gebhart/patrepeval huggingface dataset:
The Thalamic Intralaminar Nuclei: A Role in Visual Awareness (1997)

We briefly review the anatomy and functional properties of the intralaminar nuclei (ILN) of the thalamus and the neurological disorders associated with their dysfunction. The ILN project over a wide range of cortical territories and are connected to several subcortical structures that place the ILN within the distributed networks underlying arousal, attention, working memory, and gaze control. The temporal structure of the spike discharges of ILN neurons can be controlled by levels of arousal and visuomotor behavior. Taken together, the anatomy, cellular physiology, and clinical data suggest that in the state of wakefulness, the ILN neurons promote the formation of an “event-holding” function in the cortex. In the prefrontal cortex, this function facilitates the storage of target location in working memory. In the frontal eye fields, the function produces sustained activation that anticipates the onset of intended eye movements. In the posterior parietal cortex, the sustained activation can be boosted at the start of the intersaccadic interval and can operate as an attentional gate regulating the flow of information back to the prefrontal cortex. The attentional gate is of limited capacity, as is working memory, and is best utilized during the intersaccadic interval. The ILN may help to synchronize the eye movement commands of the frontal eye fields with the episodic dynamics of the attentional gate and working memory.
Optical Figure Characterization For Cylindrical Mirrors And Lenses (1981)

Evaluation of the quality of cylindrical optical elements has always presented severe difficulties. Previous techniques have depended on either indirect methods or methods providing relatively poor resolution. A new basic interferometric technique makes possible direct figure characterization for cylindrical optics utilizing conventional interferometric equipment. Several variations are possible for different test conditions for both cylindrical mirrors and cylindrical lenses. This measurement technique has been applied successfully to cylindrical mirrors and lenses. The basic technique and several variations are presented and discussed. Examples of the results of actual tests are included with test conditions specified, and a complete listing of necessary conventional interferometric equipment is given.
Optimally efficient resonance-tuned optical modulators (2009)

Based on a first-principles, physically-intuitive design approach, I propose novel resonance-tuned intensity modulators with optimal modulation efficiency and extinction, even for lossy modulation mechanisms, including higher-order designs cascadable on wavelength-division multiplexed (WDM) signal waveguides.
Three-dimensional structure of NADPH–cytochrome P450 reductase: Prototype for FMN- and FAD-containing enzymes (1997)

Microsomal NADPH-cytochrome P450 reductase (CPR) is one of only two mammalian enzymes known to contain both FAD and FMN, the other being nitric-oxide synthase. CPR is a membrane-bound protein and catalyzes electron transfer from NADPH to all known microsomal cytochromes P450. The structure of rat liver CPR, expressed in Escherichia coli and solubilized by limited trypsinolysis, has been determined by x-ray crystallography at 2.6 A resolution. The molecule is composed of four structural domains: (from the N- to C- termini) the FMN-binding domain, the connecting domain, and the FAD- and NADPH-binding domains. The FMN-binding domain is similar to the structure of flavodoxin, whereas the two C-terminal dinucleotide-binding domains are similar to those of ferredoxin-NADP+ reductase (FNR). The connecting domain, situated between the FMN-binding and FNR-like domains, is responsible for the relative orientation of the other domains, ensuring the proper alignment of the two flavins necessary for efficient electron transfer. The two flavin isoalloxazine rings are juxtaposed, with the closest distance between them being about 4 A. The bowl-shaped surface near the FMN-binding site is likely the docking site of cytochrome c and the physiological redox partners, including cytochromes P450 and b5 and heme oxygenase.
Modified silica gels as selective adsorbents for sulphur dioxide (1974)

R. L. Burwell and O. Leal, J. Chem. Soc., Chem. Commun., 1974, 342 DOI: 10.1039/C39740000342
A low-complexity face-assisted coding scheme for low-bit-rate video telephony (2003)

SUMMARY This paper presents a novel and practical faceassisted video coding scheme to enhance the visual quality of the face region in videophone applications. A low-complexity skincolor-based face detection and tracking scheme is proposed to locate the human face regions in realtime. After classifying the macroblocks (MBs) into the face and non-face regions, we present a dynamic distortion-weighting adjustment (DDWA) scheme to skip encoding the static non-face MBs, and the saved bits are used to compensate the face region by increasing the distortion weighting of the face MBs. The quality of the face regions will thus be largely enhanced. Moreover, the computation originally required for encoding the skipped MBs can also be saved. The experimental results show that the proposed method can significantly improve the PSNR and the subjective quality of face regions, while the degradation introduced on the non-face areas is relatively invisible to human perception. The proposed algorithm is fully compatible with the H.263 standard, and the low complexity feature makes it well suited to be implemented for
Immune Escape Mechanisms as a Guide for Cancer Immunotherapy (2014)

Immunotherapy has demonstrated impressive outcomes for some patients with cancer. However, selecting patients who are most likely to respond to immunotherapy remains a clinical challenge. Here, we discuss immune escape mechanisms exploited by cancer and present strategies for applying this knowledge to improving the efficacy of cancer immunotherapy.
Modified Nucleotides as Substrates of Terminal Deoxynucleotidyl Transferase (2017)

The synthesis of novel modified nucleotides and their incorporation into DNA sequences opens many possibilities to change the chemical properties of oligonucleotides (ONs), and, therefore, broaden the field of practical applications of modified DNA. The chemical synthesis of nucleotide derivatives, including ones bearing thio-, hydrazino-, cyano- and carboxy groups as well as 2-pyridone nucleobase-containing nucleotides was carried out. The prepared compounds were tested as substrates of terminal deoxynucleotidyl transferase (TdT). The nucleotides containing <i>N</i>⁴-aminocytosine, 4-thiouracil as well as 2-pyridone, 4-chloro- and 4-bromo-2-pyridone as a nucleobase were accepted by TdT, thus allowing enzymatic synthesis of 3'-terminally modified ONs. The successful UV-induced cross-linking of 4-thiouracil-containing ONs to TdT was carried out. Enzymatic post-synthetic 3'-modification of ONs with various photo- and chemically-reactive groups opens novel possibilities for future applications, especially in analysis of the mechanisms of polymerases and the development of photo-labels, sensors, and self-assembling structures.
Live‐Cell‐Permeable Poly(p‐phenylene ethynylene) (2007)

Light up my life: Stable, bright, conjugated-polymer nanoparticles (CPNs) show promise for fluorescence imaging of live cells. The cell-permeable CPNs are synthesized by a simple solvent exchange, and accumulate exclusively in the cytosol (see picture) without any noticeable inhibition of cell viability. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z701991_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Wireless intra-ocular pressure monitoring system integrated into an artificial lens (2002)

Reports the concept and first results of a hybrid integrated telemetric pressure measuring system for continuous monitoring of the intra-ocular pressure. The system is designed for glaucoma differential diagnosis and follow up. The measuring system is highly miniaturized using advanced flip-chip mounting technology to fulfil the spatial requirements of integration into the fringe of an intra-ocular lens without the necessity of a monolithically integrated sensor. The surface micro-machined pressure sensor is used in an integrated hybrid circuit comprising the sensor itself and a dedicated read-out circuit in standard CMOS technology. First experimental results of the system are presented. The concept of the telemetric data transmission, mounting and assembly, the coating and EMC problem is discussed briefly.
Selective cytokine release induced by serum and separated plasma from septic patients. (1996)

Serum and separated plasma from septic patients contained agents which induced monocytes to release mediators without additional stimulation, and modified their response to LPS. Removing plasma from septic patients may therefore reduce the deleterious effect of the inflammatory response.
RANKL and RANK as novel therapeutic targets for arthritis (2003)

The TNF-family molecule receptor activator of nuclear factor kappa B (NFkappaB) ligand (RANKL) (OPGL, TRANCE, ODF) and its receptor activator of NFkappaB (RANK) are key regulators of bone remodeling and regulate T cell/dendritic cell communications, and lymph node formation. Moreover, RANKL and RANK are expressed in mammary gland epithelial cells and control the development of a lactating mammary gland during pregnancy. Genetically, RANKL and RANK are essential for the development and activation of osteoclasts and bone loss in response to virtually all triggers tested. Inhibition of RANKL function via the natural decoy receptor osteoprotegerin (OPG, TNFRSF11B) prevents bone loss in postmenopausal osteoporosis and cancer metastases. Importantly, RANKL appears to be the pathogenetic principle that causes bone and cartilage destruction in arthritis, and OPG treatment prevents bone loss at inflamed joints and has partially beneficial effects on cartilage destruction in all arthritis models studied so far. Modulation of these systems provides a unique opportunity to design novel therapeutics to inhibit bone loss and crippling in arthritis.
Rrn3 Becomes Inactivated in the Process of Ribosomal DNA Transcription (2003)

The human homologue of yeast Rrn3, a 72-kDa protein, is essential for ribosomal DNA (rDNA) transcription. Although the importance of Rrn3 function in rDNA transcription is well established, its mechanism of action has not been determined. It has been suggested that the phosphorylation of either yeast RNA polymerase I or mammalian Rrn3 regulates the formation of RNA polymerase I.Rrn3 complexes that can interact with the committed template. These and other reported differences would have implications with respect to the mechanism by which Rrn3 functions in transcription. For example, in the yeast rDNA transcription system, Rrn3 might function catalytically, but in the mammalian system it might function stoichiometrically. Thus, we examined the question as to whether Rrn3 functions catalytically or stoichiometrically. We report that mammalian Rrn3 becomes the limiting factor as transcription reactions proceed. Moreover, we demonstrate that Rrn3 is inactivated during the transcription reactions. For example, Rrn3 isolated from a reaction that had undergone transcription cannot activate transcription in a subsequent reaction. We also show that this inactivated Rrn3 not only dissociates from RNA polymerase I, but is not capable of forming a stable complex with RNA polymerase I. Our results indicate that Rrn3 functions stoichiometrically in rDNA transcription and that its ability to associate with RNA polymerase I is lost upon transcription.
Tumor lysis syndrome occurring after the administration of rituximab in lymphoproliferative disorders: High-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia (1999)

Rituximab, an anti-CD20 antibody, has been recently approved for the treatment of low-grade or follicular non-Hodgkin's lymphoma (NHL). Because of its relatively benign side effect profile, it has been considered a nontoxic alternative to chemotherapy. Recently, however, tumor lysis syndrome (TLS) resulting from rituximab has been reported in a patient with chronic lymphocytic leukemia (CLL). We herein present two cases of rituximab-induced TLS. The first case occurred in a patient with high-grade NHL, while the second case occurred in a patient with CLL. We also present a summary of the literature regarding TLS induced by immunotherapies.
Protection from tumor necrosis factor-mediated cytolysis by overexpression of plasminogen activator inhibitor type-2. (1991)

Pretreatment of HT-1080 fibrosarcoma cells with tumor necrosis factor (TNF) induced resistance to the cytolytic activity of this cytokine in combination with cycloheximide. This resistance correlated with the synthesis of plasminogen activator inhibitor type-2 (PAI-2). HT-1080 cells were transfected with a PAI-2 expression vector in both sense and antisense orientation. The resistance to TNF-mediated cytolysis of transfected cell clones was correlated with the level of PAI-2 expression. Cells expressing antisense PAI-2 RNA showed reduced expression of PAI-2 and increased sensitivity to TNF-mediated cytolysis. Cells expressing constitutively PAI-2 were treated with TNF and cycloheximide to select cells with increased resistance to cytolysis and enhanced PAI-2 expression. PAI-2 gradually disappeared during a treatment with TNF and cycloheximide. This finding suggested that PAI-2 formed a complex with a target proteinase, which could be involved in mediating the cytolytic activity of TNF.
Profile measurements of cylindrical surfaces (1993)

We introduce an interferometric method for measuring the profiles of cylindrical surfaces. A Fizeau interferometer with a flat reference is used to test part of a cylindrical surface, and various parts of the surface can be tested by the rotation of the surface. The algorithm for linking separate measurements is described, and testing examples for measuring sagitta over 3 mm of a cylindrical surface with an elliptical cross section are included. Measurement results show that repeatability for the above test to the order of 1 microm, is feasible.
Distribution of DNA Vaccines Determines Their Immunogenicity After Intramuscular Injection in Mice (2000)

Intramuscular injection of DNA vaccines elicits potent humoral and cellular immune responses in mice. However, DNA vaccines are less efficient in larger animal models and humans. To gain a better understanding of the factors limiting the efficacy of DNA vaccines, we used fluorescence-labeled plasmid DNA in mice to 1) define the macroscopic and microscopic distribution of DNA after injection into the tibialis anterior muscle, 2) characterize cellular uptake and expression of DNA in muscle and draining lymph nodes, and 3) determine the effect of modifying DNA distribution and cellular uptake by volume changes or electroporation on the magnitude of the immune response. Injection of a standard 50-microl dose resulted in the rapid dispersion of labeled DNA throughout the muscle. DNA was internalized within 5 min by muscle cells near the injection site and over several hours by cells that were located along muscle fibers and in the draining lymph nodes. Histochemical staining and analysis of mRNA expression in isolated cells by RT-PCR showed that the transgene was detectably expressed only by muscle cells, despite substantial DNA uptake by non-muscle cells. Reduction of the injection volume to 5 microl resulted in substantially less uptake and expression of DNA by muscle cells, and correspondingly lower immune responses against the transgene product. However, expression and immunogenicity were restored when the 5-microl injection was followed by electroporation in vivo. These findings indicate that distribution and cellular uptake significantly affect the immunogenicity of DNA vaccines.
Blood pressure reduction in "borderline" hypertensives following physical training. (1973)

One hundred and sixty-five middle-aged, apparently normal men were submitted to a six-month conditioning program. On the basis of a casual blood pressure measurement during the pre-training evaluation, 37 individuals (23%) were classified as "borderline" hypertensive. The remaining subjects (n = 128) were normotensive. At the conclusion of the program both groups exhibited significant reductions in systolic and diastolic blood pressures at rest and after submaximal work. Moreover, the reductions of the resting systolic and diastolic and of the exercise (300 kg.m./min.) systolic blood pressures were significantly greater for the hypertensives.
Discovery of 2-(6-{[(6-Fluoroquinolin-2-yl)methyl]amino}bicyclo[3.1.0]hex-3-yl)-N-hydroxypyrimidine-5-carboxamide (CHR-3996), a Class I Selective Orally Active Histone Deacetylase Inhibitor (2010)

A novel series of HDAC inhibitors demonstrating class I subtype selectivity and good oral bioavailability is described. The compounds are potent enzyme inhibitors (IC₅₀ values less than 100 nM), and improved activity in cell proliferation assays was achieved by modulation of polar surface area (PSA) through the introduction of novel linking groups. Employing oral pharmacokinetic studies in mice, comparing drug levels in spleen to plasma, we selected compounds that were tested for efficacy in human tumor xenograft studies based on their potential to distribute into tumor. One compound, 21r (CHR-3996), showed good oral activity in these models, including dose-related activity in a LoVo xenograft. In addition 21r showed good activity in combination with other anticancer agents in in vitro studies. On the basis of these results, 21r was nominated for clinical development.
New initiator system for the living anionic polymerization of tert-alkyl acrylates (1987)

peer reviewed
A vasoactive intestinal peptide antagonist inhibits non-small cell lung cancer growth. (1993)

The most prevalent lung cancer, non-small cell lung cancer (NSCLC) has receptors for vasoactive intestinal peptide (VIP). Here the effects of a VIP antagonist (VIP-hyb) on NSCLC growth were investigated. In vivo, when VIPhyb (10 micrograms, s.c.) was daily injected into nude mice, xenograft formation was significantly inhibited by approximately 80%. In vitro, VIP (100 nM) stimulated colony formation approximately 2-fold, whereas 1 microM VIPhyb inhibited colony formation by approximately 50% when adenocarcinoma cell line NCI-H838 was used. The attenuation of tumor proliferation is receptor mediated, as VIPhyb inhibited specific 125I-labeled VIP binding to cell lines NCI-H157 and NCI-H838 with an IC50 of 0.7 microM. VIP (10 nM) increased the cAMP levels 5-fold when cell line NCI-H838 was used, and 10 microM VIPhyb inhibited the increase in cAMP caused by VIP. Northern blot analysis and radioimmunoassays have shown VIP mRNA and VIP-like immunoreactivity in NSCLC cells. These data suggest that VIP may be a regulatory peptide in NSCLC and that VIPhyb is a VIP receptor antagonist that inhibits proliferation.
Conformational Changes in Bcl-2 Pro-survival Proteins Determine Their Capacity to Bind Ligands (2009)

Antagonists of anti-apoptotic Bcl-2 family members hold promise as cancer therapeutics. Apoptosis is triggered when a peptide containing a BH3 motif or a small molecule BH3 peptidomimetic, such as ABT 737, binds to the relevant Bcl-2 family members. ABT-737 is an antagonist of Bcl-2, Bcl-x(L), and Bcl-w but not of Mcl-1. Here we describe new structures of mutant BH3 peptides bound to Bcl-x(L) and Mcl-1. These structures suggested a rationale for the failure of ABT-737 to bind Mcl-1, but a designed variant of ABT-737 failed to acquire binding affinity for Mcl-1. Rather, it was selective for Bcl-x(L), a result attributable in part to significant backbone refolding and movements of helical segments in its ligand binding site. To date there are few reported crystal structures of organic ligands in complex with their pro-survival protein targets. Our structure of this new organic ligand provided insights into the structural transitions that occur within the BH3 binding groove, highlighting significant differences in the structural properties of members of the Bcl-2 pro-survival protein family. Such differences are likely to influence and be important in the quest for compounds capable of selectively antagonizing the different family members.
379. MicroRNA-29 and Micro-Dystrophin Combinatorial Therapy Suppresses Fibrosis and Restores Function to mdx/utrn+/− Mice (2016)

Duchenne muscular dystrophy (DMD) is caused by dystrophin deficiency resulting in muscle loss and progressive muscle weakness and fibrotic scarring. Muscle fibrosis impairs blood flow and excludes endomysial derived constituents hampering muscle repair and regeneration. Irrespective of the success of gene restoration (molecular or pharmacologic) functional improvement is limited without reduction of muscle fibrosis. miR-29c regulates collagen levels making it an ideal candidate for decreasing muscle fibrosis. miR-29c levels are reduced in DMD and our goal is to develop an anti-fibrotic therapy by overexpressing miR-29c with adeno-associated virus (AAV) mediated delivery in combination with micro-dystrophin to improve membrane stability. We injected scAAVrh.74.CMV. miR-29c alone, co-delivered with rAAVrh.74.MCK. micro-dystrophin, and rAAVrh.74.MCK. micro-dystrophin alone by intramuscular injection (IM) into the left gastrocnemius (GAS) muscle of 3 month old mdx/utrn+/- mice, a DMD mouse model. GAS muscle was analyzed 3 months post-injection to assess collagen accumulation by Sirius Red staining and subsequent quantification with ImageJ. Additional outcomes included miR-29c and collagen transcript levels, force measurements in the GAS muscle, fiber diameter measurements and western blot analysis for proteins involved in muscle regeneration (MyoD, Myogenin). Analogous to DMD tissue, we demonstrated a significant reduction in miR-29c levels in mdx/utrn+/− muscle correlated with increased fibrosis measured by Sirius red staining. Following 3 months of treatment with scAAV. miR-29c alone, there was a significant reduction in fibrosis (treated-23.5%±1.3 vs. untreated-27.8% ±0.6, p<0.01) in the GAS muscle. When co-delivered with micro-dystrophin we see further reduction in collagen (41%) by Sirius red staining along with significantly reduced mRNA levels of Col1A, Col3A, fibronectin and TGF-β levels. We observed an increase in specific and absolute force in the muscle treated with miR-29c alone compared to the untreated limb, which when combined with micro-dystrophin led to absolute and specific force that were not significantly different than wild-type (miR-29c treated-204.7±11.7 vs. untreated-151.6±14.5 vs. combined-244.2±6.6 vs. wild type-313.1±40.69 p<0.01). We also observed a significant increase in gastroc weight in those muscles that were co-treated. Demonstration of increased fibrosis and decreased miR-29c expression in the mdx/utrn+/− mice and dystrophin-deficient patients validates the mouse model as representative of the human disease. Initial results using AAV. miR-29c as an anti-fibrotic therapy suggest that there is beneficial effect with reduction in collagen levels, a key contributor in fibrosis. Moreover, when combined with micro-dystrophin to improve membrane stability, miR-29 upregulation normalized muscle force. These data provide rationale for overexpression of miR-29c to reduce fibrosis along with dystrophin replacement as a potential treatment for DMD.