gebhart/patrepeval huggingface dataset:
Structural characterization of short hybrid urea/carbamate (U/C) foldamers: A case of partial helix unwinding (2013)

Aliphatic oligoureas−(NH−CH(R)−CH2−NH−CO)n− and oligocarbamates −(NH−CH(R)−CH2−O−CO)n− are two classes of synthetic peptidomimetic oligomers whose backbone is isosteric to that of γ-peptides. We have shown recently that the constituent units of these backbones (i.e., amide (A), carbamate (C) and urea (U) units) can be combined in various ways to generate new heterogeneous oligomers with well-defined secondary structures. For example, oligomers consisting of urea (U) and carbamate (C) linkages arranged in a 1:1 pattern adopt a helical conformation akin to that of urea homoligomers and γ-peptide foldamers. In this case, helix formation is mainly driven by U units whose propensity for folding surpasses that of C units. Here, we have investigated further the influence of the U/C ratio on the folding preference of such heterogeneous oligomers. We report the synthesis and the structural analysis of a short oligomer with a 2:3 U/C ratio and two consecutive carbamate linkages. X-ray diffraction analysis reveals a helical structure that unwinds at one end. In contrast, a cognate oligomer prepared for comparison and containing four contiguous urea units adopts a fully helical conformation in the crystalline state. These results which are supported by data in solution indicate that the balance between U and C units should be carefully adjusted and that consecutive C linkages should be avoided for optimal helix formation.
SAR amplitude probability density function estimation based on a generalized Gaussian scattering model (2004)

In the context of remotely sensed data analysis, an important problem is the development of accurate models for the statistics of the pixel intensities. Focusing on Synthetic Aperture Radar (SAR) data, this modeling process turns out to be a crucial task, for instance, for classification or for denoising purposes. In the present paper, an innovative parametric estimation methodology for SAR amplitude data is proposed, that takes into account the physical nature of the scattering phenomena generating a SAR image by adopting a generalized Gaussian (GG) model for the backscattering phenomena. A closed-form expression for the corresponding amplitude probability density function (PDF) is derived and a specific parameter estimation algorithm is developed in order to deal with the proposed model. Specifically, the recently proposed "method-of-log-cumulants" (MoLC) is applied, which stems from the adoption of the Mellin transform (instead of the usual Fourier transform) in the computation of characteristic functions, and from the corresponding generalization of the concepts of moment and cumulant. For the developed GG-based amplitude model, the resulting MoLC estimates turn out to be numerically feasible and are also analytically proved to be consistent. The proposed parametric approach was validated by using several real ERS-1, XSAR, E-SAR and NASA/JPL airborne SAR images, and the experimental results prove that the method models the amplitude probability density function better than several previously proposed parametric models for backscattering phenomena.
Adenosine A 2A receptor antagonist istradefylline (KW‐6002) reduces “off” time in Parkinson's disease: A double‐blind, randomized, multicenter clinical trial (6002‐US‐005) (2008)

Istradefylline was safe, well tolerated, and offered a clinically meaningful reduction in "off" time without increased troublesome dyskinesia.
Improved energy transfer in electrophosphorescent devices (1999)

External quantum efficiencies of up to (5.6±0.1)% at low brightness and (2.2±0.1)% at 100 cd/m2 are obtained from a red electrophosphorescent device containing the luminescent dye 2,3,7,8, 12,13,17,18-octaethyl-21H23H-phorpine platinum(II) (PtOEP) doped in a 4,4′-N,N′-dicarbazolebiphenyl (CBP) host. Due to weak overlap between excitonic states in PtOEP and CBP, efficiency losses due to nonradiative recombination are low. However, energy transfer between the species is also poor. In compensation, a thin layer of 2,9-dimethyl-4,7 diphenyl-1,10-phenanthroline is used as a barrier to exciton diffusion in CBP, improving the energy transfer to PtOEP. This technique may be applied to improve the efficiency of other electrophosphorescent devices.
Diagnosis of Sickle Cell Anemia and β-Thalassemia with Enzymatically Amplified DNA and Nonradioactive Allele-Specific Oligonucleotide Probes (1988)

We have developed a simple and rapid nonradioactive method for detecting genetic variation and have applied it to the diagnosis of sickle cell anemia and beta-thalassemia. The procedure involves the selective amplification of a segment of the human beta-globin gene with oligonucleotide primers and a thermostable DNA polymerase, followed by hybridization of the amplified DNA with allele-specific oligonucleotide probes covalently labeled with horseradish peroxidase. The hybridized probes were detected with a simple colorimetric assay. We demonstrated the usefulness of this method in a retrospective analysis of two pregnancies at risk for beta-thalassemia and one at risk for sickle cell anemia, as well as in an analysis of nine DNA samples simulating three family sets.
A phase 2, multicenter study to evaluate the efficacy and safety of autologous tumor infiltrating lymphocytes (LN-145) for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (HNSCC). (2018)

TPS6096 Background: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has demonstrated efficacy in the treatment of immunogenic tumors with high mutation loads, such as melanoma. Despite the heterogeneity of HNSCC tumors, most tumors are either virally-associated or carry high mutation loads that increase the potential antigens targeted by TIL ACT. Since outcomes for patients with recurrent and/or metastatic HNSCC remain poor despite existing approved therapies, a clear rationale exists for the potential application of ACT with TIL in patients with HNSCC. Methods: Clinical trial C-145-03 (NCT03083873) is a prospective phase 2 multicenter, open-label study evaluating the efficacy of a single autologous TIL infusion (LN-145) followed by IL-2 after a non-myeloablative lymphodepletion (NMA-LD) regimen in patients with recurrent and/or metastatic HNSCC. Patients undergo a surgical resection of a tumor lesion from which TIL are extracted and expanded at a central GMP manufacturing facility that prepares a cryo-preserved TIL (LN-145) product ready for shipment and infusion. One week prior to LN-145 infusion, patients undergo NMA-LD consisting of cyclophosphamide (60 mg/kg) daily x 2 days followed by fludarabine (25 mg/m2) daily x 5 days. LN-145 is infused 24 hours after NMA-LD followed by up to 6 doses of IL-2 (600,000 IU/kg) every 8-12 hours. The primary efficacy endpoint is the objective response rate per RECIST v1.1. Secondary endpoints include an assessment of safety & other efficacy parameters such as progression free and overall survival. Patients must have been treated with at least one systemic therapy for recurrent and/or metastatic HNSCC and, in addition to the tumor resected for TIL manufacture, must have an additional measurable lesion for assessment of response. Additional eligibility criteria include amongst others: adequate bone marrow, liver, pulmonary, cardiac, and renal function; and ECOG performance status of 0 or 1. Clinical trial information: NCT03083873.
A Novel MONOS-Type Nonvolatile Memory Using High-&lt;tex&gt;$kappa$&lt;/tex&gt;Dielectrics for Improved Data Retention and Programming Speed (2004)

This paper presents a novel metal-oxide-nitride-oxide-silicon (MONOS)-type nonvolatile memory structure using hafnium oxide (HfO/sub 2/) as tunneling and blocking layer and tantalum pentoxide (Ta/sub 2/O/sub 5/) as the charge trapping layer. The superiorities of such devices to traditional SiO/sub 2/-Si/sub 3/N/sub 4/-SiO/sub 2/ stack devices in obtaining a better tradeoff between faster programming and better retention are illustrated based on a band engineering analysis. The experimental results demonstrate that the fabricated devices can be programmed as fast as 1 /spl mu/s and erased from 10 ns at an 8-V gate bias. The retention decay rate of this device is improved by a factor more than three as compared to the conventional MONOS/SONOS type devices. Excellent endurance and read disturb performance are also demonstrated.
Performance Comparison of SPIN based Push-Pull Protocols (2007)

Multiple data-centric protocols - which can broadly be classified as push-pull, push-only, or pull-only - have been proposed in the literature. In this paper we present a framework to develop an insight into the characteristics of push-pull protocols. The performance of push-pull protocols is critically dependent on the timeout settings used to trigger failure recovery mechanisms. We perform a study of how to choose optimal timeouts to achieve best performance and use these timeouts to simulate and compare various push-pull protocols. Our starting point is a recently proposed SPIN-based protocol, called shortest-path minded SPIN (SPMS), in which meta-data negotiations take place prior to data exchange in order to minimize the number of data transmissions, thereby improving in both energy and delay compared to SPIN. We propose a redesign of SPMS, called SPMS-Rec, which reduces the energy expended in the event of failures by requiring intermediate relay nodes to try alternate routes. Our simulation results show that SPMS-Rec outperforms SPMS, and thus SPIN, yielding energy savings while reducing the delay when multiple nodes fail along a route. We further propose a modification to SPMS-Rec through request suppression which helps in reducing redundant data transmissions.
Application of soft tissue modelling to image-guided surgery (2005)

The deformation of soft tissue compromises the accuracy of image-guided surgery based on preoperative images, and restricts its applicability to surgery on or near bony structures. One way to overcome these limitations is to combine biomechanical models with sparse intraoperative data, in order to realistically warp the preoperative image to match the surgical situation. We detail the process of biomechanical modelling in the context of image-guided surgery. We focus in particular on the finite element method, which is shown to be a promising approach, and review the constitutive relationships which have been suggested for representing tissue during surgery. Appropriate intraoperative measurements are required to constrain the deformation, and we discuss the potential of the modalities which have been applied to this task. This technology is on the verge of transition into clinical practice, where it promises to increase the guidance accuracy and facilitate less invasive interventions. We describe here how soft tissue modelling techniques have been applied to image-guided surgery applications.
GPU parallel computing architecture and CUDA programming model (2007)

This article consists of a collection of slides from the author's conference presentation on NVIDIA's CUDA programming model (parallel computing platform and application programming interface) via graphical processing units (GPU). Some of the specific topics discussed include: the special features of GPUs; the importance of GPU computing; system specifications and architectures; processing capabilities; parallel memory sharing; CUDA programming models; transparent scalability; and major applications supported.
Unique palindromic sequences in synthetic oligonucleotides are required to induce IFN [correction of INF] and augment IFN-mediated [correction of INF] natural killer activity (1992)

Thirty-mer single-stranded oligonucleotides, with a sequence chosen from the known cDNA encoding the 64-kDa protein named Ag A or the MPB-70 protein of Mycobacterium bovis BCG and the human cellular proteins such as complement component 1 inhibitor and Ig rearranged lambda-chain, were used to dissect the capability to induce IFN and to augment NK cell activity of mouse spleen cells by coincubation in vitro. Three with the hexamer palindromic sequence as GACGTC were active, whereas two kinds of oligonucleotides with no palindrome were inactive. The oligonucleotides containing at least one of the different palindromic sequences showed no activity. When a portion of the sequence of the inactive oligonucleotides was substituted with either palindromic sequence of GACGTC, AGCGCT, or AACGTT, the oligonucleotide acquired the ability to augment NK activity. In contrast, the oligonucleotides substituted with another palindromic sequence such as ACCGGT was without effect. Furthermore, exchange of two neighboring mononucleotides within, but not outside, the active palindromic sequence destroyed the ability of the oligonucleotides to augment NK cell activity. Stimulation of spleen cells with the substituted oligonucleotide, A4a-AAC, induced production of significant amounts of IFN-alpha/beta and small amounts of IFN-gamma. Augmentation of NK activity of the cells by the oligonucleotide was ascribed to IFN-alpha/beta production. These results strongly suggest that the presence of the unique palindromic sequences, such as GACGTC, AGCGCT, and AACGTT, but not ACCGGT, is essential for the immunostimulatory activity of oligonucleotides.
General teleportation channel, singlet fraction and quasi-distillation (1998)

We prove a theorem on direct relation between the optimal fidelity $f_{max}$ of teleportation and the maximal singlet fraction $F_{max}$ attainable by means of trace-preserving LQCC action (local quantum and classical communication). For a given bipartite state acting on $C^d\otimes C^d$ we have $f_{max}= {F_{max}d+1\over d+1}$. We assume completely general teleportation scheme (trace preserving LQCC action over the pair and the third particle in unknown state). The proof involves the isomorphism between quantum channels and a class of bipartite states. We also exploit the technique of $U\otimes U^*$ twirling states (random application of unitary transformation of the above form) and the introduced analogous twirling of channels. We illustrate the power of the theorem by showing that {\it any} bound entangled state does not provide better fidelity of teleportation than for the purely classical channel. Subsequently, we apply our tools to the problem of the so-called conclusive teleportation, then reduced to the question of optimal conclusive increasing of singlet fraction. We provide an example of state for which Alice and Bob have no chance to obtain perfect singlet by LQCC action, but still singlet fraction arbitrarily close to unity can be obtained with nonzero probability. We show that a slight modification of the state has a threshold for singlet fraction which cannot be exceeded anymore.
CpG Still Rocks! Update on an Accidental Drug (2012)

The discovery of the CpG motif in 1995 led to a change in the perception of the immune stimulatory effects of oligodeoxynucleotides (ODN) from an unwanted nonspecific effect to a highly evolved immune defense that can be selectively triggered for a wide range of therapeutic applications. Over the last decade dozens of human clinical trials have been conducted with different CpG ODN in thousands of humans for applications ranging from vaccine adjuvant to immunotherapies for allergy, cancer, and infectious diseases. Along with many positive results have come some failures showing the limitations of several therapeutic approaches. This review summarizes these results to provide an overview of the clinical development of CpG ODN.
The Epidermal Growth Factor Receptor Modulates the Interaction of E-cadherin with the Actin Cytoskeleton (1998)

Alterations in the expression or function of molecules that affect cellular adhesion and proliferation are thought to be critical events for tumor progression. Loss of expression of the cell adhesion molecule E-cadherin and increased expression of the epidermal growth factor receptor are two prominent molecular events that are associated with tumorigenesis. The regulation of E-cadherin-dependent cell adhesion by epidermal growth factor (EGF) was therefore examined in the human breast cancer cell line, MDA-MB-468. In this study, changes were observed in the subcellular distribution of components that mediate the cytoplasmic connection between E-cadherin and the actin-based cytoskeleton in response to activation of the EGF receptor. Serum withdrawal activated E-cadherin-dependent cell-cell aggregation in MDA-MB-468 cells, and this treatment stimulated the interaction of actin, alpha-actinin, and vinculin with E-cadherin complexes, despite the absence of alpha-catenin in these cells. By contrast, the co-precipitation of actin with E-cadherin was not detected in several alpha-catenin positive epithelial cell lines. Treatment with EGF inhibited cellular aggregation but did not affect either the levels of E-cadherin or catenin expression nor the association of catenins (beta-catenin, plakoglobin/gamma-catenin, or p120(cas)) with E-cadherin. However, EGF treatment of the MDA-MB-468 cell line dissociated actin, alpha-actinin, and vinculin from the E-cadherin-catenin complex, and this coincided with a robust phosphorylation of beta-catenin, plakoglobin/gamma-catenin, and p120(cas) on tyrosine residues. Furthermore, inactivation of the EGF receptor in serum-treated MDA-MB-468 cells with either a function-blocking antibody or EGF receptor kinase inhibitors mimicked the effects of serum starvation by stimulating both cellular aggregation and assembly of E-cadherin complexes with vinculin and actin. These results demonstrate that the EGF receptor directly regulates cell-cell adhesion through modulation of the interaction of E-cadherin with the actin cytoskeleton and thus substantiates the coordinate role of both of these molecules in tumor progression and metastasis.
Inhibition of HIV-1 by multiple siRNAs expressed from a single microRNA polycistron (2008)

RNA interference (RNAi) is a powerful approach to inhibit human immunodeficiency virus type 1 (HIV-1) replication. However, HIV-1 can escape from RNAi-mediated antiviral therapy by selection of mutations in the targeted sequence. To prevent viral escape, multiple small interfering RNAs (siRNAs) against conserved viral sequences should be combined. Ideally, these RNA inhibitors should be expressed simultaneously from a single transgene transcript. In this study, we tested a multiplex microRNA (miRNA) expression strategy by inserting multiple effective anti-HIV siRNA sequences in the miRNA polycistron mir-17-92. Individual anti-HIV miRNAs that resemble the natural miRNA structures were optimized by varying the siRNA position in the hairpin stem to obtain maximal effectiveness against luciferase reporters and HIV-1. We show that an antiviral miRNA construct can have a greater intrinsic inhibitory activity than a conventional short hairpin (shRNA) construct. When combined in a polycistron setting, the silencing activity of an individual miRNA is strongly boosted. We demonstrate that HIV-1 replication can be efficiently inhibited by simultaneous expression of four antiviral siRNAs from the polycistronic miRNA transcript. These combined results indicate that a multiplex miRNA strategy may be a promising therapeutic approach to attack escape-prone viral pathogens.
Consistency based diagnosis of configuration knowledge-bases (1999)

Configuration problems are a thriving application area for declarative knowledge representation that currently experiences a constant increase in size and complexity of knowledge bases. Automated support of the debugging process of such knowledge bases is a necessary prerequisite for effective development of configurators. We show that this task can be achieved by consistency-based diagnosis techniques. Based on the formal definition of consistency-based configuration we develop a framework suitable for diagnosing configuration knowledge bases. During the test phase of configurators, valid and invalid examples are used to test the correctness of the system. In case such examples lead to unintended results, debugging of the knowledge base is initiated. Starting from a clear definition of diagnosis in the configuration domain we develop an algorithm based on conflicts. Our framework is general enough for its adaptation to diagnosing customer requirements to identify unachievable conditions during configuration sessions. A prototype
Boundary-fitted curvilinear coordinate systems for solution of partial differential equations on fields containing any number of arbitrary two-dimensional bodies (1977)

A method is presented for automatic numerical generation of a general curvilinear coordinate system with coordinate lines coincident with all boundaries of a general multi-connected two-dimensional region containing any number of arbitrarily shaped bodies. No restrictions are placed on the shape of the boundaries, which may even be time-dependent, and the approach is not restricted in principle to two dimensions. With this procedure the numerical solution of a partial differential system may be done on a fixed rectangular field with a square mesh with no interpolation required regardless of the shape of the physical boundaries, regardless of the spacing of the curvilinear coordinate lines in the physical field, and regardless of the movement of the coordinate system in the physical plane. A number of examples of coordinate systems and application thereof to the solution of partial differential equations are given. The FORTRAN computer program and instructions for use are included.
Isolation, Purification and Characterization of Intact and Pepsin-Derived Fragments of Laminin from Human Placenta (1985)

Human laminin, in intact form and as pepsin cleaved fragments, was isolated and purified from placenta. The intact laminin was extracted by 1-M NaCl at neutral pH in the presence of 10-mM EDTA and 3% Triton X-100. This recovered material was purified by DEAE-cellulose and agarose gel chromatography. The laminin fragments P1, P2 and P3 were prepared by limited pepsin proteolysis. Antibodies were prepared against fragment P2. The laminin and its fragments were characterized by amino acid composition, NaDoSO4-polyacrylamide gel electrophoresis and immunochemistry. Results from these studies show that substantial quantities of laminin can be prepared from placenta in this manner.
Coulomb Staircase at Room Temperature in a Self-Assembled Molecular Nanostructure (1996)

Double-ended aryl dithiols [alpha,alpha'-xylyldithiol (XYL) and 4,4'-biphenyldithiol] formed self-assembled monolayers (SAMs) on gold(111) substrates and were used to tether nanometer-sized gold clusters deposited from a cluster beam. An ultrahigh-vacuum scanning tunneling microscope was used to image these nanostructures and to measure their current-voltage characteristics as a function of the separation between the probe tip and the metal cluster. At room temperature, when the tip was positioned over a cluster bonded to the XYL SAM, the current-voltage data showed "Coulomb staircase" behavior. These data are in good agreement with semiclassical predictions for correlated single-electron tunneling and permit estimation of the electrical resistance of a single XYL molecule (approximately18 &plusmn; 12 megohms).