gebhart/patrepeval huggingface dataset:
Alveolar wall basement membranes in bleomycin-induced pulmonary fibrosis. (1985)

The ultrastructural characteristics of alveolar wall basement membranes (BM) were defined in an experimental model of pulmonary fibrosis. Lungs of adult hamsters were examined 2 to 60 days after a single intratracheal instillation of 0.5 units of bleomycin sulfate. Sections of lung fixed with tannic acid and glutaraldehyde were analyzed for epithelial basement membrane (EPI-BM) thickness and duplication, and tissue incubated in ruthenium red prior to fixation was evaluated for distribution of EPI-BM anionic sites. There were no major alterations in capillary EPI-BM. Six days after bleomycin, during acute inflammation, there was focal injury to alveolar epithelial cells and resultant denudation of EPI-BM. Denuded EPI-BM was folded with the lamina densa 60% thicker than in control animals, suggesting its active or passive retraction. Despite type 2 cell hyperplasia and repopulation of the epithelium, there was no duplication of EPI-BM. Thirty and 60 days after bleomycin, the epithelium was intact, inflammation had subsided, and widespread but focal fibrosis was present. This stage was characterized by thickening and duplication of the EPI-BM; 10% of EPI-BM on the thin side of the alveolar wall were duplicated at 30 days and 30% at 60 days. Duplication and thickening, although worse in fibrotic areas, also occurred in normal-appearing areas of lung, showing that EPI-BM changes may be the only residuum of previous damage. Duplication of EPI-BM in this model of pulmonary fibrosis is a late rather than an early feature of disease.(ABSTRACT TRUNCATED AT 250 WORDS)
2,3,7,8-Tetrachlorodibenzo-p-dioxin and Diindolylmethanes Differentially Induce Cytochrome P450 1A1, 1B1, and 19 in H295R Human Adrenocortical Carcinoma Cells (2001)

Diindolylmethane (DIM) is an acid-catalyzed condensation product of indole-3-carbinol, a constituent of cruciferous vegetables, and is formed in the stomach. DIM alters estrogen metabolism and inhibits carcinogen-induced mammary tumor growth in rodents. DIM is a weak agonist for the aryl hydrocarbon (Ah) receptor and blocks the effects of estrogens via inhibitory Ah receptor-estrogen receptor cross-talk. DIM and various structural analogs were examined in H295R cells for effects on 3 cytochrome P450 (CYP) enzymes involved in estrogen synthesis and/or metabolism: CYP1A1, CYP1B1, and CYP19 (aromatase). Aromatase activity was measured by conversion of 1 beta-(3)H-androstenedione to estrone and (3)H(2)O. H295R cells were exposed to the test chemicals dissolved in dimethyl sulfoxide for 24 h prior to analyses. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) (0--30 nM) and DIM (0--10 microM) induced ethoxyresorufin-O-deethylase (EROD) activity, as a measure of CYP1A1 and possibly 1B1 activity, with EC(50) values of about 0.3 nM and 3 microM, respectively. DIM, but not TCDD, induced aromatase activity with an apparently maximal 2-fold increase at 10 microM; higher concentrations of DIM and many of its analogs were cytotoxic. TCDD (30 nM) significantly increased CYP1A1 and 1B1 mRNA levels, but had no effect on mRNA for CYP19. DIM (3 microM) significantly increased mRNA levels for all three CYPS: DIM analogs with substitutions on the 5 and 5' position (3 microM) induced aromatase and EROD activity, together with mRNA levels of CYP1A1, 1B1, and 19; analogs that were substituted on the central carbon of the methane group showed little or no inductive activity toward the CYPS: In conclusion, DIM and several of its analogs appear to induce CYPs via multiple yet distinct pathways in H295R human adrenocortical carcinoma cells.
Candidacidal Activity of Salivary Histatins (1998)

Candida albicans is the predominant species of yeast isolated from patients with oral candidiasis, which is frequently a symptom of human immunodeficiency virus infection and is a criterion for staging and progression of AIDS. Salivary histatins (Hsts) are potent in vitro antifungal agents and have great promise as therapeutic agents in humans with oral candidiasis. The molecular mechanisms by which Hsts kill yeast cells are not known. We report here, that unlike other antimicrobial proteins, Hsts do not display lytic activities to lipid membranes, measured by release and dequenching of the fluorescent dye calcein. Analysis of the magnitude and time course of Hst-induced calcein release from C. albicans cells further showed that loss of cell integrity was a secondary effect following cell death, rather than the result of primary disruption of the yeast cell membrane. 125I-Hst 5 binding studies indicated that C. albicans expressed a class of saturable binding sites (KD = 1 microM), numbering 8.6 x 10(5) sites/cell. Both Hst 3 and Hst 4 competed for these binding sites with similar affinities, which is consistent with the micromolar concentration of Hsts required for candidacidal activity. Specific 125I-Hst 5 binding was not detected to C. albicans spheroplasts, which were 14-fold less susceptible to Hst 5 killing, compared with intact cells in candidacidal assays. In overlay experiments, 125I-Hst 5 bound to a 67-kDa protein detected in C. albicans whole cell lysates and crude membrane fractions, but not in the yeast cell wall fraction. Consistent with the overlay data, cross-linking of 125I-Hst 5 to C. albicans resulted in the appearance of a specific 73-kDa 125I-Hst 5-containing complex that was not detected in the cell wall. 125I-Hst 5-binding protein of similar size was also observed in susceptible S. cerevisiae strain TI#20. This is the first description of Hst 5 binding sites on C. albicans which mediate cell killing and identification of a 67-kDa yeast Hst 5-binding protein. The binding characteristics of Hst 5 are in agreement with the observed potency of its biological effect and provide crucial information to the use of Hst 5 as a therapeutic agent. The presence of a specific C. albicans Hst 5-binding protein provides further insight into the potential mechanism of yeast killing and suggests a basis for differential activity between yeast killing and the nontoxic nature of Hsts to humans.
A novel in vivo method to detect DNA sequence variation. (1995)

Mismatch repair detection (MRD) is an in vivo method that uses a change in bacterial colony color to detect DNA sequence variation. DNA fragments to be screened for variation are cloned into two MRD plasmids, and bacteria are transformed with heteroduplexes of these constructs. The resulting colonies are blue in the absence of a mismatch and white in the presence of a mismatch. MRD is capable of detecting a single mismatch in a DNA fragment as large as 10 kb in size. In addition, MRD has the potential for analyzing many fragments simultaneously, offering a powerful method for high-throughput genotyping and mutation detection in a large genomic region.
Preclinical Safety Evaluation in Rats of a Polymeric Matrix Containing an siRNA Drug Used as a Local and Prolonged Delivery System for Pancreatic Cancer Therapy (2016)

Conventional chemotherapy treatments for pancreatic cancer are mainly palliative. RNA interference (RNAi)-based drugs present the potential for a new targeted treatment. LOcal Drug EluteR (LODER(TM)) is a novel biodegradable polymeric matrix that shields drugs against enzymatic degradation and releases small interfering RNA (siRNA) against G12D-mutated KRAS (siG12D). siG12D-LODER has successfully passed a phase 1/2a clinical trial. Such a formulation necessitates biocompatibility and safety studies. We describe the safety and toxicity studies with siG12D-LODER in 192 Hsd:Sprague Dawley rats, after repeated subcutaneous administrations (days 1, 14, and 28). Animals were sacrificed on days 29 and 42 (recovery phase). In all groups, no adverse effects were noted, and all animals showed favorable local and systemic tolerability. Histopathologically, LODER implantation resulted in the expected capsule formation, composed of a thin fibrotic tissue. On the interface between the cavity and the capsule, a single layer composed of macrophages and multinucleated giant cells was observed. No difference was noted between the placebo and siG12D-LODER groups. These findings provide valuable information for future preclinical studies with siRNA-bearing biodegradable polymers and for the safety aspects of RNAi-based drugs as a targeted therapy.
Molecular Targeting of Inhibitor of Apoptosis Proteins Based on Small Molecule Mimics of Natural Binding Partners (2002)

An assay based on a solvent-sensitive fluorogenic dye molecule, badan, is used to test the binding affinity of a library of tetrapeptide molecules for the BIR3 (baculovirus IAP repeat) domain of XIAP (X-linked inhibitor of apoptosis protein). The fluorophore is attached to a tetrapeptide, Ala-Val-Pro-Cys-NH(2), through a thiol linkage and, upon binding to XIAP, undergoes a solvatochromic shift in fluorescence emission. When a molecule (e.g., a natural protein known to bind to XIAP or a tetrapeptide mimic) displaces the dye, the emission shifts back to the spectrum observed in water. As emission intensity is related to the binding of the tetrapeptide, the intensity can be used to determine the equilibrium constant, K, for the displacement of the dye by the tetrapeptide. The results permit residue-specific analysis of the interaction. Furthermore, we show that hydrophobic effects in the fourth position are general and can effectively increase overall affinity.
Differential expression of LFA-1 molecules in non-Hodgkin's lymphoma and lymphoid leukemia (1988)

We investigated the expression of adherence molecules lymphocyte function-associated antigens-1 alpha and -beta (LFA-1 alpha, -beta) and p150, 95 in 103 well-characterized non-Hodgkin's lymphomas (NHLs) and lymphoid leukemias (LLs). We found that NHLs and LLs differentially express LFA-1 molecules according to their lineage derivation, degree of clinical aggressiveness, and anatomic site of involvement. Specifically, (a) T-cell neoplasms nearly always express these molecules; (b) diffuse aggressive B-cell NHLs and mature LLs often lack LFA-1 alpha molecules; and (c) B-cell chronic lymphocytic leukemia (CLL) is often LFA-1 alpha-negative while B-cell small lymphocytic lymphomas (SLLs) are nearly always LFA-1 alpha-positive. Furthermore, the low expression of LFA-1 alpha in CLL is related to the low degree of homotypic lymphocyte adhesion after tumor promoter antigen stimulation that does not modulate the expression of LFA-1 alpha in vitro. The differential expression of LFA-1 by B-cell CLL and SLL and their degree of homotypic lymphocyte adhesion may account for the distinct anatomic compartmentalization and characteristic clinical behavior of these two morphologically and immunologically similar lymphoid malignancies.
Explorations in Off-Higway Vehicle (OHV) Recreation: a High School Driver Education Extension (2006)

The lessons within this curriculum have been designed to meet the following goals:\n● To increase knowledge about the natural world OHV recreationists will encounter in their exploration of Southern Nevada;\n● To increase knowledge of responsible use of OHVs and principles of Tread Lightly! and Leave No Trace (both are nonprofit organizations dedicated to increasing awareness about how to minimize impacts while enjoying public and private lands);\n● To increase awareness, knowledge, and understanding of land ethics;\n● To allow youth to analyze personal values regarding recreational experiences, including OHV use.
Role of Flow Enhancement Network during Filling of Fibrous Porous Media (2005)

An experimental and a numerical study of filling a system of porous medium/flow enhancement network is carried out, and its flow behavior is explored. Three types of filling systems are investigated: (i) porous medium without any flow enhancement network, (ii) porous medium coupled with a highly permeable layer (distribution layer), and (iii) porous medium with flow enhancement network consisting of channels. The porous medium/channel network system was of particular interest and hence the flow and the flow mechanisms have been characterized and analyzed by identifying their flow characteristics. Two flow mechanisms have been defined that depend on the channel size (volume) and number of channels (distance between channels). A parametric study reveals that the porous medium permeability plays a role in transition from one flow mechanism to the other. Finally, the repeatability of these filling processes has been addressed and the effect of the flow enhancement network on the repeatability of time to fill the porous media is discussed.
Ectopic expression of Hsp70 confers resistance and silencing its expression sensitizes human colon cancer cells to curcumin-induced apoptosis (2003)

We have shown earlier that heat shock renders human colon cancer cells resistant to curcumin-induced apoptosis, but the contribution of individual heat shock proteins (hsps) to this resistance has not been tested. High expression of hsp27 and hsp70 in breast, endometrial and gastric cancers has been associated with metastasis, poor prognosis and resistance to chemo- or radiotherapy. In this study, SW480 cells were transfected with hsp70 cDNA in either the sense or antisense orientation and stable clones were selected and tested for their sensitivity to curcumin. The cells were protected from curcumin-induced cell death by hsp70 while cells harboring antisense hsp70 (Ashsp70) were highly sensitive to curcumin. Curcumin-induced nuclear condensation was less in hsp70 but more in Ashsp70 cells when compared with control vector-transfected cells. Loss of mitochondrial transmembrane potential induced by curcumin was further accelerated by antisense hsp70 expression and hsp70 restored it partly. Ashsp70 cells released more cytochrome c, AIF and Smac from mitochondria upon curcumin treatment than control cells. hsp70 partly prevented the release of AIF but not the other proteins. Activation of caspases 3 and 9 induced by curcumin was also inhibited by hsp70, whereas more activation could be seen in Ashsp70 cells, although caspase 8 activation was unaffected by changes in hsp70 expression. Curcumin-induced cleavage of PARP and DFF45 was inhibited by hsp70 but enhanced in Ashsp70 cells. The present study demonstrates the potential of hsp70 in protecting SW480 cells from curcumin-induced apoptosis and highlights that silencing the expression of hsp70 is an effective approach to augment curcumin-based therapy in cancers that are resistant due to hsp70 expression.
Is bacterial translocation a clinically relevant phenomenon in burns? (2000)

Department of Surgery; Shriners Burns Hospital and The University of Texas Medical Branch; Galveston, Texas Address requests for reprints to: David N. Herndon, MD, Shriners Burns Hospital, 815 Market Street, Galveston, Texas 77550. E-mail: [email protected]
Long-lasting forms of synaptic potentiation in the mammalian hippocampus. (1996)

Y Y Huang, P V Nguyen, T Abel, and E R Kandel Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Safety and Immunogenicity of a Recombinant Parvovirus B19 Vaccine Formulated with MF59C.1 (2003)

A recombinant human parvovirus B19 vaccine (MEDI-491; MedImmune) composed of the VP1 and VP2 capsid proteins and formulated with MF59C.1 adjuvant was evaluated in a randomized, double-blind, phase 1 trial. Parvovirus B19-seronegative adults (n=24) received either 2.5 or 25 microg MEDI-491 at 0, 1, and 6 months. MEDI-491 was safe and immunogenic. All volunteers developed neutralizing antibody titers that peaked after the third immunization and were sustained through study day 364.
Characterization of murine intercellular adhesion molecule-2 (1996)

Rat mAbs were raised against murine intercellular adhesion molecule-2 (ICAM-2). Immune precipitation and purification reveal that the murine ICAM-2 glycoprotein is 55 kDa and is similar in size to human ICAM-2. ICAM-2 is expressed on a variety of leukocyte cell lines, including T and B lymphoma, mastocytoma, and macrophage lines. ICAM-2 is well expressed on endothelioma cell lines, and in contrast to ICAM-1, expression is not increased by inflammatory cytokines. One of the mAb to ICAM-2 partially or completely inhibits binding of cells expressing LFA-1 to purified ICAM-2, and binding of cells expressing ICAM-2 to purified LFA-1. The findings in the mouse are congruent with those in the human, suggesting functional conservation of ICAM-2 across species.
Five Recombinant Simian Immunodeficiency Virus Pseudotypes Lead to Exclusive Transduction of Retinal Pigmented Epithelium in Rat (2002)

The purpose of our study was to evaluate lentiviral vector-mediated rat retinal transduction using simian immunodeficiency virus (SIV) pseudotyped with envelope proteins from vesicular stomatitis virus G glycoprotein (VSV-G), Mokola virus G protein (MK-G), amphotropic murine leukemia virus envelope (4070A-Env), influenza A virus hemagglutinin (HA), lymphocytic choriomeningitis virus G protein (LCMV-G), and RD114 retrovirus envelope (RD114-Env). The six pseudotyped lentivirus vectors carried CMV-driven green fluorescent protein (GFP) or beta-galactosidase (beta-gal) reporter genes. Intravitreal and subretinal injections of each pseudotyped recombinant SIV were performed in cohorts of Wistar rats. Our results showed that no transgene expression was detected after intravitreal injection of each pseudotyped SIV vector. Also, no transduction could be detected following subretinal injection of RD114 pseudotyped SIV vectors. However, selective transduction of retinal pigment epithelium (RPE) cells was repeatedly obtained after subretinal delivery of VSV-G, MK-G, 4070A-Env, HA, and LCMV-G pseudotyped SIV. GFP expression was maximum as soon as 4 days postadministration for VSV-G, MK-G, 4070A-Env, and HA pseudotypes, with no evidence of pseudotransduction for VSV-G. Maximum transgene expression was observed 3 weeks postinjection for LCMV-6. Importantly, HA and VSV-G pseudotyped SIV lead to such a high level of transgene expression that GFP-related toxicity occurred. Therefore, when a high level of GFP synthesis is achieved, replacement of enhanced GFP (egfp, Aequorea victoria) by a low-toxicity GFP (Renilla reniformis) cDNA is necessary to allow long-term expression.
Copper-binding-site-null SOD1 causes ALS in transgenic mice: aggregates of non-native SOD1 delineate a common feature (2003)

Cu/Zn superoxide dismutase (SOD1), a crucial cellular antioxidant, can in certain settings mediate toxic chemistry through its Cu cofactor. Whether this latter property explains why mutations in SOD1 cause FALS has been debated. Here, we demonstrate motor neuron disease in transgenic mice expressing a SOD1 variant that mutates the four histidine residues that coordinately bind Cu. In-depth analyses of this new mouse model, previously characterized models and FALS human tissues revealed that the accumulation of detergent-insoluble forms of SOD1 is a common feature of the disease. These insoluble species include full-length SOD1 proteins, peptide fragments, stable oligomers and ubiquitinated entities. Moreover, chaperones Hsp25 and alphaB-crystallin specifically co-fractionated with insoluble SOD1. In cultured cells, all 11 of the FALS variants tested produced insoluble forms of mutant SOD1. Importantly, expression of recombinant peptide fragments of wild-type SOD1 in cultured cells also produced insoluble species, suggesting that SOD1 possesses elements with an intrinsic propensity to aggregate. Thus, modifications to the protein, such as FALS mutations, fragmentation and possibly covalent modification, may simply act to augment a natural, but potentially toxic, propensity to aggregate.
Pancreatic expression of interleukin-4 abrogates insulitis and autoimmune diabetes in nonobese diabetic (NOD) mice. (1996)

Diabetes in nonobese diabetic (NOD) mice is a T cell-dependent autoimmune disease. The destructive activities of autoreactive T cells have been shown to be tightly regulated by effector molecules. In particular, T helper (Th) 1 cytokines have been linked to diabetes pathogenesis, whereas Th2 cytokines and the cells that release them have been postulated to be protective from disease. To test this hypothesis, we generated transgenic NOD mice that express interleukin (IL) 4 in their pancreatic beta cells under the control of the human insulin promoter. We found that transgenic NOD-IL-4 mice, both females and males, were completely protected from insulitis and diabetes. Induction of functional tolerance to islet antigens in these mice was indicated by their inability to reject syngeneic pancreatic islets and the failure of diabetogenic spleen cells to induce diabetes in transgenic NOD-IL-4 recipients. Interestingly, however, islet expression of IL-4 was incapable of preventing islet rejection in overtly diabetic NOD recipient mice. These results demonstrate that the Th2 cytokine IL-4 can prevent the development of autoimmunity and destructive autoreactivity in the NOD mouse. Its ability to regulate the disease process in the periphery also indicates that autoimmune diabetes in NOD mice is not a systemic disease, and it can be modulated from the islet compartment.
DHT-assisted probabilistic exhaustive search in unstructured P2P networks (2008)

Existing replication strategies in unstructured P2P networks, such as square-root principle based replication, can effectively improve search efficiency. How to get optimal replication strategy, however, is not trivial. In this paper we show, through mathematical proof, that random replication strategy achieves the optimal results. By randomly distributing rather small numbers of item and query replicas in the unstructured P2P network, we can guarantee perfect search success rate comparable to exhaustive search with high probability. Our analysis also shows that the cost for such replication strategy is determined by the network size of a P2P system. We propose a hybrid P2P architecture which combines a lightweight DHT with an unstructured P2P overlay to address the problems of network size estimating and random peer sampling. We conduct comprehensive simulation to evaluate this design. Results show that our scheme achieves perfect search success rate with quite small overhead.
Bend-resistant design of conventional and microstructure fibers with very large mode area (2006)

Achieving very large mode area is a key goal in current research on microstructure and solid fibers for high power amplifiers and lasers. One particular design regime of recent interest has effective area over 1000 square microns and has effectively-single-mode operation ensured by bend losses of the higher-order modes. Simulations show that these fibers are extremely prone to bend-induced distortion and reduction in mode area. The calculated area reduction would significantly impact nonlinear impairments for bend radii relevant to any reasonable spooled package, and can be over 50 percent for bend radii tighter than 10cm. The parabolic-profile design has a natural immunity to bend-induced mode distortion and contraction, and shows superior performance in simulated fair comparisons with other fiber families, including microstructure fibers.
Dietary Restriction Benefits Learning and Motor Performance of Aged Mice (1987)

Female C3B10RF1 mice maintained on either a control (approximately 95 kcal/week) or restricted (approximately 55 kcal/week) diet since weaning were tested in a behavioral battery at 11 to 15 or 31 to 35 months of age (middle-aged vs. aged). Age-related declines observed among control groups in tests of motor coordination (rotorod) and learning (complex maze) were prevented by the restriction regime. In addition, diet restriction increased locomotor activity in a runwheel cage among mice of both ages but did not affect exploratory activity in a novel arena.