gebhart/patrepeval huggingface dataset:
Cellular detoxification of tripeptidyl aldehydes by an aldo-keto reductase. (1993)

Calpain inhibitor I, N-acetyl-leucyl-leucyl-norleucinal (ALLN), a cell-permeable synthetic tripeptide with an aldehyde at its C terminus specifically inhibits the activity of cysteine proteases. Since the regulated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase in Chinese hamster ovary (CHO) cells is blocked by ALLN and ALLN has a cytotoxic effect on cells, we attempted to isolate ALLN-resistant cells that overproduce an ALLN-sensitive protease(s). However, we obtained an ALLN-resistant cell line that overproduced P-glycoprotein (Sharma, R. C., Inoue, S., Roitelman, J., Schimke, R. T., and Simoni, R. D. (1992) J. Biol. Chem. 267, 5731-5734). To circumvent the multidrug resistance (MDR) phenotype during selection, we have stepwise selected an ALLN-resistant cell line of CHO cells in the presence of verapamil, a competitive inhibitor of P-glycoprotein. These non-MDR ALLN-resistant cells overexpress a 35-kDa protein and have increased aldo-keto reductase activity. Partial amino acid sequences of the 35-kDa protein are highly homologous to members of the aldo-keto reductase superfamily. The aldo-keto reductases are NADPH-dependent oxidoreductases and catalyze reduction of a wide range of carbonyl compounds such as aldehydes, sugars, and ketones. Our findings support the concept that a physiological function for aldo-keto reductases may be detoxification.
Role of Heteromer Formation in GABA B Receptor Function (1999)

Recently, GBR1, a seven-transmembrane domain protein with high affinity for gamma-aminobutyric acid (GABA)B receptor antagonists, was identified. Here, a GBR1-related protein, GBR2, was shown to be coexpressed with GBR1 in many brain regions and to interact with it through a short domain in the carboxyl-terminal cytoplasmic tail. Heterologously expressed GBR2 mediated inhibition of adenylyl cyclase; however, inwardly rectifying potassium channels were activated by GABAB receptor agonists only upon coexpression with GBR1 and GBR2. Thus, the interaction of these receptors appears to be crucial for important physiological effects of GABA and provides a mechanism in receptor signaling pathways that involve a heterotrimeric GTP-binding protein.
Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia (1998)

Ischemic stroke is the most common life-threatening neurological disease and has limited therapeutic options. One component of ischemic neuronal death is inflammation. Here we show that doxycycline and minocycline, which are broad-spectrum antibiotics and have antiinflammatory effects independent of their antimicrobial activity, protect hippocampal neurons against global ischemia in gerbils. Minocycline increased the survival of CA1 pyramidal neurons from 10.5% to 77% when the treatment was started 12 h before ischemia and to 71% when the treatment was started 30 min after ischemia. The survival with corresponding pre- and posttreatment with doxycycline was 57% and 47%, respectively. Minocycline prevented completely the ischemia-induced activation of microglia and the appearance of NADPH-diaphorase reactive cells, but did not affect induction of glial acidic fibrillary protein, a marker of astrogliosis. Minocycline treatment for 4 days resulted in a 70% reduction in mRNA induction of interleukin-1beta-converting enzyme, a caspase that is induced in microglia after ischemia. Likewise, expression of inducible nitric oxide synthase mRNA was attenuated by 30% in minocycline-treated animals. Our results suggest that lipid-soluble tetracyclines, doxycycline and minocycline, inhibit inflammation and are neuroprotective against ischemic stroke, even when administered after the insult. Tetracycline derivatives may have a potential use also as antiischemic compounds in humans.
Quantum Cryptography Defies Eavesdropping (1992)

Students of physics can be Students of physics can be excused for finding their quantum mechanics courses a little cryptic from time to time. Now researchers are using the properties of quantum mechanics to encrypt information for secure transmission.
An Effective Targeted Nanoglobular Manganese(II) Chelate Conjugate for Magnetic Resonance Molecular Imaging of Tumor Extracellular Matrix (2010)

Stable manganese(II) chelates are of great interest for the design and development of safe and effective non-gadolinium(III)-based targeted MRI contrast agents for MR cancer molecular imaging. In this study, a CLT1 peptide targeted G3 nanoglobular Mn(II)-DOTA monoamide conjugate was designed and synthesized as a targeted MRI contrast agent for molecular imaging of the fibrin-fibronectin complexes or oncofetal fibronectin in tumor stroma. The targeted contrast agent comprised 2 peptides and 42 Mn(II)-DOTA chelates on the surface of the G3 nanoglobule. The T(1) and T(2) relaxivities of the targeted agent at room temperature were 3.13 and 8.74 mM(-1) s(-1) per Mn(II) chelate at 3 T (tesla), respectively. It had a well-defined nanosize (5.2 nm) and could be readily excreted via renal filtration. The targeted nanoglobular contrast agent specifically bound to tumor tissue, resulting in significant tumor contrast enhancement with minimal nonspecific enhancement in the liver of tumor bearing mice as compared to a nontargeted control at a dose as low as 0.03 mmol-Mn/kg. The targeted G3 nanoglobular Mn(II)-DOTA conjugate is promising as a targeted non-gadolinium(III)-based MRI contrast agent for MR cancer molecular imaging.
Active loading liposomal irinotecan hydrochloride: Preparation, in vitro and in vivo evaluation (2013)

The aim of the present study was to investigate the effect of various transmembrane ammonium salt gradients and different lipid composition on the loading efficiency of liposomal formulations of irinotecan hydrochloride (CPT-11), their behavior in vivo and cytotoxicity. Among ammonium salts studied, ammonium sulfate was successfully used to load CPT-11 into liposomes with the highest encapsulation efficiency. Subsequently, liposomal CPT-11 with different lipid composition was prepared by ammonium sulfate gradient method. CPT-11 can be loaded to a level over 90% into liposomes composed of soybean phospholipids/cholesterol (SPC-L) or hydrogenated natural soybean phospholipids/cholesterol (HSPC-L). In vitro release profiles were also investigated, indicating that HSPC-L had a lower release than that in SPC-L. In vivo, encapsulation of CPT-11 in both liposomal formulations showed higher area under the curve (AUC), a lower rate of clearance (CL) and smaller volume of distribution for CPT-11 than those of irinotecan hydrochloride solution (CPT-11-S). However, CL and AUC of 7-ethyl-10-hydroxycamptothecin (SN-38) were moderately improved in HSPC-L group. Based on the results of comparative pharmacokinetics of liposomal CPT-11 with different lipid composition, the in vitro cytotoxicity of HSPC-L was evaluated with human tumor cell. The result indicated that liposomal CPT-11 showed a great enhancement in vitro cytotoxicity. The results suggested that entrapment of CPT-11 in liposomes especially in those with high phase-transition temperature lipid by ammonium sulfate gradient would be a promising formulation with a better in vivo behavior.
Novel Expression and Characterization of Lymphatic Vessel Endothelial Hyaluronate Receptor 1 (LYVE-1) by Conjunctival Cells (2005)

A new population of monocytic cells has been found to express LYVE-1 in normal conjunctiva. These cells that normally express LYVE-1 may act as a reservoir for lymphangiogenesis and cell recruitment when the immune system is challenged.
Generic serial and parallel on‐line direct‐injection using turbulent flow liquid chromatography/tandem mass spectrometry (2002)

The development of turbulent flow chromatography (TFC) has enabled considerable growth in the utility of on-line direct-injection technologies. TFC has now become established in a large number of varied analytical environments, particularly drug discovery/pharmacokinetics, metabolite profiling, combinatorial library purification, pre-clinical and clinical GLP applications. The utility of turbulent flow technology for in-house pre-clinical and clinical quantitative applications has necessitated extensive valve-cleaning procedures, and consequently lengthy cycle-times, to effectively remove the system carry-over. In-house requirements for assay validation require carry-over less than 20% of the lowest level of quantification (LLOQ), corresponding to 0.02% carry-over for a linear calibration range incorporating 3 orders. A generic turbulent flow chromatography protocol has been developed for drug discovery that incorporates polymeric turbulent flow extraction (cyclone) with C18-based reverse-phase chromatography. Further, multiple wash steps are incorporated within the methodology to meet in-house requirements for carry-over. Selection of novel switching-valve materials based on polyarylethyl ketone (PAEK) and Hastelloy/Valcon E autosampler injection hardware has enabled us to significantly impact the cycle-time required to reduce carry-over. Consequently, optimal usage of switching valves has enabled parallel operation for a generic on-line direct-injection methodology to successfully reduce the total cycle-time. Overall reductions from 4 min per sample to 90 s per sample are shown with comparable data quality using a proprietary target molecule from 0.1-100 ng/mL. This paper describes the hardware configuration and methodologies utilized to perform generic serial and parallel on-line direct-injection using a Turboflow HTLC 2300 system.
Injection of DNA encoding granulocyte-macrophage colony-stimulating factor recruits dendritic cells for immune adjuvant effects. (1999)

An important issue for effective vaccines is the development of potent adjuvants that can facilitate induction or augmentation of immunity. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth factor for myeloid progenitors of monocytes and dendritic cells (DC), which upon maturation are antigen-presenting cells (APC). The adjuvant effects of inoculation of DNA encoding GM-CSF into skin were studied. Initial experiments examined whether the GM-CSF gene injected into the skin of mice could affect the density of epidermal DC (Langerhans cells). DNA encoding GM-CSF delivered by particle bombardment into skin resulted in a significant increase of epidermal DC at the inoculation site. Kinetic analysis of epidermal recruitment after GM-CSF inoculation showed an increase in DC that peaked at seven days. This increase was accompanied by recruitment of DC into draining lymph nodes. The adjuvant effects of DNA encoding GM-CSF inoculated into skin were measured by the ability to augment antibody and T-cell responses against poorly immunogenic tumor antigens. Peptide immunization at skin sites containing epidermal DC newly recruited by GM-CSF DNA elicited T-cell responses against mutant p53, whereas peptide immunization of control skin sites did not elicit any detectable T-cell responses. Likewise, generation of antibodies following immunization with DNA encoding human gp75TRP1, a tyrosinase family member expressed by melanomas, was accelerated and protection from tumor challenge augmented by GM-CSF DNA.
Quantum gravity and new forces (1988)

The quantum-gravity-inspired phenomenology for gravitational forces is described. New gravitational phenomena, qualitatively similar to those attributed to the so-called )openreverse arrowquotes)fifth-force)closereverse arrowquotes) are to be expected. The parameters of a model with these features have been constrained by the geophysical tests of the inverse-square law of Stacey, et al. This model is then able to explain the apparent discrepancies between the recent resuilts of Thieberger and of Adelberger and collaborators. A striking new prediction of the model is that antiprotons should experience a substantially larger gravitational acceleration than normal matter. Gravitational red-shift experiments are also proposed as tests for the new forces. 12 refs.
Dimethylfumarate Impairs Melanoma Growth and Metastasis (2006)

Dimethylfumarate (DMF) inhibits signals transmitted by Rel proteins and is used for the treatment of inflammatory skin diseases such as psoriasis, but potential effects of DMF on tumor progression have yet not been analyzed. We show that DMF reduced melanoma growth and metastasis in severe combined immunodeficient mouse models. To identify targets of DMF action, we analyzed mRNA expression in DMF-treated melanomas by gene chip arrays. Using BiblioSphere software for data analysis, significantly regulated genes were mapped to Gene Ontology terms cell death, cell growth, and cell cycle. Indeed, we found that DMF inhibited proliferation of human melanoma cells A375 and M24met in vitro. The cell cycle was arrested at the G(2)-M boundary. Moreover, DMF was proapoptotic, as shown by cell cycle analysis and by Annexin V and Apo2.7 staining. These results were confirmed in vivo. DMF reduced proliferation rates of tumor cells as assessed by Ki-67 immunostaining and increased apoptosis as assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining. In conclusion, DMF is antiproliferative and proapoptotic and reduces melanoma growth and metastasis in animal models.
The use of spectrophotometry to estimate melanin density in Caucasians. (1998)

The density of cutaneous melanin may be the property of the skin that protects it from damage by solar radiation, but there is not an accepted, noninvasive method of measuring it. To determine whether the density of cutaneous melanin can be estimated from reflectance of visible light by the skin, reflectance of 15-nm wavebands of light by the skin of the inner upper arm of each of 82 volunteers was measured at 20-nm intervals with a Minolta 508 spectrophotometer. A 3-mm skin biopsy was then taken from the same site, and four nonserial sections of it were stained with Masson Fontana for melanin. The melanin content of the basal area was calculated using the NIH Image analysis system. We show that cutaneous melanin in Caucasians can be estimated by the difference between two measurements of reflectance of visible light by the skin: those at wavelengths 400 and 420 nm. This new spectrophotometric measurement was more highly correlated (r = 0.68) with the histological measurements of cutaneous melanin than was skin reflectance of light of wavelength 680 nm (r = 0.33). Reflectances in the range of 650-700 nm have been used previously in skin cancer research. This relatively accurate measurement of melanin is quick and noninvasive and can be readily used in the field. It should provide improved discrimination of individual susceptibility to epidermal tumors in Caucasians and information about melanin's biological role in the causation of skin cancer.
Treatment of exogenous Candida endophthalmitis in rabbits with oral fluconazole (1995)

We investigated the efficacy of oral fluconazole, alone or in combination with oral flucytosine (5FC), in treating Candida endophthalmitis using a rabbit model. Albino rabbits were infected with an intravitreal inoculation of 1,000 CFU of susceptible Candida albicans and randomized 5 days later to receive treatment with oral fluconazole alone (80 mg/kg of body weight per day), a combination of fluconazole and 5FC (100 mg/kg/12 h), or no treatment. The treatment effect was assessed at 2 and 4 weeks after therapy by funduscopy, quantitative vitreous culture, and histopathology. Intravitreal levels of fluconazole, 2 to 24 h after the first dose, were measured to be > 10 times the MIC of the drug for C. albicans. Among rabbits treated with fluconazole for 2 weeks, 67% had a > 90% reduction in fungal load (P < 0.05) and 33% were sterile. After 4 weeks, all had a > 99% reduction in fungal load (P < 0.05) and 75% were sterile (P = 0.01). This treatment effect was unchanged 4 weeks after discontinuation of fluconazole. Among rabbits treated with fluconazole and 5FC for 2 weeks, 67% died during therapy. Among the surviving rabbits, 75% had a > 90% reduction in fungal load (P < 0.05) and 25% were sterile. We conclude that oral fluconazole may be useful for treatment of Candida endophthalmitis. Addition of 5FC was associated with high toxicity and minimal additional antifungal effect in our rabbit model.
Dynamic simulation of the human red blood cell metabolic network (2001)

We have developed a Mathematica application package to perform dynamic simulations of the red blood cell (RBC) metabolic network. The package relies on, and integrates, many years of mathematical modeling and biochemical work on red blood cell metabolism. The extensive data regarding the red blood cell metabolic network and the previous kinetic analysis of all the individual components makes the human RBC an ideal 'model' system for mathematical metabolic models. The Mathematica package can be used to understand the dynamics and regulatory characteristics of the red blood cell.
Component Latent Trait Models for Paragraph Comprehension Tests (1987)

The cognitive characteristics of paragraph compre hension items were studied by comparing models that deal with two general processing stages: text represen tation and response decision. The models that were compared included the prepositional structure of the text (Kintsch &amp; van Dijk, 1978), various counts of surface structure variables and word frequency (Drum et al., 1981), a taxonomy of levels of text questions (Anderson, 1972), and some new models that combine features of these models. Calibrations from the linear logistic latent trait model allowed evaluation of the impact of the cognitive variables on item responses. The results indicate that successful prediction of item difficulty is obtained from models with wide represen tation of both text and decision processing. This sug gests that items can be screened for processing diffi culty prior to being administered to examinees. However, the results also have important implications for test validity in that the two processing stages in volve two different ability dimensions.
Carbon nanotube correlation (2010)

Carbon Nanotubes (CNTs) are grown using chemical synthesis, and the exact positioning and chirality of CNTs are very difficult to control. As a result, "small-width" Carbon Nanotube Field-Effect Transistors (CNFETs) can have a high probability of containing no semiconducting CNTs, resulting in CNFET failures. Upsizing these vulnerable small-width CNFETs is an expensive design choice since it can result in substantial area/power penalties. This paper introduces a processing/design co-optimization approach to reduce probability of CNFET failures at the chip-level. Large degree of spatial correlation observed in directional CNT growth presents a unique opportunity for such optimization. Maximum benefits from such correlation can be realized by enforcing the active regions of CNFETs to be aligned with each other. This approach relaxes the device-level failure probability requirement by 350X at the 45nm technology node, leading to significantly reduced costs associated with upsizing the small-width CNFETs.
A comparison of different circuit configurations for an advanced static VAR compensator (ASVC) (2003)

Different circuit configurations for an ASVC are introduced and compared. Investigations are restricted to the stationary behavior with a brief look at parameters for dynamic control of the system. The concepts are extended to series connection of gate turn-off thyristors (GTOs), the multilevel inverter, and the application of more than one inverter. The circuits discussed show very large differences in cost and performance. Therefore, the choice for a certain application has to be made very carefully. The appropriate power rating must be reached by putting a number of GTOs in series. Paralleling of a small number of power circuits may also be considered. For common requirements concerning harmonic distortion of the line current only the best of the circuits allow operation without any filter banks. With three-level inverters and single GTOs as switches the circuits have a power rating of about 14 MVA. To reach 100 MVA would require at least eight GTOs in series.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Potential Value of Hormone Receptor Assay in Carcinoma In Situ of Breast (1990)

The estrogen receptor (ER) expression of invasive breast cancer has been extensively studied both biochemically and with specific monoclonal antibodies against ER. Relatively few studies have attempted to characterize ER pattern in breast carcinoma in situ (CIS) and in other premalignant lesions. In the current study, the authors investigated the pattern of ER expression in 62 cases of breast CIS, 30 of which had a component of invasive cancer, and 36 cases of atypical hyperplasia. Paraffin sections of formalin-fixed breast tissue underwent enzyme pretreatment to expose nuclear antigenic sites as previously described. Breast tissues then underwent estrogen immunocytochemical assay using specific monoclonal antibodies (Abbott Laboratory, Chicago, IL). The cases were evaluated for heterogeneity, intensity of staining, and percentage of ER-positive cells. An attempt was made to study the relation between the pattern of ER expression, nuclear pleomorphism, and type of CIS. The results of ER immunocytochemical assay showed positive nuclear staining for ER in 75% of the CIS, 73% of CIS with invasive cancer, and 100% of atypical hyperplasias. ER expression in CIS agreed with that in the invasive carcinoma in 29 of 30 cases. This study also suggests that comedocarcinoma has a higher incidence of negative ER expression than the other types of CIS, particularly when it is associated with significant nuclear pleomorphism. There was no significant difference in ER tumor heterogeneity between premalignant and malignant lesions.
Simplified Structure of a New Model to Describe Urinary Excretion of Plutonium after Systemic, Liver or Pulmonary Contamination of Rats Associated with Ca-DTPA Treatments (2009)

This study validates, by targeted experiments, several modeling hypotheses for interpretation of urinary excretion of plutonium after Ca-DTPA treatments. Different formulations and doses of Ca-DTPA were administered to rats before or after systemic, liver or lung contamination with various chemical forms of plutonium. The biokinetics of plutonium was also characterized after i.v. injection of Pu-DTPA. Once formed, Pu-DTPA complexes are stable in most biological environments. Pu-DTPA present in circulating fluids is rapidly excreted in the urine, but 2-3% is retained, mainly in soft tissues, and is then excreted slowly in the urine after transfer to blood. Potentially, all intracellular monoatomic forms of plutonium could be decorporated after DTPA internalization involving slow urinary excretion of Pu-DTPA with half-lives varying from 2.5 to 6 days as a function of tissue retention. The ratio of fast to slow urinary excretion of Pu-DTPA depends on both plutonium contamination and Ca-DTPA treatment. Fast urinary excretion of Pu-DTPA corresponds to extracellular decorporation that occurs beyond a threshold of the free DTPA concentration in circulating fluids. Slow excretion corresponds mostly to intracellular decorporation and depends on the amount of intracellular DTPA. From these results, the structure of a simplified model is proposed for interpretation of data obtained with Ca-DTPA treatments after systemic, wound or pulmonary contamination by plutonium.