gebhart/patrepeval huggingface dataset:
LAN and I/O convergence: a survey of the issues (1994)

Local area networks and computer I/O are both interconnects that move information from one location to another. Despite this shared purpose, LANs have traditionally connected independent and widely separated computers. In contrast, computer I/O has traditionally connected a host to peripheral devices such as terminals, disks, and tape drives. Because these connection tasks were different, the architectures developed for one task were not suitable for the other. Consequently, the technologies used to implement one architecture could not address the issues faced by the other, and the technologies were seen as fundamentally different. However, an examination of the architectural requirements of modern I/O and LANs shows that the differences between the two technologies are now disappearing. We believe that LAN and I/O architectures are in fact converging, and that this convergence reflects significant changes in how and where computing resources are used. To illustrate this convergence and its implications, this article examines several modern LANs and channels.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Geometric packing constraints in egg phosphatidylcholine vesicles. (1978)

This investigation presents a quantitative analysis of the asymmetric transmembrane lipid packing geometry in egg phosphatidylcholine vesicles. The analysis uses hydrodynamic and nuclear magnetic resonance data obtained for homogeneous egg phosphatidylcholine vesicles and demonstrates that the average area per lipid head group and effective length of the lipid are greater on the outer monolayer than on the inner monolayer of the egg phosphatidylcholine vesicle. Results also indicate that the bilayer of the egg phosphatidylcholine vesicles has an asymmetrical interface through its center.
Effects of low-energy laser irradiation on bone remodeling during experimental tooth movement in rats (2000)

These findings suggest that low-energy laser irradiation can accelerate tooth movement accompanied with alveolar bone remodeling.
The vasoactive peptide maxadilan from sand fly saliva inhibits TNF-alpha and induces IL-6 by mouse macrophages through interaction with the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor. (1998)

Maxadilan is a vasodilatory peptide encoded by a gene cloned from Lutzomyia longipalpis salivary glands. In this study we investigated the effects of maxadilan on macrophage functions. Maxadilan treatment of LPS-stimulated BALB/c macrophages inhibited TNF-alpha release but increased IL-6. Further, it also induced IL-6 release in a dose-dependent manner from unstimulated macrophages. Maxadilan increased production of PGE2, and the inhibition of TNF-alpha was completely abrogated by indomethacin. Others have recently shown that maxadilan is a selective agonist of the pituitary adenylate cyclase-activating polypeptide (PACAP) type I receptor. Treatment with the receptor antagonist PACAP 6-38 blocked maxadilan activities on macrophages. The natural endogenous ligand, PACAP 38, had the same effects as maxadilan on TNF-alpha and IL-6 production. Finally, in a dose- and time-dependent fashion, maxadilan induced the intracellular accumulation of cAMP in macrophages. Taken together, the results presented here indicate a modulatory effect of ligands of PACAP type I receptor on cytokine production by macrophages and suggest that activation of this receptor, with the subsequent elevation of intracellular cAMP in macrophages, could participate in a negative-feedback mechanism that controls certain inflammatory responses.
Nanostructures and Surface Dewettability of Epoxy Thermosets Containing Hepta(3,3,3-trifluoropropyl) Polyhedral Oligomeric Silsesquioxane-Capped Poly(ethylene Oxide) (2007)

Hepta(3,3,3-trifluoropropyl) polyhedral oligomeric silsesquioxane (POSS)-capped poly(ethylene oxide) (PEO) was synthesized via the reaction of hydrosilylation between hepta(3,3,3-trifluoropropyl)hydrosilsesquioxane and allyl-terminated PEO. The POSS-capped PEO was characterized by means of Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. The organic-inorganic amphiphile was incorporated into epoxy resin to prepare the organic-inorganic nanostructured thermosetting composites. The morphology of the hybrid composites was characterized with field emission scanning electronic microscopy (FESEM) and transmission electronic microscopy (TEM). The formation of nanostructures was addressed on the basis of miscibility and phase behavior of the sub-components (viz. POSS and PEO chains) of the organic-inorganic amphiphile with epoxy after and before curing reaction. The static contact angle measurements indicate that the organic-inorganic nanocomposites displayed a significant enhancement in surface hydrophobicity as well as reduction in surface free energy. The atomic force microscopy (AFM) showed that there is significant migration of the POSS moiety at the surface of the thermosets. The improvement in surface properties was ascribed to the enrichment of the POSS moiety on the surface of the nanostructured thermosets, which was evidenced by X-ray photoelectron spectroscopy (XPS).
Interleukin-6 as a Therapeutic Target (2015)

Human IL6 is a cytokine produced by many cell types that has pleiotropic effects. In agreement, anti-IL6 therapy reduces inflammation, hepatic acute phase proteins, and anemia and has antiangiogenic effects. Blocking IL6 has demonstrated therapeutic efficacy with drug registration in Castleman disease and inflammatory diseases (rheumatoid arthritis) without major toxicity. Interestingly, the inhibition of C-reactive protein (CRP) production is a trustworthy surrogate marker of anti-IL6 therapy efficacy. Clinically registered IL6 inhibitors include siltuximab, an anti-IL6 mAb, and tocilizumab, an anti-IL6R mAb. In various cancers, in particular plasma cell cancers, large randomized trials showed no efficacy of IL6 inhibitors, despite a full inhibition of CRP production in treated patients in vivo, the numerous data showing an involvement of IL6 in these diseases, and initial short-term treatments demonstrating a dramatic inhibition of cancer cell proliferation in vivo. A likely explanation is the plasticity of cancer cells, with the presence of various subclones, making the outgrowth of cancer subclones possible using growth factors other than IL6. In addition, current therapeutic strategies used in these cancers already target IL6 activity. Thus, anti-IL6 therapeutics are able to neutralize IL6 production in vivo and are safe and useful in inflammatory diseases and Castleman disease.
Effect of Soluble Tissue Factor on the Kinetic Mechanism of Factor VIIa:  Enhancement of p-Guanidinobenzoate Substrate Hydrolysis (1996)

The mechanism by which the protein cofactor, tissue factor, enhances the activity of its cognate serine protease, coagulation factor VIIa (FVIIa), has been studied using the fluorogenic ester substrate 4-methylumbelliferyl p'-guanidinobenzoate (MUGB). Kinetic data were collected at pH 8.4 and pH 7.6 in the presence and absence of soluble tissue factor (sTF; recombinant human tissue factor containing only the extracellular domain). Pre-steady-state techniques allowed the determination of the individual rate constants for acylation (k2) and deacylation (k3) of the sTF.FVIIa complex as well as the dissociation constant for the noncovalent Michaelis complex with MUGB. Alternative methods were required for determination of these parameters for free FVIIa due to extremely slow hydrolysis of MUGB in the absence of sTF. Under all experimental conditions, deacylation was found to be rate-limiting. The major effect of sTF was to raise the affinity of FVIIa for MUGB (31-fold at pH 8.4 and 36-fold at pH 7.6); only minor changes in k2 and k3 were observed. Thus, we conclude that for the ester substrate MUGB, sTF exerts greater allosteric effects on substrate binding than on the later steps involved in the catalytic pathway.
Contrast Agent Mass Spectrometry Imaging Reveals Tumor Heterogeneity (2015)

Mapping intratumoral heterogeneity such as vasculature and margins is important during intraoperative applications. Desorption electrospray ionization mass spectrometry (DESI-MS) has demonstrated potential for intraoperative tumor imaging using validated MS profiles. The clinical translation of DESI-MS into a universal label-free imaging technique thus requires access to MS profiles characteristic to tumors and healthy tissues. Here, we developed contrast agent mass spectrometry imaging (CA-MSI) that utilizes a magnetic resonance imaging (MRI) contrast agent targeted to disease sites, as a label, to reveal tumor heterogeneity in the absence of known MS profiles. Human breast cancer tumors grown in mice were subjected to CA-MSI using Gadoteridol revealing tumor margins and vasculature from the localization of [Gadoteridol+K](+) and [Gadoteridol+Na](+) adducts, respectively. The localization of the [Gadoteridol+K](+) adduct as revealed through DESI-MS complements the in vivo MRI results. DESI-MS imaging is therefore possible for tumors for which no characteristic MS profiles are established. Further DESI-MS imaging of the flux of the contrast agent through mouse kidneys was performed indicating secretion of the intact label.
Oncofetal Antigen: A Tumor-Associated Fetal Antigen Immunogenic in Man<xref ref-type="fn" rid="FN2">2</xref> (1979)

Oncofetal antigen (OFA) has been defined with the use of human natural antibodies as a membrane antigen of human cancer cells that cross-reacts with human fetal brain tissues. The immunogen that elicits the antibody is unknown. The present study was undertaken to examine the immunogenicity of the OFA found on tumor cells. Postoperative melanoma patients were immunized with OFA-positive melanoma cells. Anti-OFA reactivities in the immunized sera were titrated by the immune adherence assay with the use of a known OFA-positive cultured melanoma cell line, M14, as target cell. Alloantibodies were excluded by absorption with lymphoblastoid cells autologous to M14. Anti-OFA antibody then was identified by absorption with fetal brain. In 6 months of immunization, 19 of 23 patients produced increased anti-OFA antibodies. The peak titers ranged from 1:16 to 1:2,048. Sera from 18 patients who were not immunized also were tested for 6 months postoperatively, and none had significant increases in antibody titers. The increase of anti-OFA antibody titer in response to the immunization with OFA-positive tumor cells suggests the immunogenic capability of tumor-related OFA in man.
A polymorphism of the human beta 2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. (1993)

We have recently identified several naturally occurring variants of the human beta 2-adrenergic receptor (beta 2AR). One of these polymorphisms, which is relatively uncommon, is a mutation occurring in the fourth transmembrane spanning domain, with Ile substituted for Thr at amino acid 164 within the proposed ligand binding pocket. This mutation is adjacent to Ser165 which has been predicted to interact with the beta-carbon hydroxyl group of adrenergic ligands. To determine the functional significance of this variant, we constructed by site-directed techniques a mutated beta 2AR (Ile164) with this substitution and expressed it in CHW-1102 cells. In the presence of guanine nucleotide, Ile164 displayed a lower binding affinity for epinephrine as compared with the wild-type beta 2AR (Ki = 1450 +/- 79 versus 368 +/- 39 nM; p < 0.001). A similarly decreased affinity was found with the catecholamines isoproterenol and norepinephrine, but not with dobutamine or dopamine which lack hydroxyl groups on their beta-carbons. In addition, antagonists without aromatic ring polar substituents displayed a decreased affinity for the mutated receptor. In agonist competition experiments conducted in the absence of guanine nucleotide, Ile164 failed to exhibit detectable high affinity binding, suggesting an impairment in the formation of the agonist-receptor-Gs complex. Consistent with this finding, functional coupling to Gs as determined in adenylyl cyclase assays was significantly (approximately 50%) depressed with Ile164 under both basal and agonist-stimulated conditions. beta 2AR sequestration, which is also triggered by agonist binding, was also found to be approximately 65% reduced in the Ile164 polymorphism. This study represents the first characterization of a naturally occurring mutation of a human adrenergic receptor. Our findings generally support the hypothesized role of this region of the receptor for ligand binding and receptor activation, as well as for establishing critical interactions for overall receptor conformation.
Manganese Taken Up into the CNS via the Olfactory Pathway in Rats Affects Astrocytes (2000)

Manganese (Mn), administered intranasally in rats, is effectively taken up in the CNS via the olfactory system. In the present study, Mn (as MnCl(2)) dissolved in physiological saline, was instilled intranasally in rats at doses of 0 (control), 10, 250, or 1000 microg. At the start of the experiment each rat received an intranasal instillation. Some rats were killed after one week without further treatment (the 1-w group), whereas the remaining rats received further instillations after one and two weeks and were killed after an additional week (the 3-w group). The brains were removed and either used for ELISA-determination of the astrocytic proteins glial fibrillary acidic protein (GFAP) and S-100b or histochemical staining of GFAP and S-100b, microglia (using an antibody against the iba1-protein) and the neuronal marker Fluoro-Jade. There were no indications that the Mn induced neuronal damage. On the other hand, the ELISA showed that both GFAP and S-100b decreased in the olfactory cortex, the hypothalamus, the thalamus, and the hippocampus of the 3-w group. The only effect observed in the 1-w group was a decrease of S-100b in the olfactory cortex at the highest dose. The immunohistochemistry showed no noticeable reduction in the number of astrocytes. We assume that the decreased levels of GFAP and S-100b are due to an adverse effect of Mn on the astrocytes, although this effect does not result in astrocytic demise. In the 3-w group, exposed to the highest dose of Mn, increased levels of GFAP and S-100b were observed in the olfactory bulbs, but these effects are probably secondary to a Mn-induced damage of the olfactory epithelium. Our results indicate that the astrocytes are the initial targets of Mn toxicity in the CNS.
Non‐invasive Analyte Access and Sensing through Eccrine Sweat: Challenges and Outlook circa 2016 (2016)

Abstract Despite the many ergonomic advantages of eccrine perspiration (sweat) compared to other possible biofluids (particularly in “wearable” devices), sweat remains an underrepresented source of biomarker analytes compared to the established biofluids blood, urine, and saliva. Upon closer comparison to other non‐invasive biofluids, the advantages may even extend beyond ergonomics: sweat might provide superior analyte information. A number of challenges, however, have historically kept sweat from its place in the pantheon of clinical samples. These challenges include very low sample volumes (nL to µL), unknown concentration due to evaporation, filtration and dilution of large analytes, mixing of old and new sweat, and the potential for contamination from the skin surface. More recently, rapid progress in “wearable” sweat sampling and sensing devices has resolved several of the historical challenges. However, this recent progress has also been limited to high concentration analytes (µM to mM) sampled at high sweat rates (&gt;1 nL/min/gland, e.g. athletics). Progress will be much more challenging as sweat biosensing moves towards use with sedentary users (low sweat rates or not sweating at all) and/or towards low concentration analytes (pM to nM). Addressing these unresolved challenges will require significant advances in sweat stimulation, sample collection efficiency, compact sensors, and likely more. Fortunately, none of the remaining challenges appear to be fundamentally blocking, and scientific and engineering innovations have the opportunity to enable broader application of sweat biosensing technology.
Functional Inactivation of the Human Guanylyl Cyclase C Receptor:  Modeling and Mutation of the Protein Kinase-like Domain (2001)

Receptor guanylyl cyclases possess an extracellular ligand-binding domain, a single transmembrane region, a region with sequence similar to that of protein kinases, and a C-terminal guanylyl cyclase domain. ATP regulates the activity of guanylyl cyclase C (GC-C), the receptor for the guanylin and stable toxin family of peptides, presumably as a result of binding to the kinase homology domain (KHD). Modeling of the KHD of GC-C indicated that it could adopt a structure similar to that of tyrosine kinases, and sequence comparison with other protein kinases suggested that lysine(516) was positioned in the KHD to interact with ATP. A monoclonal antibody GCC:4D7, raised to the KHD of GC-C, did not recognize ATP-bound GC-C, and its epitope mapped to a region in the KHD of residues 491--568 of GC-C. Mutation of lysine(516) to an alanine in full-length GC-C (GC-C(K516A)) dramatically reduced the ligand-stimulated activity of mutant GC-C, altered the ATP-mediated effects observed with wild-type GC-C, and failed to react with the GCC:4D7 monoclonal antibody. ATP interaction with wild-type GC-C converted a high-molecular weight oligomer of GC-C to a smaller sized oligomer. In contrast, GC-C(K516A) did not exhibit an alteration in its oligomeric status on incubation with ATP. We therefore suggest that the KHD in receptor guanylyl cyclases provides a critical structural link between the extracellular domain and the catalytic domain in regulation of activity in this family of receptors, and the presence of K(516) is critical for the possible proper orientation of ATP in this domain.
A humanin derivative, S14G‐HN, prevents amyloid‐β‐induced memory impairment in mice (2005)

Humanin (HN) is a 24-amino acid peptide that protects neuronal cells from death caused by Alzheimer's disease (AD)-related genes and amyloid-beta (Abeta). Multiple studies have revealed its biochemical and neuroprotective characteristics in vitro; however, little has been known regarding whether HN is effective in vivo in AD model systems. We examined the effect of S14G-HN, a 1,000-fold more potent derivative of HN in vitro, on amnesia induced by Abeta25-35 in mice. The Y-maze test revealed that at least 50 pmol of S14G-HN by intracerebroventricular injection prevented Abeta-induced impairment of short-term/spatial working memory; however, 5 nmol of S14A-HN, a neuroprotection-defective mutant in vitro, did not prevent Abeta-induced amnesia. These results are in agreement with the structure-function correlation shown previously in vitro. In the water-finding task, S14G-HN prevented prolongation of finding latency (the time to find water) observed in Abeta-amnesic mice, indicating that S14G-HN also blocked Abeta-induced impairment of latent learning. In accordance with these observations, immunohistochemical analysis showed that S14G-HN sustained the number of cholinergic neurons in the basal forebrain and the striata nearly to the normal level. Furthermore, genistein, a specific inhibitor of tyrosine kinases, blocked recovery from scopolamine-induced amnesia by S14G-HN, suggesting that certain tyrosine kinase(s) are involved in the inhibitory function of S14G-HN in vivo. Taking these findings together, we conclude that S14G-HN has rescue activity against memory impairment caused by AD-related insults in vivo by activating the same intracellular neuroprotective machinery as elucidated previously in vitro.
Current status of digital mammography for screening and diagnosis of breast cancer (2006)

Digital mammography is becoming the method of choice in the detection and characterization of breast cancer. Today, physical and technical protocols as well as large clinical trials are assessing the performance of this technology. A lot of work remains in the optimization of the different parts of the imaging chain: exposure setting, acceptability of detectors, dedicated post processing, viewing conditions and computer-aided detection. In parallel with these developments, newer digital technologies are being explored (tomosynthesis).
Reduction and prevention of vincristine-induced neuropathic pain symptoms by the non-benzodiazepine anxiolytic etifoxine are mediated by 3α-reduced neurosteroids (2009)

The central processing of peripheral nociceptive messages is highly controlled by the activity of local inhibitory networks in the spinal cord and supraspinal centers. Recently, it has been shown that endogenous 3alpha-reduced neurosteroids (3alphaNS) exert a significant spinal antinociception by potentiating GABA(A) receptor function. Because endogenous 3alphaNS can be produced in many relay structures of the nociceptive system, we tested the potential analgesic efficacy of promoting the production of neurosteroids by using etifoxine (ETX, 50mg/kg i.p.). This prescribed non-benzodiazepine anxiolytic was shown previously to stimulate neurosteroidogenesis in its early step after binding to the mitochondrial translocator protein complex (TSPO). Using an animal model of generalized neuropathic pain resulting from a 2-week treatment with the antitumoral agent vincristine sulfate (VCR, 0.1mg/kg i.p.), we show that injections of ETX (50mg/kg i.p.) given every day reduced the VCR-induced mechanical and thermal pain symptoms but also prevented their appearance, if used in prophylaxia 1 week before VCR. Both the curative and preventive effects of ETX on pain symptoms were mediated by the production of 3alphaNS as demonstrated in animals treated with the enzymatic inhibitor provera (6-medroxyprogesterone acetate; 20mg/kg s.c.). Altogether, this study shows for the first time that promoting 3alphaNS could be a possible therapeutic strategy to treat neuropathic pain symptoms. Since ETX is already available as an anxiolytic, its use in humans, provided that its analgesic properties are confirmed, could be rapidly considered.
Nerve growth factor and expression of its receptors in patients with diabetic neuropathy (2009)

Serum NGF level was positively associated with the presence of DPN but negatively associated with neuropathy severity in DPN patients. The change in serum NGF might be a consequence of, rather than a contributor to, the early development of DPN.