gebhart/patrepeval huggingface dataset:
Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor. (1995)

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that serves as a model for the human disease multiple sclerosis. We evaluated rolipram, a type IV phosphodiesterase inhibitor, for its efficacy in preventing EAE in the common marmoset Callithrix jacchus. In a blinded experimental design, clinical signs of EAE developed within 17 days of immunization with human white matter in two placebo-treated animals but in none of three monkeys that received rolipram (10 mg/kg s.c. every other day) beginning 1 week after immunization. In controls, signs of EAE were associated with development of cerebrospinal fluid pleocytosis and cerebral MRI abnormalities. In the treatment group, there was sustained protection from clinical EAE, transient cerebrospinal fluid pleocytosis in only one of three animals, no MRI abnormality, and marked reduction in histopathologic findings. Rolipram-treated and control animals equally developed circulating antibodies to myelin basic protein. Thus, inhibition of type IV phosphodiesterase, initiated after sensitization to central nervous system antigens, protected against autoimmune demyelinating disease.
Catheter microwave ablation therapy for cardiac arrhythmias (1999)

This article describes three microwave catheter antennas for percutaneous cardiac ablation. A particular design feature of these antennas is that there is no reflected microwave current from the antenna flowing up the transmission line. Thus, it minimizes heating of the coaxial cable. The power reflection coefficients are very low (4% or less) in phantom equivalent materials. These antennas can also serve as bipolar electrodes for sensing endocardiac electrograms. Our studies in dogs, during both cardiopulmonary bypass and closed-chest operations via the femoral vein, have shown microwave energy greater than 200 joules (J) delivered to the heart through a split-tip dipole catheter antenna can produce irreversible block of the heart rhythms. This energy was achieved either by increasing the delivered power from 20 to 40 watts or by increasing the treatment duration from 7 to 11 s (210 to 330 J per application). It produced an endocardium temperature of about 65 degrees C. We found that the percutaneous, transcatheter microwave system is capable of inducing AV blocks consistently in dogs using the flexible, curved tip, split-tip catheter antenna. In addition, our studies have shown that the width and height of SAR distributions for cap-choke and split-tip catheter antennas are similar for the same antenna length. The cap-slot design had a much longer SAR distribution compared to the others. Moreover, a longer (4 mm) split-tip antenna can also induce larger lesions. These results suggest that it could be possible to ablate a ventricular tachycardia focus using the 4 mm split-tip as well as the cap-slot microwave catheter antennas.
Potent and Selective Amidopyrazole Inhibitors of IRAK4 That Are Efficacious in a Rodent Model of Inflammation (2015)

IRAK4 is a critical upstream kinase in the IL-1R/TLR signaling pathway. Inhibition of IRAK4 is hypothesized to be beneficial in the treatment of autoimmune related disorders. A screening campaign identified a pyrazole class of IRAK4 inhibitors that were determined by X-ray crystallography to exhibit an unusual binding mode. SAR efforts focused on the identification of a potent and selective inhibitor with good aqueous solubility and rodent pharmacokinetics. Pyrazole C-3 piperidines were well tolerated, with N-sulfonyl analogues generally having good rodent oral exposure but poor solubility. N-Alkyl piperidines exhibited excellent solubility and reduced exposure. Pyrazoles possessing N-1 pyridine and fluorophenyl substituents were among the most active. Piperazine 32 was a potent enzyme inhibitor with good cellular activity. Compound 32 reduced the in vivo production of proinflammatory cytokines and was orally efficacious in a mouse antibody induced arthritis disease model of inflammation.
Gene Expression Profiling of B Cell Chronic Lymphocytic Leukemia Reveals a Homogeneous Phenotype Related to Memory B Cells (2001)

B cell-derived chronic lymphocytic leukemia (B-CLL) represents a common malignancy whose cell derivation and pathogenesis are unknown. Recent studies have shown that >50% of CLLs display hypermutated immunoglobulin variable region (IgV) sequences and a more favorable prognosis, suggesting that they may represent a distinct subset of CLLs which have transited through germinal centers (GCs), the physiologic site of IgV hypermutation. To further investigate the phenotype of CLLs, their cellular derivation and their relationship to normal B cells, we have analyzed their gene expression profiles using oligonucleotide-based DNA chip microarrays representative of approximately 12,000 genes. The results show that CLLs display a common and characteristic gene expression profile that is largely independent of their IgV genotype. Nevertheless, a restricted number of genes (<30) have been identified whose differential expression can distinguish IgV mutated versus unmutated cases and identify them in independent panels of cases. Comparison of CLL profiles with those of purified normal B cell subpopulations indicates that the common CLL profile is more related to memory B cells than to those derived from naive B cells, CD5(+) B cells, and GC centroblasts and centrocytes. Finally, this analysis has identified a subset of genes specifically expressed by CLL cells of potential pathogenetic and clinical relevance.
Intracellular kinetics of the activator calcium of rat heart after ischemic arrest and cardioplegia: quantitative comparison of right and left ventricles. (1992)

The effects of plain ischemia (34 degrees C) and the protective role of hypothermia (20 degrees C) alone or in combination with cardioplegia (St Thomas' Hospital [STH] or glucose-potassium-nifedipine [GPN]) on the intracellular kinetics of the activator calcium of cardiac muscle were quantified and compared from the interval-force behaviour (mechanical restitution) of right and left ventricles of the perfused rat heart. Plain ischemia caused a major depression in the restitution of force of contraction of both ventricles, deranged the mixed linear-exponential functions by significantly increasing the time constants of the fitted mechanical restitution curves (MRC) and altered the control right/left ventricle interval-force relationship. The right ventricle was found to be more susceptible to ischemic damage than the left ventricle, and its inotropic reserve was virtually abolished by 1 h of plain ischemia. Hypothermic preservation during ischemia improved the mechanical restitution, salvaged the inotropic reserve and optimized right/left ventricle interval-force relationship, but the time constants of the fitted MRCs were still prolonged. However, both the cardioplegic formulations were equally effective in normalizing the time constants of the fitted curves. In general, right ventricle functions were better preserved by STH cardioplegia and left ventricle functions were better preserved by GPN cardioplegia. Cardioplegic interventions did not further improve the ventricular inotropic reserve compared with hypothermic preservation. Additional beneficial effects of cardioplegic formulations were directed towards stabilizing the linear-exponential functions and hence restitution of force of contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Focal Adhesion Kinase Overexpression Enhances Ras-dependent Integrin Signaling to ERK2/Mitogen-activated Protein Kinase through Interactions with and Activation of c-Src (1997)

Cell adhesion to extracellular matrix proteins such as fibronectin (FN) triggers a number of intracellular signaling events including the increased tyrosine phosphorylation of the cytoplasmic focal adhesion protein-tyrosine kinase (PTK) and also the stimulation of the mitogen-activated protein kinase ERK2. Focal adhesion kinase (FAK) associates with integrin receptors, and FN-stimulated phosphorylation of FAK at Tyr-397 and Tyr-925 promotes the binding of Src family PTKs and Grb2, respectively. To investigate the mechanisms by which FAK, c-Src, and Grb2 function in FN-stimulated signaling events to ERK2, we expressed wild type and mutant forms of FAK in human 293 epithelial cells by transient transfection. FAK overexpression enhanced FN-stimulated activation of ERK2 approximately 4-fold. This was blocked by co-expression of the dominant negative Asn-17 mutant Ras, indicating that FN stimulation of ERK2 was Ras-dependent. FN-stimulated c-Src PTK activity was enhanced by wild type FAK expression, whereas FN-stimulated activation of ERK2 was blocked by expression of the c-Src binding site Phe-397 mutant of FAK. Expression of the Grb2 binding site Phe-925 mutant of FAK enhanced activation of ERK2, whereas a kinase-inactive Arg-454 mutant FAK did not. Expression of wild type and Phe-925 FAK, but not Phe-397 FAK, enhanced p130(Cas) association with FAK, Shc tyrosine phosphorylation, and Grb2 binding to Shc after FN stimulation. FN-induced Grb2-Shc association is another pathway leading to activation of ERK2 via Ras. The inhibitory effects of Tyr-397 FAK expression show that FAK-mediated association and activation of c-Src is essential for maximal signaling to ERK2. Moreover, multiple signaling pathways are activated upon the formation of an FAK.c-Src complex, and several of these can lead to Ras-dependent ERK2 mitogen-activated protein kinase activation.
Introduction of Foreign Genes into Tomato Protoplasts by Electroporation (1989)

Journal Article Introduction of Foreign Genes into Tomato Protoplasts by Electroporation Get access Mikako Tsukada, Mikako Tsukada Plant Genetic Engineering Laboratory, Biotechnology Institute, Akita Prefectural College of AgricultureOgata, Akita, 010-04 Japan Search for other works by this author on: Oxford Academic Google Scholar Tomonobu Kusano, Tomonobu Kusano Plant Genetic Engineering Laboratory, Biotechnology Institute, Akita Prefectural College of AgricultureOgata, Akita, 010-04 Japan Search for other works by this author on: Oxford Academic Google Scholar Yoshichika Kitagawa Yoshichika Kitagawa Plant Genetic Engineering Laboratory, Biotechnology Institute, Akita Prefectural College of AgricultureOgata, Akita, 010-04 Japan Search for other works by this author on: Oxford Academic Google Scholar Plant and Cell Physiology, Volume 30, Issue 4, June 1989, Pages 599–603, https://doi.org/10.1093/oxfordjournals.pcp.a077781 Published: 01 June 1989 Article history Received: 28 July 1988 Accepted: 23 March 1989 Published: 01 June 1989
Kinetics of Tempol for Prevention of Xerostomia Following Head and Neck Irradiation in a Mouse Model (2005)

Our results strongly suggest that tempol is a promising candidate for clinical application to protect salivary glands in patients undergoing radiotherapy for head and neck cancers.
Dihydrofolate Reductase Protein Inhibits Its Own Translation by Binding to Dihydrofolate Reductase mRNA Sequences within the Coding Region (1997)

Previous studies suggest that dihydrofolate reductase (DHFR) regulates its own translation. Moreover, intracellular levels of DHFR protein increase following exposure to the antifolate methotrexate (MTX), suggesting that MTX may release the translational inhibition mediated by DHFR [Chu et al. (1993) Biochemistry 32,4756-4760; Ercikan et al. (1993) Adv. Exp. Med. Biol. 338, 537-540]. To further investigate the role of DHFR in translational autoregulation, we have considered the possibility that DHFR directly contacts its cognate mRNA. Binding studies using a series of truncated DHFR mRNAs as probes localized the DHFR/RNA interaction to a 100-base-pair region containing two putative stem-loop structures; initial studies indicated that both of these loop structures are involved in protein binding. Moreover, the binding of MTX to DHFR prevents interaction of the protein with its cognate mRNA, thereby relieving translational autoregulation.
Identification and Design of p53‐Derived HLA‐A2‐Binding Peptides with Increased CTL Immunogenicity* (2001)

The replacement of a suboptimal amino acid in a primary anchor position with an optimal residue improves human leucocyte antigen (HLA) binding and immunogenicity, while maintaining cytotoxic T lymphocyte (CTL) specificity. Using a neural network capable of performing quantitative predictions of peptide binding to HLA-A2 molecules, we identified three p53 protein-derived nonamer peptides with intermediate binding owing to suboptimal amino acids in the P2 anchor position. These peptides were synthesized along with the corresponding analogs, where the natural P2 residue had been replaced with the optimal leucine residue. All three modified peptides bound to and more efficiently stabilized HLA-A2 molecules than the corresponding nonmodified peptides. The HLA-A2 transgenic mice were used for immunization. Two of the epitopes were more immunogenic in their modified than in their natural versions. The CTLs raised against the modified peptides efficiently killed the target cells pulsed with the corresponding native peptide. In terms of sensitizing the targets cells for the CTL killing, the modified peptides were more efficient than native peptides. Finally, the CTLs induced by modified peptide killed HLA-A2 transgenic mouse fibrosarcoma cells transfected with human p53 DNA. The data suggest that modified self-peptides derived from overexpressed tumour-associated proteins can be used in vaccine development against cancer, and that quantitative predictions of HLA binding is of value in the rational selection and improvement of target epitopes recognized by CTLs.
Infrared spectroscopic analysis of the Si/SiO2 interface structure of thermally oxidized silicon (2000)

The nature of the silicon oxide transition region in the vicinity of the Si/SiO2 interface is probed by infrared and x-ray photoelectron spectroscopies. The layer-by-layer composition of the interface is evaluated by uniformly thinning thermal oxide films from 31 Å down to 6 Å. We find that the thickness dependence of the frequencies of the transverse optical and longitudinal optical phonons of the oxide film cannot be reconciled by consideration of simple homogeneous processes such as image charge effects or stress near the interface. Rather, by applying the Bruggeman effective medium approximation, we show that film inhomogeneity in the form of substoichiometric silicon oxide species accounts for the observed spectral changes as the interface is approached. The presence of such substoichiometric oxide species is supported by the thickness dependence of the integrated Si suboxide signal in companion x-ray photoelectron spectra.
Multi-scaled line simplification of the digital maps and quantifying the comparative results: case study with USGS DLG hydrology data in the US Buffalo Region (2009)

본 연구는 선형 단순화(line simplification) 방법을 이용하여 수행된 지도 일반화(map generalization) 결과를 실증적으로 비교×검토하는 목적으로 수행되었다. 즉, 더글라스-패커(Douglas-Peucker) 알고리즘을 실제 사례연구에 적용하여, 상이한 허용오차(tolerance) 적용에 따른 결과를 라인의 총 길이와 선분의 수를 중심으로 비교하였다. 미국 뉴욕주 서부 지역을 사례지역으로 선정하여, USGS에서 제공되는 1:24,000 축척의 DLG 포맷의 수문 선형 지도 데이터가 사용되었다. 분석 결과, 허용오차가 커짐에 따라총 길이가 완만하게 줄어드는 반면, 구성 선분의 수는 급격하게 줄어들었다. 또한 이들 간의 강한 양(+)의 상관관계가 탐색되었다.
Capacitive Micromachined Ultrasonic Transducers: Theory and Technology (2003)

Capacitive micromachined ultrasonic transducers (CMUTs), introduced about a decade ago, have been shown to be a good alternative to conventional piezoelectric transducers in various aspects, such as sensitivity, transduction efficiency, and bandwidth. In this paper, we discuss the principles of capacitive transducer operation that underlie these aspects. Many of the key features of capacitive ultrasonic transducers are enabled with micromachining technology. Micromachining allows us to miniaturize device dimensions and produce capacitive transducers that perform comparably to their piezoelectric counterparts. The fabrication process is described briefly, and the performance of the CMUT transducers is evaluated by demonstrating characterization results. It is shown that the transduction efficiency as defined by the electromechanical coupling coefficient can be close to unity with proper device design and operating voltage. It is also shown that CMUTs provide large bandwidth (123% fractional bandwidth) in immersion applications which translate into high temporal and axial resolution. Finally, the feasibility of using CMUTs is demonstrated by showing imaging examples in air and in immersion.
33. Synthesis of a zeolitic mineral with chabazite-like sorptive properties (1948)

R. M. Barrer, J. Chem. Soc., 1948, 127 DOI: 10.1039/JR9480000127
Comments on Wafer Transfers and Related Problems in Urban Areas (1968)

Abstract Heavy development in certain areas of the United States and the growing shortage of additional, readily available water supplies therein have forced planners and hydrologists to resort progressively to more elaborate water‐supply systems. Among the most elaborate and most expensive systems proposed to date are the various plans for. transferring water toward the south from northward flowing Arctic rivers. A considerable portion of this water would be utilized for the expansion of already heavily urbanized areas. Meanwhile, many of the densely populated areas experiencing water shortages are subjected to other, perhaps more complex problems which appear to be, at least in part, a product of their increasing size. Therefore, the expenditure of large sums to supply them with water for indefinite growth appears to merit scrutinous study. An alternative approach designed to minimize both water diversion costs and problems associated with over‐populated areas is the stimulation of development in carefully selected regions well endowed with water and other natural resources. One such area and several of its attributes are discussed herein.
Citalopram and Bupropion-SR (2004)

The results of this cohort study suggest that combining citalopram and bupropion-SR is more effective than switching to a monotherapy. Combination treatment was well tolerated with no greater side effect burden than monotherapy. Limitations of this study include the nonrandomized design, open-label treatment, and small sample size.
A controlled field trial of liver oral typhoid vaccine Ty21a. (1980)

A controlled field trial of a live oral typhoid vaccine was carried out in Alexandria, Egypt, in 1978-79. A total of 32 388 children were included in the study. They were divided in two comparable groups, one given 3 doses of the vaccine and the other 3 doses of the placebo. Each active dose contained 1 x 10(9)-8 x 10(9) live Ty21a bacteria. From March 1978 to March 1979, the population studied was followed up and suspected typhoid cases were investigated bacteriologically and serologically. The effectiveness of the vaccine was assessed by analysis of the incidence of typhoid fever in the two groups. The results of the follow-up indicate that, in the dosage schedule used, the Ty21a mutant strain, found previously to be stable and safe, is protective against typhoid fever for at least one year.
Rearrangement and expression of endogenous immunoglobulin genes occur in many murine B cells expressing transgenic membrane IgM. (1988)

Transgenic mice carrying immunoglobulin genes coding for mu heavy chain and kappa light chain have been used to study the mechanisms involved in allelic and isotypic exclusion. We report here that individual cells from transgenic mice carrying a functionally rearranged mu heavy chain gene (capable of generating both membrane and secreted forms of IgM) can rearrange an endogenous mu heavy chain gene and simultaneously produce both transgenic and endogenous IgM. These "double-producing" cells express both endogenous and transgenic IgM in the cytoplasm (detected by immunohistology) and on the cell surface (detected by multiparameter fluorescence-activated cell sorter analysis). In addition, they secrete mixed IgM molecules containing both transgenic and endogenous mu heavy chains (detected in serum by radioimmune assay). The transgenic mice studied also have relatively large numbers of cells that produce endogenous immunoglobulin in the absence of detectable transgenic immunoglobulin ("endogenous-only cells"). The mechanisms that generate double-producing cells and endogenous-only cells appear to be under genetic control because the frequencies of these B-cell populations are characteristic for a given transgenic line. Thus, our findings indicate that more is involved in triggering allelic exclusion than the simple presence or absence of membrane mu heavy chains (as has been previously postulated).
Pioglitazone treatment enhances myelin debris phagocytosis and immunoregulatory functions of monocytes from MS patients (P1.162) (2015)

OBJECTIVE: The purpose of this study is to determine if myelin phagocytosis by monocytes is decreased in MS subjects and how it can be pharmacologically enhanced to promote remyelination. BACKGROUND: Remyelination is inhibited when monocytes and macrophages fail to phagocytose myelin debris. Animal studies have shown that providing debris-filled lesions with healthy monocytes enhances remyelination and recovery. Pioglitazone is an orally administered drug that activates peroxisome proliferator activated receptors (PPARs), which may stimulate immunomodulatory and neuroprotective pathways in blood-derived monocytes. DESIGN/METHODS: Monocytes were isolated from MS patients and healthy donors (HD) of different age groups (n=20/group) and their ability to phagocytose myelin in the presence/absence of 1 µM pioglitazone (in vivo achievable concentration) was quantified by flow cytometry. We isolated RNA from monocytes before and after myelin phagocytosis and performed microarrays. Ingenuity Pathway Analysis compared the profiles of MS patients, healthy, and pioglitazone-treated monocytes. Markers of M1/M2 differentiation were assessed by flow cytometry and ELISA. RESULTS: Microarray analysis revealed that genes in the PPAR pathway are downregulated in MS and upregulated in HD monocytes. Treatment with pioglitazone significantly altered 5 genes in this pathway to make MS monocytes more like healthy. Functionally, MS monocytes display impaired phagocytosis of myelin debris, and this impairment is reversed with pioglitazone treatment. They also display altered CD163 and CD14 surface expression compared to healthy monocytes, suggesting a change in the pro-/anti-inflammatory balance. CONCLUSIONS: Our results show that in vivo achievable pioglitazone concentrations enhance myelin debris phagocytosis and drive monocytes to a healthy state. These findings suggest that pioglitazone treatment can alter monocyte function and allow the beneficial role of monocytes to be harnessed in remyelination therapies. Study Supported by: NIH