gebhart/patrepeval huggingface dataset:
C6-ceramide synergistically potentiates the anti-tumor effects of histone deacetylase inhibitors via AKT dephosphorylation and α-tubulin hyperacetylation both in vitro and in vivo (2011)

Histone deacetylase inhibitors (HDACIs) have shown promising anti-tumor effects for a variety of malignancies, however, many tumors are reportedly resistant to them. In this study, we made a novel discovery that co-administration of HDACIs (Trichostatin A (TSA) and others) and exogenous cell-permeable short-chain ceramide (C6) results in striking increase in cancer cell death and apoptosis in multiple cancer cells. These events are associated with perturbations in diverse cell signaling pathways, including inactivation of Akt/mTOR and increase in α-tubulin acetylation (both in vivo and in vitro). TSA interacts in a highly synergistic manner with C6-ceramide to disrupt HDAC6/protein phosphatase 1 (PP1)/tubulin complex, to induce α-tubulin hyperacetylation, and to release and activate PP1, which then leads to AKT dephosphorylation and eventually causes cancer cell death. Interestingly, TSA itself results in short-term ceramide accumulation, which as a result of metabolic (glycosylation) removal, does not result in evident increase of cancer cell death. However, adding C6-ceramide led to a very pronounced increase in ceramide level and marked increase in cell death. Importantly, the effective synergistic anti-tumor activity of TSA plus C6-ceramide is also seen in in vivo mice xenograft pancreatic and ovarian cancer models, indicating that this regimen (HDACI plus C6-ceramide) may represent a more effective form of therapy against pancreatic and ovarian carcinoma.
Whole‐body imaging at 7T: Preliminary results (2008)

The objective of this study was to investigate the feasibility of whole-body imaging at 7T. To achieve this objective, new technology and methods were developed. Radio frequency (RF) field distribution and specific absorption rate (SAR) were first explored through numerical modeling. A body coil was then designed and built. Multichannel transmit and receive coils were also developed and implemented. With this new technology in hand, an imaging survey of the "landscape" of the human body at 7T was conducted. Cardiac imaging at 7T appeared to be possible. The potential for breast imaging and spectroscopy was demonstrated. Preliminary results of the first human body imaging at 7T suggest both promise and directions for further development.
Pyrosequencing in a Microfluidic Flow-Through Device (2005)

To explore genome variation meaningfully, there is a critical need for a high-throughput and inexpensive platform for DNA analysis. Pyrosequencing is a nonelectrophoretic bioluminometric DNA sequencing method that uses a four-enzyme mixture reaction to monitor nucleotide incorporation in real time. Currently, the commercialized pyrosequencing technique is limited to a 96-microtiter plate format. However, high throughput and inexpensive pyrosequencing is required to meet the need of screening large numbers of samples. We present here DNA pyrosequencing on a nanoliter-volume microfluidic platform. The microfluidic approach involves the trapping of the DNA on microbeads in an on-chip filter chamber and flow-through of the pyrosequencing reagents to monitor the reaction in real time. Two single-nucleotide polymorphisms were successfully scored to evaluate the microfluidic platform. In addition to significantly reducing reagent costs, microfluidic systems promise to improve the read length by eliminating intermediate product accumulation by constant removal of unincorporated nucleotides and elimination of dilution effects at each reaction cycle in the current plate format. Although only one filter chamber was used in this study, the platform should be readily adaptable to parallel analyses of nanoliter samples using filter chamber arrays to obtain high-throughput DNA analysis.
Opsins with mutations at the site of chromophore attachment constitutively activate transducin but are not phosphorylated by rhodopsin kinase. (1994)

More than 70 mutations in the gene encoding the visual pigment rhodopsin have been identified in patients with autosomal dominant retinitis pigmentosa. Most of these mutations are thought to interfere with proper folding of the membrane protein. However, families with a severe phenotype of retinitis pigmentosa have been identified and shown to carry a mutation at the site of chromophore attachment, Lys-296. This mutation disrupts the inactive conformation of opsin and results in a constitutively active protein that can activate the rod-specific GTP-binding protein, transducin, in the absence of light and in the absence of the chromophore 11-cis-retinal. It has been suggested that this mutant opsin molecule may cause rod degeneration by depletion of the components used to inactivate rhodopsin, such as rhodopsin kinase. In this work we test this idea by determining whether two constitutively active opsin mutants are phosphorylated by rhodopsin kinase. We found that opsin mutants where Lys-296 is replaced either by Glu (K296E) or by Gly (K296G) are not substrates of rhodopsin kinase in the absence of chromophore. However, when K296G is regenerated with a Schiff base complex of 11-cis-retinal and n-propylamine and exposed to illumination, phosphorylation of opsin occurs. These experiments suggest that in the rod photoreceptors of patients with retinitis pigmentosa carrying a mutation at Lys-296, there is persistent activation of the GTP-binding protein-mediated cascade. This may result in a situation that mimics long-term exposure to continuous illumination and results in the degeneration of photoreceptors.
Assessment of the Free Fraction of 25-Hydroxyvitamin D in Serum and Its Regulation by Albumin and the Vitamin D-Binding Protein * (1986)

We measured the free fraction of 25-hydroxyvitamin D (25OHD) in human serum and determined that 25OHD bound to a component with an affinity constant of 7 X 10(8) M-1 and a concentration of 4.5 X 10(-6) M. This concentration was equal to that of the vitamin D-binding protein (DBP) in the same serum sample. We removed DBP from the serum using actin affinity columns and found that the affinity for 25OHD of the remaining serum components was equivalent to that of human serum albumin (6 X 10(5) M-1). We then measured the free fractions of 25OHD, DBP, and albumin in normal and cirrhotic subjects. We calculated that 88 +/- 3% (+/- SD) and 83 +/- 8% of the 25OHD were bound to DBP in the serum of normal and cirrhotic subjects, respectively. We compared previously reported data for the free fraction and the free concentration of 1,25-dihydroxyvitamin D in these subjects with the current data for the free fraction and free concentration of 25OHD. The total concentrations and free fractions of both metabolites correlated to each other and to the DBP and albumin concentrations in these subjects, but the free concentrations of these metabolites did not. We conclude that 25OHD, like 1,25-dihydroxyvitamin D, is transported in blood bound primarily to DBP and albumin. Changes in the concentrations of DBP and albumin affected the total and free fractions of 25OHD in serum, but the actual free concentration of 25OHD was independent of such changes.
Regulation of tumor necrosis factor gene expression by ionizing radiation in human myeloid leukemia cells and peripheral blood monocytes. (1991)

Previous studies have demonstrated that ionizing radiation induces the expression of certain cytokines, such as TNF alpha/cachectin. However, there is presently no available information regarding the molecular mechanisms responsible for the regulation of cytokine gene expression by ionizing radiation. In this report, we describe the regulation of the TNF gene by ionizing radiation in human myeloid leukemia cells. The increase in TNF transcripts by x rays was both time- and dose-dependent as determined by Northern blot analysis. Similar findings were obtained in human peripheral blood monocytes. Transcriptional run-on analyses have demonstrated that ionizing radiation stimulates the rate of TNF gene transcription. Furthermore, induction of TNF mRNA was increased in the absence of protein synthesis. In contrast, ionizing radiation had little effect on the half-life of TNF transcripts. These findings indicate that the increase in TNF mRNA observed after irradiation is regulated by transcriptional mechanisms and suggest that production of this cytokine by myeloid cells may play a role in the pathophysiologic effects of ionizing radiation.
Applications of Ferroelectric Liquid Crystal LCOS Devices (2002)

Ferroelectric liquid crystal (FLC) liquid crystal over silicon (LCOS) devices can address large arrays of pixels at very high frame rates. They can also allow the phase of the light to be modulated in a manner that is independent of the state of polarisation of the incoming light. The optical versatility of the liquid crystal can now be matched by the electronic versatility of CMOS (complimentary metal oxide semiconductor) silicon backplanes as developments in very small feature sizes (sub micron) allows more and more complex electronic structures to be integrated into the device. In this paper, we briefly review some possible future applications of this technology in the area of displays, image processing and optical switching. In order to create these new device structures, we need suitable FLC materials.
The effect of ketamine pretreatment on propofol injection pain in 100 women (1998)

A controlled, randomised double-blind study was performed to compare the prior intravenous administration of ketamine 10 mg (1 ml) or 0.9% saline (1 ml) on propofol injection pain. One hundred patients of ASA status 1 or 2 presenting for gynaecological surgery were studied. Following an initial 5-ml bolus of propofol into a dorsal hand vein, 30 s after the treatment, 84% of the saline control patients experienced mild or severe pain compared to 26% of those who were given ketamine pretreatment (p < 0.05).
Mirrorless Lasing from Mesostructured Waveguides Patterned by Soft Lithography (2000)

Mesostructured silica waveguide arrays were fabricated with a combination of acidic sol-gel block copolymer templating chemistry and soft lithography. Waveguiding was enabled by the use of a low-refractive index (1.15) mesoporous silica thin film support. When the mesostructure was doped with the laser dye rhodamine 6G, amplified spontaneous emission was observed with a low pumping threshold of 10 kilowatts per square centimeter, attributed to the mesostructure's ability to prevent aggregation of the dye molecules even at relatively high loadings within the organized high-surface area mesochannels of the waveguides. These highly processible, self-assembling mesostructured host media and claddings may have potential for the fabrication of integrated optical circuits.
Effects of Chemical Inhomogeneities on Grain Growth and Microstructure in Al 2 O 3 (1989)

Effects of chemical inhomogeneities and single‐crystal seeds on normal and discontinuous grain growth were investigated in both undoped and MgO‐doped Al 2 O 3 . The chemical impurities in the samples were exsolved at a lower temperature than the sintering temperature and measured by SEM/EDS to determine the correlation between the distribution of impurities and the microstructure in Al 2 O 3 . A feature of this study was the use of clean‐room processing and firing procedures to maintain sample composition at the levels initially present in the starting powders. As the local concentrations of chemical impurities (i.e., Si, Ca) increased, the grain boundary–grain boundary dihedral angle distribution widened, with many angles at 180°, the grain‐size distribution widened, and pore–boundary separation was enhanced. Discontinuous grain growth was observed in regions of undoped Al 2 O 3 containing the largest Ca and Si concentrations. It is suggested that doping with MgO solute reduces the effects of impurities on grain growth by increasing the bulk solubility and decreasing interfacial segregation of impurities, especially Si, and by narrowing the distribution of grain boundary–grain boundary dihedral angles.
Monoclonal antibody therapeutic trials in seven patients with T-cell lymphoma (1983)

We have studied the clinical effects of a murine monoclonal anti-human T-cell antibody in seven patients with T-cell lymphoma. Four to 17 treatments with anti-Leu-1 were given to each patient over periods of 14–75 days. Doses of antibody ranged from 250 micrograms to 100 mg. Antibody treatments usually caused a rapid fall in circulating T cells, with return to baseline levels within 24–48 hr. The optimum dose appeared to vary for each patient. Clearance of circulating tumor cells correlated with the amount of antibody bound to cells. Other than dyspnea in one patient, no serious toxicity was noted. Five patients had definite tumor responses, but these were of short duration (1.5–4 mo). Four patients developed anti-mouse immunoglobulin (Ig) antibodies, and in three patients, this was responsible for tumor escape from therapy. Although 95% of the host anti-mouse Ig response was directed against mouse Ig constant region determinants, a small but significant component was found to be antiidiotype.
A modeling analysis of the effects of molecular size and binding affinity on tumor targeting (2009)

A diverse array of tumor targeting agents ranging in size from peptides to nanoparticles is currently under development for applications in cancer imaging and therapy. However, it remains largely unclear how size differences among these molecules influence their targeting properties. Here, we develop a simple, mechanistic model that can be used to understand and predict the complex interplay between molecular size, affinity, and tumor uptake. Empirical relationships between molecular radius and capillary permeability, interstitial diffusivity, available volume fraction, and plasma clearance were obtained using data in the literature. These relationships were incorporated into a compartmental model of tumor targeting using MATLAB to predict the magnitude, specificity, time dependence, and affinity dependence of tumor uptake for molecules across a broad size spectrum. In the typical size range for proteins, the model uncovers a complex trend in which intermediate-sized targeting agents (MW, approximately 25 kDa) have the lowest tumor uptake, whereas higher tumor uptake levels are achieved by smaller and larger agents. Small peptides accumulate rapidly in the tumor but require high affinity to be retained, whereas larger proteins can achieve similar retention with >100-fold weaker binding. For molecules in the size range of liposomes, the model predicts that antigen targeting will not significantly increase tumor uptake relative to untargeted molecules. All model predictions are shown to be consistent with experimental observations from published targeting studies. The results and techniques have implications for drug development, imaging, and therapeutic dosing.
Improved prognostic classification of patients receiving salvage systemic therapy for advanced urothelial carcinoma. (2015)

311 Background: Previously identified prognostic factors in patients (pts) receiving salvage systemic therapy for advanced urothelial carcinoma (UC) include performance status (PS), liver metastasis (LM), hemoglobin (Hb) and time from prior chemotherapy (TFPC). Given the prognostic impact of peripheral blood neutrophils (N), lymphocytes (L), thrombocytes (T) and albumin (Alb) in other malignancies, we investigated their impact in the salvage setting of advanced UC. Methods: Phase II trials of salvage systemic therapy were utilized. Data on N, L, T and Alb were required in addition to TFPC, Hb, PS and LM status. N, L, T and Alb were categorized as normal, &lt;lower limit of normal (LLN) and &gt;upper limit of normal (ULN). Cox proportional hazards regression was used to evaluate their association with overall survival (OS). An optimal regression model was constructed using forward stepwise selection and risk groups defined using number of identified adverse risk factors. Trial was a stratification factor. Results: Data was obtained from 10 trials accruing 708 pts. Of these, 682 pts had available TFPC, Hb, PS and LM status, while 631, 554, 649 and 491 had N, L, T and Alb available. Median OS was 6.8 (95% CI: 6.0-7.0) months. Neutrophilia (N&gt;ULN), thrombocytosis (T&gt;ULN) and hypoalbuminemia (Alb &lt;LLN) were significant poor prognostic factors for OS on univariate analyses. After adjustment for TFPC &lt;3 months, Hb &lt;10 g/dl, PS &gt;0 and LM status, only thrombocytosis and hypoalbuminemia remained significant (Table). Risk groups were constructed. Median OS was 8.8, 6.3, 5.0 and 3.8 months for n=290, 220, 123 and 49 patients with 0-1, 2, 3 and ≥4 factors. This 6-factor prognostic model was internally validated with an improvement in the c-index from 0.564 to 0.590. Conclusions: The addition of hypoalbuminemia and thrombocytosis to TFPC, Hb, PS and LM status enhanced the prognostic risk groupings in pts receiving salvage systemic therapy for advanced UC. [Table: see text]
System identification using Kautz models (1994)

In this paper, the problem of approximating a linear time-invariant stable system by a finite weighted sum of given exponentials is considered. System identification schemes using Laguerre models are extended and generalized to Kautz models, which correspond to representations using several different possible complex exponentials. In particular, linear regression methods to estimate this sort of model from measured data are analyzed. The advantages of the proposed approach are the simplicity of the resulting identification scheme and the capability of modeling resonant systems using few parameters. The subsequent analysis is based on the result that the corresponding linear regression normal equations have a block Toeplitz structure. Several results on transfer function estimation are extended to discrete Kautz models, for example, asymptotic frequency domain variance expressions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Sculpting (1991)

We present a new interactive modeling technique based on the notion of sculpting a solid material. A sculpting tool is controlled by a 3D input device and the material is represented by voxel data; the tool acts by modifying the values in the voxel array, much as a "paint" program's "paintbrush" modifies bitmap values. The voxel data is converted to a polygonal surface using a "marching-cubes" algorithm; since the modifications to the voxel data are local, we accelerate this computation by an incremental algorithm and accelerate the display by using a special data structure for determining which polygons must be redrawn in a particular screen region. We provide a variety of tools: one that cuts away material, one that adds material, a "sandpaper" tool, a "heat gun," etc. The technique provides an intuitive direct interaction, as if the user were working with clay or wax. The models created are free-form and may have complex topology; however, they are not precise, so the technique is appropriate for modeling a boulder or a tooth but not for modeling a crankshaft.
The Drosophila 18 wheeler is required for morphogenesis and has striking similarities to Toll (1994)

We have isolated and characterized a novel gene, named 18 wheeler (18w) for its unique segmental expression pattern in Drosophila embryos and expression in cells that migrate extensively. 18 wheeler transcripts accumulate in embryos in a pattern reminiscent of segment polarity genes. Mutations in 18w cause death during larval development and early adulthood. Escaping mutant adults often display leg, antenna, and wing deformities, presumably resulting from improper eversion of imaginal discs. Sequence analysis indicates that 18w encodes a transmembrane protein with an extracellular moiety containing many leucine rich repeats and cysteine motifs, and an intracellular domain bearing homology to the cytoplasmic portion of the interleukin-1-receptor. Expression of 18W protein in non-adhesive Schneider 2 cells promotes rapid and robust aggregation of cells. Analysis of the expression of 18w in different mutant backgrounds shows that it is under control of segment polarity and homeotic genes. The data suggest that the 18W protein participates in the developmental program specified by segmentation and homeotic genes as a cell adhesion or receptor molecule that facilitates cell movements.
PD-1+memory phenotype CD4+T cells expressing C/EBPα underlie T cell immunodepression in senescence and leukemia (2009)

Although altered T cell function plays a part in immunosenescence, the mechanisms remain uncertain. Here we identify a bona fide age-dependent PD-1(+) memory phenotype (MP) CD4(+) T cell subpopulation that hardly proliferates in response to T cell receptor (TCR) stimulation and produces abundant osteopontin at the cost of typical T cell lymphokines. These T cells demonstrate impaired repopulation in Rag2(-/-) mice, but a homeostatic proliferation in gamma-ray-irradiated mice. These T cells also reveal a unique molecular signature, including a strong expression of C/EBPalpha normally expressed in myeloid-lineage cells, with diminished c-Myc and cyclin D1. Transduction of Cebpa in regular CD4(+) T cells inhibited the TCR-mediated proliferation with c-Myc and cyclin D1 repression and caused a striking activation of Spp1 encoding osteopontin along with concomitant repression of T cell lymphokine genes. Although these T cells gradually increase in number with age and become predominant at the senescent stage in normal mice, the generation is robustly accelerated during leukemia. In both conditions, their predominance is associated with the diminution of specific CD4(+) T cell response. The results suggest that global T cell immunodepression in senescence and leukemia is attributable to the increase in PD-1(+) MP CD4(+) T cells expressing C/EBPalpha.
Nonlinear conversion efficiency in Kerr frequency comb generation (2014)

We analytically and numerically investigate the nonlinear conversion efficiency in ring microresonator-based mode-locked frequency combs under different dispersion conditions. Efficiency is defined as the ratio of the average round trip energy values for the generated pulse(s) to the input pump light. We find that the efficiency degrades with growth of the comb spectral width and is inversely proportional to the number of comb lines. It depends on the cold-cavity properties of a microresonator only and can be improved by increasing the coupling coefficient. Also, it can be increased in the multi-soliton state.