gebhart/patrepeval huggingface dataset:
A simple method for measurement of cell-substrate attachment forces: application to HIV-1 Tat (1997)

In order to understand the importance of cell attachment to HIV-1 Tat, we quantified the strength of cell attachment to immobilized Tat in microtiter plate wells by the application of buoyant force. By replacing the attachment medium with dense medium, and subjecting the attached cells in the microtiter plates to centrifugal force in the conventional upright position, weakly binding and strongly binding cells could be discriminated (and separated) by varying the centrifugal speed. The strength of attachment of HT1080 cells to Tat was compared with that of the well-known extracellular matrix (ECM) proteins fibronectin and vitronectin. We observed that all three proteins mediated significant attachment of HT1080 cells both at 4 degrees C and 37 degrees C. However, unlike the ECM proteins, Tat was unable to engage in higher strength binding when the temperature was raised to 37 degrees C. The relatively weak binding of HT1080 cells to Tat (in the order of 3.0 mudynes/picomole of coated Tat) and lack of strengthening of binding to Tat at physiologic temperature suggests that this protein does not mimic adhesion molecule function. We anticipate that the methodology developed and described here will be useful in a wide variety of cell-matrix and cell-cell interaction studies.
Positive Result by Serology Indicates Active Helicobacter pylori Infection in Patients with Atrophic Gastritis (1998)

Patients with atrophic corpus gastritis and elevated Helicobacter pylori antibody titers but 13C-urea breath test (13C-UBT) and histology results negative for H. pylori were randomized into eradication therapy or follow-up only. Antibody levels decreased significantly in six out of seven patients in the eradication group, while in the follow-up group, the titers declined in only one out of eight patients. In patients with atrophic corpus gastritis, positive serology results may indicate an ongoing infection in spite of negative 13C-UBT and histology results.
Nanopore in metal-dielectric sandwich for DNA position control (2007)

We present the concept of a nanoelectromechanical device capable of controlling the position of DNA inside a nanopore with a single nucleotide accuracy. The device utilizes the interaction of discrete charges along the backbone of a DNA molecule with the electric field inside the nanopore. In analogy to solid state transistors in which a small voltage controls the current between two electrodes, a voltage strategically located inside the nanopore can control the translocation of a single DNA molecule between a cis and a trans reservoirs. We propose an immediate application of the device as a replacement of capillary electrophoresis in DNA sequencing.
Three-dimensional materials analysis by confocal Raman microspectroscopy (2001)

Two- and three-dimensional spatial analysis of various composite materials was performed with a scanning confocal Raman microspectrometer. Samples include TiO(2) microparticles, mixtures of polymers, and the surface of an older Eprom computer chip. In the last case both structural and compositional information was obtained by means of comparing the signal intensity of the Rayleigh line with that of the silicon Raman line at 520 cm(-1). The spatial compositions of a pain-relief medicine and a pharmaceutical salt mixture could be visualized from characteristic Raman lines of the components.
Neutrophil Influx and Chemokine Production during the Early Phases of the Antitumor Response to the Vascular Disrupting Agent DMXAA (ASA404) (2009)

5,6-Dimethylxanthenone-4-acetic acid (DMXAA) acts through tumor vascular disruption and cytokine production and is the first of its class to enter phase 3 trials. We characterized leukocytes and cytokines in murine Colon 38 tumors before and after DMXAA treatment. Tumor mass declined 50% 24 hours after DMXAA administration, but the leukocyte count per gram of tumor increased threefold owing to a large influx of Ly6G(+)CD11b(+)F4/80(-) cells with the morphology of neutrophils. However, B and T lymphocytes, natural killer cells, and macrophages in the tumor all decreased in numbers. Seven chemokines were substantially induced in the tumor, spleen, and serum 4 hours after DMXAA administration. Using cultured spleen cell subpopulations, CD11b(+) cells (largely monocytes and macrophages) were shown to be the primary producers of tumor necrosis factor alpha, interleukin 6 (IL-6), and macrophage inflammatory 1alpha (MIP-1alpha). CD49b(+) natural killer cells produced IP-10, whereas CD45R(+) B lymphocytes produced regulated upon activation normal T cell express sequence. T lymphocytes were not major producers of cytokines in the response to DMXAA. Murine peripheral blood leukocytes (PBLs) produced a similar panel of cytokines in culture to that detected in mouse serum after DMXAA treatment. Cytokines in human PBL cultures were subsequently measured with the aim of identifying potential serum markers of the human response to DMXAA. IP-10 (P < .001), monocyte chemoattractant protein 1 (P < .001), and sCD40L (P < .01) were decreased, whereas IL-8 (P < .001) and MIP-1alpha (P = .03) were increased in DMXAA-treated compared with untreated PBL cultures from a group of 12 donors.
Retinoic acid regulates ornithine decarboxylase gene expression at the transcriptional level (1993)

Retinoic acid (RA) is important for normal mammalian development and growth. Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme in the biosynthesis of the polyamines, and we have previously shown that ODC mRNA levels are suppressed by RA in human skin cells. Using HeLa cells, we now show that treatment with 0.5 microM RA for 24 h suppresses endogenous ODC mRNA levels and the expression of a transfected ODC/chloramphenicol acetyltransferase plasmid (Kpn-ODCCAT), containing sequences from -1450 to +810 of the human ODC gene. Co-transfection with either the alpha-RA receptor (alpha-RAR) or a chimeric alpha-RA/oestrogen receptor (alpha-RAER) followed by treatment with the cognate hormone suppresses expression of Kpn-ODCCAT and Not-ODCCAT, which contains sequences from -250 to +514. Liganded alpha-RAR suppresses the activity of Kpn-ODCCAT more markedly than does liganded alpha-RAER (98% and 80% suppression, respectively), whereas both receptors have very similar effects on Not-ODCCAT expression (73% and 67% suppression, respectively). The unliganded alpha-RAR suppresses Kpn-ODCCAT by 76%, whereas unliganded alpha-RAER has no significant effect. These data show that RA regulates ODC-gene expression at the transcriptional level, and that alpha-RAR, but not alpha-RAER, can confer full hormonal responsiveness. This suggests that the activating function present in the alpha-RAR ligand-binding domain is required for full transcriptional regulation.
Evaluation of collagen cross‐linking techniques for the stabilization of tissue matrices (1993)

The use of glutaraldehyde (GTA) for cross-linking biological tissue implants has a number of undesirable side effects, including cytotoxicity and induction of calcification. In an attempt to find an improved cross-linking agent for tissue implants, we have evaluated a number of cross-linking procedures shown previously to be effective with pure collagen or collagenous substrates, including GTA, succinic anhydride, cyanamide, 1-ethyl-3-(dimethylaminopropyl)carbodi-imide, dimethyl suberimidate, ascorbate-copper, glucose-lysine and acyl azide treatments. Apart from GTA, only acyl azide treatment significantly cross-linked human dermis, the degree of cross-linking being better than that seen after treatment of dermis with 1 mM GTA. Acyl azide treatment of thicker vascular tissue (porcine aorta) also resulted in a significantly cross-linked tissue. Preliminary cytotoxicity studies suggested that acyl azide treatment was not toxic, and, therefore, coupled with its cross-linking ability, this treatment is worthy of further investigation and may prove to be an alternative to GTA for the treatment of bioprostheses.
Growth factors influencing bone development (1990)

We have approached the study of growth factors affecting cartilage and bone development by investigating those factors present in bone which are able to initiate new cartilage and bone formation in vivo. This has led to the identification and molecular cloning of seven novel human factors which we have named BMP-1 through BMP-7. Six of these molecules are related to each other, and are also distantly related to TGF-beta. The presence of one of these molecules, recombinant human BMP-2 (rhBMP-2) is sufficient to produce the complex developmental system of cartilage and bone formation when implanted subcutaneously in a rat assay system. In this model, administration of rhBMP-2 ultimately results in the formation of a piece of trabecular bone, which is filled with mature bone marrow. While our studies demonstrate that rhBMP-2 by itself has the ability to induce cartilage and bone formation in vivo, we find other BMP molecules present along with BMP-2 in our highly purified nonrecombinant bone-inductive material. These results suggest that the bone inductive capacity of bone-derived proteins may reside in the combinatorial or synergistic activities of this set of BMP-2 related molecules.
Flt3 Ligand Antitumor Activity in a Murine Breast Cancer Model: A Comparison with Granulocyte-Macrophage Colony-Stimulating Factor and a Potential Mechanism of Action (1999)

We have shown that Flk2/Flt3 ligand (Flt3L)-transduced tumor vaccine induces transferable T cell protection against a murine breast cancer cell line, but a direct comparison with the potent effector GM-CSF, the activity against preestablished tumors, and the mechanism of antitumor response in this breast cancer model are not known. We compared vaccination with C3L5 cells expressing Flt3L (C3Lt-Flt3L) and GM-CSF (C3L5-GMCSF) by injecting 1 x 10(4) cells subcutaneously into the chest wall and then, after 4 weeks, challenging the contralateral chest of tumor-free mice with parental C3L5 cells. C3L5-Flt3L and C3L5-GMCSF had reduced in vivo growth rates (25% tumor formation each) compared with 100% tumor formation of C3L5 cells expressing only neomycin phosphotransferase (C3L5-G1N). However, when tumor-free animals were challenged with parental C3L5 cells, C3L5-Flt3L vaccination was significantly better at preventing tumor growth (p < 0.05) than C3L5-GMCSF vaccination (33% of C3L5-Flt3L-vaccinated animals developed tumor compared with 77% of C3L5-GMCSF-vaccinated animals). Adoptive transfer of immunity for both vaccines was demonstrated; splenic T cells from tumor-free mice protected naive mice from parental tumor challenge. To simulate minimal disease, parental C3L5 cells at two concentrations (high, 5 x 10(3) cells; or low, 1 x 10(3) cells) were injected into the contralateral chest wall 4 days prior to treatment with C3L5-G1N or C3L5-Flt3L. C3L5-Flt3L treatment decreased contralateral parental tumor formation (high, 67% tumor free; low, 90% tumor free) compared with C3L5-G1N treatment (high and low, 0% tumor free). Immunodepletion of activated natural killer cells with anti-asialo-GM1 blocked C3L5-Flt3L- and C3L5 plus soluble Flt3L-mediated antitumor activity. Thus, Flt3L-transduced tumor cells manifest potent antitumor activity, apparently mediated, at least partially, by natural killer cells.
siRNA-mediated down-regulation of ceramide synthase 1 leads to apoptotic resistance in human head and neck squamous carcinoma cells after photodynamic therapy. (2012)

Our novel findings are consistent with the notion that CERS1 regulates apoptotic resistance to PDT, partly via C18- and C20-ceramide, and that CERS1 is a molecular target for controlling resistance to PDT.
GDNF‐enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons (2009)

We previously demonstrated that coadministration of glial cell line-derived neurotrophic factor (GDNF) with grafts of Schwann cells (SCs) enhanced axonal regeneration and remyelination following spinal cord injury (SCI). However, the cellular target through which GDNF mediates such actions was unclear. Here, we report that GDNF enhanced both the number and caliber of regenerated axons in vivo and increased neurite outgrowth of dorsal root ganglion neurons (DRGN) in vitro, suggesting that GDNF has a direct effect on neurons. In SC-DRGN coculture, GDNF significantly increased the number of myelin sheaths produced by SCs. GDNF treatment had no effect on the proliferation of isolated SCs but enhanced the proliferation of SCs already in contact with axons. GDNF increased the expression of the 140 kDa neural cell adhesion molecule (NCAM) in isolated SCs but not their expression of the adhesion molecule L1 or the secretion of the neurotrophins NGF, NT3, or BDNF. Overall, these results support the hypothesis that GDNF-enhanced axonal regeneration and SC myelination is mediated mainly through a direct effect of GDNF on neurons. They also suggest that the combination of GDNF administration and SC transplantation may represent an effective strategy to promote axonal regeneration and myelin formation after injury in the spinal cord.
The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America (2011)

Evidenced-based guidelines for management of infants and children with community-acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians and investigators representing community pediatrics, public health, and the pediatric specialties of critical care, emergency medicine, hospital medicine, infectious diseases, pulmonology, and surgery. These guidelines are intended for use by primary care and subspecialty providers responsible for the management of otherwise healthy infants and children with CAP in both outpatient and inpatient settings. Site-of-care management, diagnosis, antimicrobial and adjunctive surgical therapy, and prevention are discussed. Areas that warrant future investigations are also highlighted.
Design and expression of organophosphorus acid anhydride hydrolase activity in human butyrylcholinesterase (1995)

Serine esterases and proteases are rapidly and irreversibly inhibited by organophosphorus (OP) nerve agents. To overcome this limitation, we selected several residues that were predicted to be within 3-10 A of both the active site Ser O gamma and the oxyanion hole of human butyrylcholinesterase for mutation to His (G115H, G117H, Q119H, and G121H). In remarkable contrast with wild-type (WT) and all other His mutants tested, G117H underwent spontaneous reactivation following OP inhibition to regain 100% of original esterase activity with maximum k3 values of approximately 6.8 x 10(-5) and 16 x 10(-5) s-1 for GB (sarin) and VX, respectively, in 0.1 M Bis-Tris, 25 degrees C. The free energy of activation for k3 was 19 kcal mol-1, and measurement of pH dependence suggested that reactivation resulted from an acidic group with pKa 6.2. To evaluate further the importance of His in achieving this result, we changed the same Gly to Lys (G117K) and compared its substrate and inhibitor kinetics with those of G117H. Both mutants retained esterase activity with Km values similar to those of WT for neutral ester hydrolysis, but G117K did not reactivate. Complete reactivation proves that G117H is not irreversibly inhibited but instead functions as a catalyst for OP hydrolysis. Dephosphonylation is the rate-limiting step, and G117H effects overall rate constant enhancements of approximately 100- and 2000-fold above the uncatalyzed hydrolysis of GB and VX, respectively, at pH 6.0, 25.0 degrees C. We conclude that an appropriately positioned imidazolium ion in the oxyanion hole catalyzes dephosphonylation and, thereby, confers a novel organophosphorus acid anhydride hydrolase activity upon butyrylcholinesterase.
Characterization and optimization of antigen-specific T cell responses during ex vivo expansion of melanoma tumor-infiltrating lymphocytes (2010)

Treatment of metastatic melanoma with tumor reactive T cells (adoptive T cell therapy, ACT) is a promising approach associated with a high clinical response rate. However, further optimization of this treatment modality is required to increase the clinical response after this therapy. ACT in melanoma involves an initial phase (pre-REP) of tumor-infiltrating lymphocyte (TIL) expansion ex vivo from tumor isolates followed by a second phase, “rapid expansion protocol” (REP) generating the billions of cells used as the TIL infusion product. The main question addressed in this thesis was how the currently used REP affected the responsiveness of the CD8+ T cells to defined melanoma antigens. We hypothesized that the REP drives the TIL to further differentiate and become hyporesponsive to antigen restimulation, therefore, proper cytokine treatment or other ways to expand TIL is required to improve upon this outcome. We evaluated the response of CD8+ TIL to melanoma antigen restimulation using MART-1 peptide-pulsed mature DC in vitro. Post-REP TILs were mostly hypo-responsive with poor proliferation and higher apoptosis. Phenotypic analysis revealed that the expression of CD28 was significantly reduced in post-REP TILs. By sorting experiment and microarray analysis, we confirmed that the few CD28+ post-REP TILs had superior survival capacity and proliferated after restimulation. We then went on to investigate methods to maintain CD28 expression during the REP and improve TIL responsiveness. Firstly, IL-15 and IL-21 were found to synergize in maintaining TIL CD28 expression and antigenic responsiveness during REP. Secondly, we found IL-15 was superior as compared to IL-2 in supporting the long-term expansion of antigen-specific CD8+ TIL after restimulation. These results suggest that current expansion protocols used for adoptive T-cell therapy in melanoma yield largely hyporesponsive products containing CD8+ T cells unable to respond in vivo to re-stimulation with antigen. A modification of our current approaches by using IL-15+IL-21 as supporting cytokines in the REP, or/and administration of IL-15 instead of IL-2 after TIL infusion, may enhance the anti-tumor efficacy and long-term persistence of infused T cells in vivo.
Discussion of the Epsilon-Near-Zero Effect of Graphene in a Horizontal Slot Waveguide (2014)

Horizontal slot waveguides based on graphene have been considered an attractive structure for optical waveguide modulators for transverse magnetic (TM) modes. Graphene is embedded in the slot region of a horizontal slot waveguide. If graphene were treated as an isotropic material and its dielectric constant were made close to zero by adjusting its Fermi level, the surface-normal electric field component of the fundamental TM mode of a horizontal slot waveguide might be highly enhanced in graphene. This could cause a large increase in the attenuation coefficient of the mode. This is called the epsilon-near-zero (ENZ) effect. This paper discusses that graphene needs to be treated as an anisotropic material that has an almost real surface-normal dielectric constant component. Then, the ENZ effect does not exist. Approximate analytic expressions and numerical simulation are used for the discussion, and they demonstrate that horizontal slot waveguides are not appropriate for graphene-based modulators for TM modes.
Blocking cytokines with genes (1998)

The pathophysiology of rheumatoid arthritis (RA) is primarily driven by proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha. Several biological agents have been identified that effectively block the activity of these cellular messengers, and administration of these agents to animal models of RA and human patients has been found to have therapeutic benefit. The application of gene therapy for the treatment of RA and other articular diseases is being explored to overcome current limitations with delivery of therapeutics to joint tissues. To date, laboratory research has focused on two main areas: (1) evaluation of gene delivery approaches and (2) identification of therapeutic gene products. Considerable progress has been reported with the use of local gene delivery to synovial cells by both in vivo and ex vivo methods and by systemic administration of gene delivery vectors via the circulation. Gene products that have therapeutic efficacy in animal models of RA include: IL-1 receptor antagonist, soluble IL-1 receptor I, soluble tumor necrosis factor receptor II, viral IL-10, and transforming growth factor beta, among others. The success of these laboratory studies has led to the implementation of a Phase I clinical trial to asses the safety and feasibility of using gene therapy in the treatment of RA.
Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine. (1996)

Borrelia burgdorferi, the spirochetal agent of Lyme disease, is transmitted by Ixodes ticks. A vaccine based on B. burgdorferi outer surface protein (Osp) A protects mice from spirochete infection. Here we report on the expression of OspA on spirochetes inside engorging ticks and relate OspA expression to antispirochetal immunity. Spirochetes in the gut of unfed nymphal ticks were stained by an OspA antibody, whereas in feeding ticks, the majority of spirochetes in the gut and salivary glands did not stain with the antibody. Thus, OspA was not expressed on most spirochetes during transmission from the vector to the vertebrate host. To examine the mechanism of protection afforded by OspA antibody, mice were passively immunized with OspA antibody at different times relative to tick attachment. When OspA antibody was administered to mice before or at the time of tick attachment, spirochetal development events in the vector, such as growth and salivary gland invasion, were blocked and the mice were protected from B. burgdorferi infection. When OspA antibody was administered to mice 48 h after tick attachment, spirochetes persisted in the nymphs and the mice were not protected despite the presence of circulating antibodies in the host as well as in the tick blood meal. Thus, OspA immunity appears to be effective only during a narrow window time at the beginning of the blood meal when antibodies bind to OspA-expressing spirochetes in the tick gut and block transmission from the vector to the host.
Effect of dual inhibition of apoptosis and autophagy in prostate cancer (2012)

We demonstrated that autophagy inhibition with HCQ enhances ABT-737 cytotoxicity in vitro and in vivo, that LC-3 and p62 represent assessable markers in human tissue for future clinical trials, and that ROS induction is a mechanism of cytotoxicity. These results support a new paradigm of dual targeting of apoptosis and autophagy in future clinical studies.