gebhart/patrepeval huggingface dataset:
Attenuation of phagocytosis of xenogeneic cells by manipulating CD47 (2006)

Signal regulatory protein alpha (SIRPalpha) is a critical immune inhibitory receptor on macrophages, and its interaction with CD47, a ligand for SIRPalpha, prevents autologous phagocytosis. We hypothesized that interspecies incompatibility of CD47 may contribute to the rejection of xenogeneic cells by macrophages. Here, we show that pig CD47 does not interact with mouse SIPRalpha. Similar to CD47-/- mouse cells, porcine red blood cells (RBCs) failed to induce SIRPalpha tyrosine phosphorylation in mouse macrophages. Blocking SIRPalpha with antimouse SIRPalpha mAb (P84) significantly enhanced the phagocytosis of CD47+/+ mouse cells, but did not affect the engulfment of porcine or CD47-/- mouse cells by mouse macrophages. CD47-deficient mice, whose macrophages do not phagocytose CD47-/- mouse cells, showed markedly delayed clearance of porcine RBCs compared with wild-type mouse recipients. Furthermore, mouse CD47 expression on porcine cells markedly reduced their phagocytosis by mouse macrophages both in vitro and in vivo. These results indicate that interspecies incompatibility of CD47 contributes significantly to phagocytosis of xenogeneic cells by macrophages and suggest that genetic manipulation of donor CD47 to improve its interaction with the recipient SIRPalpha may provide a novel approach to prevent phagocyte-mediated xenograft rejection.
가입자 편익 극대화 관점에서의 역모기지 최적 보증료율 체계 산출 방법론에 관한 연구 (2018)

본 연구는 국내외적으로 연구가 많이 이루어지지 않은 역모기지 보증료율 체계에 관한 연구이다. 국내외에서 운영되고 있는 역모기지 제도의 보증료율 체계를 살펴보면 대부분 가입 당시 주택가격의 일정비율로 결정되는 초기보증료와 매월 월지급금 지급 당시 대출잔액의 일정비율로 결정되는 월보증료의 2가지로 구분된다. 그런데 역모기지 가입자 입장에서 보증료율 체계는 당장 받을 수 있는 월지급금 크기와 관련될 뿐만 아니라, 대출종료 시 대출금을 상환하고 본인이 받을 수 있는 잔여지분의 크기에도 크게 영향을 미치게 된다. 본 연구는 이러한 점에 착안에 역모기지 가입자의 편익요소를 1) 월지급금으로부터 발생하는 편익과 2) 잔여지분으로부터 발생하는 편익으로 구분하고, 이 두 가지를 독립변수로 하는 일반적인 효용함수를 상정한 뒤, 가입자의 효용을 극대화할 수 있는 최적 역모기지 보증료율 체계를 찾아낼 수 있는 수치적 산출방법론을 제시해 보고자 하였다. 그리고 분석결과 가입자의 두 가지 편익에 대한 선호도 조합에 따라 최적의 보증료율 체계가 산출됨이 확인되었으며, 이러한 최적 보증료율 체계의 산출방법론을 적용해 현 주택연금제도의 단일보증료율 체계가 가입자 선호에 따라 상당한 비효율성을 가져다 줄 수 있음을 확인할 수 있었다.
Reproductive and Teratogenic Effects of Lidocaine in Sprague-Dawley Rats (1986)

The reproductive and teratogenic effects of lidocaine were studied in 155 Sprague-Dawley rats chronically implanted with osmotic minipumps. Three different lidocaine doses were used as follows: a low dose (100 mg X kg-1 X day-1); an intermediate dose (250 mg X kg-1 X day-1); and a high dose (500 mg X kg-1 X day-1). In the low and intermediate dose groups, lidocaine was administered for two weeks before mating and throughout pregnancy to evaluate reproductive and teratogenic effects. In the high-dose group, lidocaine was administered from days 3 to 17 of pregnancy to evaluate teratogenic effects. On day 21, cesarean section was performed and all of the 1,040 offspring, including those from control and positive control (retinoic acid) groups, were preserved and subsequently examined microscopically to detect external, visceral, and skeletal abnormalities. None was found in lidocaine-treated groups; reproductive indices also were normal. The only treatment effect was a reduction in mean fetal weight in the high-dose group. In a subsequent experiment this was found to be secondary to slightly delayed fetal development. It is concluded that lidocaine is devoid of significant adverse reproductive and teratogenic effects in Sprague-Dawley rats.
Using Microfluidics to Decouple Nucleation and Growth of Protein Crystals (2007)

A high throughput, low volume microfluidic device has been designed to decouple the physical processes of protein crystal nucleation and growth. This device, called the Phase Chip, is constructed out of poly(dimethylsiloxane) (PDMS) elastomer. One of the Phase Chip's innovations is to exploit surface tension forces to guide each drop to a storage chamber. We demonstrate that nanoliter water-in-oil drops of protein solutions can be rapidly stored in individual wells thereby allowing the screening of 1000 conditions while consuming a total of only 10 mug protein on a 20 cm(2) chip. Another significant advance over current microfluidic devices is that each well is in contact with a reservoir via a dialysis membrane through which only water and other low molecular weight organic solvents can pass, but not salt, polymer, or protein. This enables the concentration of all solutes in a solution to be reversibly, rapidly, and precisely varied in contrast to current methods, such as the free interface diffusion or sitting drop methods, which are irreversible. The Phase Chip operates by first optimizing conditions for nucleation by using dialysis to supersaturate the protein solution, which leads to nucleation of many small crystals. Next, conditions are optimized for crystal growth by using dialysis to reduce the protein and precipitant concentrations, which leads small crystals to dissolve while simultaneously causing only the largest ones to grow, ultimately resulting in the transformation of many small, unusable crystals into a few large ones.
A Polypeptide from Tomato Leaves Induces Wound-Inducible Proteinase Inhibitor Proteins (1991)

Defensive genes in plants can be activated by several different types of nonpeptide signaling molecules. An endogenous polypeptide, consisting of 18 amino acids, was isolated from tomato leaves and was able at very low concentrations to induce the synthesis of two wound-inducible proteinase inhibitor proteins when supplied to young tomato plants. The sequence of the polypeptide was determined, and an identical polypeptide was synthesized that possessed full inducing activity. These data establish that a polypeptide factor can initiate signal transduction to regulate the synthesis of defensive proteins in plant tissues.
T cell memory. Long-term persistence of virus-specific cytotoxic T cells. (1989)

This study documents that virus-specific CTL can persist indefinitely in vivo. This was accomplished by transferring Thy-1.1 T cells into Thy-1.2 recipient mice to specifically identify the donor T cell population and to characterize its antigenic specificity and function by using a virus-specific CTL assay. Thy-1.1+ T cells from mice previously immunized with lymphocytic choriomeningitis virus (LCMV) were transferred into Thy-1.2 mice persistently infected with LCMV. The transferred LCMV-specific CTL (Thy-1.1+ CD8+) eliminate virus from the chronically infected carriers and persist in the recipient mice in small numbers, comprising only a minor fraction of the total T cells. Upon re-exposure to virus, these long-lived "resting" CD8+ T cells proliferate in vivo to become the predominant cell population. These donor CD8+ T cells can be recovered up to a year post-transfer and still retain antigenic specificity and biological function. They kill LCMV infected H-2-matched cells in vitro and can eliminate virus upon transfer into a second infected host. In addition, these long-lived CD8+ T cells appear not to be dependent on help from CD4+ T cells, since depletion of CD4+ T cells has minimal or no effect on their biological properties (proliferation, CTL response, viral clearance). These donor CTL also exhibit an immunodominance over the host-derived LCMV-specific CTL response. When both host and donor T cells are present, the donor CTL response is dominant over the potential CTL response of the cured carrier host. Taken together, these results suggest that virus-specific CTL can persist for the life span of the host as memory cells.
Electrophysiological responses of serotoninergic dorsal raphe neurons to 5‐HT1A and 5‐HT1B agonists (1987)

A direct comparison was made of the effects of serotonin 5-HT1A and 5-HT1B selective compounds on the spontaneous firing rate of dorsal raphe serotoninergic neurons in chloral-hydrate-anesthetized rats. Following intravenous administration, the 5-HT1A selective compounds ipsapirone (TVX Q 7821) and LY 165163 potently inhibited single-unit activity in a dose-dependent manner whereas the 5-HT1B selective compounds, m-chlorophenylpiperazine (mCPP) and trifluoromethylphenylpiperazine (TFMPP), displayed only weak or irregular actions. Low microiontophoretic currents of ipsapirone and LY 165163 were also effective in suppressing spontaneous firing; dose-response relationships for the 5-HT1A compounds were indistinguishable from that of 5-HT itself. In contrast, dorsal raphe neurons were only weakly responsive to microiontophoretic application of mCPP and TFMPP; dose-response relationships for the 5-HT1B compounds were significantly displaced from that of 5-HT. In intracellular studies, ipsapirone and LY 165163, when added to the media bathing brain slices, mimicked the actions of 5-HT in hyperpolarizing dorsal raphe cell membranes and decreasing input resistance; however, the maximal effects of the 5-HT1A compounds on these membrane properties exceeded those of 5-HT. In summary, dorsal raphe 5-HT neurons appear highly responsive to 5-HT1A, but not to 5-HT1B compounds; these findings are discussed with regard to the 5-HT receptor subtypes as candidates for the somatodendritic autoreceptor of dorsal raphe neurons.
Combatting wound biofilm and recalcitrance with a novel anti-biofilm Hydrofiber® wound dressing (2016)

Biofilm is an impediment to wound healing as a consequence of its proven ability to impair epithelialization, granulation tissue formation and normal inflammatory processes, as well as protecting wound pathogens from antibiotics and antiseptics. With this in mind, a project was initiated to develop a combined anti-biofilm/antimicrobial technology that could be incorporated into a wound dressing to maximize effectiveness against wound pathogens existing in their predominant biofilm form. Initially, a wide range of anti-biofilm agents in combination with ionic silver were screened in a rapid throughput in vitro biofilm model. Selected agents were incorporated into a new wound dressing format and subsequently tested in vitro against antibiotic-resistant pathogens in their most tolerant biofilm form. The combination of ionic silver with a metal chelating agent and a surfactant was shown to produce a synergistic effect (referred to as Ag+ Technology) that substantially improved the antimicrobial efficacy of ionic silver against biofilm pathogens in a simulated wound biofilm model. By combining anti-biofilm and antimicrobial components that work in synergy to disrupt biofilm and expose associated wound pathogens to the antimicrobial action of ionic silver, it is anticipated that this new technology incorporated into an advanced Hydrofiber® wound dressing will contribute significantly to managing biofilm infections and encouraging healing in patients debilitated by recalcitrant wounds.
Characterization of Hepatitis C Virus (HCV) and HCV E2 Interactions with CD81 and the Low-Density Lipoprotein Receptor (2000)

Hepatitis C virus (HCV) or HCV-low-density lipoprotein (LDL) complexes interact with the LDL receptor (LDLr) and the HCV envelope glycoprotein E2 interacts with CD81 in vitro. However, E2 interactions with LDLr and HCV interactions with CD81 have not been clearly described. Using sucrose gradient-purified low-density particles (1.03 to 1.07 g/cm(3)), intermediate-density particles (1. 12 to 1.18 g/cm(3)), recombinant E2 protein, or control proteins, we assessed binding to MOLT-4 cells, foreskin fibroblasts, or LDLr-deficient foreskin fibroblasts at 4 degrees C by flow cytometry and confocal microscopy. Viral entry was determined by measuring the coentry of alpha-sarcin, a protein synthesis inhibitor. We found that low-density HCV particles, but not intermediate-density HCV or controls bound to MOLT-4 cells and fibroblasts expressing the LDLr. Binding correlated with the extent of cellular LDLr expression and was inhibited by LDL but not by soluble CD81. In contrast, E2 binding was independent of LDLr expression and was inhibited by human soluble CD81 but not mouse soluble CD81 or LDL. Based on confocal microscopy, we found that low-density HCV particles and LDL colocalized on the cell surface. The addition of low-density HCV but not intermediate-density HCV particles to MOLT-4 cells allowed coentry of alpha-sarcin, indicating viral entry. The amount of viral entry also correlated with LDLr expression and was independent of the CD81 expression. Using a solid-phase immunoassay, recombinant E2 protein did not interact with LDL. Our data indicate that E2 binds CD81; however, virus particles utilize LDLr for binding and entry. The specific mechanism by which HCV particles interact with LDL or the LDLr remains unclear.
The roles of cathelicidin LL-37 in immune defences and novel clinical applications (2008)

The understanding of the biological properties and functions of LL-37 and other host defence peptides advances our knowledge of innate immunity, the interactions of the host with pathogens and the microflora, as well as the pathology of infectious and inflammatory diseases, creating many strategies and opportunities for therapeutic intervention.
Generalized Biot's theory and Mandel's problem of multiple‐porosity and multiple‐permeability poroelasticity (2014)

Abstract This paper finds in Biot's theory of poroelasticity a complete and consistent extension to the general case of multiple‐porosity and multiple‐permeability, fluid‐saturated, and linearly elastic media. The constitutive stress‐strain relations for a medium identified with this extension are presented, and the coefficient matrix of mechanical properties associated with these relations is derived from the corresponding intrinsic properties of its single‐porosity constituents. The closed form analytical solution to Mandel's problem is upgraded to the case being considered in this study. This problem addresses the transient consolidation of a porous elastic slab of rectangular geometry, when confined from the top and bottom. A numerical example solution for shale with laboratory setup of Mandel's problem is provided. Results are compared for the cases of single‐, double‐, and triple‐porosity solutions.
Iridium complexes containing p-phenylene units. The influence of the conjugation on the excited state properties (2005)

The synthesis, characterisation and photophysical properties of a series of heteroleptic iridium complexes are reported. The complexes contain two orthometalating ligands, 2-(2,4-difluorophenyl)pyridine and a bipyridine derivative as the third chelating unit, substituted by 1–3 oligo(para-phenylene) units. We also describe a dinuclear complex in which the two iridium units are connected by a tetra-p-phenylene bridging ligand. All the complexes are strongly luminescent at room temperature and, interestingly, for the longest complexes, the deaerated solution shows an excited state lifetime of several microseconds. The presence of dioxygen reduces the lifetime, dramatically suggesting their potential use as oxygen sensors. At low temperature the emission predominantly originates from the triplet excited state of the ligand involving the poly(phenylene) units and the phosphorescence lifetime increases to several hundreds of microseconds.
Die Stacking (3D) Microarchitecture (2006)

3D die stacking is an exciting new technology that increases transistor density by vertically integrating two or more die with a dense, high-speed interface. The result of 3D die stacking is a significant reduction of interconnect both within a die and across dies in a system. For instance, blocks within a microprocessor can be placed vertically on multiple die to reduce block to block wire distance, latency, and power. Disparate Si technologies can also be combined in a 3D die stack, such as DRAM stacked on a CPU, resulting in lower power higher BW and lower latency interfaces, without concern for technology integration into a single process flow. 3D has the potential to change processor design constraints by providing substantial power and performance benefits. Despite the promising advantages of 3D, there is significant concern for thermal impact. In this research, we study the performance advantages and thermal challenges of two forms of die stacking: Stacking a large DRAM or SRAM cache on a microprocessor and dividing a traditional micro architecture between two die in a stack
Contribution to the theory of chromatography: linear non-equilibrium elution chromatography. (1965)

Abstract The model of elution chromatography is solved using a Hermite polynomials expansion. The column is infinitely long and filled along the whole length, the detector being placed at a distance L from the feeding point. The following factors were considered: longitudinal diffusion in the mobile phase, finite rate of mass transfer through the surface of porous grains, radial diffusion inside the grains and finite rate of sorption on the internal surface of the grains. Uniform shape of the grains and uniform distribution of the filling in the column are assumed. The effect of the eddy diffusion may be included in the longitudinal diffusion coefficient. The effect of the pressure gradient and non-uniform concentration in the cross-section of the column and along the boundary of individual grains is neglected. A method of describing chromatographic peaks by means of statistical moments was used and the central moments up to the fifth order were calculated. The first moment is of basic significance for the determination of retention time. It is shown that it depends only on the partition coefficients and on the longitudinal diffusion, while it is not affected by transport phenomena in the grain and across the surface film or by the shape and size of the grain. The effect of the longitudinal diffusion on the determination of retention time from the first moment (i.e. the center of gravity) of the peak is not significant. The second central moment has a significance for the determination of the peak width and like all higher moments it depends on all factors characterizing theoretically the optimum velocity of the carrier for which the relative width of the peak reaches a minimum value.
Emerging role of radiolabeled nanoparticles as an effective diagnostic technique (2012)

Nanomedicine is emerging as a promising approach for diagnostic applications. Nanoparticles are structures in the nanometer size range, which can present different shapes, compositions, charges, surface modifications, in vitro and in vivo stabilities, and in vivo performances. Nanoparticles can be made of materials of diverse chemical nature, the most common being metals, metal oxides, silicates, polymers, carbon, lipids, and biomolecules. Nanoparticles exist in various morphologies, such as spheres, cylinders, platelets, and tubes. Radiolabeled nanoparticles represent a new class of agent with great potential for clinical applications. This is partly due to their long blood circulation time and plasma stability. In addition, because of the high sensitivity of imaging with radiolabeled compounds, their use has promise of achieving accurate and early diagnosis. This review article focuses on the application of radiolabeled nanoparticles in detecting diseases such as cancer and cardiovascular diseases and also presents an overview about the formulation, stability, and biological properties of the nanoparticles used for diagnostic purposes.
Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity (2011)

The present study examined the glucose-lowering and insulinotropic properties of acylated GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) peptides in Type 2 diabetes and obesity. GLP-1, GIP, Liraglutide, N-AcGIP(Lys(37)Myr) (N-acetylGIP with myristic acid conjugated at Lys(37)), a simple combination of both peptides and a Lira-AcGIP preparation [overnight preparation of Liraglutide and N-AcGIP(Lys(37)Myr)] were incubated with DPP-IV (dipeptidyl peptidase-IV) to assess peptide stability, and BRIN-BD11 cells were used to evaluate cAMP production and insulin secretion. Acute glucose-lowering and insulinotropic actions were evaluated in Swiss TO mice. Subchronic studies on glucose homoeostasis, insulin secretion, food intake and bodyweight were evaluated in ob/ob mice. Liraglutide, N-AcGIP(Lys(37)Myr), a simple combination of both peptides and the Lira-AcGIP preparation demonstrated improved DPP-IV resistance (P<0.001), while stimulating cAMP production and insulin secretion (1.4-2-fold; P<0.001). The Lira-AcGIP preparation was more potent at lowering plasma glucose (20-51% reduction; P<0.05-P<0.001) and stimulating insulin secretion (1.5-1.8-fold; P<0.05-P<0.001) compared with Liraglutide and N-AcGIP(Lys(37)Myr) or a simple peptide combination. Daily administration of the Lira-AcGIP preparation to ob/ob mice lowered bodyweight (7-9%; P<0.05), food intake (23%; P<0.05) and plasma glucose (46% reduction; P<0.001), while increasing plasma insulin (1.5-1.6-fold; P<0.001). The Lira-AcGIP preparation enhanced glucose tolerance, insulin response to glucose and insulin content (P<0.05-P<0.001). These findings demonstrate that a combined preparation of the acylated GLP-1 and GIP peptides Liraglutide and N-AcGIP(Lys(37)Myr) markedly improved glucose-lowering and insulinotropic properties in diabetic obesity compared with either incretin mimetic given individually.
Pathogenic function of IL-1βin psoriasiform skin lesions of flaky skin (fsn/fsn) mice (2001)

IL-1 acts on many cells as an inflammatory mediator. Its two forms, IL-1 alpha and IL-1 beta, are regulated differentially within hyperproliferative inflammatory skin conditions, such as psoriasis. While IL-1 alpha is down-regulated within psoriatic lesions, the levels of IL-1 beta are increased. However, some investigators have described an inactive form of IL-1 beta in psoriasis, while others have detected increased IL-1 beta activity within these lesions. Thus, its in vivo role remains unclear. We have assessed expression and function of IL-1 beta within psoriasiform skin lesions of the spontaneous mouse mutation flaky skin (fsn/fsn ). It was found that IL-1 beta was increased by 357% within psoriasiform lesions of fsn/fsn mice compared with their wild-type or heterozygous (+/?) littermates (P < 0.00001). When the IL-1 beta function was inhibited by i.p. injection with a neutralizing MoAb, no effects were seen in +/? mice. In contrast, psoriasiform features in fsn/fsn mice were alleviated dramatically, as demonstrated by a 40% decrease of the epidermal thickness and a diminished number of intra-epidermal microabscesses. In addition, infiltrating epidermal CD4(+) and CD8(+) T cells were decreased by 68% and 81%, respectively (P < 0.05), and epidermal Langerhans cells also were reduced by 36% (P < 0.005). In contrast, mast cells were not affected, suggesting differential responses of various cutaneous cell types. Our results demonstrate an important in vivo role of IL-1 beta for the generation of hyperproliferative inflammatory skin lesions in the fsn/fsn model.
A Distinct Pathway of Cell-Mediated Apoptosis Initiated by Granulysin (2001)

Granulysin is an antimicrobial and tumoricidal molecule expressed in granules of CTL and NK cells. In this study, we show that granulysin damages cell membranes based upon negative charge, disrupts the transmembrane potential (Deltapsi) in mitochondria, and causes release of cytochrome c. Granulysin-induced apoptosis is blocked in cells overexpressing Bcl-2. Despite the release of cytochrome c, procaspase 9 is not processed. Nevertheless, activation of caspase 3 is observed in granulysin-treated cells, suggesting that granulysin activates a novel pathway of CTL- and NK cell-mediated death distinct from granzyme- and death receptor-induced apoptosis.