gebhart/patrepeval huggingface dataset:
First-in-human phase I trial of a cyclodextrin-containing polymer-camptothecin nanoparticle in patients with solid tumors (2007)

14078 Background: IT-101 is a de novo designed experimental therapeutic comprised of linear, cyclodextrin(CD)-containing polymer conjugates of camptothecin(CPT) that assemble into ca. 40 nm diameter nanoparticles via polymer-polymer interactions that involve inclusion complex formation between the CPT and the CD. Particle size, near neutral surface charge and CPT release rate were specifically designed into IT-101. Published pre-clinical animal studies show extended circulation times (t 1/2 of ca. 20 h in rodents), tumor accumulation, slow release of the CPT and anti-tumor efficacy that directly correlate to the properties of the nanoparticle. Release of CPT can disassemble the nanoparticle into individual polymer chains that have size ca. 10 nm that are capable of renal clearance (t 1/2 of several minutes in rodents). Methods: Patients with relapsed or refractory cancer were evaluated every two cycles of therapy (90 minute IV infusions of IT- 101 in D5W on days 1, 8 and 15 of a 28 day cycle). Three dose levels of 6, 12 and 18 mg CPT eq./m 2 have been tested. Results: At the time of this interim analysis, eight patients have been enrolled and five evaluated. In general, IT-101 is well tolerated and pancytopenia is the DLT. The expected MTD is 12 mg/ m 2 .Three out of five patients demonstrated stable disease on CT scan evaluation. One pancreatic cancer patient remains stable for 6 months. PK data are available from the first 5 patients. Total and free CPT display biphasic elimination from plasma with mean terminal elimination half lives of 38±3.7 and 61±43 hours, respectively. The mean Vd and CLsys of total CPT are 6.1±1.4 L and 0.1±0.03 L/h and are unrelated to dose over the range tested, with a mean total-to-free AUC ratio of 10.7±3.7. Conclusions: These first in human PK data for IT-101 confirm that 40 nm particles with near neutral surface charge provide favorable PK properties. The stable disease rate, although not yet conclusive, is consistent with promising efficacy. The preliminary results of this phase I study warrant continued enrollment that is ongoing. No significant financial relationships to disclose.
A Novel Nuclear Human Poly(A) Polymerase (PAP), PAPγ (2001)

Poly(A) polymerase (PAP) is present in multiple forms in mammalian cells and tissues. Here we show that the 90-kDa isoform is the product of the gene PAPOLG, which is distinct from the previously identified genes for poly(A) polymerases. The 90-kDa isoform is referred to as human PAP gamma (hsPAP gamma). hsPAP gamma shares 60% identity to human PAPII (hsPAPII) at the amino acid level. hsPAP gamma exhibits fundamental properties of a bona fide poly(A) polymerase, specificity for ATP, and cleavage and polyadenylation specificity factor/hexanucleotide-dependent polyadenylation activity. The catalytic parameters indicate similar catalytic efficiency to that of hsPAPII. Mutational analysis and sequence comparison revealed that hsPAP gamma and hsPAPII have similar organization of structural and functional domains. hsPAP gamma contains a U1A protein-interacting region in its C terminus, and PAP gamma activity can be inhibited, as hsPAPII, by the U1A protein. hsPAPgamma is restricted to the nucleus as revealed by in situ staining and by transfection experiments. Based on this and previous studies, it is obvious that multiple isoforms of PAP are generated by three distinct mechanisms: gene duplication, alternative RNA processing, and post-translational modification. The exclusive nuclear localization of hsPAP gamma establishes that multiple forms of PAP are unevenly distributed in the cell, implying specialized roles for the various isoforms.
5PbO·3GeO2 CRYSTAL; A NEW FERROELECTRIC (1971)

Dielectric constants and refractive indices of a 5PbO · 3GeO2 crystal, which was grown from the melt by by the Czochralski method, were measured as a function of temperature. The crystal was identified as a new type of ferroelectric with spontaneous polarization Ps = 0.046 C/m2, coercive field Ec ∼ 2.3 × 106 V/m at room temperature, and Tc = 177°C.
Epstein-Barr Virus Latent Infection and BAFF Expression in B Cells in the Multiple Sclerosis Brain: Implications for Viral Persistence and Intrathecal B-Cell Activation (2010)

A cardinal feature of multiple sclerosis (MS) is the persistent intrathecal synthesis of antibodies. Our previous finding that a large fraction of B cells infiltrating the MS brain are infected with Epstein-Barr virus (EBV) raises the possibility that this virus, because of its ability to establish a latent infection in B cells and interfere with their differentiation, contributes to B-cell dysregulation in MS. The aim of this study was to gain further insight into EBV latency programs and their relationship to B-cell activation in the MS brain. Immunohistochemical analysis of postmortem MS brain samples harboring large EBV deposits revealed that most B cells in white matter lesions, meninges, and ectopic B-cell follicles are CD27+ antigen-experienced cells and coexpress latent membrane protein 1 and latent membrane protein 2A, 2 EBV-encoded proteins that provide survival and maturation signals to B cells. By combining laser-capture microdissection with preamplification reverse transcription-polymerase chain reaction techniques, EBV latency transcripts (latent membrane protein 2A, EBV nuclear antigen 1) were detected in all MS brain samples analyzed. We also found that B cell-activating factor of the tumor necrosis factor family is expressed in EBV-infected B cells in acute MS lesions and ectopic B-cell follicles. These findings support a role for EBV infection in B-cell activation in the MS brain and suggest that B cell-activating factor of the tumor necrosis factor family produced by EBV-infected B cells may contribute to this process resulting in viral persistence and, possibly, disruption of B-cell tolerance.
Characterization of the <i>cis</i>‐acting elements of the mouse myelin P<sub>2</sub> promoter (1993)

Abstract Myelin P 2 is a basic protein of an apparent molecular weight of 14,800. Expression of P 2 has been found largely in the cytosol of Schwann cells in the peripheral nervous system. Although the function of P 2 is unknown, its striking homology to a family of fatty acid binding proteins has led to the idea that P 2 may function as a fatty acid transport molecule. To investigate the DNA elements that control the expression of P 2 , sequences 5′ to the coding region were cloned upstream of the cat reporter gene. A series of 3′ and 5′ promoter mutants was constructed and their activity determined following transfection into secondary Schwann cells and the MT 4 H1 Schwann cell line. Using this strategy, we have identified a 217 bp silencer region and a 142 bp positive regulatory region. In addition, we have localized the 5′ flanking sequences in the promoter that are responsive to cAMP induction and to the transcription factor CCAAT/enhancer binding protein (C/EBP). © 1993 Wiley‐Liss, Inc.
Bragg cell heterodyne interferometry of fast plasma events (1976)

Plasma interferometry using the fringe shift technique has been extended to the 100-MHz range by the use of Bragg diffraction in a lead molybdate acousto-optic cell. The cell splits a 633-nm laser beam into zero and first-order beams, which are separated in frequency by 80 MHz. These beams are used in the scene and reference arms of a modified Michelson interferometer and are then recombined on a silicon photodetector. Phase changes are deduced from the variations in time separation of consecutive peaks in the beat signal. The technique has been used to make electron density measurements in a 1-m-long, shock heated theta pinch with 6-nsec time resolution. Density variations during the implosion produce a total phase shift of nearly 1 fringe in 150 nsec. Phase noise in vacuum shots (without plasma) is 1/40 fringe rms; the peak-to-peak noise is 1/10 fringe, thus corresponding to a maximum area density (ℱn dl) uncertainty of 2×1016 cm−2.
Generalization of orthogonal multiprocessor for massively parallel computation (2003)

The authors present a multidimensional orthogonal multiprocessor (OMP) conceived for massively parallel computation. The OMP compares favorably with the generalized hypercube and spanning-bus hypercube. All three architectures extend the original concept of binary n-cube. Among the three, the OMP requires equal or less hardware and yet presents some interesting application potentials in massively parallel computation. The orthogonal architecture is a viable alternative to the conventional single-instruction multiple-data (SIMD) array computers which use distributed local memories. A detailed description of binary and k-ary OMP architecture is provided. Interprocessor communication strategy and network characteristics are presented. Potential applications and conclusions are included.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Oxalic acid in clear and cloudy atmospheres: Analysis of data from International Consortium for Atmospheric Research on Transport and Transformation 2004 (2006)

Oxalic acid is often the leading contributor to the total dicarboxylic acid mass in ambient organic aerosol particles. During the 2004 International Consortium for Atmospheric Research on Transport and Transformation (ICARTT) field campaign, nine inorganic ions (including SO 4 2− ) and five organic acid ions (including oxalate) were measured on board the Center for Interdisciplinary Remotely Piloted Aircraft Studies (CIRPAS) Twin Otter research aircraft by a particle‐into‐liquid sampler (PILS) during flights over Ohio and surrounding areas. Five local atmospheric conditions were studied: (1) cloud‐free air, (2) power plant plume in cloud‐free air with precipitation from scattered clouds overhead, (3) power plant plume in cloud‐free air, (4) power plant plume in cloud, and (5) clouds uninfluenced by local pollution sources. The aircraft sampled from two inlets: a counterflow virtual impactor (CVI) to isolate droplet residuals in clouds and a second inlet for sampling total aerosol. A strong correlation was observed between oxalate and SO 4 2− when sampling through both inlets in clouds. Predictions from a chemical cloud parcel model considering the aqueous‐phase production of dicarboxylic acids and SO 4 2− show good agreement for the relative magnitude of SO 4 2− and oxalate growth for two scenarios: power plant plume in clouds and clouds uninfluenced by local pollution sources. The relative contributions of the two aqueous‐phase routes responsible for oxalic acid formation were examined; the oxidation of glyoxylic acid was predicted to dominate over the decay of longer‐chain dicarboxylic acids. Clear evidence is presented for aqueous‐phase oxalic acid production as the primary mechanism for oxalic acid formation in ambient aerosols.
Lighting porphyrins and phthalocyanines for molecular photovoltaics (2010)

The field of organic photovoltaics (OPV) represents one of the most promising technological areas. Porphyrins and phthalocyanines are perfectly suited for their integration in light energy conversion systems. These colored macrocycles exhibit very attractive physical properties, particularly very high extinction coefficients in the visible and near IR regions, where the maximum of the solar photon flux occurs, that is necessary for efficient photon harvesting, besides a rich redox chemistry, as well as photoinduced electron transfer and semiconducting capabilities.
Mobile location estimation based on differences of signal attenuations for GSM systems (2004)

Radio location by time advance for GSM systems had been published. However, the resolution of time advance in GSM systems is too coarse to locate a mobile's position. The paper proposes a mobile location estimation based on the differences of downlink signal attenuations. This provides a possible mobile location method if the relationship between distance and signal attenuation is determined. Then, the mobile location can be estimated from those possible locations. The error of the proposed method is much smaller than the error of the cell-ID method in the practical microcell system. The greatest advantage of this method is the non-necessity of a known and accurate path loss model and the reduction of the shadowing effect.
Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells (2005)

Folate is a B vitamin, deficiency of which appears to increase the risk of developing several malignancies including colorectal cancer. In contrast to the cancer-promoting effect of folate deficiency in normal tissues, several lines of evidence indicate that folate depletion suppresses the progression of existing neoplasms and enhance the sensitivity of cancer cells to chemotherapy. Folate mediates the transfer of one-carbon necessary for the de novo biosynthesis of purines and thymidylate, and hence is an essential factor for DNA synthesis and repair, and the maintenance of DNA integrity and stability. Folate deficiency induces DNA strand breaks, increases uracil misincorporation into DNA, impairs DNA repair and appears to induce apoptosis. Although the effects of folate depletion on DNA integrity and apoptosis and on subsequent cancer development, progression and treatment in colonic epithelial cells have been well characterized, it is largely unknown at present how folate depletion modulates specific upstream genes in apoptosis and cancer pathways that regulate these processes. We therefore investigated the effects of folate depletion on expression of genes involved in apoptosis and cancer pathways in four human colon adenocarcinoma cell lines in an in vitro model of folate deficiency. Apoptosis and cancer pathway-specific mini-microarray were used to screen for differentially expressed genes in response to folate deficiency, and the expression of seven most notably and consistently affected genes was confirmed by real time RT-PCR. Our data suggest that folate deficiency affects the expression of key genes that are related to cell cycle control, DNA repair, apoptosis and angiogenesis in a cell-specific manner. Cell-specificity in gene expression changes in response to folate deficiency is likely due to significant differences in molecular and phenotypic characteristics, growth rates and intracellular folate concentrations among the four cell lines.
Properties of Escherichia coli expressing bacteriophage P22 Abc (anti-RecBCD) proteins, including inhibition of Chi activity (1993)

Escherichia coli strains bearing plasmids expressing phage P22 anti-RecBCD functions abc1 and abc2 were tested for the presence of recBC-like phenotypes. Abc2 induces moderate sensitivity to UV light in wild-type and recD mutant strains but severely sensitizes both recF and recJ mutants. Abc1 has little effect on UV sensitivity in wild-type or recF or recJ mutant hosts but increases the sensitivity of recD mutants to a UV dose of 20 J/m2 about 10-fold. Abc2 induces E. coli to segregate inviable cells during growth, interferes with the growth of lambda red gam chi+ and chi 0 phage (the effect is greater with chi+ phage), inhibits Chi and Chi-like activity as measured by lambda red gam crosses, and prevents SOS induction in response to nalidixic acid; Abc1 has no effect in these tests. Abc2, alone or with Abc1, does not allow the growth of lambda red gam in the presence of a P2 prophage but does not kill the P2 lysogenic host (as lambda Gam does). Finally, Abc2 inhibits conjugational recombination in wild-type cells to the level seen in recBC mutants. These data suggest that Abc2 inhibits the recombination-promoting ability of RecBCD but leaves the exonuclease functions intact.
CD11b is a therapy resistance– and minimal residual disease–specific marker in precursor B-cell acute lymphoblastic leukemia (2010)

Abstract A consistently increased mRNA expression of the adhesion receptor CD11b is a hallmark of the reported genomewide gene expression changes in precursor B-cell acute lymphoblastic leukemia (PBC-ALL) after 1 week of induction therapy. To investigate its clinical relevance, CD11b protein expression in leukemic blasts has been prospectively measured at diagnosis (159 patients) and during therapy (53 patients). The initially heterogeneous expression of CD11b inversely correlated with cytoreduction rates measured at clinically significant time points of induction therapy in the ALL–Berlin-Frankfurt-Münster 2000 protocol. CD11b positivity conferred a 5-fold increased risk of minimal residual disease (MRD) after induction therapy (day 33) and of high-risk group assignment after consolidation therapy (day 78). In the multivariate analysis CD11b expression was an independent prognostic factor compared with other clinically relevant parameters at diagnosis. During therapy, CD11b expression increased early in most ALL cases and remained consistently increased during induction/consolidation therapy. In more than 30% of MRD-positive cases, the CD11b expression on blast cells exceeded that of mature memory B cells and improved the discrimination of residual leukemic cells from regenerating bone marrow. Taken together, CD11b expression has considerable implications for prognosis, treatment response monitoring, and MRD detection in childhood PBC-ALL.
CMOS leaf-cell design using simulated annealing (2003)

Describes a program which uses simulated annealing to optimize two-dimensional, full-custom, symbolic CMOS leaf-cell layouts given a circuit-level netlist. User input specifies groups of series and parallel transistor connections with up to three levels of logic hierarchy. Simulated annealing is used for selecting group placements. A new cost function is presented for the simulated annealing algorithm which is based on channel congestion as well as estimated interconnect cost.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Regulation of Mitotic Homeologous Recombination in Yeast: Functions of Mismatch Repair and Nucleotide Excision Repair Genes (2000)

The Saccharomyces cerevisiae homologs of the bacterial mismatch repair proteins MutS and MutL correct replication errors and prevent recombination between homeologous (nonidentical) sequences. Previously, we demonstrated that Msh2p, Msh3p, and Pms1p regulate recombination between 91% identical inverted repeats, and here use the same substrates to show that Mlh1p and Msh6p have important antirecombination roles. In addition, substrates containing defined types of mismatches (base-base mismatches; 1-, 4-, or 12-nt insertion/deletion loops; or 18-nt palindromes) were used to examine recognition of these mismatches in mitotic recombination intermediates. Msh2p was required for recognition of all types of mismatches, whereas Msh6p recognized only base-base mismatches and 1-nt insertion/deletion loops. Msh3p was involved in recognition of the palindrome and all loops, but also had an unexpected antirecombination role when the potential heteroduplex contained only base-base mismatches. In contrast to their similar antimutator roles, Pms1p consistently inhibited recombination to a lesser degree than did Msh2p. In addition to the yeast MutS and MutL homologs, the exonuclease Exo1p and the nucleotide excision repair proteins Rad1p and Rad10p were found to have roles in inhibiting recombination between mismatched substrates.
Distributed shared memory: a survey of issues and algorithms (1991)

An overview of distributed shared memory (DSM) issues is presented. Memory coherence, design choices, and implementation methods are included. The discussion of design choices covers structure and granularity, coherence semantics, scalability, and heterogeneity. Implementation issues concern data location and access, the coherence protocol, replacement strategy, and thrashing. Algorithms that support process synchronization and memory management are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Bistabilité optique des lasers couplés (1987)

On écrit le principe et les méthodes de réalisation d'une classe de bistable optique à basculement symétrique, basée sur l'inhibition réciproque de deux lasers à grand gain. L'analyse théorique permet de décrire les conditions d'obtention du régime bistable et les possibilités de commutation par voie purement optique. Une expérience menée avec une paire de lasers à colorant confirme la validité de ce principe et démontre la possibilité de commutations sub-nanoseconde. L'extension aux lasers à semi-conducteurs est discutée et les caractéristiques fonctionnelles de ces dispositifs sont comparées à celles des autres bistables optiques.
Selective Surface Functionalization and Metal Deposition in the Micropores of Mesoporous Silica SBA-15 (2007)

A procedure for the selective surface functionalization of the mesopores and micropores of mesoporous silica SBA-15 has been developed. The resulting bifunctional material has been used to incorporate Pd nanoparticles in the micropores. The method described provides a general route for creating different local environments within the nanometer-sized pore structure and for the selective deposition of guest species in the micropores of this type of bimodal porous materials.
CNG/Methane-Combustion in a Homogeneous-Combustion Radical-Ignition D.I. Diesel Engine (2007)

<div class="htmlview paragraph">A detailed examination is made of the effects of internally generated “radicals” on the chemical-kinetics mechanism for CNG (compressed natural gas) combustion in a direct-injection (DI) diesel engine operating under ultra-lean fuel conditions at normal diesel compression ratios. The primary generating site for these “radical” chemical species is a set of mini-chambers located within the cylinder head. Explored in this study is the potential for controlling the autoignition timing of the engine by altering the rates of this radical generation process via the temperature management of these chambers. The study suggests that the temperature management of these secondary chambers may help enable the control of the ignition timings in response to engine load changes. The simulation involves the chemical-kinetics of 29 species and 84 chemical reactions solved simultaneously within the mini and main chambers as these chambers interact with each other, with the engine housing and with the manifold (exchanging energy, momentum, mass and chemical species).</div>
Serum vascular endothelial growth factor is a biomolecular biomarker of severity of diabetic retinopathy (2019)

Serum VEGF level is a simple, effective laboratory investigative test in predicting the onset of DR in eyes showing no evidence of DR and serves as a reliable biomolecular biomarker for severity of DR.