gebhart/patrepeval huggingface dataset:
Thermal management of BioMEMS: Temperature control for ceramic-based PCR and DNA detection devices (2003)

Integrated microfluidic devices for amplification and detection of biological samples that employ closed-loop temperature monitoring and control have been demonstrated within a multilayer low temperature co-fired ceramics (LTCC) platform. Devices designed within this platform demonstrate a high level of integration including integrated microfluidic channels, thick-film screen-printed Ag-Pd heaters, surface mounted temperature sensors, and air-gaps for thermal isolation. In addition, thermal-fluidic finite element models have been developed using CFDRC ACE+ software which allows for optimization of such parameters as heater input power, fluid flow rate, sensor placement, and air-gap size and placement. Two examples of devices that make use of these concepts are provided. The first is a continuous flow polymerase chain reaction (PCR) device that requires three thermally isolated zones of 94/spl deg/C, 65/spl deg/C, and 72/spl deg/C, and the second is an electronic DNA detection chip which requires hybridization at 35/spl deg/C. Both devices contain integrated heaters and surface mount silicon transistors which function as temperature sensors. Closed loop feedback control is provided by an external PI controller that monitors the temperature dependant I-V relationship of the sensor and adjusts heater power accordingly. Experimental data confirms that better than /spl plusmn/0.5/spl deg/C can be maintained for these devices irrespective of changing ambient conditions. In addition, good matching with model predictions has been achieved, thus providing a powerful design tool for thermal-fluidic microsystems.
Nerve Growth Factor Gene Therapy in Alzheimer Disease (2007)

Nervous system growth factors potently stimulate cell function and prevent neuronal death. These broad effects on survival and function arise from direct downstream activation of antiapoptotic pathways, inhibition of proapoptotic pathways, and stimulation of functionally important cellular mechanisms including ERK/MAP kinase and CREB. Thus, as a class, growth factors offer the potential to treat neurodegenerative disorders for the first time by preventing neuronal degeneration rather than compensating for cell loss after it has occurred. Different growth factors affect distinct and specific populations of neurons: the first nervous system growth factor identified, nerve growth factor, potentially stimulates the survival and function of basal forebrain cholinergic neurons, suggesting that nerve growth factor could be a means for reducing the cholinergic component of cell degeneration in Alzheimer disease. This review will discuss the transition of growth factors from preclinical studies to human clinical trials in Alzheimer disease. The implementation of clinical testing of growth factor therapy for neurologic disease has been constrained by the dual need to achieve adequate concentrations of these proteins in specific brain regions containing degenerating neurons, and preventing growth factor spread to nontargeted regions to avoid adverse effects. Gene therapy is one of a limited number of potential methods for achieving these requirements.
Single-stranded DNA from abutilon mosaic virus is present in the plastids of infected Abutilon sellovianum (1987)

The leaf mosaic of Abutilon sellovianum is caused by abutilon mosaic virus (AbMV), a geminivirus that has a circular single-stranded DNA genome. DNA was isolated from intact plastids of AbMV-infected and noninfected plants. Plastids from infected plants were shown to contain the single-stranded AbMV DNA by Southern-blot hybridization experiments that used a probe made from highly purified AbMV DNA. The possibility of adsorption of AbMV virions or viral DNA onto the plastid envelope was ruled out by several in vitro experiments with DNase I and protease. Furthermore, the lamellar system of plastids from AbMV-infected plants was degenerated and substituted by amorphous electron-dense material. The transport of AbMV DNA across the plastid envelope has implications for the development of a chloroplast transformation vector.
Cationic Transfection Lipids (2003)

This review focuses on the recent developments in study of cationic lipids as carriers for DNA delivery. Emphasis is placed on a class of compounds as exemplifies by their similarity in structures and transfection activities. The technical aspects are also reviewed on how to prepare DNA-lipid complexes and to perform transfection. A brief discussion of the current views on the mechanism of cationic lipid-mediated DNA transfer is intended to provide new prospects for future developments and further improvement of the current systems.
Fine structural analysis of the Zoogloea ramigera phbA‐phbB locus encoding β‐ketothiolase and acetoacetyl‐CoA reductase: nucleotide sequence of phbB (1989)

A series of expression plasmids containing either the complete insert from plasmid pUCDBK1 (Peoples et al., 1987) or sub-fragments thereof were constructed in a tac promoter vector. Analysis of protein lysates of induced cultures of these clones identified the gene encoding NADPH-specific acetoacetyl-CoA reductase in the 2.3kb of sequence located downstream from the beta-ketothiolase gene in plasmid pUCDBK1. The complete nucleotide sequence (2.1kb) of this region was determined. An open reading frame was located 88bp downstream from the stop codon of the thiolase gene encoding a potential polypeptide of Mr 25,000, which is in good agreement with that observed for the overexpressed protein on SDS-PAGE. N-terminal protein sequence data obtained by Edman degradation of the purified Mr = 25,000 polypeptide were used to identify the correct start of the NADPH-specific acetoacetyl-CoA reductase gene. Hence in Z. ramigera, the genes encoding beta-ketothiolase (phbA) and NADPH-specific acetoacetyl-CoA reductase (phbB) are organized as phbA-phbB. S1-nuclease analysis of Z. ramigera RNA identified a transcription start site 85 bp upstream from the phbA structural gene locating the promoter region.
Polyethylene Glycol (PEG)-induced Mouse Model of Choroidal Neovascularization (2011)

In this study, we describe a new method for inducing choroidal neovascularization (CNV) in C57BL/6 mice, an animal model of wet age-related macular degeneration (AMD). AMD is a disease that causes central blindness in humans. We injected PEG-8 subretinally in different doses (0.125-2 mg) to induce CNV. After PEG-8 injection, we examined CNV at several time points (days 3-42). We also used Western blotting, immunohistochemistry, and ELISA to examine the complement component C3 split products, C9, VEGF, TGF-β2, and basic FGF. As early as day 1 after treatment, we found that a single subretinal injection of 1 mg of PEG-8 increased the C3 split products and the C9, TGF-β2, and basic FGF levels in the retinal pigment epithelium-choroid tissue. By day 3 after PEG-8 injection, the intraocular activation of the complement system caused induction and progression of CNV, including new vessels penetrating the Bruch's membrane. At day 5 after PEG-8 injection, we observed a fully developed CNV and retinal degeneration. Thus, in this study, we present a new, inexpensive, and accelerated mouse model of CNV that may be useful to study AMD.
Metalloprotease-mediated cleavage secretion of pulmonary ACE by vascular endothelial and kidney epithelial cells (1996)

The pulmonary isozyme of angiotensin-converting enzyme (ACEP) is present in the body both as a cell-associated protein in endothelial, epithelial, and monocytic cells and as a soluble protein in various body fluids including serum. The mechanism by which soluble ACEP is produced in vivo is unknown. Using in vitro transfected cell culture systems, we previously demonstrated that the rabbit testicular isozyme of ACE (ACET), which shares extensive homology with ACEP, is first synthesized as a plasma membrane-anchored ectoprotein and then secreted to the culture medium by cleavage removal of its COOH-terminal membrane-anchored tail. Here, using in vitro cultures of arterial endothelial cells and acutely isolated renal epithelial cells, we demonstrate that ACEP is also cleavage secreted from their natural producer cells. Biochemical and immunological characterization of the in vitro secreted ACEP protein revealed that it is missing the COOH-terminal membrane-anchored region of the cell-associated ACEP. Similar analysis of ACEP proteins present in rabbit serum, lung, and kidney established that ACEP secretion in vivo is also caused by the cleavage removal of the COOH-terminal region of the cell-associated protein. To characterize the proteolytic enzyme responsible for ACEP secretion, we employed rabbit renal proximal tubular epithelial cells and demonstrated significant inhibition of secretion by compound 3, a hydroxamic acid-based inhibitor of specific metalloproteases. In contrast, the inhibitors of chymotrypsin, trypsin, serine, aspartate, and cysteine proteases were ineffective. These results indicate that soluble ACEP production by vascular endothelial and renal epithelial cells, both in vitro and in vivo, is achieved by cleavage removal of its membrane-anchoring COOH-terminal tail by a metalloprotease.
Probucol and Multivitamins in the Prevention of Restenosis after Coronary Angioplasty (1997)

The antioxidant probucol is effective in reducing the rate of restenosis after balloon coronary angioplasty.
The Novel Role of Tyrosine Kinase Inhibitor in the Reversal of Immune Suppression and Modulation of Tumor Microenvironment for Immune-Based Cancer Therapies (2009)

In tumor-bearing hosts, myeloid-derived suppressor cells (MDSC) and T regulatory cells (Treg) play important roles in immune suppression, the reversal of which is vitally important for the success of immune therapy. We have shown that ckit ligand is required for MDSC accumulation and Treg development. We hypothesized that sunitinib malate, a receptor tyrosine kinase inhibitor, could reverse MDSC-mediated immune suppression and modulate the tumor microenvironment, thereby improving the efficacy of immune-based therapies. Treatment with sunitinib decreased the number of MDSC and Treg in advanced tumor-bearing animals. Furthermore, it not only reduced the suppressive function of MDSCs but also prevented tumor-specific T-cell anergy and Treg development. Interestingly, sunitinib treatment resulted in reduced expression of interleukin (IL)-10, transforming growth factor-beta, and Foxp3 but enhanced expression of Th1 cytokine IFN-gamma and increased CTL responses in isolated tumor-infiltrating leukocytes. A significantly higher percentage and infiltration of CD8 and CD4 cells was detected in tumors of sunitinib-treated mice when compared with control-treated mice. More importantly, the expression of negative costimulatory molecules CTLA4 and PD-1 in both CD4 and CD8 T cells, and PDL-1 expression on MDSC and plasmacytoid dendritic cells, was also significantly decreased by sunitinib treatment. Finally, sunitinib in combination with our immune therapy protocol (IL-12 and 4-1BB activation) significantly improves the long-term survival rate of large tumor-bearing mice. These data suggest that sunitinib can be used to reverse immune suppression and as a potentially useful adjunct for enhancing the efficacy of immune-based cancer therapy for advanced malignancies.
Fluid retention in cirrhosis: pathophysiology and management (2008)

Accumulation of fluid as ascites is the most common complication of cirrhosis. This is occurring in about 50% of patients within 10 years of the diagnosis of cirrhosis. It is a prognostic sign with 1-year and 5-year survival of 85% and 56%, respectively. The most acceptable theory for ascites formation is peripheral arterial vasodilation leading to underfilling of circulatory volume. This triggers the baroreceptor-mediated activation of renin-angiotensin-aldosterone system, sympathetic nervous system and nonosmotic release of vasopressin to restore circulatory integrity. The result is an avid sodium and water retention, identified as a preascitic state. This condition will evolve in overt fluid retention and ascites, as the liver disease progresses. Once ascites is present, most therapeutic modalities are directed on maintaining negative sodium balance, including salt restriction, bed rest and diuretics. Paracentesis and albumin infusion is applied to tense ascites. Transjugular intrahepatic portosystemic shunt is considered for refractory ascites. With worsening of liver disease, fluid retention is associated with other complications; such as spontaneous bacterial peritonitis. This is a primary infection of ascitic fluid caused by organisms originating from large intestinal normal flora. Diagnostic paracentesis and antibiotic therapy plus prophylactic regimen are mandatory. Hepatorenal syndrome is a state of functional renal failure in the setting of low cardiac output and impaired renal perfusion. Its management is based on drugs that restore normal renal blood flow through peripheral arterial and splanchnic vasoconstriction, renal vasodilation and/or plasma volume expansion. However, the definitive treatment is liver transplantation.
Umbilical Cord-Derived Mesenchymal Stem Cells Isolated by a Novel Explantation Technique Can Differentiate into Functional Endothelial Cells and Promote Revascularization (2010)

Stem cells transplantation holds great promise for the treatment of ischemic diseases through functional revascularization. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are also an ideal candidate for cell-based bioengineering. Herein, we report on the development of a simple and effective protocol to isolate UC-MSCs, and confirm their endothelial potential both in vitro and in vivo. UC-MSCs were isolated by a novel explantation technique and induced to differentiate into endothelial-like cells. Then UC-MSCs were transplanted into ischemic mouse model and cultured on 3D gel/MMT-CS composite scaffolds. Morphological and proliferation assessments show that sufficient UC-MSCs can be generated during a relatively short culture period with explantation technique. Increased expression of endothelial-specific markers (KDR and vWF), and functional markers (ac-LDL uptake and UEA-1 binding), indicate that functional endothelial progenitor cells are induced after 9 days of in vitro culture. In an ischemic hindlimb mouse model, the ratio of ischemic/nonischemic limb perfusion 4 weeks after MSCs transplantation reached 0.84 +/- 0.09. The capillary density of this group was 2.57-fold greater than that of sham-injected mice (P < 0.05). Immunofluorescence and immunohistological analyses indicate that MSCs may act to salvage the ischemic tissue by incorporating into the local vasculature. In vitro, UC-MSCs were observed to incorporate into 3D gel/MMT-CS composite scaffolds, to secrete extracellular matrix, to remain viable, and to retain their proliferation capacity. In conclusion, UC-MSCs isolated by novel yet simple explantation technique are well suited for application in the development of novel stem cell-based revascularization therapies.
Modeling Energy Dynamics in Mice with Skeletal Muscle Hypertrophy Fed High Calorie Diets (2016)

Retrospective and prospective studies show that lean mass or strength is positively associated with metabolic health. Mice deficient in myostatin, a growth factor that negatively regulates skeletal muscle mass, have increased muscle and body weights and are resistant to diet-induced obesity. Their leanness is often attributed to higher energy expenditure in the face of normal food intake. However, even obese animals have an increase in energy expenditure compared to normal weight animals suggesting this is an incomplete explanation. We have previously developed a computational model to estimate energy output, fat oxidation and respiratory quotient from food intake and body composition measurements to more accurately account for changes in body composition in rodents over time. Here we use this approach to understand the dynamic changes in energy output, intake, fat oxidation and respiratory quotient in muscular mice carrying a dominant negative activin receptor IIB expressed specifically in muscle. We found that muscular mice had higher food intake and higher energy output when fed either chow or a high-fat diet for 15 weeks compared to WT mice. Transgenic mice also matched their rate of fat oxidation to the rate of fat consumed better than WT mice. Surprisingly, when given a choice between high-fat diet and Ensure® drink, transgenic mice consumed relatively more calories from Ensure® than from the high-fat diet despite similar caloric intake to WT mice. When switching back and forth between diets, transgenic mice adjusted their intake more rapidly than WT to restore normal caloric intake. Our results show that mice with myostatin inhibition in muscle are better at adjusting energy intake and output on diets of different macronutrient composition than WT mice to maintain energy balance and resist weight gain.
Cytokine release syndrome in severe COVID-19 (2020)

Lessons from arthritis and cell therapy in cancer patients point to therapy for severe disease
Structure, function, and expression of SEL-1, a negative regulator of LIN-12 and GLP-1 in C. elegans (1997)

Previous work indicated that sel-1 functions as a negative regulator of lin-12 activity, and predicted that SEL-1 is a secreted or membrane associated protein. In this study, we describe cell ablation experiments that suggest sel-1 mutations elevate lin-12 activity cell autonomously. We also use transgenic approaches to demonstrate that the predicted signal sequence of SEL-1 can direct secretion and is important for function, while a C-terminal hydrophobic region is not required for SEL-1 function. In addition, by analyzing SEL-1 localization using specific antisera we find that SEL-1 is localized intracellularly, with a punctate staining pattern suggestive of membrane bound vesicles. We incorporate these observations, and new information about a related yeast gene, into a proposal for a possible mechanism for SEL-1 function in LIN-12 turnover.
Automated Confocal Laser Scanning Microscopy and Semiautomated Image Processing for Analysis of Biofilms (1998)

ABSTRACT The purpose of this study was to develop and apply a quantitative optical method suitable for routine measurements of biofilm structures under in situ conditions. A computer program was designed to perform automated investigations of biofilms by using image acquisition and image analysis techniques. To obtain a representative profile of a growing biofilm, a nondestructive procedure was created to study and quantify undisturbed microbial populations within the physical environment of a glass flow cell. Key components of the computer-controlled processing described in this paper are the on-line collection of confocal two-dimensional (2D) cross-sectional images from a preset 3D domain of interest followed by the off-line analysis of these 2D images. With the quantitative extraction of information contained in each image, a three-dimensional reconstruction of the principal biological events can be achieved. The program is convenient to handle and was generated to determine biovolumes and thus facilitate the examination of dynamic processes within biofilms. In the present study, Pseudomonas fluorescens or a green fluorescent protein-expressing Escherichia coli strain, EC12, was inoculated into glass flow cells and the respective monoculture biofilms were analyzed in three dimensions. In this paper we describe a method for the routine measurements of biofilms by using automated image acquisition and semiautomated image analysis.
A 180-day clinical investigation of the tooth whitening efficacy of a bleaching gel with added amorphous calcium phosphate. (2005)

This study demonstrated that the ACP product offers 10% better long-term (6-months) whitening efficacy than the traditional bleaching gel tested. The long-term safety of the product has also been demonstrated, as there were no adverse gingival or other effects seen at either day +90 or day +180.
An open agent architecture (1997)

The goal of this ongoing project is to develop an open agent architecture and accompanying user interface for networked desktop and handheld machines. The system we are building should support distributed execution of a user&amp;apos;s requests, interoperability of multiple application subsystems, addition of new agents, and incorporation of existing applications. It should also be transparent; users should not need to know where their requests are being executed, nor how. Finally, in order to facilitate the user&amp;apos;s delegating tasks to agents, the architecture will be served by a multimodal interface, including pen, voice, and direct manipulation. Design considerations taken to support this functionality will be discussed below. INTRODUCTION Agents are all the rage. &amp;quot;Visioneering&amp;quot; videos, such as Apple Computer&amp;apos;s Knowledge Navigator, have helped to popularize the notion that programs endowed with agency, if not intelligence, are just around the corner. Soon, users need not themselves wade into...
ERK/p38 MAP‐kinases and PI3K are involved in the differential regulation of B7‐H1 expression in DC subsets (2009)

Regulatory molecules of the B7-H-family expressed by DC are important for immune homeostasis, but their regulation is largely unknown. When investigating the pathways regulating B7-H1 expression in monocyte-derived DC (MoDC), freshly isolated myeloid DC (mDC) and plasmacytoid DC, respectively, we showed that in MoDC and mDC B7-H1 expression was upregulated by a standard cytokine cocktail, poly I:C or LPS. MoDC utilize ERK and PI3K pathways to upregulate B7-H1 in response to cytokines, whereas p38 kinase was predominantly utilized in response to poly I:C. In mDC, ERK and p38 pathways are involved in B7-H1 regulation, and similar to MoDC, mainly p38 signaling was required for poly I:C-induced expression of B7-H1. Plasmacytoid DC responded only to CpG with upregulation of B7-H1 and in addition to p38 also utilized the PI3K and ERK pathways to regulate B7-H1 expression. As a functional consequence of B7-H1 expression on DC, we demonstrate downmodulation of IFN-gamma production in T cells. Thus, the differential regulation of B7-H1 on DC subsets may suppress immune responses variably, depending on the target DC population. Further analysis of the regulatory mechanisms may facilitate the development of new immunosuppressive therapies, utilizing the regulation of B7-H1 expression on DC.
Molecular cloning of the CD9 antigen. A new family of cell surface proteins. (1991)

The CD9 antigen was described originally as a 24-kDa surface protein of non-T acute lymphoblastic leukemia cells and developing B-lymphocytes. It is also strongly expressed on platelets, among other cells, where it shows the property of mediating platelet activation and aggregation upon binding with mAbs. The primary structure has been elucidated by cloning the cDNA from a lambda gt11 expression vector library constructed with megakaryocytic mRNA. Monoclonal antibodies were used as probes with an APAAP amplification of the signal. The 5' region was further cloned in a lambda gt10 randomly primed cDNA library. The initiation codon was immediately followed by a sequence coding for the tetrapeptide corresponding to the NH2-terminal sequence identified in a microsequencing procedure. Only one species of mRNA was found with an estimated size of 1.4 kilobase. CD9 antigen appears to be a 227-amino acid molecule with four hydrophobic domains and one N-glycosylation site. Sequence and structural comparisons showed extensive similarity of the CD9 antigen with a 237-amino acid molecule described previously as the human melanoma-associated antigen ME491 and a Schistosoma mansoni membrane protein of 218 amino acids. These three proteins identify a new family of cell-surface proteins.