gebhart/patrepeval huggingface dataset:
Function and clinical use of interleukin-12 (1997)

Interleukin-12 is a heterodimeric cytokine produced by phagocytic cells, professional antigen-presenting cells such as dendritic cells and skin Langerhans cells, and B cells. Interleukin-12 production is induced by bacteria, intracellular pathogens, fungi, viruses, or their products in a T-cell-independent pathway or a T-cell-dependent pathway, the latter mediated through CD40 ligand-CD40 interaction. Interleukin-12 is produced rapidly after infection and acts as a proinflammatory cytokine eliciting production of interferon gamma, by T and natural killer cells, which activates phagocytic cells. The production of interleukin-12 is strictly regulated by positive and negative feedback mechanisms. If interleukin-12 and interleukin-12-induced interferon gamma are present during early T-cell expansion in response to antigen, T-helper type-1 cell generation is favored and generation of T-helper type-2 cells is inhibited. Thus interleukin-12 is also a potent immunoregulatory cytokine that promotes T-helper type-1 differentiation and is instrumental in the T-helper type-1-dependent resistance to infections by bacteria, intracellular parasites, fungi, and certain viruses. By inhibiting T-helper type-2 cell response, interleukin-12 has a suppressive effect on allergic reactions; by promoting T-helper type-1 responses it participates in the immunopathology responsible for several organ-specific autoimmune diseases. Viruses inducing a permanent or transient immunodepression, such as HIV and measles, may act, in part, by suppressing interleukin-12 production. Because of its ability to enhance resistance to several infectious diseases and to act as an adjuvant in vaccination, and because of its powerful antitumor effect in vivo, interleukin-12 is currently in clinical trials in cancer patients and HIV-infected patients, and it is being considered for therapeutic use in other diseases.
[Cardiovascular manifestations of obstructive sleep apnea. Effects of the treatment]. (1998)

There is a direct relationship between obstructive sleep apnea and high blood pressure, ischemic heart disease and cerebrovascular disorders. Obstructive sleep apnea, defined as an intermittent complete or partial upper airway obstruction during sleep, occurs in approximately 4% of adults, although some authors suggest a 9% prevalence in women and 24% in men. Due to its high frequency, this condition must be considered as another cardiovascular risk factor that should be prevented and adequately treated.
Monolithic integration of In 0.2 Ga 0.8 Asvertical-cavity surface-emitting lasers with resonance-enhanced quantum well photodetectors (1996)

Vertical-cavity surface-emitting lasers (VCSELs) have been monolithically integrated with resonance-enhanced photo-detectors (REPDs) using a single epilayer design, to produce a simple array of sources and detectors for optical interconnect applications. The detectors, which contain a three quantum well InGaAs absorption region, achieve quantum efficiencies as high as 85%, and the VCSELs achieved threshold current densities as low as 850 A/cm2 and differential quantum efficiencies as high as 50%.
Orbital Angular Momentum (OAM) Multiplexing: An Enabler of a New Era of Wireless Communications (2017)

This paper explores the potential of orbital angular momentum (OAM) multiplexing as a means to enable high-speed wireless transmission. OAM is a physical property of electro-magnetic waves that are characterized by a helical phase front in the propagation direction. Since the characteristic can be used to create multiple orthogonal channels, wireless transmission using OAM can enhance the wireless transmission rate. Comparisons with other wireless transmission technologies clarify that OAM multiplexing is particularly promising for point-to-point wireless transmission. We also clarify three major issues in OAM multiplexing: beam divergence, mode-dependent performance degradation, and reception (Rx) signal-to-noise-ratio (SNR) reduction. To mitigate mode-dependent performance degradation we first present a simple but practical Rx antenna design method. Exploiting the fact that there are specific location sets with phase differences of 90 or 180 degrees, the method allows each OAM mode to be received at its high SNR region. We also introduce two methods to address the Rx SNR reduction issue by exploiting the property of a Gaussian beam generated by multiple uniform circular arrays and by using a dielectric lens antenna. We confirm the feasibility of OAM multiplexing in a proof of concept experiment at 5.2 GHz. The effectiveness of the proposed Rx antenna design method is validated by computer simulations that use experimentally measured values. The two new Rx SNR enhancement methods are validated by computer simulations using wireless transmission at 60 GHz.
The Epstein-Barr virus latent membrane protein 1 induces expression of the epidermal growth factor receptor (1995)

The Epstein-Barr virus (EBV)-encoded LMP1 protein is an important component of the process of transformation by EBV. LMP1 is essential for transformation of B lymphocytes, most likely because of its profound effects on cellular gene expression. Although LMP1 is expressed in the majority of nasopharyngeal carcinoma (NPC) tumors, the effect of LMP1 on cellular gene expression and its contribution to the development of malignancy in epithelial cells is largely unknown. In this study the effects of LMP1 on the expression and tyrosine kinase activity of the epidermal growth factor receptor (EGFR) were investigated in C33A human epithelial cells. Stable or transient expression of LMP1 in C33A cells increased expression of the EGFR at both the protein and mRNA levels. In contrast, expression of the EGFR was not induced by LMP1 in EBV-infected B lymphocytes. Stimulation of LMP1-expressing C33A cells with epidermal growth factor (EGF) caused rapid tyrosine phosphorylation of the EGFR (pp170) as well as several other proteins, including pp120, pp85, pp75, and pp55, indicating that the EGFR induced by LMP1 is functional. LMP1 also induced expression of the A20 gene in C33A epithelial cells. In C33A cells, LMP1 expression increased the proliferative response to EGF, as LMP1-expressing C33A cells continued to increase in number when plated in serum-free media supplemented with EGF, while the neo control cells exhibited very low levels of viability and did not proliferate. Immunoblot analysis of protein extracts from nude mouse-passaged NPC tumors also demonstrated that the EGFR is overexpressed in primary NPC tumors as well as those passaged in nude mice. This study suggests that the alteration in the growth patterns of C33A cells expressing LMP1 is a result of increased proliferative signals due to enhanced EGFR expression, as well as protection from cell death due to LMP1-induced A20 expression. The induction of EGFR and A20 by LMP1 may be an important component of EBV infection in epithelial cells and could contribute to the development of epithelial malignancies such as NPC.
Mannose‐binding lectin in innate immunity: past, present and future (2006)

The human collectin, mannose-binding lectin (MBL), is an important protein of the humoral innate immune system. With multiple carbohydrate-recognition domains, it is able to bind to sugar groups displayed on the surfaces of a wide range of microorganisms and thereby provide first-line defence. Importantly, it also activates the complement system through a distinctive third pathway, independent of both antibody and the C1 complex. Three single point mutations in exon 1 of the expressed human MBL-2 gene appear to impair the generation of functional oligomers. Such deficiencies of functional protein are common in certain populations, e.g. in sub-Saharan Africa, but virtually absent in others, e.g. indigenous Australians. MBL disease association studies have been a fruitful area of research and implicate a role for MBL in infective, inflammatory and autoimmune disease processes. Overall, there appears to be a genetic balance in which individuals generally benefit from high levels of the protein. However, in certain situations, reduced levels of circulating MBL may be beneficial to the host and this may explain the persistence of the deleterious gene polymorphisms in many population groups.
A VHF Implementation of a LINC Amplifier (1976)

LINC is a technique that uses signal processing to produce Linear amplification of bandpass signals with grossly Nonlinear circuit Components. The important signal processing functions in LINC are forming two constant envelope phase modulated signal components from the bandpass input signal and recombining the amplified components to produce an amplified replica of the input signal. Two- and three-tone laboratory tests of a complete LINC amplifier show that, at full output, spurious levels 40 dB below tone level are achievable for tone spacings of 100 kHz. Because the laboratory model is operated at relatively low frequencies (hundreds of MHz), scaling up in frequency should result in a LINC with < 40 dB spurious over a considerably wider band. Lower spurious levels or bandwidths of several tens of MHz will require a <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\sin^{-1}</tex> phase modulator that is less sensitive to delay in a feedback loop and a wider-bandwidth lower-distortion input limiter.
Studies on the properties of the inextractable proteoglycans from bovine nasal cartilage. (1983)

Bovine nasal cartilage was repeatedly extracted with the dissociative solvent, 4 M guanidinium chloride. About 25% of the total tissue proteoglycans could not be solubilized as judged by galactosamine analysis. The inextractable proteoglycan could be at least partially solubilized by treating the guanidine-extracted tissue with reagents which completely or partially degraded the proteoglycan protein core. Digestion with papain or cyanogen bromide completely solubilized the tissue and released all of the galactosamine-containing material while trypsin or hydroxylamine treatment left the cartilage macroscopically unchanged and extracted about 50% of the residual galactosamine. The degradatively solubilized material was compared to that extracted with guanidinium chloride. The papain-released glycosaminoglycan chains from the two proteoglycan preparations were similar with respect to size, degree of sulfation, position of sulfation, and hexosamine content. Furthermore, the fragments released from the cartilage residue by either cyanogen bromide, trypsin, or hydroxylamine treatment were of the same size, as judged by gel chromatography, as those derived from similarly digested guanidine-extracted proteoglycan. Trypsin digestion also released the keratan sulfate-enriched peptide as well as peptides from the hyaluronic acid-binding region. By the methods used, the inextractable proteoglycan appears to be similar to the fraction which is readily soluble under dissociative conditions and thus may be held tightly within the tissue by a nonspecific mechanism(s) such as entanglement in the collagen fibril network.
pH-Dependent Fluorescence of a Heterologously Expressed Aequorea Green Fluorescent Protein Mutant: In Situ Spectral Characteristics and Applicability to Intracellular pH Estimation, (1998)

The green fluorescent protein of Aequorea victoria (GFP) is a natural peptide chromophore without substrate or cofactor requirements for fluorescence. In vitro, a recombinant F64L/S65T GFP mutant (GFPmut1) exhibited pH sensitive fluorescence within the physiologic range. When heterologously expressed in BS-C-1 cells or rabbit proximal tubule cells, uniform cytosolic and nuclear fluorescence was observed. Cytosolic fluorescence constituted over 80% of the total. Excitation scanning of transfected cells revealed two GFPmut1-specific regions that were pH-sensitive over the physiologic range, and each region exhibited a unique pH "bias" in fluorescence emission. Excitation at or near the expected maximum of 488 nm (region II) uniformly resulted in fluorescence that was preferentially altered at acidic pH. In contrast, a novel "wild-type" excitation peak at 400 nm (region I) resulted in alkaline-biased fluorescence similar to that described for the wild-type chromophore in vitro, suggesting that wild-type spectral features disrupted in vitro by mutagenesis may be recovered in intact cells. Calibration of intracellular pH (pHi) with in situ fluorescence following excitation in either region revealed a semilogarithmic relationship between fluorescence intensity and pH within the physiologic range. We therefore measured pHi changes attributable to altered Na/HCO3 cotransport (NBC) activity both in GFPmut1-expressing cells and in paired untransfected cells loaded with BCECF. Basal NBC activity was the same in each group, as was the stimulation of activity by 10% CO2, thus validating the utility of GFPmut1 as a fluorescent probe for pHi and establishing a novel, useful, and practical application for GFPmut1 in monitoring pHi in real time.
Exenatide (2006)

Exenatide offers a novel treatment option for patients with type 2 diabetes mellitus who are refractory to metformin or sulfonylurea therapy or both.
Safe Direct Current Stimulation to Expand Capabilities of Neural Prostheses (2013)

While effective in treating some neurological disorders, neuroelectric prostheses are fundamentally limited because they must employ charge-balanced stimuli to avoid evolution of irreversible electrochemical reactions and their byproducts at the interface between metal electrodes and body fluids. Charge-balancing is typically achieved by using brief biphasic alternating current (AC) pulses, which typically excite nearby neural tissues but cannot efficiently inhibit them. In contrast, direct current (DC) applied via a metal electrode in contact with body fluids can excite, inhibit and modulate sensitivity of neurons; however, chronic DC stimulation is incompatible with biology because it violates charge injection limits that have long been considered unavoidable. In this paper, we describe the design and fabrication of a Safe DC Stimulator (SDCS) that overcomes this constraint. The SCDS drives DC ionic current into target tissue via salt-bridge micropipette electrodes by switching valves in phase with AC square waves applied to metal electrodes contained within the device. This approach achieves DC ionic flow through tissue while still adhering to charge-balancing constraints at each electrode-saline interface. We show the SDCS's ability to both inhibit and excite neural activity to achieve improved dynamic range during prosthetic stimulation of the vestibular part of the inner ear in chinchillas.
Wisconsinan Late‐glacial environmental change in Newfoundland: A regional review (1994)

Abstract The distribution of 75 lake and bog sites, from which pollen stratigraphical evidence relevant to the late Quaternary of Newfoundland has been obtained, is presented. The detailed records of lithology, pollen and diatoms, supplemented by geochemical data, are discussed for three of the sites — Southwest Brook Lake, Woody Hill Brook Pond and Leading Tickles — and interpretations made are based on vegetational history, relative climatic changes and extent of ice cover. Radiocarbon data from 14 sites are summarised. A summary chart of Late‐glacial environmental changes, including a qualitative palaeotemperature curve, is provided.
Use of Soil Amendments to Reduce Nitrogen, Phosphorus and Heavy Metal Availability (1998)

The primary objectives of this study were to determine (1) the exchange characteristics of various soil amendments using a range of salt solutions, (2) the effect of selected soil amendments on heavy metal (Cu2+, Pb2+, and Zn2+) availability, and (3) the effect of selected soil amendments on NH4 + and P availability. The CEC of zeolite and red mud obtained using solutions of 0.1 M BaCl2 and 0.1 M BaCl2/NH4Cl were significantly lower than values obtained using 1 M KCl and 1 M NH4Cl. The higher CEC obtained with monovalent cations indicated that larger divalent cations could not enter the mineralogical framework of zeolite and red mud, and, consequently, a number of exchange sites were only accessible to the smaller monovalent cations. These findings suggest that 1 M KCl and 1 M NH4NO3 should be used as the extracting solutions to obtain the best estimation of CEC and ECEC of red mud and zeolite. The ability of red mud, zeolite, and calcium phosphate (Ca-P), mixed at rates of 0%, 5%, 10%, and 20% (w/w), to sorb Cu2+, Pb2+, and Zn2+ generally followed the order: red mud>zeolite>>Ca-P, while the affinity sequence for these metals followed the order: Pb2+≥Cu2+>>Zn2+. The higher affinity of the sand/amendment mixtures for Pb2+ and Cu2+ relative to Zn2+ was attributed to metal hydrolysis and subsequent specific adsorption as Pb(OH)+ and Cu(OH)+. Zinc was considered to have been primarily sorbed as the divalent cation species. Rates of 5% (w/w) adequately reduced the availability of heavy metals to concentrations below environmental guidelines based on the Toxicity Characteristic Leaching Procedure. Red mud and zeolite added at a rate of 10% (w/w) to the A and B horizon of a sandy soil significantly increased their ability to remove NH4 + from solution, but had negligible effect on P sorption compared with unamended soils. Increased NH4 + removal was attributed to the associated increase in CEC and the greater selectivity of the exchange sites for this cation relative to resident exchangeable Ca2+ and Na+. The absence of P sorption by these two amendments was attributed to the high pH and predominantly negative surface charge of the red mud and the lack of sorption sites in zeolite. Gypsum, on the other hand, tended to depress NH4 + retention but markedly increased P sorption. The depressive effect on NH4 + was due to increased competition between NH4 + and Ca2 + for a limited number of exchange sites, while formation of calcium phosphates of low solubility was the possible mechanism for increased P sorption.
Fabrication of low-temperature bottom-gate poly-Si TFTs on large-area substrate by linear-beam excimer laser crystallization and ion doping method (2002)

A novel crystallization procedure of Si films using a linear-beam excimer laser combined with a non-mass-separated ion doping method on a large-area is proposed for fabrication of poly-Si TFTs with maximum process temperature of 400/spl deg/C. Fabricated TFTs show sufficiently high mobilities to drive peripheral circuitry and yet retain a low leakage current suitable to pixel transistors. TFTs' on-current deviation of well under /spl plusmn/20% has been obtained for both nand p-channel TFTs over an entire substrate. Long-term reliability of the TFTs has also been confirmed using a CMOS ring oscillator.
Productive human immunodeficiency virus type 1 (HIV-1) infection of nonproliferating human monocytes. (1991)

Human immunodeficiency virus type 1 (HIV-1) infection of T lymphocytes requires cellular proliferation and DNA synthesis. Human monocytes were shown to have low DNA synthesis rates, yet the monocytotropic BaL isolate of HIV-1 was able to infect these cells efficiently. Monocytes that were irradiated to assure no DNA synthesis could also be readily infected with HIV-1BaL. Such infections were associated with the integration of HIV-1BaL DNA into the high molecular weight, chromosomal DNA of monocytes. Thus, normal, nonproliferating monocytes differ from T lymphocytes in that a productive HIV-1 infection can occur independently of cellular DNA synthesis. These results suggest that normal nonproliferating mononuclear phagocytes, which are relatively resistant to the destructive effects of this virus, may serve as persistent and productive reservoirs for HIV-1 in vivo.
Overexpression of vascular endothelial growth factor 165 drives peritumor interstitial convection and induces lymphatic drain: magnetic resonance imaging, confocal microscopy, and histological tracking of triple-labeled albumin. (2002)

Increased expression of vascular endothelial growth factor (VEGF) has been associated with increased lymph node metastases. The aim of this work was to determine whether VEGF-induced hyperpermeability affects peritumor interstitial convection and lymphatic drain, thus linking this growth factor with lymphatic function. Noninvasive imaging of lymphatic function induced by vascular hyperpermeability was achieved by following the distribution of albumin triple-labeled with biotin, fluorescein, and gadolinium-diethylene triamine pentaacetic acid. This contrast material allowed for multimodality imaging using magnetic resonance imaging (MRI), confocal microscopy, and histology. Overexpression of VEGF in C6-pTET-VEGF165 tumors, inoculated in hind limbs of nude mice, elevated vascular permeability, interstitial convection, and lymphatic drain. These were manifested in dynamic MRI measurements by outward flux of the contrast material, the rate of which correlated with tumor volume followed by directional flow toward the popliteal lymph node. Avidin-chase, namely i.v. administration of avidin, was applied for inducing rapid clearance of the intravascular biotinylated contrast material, thus allowing early experimental separation between vascular leak and lymphatic drain. Repeated MRI measurements of the same mice were conducted 48 h after withdrawal of VEGF by addition of tetracycline to the drinking water. VEGF withdrawal decreased tumor blood-plasma volume fraction by 43%, reduced tumor permeability by 75%, and abolished interstitial convection of the contrast material. Histological sections and whole-mount confocal microscopy confirmed VEGF-induced changes in permeability and interstitial accumulation of the contrast material, as well as uptake of the contrast material into peritumor lymphatic vessels. These results revealed a direct link between expression of VEGF165 and peritumor lymphatic drain, thus suggesting a possible role for tumor-derived VEGF in metastatic spread to sentinel lymph nodes.
Role of Interleukin-18 (IL-18) during Lethal Shock: Decreased Lipopolysaccharide Sensitivity but Normal Superantigen Reaction in IL-18-Deficient Mice (2000)

Lethal shock can be associated with excessive secretion of cytokines such as tumor necrosis factor (TNF) and gamma interferon (IFN-gamma). IFN-gamma mediates macrophage activation and appears to be controlled by interleukin (IL)-12 and IL-18. To investigate the role of IL-18 in vivo, we generated IL-18-deficient mice by gene targeting. IL-18(-/-) mice showed decreased sensitivity towards lipopolysaccharide (LPS)-induced shock. LPS-induced IFN-gamma production was abrogated, yet induction of IL-12 and TNF was not affected. Both wild-type and IL-18-deficient mice succumbed to LPS-induced lethal shock after sensitization with D-galactosamine. However, in marked contrast to LPS, the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) induced comparable serum levels of IFN-gamma in IL-18(+/+) and IL-18(-/-) mice, accompanied by an upregulation of cell surface markers CD14, CD122 (IL-2Rbeta), and CD132 (IL-2Rgamma) on peritoneal macrophages. Moreover, SEB injection rendered IL-18-deficient mice sensitive for subsequent challenge with LPS. The degree of sensitization was comparable to that in wild-type controls with respect to lethality. However, LPS-induced TNF levels in serum were significantly reduced in SEB-sensitized IL-18-deficient mice. These results imply that IL-18 plays an important role in induction of IFN-gamma and lethality in response to LPS.
Possible Strategies for the Formulation of Antineoplastic Drugs (1986)

(1986). Possible Strategies for the Formulation of Antineoplastic Drugs. Drug Development and Industrial Pharmacy: Vol. 12, No. 7, pp. 1041-1106.