gebhart/patrepeval huggingface dataset:
Intranasal Gene Transfer by Chitosan–DNA Nanospheres Protects BALB/c Mice Against Acute Respiratory Syncytial Virus Infection (2002)

Respiratory syncytial virus (RSV) infection is often associated in infancy with life-threatening bronchiolitis, which is also a major risk factor for the development of asthma. At present, no effective prophylaxis is available against RSV infection. Herein, we describe an effective prophylactic intranasal gene transfer strategy utilizing chitosan-DNA nanospheres (IGT), containing a cocktail of plasmid DNAs encoding all RSV antigens, except L. A single administration of IGT (25 microg/mouse) induces expression of the mRNA and proteins of all antigens in the lung and results in a significant reduction of viral titers and viral antigen load after acute RSV infection of these mice. IGT-administered mice show no significant change in airway reactivity to methacholine and no apparent pulmonary inflammation. Furthermore, IGT results in significant induction of RSV-specific IgG antibodies, nasal IgA antibodies, cytotoxic T lymphocytes, and interferon-gamma production in the lung and splenocytes compared with controls. Together, these results demonstrate the potential of IGT against acute RSV infection.
Prognostic Value of Tumor-Infiltrating Dendritic Cells in Colorectal Cancer: Role of Maturation Status and Intratumoral Localization (2005)

The clinical significance of tumor-infiltrating dendritic cells has been reported in a variety of human solid tumors as shown by the correlations found between the presence of tumor-infiltrating dendritic cells and clinical prognosis. In this study, we evaluated whether there is an association between the presence and maturation status of tumor-infiltrating dendritic cells, T lymphocytes, and clinical course in 104 primary tumor samples of patients with colorectal cancer. Dendritic cells were identified with four different markers (S-100, HLA class II, CD208, and CD1a) in double immunohistochemistry, with laminin as second marker to support the exact localization. Tumor-infiltrating dendritic cells showed a distinct infiltration pattern based on their maturation status. CD1a-positive dendritic cells resided in the advancing tumor margins in relatively high numbers, whereas mature CD208-positive dendritic cells were sparsely present in the tumor epithelium but mainly distributed in the tumor stroma and advancing tumor margin. Furthermore, high infiltration of CD1a-positive dendritic cells in the tumor epithelium was significantly correlated to the infiltration of CD4 lymphocytes (P = 0.006). Patients with relatively high numbers of mature CD208-positive infiltrating dendritic cells in the tumor epithelium had a shorter overall survival (P = 0.004). In addition, patients with relatively high numbers of CD1a-positive dendritic cells in the advancing margin of the tumor had a shorter disease-free survival (P = 0.03). We found that tumor-infiltrating dendritic cells had preferential infiltration sites within a tumor, affected local tumor cell-immune cell interactions, and correlated to the clinical prognosis of colorectal cancer patients.
Specificity of Bacillus thuringiensisδ‐endotoxins (1989)

To study the molecular basis of differences in the insecticidal spectrum of Bacillus thuringienesis delta-endotoxins, we have performed binding studies with three delta-endotoxins on membrane preparations from larval insect mid-gut. Conditions for a standard binding assay were established through a detailed study of the binding of 125I-labeled Bt2 toxin, a recombinant B. thuringiensis delta-endotoxin, to brush border membrane vesicles of Manduca sexta. The toxins tested (Bt2, Bt3 and Bt73 toxins) are about equally toxic to M. sexta but differ in their toxicity against Heliothis virescens. Equilibrium binding studies revealed saturable, high-affinity binding sites on brush border membrane vesicles of M. sexta and H. virescens. While the affinity of the three toxins was not significantly different on H. virescens vesicles, marked differences in binding site concentration were measured which reflected the differences in in vivo toxicity. Competition experiments revealed heterogeneity in binding sites. For H. virescens, a three-site model was proposed. In M. sexta, one population of binding sites is shared by all three toxins, while another is only recognized by Bt3 toxin. Several other toxins, non-toxic or much less toxic to M. sexta than Bt2 toxin, did not or only marginally displace binding of 125I-labeled Bt2 toxin in this insect. No saturable binding of this toxin was observed to membrane preparations from tissues of several non-susceptible organisms. Together, these data provide new evidence that binding to a specific receptor on the membrane of gut epithelial cells is an important determinant with respect to differences in insecticidal spectrum of B. thuringiensis insecticidal crystal proteins.
Induction of ecto-5'-nucleotidase of rat cultured mesangial cells by interleukin-1 beta and tumour necrosis factor-alpha. (1990)

Because ecto-5'-nucleotidase activity of rat glomerular mesangial cells has been shown to increase upon interaction with macrophages in vitro, it was examined whether interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha), two macrophage-released cytokines, were responsible for this effect. IL-1 beta and TNF-alpha stimulated mesangial cell 5'-nucleotidase activity in a dose-dependent manner after treatment for 24 hr. Maximum increases reached 4.5 times and 1.7 times basal values for IL-1 beta (20 U/ml) and TNF-alpha (25 ng/ml), respectively. The effects of both cytokines were additive. Stimulation of 5'-nucleotidase by IL-1 beta and TNF-alpha was specific since the activity of other ectoenzymes, such as Mg2(+)-ATPase, was unchanged. Cycloheximide, a blocker of protein synthesis, suppressed the cytokine-dependent increase of 5'-nucleotidase activity. Cyclo-oxygenase inhibitors such as indomethacin and ibuprofen inhibited approximately 50% of the effects of both cytokines. Their inhibitory effect was abolished in the presence of prostaglandin E2 (PGE2). In addition, PGE2 itself produced a dose-related (0.1-10 microM) increase of 5'-nucleotidase activity with a maximum of 2.2 times basal value. Taken together, these results indicate that IL-1 beta, essentially, and TNF-alpha, to a lesser extent, regulate 5'-nucleotidase expression in the plasma membrane of cultured mesangial cells and that their effect depends in part on PGE2 synthesis. Therefore, macrophages, via their products of secretion acting on 5'-nucleotidase, could modulate adenosine production in the glomerular capillaries.
Development of Novel ACK1/TNK2 Inhibitors Using a Fragment-Based Approach (2015)

The tyrosine kinase ACK1, a critical signal transducer regulating survival of hormone-refractory cancers, is an important therapeutic target, for which there are no selective inhibitors in clinical trials to date. This work reports the discovery of novel and potent inhibitors for ACK1 tyrosine kinase (also known as TNK2) using an innovative fragment-based approach. Focused libraries were designed and synthesized by selecting fragments from reported ACK inhibitors to create hybrid structures in a mix and match process. The hybrid library was screened by enzyme-linked immunosorbent assay-based kinase inhibition and (33)P HotSpot assays. Systematic structure-activity relationship studies led to the identification of compound (R)-9b, which shows potent in vitro (IC50 = 56 nM, n = 3, (33)P HotSpot assay) and in vivo (IC50 < 2 μM, human cancer cell lines) ACK1 inhibition. Both (R)-9b and (S)-9b were stable in human plasma and displayed a long half-life (t(1/2) > 6 h).
Apolipoproteins of HDL can directly mediate binding to the scavenger receptor SR-BI, an HDL receptor that mediates selective lipid uptake (1997)

The class B type I scavenger receptor, SR-BI, binds HDL, mediates selective uptake of HDL cholesteryl esters by cultured cells, and its expression is coordinately regulated with steroidogenesis in several endocrine tissues (adrenal, ovary, testes). SR-BI can also bind LDL and anionic phospholipids, which raised the possibility that HDL apolipoproteins might not participate directly in HDL binding. We have examined the ability of individual human HDL apolipoproteins (apoA-I, apoA-II, and apoC-III) reconstituted into phospholipid/unesterified cholesterol complexes to bind to murine SR-BI (mSR-BI) expressed in stably transfected cultured cells. All three apolipoprotein/phospholipid/unesterified cholesterol complexes specifically associated with mSR-BI expressing cells with high affinity and competed for the binding of HDL, while apolipoprotein-free complexes did not. Furthermore, lipid-free forms of these soluble apolipoproteins also competed for HDL and apolipoprotein/ phospholipid/cholesterol complex association with mSR-BI, but locust high density lipophorin and bovine serum albumin were not effective competitors.Thus, all three of the HDL apolipoproteins (apoA-I, apoA-II, and apoC-III) tested can directly mediate binding to mSR-BI, and this multiligand apolipoprotein receptor may be responsible for at least some of the multilipoprotein and apolipoprotein binding activity previously observed in cells and tissues.
Endlessly single-mode photonic crystal fiber (1997)

We made an all-silica optical fiber by embedding a central core in a two-dimensional photonic crystal with a micrometer-spaced hexagonal array of air holes. An effective-index model confirms that such a fiber can be single mode for any wavelength. Its useful single-mode range within the transparency window of silica, although wide, is ultimately bounded by a bend-loss edge at short wavelengths as well as at long wavelengths.
Astatine-211-Labeled Radiotherapeutics An Emerging Approach to Targeted Alpha-Particle Radiotherapy (2000)

Targeted radiotherapy or endoradiotherapy is an appealing approach to cancer treatment because of the potential for delivering curative doses of radiation to tumor while sparing normal tissues. Radionuclides that decay by the emission of alpha-particles such as the heavy halogen astatine-211 (211At) offer the exciting prospect of combining cell-specific molecular targets with radiation having a range in tissue of only a few cell diameters. Herein, the radiobiological advantages of alpha-particle targeted radiotherapy will be reviewed, and the rationale for using 211At for this purpose will be described. The chemistry of astatine is similar to that of iodine; however, there are important differences which make the synthesis and evaluation of 211At-labeled compounds more challenging. Perhaps the most successful approach that has been developed involves the astatodemetallation of tin, silicon or mercury precursors. Astatine-211 labeled agents that have been investigated for targeted radiotherapy include [211At]astatide, 211At- labeled particulates, 211At-labeled naphthoquinone derivatives, 211At-labeled methylene blue, 211At-labeled DNA precursors, meta-[211At]astatobenzylguanidine, 211At-labeled biotin conjugates, 211At-labeled bisphosphonates, and 211At-labeled antibodies and antibody fragments. The status of these 211At-labeled compounds will be discussed in terms of their labeling chemistry, cytotoxicity in cell culture, as well as their tissue distribution and therapeutic efficacy in animal models of human cancers. Finally, an update on the status of the first clinical trial with an 211At-labeled targeted therapeutic, 211At-labeled chimeric anti-tenascin antibody 81C6, will be provided.
CXCL10 plays a key role as an inflammatory mediator and a non-invasive biomarker of non-alcoholic steatohepatitis (2014)

We demonstrate for the first time that CXCL10 plays a pivotal role in the pathogenesis of experimental steatohepatitis. CXCL10 maybe a potential non-invasive biomarker for NASH patients.
A human inhibitor of tumor necrosis factor alpha. (1988)

Urine of some febrile patients exhibits a TNF-alpha inhibitory activity (TNF-alpha INH), sensitive to heat and trypsin, with an apparent mol wt of 40-60 X 10(3) and a pI range of 5.5-6.1. As for the Il-1 INH, the TNF INH activity involves a competitive mechanism of action suggesting the existence of a family of negative feedback-regulating molecules interfering with cytokines actions.
Kidney Regeneration in Mammals (2014)

Kidney regeneration in mammals is feasible but limited and may be enhanced by multitargeting key mechanisms.
Subantimicrobial Dose Doxycycline for Acne and Rosacea (2003)

Acne vulgaris and rosacea present therapeutic challenges due to their chronicity, potential for disfigurement, and psychosocial impact. Although pathophysiologically distinct, both conditions have major inflammatory components. Consequently, topical and systemic antimicrobial agents are routinely prescribed for extended periods. Emergence of resistant strains of Propionibacterium acnes, adverse events, and compliance issues associated with chronic systemic tetracycline use have led to new treatment approaches. At subantimicrobial doses, tetracyclines reduce inflammation via anticollagenolytic, antimatrix-degrading metalloproteinase, and cytokine down-regulating properties. Subantimicrobial dose (SD) doxycycline (Periostat 20 mg) has clinical utility in periodontitis and has been investigated in a double-blind, placebo-controlled trial in the treatment of moderate facial acne as well as in an open label study in the treatment of rosacea. The results of subantimicrobial dose doxycycline treatment in early trials support its benefits and further investigation in acne and rosacea.
Field trapping of male midges Rheotanytarsus kyotoensis (Diptera : Chironomidae) by sounds (1992)

The swarming males of Rheotanytarsus kyotoensis were caught by sound traps in the field. The swarms were formed at 0.3-2.5m above the water surface of a river. More than 97% of R. kyotoensis caught from the swarm were males. The swarming males were mainly caught by the sound traps emitting the sound of frequencies between 180 and 300Hz during the experimental period from October to December. However, the most attractive frequency changed to ca. 11Hz/℃ between 8.8 and 18.2℃. Moreover, the swarming males responded to a narrow range of sound frequency at an ambient air temperature.
Role of surface proteins in staphylococcal adherence to fibers in vitro. (1989)

To study the role of surface proteins in the adherence of Staphylococcus aureus to fibers that are used in tampon and surgical gauze pad manufacture, we have developed an adherence assay with S. aureus cells and cotton and rayon fibers. Results suggest that staphylococcal adherence is dependent on both the substrate and the material used to coat these fibers. Scanning electron micrographs supported the adherence results and revealed more cells on the surface of cotton than rayon fibers. Treatment of staphylococcal cells with proteolytic enzymes significantly reduced binding to pure cotton and detergent-treated cotton fibers. Immunoblot analysis of cell wall proteins suggested that surface proteins in the mol wt range of 120-220 kD were involved in the adherence of S. aureus to cotton fibers. Although the adherence of S. aureus to cotton fibers alone appeared to be mediated through surface charge or hydrophobic interactions, bacterial binding to fibers which have been pretreated with defibrinated blood appeared to be more specific and independent of the surface constituents of the fibers. The results of these studies implicate staphylococcal surface proteins in the adherence of S. aureus to commercially available tampon fibers and surgical gauze pads.
Reduced brain activation in violent adolescents during response inhibition (2016)

Deficits in inhibitory control have been linked to aggression and violent behaviour. This study aimed to observe whether violent adolescents show different brain activation patterns during response inhibition and to ascertain the roles these brain regions play. A self-report method and modified overt aggression scale (MOAS) were used to evaluate violent behaviour. Functional magnetic resonance imaging was performed in 22 violent adolescents and 17 matched healthy subjects aged 12 to 18 years. While scanning, a go/no-go task was performed. Between-group comparisons revealed that activation in the bilateral middle and superior temporal gyrus, hippocampus, and right orbitofrontal area (BA11) regions were significantly reduced in the violent group compared with the control group. Meanwhile, the violent group had more widespread activation in the prefrontal cortex than that observed in the control group. Activation of the prefrontal cortex in the violent group was widespread but lacking in focus, failing to produce intensive activation in some functionally related regions during response inhibition.
EXTRACTION OF OIL FROM CORN DISTILLERS DRIED GRAINS WITH SOLUBLES (1998)

The feasibility of extracting crude corn oil from distillers dried grains with solubles (DDGS) of corn wasstudied using anhydrous ethanol as a solvent. Total solids, fat, glycerol, and protein extracted from DDGS increased withincreased ethanol-to-DDGS ratio at 50C and an extraction time of 30 min. However, ethanol-to-DDGS ratios above6 mL ethanol per g DDGS did not significantly increase the amount of oil extracted, but did increase glycerol extraction.At the optimum ethanol-to-DDGS ratio of 6, about 50% of the crude corn oil can be extracted from DDGS in a singleextraction step.
Informational Paper: Modulation of the Host Response in Periodontal Therapy (2002)

This paper was prepared by the Research, Science, and Therapy Committee of the American Academy of Periodontology to provide the dental profession an overview of current and potential methods to modulate the host response in the treatment of periodontal diseases. Specifically, it discusses components of periodontal disease pathogenesis (i.e., immune and inflammatory responses, excessive production of matrix metalloproteinases and arachidonic acid metabolites, and regulation of bone metabolism) and their modulation. J Periodontol 2002;73:460-470.
Aripiprazole as Augmentation Treatment of Refractory Generalized Anxiety Disorder and Panic Disorder (2008)

These data provide preliminary evidence that aripiprazole may be a useful augmentation strategy for individuals with generalized anxiety disorder or panic disorder who show a limited response to initial pharmacotherapy.
On the controllability of nanorod alignment in magnetic fluids (2008)

The controllability of orienting colloidal nanorods suspended in ferrofluid is investigated as a function of the external magnetic field intensity and the concentration of conventional ferrofluid. The expected value for the nanorod orientation was derived from the competition between the potential energy variation of an ellipsoid in a uniform magnetic field and randomizing rotational thermal energy. The agreement between experiment and theory is found to be quite accurate when the measured nanorod volume and vendor-supplied values for the ferrofluid’s magnetic susceptibility are used as inputs in the model. Our investigations confirm that local magnetic susceptibility surrounding the nanorod is equivalent to the bulk fluid susceptibility, indicating that ferrofluid composed of 12nm iron oxide particles can be treated as a continuum on the 100–1000nm length scale.
Progress in Neutron Capture Therapy for Cancer (1992)

Despite the many advances made in the diagnosis and therapy of cancer, the mortality rate is still about half that of the incidence rate. However, the odds are not evenly distributed. Prognosis for so
Administration of Dehydroepiandrosterone to Burned Mice Preserves Normal Immunologic Competence (1993)

Burned individuals display a reduced ability to elicit cellular and humoral immune responses and a depression in the vitro production of certain T-cell lymphokines. Treatment of burned mice with 100 micrograms of dehydroepiandrosterone within 1 hour after injury resulted in preserving a completely normal capacity to produce T-cell-derived lymphokines and to generate cellular immune responses. In addition, dehydroepiandrosterone-treated thermally injured mice demonstrated an above-normal ability to resist an induced infection with the intracellular pathogen, Listeria monocytogenes. Dehydroepiandrosterone-treated animals also did not exhibit the sustained plasma levels of interleukin 6 that normally accompany thermal injury and infection. Because of its antiglucocorticoid effects and positive immunoregulatory influences, we believe dehydroepiandrosterone to be a beneficial form of therapy for thermally injured individuals.
The Gabriel Synthesis of Primary Amines (1968)

Abstract Reaction of potassium phthalimide with halogenoalkanes and with a variety of other alkylating agents leads to the N‐alkylphthalimide. N‐Substituted phthalimides may be converted into the corresponding primary amine by hydrolysis or hydrazinolysis. The scope and limitations of these reactions, which together constitute the Gabriel Synthesis of primary amines, are reviewed.
The specific role of chemokines in atherosclerosis (2007)

Atherosclerosis is a chronic inflammatory disease that represents the primary cause of heart disease and stroke. The recruitment of inflammatory cells in the intima is an essential step in the development and progression of atherosclerosis. This process is triggered by local production of chemokines and chemokine receptors from activated endothelial cells and inflammatory cells. Various members of the CC chemokine family (e.g. MCP-1/CCL2) as well as CXC family (e.g. IL-8/CCL8, IP-10/CXCL10, SDF-1/CXCL12) and, more recently, fractalkine/CX3CL1 have been implicated in atherosclerosis development. Latest findings in animal models suggest that blocking chemokine/chemokine receptor interactions may serve as a suitable approach to treat atherosclerosis. Likewise, chemokine antagonists that inhibit leukocyte recruitment could particularly be interesting to treat inflammation in response to myocardial infarction, the major consequence of atherosclerosis.
Design and synthesis of 18F-labeled neurotoxic analogs of MPTP (1993)

We report on the synthesis of two fluorine-18 labeled analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A piperidyl triazene was fluorinated to produce [18F]-1-methyl-4-(2-fluorophenyl)-1,2,3,6-tetrahydropyridine (2'-F-MPTP, 12) in very low yield, and 1-methyl-4-[2-(fluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine (2'-FCH2-MPTP, 11) was labeled with 18F by nucleophilic displacement of the corresponding chloride in 60% yield. The biodistribution in mice of the latter radiotracer and its oxidation to 1-methyl-4-[2-(fluoromethyl)phenyl]pyridinium (2'-FCH2-MPP+, 6) is also reported. The kinetics of oxidation of 2'-FCH2-MPTP and its solvolysis products (the corresponding 2'-hydroxymethyl and 2'-chloromethyl analogs) by rat liver monoamine oxidase were investigated. 2'-FCH2-MPTP accumulated to a useful degree in the brain, was oxidized by monoamine oxidase in vitro, was converted to the oxidation product in brain in vivo, and had a neurotoxic potency similar to that of MPTP. We feel it may be useful as an 18F-labeled radiopharmaceutical for positron tomographic studies of the mechanisms of MPTP toxicity.