two different methods, and 22 hydrogen bonds. The overall structure has a two and half turn alpha-helix (residues 24-32), three strands of antiparallel beta-sheet (residues 2-4, 37-40 and 45-48), and a type II turn (residues 41-44). The amino-acid sequence of Cn12 resembles the beta scorpion toxin class, although patch-clamp experiments showed the induction of supplementary slow inactivation of Na(+) channels in F-11 cells (mouse neuroblastoma N18TG-2 x rat DRG2), which means that it behaves more like an alpha scorpion toxin. This behaviour prompted us to analyse Na(+) channel binding sites using information from 112 Na(+) channel gene clones available in the literature, focusing on the extracytoplasmic loops of the S5-S6 transmembrane segments of domain I and the S3-S4 segments of domain IV, sites considered to be responsible for binding alpha scorpion toxins.