gebhart/patrepeval huggingface dataset:
Neuroprotective effects of cannabidiol in endotoxin-induced uveitis: critical role of p38 MAPK activation. (2008)

Retinal inflammation and degeneration in uveitis are caused by oxidative stress. CBD exerts anti-inflammatory and neuroprotective effects by a mechanism that involves blocking oxidative stress and activation of p38 MAPK and microglia.
Silanized nucleic acids: a general platform for DNA immobilization (2000)

We have developed a method for simultaneous deposition and covalent cross-linking of oligonucleotide or PCR products on unmodified glass surfaces. By covalently conjugating an active silyl moiety onto oligonucleotides or cDNA in solutions we have generated a new class of modified nucleic acids, namely silanized nucleic acids. Such silanized molecules can be immobilized instantly onto glass surfaces after manual or automated deposition. This method provides a simple and rapid, yet very efficient, solution to the immobilization of prefabricated oligonucleotides and DNA for chip production.
Sub-second quantum cascade laser based infrared spectroscopic ellipsometry (2019)

Laser-based infrared spectroscopic ellipsometry (SE) is demonstrated for the first time, to the best of our knowledge, by applying a tunable quantum cascade laser (QCL) as a mid-infrared light source. The fast tunability of the employed QCL, combined with phase-modulated polarization, enabled the acquisition of broadband (900<i>-</i>1204 <i>cm</i><sup>-1</sup>), high-resolution (1 <i>cm</i><sup>-1</sup>) ellipsometry spectra in less than 1 second. A comparison to a conventional Fourier-transform spectrometer-based IR ellipsometer resulted in an improved signal-to-noise ratio (SNR) by a factor of at least 290. The ellipsometry setup was finally applied for the real-time monitoring of molecular reorientation during the stretching process of an anisotropic polypropylene film, thereby illustrating the advantage of sub-second time resolution. The developed method exceeds existing instrumentation by its fast acquisition and high SNR, which could open up a set of new applications of SE such as ellipsometric inline process monitoring and quality control.
Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (Trail) Is an Inhibitor of Autoimmune Inflammation and Cell Cycle Progression (2000)

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis of tumor cells but not normal cells; its role in normal nontransformed tissues is unknown. We report here that chronic blockade of TRAIL in mice exacerbated autoimmune arthritis, and that intraarticular TRAIL gene transfer ameliorated the disease. In vivo, TRAIL blockade led to profound hyperproliferation of synovial cells and arthritogenic lymphocytes and heightened the production of cytokines and autoantibodies. In vitro, TRAIL inhibited DNA synthesis and prevented cell cycle progression of lymphocytes. Interestingly, TRAIL had no effect on apoptosis of inflammatory cells either in vivo or in vitro. Thus, unlike other members of the tumor necrosis factor superfamily, TRAIL is a prototype inhibitor protein that inhibits autoimmune inflammation by blocking cell cycle progression.
Large-Scale Optical Neural Networks Based on Photoelectric Multiplication (2019)

A scheme for implementing optical neural networks offers the energy benefits of optical components while being scalable to large systems, promising low-energy processing with order-of-magnitude improvements in network performance.
Region of interest editing of MPEG-2 video streams in the compressed domain (2005)

We describe a method for dynamically variable region-of-interest editing of MPEG-2 video streams in the compressed domain to reduce bandwidth. This method is used in our second-generation mutually immersive mobile telepresence system, where only the region containing a user's head in an acquired video stream needs to be displayed at the remote location. This editing is performed in a way that leaves the resulting stream consistent with the MPEG-2 standard. We currently reduce the transmission of data by skipping macroblocks or deleting DCT coefficients outside the region of interest in P and B pictures, and deleting DCT coefficients in I frames. This results in a savings of approximately 50% of the bandwidth of the original stream for our application. Since we are transmitting four video streams to the surrogate over our wireless network, the total bandwidth is reduced by about 5 Mbit/s. As an added benefit, the CPU requirements for decoding the edited stream in software are also reduced by approximately 16%.
Combined expression of pTα and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis (2002)

Notch receptors are conserved regulators of cell fate and have been implicated in the regulation of T cell differentiation and lymphomagenesis. However, neither the generality of Notch involvement in leukemia, nor the molecules with which Notch may interact have been clarified. Recently, we showed that transgenic mice expressing the constitutively active intracellular domain of Notch3 in thymocytes and T cells developed early and aggressive T cell neoplasias. Although primarily splenic, the tumors sustained features of immature thymocytes, including expression of pTalpha, a defining component of the pre T cell receptor, known to be a potent signaling complex provoking thymocyte survival, proliferation, and activation. Thus, enforced expression of Notch3, which is ordinarily down-regulated as thymocytes mature, may sustain pre T cell receptor expression, causing dysregulated hyperplasia. This hypothesis has been successfully tested in this article by the observation that deletion of pTalpha in Notch3 transgenic mice abrogates tumor development, indicating a crucial role for pTalpha in T cell leukemogenesis. Parallel observations were made in humans, in that all T cell acute lymphoblastic leukemias examined showed expression of Notch3 and of the Notch target gene HES-1, as well as of pTalpha a and b transcripts, whereas the expression of all these genes was dramatically reduced or absent in remission. Together, these results suggest that the combined expression of Notch3 and pTalpha sustains T cell leukemogenesis and may represent pathognomonic molecular features of human T-ALL.
Dose-dependent inhibition of the EGFR and signalling pathways with the anti-EGFR monoclonal antibody (MAb) EMD 72000 administered every three weeks (q3w). A phase I pharmacokinetic/pharmacodynamic (PK/PD) study to define the optimal biological dose (OBD) (2004)

2002 Background: EMD 72000, an IgG1 humanized anti-EGFR MAb, has a prolonged half life and we showed that 1200q3w has favorable PK profile when compared to more frequent schedules (Tabernero et al, Proc ASCO 2003, abst 770). To define the OBD of q3w EMD 72000, we have now studied additional dose levels: 400, 800 and 1600 mg. Methods: Skin and tumor biopsies were performed at - 24 hrs and + 43 days of treatment. pEGFR, pMAPK, Ki67 and p27 were done by immunohistochemistry. Results: 51 patients (p) with EGFR+ tumors were treated, including the 1200 mg cohorts (also q1w and q2w). Patient characteristics, median (range): Karnofsky 90% (80%–100%), age 59 (43–79), and prior chemotherapy 3 (1–11). To date, 22 paired skin samples have been analyzed. Data on 1600 mg are not yet available. EMD 72000 induced decreases in Ki67, pMAPK, pEGFR and an increase in p27. The two best discriminating markers were pEGFR and pMAPK with a dose-dependent incremental inhibition and near complete signaling suppression at the 1200 mg dose level (Table). Data is reported as mean inhibition from baseline and as number of p with complete inhibition (<5% residual positivity). Grade 1 and 2 skin toxicity was observed in 43% and 35% of p, respectively. Skin toxicity was lower in the 400 mg. Drug troughs at 800-1200 mg q3w were 4–10 times higher than preclinical active levels. Activity: 3 PRs, 4 prolonged SD out of 39 evaluable p with colon cancer. Conclusions: This PD skin study with EMD 72000 shows a dose response effect on EGFR pathway inhibition. The dose level with suboptimal receptor inhibition also resulted in lower skin rash. Our findings suggest that the OBD will be close to 1200 mg q3w and supports a surrogate marker approach to OBD identification with anti-EGFR agents. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Merck KGaA
Creating Long-Lived Superhydrophobic Polymer Surfaces Through Mechanically Assembled Monolayers (2000)

We show that elastomeric surfaces can be tailored using "mechanically assembled monolayers" (MAMs), structures that are fabricated by combining self-assembly of surface grafting molecules with mechanical manipulation of the grafting points in the underlying elastic surface. The versatility of this surface modification method is demonstrated by fabricating MAMs with semifluorinated (SF) molecules. These SF-MAMs have superior nonwetting and barrier properties in that they are "superhydrophobic" and nonpermeable. We also establish that these material characteristics do not deteriorate even after prolonged exposure to water, which usually causes surface reconstruction in conventionally prepared SF self-assembled monolayers.
Stem cells of the adult cornea: From cytometric markers to therapeutic applications (2008)

The cornea is a major protective shield of the interior of the eye and represents two thirds of its refractive power. It is made up of three tissue layers that have different developmental origins: the outer, epithelial layer develops from the ectoderm overlying the lens vesicle, whereas the stroma and the endothelium have mesenchymal origin. In the adult organism, the outermost corneal epithelium is the most exposed to environmental damage, and its constant renewal is assured by the epithelial stem cells that reside in the limbus, the circular border of the cornea. Cell turnover in the stromal layer is very slow and the endothelial cells probably do not reproduce in the adult organism. However, recent experimental evidence indicates that stem cells may be found in these layers. Damage to any of the corneal layers leads to loss of transparency and low vision. Corneal limbal stem cell deficiency results in severe ocular surface disease and its treatment by transplantating ex vivo expanded limbal epithelial cells is becoming widely accepted today. Stromal and endothelial stem cells are potential tools of tissue engineering and regenerative therapies of corneal ulcers and endothelial cell loss. In the past few years, intensive research has focused on corneal stem cells aiming to improve the outcomes of the current corneal stem cell transplantation techniques. This review summarizes the current state of knowledge on corneal epithelial, stromal and endothelial stem cells. Special emphasis is placed on the molecular markers that may help to identify these cells, and the recently revealed mechanisms that could maintain their "stemness" or drive their differentiation. The techniques for isolating and culturing/expanding these cells are also described.
Vascular risk factors, incidence of MCI, and rates of progression to dementia (2004)

In this population, among those who progressed to dementia, 60% progressed to AD and 33% to VaD. Vascular risk factors influence incident mild cognitive impairment and the rate of progression to dementia.
Are opioids effective in relieving neuropathic pain? (1999)

The purpose of this review is to identify important issues and to review the data that underlie the controversial effectiveness of opioids in relieving neuropathic pain. This controversy seems related to the use of multiple definitions of neuropathic pain together with its distinct mechanisms in both experimental animal models and human neuropathic pain syndromes, methodological shortcomings in available randomized controlled clinical trials, different methods of pain assessment, the inappropriate use of terms like efficacy and responsiveness, differential responses in spontaneous versus evoked pains, interindividual differences to specific opioids and opioid doses, and duration of follow-up. New randomized controlled clinical trials with opioids in neuropathic pain are still needed. These studies should include larger patient samples with rigorously defined homogeneous neuropathic pain syndromes. Active placebo's mimicking side-effects should be included in the double-blind design, and control of unmasking should be performed. Individual titration of the opioid dose and active management of side-effects in long-term follow-up studies need to measure both pain relief and quality of life.
Glycation and inactivation of human Cu-Zn-superoxide dismutase. Identification of the in vitro glycated sites. (1987)

The nonenzymatic glycosylation (glycation) of Cu-Zn-superoxide dismutase led to gradual inactivation of the enzyme (Arai, K. Iizuka, S., Tada, Y., Oikawa, K., and Taniguchi, N. (1987) Biochim. Biophys. Acta 924, 292-296). The purified superoxide dismutase from human erythrocytes comprises both glycated and nonglycated forms. The nonglycated Cu-Zn-superoxide dismutase was isolated by boronate affinity chromatography. Incubation of the nonglycated superoxide dismutase with D-[6-3H]glucose in vitro resulted in the gradual accumulation of radioactivity in the enzyme protein, and Schiff base adducts were trapped by NaBH4. The sites of glycation of the superoxide dismutase were identified by amino acid analysis after reverse-phase high performance liquid chromatography of the trypsin-treated peptides. Lysine residues, i.e. Lys3, Lys9, Lys30, Lys36, Lys122, and Lys128, were found to be glycated. Three of the glycated sites lie in Lys-Gly, two in Lys-Ala, and one in Lys-Val. The inactivation of the superoxide dismutase on the glycation is due mainly to the glycation of Lys122 and Lys128, which are supposed to be located in an active site liganding loop. The remaining five sites, such as Lys-Glu, Lys-Asp, Lys-His, and Lys-Thr are relatively inactive as to the formation of either a Schiff base or an Amadori adduct.
High-power single-mode fiber amplifiers using multimode fibers (2002)

Summary form only given. As the optical power levels extractable from current single-mode (SM) fiber amplifiers are reaching regions where optical nonlinearities become significant, even under cw operation, it is becoming increasingly important to develop methods for reducing these nonlinearities to further boost the amplifier performance. Here we demonstrate a simple new approach, namely the SM excitation of specially designed large-core multimode (MM) fibers. Cladding-pumped Er/Yb amplifier versions of such fibers allow the direct amplification of diffraction-limited optical soliton pulses with peak powers up to 12 kW, about one order of magnitude larger than possible with conventional fiber amplifiers.
Western Blot Detection of Scrapie-associated Fibril Protein in Tissues outside the Central Nervous System from Preclinical Scrapie-infected Mice (1988)

We describe a method of sample preparation to detect scrapie-associated fibril (SAF) proteins in small amounts of scrapie-infected mouse tissues by Western blot analysis using an antiserum to a synthetic peptide that corresponds to the N-terminal region of hamster prion protein. SAF proteins were efficiently detected in brain tissue by this procedure. The proteins were also detected in preparations from spleen and lymph node. SAF proteins were detected in brain samples at 24 weeks after intraperitoneal infection. Using spleen samples, the proteins were detected from mice in the preclinical stage (from 4 weeks after infection), clinical symptoms of scrapie were observed in some mice from 22 weeks after infection.
Vertical Pillar-Superlattice Array and Graphene Hybrid Light Emitting Diodes (2010)

We report a type of device that combines vertical arrays of one-dimensional (1D) pillar-superlattice (PSL) structures with 2D graphene sheets to yield a class of light emitting diode (LED) with interesting mechanical, optical, and electrical characteristics. In this application, graphene sheets coated with very thin metal layers exhibit good mechanical and electrical properties and an ability to mount, in a freely suspended configuration, on the PSL arrays as a top window electrode. Optical characterization demonstrates that graphene exhibits excellent optical transparency even after deposition of the thin metal films. Thermal annealing of the graphene/metal (Gr/M) contact to the GaAs decreases the contact resistance, to provide enhanced carrier injection. The resulting PSL-Gr/M LEDs exhibit bright light emission over large areas. The result suggests the utility of graphene-based materials as electrodes in devices with unusual, nonplanar 3D architectures.
Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases (2010)

High-resolution imaging of molecules intrinsically involved in malignancy and metastasis would be of great value for clinical detection and staging of tumors. We now report in vivo visualization of matrix metalloproteinase activities by MRI and fluorescence of dendrimeric nanoparticles coated with activatable cell penetrating peptides (ACPPs), labeled with Cy5, gadolinium, or both. Uptake of such nanoparticles in tumors is 4- to 15-fold higher than for unconjugated ACPPs. With fluorescent molecules, we are able to detect residual tumor and metastases as small as 200 microm, which can be resected under fluorescence guidance and analyzed histopathologically with fluorescence microscopy. We show that uptake via this mechanism is comparable to that of other near infrared protease sensors, with the added advantage that the approach is translatable to MRI. Once activated, the Gd-labeled nanoparticles deposit high levels (30-50 microM) of Gd in tumor parenchyma with even higher amounts deposited in regions of infiltrative tumor, resulting in useful T(1) contrast lasting several days after injection. These results should improve MRI-guided clinical staging, presurgical planning, and intraoperative fluorescence-guided surgery. The approach may be generalizable to deliver radiation-sensitizing and chemotherapeutic agents.
Linearization of a 65nm CMOS power amplifier with a Cartesian Feedback for W-CDMA standard (2009)

A study based on improving linearity of an integrated RF power amplifier (PA) has been done for W-CDMA standard. This power amplifier had been designed in 65 nm CMOS of STMicroelectronics under Cadence. The chosen linearization technique is a Cartesian Feedback (CFB). Thanks to this linearization technique, the ACPR has been improved by 22 dB at 5 MHz from the carrier for an output power of 18 dBm.
Olympic boxing is associated with elevated levels of the neuronal protein tau in plasma (2013)

Olympic boxing is associated with elevation of tau in plasma. The repetitive minimal head injury in boxing may lead to axonal injuries that can be diagnosed with a blood test.
The effects of acute nicotine on contextual safety discrimination (2014)

Anxiety disorders, such as post-traumatic stress disorder (PTSD), may be related to an inability to distinguish safe versus threatening environments and to extinguish fear memories. Given the high rate of cigarette smoking in patients with PTSD, as well as the recent finding that an acute dose of nicotine impairs extinction of contextual fear memory, we conducted a series of experiments to investigate the effect of acute nicotine in an animal model of contextual safety discrimination. Following saline or nicotine (at 0.0275, 0.045, 0.09 and 0.18 mg/kg) administration, C57BL/6J mice were trained in a contextual discrimination paradigm, in which the subjects received presentations of conditioned stimuli (CS) that co-terminated with a foot-shock in one context (context A (CXA)) and only CS presentations without foot-shock in a different context (context B (CXB)). Therefore, CXA was designated as the 'dangerous context', whereas CXB was designated as the 'safe context'. Our results suggested that saline-treated animals showed a strong discrimination between dangerous and safe contexts, while acute nicotine dose-dependently impaired contextual safety discrimination (Experiment 1). Furthermore, our results demonstrate that nicotine-induced impairment of contextual safety discrimination learning was not a result of increased generalized freezing (Experiment 2) or contingent on the common CS presentations in both contexts (Experiment 3). Finally, our results show that increasing the temporal gap between CXA and CXB during training abolished the impairing effects of nicotine (Experiment 4). The findings of this study may help link nicotine exposure to the safety learning deficits seen in anxiety disorder and PTSD patients.
Specific uptake of m-[125I]iodobenzylguanidine in the human neuroblastoma cell line SK-N-SH. (1985)

The uptake of m-[125I]iodobenzylguanidine (mIBG), a compound structurally analogous to the antihypertensive drug guanethidine, was examined in various human cell lines. Of three neuroblastoma lines, SK-N-LO, IMR-32, and SK-N-SH, only the last showed specific uptake of the compound. In contrast, only a nonspecific uptake could be demonstrated for the other neuroblastoma lines, as well as for an osteogenic sarcoma line (SAOS-2) and a melanoma line (IgR 3). Based on analyses of uptake characteristics from Lineweaver-Burk plots it is evident that two different transport mechanisms are responsible for mIBG uptake into SK-N-SH cells: a nonspecific diffusion mechanism, and a specific, active uptake system. The latter was dramatically reduced at 4 degrees compared to 37 degrees, as well as in the presence of ouabain or the absence of oxygen. A competitive inhibition of the transport of mIBG by norepinephrine was observed. When drug-treated SK-N-SH cells were incubated in fresh medium, 20 to 30% of mIBG was still retained in the SK-N-SH cells 24 h after the end of incubation with mIBG, whereas no mIBG was detectable in SK-N-LO cells already after 1 h.
Optical tomography in medical imaging (1999)

We present a review of methods for the forward and inverse problems in optical tomography. We limit ourselves to the highly scattering case found in applications in medical imaging, and to the problem of absorption and scattering reconstruction. We discuss the derivation of the diffusion approximation and other simplifications of the full transport problem. We develop sensitivity relations in both the continuous and discrete case with special concentration on the use of the finite element method. A classification of algorithms is presented, and some suggestions for open problems to be addressed in future research are made.
The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity (2017)

Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis. These findings reveal a direct molecular link between TP53 and DPP4 in the control of lipid metabolism and may provide a precision medicine strategy for the treatment of colorectal cancer by induction of ferroptosis.