gebhart/patrepeval huggingface dataset:
Major DNA Fragmentation Is a Late Event in Apoptosis (1997)

Apoptosis, the terminal morphological and biochemical events of programmed cell death, is characterized by specific changes in cell surface and nuclear morphology. In addition, DNA fragmentation in an internucleosomal pattern is detectable in mass cultures of apoptotic cells. However, DNA fragmentation and nuclear morphological changes may not necessarily be associated events. In this study, we examined OVCAR-3 and KB human carcinoma cells using time-lapse video phase-contrast microscopy to characterize the surface and nuclear morphological features of apoptosis in response to treatment with either taxol or ricin. The surface morphological features of apoptosis were the same in both cell types and with both drugs. Using an in situ nick-translation histochemical assay, these single cells were also examined for DNA strand breaks during apoptosis. Surface morphological changes demonstrated discrete stages of cell rounding, surface blebbing, followed by cessation of movement and the extension of thin surface microspikes, followed much later by surface blistering and cell lysis. Nuclear features examined by DAPI cytochemistry demonstrated apoptotic nuclear condensation very early in this sequence, usually at the time of initial surface blebbing. The nick-translation assay, however, demonstrated DNA strand breaks at a much later time, only after the formation of separated apoptotic bodies or after final cell lysis. This study points out the differences between surface and nuclear morphological changes in apoptosis, and the large temporal separation between nuclear morphological changes and major DNA fragmentation detectable by this in situ technique. This result suggests caution in using in situ nick-translation as a direct correlate of internucleosomal DNA fragmentation in apoptosis.
Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons. (1989)

Human basic fibroblast growth factor (bFGF) is an angiogenic polypeptide mitogen present in a wide variety of mesoderm- and neuroectoderm-derived tissues. bFGF cDNA and genomic clones predict a 17.8-kDa (155-amino acid) gene product based on the presence of a single putative translational initiator ATG codon. However, a bFGF protein isolated from human placenta contains two additional amino acids NH2-terminal to the predicted initiator methionine. We report here that the human cell line SK-HEP-1 coexpresses four molecular forms (17.8, 22.5, 23.1, and 24.2 kDa) of bFGF. The 17.8-kDa bFGF protein is translationally initiated at the previously predicted methionine (AUG) codon, whereas the 22.5-, 23.1-, and 24.2-kDa proteins initiate at unusual non-AUG codons. The higher molecular weight forms are colinear NH2-terminal extensions of the 18-kDa bFGF.
Expression of proteoglycans and hyaluronan during wound healing. (1995)

We investigated the expression of proteoglycans (PGs) and hyaluronan (HA) during healing of human mucosal wounds. Biopsy specimens of experimental wounds were taken 1, 3, and 7 days after wounding. Frozen sections were used for immunolocalization of CD44, syndecan-1, basement membrane-associated heparan sulfate proteoglycan (BM-HSPG), decorin, and biglycan. HA was localized in paraffin sections with a specific HA-binding probe. Epithelium showed first signs of migration on Day 1, more progressive migration on Day 3, and epithelial sheets confronted on Day 7. CD44 surrounded migrating keratinocytes at all stages of wound healing. In epithelium, CD44 and HA remarkably localized to the same region. Expression of syndecan-1 was switched from the suprabasal cell layer of unwounded epithelium to the basal cell layer of the migrating wound epithelium. BM-HSPG was absent under migrating keratinocytes. It started to reappear at the basement membrane zone on Day 7. The area under the wound epithelium containing newly synthesized collagen fibers first became positive for decorin on Day 7, whereas staining of biglycan was negative. Granulation tissue was also strongly positive for CD44 and hyaluronan. Our results indicate that migrating keratinocytes express both CD44 and syndecan-1 but not BM-HSPG. During differentiation of keratinocytes, expression of CD44 preceded that of syndecan-1. The results suggest that different HSPGs have multiple functions in keratinocyte migration and differentiation during reepithelialization.
In situ analysis of nitrogen fixation and metabolic switching in unicellular thermophilic cyanobacteria inhabiting hot spring microbial mats (2006)

Genome sequences of two Synechococcus ecotypes inhabiting the Octopus Spring microbial mat in Yellowstone National Park revealed the presence of all genes required for nitrogenase biosynthesis. We demonstrate that nif genes of the Synechococcus ecotypes are expressed in situ in a region of the mat that varies in temperature from 53.5 degrees C to 63.4 degrees C (average 60 degrees C); transcripts are only detected at the end of the day when the mat becomes anoxic. Nitrogenase activity in mat samples was also detected in the evening. Hitherto, N2 fixation in hot spring mats was attributed either to filamentous cyanobacteria (not present at >50 degrees C in these mats) or to heterotrophic bacteria. To explore how energy-generating processes of the Synechococcus ecotypes track natural light and O2 conditions, we evaluated accumulation of transcripts encoding proteins involved in photosynthesis, respiration, and fermentation. Transcripts from photosynthesis (cpcF, cpcE, psaB, and psbB) and respiration (coxA and cydA) genes declined in the evening. In contrast, transcripts encoding enzymes that may participate in fermentation fell into two categories; some (ldh, pdhB, ald, and ackA) decreased in the evening, whereas others (pflB, pflA, adhE, and acs) increased at the end of the day and remained high into the night. Energy required for N2 fixation during the night may be derived from fermentation pathways that become prominent as the mat becomes anoxic. In a broader context, our data suggest that there are critical regulatory switches in situ that are linked to the diel cycle and that these switches alter many metabolic processes within the microbial mat.
Intrastromal Delivery of Bevacizumab Using Microneedles to Treat Corneal Neovascularization (2014)

This study shows that microneedles can target drug delivery to corneal stroma in a minimally invasive way and demonstrates effective suppression of corneal neovascularization after suture-induced injury using a much lower dose compared with conventional methods.
Experimental Investigation of the Propeller Design for future QESTOL Aircraft in the BNF Project (2014)

Due to increasing airport congestion the German research project ’Burgernahes Flugzeug’ (BNF, citizen friendly airplane) investigates the potential of aircraft concepts for a possible future air transportation system integrating small airports. Key technologies in aerodynamics for developing new generation quiet, efficient, short take-off and landing (QESTOL) aircraft are studied through the synergistic exploitationof Computational Fluid Dynamics (CFD) and new wind tunnel data. One subject of the conducted investigations is a ninebladed high power propeller mounted in tractor configuration on a wing that is equipped with an active gapless high-lift system. As the aerodynamic focus of the BNF project is on the interaction between the propeller slipstream and the high-lift flowfield, this paper is focussed on the experimental investigation of the propeller performance in comparison with simulation data.
Combination of Interleukin 12 and Interferon α Gene Therapy Induces a Synergistic Antitumor Response against Colon and Renal Cell Carcinoma (2000)

The antitumor effect and mechanism of action of IL-12 gene therapy combined with IFN-alpha gene therapy were investigated in tumor-bearing mice using renal and colon carcinoma models, Renca and CT26, respectively. Tumors were treated with murine IL-12 plasmid alone or in combination with IFN-alpha plasmid formulated with a polymeric interactive noncondensing (PINC) gene delivery system. Intratumoral injection of IL-12 DNA/polyvinyl pyrrolidone (PVP) alone induced rejection of 58 and 17% of Renca and CT26 tumors, respectively, whereas 25% (Renca) and 0% (CT26) rejection was observed in mice treated with IFN-alpha plasmid/PVP. Combination gene therapy of formulated plasmids, IL-12 with IFN-alpha, synergistically increased the antitumor response against Renca (100% tumor rejection) and CT26 (50%). In vivo depletion of leukocyte subsets indicated that CD8(+) T and NK cells were the primary effectors of the antitumor response induced by the combined cytokine gene therapy. Moreover, mice that rejected the primary tumors after combined treatment with IL-12 and IFN-alpha plasmid formulation developed protective immunity against a subsequent tumor challenge. Analysis of tumor-infiltrating leukocytes from mice treated with the combined IL-12 and IFN-alpha gene therapy showed upregulation of CD40 molecules on antigen-presenting cells (Mac-1(hi) cells). Finally, levels of mRNA for the chemokines IP-10 and TCA-3 were higher in tumors treated with the combination of cytokine plasmids than in tumors treated with either cytokine gene alone. These data provide evidence that IL12 gene therapy combined with IFN-alpha gene therapy synergistically induces regression of established tumors and may represent a novel therapeutic strategy for cancer treatment.
Bupropion SR Enhances Weight Loss: A 48‐Week Double‐Blind, Placebo‐ Controlled Trial (2002)

Bupropion SR 300 and 400 mg/d were well-tolerated by obese adults and were associated with a 24-week weight loss of 7.2% and 10.1% and sustained weight losses at 48 weeks.
Functionalized Conjugated Polymers for Signal Amplifying Biosensors and Sensor Arrays. (2008)

Conjugated polymers (CPs) are great alternatives to the conventional fluorescence dyes as signaling reporters in biosensor design due to the fluorescent signal amplification property of CPs. Two series of CPs, poly(p-phenyleneethynylene) (PPE) and poly(poxadiazole- co-phenylene) (POX) derivatives, have been systematically designed, developed, and studied in this thesis to devise highly sensitive and selective novel molecular biosensors and sensor arrays for the detection of clinically important biological molecules. The key concept developed in the thesis work was the molecular design principles to combine biological receptor molecules for specific detection of target oligonucleotides and CPs as the signal transduction and amplification unit. To achieve this goal, a series of completely water-soluble and highly emissive conjugated polyelectrolytes (CPEs) were first developed through systematic investigation on the xxii correlation between the polymer structure and its water-solubility. We also developed a method to bioconjugate CPEs to peptides and DNA by end-modification of the CPEs with a carboxylic acid group to develop hybrid bio/-synthetic sensory CPs and to achieve selective detection of target with amplified fluorescence signal in aqueous solution. DNA detection results using the CPE-DNA hybrid system confirmed large signal amplification by means of efficient Förster energy transfer from the energy harvesting CPEs to the fluorescent dye attached to the complementary analyte DNA. To apply the signal amplification scheme to practically more useful solid-state microarray novel conjugated polymers, POXs, having unique photochemical stabilities were developed. By applying on-chip DNA synthesis on the POXs and achieving efficient Förster energy transfer from POXs to the dye-labeled target DNA we successfully developed signal amplifying DNA microarrays. The signal amplifying scheme was combined with a self-signaling concept by means of introducing intercalating dyes and molecular beacon into the CPs for labelfree detection. As a result of sensitive and selective prostate specific antigen detection has been demonstrated. In addition to the biosensor development, the developed bioconjugation technique between biological molecules and CPEs was uniquely applied to the development of CPE-antibody for live cell imaging. Selective live cell imaging of human B-cell lymphoma and human T-cell leukemia having largely enhanced sensitivity and excellent selectivity was demonstrated by using the CPE-antibody.
A protein encoded by a group I intron in Aspergillus nidulans directly assists RNA splicing and is a DNA endonuclease (1997)

Some group I introns self-splice in vitro, but almost all are thought to be assisted by proteins in vivo. Mutational analysis has shown that the splicing of certain group I introns depends upon a maturase protein encoded by the intron itself. However the effect of a protein on splicing can be indirect. We now provide evidence that a mitochondrial intron-encoded protein from Aspergillus nidulans directly facilitates splicing in vitro. This demonstrates that a maturase is an RNA splicing protein. The protein-assisted reaction is as fast as that of any other known group I intron. Interestingly the protein is also a DNA endonuclease, an activity required for intron mobilization. Mobile elements frequently encode proteins that promote their propagation. Intron-encoded proteins that also assist RNA splicing would facilitate both the transposition and horizontal transmission of introns.
Neuropilin-1 exerts co-receptor function for TGF-beta-1 on the membrane of cancer cells and enhances responses to both latent and active TGF-beta (2010)

Neuropilin (Nrp)-1 and Nrp-2 are multifunctional proteins frequently expressed by cancer cells and contribute to tumor progression by mechanisms that are not well understood. They are co-receptors for vascular endothelial growth factor and class 3 semaphorins, but recently we found that Nrp1 also binds latent and active transforming growth factor (TGF)-β1, and activates the latent form latency-associated peptide (LAP)-TGF-β1. Here, we report that Nrp1 has affinity for TGF-β receptors TβRI and TβRII, the signaling TGF-β receptors, as well as TβRIII (betaglycan), as determined in binding assays, pull down assays and confocal microscopy. Nrp1 had a higher affinity for TβRI than TβRII and could form a complex with these receptors. In breast cancer cells, Nrp1 and TβRI cointernalized in the presence of TGF-β1. Nrp1 acted as a TGF-β co-receptor by augmenting canonical Smad2/3 signaling. Importantly, Nrp-positive cancer cells, unlike negative cells, were able to activate latent TGF-β1 and respond. We examined two other membrane proteins that bind LAP-TGF-β, i.e. an RGD-binding integrin (αvβ3) and Glycoprotein A repetitions predominant (CLRRC32). RGD-binding integrins are frequently expressed by cancer cells, and glycoprotein A repetitions predominant is expressed by activated regulatory T cells that appear linked to poor tumor immunity. In vitro, these receptors did not activate LAP-TGF-β1, but subsequent addition of Nrp1 activated the cytokine. Thus, Nrp1 might collaborate with other latent TGF-β receptors in TGF-β capture and activation. We also show that Nrp2 has activities similar to Nrp1. We conclude that Nrp1 is a co-receptor for TGF-β1 and augments responses to latent and active TGF-β. Since TGF-β promotes metastasis this is highly relevant to cancer biology.
Molecular cloning and chromosomal localization of the human T-cell receptor zeta chain: distinction from the molecular CD3 complex. (1988)

The T-cell antigen receptor (TCR) is a multisubunit receptor complex specific to T cells subserving both antigen recognition and signal transduction functions. The zeta chain of the TCR is a component of all surface receptor complexes. This chain was first identified in murine T cells by virtue of the fact that it coimmunoprecipitates with the TCR complex using antibodies directed against either the clone-specific subunits or invariant CD3 subunits of the receptor. Recently, we have isolated a cDNA encoding the murine zeta. Using this as a probe, we have now isolated cDNAs encoding the human zeta. Sequence analysis of cDNAs encoding human and murine zeta reveals that it is a highly conserved protein. In addition to amino acid homology, there is remarkable interspecies conservation in the nucleotide sequence of the 5' and 3' untranslated regions of the zeta mRNA. The previously characterized invariant delta, epsilon, and gamma chains of the TCR, referred to as the CD3 complex, share significant sequence and structural homology with each other and are all located within 300 kilobases of each other on human chromosome 11 (11q23). zeta has no sequence similarity to the CD3 chains and the localization of the human zeta gene to the centromeric region of chromosome 1 underscores the fact that it is a distinct genetic component of the TCR.
Application of sucrose-gradient centrifugation for selective isolation of Nocardia spp. from soil (2003)

The development and application of new methodologies with which to isolate less-explored actinomycete taxa is important for improving our knowledge about their taxonomy, ecology and industrial applications.
The Role of Osteochondral Progenitor Cells in Fracture Repair (1998)

The repair of a fracture necessarily entails synthesis of osseous tissue requiring the transformation of undifferentiated osteochondral progenitor cells to mature osteoblasts and chondrocytes. Owen and Friedenstein proposed that there are stem cells for all mesenchymal tissues, resident in bone marrow throughout life, that have a lineage comparable to that described for hematopoiesis. Subsequent with this initial study, marrow derived and periosteal derived progenitor cells have been shown to produce bone and cartilage in numerous in vivo and in vitro studies. The differentiation process appears to depend heavily on the influences of numerous cytokines, especially the transforming growth factor beta superfamily. Initial cartilage formation from progenitor cells is important in any secondary fracture repair. In the in vitro study of chondrogenesis, the marrow derived progenitor cells were shown to differentiate into their terminal phenotype, the hypertrophic chondrocyte, as indicated by the detection of Type X collagen messenger ribonucleic acid and protein. A concomitant elevation in the alkaline phosphatase level suggests that these cells are ready to mineralize. Despite the importance of these cells in fracture repair, the characterization of these cells and the mechanism of their differentiation have only begun to be explored.
Design Concept for Large Output Graz Cycle Gas Turbines (2007)

The introduction of closed cycle gas turbines with their capability of retaining combustion generated CO2 can offer a valuable contribution to the Kyoto goal and to future power generation. Therefore research and development work at the Graz University of Technology since the 1990s has led to the Graz Cycle, a zero emission power cycle of highest efficiency. It burns fossil fuels with pure oxygen which enables the cost-effective separation of the combustion CO2 by condensation. The efforts for the oxygen supply in an air separation plant are partly compensated by cycle efficiencies far higher than for modern combined cycle plants. Upon the basis of the previous work, the authors present the design concept for a large power plant of 400 MW net power output making use of the latest developments in gas turbine technology. The Graz Cycle configuration is changed, insofar as condensation and separation of combustion generated CO2 takes place at the 1 bar range in order to avoid the problems of condensation of water out of a mixture of steam and incondensable gases at very low pressure. A final economic analysis shows promising CO2 mitigation costs in the range of $20–30/ton CO2 avoided. The authors believe that they present here a partial solution regarding thermal power production for the most urgent problem of saving our climate.
PD-1 Blockade by CT-011, Anti-PD-1 Antibody, Enhances Ex Vivo T-cell Responses to Autologous Dendritic Cell/Myeloma Fusion Vaccine (2011)

We have developed a cancer vaccine in which autologous tumor is fused with dendritic cells (DCs) resulting in the presentation of tumor antigens in the context of DC-mediated costimulation. In clinical trials, immunologic responses have been observed, however responses may be muted by inhibitory pathways. The PD1/PDL1 pathway is an important element contributing to tumor-mediated immune suppression. In this study, we demonstrate that myeloma cells and DC/tumor fusions strongly express PD-L1. Compared with a control population of normal volunteers, increased PD-1 expression was observed on T cells isolated from patients with myeloma. It is interesting to note that after autologous transplantation, T-cell expression of PD-1 returned to levels seen in normal controls. We examined the effect of PD-1 blockade on T-cell response to DC/tumor fusions ex vivo. Presence of CT-011, an anti-PD1 antibody, promoted the vaccine-induced T-cell polarization towards an activated phenotype expressing Th1 compared with Th2 cytokines. A concomitant decrease in regulatory T cells and enhanced killing in a cytotoxicity assay was observed. In summary, we demonstrate that PD-1 expression is increased in T cells of patients with active myeloma, and that CT-011 enhances activated T-cell responses after DC/tumor fusion stimulation.
Outline for a Logical Theory of Adaptive Systems (1962)

article Free AccessOutline for a Logical Theory of Adaptive Systems Author: John H. Holland University of Michigan, Ann Arbor, Michigan University of Michigan, Ann Arbor, MichiganView Profile Authors Info & Claims Journal of the ACMVolume 9Issue 3July 1962 pp 297–314https://doi.org/10.1145/321127.321128Published:01 July 1962Publication History 699citation3,418DownloadsMetricsTotal Citations699Total Downloads3,418Last 12 Months422Last 6 weeks67 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Metabolic Differences between AGA‐ and SGA‐Infants of Very Low Birthweight (1988)

Metabolic response to human milk feeding was studied in 12 appropriate (AGA) and 12 small for gestational age (SGA) infants of very low birthweight (VLBW) on the eighth day of life. Protein intake ranged from 1.98 to 2.47 g/kg/day and caloric intake from 94 to 126 kcal/kg/day with no significant differences between the groups. Alpha-amino-nitrogen, the total bile acid concentration in serum and total- as well as alpha-amino-nitrogen excretion in the urine were estimated. The alpha-amino-nitrogen and the total bile acid concentration in serum increased with increasing degree of intrauterine growth retardation. Also renal total- and alpha-amino-nitrogen excretion increased significantly in relation to the degree of intrauterine growth retardation. Thus, despite a relatively low protein intake in severely growth retarded VLBW-infants, metabolic changes could be found similar to those observed in AGA-infants on high protein intakes. The data suggest that during the first weeks of postnatal life VLBW-infants with intrauterine growth retardation have a decreased capacity to utilize or to metabolize protein when compared to AGA-infants with comparable birthweights. These metabolic differences have to be considered in the nutritional management of VLBW-infants.