gebhart/patrepeval huggingface dataset:
CD40 stimulation leads to effective therapy of CD40−tumors through induction of strong systemic cytotoxic T lymphocyte immunity (2002)

Adequate spontaneous activation of tumor-specific T lymphocytes in tumor-bearing hosts is rare, despite the expression of tumor antigens that are potentially highly immunogenic. For example, failure of the immune system to raise competent responses against established tumors expressing the human adenovirus E1A-antigen allows this tumor to grow in immunocompetent mice. We show that systemic in vivo administration of agonistic anti-CD40 antibodies into tumor-bearing mice results in tumor eradication mediated by CD8(+) T cells. Treatment resulted in a strong expansion and systemic accumulation of E1A-specific CTL and depended on CD40 expression on host cells, as the tumor was CD40(-), and therapy failed in CD40-deficient mice. Local intratumoral administration of anti-CD40 mAb is equally effective in licensing strong, systemic CTL immunity, resulting in the clearance of distant tumor nodules. Our data indicate that the immune response after cancer-host interactions can be directed toward competence, leading to the cure of established tumors merely by delivery of a CD40-dependent "license to kill" signal.
Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy (1996)

In a distinct autosomal recessive variant of epidermolysis bullosa, EB-MD, life-long skin blistering is associated with late-onset muscular dystrophy of unknown etiology. Electron microscopy of these patients' skin suggests that tissue separation occurs intracellularly at the level of the hemidesmosomal inner plaque, which contains plectin, a high molecular weight cytoskeletal associated protein, also expressed in the sarcolemma of the muscle. In this study, we report two patients with EB-MD, each with a homozygous deletion mutation in the plectin gene, PLEC1. In the first case, the proband and her similarly affected sister had a homozygous 9 bp deletion mutation, designated as 2719de19, which resulted in elimination of three amino acids, QEA, in a sequence of 23 amino acids entirely conserved between the mouse and human sequences. The proband in the second family demonstrated a single nucleotide deletion at position 5866, designated as 5866delC, which resulted in frameshift and a premature termination codon for translation 16 bp downstream from the site of deletion. The absence of plectin in the hemidesmosomes, as reflected by negative immunofluorescence with an anti-plectin antibody (HD-1), associated with fragility of basal keratinocytes, implicates plectin as critical for binding of intermediate keratin filament network to hemidesmosomal complexes. The function of plectin as a putative attachment protein also in the muscle would explain the clinical phenotype consisting of cutaneous fragility and muscular dystrophy in EB-MD.
The common rejection module in chronic rejection post lung transplantation (2018)

Transcriptional tissue analysis for CRM genes in CLAD can identify acute rejection and distinguish RAS from BOS. The immune activation in RAS seems similar to acute rejection after kidney/liver/heart transplantation.
Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function (1998)

A novel and robust automated docking method that predicts the bound conformations of flexible ligands to macromolecular targets has been developed and tested, in combination with a new scoring function that estimates the free energy change upon binding. Interestingly, this method applies a Lamarckian model of genetics, in which environmental adaptations of an individual's phenotype are reverse transcribed into its genotype and become heritable traits (sic). We consider three search methods, Monte Carlo simulated annealing, a traditional genetic algorithm, and the Lamarckian genetic algorithm, and compare their performance in dockings of seven protein–ligand test systems having known three-dimensional structure. We show that both the traditional and Lamarckian genetic algorithms can handle ligands with more degrees of freedom than the simulated annealing method used in earlier versions of AUTODOCK, and that the Lamarckian genetic algorithm is the most efficient, reliable, and successful of the three. The empirical free energy function was calibrated using a set of 30 structurally known protein–ligand complexes with experimentally determined binding constants. Linear regression analysis of the observed binding constants in terms of a wide variety of structure-derived molecular properties was performed. The final model had a residual standard error of 9.11 kJ mol−1 (2.177 kcal mol−1) and was chosen as the new energy function. The new search methods and empirical free energy function are available in AUTODOCK, version 3.0. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1639–1662, 1998
[Pharmaceutical applications of sulfobuthylether-beta-cyclodextrin]. (2013)

Sulfobuthylether-beta-cyclodextrin (SBECD) is a substituted derivative of a cyclic oligosaccharide containing seven glucopyranose units, which bear pH-independent negative charges because of sulfonate groups. This derivative has better solubility and toxicological characteristics than the unsubstituted beta-cyclodextrin, and the presence of sulfobuthyl groups opens new dimensions in the interactions acting the part of the complex formation. These create opportunities for the pharmaceutical applications of this compound. Currently six pharmaceutical preparations circulate--moiety of these circulates in Hungary also--which have a composition containing SBECD as pharmaceutical excipient. Out of the main effects of the complex-forming agent the solubility enhancement is utilized in these compositions to achieve the solution of a therapeutic dose in the case of intravascular administration. Available experimental evidences and published patents are indicative of broadening the circle of the applications in point of both technological advantages and dosage forms.
Several HLA alleles share overlapping peptide specificities. (1995)

Herein we describe the establishment of assays to measure peptide binding to purified HLA-B*0701, -B*0801, -B*2705, -B*3501-03, -B*5401, -Cw*0401, -Cw*0602, and -Cw*0702 molecules. The binding of known peptide epitopes or naturally processed peptides correlates well with HLA restriction or origin, underscoring the immunologic relevance of these assays. Analysis of the sequences of various HLA class I alleles suggested that alleles with peptide motifs characterized by proline in position 2 and aromatic or hydrophobic residues at their C-terminus shared key consensus residues at positions 9, 63, 66, 67, and 70 (B pocket) and residue 116 (F pocket). Prediction of the peptide-binding specificity of HLA-B*5401, on the basis of this consensus B and F pocket structure, verified this hypothesis and suggested that a relatively large family of HLA-B alleles (which we have defined as the HLA-B7-like supertype) may significantly overlap in peptide binding specificity. Availability of quantitative binding assays allowed verification that, indeed, many (25%) of the peptide ligands carrying proline in position 2 and hydrophobic/aromatic residues at the C-terminus (the B7-like supermotif) were capable of binding at least three of five HLA-B7-like supertype alleles. Identification of epitopes carrying the B7-like supermotif and binding to a family of alleles represented in over 40% of individuals from all major ethnic groups may be of considerable use in the design of peptide vaccines.
Determination of mercury in filtered sea-water by flow injection with on-line oxidation and atomic fluorescence spectrometric detection (1996)

A flow injection (FI) atomic fluorescence method incorporating an on-line bromide–bromate oxidation step to determine mercury in filtered sea-water samples at the ng l–1 level is described. A heated reaction coil was incorporated in the FI manifold to increase the conversion of organic mercury into inorganic mercury(II) chloride from 50 to approaching 100%. Detection limits (3σ) for mercury(II) chloride and methylmercury chloride were 25 and 23 ng l–1 Hg, respectively. The FI manifold could also be used to determine the total mercury concentration in biological materials and was validated by analysing the CRM TORT-1 Lobster Hepatopancreas. Good agreement with the certified (330 ± 60 µg l–1) value was achieved (353 ± 64 µg l–1). The analysis of coastal water samples from Sutton Harbour, Plymouth, showed that mercury levels ranged from 24 ± 5 to 54 ± 10 ng l–1.
Optimal Point Spread Function Design for 3D Imaging (2014)

To extract from an image of a single nanoscale object maximum physical information about its position, we propose and demonstrate a framework for pupil-plane modulation for 3D imaging applications requiring precise localization, including single-particle tracking and superresolution microscopy. The method is based on maximizing the information content of the system, by formulating and solving the appropriate optimization problem--finding the pupil-plane phase pattern that would yield a point spread function (PSF) with optimal Fisher information properties. We use our method to generate and experimentally demonstrate two example PSFs: one optimized for 3D localization precision over a 3 μm depth of field, and another with an unprecedented 5 μm depth of field, both designed to perform under physically common conditions of high background signals.
Immediate pigment darkening: its evolutionary roles may include protection against folate photosensitization (2011)

The evolution of dark human skin colors in tropical areas is possibly related to photoprotection of folates. However, natural folates absorb mainly UVB radiation, and too little UVB can penetrate down to folates in dermal vessels to cause serious damage. However, endogenous photosensitizers, like riboflavin and uroporphyrin, absorbing UVA and visible light, can cause photosensitization of folates. Immediate pigment darkening (IPD), generated by UVA, has an absorption spectrum covering those of the endogenous photosensitizers. IPD is most prominent for darker skin types, which were typical for populations living under tropical solar fluences. We here propose that the biological role of IPD is protection of folates against photodegradation, which would be of large evolutionary importance for early hominids.
Site-specific integration of bacteriophage VWB genome into Streptomyces venezuelae and construction of a VWB-based integrative vector (1998)

The temperate bacteriophage VWB integrates into the chromosome of Streptomyces venezuelae ETH14630 via site-specific integration. Following recombination of the VWB attP region with the chromosomal attB sequence, the host-phage junctions attL and attR are formed. Nucleotide sequence analysis of attP, attB, attL and attR revealed a 45 bp common core sequence. In attB this 45 bp sequence consists of the 3' end of a putative tRNA Arg(AGG) gene with a 3'-terminal CCA sequence which is typical for prokaryotic tRNAs. Phage DNA integration restores the putative tRNA Arg(AGG) gene in attL. However, following recombination the CCA sequence is missing as is the case for most Streptomyces tRNA genes described so far. Adjacent to VWB attP, an ORF encoding a 427 aa protein was detected. The C-terminal region of this protein shows high similarity to the conserved C-terminal domain of site-specific recombinases belonging to the integrase family. To prove the functionality of this putative integrase gene (int), an integrative vector pKT02 was constructed. This vector consists of a 2.3 kb HindIII-SphI restriction fragment of VWB DNA containing attP and int cloned in a non-replicative Escherichia coli vector carrying a thiostrepton-resistance (tsr) gene. Integration of pKT02 was obtained after transformation of Streptomyces venezuelae ETH14630 and Streptomyces lividans TK24 protoplasts. This vector will thus be useful for a number of additional Streptomyces species in which a suitable tRNA gene can be functional as integration site.
Distributed Representations of Sentences and Documents (2014)

Many machine learning algorithms require the input to be represented as a fixed-length feature vector. When it comes to texts, one of the most common fixed-length features is bag-of-words. Despite their popularity, bag-of-words features have two major weaknesses: they lose the ordering of the words and they also ignore semantics of the words. For example, "powerful," "strong" and "Paris" are equally distant. In this paper, we propose Paragraph Vector, an unsupervised algorithm that learns fixed-length feature representations from variable-length pieces of texts, such as sentences, paragraphs, and documents. Our algorithm represents each document by a dense vector which is trained to predict words in the document. Its construction gives our algorithm the potential to overcome the weaknesses of bag-of-words models. Empirical results show that Paragraph Vectors outperform bag-of-words models as well as other techniques for text representations. Finally, we achieve new state-of-the-art results on several text classification and sentiment analysis tasks.
Molecular studies on the mechanism of tetracycline resistance mediated by Tet(O) (1990)

The mechanism of resistance to tetracycline in Escherichia coli mediated by the Campylobacter jejuni-derived resistance determinant Tet(O) was investigated. The cloned Tet(O) protein had no detectable effect on the intracellular accumulation of tetracycline. The presence of Tet(O) markedly diminished the inhibitory effect of tetracycline on protein synthesis both in vivo and in vitro. Ribosomes prepared from tetracycline-resistant and susceptible E. coli cells bound almost identical amounts of radiolabeled tetracycline. Thus, a reduction in the binding of the antibiotic to its target site on the ribosome is not the primary mechanism of resistance. Poly(U)-directed polyphenylalanine synthesis revealed that an S-100 fraction prepared from tetracycline-resistant cells made the ribosomes prepared from susceptible cells considerably more resistant to the inhibitory action of tetracycline. The N-terminal portion (1 to 150 residues) of Tet(O) is highly homologous to the GTP-binding domain of elongation factor Tu and to elongation factor G, indicating that the Tet(O) protein has the potential to bind GTP. These data suggest that the Tet(O) protein could function either as a tetracycline-resistant analog of this elongation factor(s) or by modifying the target sites on the ribosomes in a catalytic fashion.
The buzz on buzz. (2000)

Word-of-mouth promotion has become an increasingly potent force, capable of catapulting products from obscurity into runaway commercial successes. Harry Potter, collapsible scooters, the Chrysler PT Cruiser, and The Blair Witch Project are all recent examples of the considerable power of buzz. Yet many top executives and marketing managers are misinformed about the phenomenon and remain enslaved to some common myths. In her article, author Renée Dye explores the truth behind these myths. Myth 1: Only outrageous or edgy products are buzz-worthy. That's simply not true. The most unlikely products, like prescription drugs, can generate tremendous buzz. Myth 2: Buzz just happens. Not so, says Dye. Buzz is increasingly the result of shrewd marketing tactics in which companies seed a vanguard group, ration supplies, use celebrity endorsements, leverage the power of lists, and initiate grassroots marketing. Myth 3: The best buzz-starters are your best customers. Often, a counterculture has a greater ability to start buzz. Myth 4: To profit from buzz, you must act first and fast. In fact, copycat companies can reap substantial profits if they know when and when not to jump in. Myth 5: The media and advertising are needed to create buzz. When used either too early or too much, the media and advertising can squelch buzz before it ignites. As globalization and brand proliferation continue, writes Dye, buzz may come to dominate the shaping of markets. Indeed, companies that are unable to control buzz may soon find the phenomenon controlling them.
Evolution of hydrogen and helium co-implanted single-crystal silicon during annealing (2001)

H + was implanted into single-crystal silicon with a dose of 1×1016/cm2 and an energy of 30 KeV, and then He+ was implanted into the same sample with the same dose and an energy of 33 KeV. Both of the implantations were performed at room temperature. Subsequently, the samples were annealed in a temperature range from 200 to 450 °C for 1 h. Cross-sectional transmission electron microscopy, Rutherford backscattering spectrometry/channeling, elastic recoil detection, and high resolution x-ray diffraction were employed to characterize the strain, defects, and the distribution of H and He in the samples. The results showed that co-implantation of H and He decreases the total implantation dose, with which the surface could exfoliate during annealing. During annealing, the distribution of hydrogen did not change, but helium moved deeper and its distribution became sharper. At the same time, the maximum of the strain in the samples decreased a lot and also moved deeper. Furthermore, the defects introduced by ion implantation and annealing were characterized by slow positron annihilation spectroscopy, and two positron trap peaks were found. After annealing, the maximum of these two peaks decreased at the same time and their positions moved towards the surface. No bubbles or voids but cracks and platelets were observed by cross-sectional transmission electron microscopy. Finally, the relationship between the total implantation dose and the fraction of hydrogen in total implantation dose was calculated.
The intramolecular Stille reaction (1999)

M. A. J. Duncton and G. Pattenden, J. Chem. Soc., Perkin Trans. 1, 1999, 1235 DOI: 10.1039/A808261H
Transcriptional Consequences of Topoisomerase Inhibition (2001)

In principle, the generation, transmission, and dissipation of supercoiling forces are determined by the arrangement of the physical barriers defining topological boundaries and the disposition of enzymes creating (polymerases and helicases, etc.) or releasing (topoisomerases) torsional strain in DNA. These features are likely to be characteristic for individual genes. By using topoisomerase inhibitors to alter the balance between supercoiling forces in vivo, we monitored changes in the basal transcriptional activity and DNA conformation for several genes. Every gene examined displayed an individualized profile in response to inhibition of topoisomerase I or II. The expression changes elicited by camptothecin (topoisomerase I inhibitor) or adriamycin (topoisomerase II inhibitor) were not equivalent. Camptothecin generally caused transcription complexes to stall in the midst of transcription units, while provoking little response at promoters. Adriamycin, in contrast, caused dramatic changes at or near promoters and prevented transcription. The response to topoisomerase inhibition was also context dependent, differing between chromosomal or episomal c-myc promoters. In addition to being well-characterized DNA-damaging agents, topoisomerase inhibitors may evoke a biological response determined in part from transcriptional effects. The results have ramifications for the use of these drugs as antineoplastic agents.
Clonal Sequences Recovered from Plasma from Patients with Residual HIV-1 Viremia and on Intensified Antiretroviral Therapy Are Identical to Replicating Viral RNAs Recovered from Circulating Resting CD4 + T Cells (2011)

Despite successful antiretroviral therapy (ART), low-level viremia (LLV) may be intermittently detected in most HIV-infected patients. Longitudinal blood plasma and resting CD4(+) T cells were obtained from two patients on suppressive ART to investigate the source of LLV. Single-genome sequencing of HIV-1 env from LLV plasma was performed, and the sequences were compared to sequences recovered from limiting-dilution outgrowth assays of resting CD4(+) T cells. The circulating LLV virus clone was identical to virus recovered from outgrowth assays from pools of millions of resting CD4(+) T cells. Understanding the sources of LLV requires evaluation of all possible reservoirs of persistent HIV infection.
Interaction of Nuclear Factors with Upstream Sequences of a Lipid Body Membrane Protein Gene from Carrot (1990)

Polydefkis Hatzopoulos, Gerald Franz, Lisa Choy, Renee Z. Sung, Interaction of Nuclear Factors with Upstream Sequences of a Lipid Body Membrane Protein Gene from Carrot, The Plant Cell, Vol. 2, No. 5 (May, 1990), pp. 457-467
'Breaking' and formation of hydrogen bonds by proton donor anesthetics (1977)

It has been shown previously that halofluorocarbons having anesthetic potency hinder the formation of hydrogen bonds (HB) of the [Formula: see text] types and it has been suggested that this is linked to a competitive mechanism involving another type of association. Since some of the most potent and widely used fluorocarbon anesthetics contain a mobile hydrogen atom the question arises if in such molecules the competitive mechanism involves the formation of HB's with the anesthetic as the proton donor instead of, or in addition to, association due to the electron acceptor properties of the higher halogens as seems to be the case for those fluorocarbon anesthetics which contain no hydrogen. Chloroform, halothane, methoxyflurane, enflurane, and 4,5-dichloro-2,2-difluoro-l,3-dioxolane have been studied from this point of view with the result that both mechanisms appear to operate.
Use of glycyl-l-phenylalanine 2-naphthylamide, a lysosome-disrupting cathepsin C substrate, to distinguish between lysosomes and prelysosomal endocytic vacuoles (1994)

Lysosome-disrupting enzyme substrates have been used to distinguish between lysosomal and prelysosomal compartments along the endocytic pathway in isolated rat hepatocytes. The cells were incubated for various periods of time with 125I-labelled tyramine cellobiose (125I-TC) covalently coupled to asialoorosomucoid (AOM) (125I-TC-AOM); this molecule is internalized by receptor-mediated endocytosis and degraded in lysosomes, where the degradation products (acid-soluble, radio-labelled short peptides) accumulate, Glycyl-L-phenylalanine 2-naphthylamide (GPN) and methionine O-methyl ester (MOM), which are hydrolysed by lysosomal cathepsin C and a lysosomal esterase respectively, both diffused into hepatocytic lysosomes after electrodisruption of the cells. Intralysosomal accumulation of the hydrolysis products (amino acids) of these substrates caused osmotic lysis of more than 90% of the lysosomes, as measured by the release of acid-soluble radioactivity derived from 125I-TC-AOM degradation. The acid-soluble radioactivity coincided in sucrose-density gradients with a major peak of the lysosomal marker enzyme acid phosphatase at 1.18 g/ml; in addition a minor, presumably endosomal, acid phosphatase peak was observed around 1.14 g/ml. The major peak of acid phosphatase was almost completely released by GPN (and by MOM), while the minor peak seemed unaffected by GPN. Acid-insoluble radioactivity, presumably in endosomes, banded (after 1 h of 125I-TC-AOM uptake) as a major peak at 1.14 and a minor peak at 1.18 g/ml in sucrose gradients, and was not significantly released by GPN. GPN thus appears to be an excellent tool by which to distinguish between endosomes and lysosomes. MOM, on the other hand, released some radioactivity and acid phosphatase from endosomes as well as from lysosomes.