gebhart/patrepeval huggingface dataset:
The Influence of the Thymine C5 Methyl Group on Spontaneous Base Pair Breathing in DNA (2002)

Sequences of four or more AT base pairs without a 5'-TA-3' step, so-called A-tracts, influence the global properties of DNA by causing curvature of the helix axis if phased with the helical repeat and also influence nucleosome packaging. Hence it is interesting to understand this phenomenon on the molecular level, and numerous studies have been devoted to investigations of dynamical and structural features of A-tract DNA. It was early observed that anomalously slow base pair-opening kinetics were a striking physical property unique to DNA A-tracts (Leroy, J. L., Charretier, E., Kochoyan, M., and Gueron, M. (1988) Biochemistry 27, 8894-8898). Furthermore, a strong correlation between DNA curvature and anomalously slow base pair-opening dynamics was found. In the present work it is shown, using imino proton exchange measurements by NMR spectroscopy that the main contribution to the dampening of the base pair-opening fluctuations in A-tracts comes from the C5 methylation of the thymine base. Because the methyl group has been shown to have a very limited effect on the DNA curvature as well as the structure of the DNA helix, the thymine C5 methyl group stabilizes the helix directly. Empirical potential energy calculations show that methylation of the tract improves the stacking energy of a base pair with its neighbors in the tract by 3-4 kcal/mol.
THE GENETICS OF FLOWER DEVELOPMENT: From Floral Induction to Ovule Morphogenesis (1995)

Flower development consists of several phases. The first step is the transition from vegetative to reproductive development, regulated by floral induction. Later steps include the initiation of individual flowers, the determination of organ identity, and organ-specific differentiation. One of the major discoveries of plant biology is that the genetic network controlling flower development is highly conserved in two distantly related dicots, Arabidopsis thaliana and Antirrhinum majus, and probably in other species as well. Classical genetics has identified a sizable number of genes regulating flower development, and many of these regulatory genes have been cloned. This review summarizes recent advances in the understanding of the genetic control of floral induction and determination of flower-meristem identity, with the focus on Arabidopsis thaliana. In addition, recent work on ovule morphogenesis, a late process in flower development, is discussed.
Inhibition of C1-mediated immune hemolysis by monomeric and dimeric peptides from the second constant domain of human immunoglobulin G. (1981)

Activation of the classical complement cascade by immunoglobulin G involves binding of the first complement component (C1) to a multivalent antigen-IgG complex. Binding occurs by interaction of a site on the surface of the C gamma 2 domain of IgG with a globular head of the C1q subcomponent of C1. Previously we found that the synthetic decapeptide consisting of residues 281-290 from the second constant domain of the gamma-chain of the human IgG1 protein Eu inhibited the binding of human C1 to sensitized erythrocytes. The present study describes inhibition of monomeric and dimeric peptides containing residues 289-292 or 282-292: (formula: see text). On a molar basis, monomeric peptide 282-292 is just as active an inhibitor of C1 binding as peptide 281-290, whereas monomeric peptide 289-292 (tuftsin) is 4 times less active. Peptides 282-292 and 289-292 were each cross-linked at the amino terminus through terephthaloyl-bis(iminodiacetic acid) (Tid). Each dimeric peptide is twice as active on a molar basis as the corresponding monomeric peptide. Dimeric peptide Tid(282-292)2 is just as active on a molar basis as the monomeric 7S form of human IgG1 and 60% as active as the Fc fragment of IgG in inhibiting the binding of human C1 to sensitized erythrocytes. These results suggest that the positively charged residues His-285, Lys-288, Lys-290, and Arg-292, which are located on the outer surface of the C gamma 2 domain, may be involved in the C1q-binding site of human IgG.
CpG DNA Induces Maturation of Dendritic Cells with Distinct Effects on Nascent and Recycling MHC-II Antigen-Processing Mechanisms (2000)

Murine bone marrow cultured with GM-CSF produced dendritic cells (DCs) expressing MHC class II (MHC-II) but little CD40, CD80, or CD86. Oligodeoxynucleotides (ODN) containing CpG motifs enhanced DC maturation, increased MHC-II expression, and induced high levels of CD40, CD80, and CD86. When added with Ag to DCs for 24 h, CpG ODN enhanced Ag processing, and the half-life of peptide:MHC-II complexes was increased. However, Ag processing was only transiently enhanced, and exposure of DCs to CpG ODN for 48 h blocked processing of hen egg lysozyme (HEL) to HEL(48-61):I-A(k) complexes. Processing of this epitope required newly synthesized MHC-II and was blocked by brefeldin A (BFA), suggesting that reduced MHC-II synthesis could explain decreased processing. Real-time quantitative PCR confirmed that CpG ODN decreased I-A(beta)(k) mRNA in DCs. In contrast, RNase(42-56):I-A(k) complexes were generated via a different processing mechanism that involved recycling MHC-II and was partially resistant to BFA. Processing of RNase(42-56):I-A(k) persisted, although at reduced levels, after CpG-induced maturation of DCs, and this residual processing by mature DCs was completely resistant to BFA. Changes in endocytosis, which was transiently enhanced and subsequently suppressed by CpG ODN, may affect Ag processing by both nascent and recycling MHC-II mechanisms. In summary, CpG ODN induce DC maturation, transiently increase Ag processing, and increase the half-life of peptide-MHC-II complexes to sustain subsequent presentation. Processing mechanisms that require nascent MHC-II are subsequently lost, but those that use recycling MHC-II persist even in fully mature DCs.
Automatic parallelization and scheduling of programs on multiprocessors using CASCH (2002)

The lack of a versatile software tool for parallel program development has been one of the major obstacles for exploiting the potential of high-performance architectures. In this paper, we describe an experimental software tool called CASCH (Computer Aided SCHeduling) for parallelizing and scheduling applications to parallel processors. CASCH transforms a sequential program to a parallel program with automatic scheduling, mapping, communication, and synchronization. The major strength of CASCH is its extensive library of scheduling and mapping algorithms representing a broad range of state-of-the-art work reported in the recent literature. These algorithms are applied for allocating a parallelized program to the processors, and thus the algorithms can be interactively analyzed, tested and compared using real data on a common platform with various performance objectives. CASCH is useful for both novice and expert programmers of parallel machines, and can serve as a teaching and learning aid for understanding scheduling and mapping algorithms.
Relaxed Min-Max Decoder Architectures for Nonbinary Low-Density Parity-Check Codes (2012)

Compared to binary low-density parity-check (LDPC) codes, nonbinary (NB) LDPC codes can achieve higher coding gain when the codeword length is moderate, but at the cost of higher decoding complexity. One major bottleneck of NB-LDPC decoding is the complicated check node processing. In this paper, a novel relaxed check node processing scheme is proposed for the min-max NB-LDPC decoding algorithm. Each finite field element of GF(2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</sup> ) can be uniquely represented by a linear combination of p independent field elements. Making use of this property, an innovative method is developed in this paper to first find a set of the p most reliable variable-to-check messages with independent field elements, called the minimum basis. Then, the check-to-variable messages are efficiently computed from the minimum basis. With very small performance loss, the complexity of the check node processing can be substantially reduced using the proposed scheme. In addition, efficient VLSI architectures are developed to implement the proposed check node processing and the overall NB-LDPC decoder. Compared to the most efficient prior design, the proposed decoder for a (837, 726) NB-LDPC code over GF(2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> ) can achieve 52% higher efficiency in terms of throughput-over-area ratio.
Response to histone deacetylase inhibition of novel PML/RARα mutants detected in retinoic acid–resistant APL cells (2002)

Resistance to all-trans retinoic acid (ATRA) remains a clinical problem in the treatment of acute promyelocytic leukemia (APL) and provides a model for the development of novel therapies. Molecular alterations in the ligand-binding domain (LBD) of the PML/RARalpha fusion gene that characterizes APL constitute one mechanism of acquired resistance to ATRA. We identified missense mutations in PML/RARalpha from an additional ATRA-resistant patient at relapse and in a novel ATRA-resistant cell line, NB4-MRA1. These cause altered binding to ligand and transcriptional coregulators, leading to a dominant-negative block of transcription. These mutations are in regions of the LBD that appear to be mutational hot spots occurring repeatedly in ATRA-resistant APL patient cells. We evaluated whether histone deacetylase (HDAC) inhibition could overcome the effects of these mutations on ATRA-induced gene expression. Cotreatment with ATRA and TSA restored RARbeta gene expression in NB4-MRA1 cells, whose PML/RARalpha mutation is in helix 12 of the LBD, but not in an APL cell line harboring the patient-derived PML/RARalpha mutation, which was between helix 5 and 6. Furthermore, ATRA combined with TSA increases histone 4 acetylation on the RARbeta promoter only in NB4-MRA1 cells. Consistent with these results, the combined treatment induces differentiation of NB4-MRA1 only. Thus, the ability of an HDAC inhibitor to restore ATRA sensitivity in resistant cells may depend on their specific molecular defects. The variety of PML/RARalpha mutations arising in ATRA-resistant patients begins to explain how APL patients in relapse may differ in response to transcription therapy with HDAC inhibitors.
Cross‐Species Differential Plasma Protein Binding of MBX‐102/JNJ39659100: A Novel PPAR‐γAgonist (2008)

Drug binding to plasma proteins restricts their free and active concentrations, thereby affecting their pharmacokinetic properties. Species differences in plasma protein levels complicate the understanding of interspecies pharmacodynamic and toxicological effects. MBX-102 acid/JNJ39659100 is a novel PPAR-gamma agonist in development for the treatment of type 2 diabetes. Studies were performed to evaluate plasma protein binding to MBX-102 acid and evaluate species differences in free drug levels. Equilibrium dialysis studies demonstrated that MBX-102 acid is highly bound (>98%) to human, rat and mouse albumin and that free MBX-102 acid levels are higher in rodent than in human plasma. Interspecies differences in free drug levels were further studied using PPAR-gamma transactivation assays and a newly developed PPAR-gamma corepressor displacement (biochemical) assay. PPAR-gamma transactivation and corepressor displacement by MBX-102 acid was higher in rat and mouse serum than human serum. These results confirm the relevance of interspecies differences in free MBX-102 acid levels.
Enhancing simulation with BDDs and ATPG (1999)

We introduce Simulation Verification with Augmentation (SIVA), a tool for checking safety properties on digital hardware designs. SIVA integrates simulation with symbolic techniques for vector generation. Specifically, the core algorithm uses a combination of ATPG and BDDs to generate input vectors which cover behavior not excited by simulation. Experimental results demonstrate considerable improvement in state space coverage compared with either simulation or formal verification in isolation.
Operative technique and early experience for robotic-assisted laparoscopic nephroureterectomy (RALNU) using da Vinci Xi (2015)

The use of da Vinci Xi with a novel, oblique "in line" port configuration and camera port hopping technique allows for an efficient and reproducible method for RALNU without the need for repositioning the patient or the robot during surgery.
APACHE II (1985)

This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status to provide a general measure of severity of disease. An increasing score (range 0 to 71) was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals. This relationship was also found for many common diseases.When APACHE II scores are combined with an accurate description of disease, they can prognostically stratify acutely ill patients and assist investigators comparing the success of new or differing forms of therapy. This scoring index can be used to evaluate the use of hospital resources and compare the efficacy of intensive care in different hospitals or over time.
The edge volume heuristic - robust triangle subdivision for improved BVH performance (2008)

The use of axis-aligned bounding boxes is a basic technique to accelerate geometric algorithms as for example ray tracing. It is a known problem that efficiency suffers, if the axis-aligned bounding volume contains major parts of empty space, which, in the case of ray tracing, causes more ray-object-intersection tests than required. The impact of this problem can be reduced by subdividing triangles at the cost of a larger memory footprint. We present a subdivision algorithm that is designed to generate only very few additional triangle references. Compared to previous approaches the algorithm is numerically robust, and simpler to implement and use. For formerly problematic scenes a speedup of up to a factor of 10 could be achieved, while the number of triangle references increased only by 16%.
Least-Squares Fitting of Two 3-D Point Sets (1987)

Two point sets {pi} and {p'i}; i = 1, 2,..., N are related by p'i = Rpi + T + Ni, where R is a rotation matrix, T a translation vector, and Ni a noise vector. Given {pi} and {p'i}, we present an algorithm for finding the least-squares solution of R and T, which is based on the singular value decomposition (SVD) of a 3 × 3 matrix. This new algorithm is compared to two earlier algorithms with respect to computer time requirements.
Distinct Poly(I-C) and Virus-activated Signaling Pathways Leading to Interferon-β Production in Hepatocytes (2005)

Innate cellular antiviral defenses are likely to influence the outcome of infections by many human viruses, including hepatitis B and C viruses, agents that frequently establish persistent infection leading to chronic hepatitis, cirrhosis, and liver cancer. However, little is known of the pathways by which hepatocytes, the cell type within which these hepatitis agents replicate, sense infection, and initiate protective responses. We show that cultured hepatoma cells, including Huh7 cells, do not activate the interferon (IFN)-beta promoter in response to extracellular poly(I-C). In contrast, the addition of poly(I-C) to culture media activates the IFN-beta promoter and results in robust expression of IFN-stimulated genes (ISG) in PH5CH8 cells, which are derived from non-neoplastic hepatocytes transformed with large T antigen. Small interfering RNA knockdown of TLR3 or its adaptor, Toll-interleukin-1 receptor domain-containing adaptor inducing IFN-beta (TRIF), blocked extracellular poly(I-C) signaling in PH5CH8 cells, whereas poly(I-C) responsiveness could be conferred on Huh7 hepatoma cells by ectopic expression of Toll-like receptor 3 (TLR3). In contrast to poly(I-C), both cell types signal the presence of Sendai virus infection through a TLR3-independent intracellular pathway requiring expression of retinoic acid-inducible gene I (RIG-I), a putative cellular RNA helicase. Silencing of RIG-I expression impaired only the response to Sendai virus and not extracellular poly(I-C). We conclude that hepatocytes contain two distinct antiviral signaling pathways leading to expression of type I IFNs, one dependent upon TLR3 and the other dependent on RIG-I, with little cross-talk between these pathways.
In vitro inhibition of adenosine deaminase by a group of steroid and Triterpenoid compounds (1994)

Abstract The effects of several sapogenins and saponins of the steroid and triterpenoid classes, as well as of a few common phytosterols, have been tested for their inhibitory action towards adenosine deaminase (ADA). It was found that the acidic sapogenins strongly inhibit the enzyme. The mean inhibitory concentration (IC 50 ) was in the range 10 −3 to 10 −2 mg/mL, while the inhibitor constants ( K i ) have been estimated as about 10 −6 M. In contrast to this finding is the complete absence of any influence on the enzyme of the neutral sapo(ge)nins and the phytosterols. It is suggested that ADA is a worthwhile therapeutic target and that the (acidic) sapogenins, which are regular constituents of many medicinal plant species, presumably contribute their activity through an interaction with this enzyme.
DMT signals with low peak-to-average power ratio (2003)

This contribution proposes a new family of methods to reduce the peak-to-average power ratio (PAR) in discrete multi-tone (DMT) and orthogonal frequency division multiplexing (OFDM) systems. This method avoids the use of extra inverse fast Fourier transformations (IFFT) as were used in some previously published techniques, but instead is based on transformations in the time domain of the original sequence available at the output of the IFFT processor. The improved statistics of peak power in the optimized transmit signal are demonstrated by simulation results.
Design of a Massively Parallel Processor (1980)

The massively parallel processor (MPP) system is designed to process satellite imagery at high rates. A large number (16 384) of processing elements (PE's) are configured in a square array. For optimum performance on operands of arbitrary length, processing is performed in a bit-serial manner. On 8-bit integer data, addition can occur at 6553 million operations per second (MOPS) and multiplication at 1861 MOPS. On 32-bit floating-point data, addition can occur at 430 MOPS and multiplication at 216 MOPS.
Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro (2003)

Bisphosphonates (BPs) are an emerging class of drugs mostly used in the palliative care of cancer patients. We investigated the in vitro activity of the most potent antiresorptive BP, zoledronic acid (ZOL), on the growth and survival of three human pancreatic cancer (PC) cell lines (BxPC-3, CFPAC-1 and PANC-1). Pancreatic cancer frequently has a dysregulated p21(ras) pathway and therefore appears to be a suitable target for BPs that interfere with the prenylation of small GTP-binding proteins such as p21(ras). We found that ZOL induces growth inhibition (IC(50):10-50 micro M) and apoptotic death of PC cells. The proapoptotic effect was correlated to cleavage/activation of caspase-9 and poly(ADP)-ribose polymerase, but not of caspase-3. Moreover, we studied the p21(ras) signalling in cells exposed to ZOL and detected a reduction of p21(ras) and Raf-1 content and functional downregulation of the terminal enzyme ERK/MAPkinase and of the pKB/Akt survival pathway. Finally, we observed that ZOL induces significant cytoskeletal rearrangements. In conclusion, we demonstrated that ZOL induces growth inhibition and apoptosis on PC cells and interferes with growth and survival pathways downstream to p21(ras). These findings might be relevant for expanding application of BPs in cancer treatment.
Isolation and characterization of hepatitis A virus. (1976)

This paper presents current isolation technics of hepatitis A virus (HAV) from human and chimpanzee stool, liver, and bile specimens, as well as comparative characterizations of HAV buoyant density properties of human and chimpanzee stool-derived particles. In addition, methods designed for the extraction and purification of HAV from large samples of stool and liver tissues, including agar gel filtration, are discussed in detail.
Image-Guidance Enables New Methods for Customizing Cochlear Implant Stimulation Strategies (2013)

Over the last 20 years, cochlear implants (CIs) have become what is arguably the most successful neural prosthesis to date. Despite this success, a significant number of CI recipients experience marginal hearing restoration, and, even among the best performers, restoration to normal fidelity is rare. In this paper, we present image processing techniques that can be used to detect, for the first time, the positions of implanted CI electrodes and the nerves they stimulate for individual CI users. These techniques permit development of new, customized CI stimulation strategies. We present one such strategy and show that it leads to significant hearing improvement in an experiment conducted with 11 CI recipients. These results indicate that image-guidance can be used to improve hearing outcomes for many existing CI recipients without requiring additional surgical procedures.
Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment (2014)

During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.