gebhart/patrepeval huggingface dataset:
Multiple N-acyl-L-homoserine lactone signal molecules regulate production of virulence determinants and secondary metabolites in Pseudomonas aeruginosa. (1995)

Pseudomonas aeruginosa produces a spectrum of exoproducts many of which have been implicated in the pathogenesis of human infection. Expression of some of these factors requires cell-cell communication involving the interaction of a small diffusible molecule, an "autoinducer," with a positive transcriptional activator. In P. aeruginosa PAO1, LasI directs the synthesis of the autoinducer N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), which activates the positive transcriptional activator, LasR. Recently, we have discovered a second signaling molecule-based modulon in PAO1, termed vsm, which contains the genes vsmR and vsmI. Using HPLC, mass spectrometry, and NMR spectroscopy we now establish that in Escherichia coli, VsmI directs the synthesis of N-butanoyl-L-homoserine lactone (BHL) and N-hexanoyl-L-homoserine lactone (HHL). These compounds are present in the spent culture supernatants of P. aeruginosa in a molar ratio of approximately 15:1 and their structures were unequivocally confirmed by chemical synthesis. Addition of either BHL or HHL to PAN067, a pleiotropic P. aeruginosa mutant unable to synthesize either of these autoinducers, restored elastase, chitinase, and cyanide production. In E. coli carrying a vsmR/vsmI'::lux transcriptional fusion, BHL and HHL activated VsmR to a similar extent. Analogues of these N-acyl-L-homoserine lactones in which the N-acyl side chain has been extended and/or oxidized at the C-3 position exhibit substantially lower activity (e.g., OdDHL) or no activity (e.g., dDHL) in this lux reporter assay. These data indicate that multiple families of quorum sensing modulons interactively regulate gene expression in P. aeruginosa.
A pipelined memory architecture for high throughput network processors (2004)

Designing ASICs for each new generation of backbone routers is a time intensive and fiscally draining process. In this paper we focus on the design of a programmable architecture for backbone routers, based on the manipulation of wide irregular memory words, that can provide a feasible design alternative to custom ASICs. We propose a pipelined memory design that emphasizes worst-case throughput over latency, and co-explore architectural tradeoffs with the design of several important network algorithms. Through this co-exploration, we show that a programmable architecture can efficiently exploit behavior inherent to most common network algorithms to keep up with next generation network speeds.
Human Cortical Responses to the Speech Envelope (2008)

These results show that the human auditory cortex either directly follows the speech envelope or consistently reacts to changes in this envelope. The delay between the envelope and the response is approximately 180 msec.
Rapid Characterization of Microorganisms by Mass Spectrometry—What Can Be Learned and How? (2013)

Strategies for the rapid and reliable analysis of microorganisms have been sought to meet national needs in defense, homeland security, space exploration, food and water safety, and clinical diagnosis. Mass spectrometry has long been a candidate technique because it is extremely rapid and can provide highly specific information. It has excellent sensitivity. Molecular and fragment ion masses provide detailed fingerprints, which can also be interpreted. Mass spectrometry is also a broad band method--everything has a mass--and it is automatable. Mass spectrometry is a physiochemical method that is orthogonal and complementary to biochemical and morphological methods used to characterize microorganisms.
Effects of T antigen and replication protein A on the initiation of DNA synthesis by DNA polymerase alpha-primase. (1991)

Studies of simian virus 40 (SV40) DNA replication in a reconstituted cell-free system have established that T antigen and two cellular replication proteins, replication protein A (RP-A) and DNA polymerase alpha-primase complex, are necessary and sufficient for initiation of DNA synthesis on duplex templates containing the SV40 origin of DNA replication. To better understand the mechanism of initiation of DNA synthesis, we analyzed the functional interactions of T antigen, RP-A, and DNA polymerase alpha-primase on model single-stranded DNA templates. Purified DNA polymerase alpha-primase was capable of initiating DNA synthesis de novo on unprimed single-stranded DNA templates. This reaction involved the synthesis of a short oligoribonucleotide primer which was then extended into a DNA chain. We observed that the synthesis of ribonucleotide primers by DNA polymerase alpha-primase is dramatically stimulated by SV40 T antigen. The presence of T antigen also increased the average length of the DNA product synthesized on primed and unprimed single-stranded DNA templates. These stimulatory effects of T antigen required direct contact with DNA polymerase alpha-primase complex and were most marked at low template and polymerase concentrations. We also observed that the single-stranded DNA binding protein, RP-A, strongly inhibits the primase activity of DNA polymerase alpha-primase, probably by blocking access of the enzyme to the template. T antigen partially reversed the inhibition caused by RP-A. Our data support a model in which DNA priming is mediated by a complex between T antigen and DNA polymerase alpha-primase with the template, while RP-A acts to suppress nonspecific priming events.
Tissue-Engineered Fabrication of an Osteochondral Composite Graft Using Rat Bone Marrow-Derived Mesenchymal Stem Cells (2001)

This study tested the tissue engineering hypothesis that construction of an osteochondral composite graft could be accomplished using multipotent progenitor cells and phenotype-specific biomaterials. Rat bone marrow-derived mesenchymal stem cells (MSCs) were culture-expanded and separately stimulated with transforming growth factor-beta1 (TGF-beta1) for chondrogenic differentiation or with an osteogenic supplement (OS). MSCs exposed to TGF-beta1 were loaded into a sponge composed of a hyaluronan derivative (HYAF-11) for the construction of the cartilage component of the composite graft, and MSCs exposed to OS were loaded into a porous calcium phosphate ceramic component for bone formation. Cell-loaded HYAFF-11 sponge and ceramic were joined together with fibrin sealant, Tisseel, to form a composite osteochondral graft, which was then implanted into a subcutaneous pocket in syngeneic rats. Specimens were harvested at 3 and 6 weeks after implantation, examined with histology for morphologic features, and stained immunohistochemically for type I, II, and X collagen. The two-component composite graft remained as an integrated unit after in vivo implantation and histologic processing. Fibrocartilage was observed in the sponge, and bone was detected in the ceramic component. Observations with polarized light indicated continuity of collagen fibers between the ceramic and HYAFF-11 components in the 6-week specimens. Type I collagen was identified in the neo-tissue in both sponge and ceramic, and type II collagen in the fibrocartilage, especially the pericellular matrix of cells in the sponge. These data suggest that the construction of a tissue-engineered composite osteochondral graft is possible with MSCs and different biomaterials and bioactive factors that support either chondrogenic or osteogenic differentiation.
Heparin selectively inhibits a protein kinase C-dependent mechanism of cell cycle progression in calf aortic smooth muscle cells [published erratum appears in J Cell Biol 1990 Mar;110(3):863] (1989)

The proliferation of arterial smooth muscle cells (SMCs) plays a critical role in the pathogenesis of arteriosclerosis. Previous studies have indicated that the glycosaminoglycan heparin specifically inhibited the growth of vascular SMCs in vivo and in culture, although the precise mechanism(s) of action have not been elucidated. In this study, we have examined the ability of specific mitogens (PDGF, EGF, heparin-binding growth factors, phorbol esters, and insulin) to stimulate SMC proliferation. Our results indicate that SMCs derived from different species and vascular sources respond differently to these growth factors. We next examined the ability of heparin to inhibit the proliferative responses to these mitogens. In calf aortic SMCs, heparin inhibits a protein kinase C-dependent pathway for mitogenesis. Detailed cell cycle analysis revealed several new features of the effects of heparin on SMCs. For example, heparin has two effects on the Go----S transition: it delays entry into S phase and also reduces the number of cells entering the cycle from Go. Using two separate experimental approaches, we found that heparin must be present during the last 4 h before S phase, suggesting a mid-to-late G1 heparin block. In addition, our data indicate that heparin-treated SMCs, while initially blocked in mid-to-late G1, slowly move back into a quiescent growth state in the continued presence of heparin. These results suggest that heparin may have multiple targets for its antiproliferative effect.
Expression of Schwann cell markers by mammalian neural crest cells in vitro (1989)

During embryonic development, neural crest cells differentiate into a wide variety of cell types including Schwann cells of the peripheral nervous system. In order to establish when neural crest cells first start to express a Schwann cell phenotype immunocytochemical techniques were used to examine rat premigratory neural crest cell cultures for the presence of Schwann cell markers. Cultures were fixed for immunocytochemistry after culture periods ranging from 1 to 24 days. Neural crest cells were identified by their morphology and any neural tube cells remaining in the cultures were identified by their epithelial morphology and immunocytochemically. As early as 1 to 2 days in culture, approximately one third of the neural crest cells stained with m217c, a monoclonal antibody that appears to recognize the same antigen as rat neural antigen-1 (RAN-1). A similar proportion of cells were immunoreactive in cultures stained with 192-IgG, a monoclonal antibody that recognizes the rat nerve growth factor receptor. The number of immunoreactive cells increased with time in culture. After 16 days in culture, nests of cells, many of which had a bipolar morphology, were present in the area previously occupied by neural crest cells. The cells in the nests were often associated with neurons and were immunoreactive for m217c, 192-IgG and antibody to S-100 protein and laminin, indicating that the cells were Schwann cells. At all culture periods examined, neural crest cells did not express glial fibrillary acidic protein. These results demonstrate that cultured premigratory neural crest cells express early Schwann cell markers and that some of these cells differentiate into Schwann cells. These observations suggest that some neural crest cells in vivo may be committed to forming Schwann cells and will do so provided that they then proceed to encounter the correct environmental cues during embryonic development.
Aggrecan Protects Cartilage Collagen from Proteolytic Cleavage (2003)

The matrix components responsible for cartilage mechanical properties, type II collagen and aggrecan, are degraded in osteoarthritis through proteolytic cleavage by matrix metalloproteinases (MMPs) and aggrecanases, respectively. We now show that aggrecan may serve to protect cartilage collagen from degradation. Although collagen in freeze-thawed cartilage depleted of aggrecan was completely degraded following incubation with MMP-1, collagen in cartilage with intact aggrecan was not. Using interleukin-1-stimulated bovine nasal cartilage explants where aggrecan depletion occurs during the first week of culture, followed by collagen loss during the second week, we evaluated the effect of selective MMP and aggrecanase inhibitors on degradation. A selective MMP inhibitor did not block aggrecan degradation but caused complete inhibition of collagen breakdown. Similar inhibition was seen with inhibitor addition following aggrecan depletion on day 6-8, suggesting that MMPs are not causing significant collagen degradation prior to the second week of culture. Inclusion of a selective aggrecanase inhibitor blocked aggrecan degradation, and, in addition, inhibited collagen degradation. When the inhibitor was introduced following aggrecan depletion, it had no effect on collagen breakdown, ruling out a direct effect through inhibition of collagenase. These data suggest that aggrecan plays a protective role in preventing degradation of collagen fibrils, and that an aggrecanase inhibitor may impart overall cartilage protection.
Immunologic and Clinical Responses after Vaccinations with Peptide-Pulsed Dendritic Cells in Metastatic Renal Cancer Patients (2006)

A phase I trial was conducted to evaluate the feasibility, safety, and efficacy of a dendritic cell-based vaccination in patients with metastatic renal cell carcinoma (RCC). Autologous mature dendritic cells derived from peripheral blood monocytes were pulsed with the HLA-A2-binding MUC1 peptides (M1.1 and M1.2). For the activation of CD4(+) T-helper lymphocytes, dendritic cells were further incubated with the PAN-DR-binding peptide PADRE. Dendritic cell vaccinations were done s.c. every 2 weeks for four times and repeated monthly until tumor progression. After five dendritic cell injections, patients additionally received three injections weekly of low-dose interleukin-2 (1 million IE/m(2)). The induction of vaccine-induced T-cell responses was monitored using enzyme-linked immunospot and Cr release assays. Twenty patients were included. The treatment was well tolerated with no severe side effects. In six patients, regression of the metastatic sites was induced after vaccinations with three patients achieving an objective response (one complete response, two partial responses, two mixed responses, and one stable disease). Additional four patients were stable during the treatment for up to 14 months. MUC1 peptide-specific T-cell responses in vivo were detected in the peripheral blood mononuclear cells of the six patients with objective responses. Interestingly, in patients responding to the treatment, T-cell responses to antigens not used for vaccinations, such as adipophilin, telomerase, or oncofetal antigen, could be detected, indicating that epitope spreading might occur. This study shows that MUC1 peptide-pulsed dendritic cells can induce clinical and immunologic responses in patients with metastatic RCC.
Shared solar-powered EV charging stations: Feasibility and benefits (2016)

Electric vehicles (EV) are growing in popularity as a credible alternative to gas-powered vehicles. These vehicles require their batteries to be “fueled up” for operation. While EV charging has traditionally been grid-based, use of solar powered chargers has emerged as an interesting opportunity. These chargers provide clean electricity to electric-powered cars that are themselves pollution free resulting in positive environmental effects. In this paper, we design a solar-powered EV charging station in a parking lot of a car-share service. In such a car-share service rental pick up and drop off times are known. We formulate a Linear Programming approach to charge EVs that maximize the utilization of solar energy while maintaining similar battery levels for all cars. We evaluate the performance of our algorithm on a real-world and synthetically derived datasets to show that it fairly distributes the available electric charge among candidate EVs across seasons with variable demand profiles. Further, we reduce the disparity in the battery charge levels by 60% compared to best effort charging policy. Moreover, we show that 80 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sup> percentile of EVs have at least 75% battery level at the end of their charging session. Finally, we demonstrate the feasibility of our charging station and show that a solar installation proportional to the size of a parking lot adequately apportions available solar energy generated to the EVs serviced.
In Pursuit of a Missing Link: (1994)

This paper reports results of an exploratory study of a child welfare training project in work with involuntary clients. During this project social workers and supervisors from three public agencies were trained in a collaborative practice model. The study attempted to identify connections between supervisors' activities and practitioners' initial engagement with clients. Findings indicated that trainees gained understanding and skills in working with involuntary clients whether or not their supervisors also participated in the training. A supervisor's skills or participant's skills in using supervision seemed to have more influence than presence of the supervisor in the project. Guidelines for supervisors are offered.
Abstract B6: PEGPH20 depletion of pericellular hyaluronan sensitizes high hyaluronan-producing tumor cells in antibody-dependent cell-mediated cytotoxicity (2012)

Abstract Monoclonal antibodies (MAbs) have been developed successfully as part of the anticancer armamentarium. However, even in cases where the target of the antibody is stably and abundantly expressed, efficacy often falls below expectations. The tumor microenvironment (TME) has previously been shown to contribute to resistance to MAb therapy because matrix-associated high interstitial fluid pressure inhibits efficient drug penetration (1). Hyaluronan is an important component of the extracellular matrix (ECM) in about 25% of tumors, and 56% of breast cancers. This glycosaminoglycan is produced by malignant and stromal cells and acts to cross-link ECM proteins, contributing to the desmoplastic phenotype. Accumulation of HA has been associated with more aggressive malignancy (2).In this work, we show that &amp;gt;50% of p185HER2-overexpressing breast tumors have a high accumulation of HA (HA+3). We hypothesized that tumor cells which overexpress HA create a protective “turtle shell” when it cross-links other ECM proteins (e.g., versican), and this pericellular structure protects the HER2-overexpressing tumor cell from attack by antibody-mediated cellular cytotoxicity (ADCC). SKBR3 (overexpressing p185HER2) and MDA-MB-231 (expressing EGFR) breast tumor cells were transfected with hyaluronan synthase 2 (HAS2), creating SKBR3/HAS2 (HA+3) and MDA-MB-231/HAS2 (HA+2), enabling these cells to form substantial pericellular matrices. NK-cell/trastuzumab/cetuximab-mediated ADCC is diminished in both of the HAS2-transfected cell types, suggesting that HA accumulation may contribute to tumor cell resistance to ADCC. Similarly, when these cells are treated in vitro with PEGPH20, a pegylated PH20 hyaluronidase (3), sensitivity to trastuzumab/cetuximab-mediated ADCC of the HAS2-overexpressing tumor cells is increased by up to 2-fold. These experiments show that the pericellular matrix coat (“turtle shell”) of high HA-producing tumor cells can inhibit the access of human immune cells to target cells, and that this effect can be reversed by depleting HA using PEGPH20. In vivo studies have shown that only PEGPH20, and not native PH20, has the bioavailability to induce antitumor activity in vivo. Models are currently in development to test whether PEGPH20 will enhance the activity of therapeutic MAbs in vivo.
Ovalbumin gene: evidence for a leader sequence in mRNA and DNA sequences at the exon-intron boundaries. (1978)

Selected regions of cloned EcoRI fragments of the chicken ovalbumin gene have been sequenced. The positions where the sequences coding for ovalbumin mRNA (ov-mRNA) are interrupted in the genome have been determined, and a previously unreported interruption in the DNA sequences coding for the 5' nontranslated region of the messenger has been discovered. Because directly repeated sequences are found at exon-intron boundaries, the nucleotide sequence alone cannot define unique excision-ligation points for the processing of a possible ov-mRNA precursor. However, the sequences in these boundary regions share common features; this leads to the proposal that there are, in fact, unique excision-ligation points common to all boundaries.
Effect of Vertebral, Carotid and Intravenous Infusions of Lysine Vasopressin on Plasma Vasopressin and Cardiovascular Function (1984)

The cardiovascular and vasopressin-releasing effects of vertebral artery, carotid artery and intravenous (i.v.) infusions of lysine vasopressin (150 microU/kg X min) were studied in anesthetized dogs. Vertebral and carotid artery infusions of lysine vasopressin led to similar decreases in cardiac output as i.v. infusions. Heart rate, however, decreased to a greater extent with vertebral and carotid artery infusions of lysine vasopressin than i.v. infusions. There were no changes in either mean arterial blood pressure or the plasma vasopressin concentration. The results indicate that peripheral vasopressin: has a central effect to reduce heart rate; has a peripheral effect on the heart to reduce cardiac output, and probably does not feed back to inhibit its own release.
BCL-2 is dispensable for thrombopoiesis and platelet survival (2015)

Navitoclax (ABT-263), an inhibitor of the pro-survival BCL-2 family proteins BCL-2, BCL-XL and BCL-W, has shown clinical efficacy in certain BCL-2-dependent haematological cancers, but causes dose-limiting thrombocytopaenia. The latter effect is caused by Navitoclax directly inducing the apoptotic death of platelets, which are dependent on BCL-XL for survival. Recently, ABT-199, a selective BCL-2 antagonist, was developed. It has shown promising anti-leukaemia activity in patients whilst sparing platelets, suggesting that the megakaryocyte lineage does not require BCL-2. In order to elucidate the role of BCL-2 in megakaryocyte and platelet survival, we generated mice with a lineage-specific deletion of Bcl2, alone or in combination with loss of Mcl1 or Bclx. Platelet production and platelet survival were analysed. Additionally, we made use of BH3 mimetics that selectively inhibit BCL-2 or BCL-XL. We show that the deletion of BCL-2, on its own or in concert with MCL-1, does not affect platelet production or platelet lifespan. Thrombocytopaenia in Bclx-deficient mice was not affected by additional genetic loss or pharmacological inhibition of BCL-2. Thus, BCL-2 is dispensable for thrombopoiesis and platelet survival in mice.