gebhart/patrepeval huggingface dataset:
Elucidating the Autoimmune and Antitumor Effector Mechanisms of a Treatment Based on Cytotoxic T Lymphocyte Antigen-4 Blockade in Combination with a B16 Melanoma Vaccine (2001)

We have previously shown that small B16 melanomas can be successfully treated using a combination of anti-cytotoxic T lymphocyte antigen (CTLA)-4 monoclonal antibody with a granulocyte/macrophage colony-stimulating factor (GM-CSF) producing irradiated tumor cell vaccine. Regression of tumors results in long-lasting immunity and is frequently accompanied by autoimmune depigmentation. Here we examine the cellular and molecular mechanisms of this combined treatment. Histological examination of depigmented lesions revealed infiltration of polymorphonuclear cells and deposition of antibody. The combination therapy also induced tumor rejection and skin depigmentation in B cell-deficient and in CD4(+) T cell-depleted mice. Both effects of the treatment absolutely required CD8(+) T cells. Analysis of the response in successfully treated mice revealed elevated levels of CD8(+) T cells specific for a nonameric peptide consisting of residues 180-188 of the melanocyte differentiation antigen tyrosinase-related protein (TRP)2. There was no evidence of reactivity to the melanocyte antigens gp100, tyrosinase, Mart1/MelanA, or TRP1. Fas-FasL interactions and perforin played a role in mounting the effector response, whereas the tumor necrosis factor pathway was not required. The cellular requirements for tumor rejection in this therapeutic setting were strikingly different from those in a prophylactic setting. In particular, if mice received a prophylactic vaccine consisting of anti-CTLA-4 and B16-GM-CSF before tumor challenge, full protection was obtained even in the absence of CD8(+) T cells. Our data demonstrate that therapeutic autoreactive CD8(+) T cell responses can effectively be generated in tumor-bearing mice and stresses the value of studying tumor immunity in a therapeutic rather than a prophylactic setting.
WNT signaling in the normal intestine and colorectal cancer (2006)

The intestinal epithelium is a self-renewing tissue that represents a unique model for studying interconnected cellular processes such as proliferation, differentiation, cell migration and carcinogenesis. This review covers work from the past decade and highlights the importance of the canonical Wnt pathway in regulating multiple aspects of intestinal homeostasis. Numerous in vivo studies combined with gene profiling experiments have shown that Wnt signaling promotes maintenance of epithelial stem cells and early progenitors by driving transcription of genes associated with proliferation. These studies also revealed strong similarities between the genetic program initiated by Wnt signals in normal crypt progenitors and in colorectal cancer cells. More recently it has become apparent that Wnts do not act alone but rather cooperate with Notch signals in maintaining progenitor cell populations. Processes associated with differentiated epithelial cells also appear to be regulated by Wnt signals. For instance, Paneth cells employ active Wnt signals for terminal differentiation. Moreover, through transcriptional regulation of members of the Eph and Ephrin families, Wnt signaling promotes compartmentalization of epithelial cells along the crypt-villus axis. The Eph/Ephrin system also operates to limit progression of colorectal cancer beyond the early stages.
Characterization of the ethanol‐inducible alc gene‐expression system in Arabidopsis thaliana (2001)

Controlled expression of transgenes in plants is key to the characterization of gene function and the regulated manipulation of growth and development. The alc gene-expression system, derived from the filamentous fungus Aspergillus nidulans, has previously been used successfully in both tobacco and potato, and has potential for use in agriculture. Its value to fundamental research is largely dependent on its utility in Arabidopsis thaliana. We have undertaken a detailed function analysis of the alc regulon in A. thaliana. By linking the alcA promoter to beta-glucuronidase (GUS), luciferase (LUC) and green fluorescent protein (GFP) genes, we demonstrate that alcR-mediated expression occurs throughout the plant in a highly responsive manner. Induction occurs within one hour and is dose-dependent, with negligible activity in the absence of the exogenous inducer for soil-grown plants. Direct application of ethanol or exposure of whole plants to ethanol vapour are equally effective means of induction. Maximal expression using soil-grown plants occurred after 5 days of induction. In the majority of transgenics, expression is tightly regulated and reversible. We describe optimal strategies for utilizing the alc system in A. thaliana.
Simulating the power consumption of large-scale sensor network applications (2004)

Developing sensor network applications demands a new set of tools to aid programmers. A number of simulation environments have been developed that provide varying degrees of scalability, realism, and detail for understanding the behavior of sensor networks. To date, however, none of these tools have addressed one of the most important aspects of sensor application design: that of power consumption. While simple approximations of overall power usage can be derived from estimates of node duty cycle and communication rates, these techniques often fail to capture the detailed, low-level energy requirements of the CPU, radio, sensors, and other peripherals.
Riboflavin synthases of Bacillus subtilis. Purification and amino acid sequence of the alpha subunit. (1990)

Bacillus subtilis has two different riboflavin synthases characterized by the subunit structures alpha3 (light enzyme) and alpha3beta60 (heavy enzyme). The light enzyme was purified by a novel procedure with increased yield and excellent reproducibility. The proposed trimer structure was confirmed by cross-linking experiments with dimethyl suberimidate. Fragments of alpha subunits were prepared by cleavage with cyanogen bromide, trypsin, protease Lys-C, and Staphylococcus aureus protease V8, respectively. Sequences were determined by automated liquid or gas phase Edman degradation. The complete sequence (202 amino acids) was established by direct sequencing of the N terminus and sequencing of overlapping peptides. The sequence shows marked internal homology between the NH2-terminal and COOH-terminal half encompassing 26 identical positions and 23 conservative replacements. This suggests that the protomer forms two structurally similar domains. Since it is known that the enzyme has two binding sites per subunit for the substrate 6,7-dimethyl-8-ribityllumazine, it appears likely that each of the homologous protein domains provides one binding site. The stereochemical features of the enzyme mechanism and the structural relation of the alpha trimer to the beta60 capsid of heavy riboflavin synthase suggest that the six domains corresponding to the alpha subunit trimer are related by pseudo 32 symmetry.
Effects of Ferric Carboxymaltose on Hospitalisations and Mortality Rates in Iron-Deficient Heart Failure Patients: An Individual Patient data Meta-Analysis (2017)

Treatment with i.v. FCM was associated with a reduction in recurrent CV hospitalisations in systolic HF patients with ID.
Expression of a full-length cDNA for the human "MDR1" gene confers resistance to colchicine, doxorubicin, and vinblastine. (1987)

Intrinsic and acquired multidrug resistance (MDR) is an important problem in cancer therapy. MDR in human KB carcinoma cells selected for resistance to colchicine, vinblastine, or doxorubicin (former generic name adriamycin) is associated with overexpression of the "MDR1" gene, which encodes P-glycoprotein. We previously have isolated an overlapping set of cDNA clones for the human MDR1 gene from multidrug-resistant KB cells. Here we report the construction of a full-length cDNA for the human MDR1 gene and show that this reconstructed cDNA, when inserted into a retroviral expression vector containing the long terminal repeats of Moloney leukemia virus or Harvey sarcoma virus, functions in mouse NIH 3T3 and human KB cells to confer the complete multidrug-resistance phenotype. These results suggest that the human MDR1 gene may be used as a positive selectable marker to introduce genes into human cells and to transform human cells to multidrug resistance without introducing nonhuman antigens.
Structure of the human neutrophil elastase gene. (1988)

The gene for human neutrophil elastase (NE), a powerful serine protease carried by blood neutrophils and capable of destroying most connective tissue proteins, was cloned from a genomic DNA library of a normal individual. The NE gene consists of 5 exons and 4 introns included in a single copy 4-kilobase segment of chromosome 11 at q14. The coding exons of the NE gene predict a primary translation product of 267 residues including a 29-residue N-terminal precursor peptide and a 20-residue C-terminal precursor peptide. Analysis of the N-terminal peptide sequence suggests it contains a 27-residue pre signal peptide followed by a proN dipeptide, similar to that of other blood cell lysosomal proteases. The sequences for the mature 218-residue NE protein are included in exons II-V. The 5'-flanking region of the gene includes typical TATA, CAAT, and GC sequences within 61 base pairs (bp) of the cap site. The sequence 1.5 kilobases 5' to exon I contains several interesting repetitive sequences including six tandem repeats of unique 52- or 53-bp sequences. The 5'-flanking region also contains a 19-bp segment with 90% homology to a segment of the 5'-flanking region of the human myeloperoxidase (MPO) gene, a gene also expressed in bone marrow precursor cells and a protein stored in the same neutrophil granules as NE. In addition, like the MPO gene, the NE 5'-flanking region has several regions with greater than or equal to 75% homology to sequences 5' to c-myc, but there is no overlap between the NE-c-myc and MPO-c-myc homologous sequences.
Nanocrystalline Chalcopyrite Materials (CuInS2and CuInSe2) via Low-Temperature Pyrolysis of Molecular Single-Source Precursors (2003)

Nanometer-sized particles of the chalcopyrite compounds CuInS2 and CuInSe2 were synthesized by thermal decomposition of molecular single-source precursors (PPh3)2CuIn(SEt)4 and (PPh3)2CuIn(SePh)4, respectively, in the noncoordinating solvent dioctyl phthalate at temperatures between 200 and 300 °C. The nanoparticles range in size from 3 to 30 nm and are aggregated to form roughly spherical clusters of about 500 nm in diameter. X-ray diffraction of the nanoparticle powders shows greatly broadened lines, indicative of very small particle sizes, which is confirmed by TEM. Peaks present in the XRD can be indexed to reference patterns for the respective chalcopyrite compounds. Optical spectroscopy and elemental analysis by energy dispersive spectroscopy support the identification of the nanoparticles as chalcopyrites.
P(AAm-co-EG) Interpenetrating Polymer Networks Grafted to Oxide Surfaces:  Surface Characterization, Protein Adsorption, and Cell Detachment Studies (1997)

We investigated the composition, properties, and utility of a novel copolymer of P(AAm-co-EG) designed to be an adaptable, durable, and biocompatible surface treatment of metallic, polymeric, and ceramic materials. Solution deposition and photoinitiation reactions were employed to graft a silane layer and then two sequential polymer layers (a discontinuous two stage polymerization) onto oxide surfaces. Different solvents, polymer concentrations, and cross-linker concentrations in the top polymer layer were compared. Contact angle measurements, spectroscopic ellipsometry, and X-ray photoelectron spectroscopy were used to characterize layer wettability, thickness, and chemistry, respectively. A sandwich type network formed between acrylamide and poly(ethylene glycol) when acetone was used as the solvent for both layers. In contrast, an interpenetrating polymer network between acrylamide and poly(ethylene glycol) formed when acetone and methanol were used as the solvents for polymerization of the acrylamide and poly(ethylene glycol) layers, respectively. Interpenetrating polymer network configured samples were tested for protein adsorption and strength of cell attachment. Protein adsorption experiments in 15% fetal bovine serum indicated that significant amounts of protein do not adsorb to the surface of the thin polymer films (∼20 nm). Cell detachment experiments indicated that cells contacting copolymer-modified surfaces were removed by lower shear stresses than cells contacting clean and amine-terminated, (N-(2-aminoethyl)-3-aminopropyl)trimethoxysilane modified surfaces.
Tamoxifen therapy in premenopausal patients with metastatic breast cancer. (1981)

Tamoxifen was evaluated in a phase II trial as initial hormonal therapy in premenopausal patients with metastatic breast cancer. The study design was such that responders remained on tamoxifen therapy; those who initially or subsequently progressed went on to ovarian ablation either by surgery or irradiation. Of 42 evaluable patients treated with tamoxifen, three had complete responses (CR), ten had partial responses (PR), and four remained stable (ST), giving total response rates of 32% (CR + PR) or 41% (CR + PR + ST). Among the 18 patients with positive estrogen (ER) or progesterone (PgR) receptors, there were eight responders, but only one responder (ST) in the nine patients with negative ER or PgR. Of the 25 patients who failed to respond to tamoxifen, 13 underwent ovarian ablation; all failed to respond. These 13 included four patients who were ER positive or equivocal and PgR positive or unknown. Nine tamoxifen responders (CR + PR + ST) have subsequently progressed; of these, eight have gone on to ovarian ablation. Six of these eight have responded (five PR and one ST) to ovarian ablation, and one has failed to respond. Thus, steroid receptors generally predicted a patient's response to tamoxifen therapy, but response to tamoxifen also strongly predicted a patient's subsequent response to ovarian ablation.
A perspective on drug discovery and development through the genetic engineering of antibiotic-producing microorganisms (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA perspective on drug discovery and development through the genetic engineering of antibiotic-producing microorganismsC. Richard Hutchinson, Christopher W. Borell, Sharee L. Otten, Kim J. Stutzman-Engwall, and Yi Guang WangCite this: J. Med. Chem. 1989, 32, 5, 929–937Publication Date (Print):May 1, 1989Publication History Published online1 May 2002Published inissue 1 May 1989https://pubs.acs.org/doi/10.1021/jm00125a001https://doi.org/10.1021/jm00125a001research-articleACS PublicationsRequest reuse permissionsArticle Views266Altmetric-Citations23LEARN 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
A novel circuit technology with surrounding gate transistors (SGT's) for ultra high density DRAM's (1995)

This paper describes a novel circuit technology with Surrounding Gate Transistors (SGT's) For ultra high density DRAM's. In order to reduce the chip size drastically, an SGT is employed to all the transistors within a chip. SGT's connected in series and a common source SGT have been newly developed for the core circuit, such as a sense amplifier designed by a tight design rule. Furthermore, to reduce the inherent cell array noise caused by a relaxed open bit line (BL) architecture, a noise killer circuit placed in the word line (WL) shunt region and a twisted BL architecture within the sense amplifier region combined with a novel separation sensing scheme have been newly introduced. Using the novel circuit technology, a 32.9% smaller chip size can be successfully achieved for a 64-Mb DRAM and 34.4% for a 1-Gb DRAM compared with a DRAM composed of the planar transistor without sacrificing the access time, power dissipation, and V/sub cc/ margin. Furthermore,the effectiveness of this technology is verified by using the circuit simulation of the internal main nodes such as WL and BL.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Frequency-domain linear prediction for temporal features (2004)

Current speech recognition systems uniformly employ short-time spectral analysis, usually over windows of 10-30 ms, as the basis for their acoustic representations. Any detail below this timescale is lost, and even temporal structures above this level are usually only weakly represented in the form of deltas etc. We address this limitation by proposing a novel representation of the temporal envelope in different frequency bands by exploring the dual of conventional linear prediction (LPC) when applied in the transform domain. With this technique of frequency-domain linear prediction (FDLP), the 'poles' of the model describe temporal, rather than spectral, peaks. By using analysis windows on the order of hundreds of milliseconds, the procedure automatically decides how to distribute poles to model the temporal structure best within the window. While this approach offers many possibilities for novel speech features, we experiment with one particular form, an index describing the 'sharpness' of individual poles within a window, and show a relatively large word error rate improvement from 4.97% to 3.81% in a recognizer trained on general conversational telephone speech and tested on a small-vocabulary spontaneous numbers task. We analyze this improvement in terms of the confusion matrices and suggest how the newly-modeled fine temporal structure may be helping.
Prostaglandin E2 Induces the Final Maturation of IL-12-Deficient CD1a+CD83+ Dendritic Cells: The Levels of IL-12 Are Determined During the Final Dendritic Cell Maturation and Are Resistant to Further Modulation (1998)

Activation of immature dendritic cells (DC) in peripheral tissues induces their migration to lymph nodes and their maturation into CD83+ DC, which are able to prime naive T cells. The inflammatory cytokines IL-1beta and TNF-alpha induce mature DC, which can secrete IL-12 and promote the development of Th0/Th1-biased cells. DC maturation factors with a Th2-promoting function have not been described. Here we show that PGE2, although it does not induce final DC maturation by itself, synergizes with IL-1beta and TNF-alpha, and allows their effectiveness at 100-fold lower concentrations. While being phenotypically identical with the DC matured in the presence of high concentrations of IL-1beta and TNF-alpha alone, DC matured in the additional presence of PGE2 show impaired IL-12 production and bias naive Th cell development toward the Th2. The ability of DC to produce IL-12 is also suppressed by IL-10, which in contrast to PGE2, inhibits their maturation. The differences in the ability to produce IL-12, established during the final DC maturation, are stable after the removal of modulatory factors. Importantly, fully mature DC become unsusceptible to PGE2 and IL-10. This indicates that the levels of IL-12 production in vivo, in mature DC interacting with Th cells within the lymph nodes, are mainly predetermined at the stage of immature DC in peripheral tissues. These data imply that the character of pathogen-induced local inflammatory reaction can "instruct" local DC to initiate Th1 or Th2-biased responses.
A bifurcated hydrogen-bonded conformation in the d(A.T) base pairs of the DNA dodecamer d(CGCAAATTTGCG) and its complex with distamycin. (1987)

The crystal structures of d(CGCA3T3GCG) complex to the antitumor drug distamycin and the DNA fragment alone were solved by x-ray diffraction at 2.2 and 2.5 A resolution, respectively. The drug lies in the narrow minor groove near the center of the B-DNA fragment covering 5 of the 6 A.T base pairs. It is bound to the DNA by hydrogen bonding, van der Waals, and electrostatic interactions. In addition, the DNA was found to have an unusual conformation in the (dA)3.(dT)3 regions. These base pairs have a high positive propeller twist so that in the major groove the adenine amino group is located intermediate between the carbonyl O-4 groups of two adjacent thymines of the opposite strand, making bifurcated hydrogen bonds to the two thymine residues. This suggests a model to explain the unusual properties of poly-(dA).poly(dT) in which a modified B conformation is associated with a large propeller twist of the bases and a set of continuous bifurcating hydrogen bonds along the major groove, which may provide incremental stability to these segments. In addition, shorter segments of (dA)3-6.(dT)3-6 may have this conformation in the midst of B-DNA and stabilize bends in the DNA that may be associated with stacking on one of the high propeller-twisted bases at the ends of these segments.
Involvement of genetic factors in the response to a variable-dosing ranibizumab treatment regimen for age-related macular degeneration. (2010)

Visual acuity did not improve during the study in patients homozygous for ARMS2 69S, despite a decrease in CSRT. Further investigation is needed to confirm our findings and understand the mechanisms involved.
Potassium in preventing and treating high blood pressure. (1999)

Our objective was to assess the effects of supplementation with oral potassium on blood pressure (BP) in humans, using pooled analysis of randomized, controlled trials. Results from 33 randomized, controlled trials (2,609 participants) in which potassium supplementation was the only difference between the intervention and control conditions were used. Information on sample size, duration, study design, potassium dose, participant characteristics, and treatment results was independently obtained by the authors using a standardized protocol. The findings from each trial were pooled after weighting the results for individual studies by the inverse of its variance. Using a random-effects model, potassium supplementation was associated with a significant reduction in mean (95% confidence interval) systolic and diastolic BP of -4.44 (range, -2.53 to -6.36) and -2.45 (range, -0.74 to -4.16) mm Hg, respectively. After exclusion of a trial with extreme results, potassium supplementation was still associated with a significant reduction in mean (95% confidence interval) systolic and diastolic BP of -3.11 (range, -1.91 to -4.31) and -1.97 (range, -0.52 to -3.42) mm Hg, respectively. The BP effects of potassium administration appeared to be enhanced in studies where participants were concurrently exposed to a high intake of sodium. Increased potassium intake should be included as a recommendation for prevention and treatment of hypertension, especially in those who are unable to reduce their intake of sodium.