gebhart/patrepeval huggingface dataset:
Reactivity toward cysteine of antimicrobial carbamimidothioic acid phenylalkylesters salts. (1991)

The rates of reaction toward cysteine of a series of carbamimidothioic acid phenylmethylesters halides were investigated in phosphate buffer pH 7.4 at 37 degrees C under pseudo-first-order conditions. The reaction involves nucleophilic attack of cysteine on the C-S bond of isothiouronium mojety and corresponding benzenemethanethiols were detected as product of the reaction. Apparent first-order rate constants were determined.
Integration of Single Multi-Walled Carbon Nanotube on Micro Systems (2002)

This paper presents new techniques for depositing single multi-walled carbon nanotube (MWCNT) on metal electrodes based on micro-fabrication and an electric-field-guided assembly technique. It was demonstrated that a single MWCNT can be directionally deposited across a microscale gap guided by a biased AC electric field. The biased AC method could effectively avoid the deposition of undesirable particles, and yet maintained highly ordered deposition results. A specific AC frequency component was applied to attract only desired CNTs into a gap and a DC component was used to diminish electric field significantly when the first CNT is deposited. This method can be easily combined with other micromachining process and possibly applied to batch production.
Amino acid and dipeptide derivatives of daunorubicin. 2. Cellular pharmacology and antitumor activity of L1210 leukemic cells in vitro and in vivo (1980)

The accumulation of amino acid and dipeptide derivatives of DNR has been studied in vitro on L1210 cells. Only Leu-DNR reaches accumulation levels close to DNR, while Val-DNR, Ile-DNR, and Leu-Leu-DNR reach intermediate values. Intracellular DNR was found when the L1210 cells were incubated in the presence of DNR, Leu-Leu-DNR, Leu-Ala-DNR, and Leu-DNR. The cytostatic activity of the derivatives in vitro on L1210 cells cannot be correlated with their uptake or conversion into DNR. At equitoxic doses given iv on the iv inoculated form of L1210 leukemia, all the derivatives are less active than DNR. When given iv on the sc inoculated L1210 leukemia, Leu-DNR, Ala-Leu-DNR and Leu-Leu-DNR are much more active than DNR with a striking increase in ILS and reduction of tumor progression. The superiority of those compounds could be due to their greater hydrophobicity and to their hydrolysis in situ by enzymes secreted by tumor cells or present on the tumor cells surface.
Quasispecies dynamics and the emergence of drug resistance during zidovudine therapy of HIV infection (1994)

The short-term reduction in viral replication at the initiation of therapy generates a pool of uninfected cells which cause the eventual increase in viral burden. This increase is associated with (but not caused by) a rise in frequency of resistant strains which are at a competitive advantage in the presence of the drug. When therapy is ceased, reversion of resistance is slow as resistant strains are nearly as fit as sensitive strains in the absence of drug.
Structures and mode of membrane interaction of a short α helical lytic peptide and its diastereomer determined by NMR, FTIR, and fluorescence spectroscopy (2002)

The interaction of many lytic cationic antimicrobial peptides with their target cells involves electrostatic interactions, hydrophobic effects, and the formation of amphipathic secondary structures, such as alpha helices or beta sheets. We have shown in previous studies that incorporating approximately 30%d-amino acids into a short alpha helical lytic peptide composed of leucine and lysine preserved the antimicrobial activity of the parent peptide, while the hemolytic activity was abolished. However, the mechanisms underlying the unique structural features induced by incorporating d-amino acids that enable short diastereomeric antimicrobial peptides to preserve membrane binding and lytic capabilities remain unknown. In this study, we analyze in detail the structures of a model amphipathic alpha helical cytolytic peptide KLLLKWLL KLLK-NH2 and its diastereomeric analog and their interactions with zwitterionic and negatively charged membranes. Calculations based on high-resolution NMR experiments in dodecylphosphocholine (DPCho) and sodium dodecyl sulfate (SDS) micelles yield three-dimensional structures of both peptides. Structural analysis reveals that the peptides have an amphipathic organization within both membranes. Specifically, the alpha helical structure of the L-type peptide causes orientation of the hydrophobic and polar amino acids onto separate surfaces, allowing interactions with both the hydrophobic core of the membrane and the polar head group region. Significantly, despite the absence of helical structures, the diastereomer peptide analog exhibits similar segregation between the polar and hydrophobic surfaces. Further insight into the membrane-binding properties of the peptides and their depth of penetration into the lipid bilayer has been obtained through tryptophan quenching experiments using brominated phospholipids and the recently developed lipid/polydiacetylene (PDA) colorimetric assay. The combined NMR, FTIR, fluorescence, and colorimetric studies shed light on the importance of segregation between the positive charges and the hydrophobic moieties on opposite surfaces within the peptides for facilitating membrane binding and disruption, compared to the formation of alpha helical or beta sheet structures.
Peptidomimetics: Fmoc Solid-Phase Pseudopeptide Synthesis (2008)

Peptidomimetic modifications or cyclization of linear peptides are frequently used as attractive methods to provide more conformationally constrained and thus more stable and bioactive peptides. Among numerous peptidomimetic approaches described recently in the literature, particularly attractive are pseudopeptides or peptide bond surrogates in which peptide bonds have been replaced with other chemical groups. In these peptidomimetics the amide bond surrogates possess three-dimensional structures similar to those of natural peptides, yet with significant differences in polarity, hydrogen bonding capability, and acid-base character. The introduction of such modifications to the peptide sequence is expected to completely prevent protease cleavage of amide bond and significantly improve peptides' metabolic stability. In this chapter we consider Fmoc solid-phase synthesis of peptide analogs containing the amide surrogate that tend to be isosteric with the natural amide. This includes synthesis of peptidosulfonamides, phosphonopeptides, oligoureas, depsides, depsipeptides, and peptoids.
Phase I clinical trial of the intraperitoneal (IP) administration of a novel nanoparticle formulation of paclitaxel (NTX). (2013)

2558 Background: IP therapy is an attractive option for patients with IP carcinomatosis as many of these malignancies remain confined IP. Agents whose plasma clearance rates substantially exceed their rates of uptake from the peritoneal cavity are especially suited for IP administration. Pre-clinical studies of a novel formulation of nanoparticulate paclitaxel in animal tumor models demonstrated superior activity and substantially reduced systemic toxicity. This allowed for significant IP doses and concentrations, yet yielded very low systemic concentrations of paclitaxel. We report here the results of a Phase I trial of IP administered NTX. Methods: Patients (ECOG≤2) had relapsed, treatment refractory solid IP tumors and adequate organ function. NTX was administered IP as a bolus injection after 500 ml saline followed by IP administration of up to 2 L of saline. We utilized an accelerated dose escalation scheme until one DLT occurred during cycle 1, followed by a standard dose escalation (3+3 design) based on CTCAE V3 toxicities. The pharmacokinetics of IP administered NTX were characterized in plasma and ascites fluid. Secondary objectives were to define the recommended phase 2 dose of NTX, and characterize preliminary activity and toxicity. Results: 20 patients were treated at dose levels from 50 – 275 mg/M2 q 28 days. Primary malignancy was ovarian cancer (74%). Treatment was well tolerated at all dose levels. Common toxicities potentially related to NTX were: gastrointestinal (68%), constitutional (42%), and pain (42%). Average number of cycles received was 2 (range 1 to 6). Best response was stable disease (4 patients, 21%). Median length of disease stability was 99 days (range 85 to 151 days); median time on study patients with stable disease was 313 days (range 142 to 740 days). All Cmax in plasma were less than 35 ng/mL, with ascites fluid Cmax generally greater than 1000 ng/mL. Conclusions: IP NTX is well tolerated. MTD has not yet been reached. Pharmacokinetic data demonstrate significant, persistent IP exposure to paclitaxel with minimal systemic exposure. Accrual at the 275 mg/M2 dose level continues; updated results will be presented. Further clinical development of NTX is indicated. Clinical trial information: NCT00666991.
PolySwitch PTC Devices-A New Low-Resistance Conductive Polymer-Based PTC Device for Overcurrent Protection (1981)

Positive temperature coefficient (PTC) resistors for use as overcurrent protectors are now available with normal conduction mode resistances of about 0.04 <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\Omega</tex> . This resistance is significantly lower than devices made from heretofore available barium titanate ceramics. PolySwitchTM overcurrent protectors are made from conductive polymer compositions, which are newly developed materials. Fabrication of a PolySwitch device includes the creation of the base conductive polymer composite, melt forming it to device shape, attachment of leads, and packaging. The final product looks like a disc capacitor but acts like a solid-state circuit breaker or resettable fuse. The source of the PTC effect in these compositions is volume expansion upon heating and the subsequent disruption of connecting carbon black chains. Resistance characteristics of these compositions are reproducible and consistent from device to device; the concepts of a minimum and maximum base resistance and a resistance recovery curve are discussed. Polymer volume compaction processes are responsible for the recovery behavior. The physics of PolySwitch device behavior is explained by Joule heating. The characteristics important to the designer are ultimate trip current as a function of ambient temperature, a property of thermal and electrical equilibrium; and the trip-time characteristic, a property of the nonequilibrium dynamic response. Knowledge of both these charactistics allows the designer to quickly choose a PolySwitch device for his particular job.
The nature of unexplained chronic aminotransferase elevations of a mild to moderate degree in asymptomatic patients (1989)

To determine the nature of unexplained chronic serum aspartate aminotransferase elevations of a mild to moderate degree in asymptomatic patients, we performed systematic clinical, biochemical and histologic examinations in 47 individuals who had been screened for virus-, alcohol- or drug-related disease. Serum aspartate aminotransferase levels ranged from 3- to 8-fold normal (mean: 156 +/- 7 units per liter) for at least 6 months (mean: 30 +/- 6 months). Serum alanine aminotransferase levels were also increased but to a lesser degree in most patients. Thirty-four patients (72%) had histologic features of chronic active hepatitis, including 16 with cirrhosis. Ten patients (21%) had steatohepatitis and three (6%) had miscellaneous disorders. Patients with chronic active hepatitis and cirrhosis could not be distinguished from counterparts without cirrhosis by individual clinical or laboratory findings. Antinuclear or smooth muscle antibodies were detected in 18 of the patients with chronic active hepatitis (53%). All patients with steatohepatitis were women, and they had laboratory changes at presentation, including seropositivity for antinuclear antibodies, that overlapped with those of patients with chronic active hepatitis. We conclude that asymptomatic patients with unexplained chronic aspartate aminotransferase elevations of a mild to moderate degree frequently have chronic active hepatitis and that many have cirrhosis. Immunoserologic findings compatible with autoimmune hepatitis are commonly present. Steatohepatitis is the most frequent alternative diagnosis, especially in women, and it is not excluded by the presence of antinuclear antibodies. Differentiation of the disorders is possible only by histologic examination.
Drug-resistance in multiple myeloma and non-Hodgkin's lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy. (1989)

The B-cell neoplasms, multiple myeloma and non-Hodgkin's lymphoma, frequently become drug resistant, despite initial responses to chemotherapeutic drugs. Tumor cells from eight patients with clinically drug-refractory disease were evaluated by immuno-histochemical staining for monoclonal immunoglobulin (Ig) expression, nuclear proliferation antigen, P-glycoprotein (P-gly) expression, and other cellular antigens. P-gly was detected on tumor cells from six of eight patients with drug-resistant disease. Of the six patients with P-gly-positive tumors, five patients had advanced multiple myeloma and one had a drug-refractory non-Hodgkin's lymphoma. Cellular RNA analysis confirmed the over-expression of P-gly. In an effort to overcome drug resistance, a pilot study evaluated possible verapamil enhancement of chemotherapy in these eight patients. All patients had developed progressive disease while receiving a regimen containing vincristine and doxorubicin, and seven of eight patients had previously received continuous infusion vincristine and doxorubicin plus oral dexamethasone (VAD). At the time of progressive disease, continuous infusion verapamil was added to the VAD regimen. Three of the eight patients who were refractory to vincristine and doxorubicin alone responded when verapamil was added to VAD. The three patients who responded had P-gly-positive tumors. Verapamil increased the intracellular accumulation of doxorubicin and vincristine in vitro for both a P-gly-positive myeloma cell line and tumor cells from two patients with end-stage myeloma which over-expressed P-gly. The dose-limiting side effect associated with the addition of verapamil to chemotherapy was temporary impairment of cardiac function, manifest as hypotension and cardiac arrhythmia. We conclude that P-gly expression occurs in drug-refractory B-cell neoplasms and may contribute to the development of clinical drug resistance. However, other factors, such as the proliferative activity of the tumor, may also play a role in determining response to chemotherapy. The administration of verapamil along with VAD chemotherapy may partially circumvent drug resistance in patients whose tumors over-express P-gly.
Modeling, Analysis and Testing of Autonomous Operation of an Inverter-Based Microgrid (2007)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> The analysis of the small-signal stability of conventional power systems is well established, but for inverter based microgrids there is a need to establish how circuit and control features give rise to particular oscillatory modes and which of these have poor damping. This paper develops the modeling and analysis of autonomous operation of inverter-based microgrids. Each sub-module is modeled in state-space form and all are combined together on a common reference frame. The model captures the detail of the control loops of the inverter but not the switching action. Some inverter modes are found at relatively high frequency and so a full dynamic model of the network (rather than an algebraic impedance model) is used. The complete model is linearized around an operating point and the resulting system matrix is used to derive the eigenvalues. The eigenvalues (termed “modes”) indicate the frequency and damping of oscillatory components in the transient response. A sensitivity analysis is also presented which helps identifying the origin of each of the modes and identify possible feedback signals for design of controllers to improve the system stability. With experience it is possible to simplify the model (reduce the order) if particular modes are not of interest as is the case with synchronous machine models. Experimental results from a microgrid of three 10-kW inverters are used to verify the results obtained from the model. </para>
A Proinflammatory Cytokine Inhibits P53 Tumor Suppressor Activity (1999)

p53 has a key role in the negative regulation of cell proliferation, in the maintenance of genomic stability, and in the suppression of transformation and tumorigenesis. To identify novel regulators of p53, we undertook two functional screens to isolate genes which bypassed either p53-mediated growth arrest or apoptosis. In both screens, we isolated cDNAs encoding macrophage migration inhibitory factor (MIF), a cytokine that was shown previously to exert both local and systemic proinflammatory activities. Treatment with MIF overcame p53 activity in three different biological assays, and suppressed its activity as a transcriptional activator. The observation that a proinflammatory cytokine, MIF, is capable of functionally inactivating a tumor suppressor, p53, may provide a link between inflammation and tumorigenesis.
The core polypeptide of cystic fibrosis tracheal mucin contains a tandem repeat structure. Evidence for a common mucin in airway and gastrointestinal tissue. (1990)

A cystic fibrosis trachea cDNA library was constructed and probed with a synthetic oligonucleotide containing a consensus sequence recently identified in human intestinal mucin. One of the isolated clones, AMN-22, has been characterized extensively. The cDNA sequence of this 884-bp fragment was determined, and revealed a tandem repeat structure rich in threonine and proline residues. The repeating sequence of AMN-22 was similar but not identical to that determined for gut mucin. When examined by Northern analysis, the mRNA hybridizing to AMN-22 is extremely polydisperse in cystic fibrosis (CF) trachea, with apparent message length varying from approximately 2 kb to greater than 10 kb. A similar pattern was observed, with less abundant message, in CF bronchiectatic lung parenchyma. The lung cDNA hybridized to a similarly polydisperse message in ulcerative colitis colon RNA, but did not hybridize to control RNA from U937 lymphoma cells or stomach RNA. Pedigree analysis of restriction digests of genomic DNA revealed a pattern indicating a single polymorphic locus for the mucin gene expressed in the lung and the intestine. Southern analyses of human:mouse somatic cell hybrid cell lines allow a chromosomal localization for the mucin gene to human chromosome II, within the region 11p13-11pTer. Taken together, these data demonstrate that a polymorphic gene encodes a mucin core polypeptide expressed in both lung and intestine.
Imaging hNET Reporter Gene Expression with 124I-MIBG (2007)

These studies demonstrate the potential for a wider application of hNET reporter imaging and the future translation to patient studies using radiopharmaceuticals that are currently available for both SPECT and PET.
Beamforming in combination with space-time diversity for broadband OFDM systems (2003)

We investigate broadband OFDM systems which apply beamforming in combination with different space-time diversity techniques. Various beamforming scenarios with transmitter and/or receiver sided beamforming are considered. Space-time diversity is obtained by cyclic delay diversity (CDD) in order to artificially shape the spectrum of the received signal. Thus, an advantageous distribution of the errors before a Viterbi channel decoder is obtained. Simulation results for the bit error rate performance are presented and compared for OFDM systems applying different beamforming scenarios and CDD in a Rayleigh fading channel. Maximum ratio combining (MRC) of the signals received on multiple beams/antennas is also taken into account in the performance analysis.
Reduced intravascular catheter infection by antibiotic bonding. A prospective, randomized, controlled trial. (1991)

We report a prospective, randomized, controlled clinical trial to evaluate the efficacy of antibiotic-bonded catheters in reducing the incidence of intravascular catheter-related infections. Ninety-three central venous catheters and 85 arterial catheters were studied in the surgical intensive care unit. Study catheters were pretreated with the cationic surfactant tridodecylmethylammonium chloride. The anionic antibiotic, cefazolin, was bonded before insertion of the catheters by immersing them in a 50-mg/mL solution. Fourteen percent of the 81 catheters in the control group were infected, compared with 2% of the 97 antibiotic-bonded catheters. Staphylococcus epidermidis was the most common organism obtained. There was no significant difference in the number of colonized or clinically inflamed catheter insertion sites. None of the 100 antibiotic immersion solutions yielded anything on microbiologic culture. We conclude that antibiotic bonding is an efficient, safe, and cost-effective method of reducing intravascular catheter infection in patients who are in intensive care units.
MGD011, A CD19 x CD3 Dual-Affinity Retargeting Bi-specific Molecule Incorporating Extended Circulating Half-life for the Treatment of B-Cell Malignancies (2016)

<b>Purpose:</b> CD19, a B-cell lineage-specific marker, is highly represented in B-cell malignancies and an attractive target for therapeutic interventions. MGD011 is a CD19 x CD3 DART bispecific protein designed to redirect T lymphocytes to eliminate CD19-expressing cells. MGD011 has been engineered with a modified human Fc domain for improved pharmacokinetic (PK) properties and designed to cross-react with the corresponding antigens in cynomolgus monkeys. Here, we report on the preclinical activity, safety and PK properties of MGD011.<b>Experimental Design:</b> The activity of MGD011 was evaluated in several <i>in vitro</i> and <i>in vivo</i> models. PK, safety and pharmacodynamic activity was also assessed in dose-escalation and repeat-dose studies of MGD011 administered once weekly in cynomolgus monkeys.<b>Results:</b> MGD011 mediated killing of human B-cell lymphoma lines by human or cynomolgus monkey PBMCs as well as autologous B-cell depletion in PBMCs from both species. MGD011-mediated killing was accompanied by target-dependent T-cell activation and expansion, cytokine release and upregulation of perforin and granzyme B. MGD011 demonstrated antitumor activity against localized and disseminated lymphoma xenografts reconstituted with human PBMCs. In cynomolgus monkeys, MGD011 displayed a terminal half-life of 6.7 days; once weekly intravenous infusion of MGD011 at doses up to 100 μg/kg, the highest dose tested, was well tolerated and resulted in dose-dependent, durable decreases in circulating B cells accompanied by profound reductions of B lymphocytes in lymphoid organs.<b>Conclusions:</b> The preclinical activity, safety and PK profile support clinical investigation of MGD011 as a therapeutic candidate for the treatment of B-cell malignancies. <i>Clin Cancer Res; 23(6); 1506-18. ©2016 AACR</i>.
Sensors for sub-ppm NO2 gas detection based on carbon nanotube thin films (2003)

Carbon nanotubes (CNTs) deposited by plasma-enhanced chemical vapor deposition on Si3N4/Si substrates have been investigated as resistive gas sensors for NO2. Upon exposure to NO2, the electrical resistance of the CNTs was found to decrease. The maximum variation of resistance to NO2 was found at an operating temperature of around 165 °C. The sensor exhibited high sensitivity to NO2 gas at concentrations as low as 10 ppb, fast response time, and good selectivity. A thermal treatment method, based on repeated heating and cooling of the films, adjusted the resistance of the sensor film and optimized the sensor response to NO2.