gebhart/patrepeval huggingface dataset:
Functionally integrated systems on a chip: technologies, architectures, CAD tools, and applications (2002)

The most important challenge in developing next-generation electronics is producing devices that exceed today's performance levels while achieving ultra low-power efficiency and smaller package dimensions. The enabling technology is the evolution of digital, analog, and radio-frequency (RF) integrated circuits toward a monolithic implementation as a system on a chip (SOC). Applications range from consumer electronics like portable computing and mobile wireless communications, to aerospace and military for mobile intelligence systems and low-power satellites in scientific missions. Designs of this complexity require significant advanced in semiconductor technology to address the needs of diverse system components and ensure high-yield manufacturing. Systems will leverage conventional architectures, but the functional integration will also foster the development of novel circuit topologies. Finally, time-to-market demands motivate the emergence of a virtual wafer fab in which products can be designed, modeled, and simulated for validation before actual fabrication.
Stable field emission of single B-doped Si tips and linear current scaling of uniform tip arrays for integrated vacuum microelectronic devices (2012)

Advanced Si-based semiconductor technology is most suitable to fabricate uniform nanostructures as integrated field emitter arrays for novel vacuum electronic devices. In order to improve the field emission homogeneity and stability of p-type silicon tip arrays for pulsed sensor applications, the authors have systematically studied the influence of the fabrication parameters on the tip shape and on the specific operating conditions. Based on detailed design calculations of the field enhancement, they have fabricated two series of hexagonal arrays of B-doped Si-tips in a triangular arrangement. The first (second) type contains three (four) patches with different number of tips (1, 91, 547 and 1, 19, 1027, 4447 for the first and second type, respectively) of about 1 (2.5) μm height, ∼20 (20) nm apex radius, and 20 (10) μm pitch. The field emission properties of both individual tips and complete arrays were investigated with a field emission scanning microscope at a pressure of 10−9 mbar. The current plateau of these tips typically occurs at about 10 (3) nA and around 65 (25) V/μm field level. In this carrier saturation range, single tips provide the highest current stability (&amp;lt;5%) and optical current switching ratio (∼2.5). Fairly homogeneous emission of the tip arrays leads to an undershooting of the expected linear scaling of the mean plateau current as well as to a much improved current stability (&amp;lt;1%).
In Situ Expression of Angiopoietins in Astrocytomas Identifies Angiopoietin-2 as an Early Marker of Tumor Angiogenesis (1999)

Angiopoietin-1 (Ang-1) and its naturally occurring antagonist angiopoietin-2 (Ang-2) are novel ligands that regulate tyrosine phosphorylation of the Tie2/Tek receptor on endothelial cells. Proper regulation of Tie2/Tek is absolutely required for normal vascular development, seemingly by regulating vascular remodeling and endothelial cell interactions with supporting pericytes/smooth muscle cells. We investigated the expression of Ang-1 and Ang-2 in human astrocytomas by in situ hybridization and compared them to the distribution of pericytes/smooth muscle cells by immunohistochemistry for alpha-smooth muscle actin (SMA). Ang-1 mRNA was localized in tumor cells and Ang-2 mRNA was detected in endothelial cells of hyperplastic and nonhyperplastic tumor vessels. Ang-2 was also expressed in partially sclerotic vessels and in vascular channels surrounded by tumor cells in brain adjacent to the tumor. Neither Ang-1 nor Ang-2 was detected in normal brain. Dynamic changes in SMA expression during glioma tumorigenesis appear to progress from fragmentation in early vascular hyperplasia to subsequent reassociation and enhanced expression in later stages of vascular proliferation in hyperplastic complexes in high-grade gliomas. All these vessels displaying dynamic changes in SMA immunoreactivity also expressed Ang-2 mRNA. Moreover, SMA immunoreactive intratumoral vascular channels lacking morphological evidence of hyperplasia also showed upregulation of Ang-2. These results suggest that angiopoietins are involved in the early stage of vascular activation and in advanced angiogenesis, and they identify Ang-2 as an early marker of glioma-induced neovascularization. The association between Ang-2 expression and alterations in SMA immunoreactivity suggests a role for Ang-2 in tumor-associated activation of pericytes/smooth muscle cells.
Inhibitors of Dipeptidyl Peptidase IV - Recent Advances and Structural Views (2005)

Prevalence of type 2 diabetes has increased dramatically in the last decades. Current medicines are not yet capable to efficiently prevent or reverse progression of the disease and its associated comorbidities. As a consequence, there is a great need for novel antidiabetic drugs. Treatments of type 2 diabetes that are based on enhanced and sustained action of insulinotropic incretin hormones such as GLP-1 have received much attention in the past years. Treatment strategies include administration of: 1) GLP-1 analogues that are resistant to degradation by the serine protease DPP-IV, and 2) small molecule DPP-IV inhibitors that are able to provide sustained action of endogenous GLP-1, again by preventing its degradation. This review summarizes recent research results for the second approach. It briefly touches upon the advantages that treatment of type 2 diabetes with DPP-IV inhibitors may offer over current medications. In the main section, several important structural classes of DPP-IV inhibitors are described and compared based on literature data. Specific attention is given to the analysis of several X-ray structures of enzyme-inhibitor co-crystals. Finally, as clinical data are steadily emerging for some of the most advanced development candidates, the last section of this review is providing a brief overview of some efficacy data from recent clinical studies with DPP-IV inhibitors.
A volumetric method for building complex models from range images (1996)

A number of techniques have been developed for reconstructing surfaces by integrating groups of aligned range images. A desirable set of properties for such algorithms includes: incremental updating, representation of directional uncertainty, the ability to fill gaps in the reconstruction, and robustness in the presence of outliers. Prior algorithms possess subsets of these properties. In this paper, we present a volumetric method for integrating range images that possesses all of these properties. Our volumetric representation consists of a cumulative weighted signed distance function. Working with one range image at a time, we first scan-convert it to a distance function, then combine this with the data already acquired using a simple additive scheme. To achieve space efficiency, we employ a run-length encoding of the volume. To achieve time efficiency, we resample the range image to align with the voxel grid and traverse the range and voxel scanlines synchronously. We generate the final manifold by extracting an isosurface from the volumetric grid. We show that under certain assumptions, this isosurface is optimal in the least squares sense. To fill gaps in the model, we tessellate over the boundaries between regions seen to be empty and regions never observed. Using this method, we are able to integrate a large number of range images (as many as 70) yielding seamless, high-detail models of up to 2.6 million triangles. CR Categories: I.3.5 [Computer Graphics] Computational Geometry and Object Modeling Additional keywords: Surface fitting, three-dimensional shape recovery, range image integration, isosurface extraction 1
<title>Quasi-phase-matched frequency conversion in lithium niobate and lithium tantalate waveguides</title> (1991)

We discuss second harmonic generation of green and blue light in periodically-poled LiNbO3 and LiTaO3 waveguides, and difference frequency generation of infrared radiation in periodically-poled LiNbO3 waveguides.
Polyclonal and monoclonal antibody therapy for experimental Pseudomonas aeruginosa pneumonia (1986)

A human immunoglobulin G preparation, enriched in antibodies to lipopolysaccharide (LPS) Pseudomonas aeruginosa antigens (PA-IGIV) and murine monoclonal antibodies (MAb) to P. aeruginosa Fisher immunotype-1 (IT-1) LPS antigen and outer membrane protein F (porin), were evaluated for therapeutic efficacy in a guinea pig model of P. aeruginosa pneumonia. The concentration of antibodies to IT-1 LPS was 7.6 micrograms/ml in PA-IGIV and 478 micrograms/ml in the IT-1 MAb preparation. No antibody to IT-1 was detected in MAb to porin. For study, animals were infected by intratracheal instillation of IT-1 P. aeruginosa and then treated 2 h later with intravenous infusions of PA-IGIV, IT-1 MAb, or porin MAb. Control groups received intravenous albumin, and routinely died from pneumonia. Both PA-IGIV (500 mg/kg) and IT-1 MAb (greater than or equal to 2.5 mg/kg) treatment resulted in increased survival (P less than 0.01 to 0.001), and also improved intrapulmonary killing of bacteria. Porin MAb failed to protect from fatal pneumonia. IT-1 MAb treatment produced more survivals than did PA-IGIV treatment but only at dosages of MAb resulting in serum antibody concentrations greater than those achieved with PA-IGIV. PA-IGIV and IT-1 MAb demonstrated in vitro and in vivo (posttreatment guinea pig serum) opsonophagocytic activity for the IT-1 challenge strain. However, the polyclonal preparation required complement, whereas the MAb did not. We conclude that passive immunization with polyclonal hyperimmune P. aeruginosa globulin or with MAb to LPS antigens may be useful in the treatment of acute P. aeruginosa pneumonia. The relative efficacies of such preparations may be limited, however, by their type-specific LPS antibody concentrations.
Inhibitory Receptor Expression Depends More Dominantly on Differentiation and Activation than “Exhaustion” of Human CD8 T Cells (2013)

Under conditions of chronic antigen stimulation, such as persistent viral infection and cancer, CD8 T cells may diminish effector function, which has been termed "exhaustion." Expression of inhibitory Receptors (iRs) is often regarded as a hallmark of "exhaustion." Here we studied the expression of eight different iRs by CD8 T cells of healthy humans, including CTLA-4, PD1, TIM3, LAG3, 2B4, BTLA, CD160, and KLRG1. We show that many iRs are expressed upon activation, and with progressive differentiation to effector cells, even in absence of long-term ("chronic") antigenic stimulation. In particular, we evaluated the direct relationship between iR expression and functionality in CD8 T cells by using anti-CD3 and anti-CD28 stimulation to stimulate all cells and differentiation subsets. We observed a striking up-regulation of certain iRs following the cytokine production wave, in agreement with the notion that iRs function as a negative feedback mechanism. Intriguingly, we found no major impairment of cytokine production in cells positive for a broad array of iRs, as previously shown for PD1 in healthy donors. Rather, the expression of the various iRs strongly correlated with T cell differentiation or activation states, or both. Furthermore, we analyzed CD8 T cells from lymph nodes (LNs) of melanoma patients. Interestingly, we found altered iR expression and lower cytokine production by T cells from metastatic LNs, but also from non-metastatic LNs, likely due to mechanisms which are not related to exhaustion. Together, our data shows that expression of iRs per se does not mark dysfunctional cells, but is rather tightly linked to activation and differentiation. This study highlights the importance of considering the status of activation and differentiation for the study and the clinical monitoring of CD8 T cells.
Applications of High-Throughput RNA Interference Screens to Problems in Cell and Developmental Biology (2007)

RNA interference (RNAi) in tissue culture cells has emerged as an excellent methodology for identifying gene functions systematically and in an unbiased manner. Here, we describe how RNAi high-throughput screening (HTS) in Drosophila cells are currently being performed and emphasize the strengths and weaknesses of the approach. Further, to demonstrate the versatility of the technology, we provide examples of the various applications of the method to problems in signal transduction and cell and developmental biology. Finally, we discuss emerging technological advances that will extend RNAi-based screening methods.
Efficient backtracking instruction schedulers (2002)

Current schedulers for acyclic regions schedule operations in dependence order and never undo a scheduling decision. In contrast, backtracking schedulers may unschedule operations and can often generate better schedules. In this paper, we describe a conventional cycle schedule, followed by two novel backtracking schedulers, OperBT and ListBT. The full-backtracking OperBT scheduler enables backtracking for all operations and unschedules operations to make space for the current operation. The OperBT scheduler increases the percentage of super-blocks scheduled optimally over a conventional non-backtracking scheduler from an average of 66.9% to 81.4%, an increase of 21.7%. The selective backtracking ListBT scheduler enables backtracking only when scheduling operations for which backtracking is likely to be advantageous. This hybrid scheduler is almost as good as the OperBT backtracking scheduler in terms of generated code quality, but backtracks about four times less often.
Central Amygdala Metabotropic Glutamate Receptor 5 in the Modulation of Visceral Pain (2012)

Painful bladder syndrome is a debilitating condition that affects 3-6% of women in the United States. Multiple lines of evidence suggest that changes in CNS processing are key to the development of chronic bladder pain conditions but little is known regarding the underlying cellular, molecular, and neuronal mechanisms. Using a mouse model of distention-induced bladder pain, we found that the central nucleus of the amygdala (CeA) is a critical site of neuromodulation for processing of bladder nociception. Furthermore, we demonstrate that metabotropic glutamate receptor 5 (mGluR5) activation in the CeA induces bladder pain sensitization by increasing CeA output. Thus, pharmacological activation of mGluR5 in the CeA is sufficient to increase the response to bladder distention. Additionally, pharmacological blockade or virally mediated conditional deletion of mGluR5 in the CeA reduced responses to bladder distention suggesting that mGluR5 in the CeA is also necessary for these responses. Finally, we used optogenetic activation of the CeA and demonstrated that this caused a robust increase in the visceral pain response. The CeA-localized effects on responses to bladder distention are associated with changes in extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation in the spinal cord. Overall, these data demonstrate that mGluR5 activation leads to increased CeA output that drives bladder pain sensitization.
DNA mimics a self-protein that may be a target for some anti-DNA antibodies in systemic lupus erythematosus. (1995)

Recent studies suggest that some anti-DNA Abs in systemic lupus erythematosus may actually be Abs to specific proteins and that binding to dsDNA is a nonspecific cross-reactive event. To identify such proteins that bind to anti-DNA Abs, a cDNA expression library from human placenta was screened with mAb 3E10, a pathogenic anti-dsDNA Ab. MAb 3E10 was shown to bind to a 44-amino-acid fragment of HP8, a newly identified protein with amino acid sequence homology to the family of SPARC extracellular matrix proteins. To determine if Ab binding to both dsDNA and HP8 protein occurs through a common binding site, and therefore represents molecular mimicry, the Ab binding domains for protein and DNA were mapped. Chain recombinations between mAb 3E10 and a non-anti-DNA mAb showed that both the heavy and the light chains of mAb 3E10 were essential for anti-dsDNA and anti-HP8 reactivity. Mutagenesis experiments demonstrated that dsDNA and HP8 shared several critical binding residues located in all three complementarity-determining regions of mAb 3E10 VH. Moreover, Abs to HP8 were demonstrated in the sera of a subset of lupus patients. These results indicate that DNA mimics the HP8 protein in binding a lupus Ab, and that this protein may be a target for a subpopulation of anti-dsDNA Abs in systemic lupus erythematosus.
Effect of LNA Modifications on Small Molecule Binding to Nucleic Acids (2004)

Locked nucleic acid (LNA) is a conformationally constrained DNA analogue that exhibits exceptionally high affinity for complementary DNA and RNA strands. The deoxyribose sugar is modified by a 2'-O, 4'-C oxymethylene bridge, which projects into the minor groove. In addition to changing the distribution of functional groups in the groove and the overall helical geometry relative to unmodified DNA, the bridge likely alters the hydration of the groove. Each of these factors will impact the ability of small molecules, proteins and other nucleic acids to recognize LNA-containing hybrids. This report describes the ability of several DNA-intercalating ligands and one minor groove binder to recognize LNA-DNA and LNA-RNA hybrid duplexes. Using UV-vis, fluorescence and circular dichroism spectroscopies, we find that the minor groove binder as well as the intercalators exhibit significantly lower affinity for LNA-containing duplexes. The lone exception is the alkaloid ellipticine, which intercalates into LNA-DNA and LNA-RNA duplexes with affinities comparable to unmodified DNA-DNA and RNA-DNA duplexes.
Super-Elastic Graphene Ripples for Flexible Strain Sensors (2011)

In this study, we report a buckling approach for graphene and graphene ribbons on stretchable elastomeric substrates. Stretched polydimethylsiloxane (PDMS) films with different prestrains were used to receive the transferred graphene, and nanoscale periodical buckling of graphene was spontaneously formed after strain release. The morphology and periodicity of the as-formed graphene ripples are dependent strongly on their original shapes and substrates' prestrains. Regular periodicity of the ripples preferred to form for narrow graphene ribbons, and both the amplitude and periodicity are reduced with the increase of prestrain on PDMS. The graphene ripples have the ability to afford large strain deformation, thus making it ideal for flexible electronic applications. It was demonstrated that both graphene ribbon and nanographene film ripples could be used for strain sensors, and their resistance changes upon different strains were studied. This simple and controllable process of buckled graphene provides a feasible fabrication for graphene flexible electronic devices and strain sensors due to its novel mechanical and electrical properties.
Defect correction iteration and splitting methods for time-dependent partial differential equations : (preprint) (1981)

Nonlinear defect correction iteration is applied for solving the implicit relations which arise when an implicit linear multistep method is used in order to integrate semi-discrete initial value problems for partial differential equations.The approximate inverse occurring in the defect correction process is obtained by employing splitting methods.In order to accelerate convergence second degree Chebyshev iteration is used which is tuned in such a way that the lower frequencies in the iteration error are strongly damped without using a large number of iterations.
Adeno-Associated Virus Serotype 9 Transduction in the Central Nervous System of Nonhuman Primates (2011)

Widespread distribution of gene products at clinically relevant levels throughout the CNS has been challenging. Adeno-associated virus type 9 (AAV9) vector has been reported as a good candidate for intravascular gene delivery, but low levels of preexisting antibody titers against AAV in the blood abrogate cellular transduction within the CNS. In the present study we compared the effectiveness of vascular delivery and cerebrospinal fluid (CSF) delivery of AAV9 in transducing CNS tissue in nonhuman primates. Both delivery routes generated similar distribution patterns, although we observed a more robust level of transduction after CSF delivery. Consistent with previous reports administering AAV9, we found greater astrocytic than neuronal tropism via both routes, although we did find a greater magnitude of CNS transduction after CSF delivery compared with intravascular delivery. Last, we have demonstrated that delivery of AAV9 into the CSF does not shield against AAV antibodies. This has obvious implications when developing and/or implementing any clinical trial studies.
Antimicrobial susceptibility of ileal symbiont intracellularis isolated from pigs with proliferative enteropathy (1995)

Proliferative enteropathy is caused by the microaerophilic obligate intracellular bacterium ileal symbiont (IS) intracellularis. Treatment of this disease is problematic because of the lack of in vivo or in vitro data on the activities of antimicrobial agents. A new procedure for determining the susceptibility of IS intracellularis was developed by using a tissue culture system which promotes the in vitro multiplication of this organism. Nineteen antimicrobial agents were evaluated in triplicate cultures for their intracellular and extracellular activities against up to three IS intracellularis strains isolated from pigs with proliferative enteropathy. The MIC was defined as the lowest concentration which prevented multiplication of 99% of the IS intracellularis isolates. Penicillin, erythromycin, difloxacin, virginiamycin, and chlortetracycline were the most active compounds tested, all with MICs of < or = 1 microgram/ml. Tiamulin and tilmicosin were the next most active compounds, with MICs of < or = 4 micrograms/ml. The MICs of aminoglycosides were generally > 32 micrograms/ml. Both lincomycin and tylosin were relatively inactive against the IS intracellularis strains tested, with MICs of 32 and 64 micrograms/ml, respectively. These results indicate that some compounds capable of intracytoplasmic accumulation and blocking bacterial protein synthesis were active against IS intracellularis strains isolated from pigs with proliferative enteropathy. The in vitro cultivation system shows promise as a method for studying the interaction between IS intracellularis and antimicrobial agents and for screening new antibiotics for use in therapy.