gebhart/patrepeval huggingface dataset:
Use of dielectrophoresis in the fabrication of an atomic force microscope tip with a carbon nanotube: a numerical analysis (2005)

To fabricate an atomic force microscope tip with an attached carbon nanotube (CNT), we simulated dielectrophoresis, produced by a nonuniform electric field. We calculated the dielectrophoretic force and torque of CNTs dispersed in a fluid. We then investigated the effect of various parameters such as the initial conditions of the CNT, the distance between the tip and the electrode, and the shape of the tip's apex. Using the results of the simulation, we examined the assembly conditions for achieving a high success rate. In particular, we found that the optimal distance between the tip and the electrode was 10 microm.
HPMPC (cidofovir), PMEA (adefovir) and Related Acyclic Nucleoside Phosphonate Analogues: A Review of their Pharmacology and Clinical Potential in the Treatment of Viral Infections (1997)

The acyclic nucleoside phosphonate (ANP) analogues are broad-spectrum antiviral agents, with potent and selective antiviral activity in vitro and in vivo. The prototype compounds are: ( S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC, cidofovir), which is active against a wide variety of DNA viruses; 9-(2-phosphonylmethoxyethyl)adenine (PMEA, adefovir), which is active against retro-, herpes- and hepadnaviruses, and ( R)-9-(2-phosphonylmethoxypropyl) adenine (PMPA), which is active against retro- and hepadnaviruses. The antiviral action of the ANP analogues is based on a specific interaction of the active diphosphorylated metabolite with the viral DNA polymerase. The long intracellular half-life of the active metabolite accounts for the optimal efficacy in infrequent dosing schedules. The potential of HPMPC as a broad-spectrum anti-DNA virus agent, as originally observed in vitro and in vivo, has been confirmed in clinical trials. HPMPC has recently been commercially released in the USA for the treatment of cytomegalovirus retinitis in AIDS patients. In addition, topical systemic HPMPC is being (or will be) explored for use against other herpesviruses (i.e. herpes simplex virus, Epstein-Barr virus, or varicella-zoster virus), by adenoviruses, or by human papilloma- or polyomaviruses. Intravenous HPMPC is associated with dose-dependent nephrotoxicity, that should be counteracted by prehydration and concomitant administration of probenecid, and by the application of an infrequent dosing schedule. The oral prodrug of PMEA, bis(pivaloyloxymethyl)-PMEA, is currently being evaluated in patients infected with human immunodeficiency virus (HIV) or hepatitis B virus. Finally, preclinical data on the efficacy of PMPA in animal retrovirus models point to its potential usefulness against HIV infections, when given either prophylactically or therapeutically in the treatment of established HIV infections.
Micro heat spreader enhanced heat transfer in MCMs (2002)

The peak thermal power generated in microelectronics assemblies has risen from less than 1 W/cm/sup 2/ in 1980 to greater than 40 W/cm/sup 2/ today, due primarily to increasing densities at both the IC and packaging levels. We have demonstrated enhanced heat transfer in a prototype Si substrate with a backside micro heat channel structure. Unlike conventional micro heat pipes, these channels are biaxial with a greater capacity for fluid transfer. Thermal modeling and preliminary experiments have shown an equivalent increase in substrate thermal conductivity to over 500 W/m.K, or a four times improvement. Optimization of the structure and alternative liquids will further increase the thermal conductivity of the micro heat channel substrate with the objective being polycrystalline diamond, or about 1200 W/m.K. The crucial design parameters for the micro heat channel system and the thermal characteristics of the system are covered.
Recent Trends in Covalent and Metal Organic Frameworks for Biomedical Applications (2018)

Materials science has seen a great deal of advancement and development. The discovery of new types of materials sparked the study of their properties followed by applications ranging from separation, catalysis, optoelectronics, sensing, drug delivery and biomedicine, and many other uses in different fields of science. Metal organic frameworks (MOFs) and covalent organic frameworks (COFs) are a relatively new type of materials with high surface areas and permanent porosity that show great promise for such applications. The current study aims at presenting the recent work achieved in COFs and MOFs for biomedical applications, and to examine some challenges and future directions which the field may take. The paper herein surveys their synthesis, and their use as Drug Delivery Systems (DDS), in non-drug delivery therapeutics and for biosensing and diagnostics.
Temperature sensitivity of the body surface over the life span (1998)

Detection thresholds to warming and cooling were measured in 13 regions of the body in 60 adults aged between 18 and 88 years. From these thresholds were constructed maps of thermal sensitivity homologous to body maps of spatial acuity (in the older literature two-point discrimination), long known to the somatosensory scientist. Maps of cold and warm sensitivity for young, middle-aged and elderly adults, show how sensitivity changes with age in the various body regions. Three characteristics emerge, irrespective of age: (1) sensitivity varies approximately 100-fold over the body surface. The face, especially near the mouth, is exquisitely sensitive, the extremities, by comparison, poor, other regions, intermediate. (2) All body regions are more sensitive to cold than to warm. (3) The better a region is at detecting cold, the better it is at detecting warm. With age, thermal sensitivity declines. The greatest changes take place in the extremities, especially the foot, where thresholds often become too large to measure. Central regions give up their sensitivity with age more slowly, and even (as in the lips) inconsequentially. Similar age-related changes have also previously been shown to characterize spatial acuity.
Identification and differential expression of a novel alternative splice isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells. (1992)

The gene for the beta A4-amyloid precursor protein (APP) consists of 19 exons which code for a typical N- and O-glycosylated transmembrane protein with four extracellular domains followed by the transmembrane domain and a short cytoplasmic domain. The beta A4-amyloid sequence is part of exons 16 and 17. Several APP isoforms can be generated by alternative splicing of exons 7 and 8, encoding domains with homologies to Kunitz-type protease inhibitors and the MRC OX-2 antigen, respectively. The mechanism by which the pathological beta A4 is generated is unknown, it is however a critical event in Alzheimer's disease and is distinct from the normally occurring cleavage and secretion of APPs within the beta A4 sequence. We report here for the first time considerable APP mRNA expression by rat brain microglial cells. In addition we showed by S1 nuclease protection and polymerase chain reaction analysis of reverse transcribed RNA (RT-PCR) that T-lymphocytes, macrophages, and microglial cells expressed a new APP isoform by selection of a novel alternative splice site and exclusion of exon 15 of the APP gene. This leads to a transmembrane, beta A4 sequence containing APP variant, lacking 18 amino acid residues close to the amyloidogenic region. The use of this novel alternative splice site alters the structure of APP in close proximity to the beta A4 region and thus may determine a variant, potentially pathogenic processing of leukocyte-derived APP in brain.
Cerebral small vessel disease-related protease HtrA1 processes latent TGF-β binding protein 1 and facilitates TGF-β signaling (2014)

High temperature requirement protein A1 (HtrA1) is a primarily secreted serine protease involved in a variety of cellular processes including transforming growth factor β (TGF-β) signaling. Loss of its activity causes cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), an inherited form of cerebral small vessel disease leading to early-onset stroke and premature dementia. Dysregulated TGF-β signaling is considered to promote CARASIL pathogenesis, but the underlying molecular mechanisms are incompletely understood. Here we present evidence from mouse brain tissue and embryonic fibroblasts as well as patient skin fibroblasts for a facilitating role of HtrA1 in TGF-β pathway activation. We identify latent TGF-β binding protein 1 (LTBP-1), an extracellular matrix protein and key regulator of TGF-β bioavailability, as a novel HtrA1 target. Cleavage occurs at physiological protease concentrations, is prevented under HtrA1-deficient conditions as well as by CARASIL mutations and disrupts both LTBP-1 binding to fibronectin and its incorporation into the extracellular matrix. Hence, our data suggest an attenuation of TGF-β signaling caused by a lack of HtrA1-mediated LTBP-1 processing as mechanism underlying CARASIL pathogenesis.
Distribution of the enantiomers of hydroxychloroquine and its metabolites in ocular tissues of the rabbit after oral administration of racemic‐hydroxychloroquine (1994)

The disposition of the enantiomers of hydroxychloroquine (HCQ) and its major metabolites in ocular tissues of rabbits has been studied. Both albino, New Zealand White (NZW), and pigmented animals were administered daily oral doses of rac-HCQ, (S)-HCQ or (R)-HCQ (20 mg/kg) over 1, 6, or 8 day periods or for 8 days followed by a 7-day washout period. At the end of the study periods, plasma and whole blood samples were collected and the rabbits were sacrificed. The eyes were collected, the aqueous humor removed with a syringe, and the eyes separated into the cornea, lens, vitreous body, iris, choroid-retina, sclera, and conjunctiva. The concentrations of (R)-HCQ, (S)-HCQ, and their respective metabolites were determined using a validated enantioselective liquid chromatographic assay. The data from these studies indicate that HCQ accumulated in both pigmented and nonpigmented ocular tissues. In the pigmented tissues, HCQ and its metabolites were bound to melanin and the binding was not enantiospecific. In the nonpigmented tissues and in the iris and retina-choroid of the NZW rabbits, the accumulation appeared to be the result of a reversible and enantioselective binding of HCQ and its metabolites to an unidentified biopolymer present in these ocular tissues.
Antibacterial action on pathogenic bacterial spore by green tea catechins (2005)

Abstract Antibacterial effects of catechins, the major green tea polyphenols, were studied using Clostridium and Bacillus spores. Incubation with crude catechins decreased the number of C botulinum and C butyricum spores but not B cereus spores. Furthermore, the effects of six catechin derivatives on spores were investigated. (−)‐Epicatechin gallate (ECg), (−)‐epigallocatechin (EGC), (−)‐epigallocatechin gallate (EGCg) and (+)‐gallocatechin gallate (GCg) were more effective in decreasing C botulinum and C butyricum spore numbers than (+)‐catechin (C) and (−)‐epicatechin (EC). The vegetative growth of C botulinum and B cereus was inhibited by crude extracts of the catechins. Specifically, purified GCg and EGCg inhibited the vegetative growth of C botulinum and B cereus . The inhibitory effect of ECg on B cereus was similar to that of GCg. However, toxin‐production by B cereus was not inhibited by catechin. Damage to the membrane of C butyricum spores by catechin derivatives was shown using fluorescent microscopy. This study shows that low concentrations of catechins, although requiring a long exposure time, inhibited the growth of bacterial spores. However, the effects of the purified derivatives of the catechins were not the same and GCg and EGCg were found to be the most potent. Spores that are generally resistant to many disinfectants were sensitive to catechins. Copyright © 2005 Society of Chemical Industry
Cannabinoids, inflammation, and fibrosis (2016)

Cannabinoids apparently act on inflammation through mechanisms different from those of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs). As a class, the cannabinoids are generally free from the adverse effects associated with NSAIDs. Their clinical development thus provides a new approach to treatment of diseases characterized by acute and chronic inflammation and fibrosis. A concise survey of the anti-inflammatory actions of the phytocannabinoids Δ<sup>9</sup>-tetrahydrocannabinol (THC), cannabidiol, cannabichromene, and cannabinol is presented. Mention is also made of the noncannabinoid plant components and pyrolysis products, followed by a discussion of 3 synthetic preparations-Cesamet (nabilone; Meda Pharmaceuticals, Somerset, NJ, USA), Marinol (dronabinol; THC; AbbVie, Inc., North Chicago, IL, USA), and Sativex (Cannabis extract; GW Pharmaceuticals, Cambridge United Kingdom)-that have anti-inflammatory effects. A fourth synthetic cannabinoid, ajulemic acid (AJA; CT-3; Resunab; Corbus Pharmaceuticals, Norwood, MA, USA), is discussed in greater detail because it represents the most recent advance in this area and is currently undergoing 3 phase 2 clinical trials by Corbus Pharmaceuticals. The endogenous cannabinoids, including the closely related lipoamino acids, are then discussed. The review concludes with a presentation of a possible mechanism for the anti-inflammatory and antifibrotic actions of these substances. Thus, several cannabinoids may be considered candidates for development as anti-inflammatory and antifibrotic agents. Of special interest is their possible use for treatment of chronic inflammation, a major unmet medical need.-Zurier, R. B., Burstein, S. H. Cannabinoids, inflammation, and fibrosis.
<title>Masking models and watermark undetection</title> (2001)

Masking models are mostly used in data compression algorithms and serve to shape the quantization noise. They were introduced in watermarking as to indicate the regions where the watermark could be introduced without perceptible artifacts. This allowed to embed more watermark energy, for a given absolute distortion constraint, than if no mask is used. Yet, little attention has been paid to the consequences of using these masks with respect to detection performance. In this work, it is shown that blind use of masking models facilitates the attacker's role, and eventually results in severe decreases of detection statistic at the detector, even for reasonable attack distortions.
Enteral Feeding in Burn Hypermetabolism: Nutritional and Metabolic Effects of Different Levels of Calorie and Protein Intake (1985)

Enteral nutrition was provided by continuous pump-controlled gastrostomy tube feeding for 14 days in 97 guinea pigs bearing a 30% full thickness burn. Seven defined combinations of caloric and protein intake were studied. With a caloric intake of 175 kcal/kg/day, equaling the measured energy expenditure, the animals receiving 10% of calories as protein had a significantly greater postburn weight loss (p less than 0.05) and muscle mass depletion (p less than 0.05), and a significantly lower muscle nitrogen concentration (p less than 0.05), serum albumin level (p less than 0.01) and liver nitrogen content (p less than 0.01). With the same caloric intake but with more than 20% of calories as protein, the weight loss and the muscle wasting were reduced, but not abolished, and the serum albumin level and liver nitrogen content were normalized. Also with the diets containing 200 kcal/kg/day the muscle tissue depletion could not be abolished. However, with this caloric intake, the animals given 20% of calories as protein had a lower weight loss and a higher serum albumin level (p less than 0.01), but also a greater fat infiltration of the liver (p less than 0.01). At both levels of caloric intake, the nitrogen balance correlated significantly with the level of nitrogen intake but did not correlate with the changes of body weight. The incidence of diarrhea was lowest in animals fed 20% protein calories at a caloric intake of 175 kcal/kg/day. All things considered, the best metabolic and nutritional results were obtained with diets containing 20 to 30% of calories as protein and providing a caloric intake that paralleled the measured energy expenditure.
Cutaneously applied 4-hydroxytamoxifen is not carcinogenic in female rats (1999)

Tamoxifen is widely used to treat oestrogen-dependent carcinoma of the breast. Previous long-term studies have shown that oral administration of tamoxifen induces hepatoproliferative lesions and hepatocellular tumours in rats. 4-hydroxytamoxifen is an active metabolite of tamoxifen undergoing clinical evaluation for the treatment of various non-malignant breast diseases by topical application. In the present study, 4-hydroxytamoxifen was administered daily by cutaneous application for 101 weeks to groups of 50 female Sprague-Dawley rats at 20, 140 or 1000 microg/kg/day. The product was applied with no occlusive bandage and oral ingestion was avoided by application of an Elizabethan collar for 6 h after administration. Treatment with 4-hydroxytamoxifen was clinically well tolerated and induced changes such as decreased food consumption and body weight gain, uterine and ovarian atrophy, mucification of vaginal epithelium and reduced mammary development, all of which were attributed to its pharmacological action. Mortality was significantly lower in the treated animals. The number of animals with palpable masses was similarly reduced. The incidence of mammary tumours and hypophyseal tumours was markedly lower in 4-hydroxytamoxifen-treated animals. The incidence of chronic tubulo-interstitial nephropathies, a common cause of mortality, was also lowered. There was no evidence of a carcinogenic action of 4-hydroxytamoxifen on the liver, genital organs or skin. Plasma levels of 4-hydroxytamoxifen were stable over the duration of the study and were proportional to the administered dose, exceeding clinical plasma levels by 60-fold at the high dose-level. In conclusion, 4-hydroxytamoxifen is not carcinogenic in the rat and reduces the incidence of spontaneous mammary and hypophyseal tumours.
Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini (2001)

Protein expression after delivery of plasmid DNA to the cell nucleus depends on the processes of transcription and translation. Cytotoxic gene-delivery systems may compromise these processes and limit protein expression. This situation is perhaps most prevalent in current nonviral polycationic gene-delivery systems in which the polycationic nature of the delivery system can lead to cytotoxicity. To approach the problem of creating nontoxic but effective gene-delivery systems, we hypothesized that by optimizing the balance between polymer cationic density with endosomal escape moieties, effective gene transfer with low cytotoxicity could be created. As a model system, we synthesized a series of polymers whose side-chain termini varied with respect to the balance of cationic centers and endosomal escape moieties. Specifically, by polymer-analogous amidation we conjugated imidazole groups to the epsilon-amines of polylysine in varying mole ratios (73.5 mol % imidazole, 82.5 mol % imidazole, and 86.5 mol % imidazole). The primary epsilon-amine terminus of polylysine served as a model for the cationic centers, whereas the imidazole groups served as a model for the endosomal escape moieties. These polymers condensed plasmid DNA into nanostructures <150 nm and possessed little cytotoxicity in vitro. Transfection efficiency, as measured by luciferase protein expression, increased with increasing imidazole content of the polymers in a nonlinear relationship. The polymer with the highest imidazole content (86.5 mol %) mediated the highest protein expression, with levels equal to those mediated by polyethylenimine, but with little to no cytotoxicity.
A Noninvasive Imaging Approach to Assess Plaque Severity: The Carotid Atherosclerosis Score (2010)

LRNC quantification may be an effective complementary strategy to stenosis for classifying carotid atherosclerotic disease severity. CAS forms the foundation for a simple imaging-based risk-stratification system in the carotid artery to classify severity of atherosclerotic disease.
Interferon Alpha Adjuvant Therapy in Patients With High-Risk Melanoma: A Systematic Review and Meta-analysis (2010)

In patients with high-risk cutaneous melanoma, IFN-alpha adjuvant treatment showed statistically significant improvement in both DFS and OS.
Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma (2003)

Little is known about mechanisms involved in skin-specific homing of cutaneous T-cell lymphoma (CTCL). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites. We investigated tissue samples and tumor cell suspensions of patients with CD30(+) CTCL (n = 8) and CD30(-) CTCL (mycosis fungoides, n = 6; Sézary syndrome, n = 6) for expression of the chemokine receptors CCR3, CCR4, and CCR8 and the CCR3 ligands eotaxin/CCL11, monocyte chemoattractant protein 3 (MCP-3)/CCL7, and RANTES (regulated on activation, normal T expressed and secreted)/CCL5. Of 8 CD30(+) CTCLs, 7 expressed CCR3, 4 CCR4, and none CCR8. CCR3 expression was not found in skin tissue samples from 12 CD30(-) CTCLs. Coexpression of CCR3 and CD30 was demonstrated by flow cytometry in tumor cell suspensions. Internalization experiments demonstrated functionality of CCR3 expressed by freshly isolated tumor cells. Actin polymerization as well as migration in response to eotaxin was demonstrated in a CD30(+) cutaneous lymphoma cell line. CCR3 ligand eotaxin/CCL11 was detected in lesional skin of CD30(+) CTCL by immunohistochemistry, preferentially in tumor cells. Eotaxin/CCL11 expression in tumor cells was confirmed by intracellular immunofluorescence. Analysis of cytokine expression pattern of CCR3-bearing infiltrating cells showed a predominance of interleukin-4 (IL-4) but not interferon-gamma (IFN-gamma) protein expression,1 consistent with a T-helper 2 (Th-2) profile. These results suggest that expression of CCR3 and its ligand eotaxin/CCL11 plays a role in the recruitment and retention of CD30(+) malignant T cells to the skin.
A universal information appliance (1999)

The consumer's view of a universal information appliance (UIA) is a personal device, such as a PDA (personal digital assistant) or a wearable computer that can interact with any application, access any information store, or remotely operate any electronic device. The technologist's view of the UIA is a portable computer, communicating over a bi-directional wireless link to an elaborate software system through which all programs, information stores, and electronic devices can export their interfaces to the UIA. Using an exported interface, the UIA can interoperate with the exporting entity, whether a home security system, a video cassette recorder, corporate application, or an automobile navigation system. Furthermore, interfaces presented by the UIA can be tailored to the user's context, such as the user's preferences, behavior, and current surroundings. The UIA programming model supports dynamic interface style and content triggered on activity detected from the user's real-world and software context. In this paper we describe the design and first implementation of a UIA, a PDA that, through a wireless link, can interact with any program, access any database, or direct most electronic devices through a remote interface. The UIA model uses IBM's TSpaces software package as the interface delivery mechanism and resource database, and as the network communication glue. TSpaces supports communication between the UIA and any peer over a dual-mode wireless link. Using a popular application example, we present a generalized architecture in which the UIA is the mobile user's software portal for interoperating with any peer: another UIA, a common network service, a legacy application, or an electronic device.