gebhart/patrepeval huggingface dataset:
Cyclin D3 expression in normal, reactive and neoplastic tissues (1998)

Cyclin D3 immunohistochemical expression was investigated in normal, reactive, and neoplastic human embryonal and adult tissues. In the fetus, cyclin D3 was expressed in selected developmental phases of a limited number of cell systems. In normal adult tissues, cyclin D3 showed two patterns of distribution: in lymphoid tissues it was expressed in proliferative compartments, while in most other tissues it was expressed by terminally differentiated/quiescent cells. This dual role in proliferation and differentiation was partially conserved in neoplasms. In non-Hodgkin lymphomas, cyclin D3 immunolabelling was correlated with proliferative activity and progression; a significant exception was seen in cyclin D1-positive mantle cell lymphomas, which were cyclin D-negative. Benign endocrine tumours were frequently strongly cyclin D3-positive, while high-grade (small cell) neuroendocrine carcinomas were always negative. In most other epithelial neoplasms, cyclin D3 immunostaining was heterogeneous. In breast carcinomas, no relationship was seen between ER status and MIB1 labelling; cyclins D3 and D1 were frequently expressed in the same tumour, while occasional tumours showed an inverse quantitative relationship between cyclins D1 and D3, and rare tumours were negative for both. In soft tissue neoplasms, cyclin D3 was consistently expressed in some tumours, such as stromal tumours of the gastrointestinal tract and embryonal rhabdomyosarcomas. Our data suggest that cyclin D3 has a dual role in proliferation and differentiation in normal tissues and in some neoplastic conditions; that the cyclin D3 expression pattern is different from cyclin D1, suggesting non-redundant functions; that cyclin D3 expression is strong in endocrine cells secreting steroid hormones, and in their neoplastic counterparts; and that cyclin D3 deregulation may be of pathogenetic relevance in lymphomagenesis and could be diagnostically useful.
Road Tests of a Misfire Detection System (1994)

&lt;div class="htmlview paragraph"&gt;This paper presents the theory and experimental performance of a system for detecting engine misfires in automobiles. The method is potentially suitable for meeting the California Air Resources Board (CARB) requirements under On Board Diagnostics II (OBDII) rules.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The instrumentation for the present method measures (noncontacting) crankshaft instantaneous angular speed. Highly efficient signal processing algorithms permit detection of each individual misfire.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The performance of the present method is expressed in terms of error rates made in detecting individual misfires. Normal operating conditions yield error rates under 10&lt;sup&gt;-4&lt;/sup&gt;. Under worst case conditions consisting of light load, high RPM and rough roads with the torque converter in lockup are under 10&lt;sup&gt;-3&lt;/sup&gt;.&lt;/div&gt;
Taxol: mechanisms of action and resistance. (1993)

Information on the mechanisms of action and of resistance to Taxol, as well as new data from our laboratory on the promoter regions of the genes that encode P-glycoprotein in a murine Taxol-resistant cell line, is discussed. Taxol induces the formation of stable bundles of microtubules, thereby interfering with the normal function of cellular microtubules. The drug can induce the multidrug-resistance (MDR) phenotype that includes the overproduction of P-glycoprotein, a membrane glycoprotein that acts as a drug efflux pump. In human tumors resistant to Taxol, P-glycoprotein could be responsible for maintaining the drug below cytotoxic levels. Analyses of the MDR promoters that are involved in P-glycoprotein expression and overproduction revealed an interesting recombination event in a Taxol-resistant cell line. As an important new clinical agent for the treatment of malignancies, Taxol requires further mechanistic investigations at the preclinical level.
Identification of a Family of Streptococcal Surface Proteins with Extremely Repetitive Structure (1996)

The group B Streptococcus (GBS) causes the majority of life-threatening bacterial infections in newborn children. Most GBS strains isolated from such infections express a surface protein, designated Rib, that confers protective immunity and therefore is of interest for analysis of pathogenetic mechanisms. Sequence analysis demonstrated that Rib has an exceptionally long signal peptide (55 amino acid residues) and 12 repeats (79 amino acid residues each) that account for >80% of the sequence of the mature protein. The repeats are identical even at the DNA level, indicating that an efficient mechanism operates to maintain a highly repetitive structure in Rib. The structure of Rib is similar to that of alpha, a previously characterized surface protein that is common among GBS strains lacking Rib. However, highly purified preparations of Rib and alpha did not cross-react immunologically, although the two proteins show extensive amino acid residue identity (47% in the repeat region). When analyzed in Western blots, Rib and alpha give rise to a regularly spaced ladder pattern, apparently due to hydrolysis of acid-labile Asp-Pro bonds in the repeats. We conclude that Rib and alpha are members of a novel family of streptococcal surface proteins with unusual repetitive structure.
<title>Optimization of real phase-mask performance</title> (1992)

Classical phase mask lithography designs can be understood by the application of Fourier optics to the phase mask pattern. For maximum resolution, the mask design for a circularly symmetric contact hole will have a Fourier pattern with most of the energy near the edge of the system aperture. The inverse Fourier transform of an ideal annular Fourier plane pattern is the Bessel function, Jo. This function consists of a central lobe and an infinite number of rings, with each ring having equal energy and alternating phase shifts. This function is a solution to the wave equation in cylindrical coordinates. A characteristic of this solution is that the field has the same transverse profile, independent of the position along the axis. Therefore, the diameter of the central lobe of an ideal Bessel beam will have infinite depth of focus. Although approximations to such diffraction free beams have been reported for coherent light, the depth of focus depends on the number of outer lobes of the Bessel function that can be produced. Practical mask design and imperfect coherence limit the number of lobes that are actually useful. However, a coarse approximation to the Bessel beam can be created with only one or two phase shifted lobes. This is what is attempted in the optimized "outrigger" patterns. The ideal design, however, is one in which one phase- edge is placed at the zero of the Jo function, and a second is placed so that the power in the outer lobe approximates that of the Bessel function. Masks were fabricated with such designs, and the wafer exposures show that the image is significantly brighter than with other techniques, and the depth of focus is also significantly increased.
Tandem Mass Spectrometry of Large Biomolecule Ions by Blackbody Infrared Radiative Dissociation (1996)

A new method for the dissociation of large ions formed by electrospray ionization is demonstrated. Ions trapped in a Fourier transform mass spectrometer at pressures below 10(-)(8) Torr are dissociated by elevating the vacuum chamber to temperatures up to 215 °C. Rate constants for dissociation are measured and found to be independent of pressure below 10(-)(7) Torr. This indicates that the ions are activated by absorption of blackbody radiation emitted from the chamber walls. Dissociation efficiencies as high as 100% are obtained. There is no apparent mass limit to this method; ions as large as ubiquitin (8.6 kDa) are readily dissociated. Thermally stable ions, such as melittin 3+ (2.8 kDa), did not dissociate at temperatures up to 200 °C. This method is highly selective for low-energy fragmentation, from which limited sequence information can be obtained. From the temperature dependence of the dissociation rate constants, Arrhenius activation energies in the low-pressure limit are obtained. The lowest energy dissociation processes for the singly and doubly protonated ions of bradykinin are loss of NH(3) and formation of the b(2)/y(7) complementary pair, with activation energies of 1.3 and 0.8 eV, respectively. No loss of NH(3) is observed for the doubly protonated ion; some loss of H(2)O occurs. These results show that charge-charge interactions not only lower the activation energy for dissociation but also can dramatically change the fragmentation, most likely through changes in the gas-phase conformation of the ion. Dissociation of ubiquitin ions produces fragmentation similar to that obtained by IRMPD and SORI-CAD. Higher charge state ions dissociate to produce y and b ions; the primary fragmentation process for low charge state ions is loss of H(2)O.
Glycogen Synthase Kinase 3β Phosphorylates Tau at Both Primed and Unprimed Sites (2002)

Glycogen synthase kinase 3beta (GSK3beta) phosphorylates substrates, including the microtubule-associated protein tau, at both primed and unprimed epitopes. GSK3beta phosphorylation of tau negatively regulates tau-microtubule interactions; however the differential effects of phosphorylation at primed and unprimed epitopes on tau is unknown. To examine the phosphorylation of tau at primed and unprimed epitopes and how this impacts tau function, the R96A mutant of GSK3beta was used, a mutation that prevents phosphorylation of substrates at primed sites. Both GSK3beta and GSK3beta-R96A phosphorylated tau efficiently in situ. However, expression of GSK3beta-R96A resulted in significantly less phosphorylation of tau at primed sites compared with GSK3beta. Conversely, GSK3beta-R96A phosphorylated unprimed tau sites to a significantly greater extent than GSK3beta. Prephosphorylating tau with cdk5/p25 impaired the ability of GSK3beta-R96A to phosphorylate tau, whereas GSK3beta-R96A phosphorylated recombinant tau to a significantly greater extent than GSK3beta. Moreover, the amount of tau associated with microtubules was reduced by overexpression of GSK3beta but only when tau was phosphorylated at primed sites, as phosphorylation of tau by GSK3beta-R96A did not negatively regulate the association of tau with microtubules. These results demonstrate that GSK3beta-mediated phosphorylation of tau at primed sites plays a more significant role in regulating the interaction of tau with microtubules than phosphorylation at unprimed epitopes.
VALIDATION OF A NOMOGRAM FOR PREDICTING POSITIVE REPEAT BIOPSY FOR PROSTATE CANCER (2005)

Our corrected nomogram for predicting positive repeat biopsy performed well when applied to a sample of men at the Brooklyn Veterans Administration Medical Center. This nomogram can provide important additional information to aid the urologist and patient with a negative biopsy in evaluating clinical options.
Cladistic Structure Within the HumanLipoprotein LipaseGene and Its Implications for Phenotypic Association Studies (2000)

Haplotype variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase (LPL) gene was scored in three populations: African-Americans from Jackson, Mississippi (24 individuals), Finns from North Karelia, Finland (24), and non-Hispanic whites from Rochester, Minnesota (23). Earlier analyses had indicated that recombination was common but concentrated into a hotspot and that recurrent mutations at multiple sites may have occurred. We show that much evolutionary structure exists in the haplotype variation on either side of the recombinational hotspot. By peeling off significant recombination events from a tree estimated under the null hypothesis of no recombination, we also reveal some cladistic structure not disrupted by recombination during the time to coalescence of this variation. Additional cladistic structure is estimated to have emerged after recombination. Many apparent multiple mutational events at sites still remain after removing the effects of the detected recombination/gene conversion events. These apparent multiple events are found primarily at sites identified as highly mutable by previous studies, strengthening the conclusion that they are true multiple events. This analysis portrays the complexity of the interplay among many recombinational and mutational events that would be needed to explain the patterns of haplotype diversity in this gene. The cladistic structure in this region is used to identify four to six single-nucleotide polymorphisms (SNPs) that would provide disequilibrium coverage over much of this region. These sites may be useful in identifying phenotypic associations with variable sites in this gene. Evolutionary considerations also imply that the SNPs in the 3' region should have general utility in most human populations, but the 5' SNPs may be more population specific. Choosing SNPs at random would generally not provide adequate disequilibrium coverage of the sequenced region.
Basic problems and applications (1989)

38. Line Defects in Interfaces (R.C. Pond). 39. The Dislocation Core and Plasticity (M.S. Duesbery). 40. Conduction Electron Scattering in Dislocated Metals (B.R. Watts). 41. The Prediction of Critical Misfit and Thickness in Epitaxy (W.A. Jesser, J.H. van der Merwe). 42. Microstresses and the Mechanical Properties of Crystals (P.J. Jackson). 43. The Electroplastic Effect in Metals (H. Conrad, A.F. Sprecher). Author Index. Subject Index. Cumulative Index.
Mesenchymal stem cells avoid allogeneic rejection (2005)

Abstract Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched allogeneic tissue would appear to prevent the realisation of such ambitions. In fact mesenchymal stem cells avoid allogeneic rejection in humans and in animal models. These finding are supported by in vitro co-culture studies. Three broad mechanisms contribute to this effect. Firstly, mesenchymal stem cells are hypoimmunogenic, often lacking MHC-II and costimulatory molecule expression. Secondly, these stem cells prevent T cell responses indirectly through modulation of dendritic cells and directly by disrupting NK as well as CD8+ and CD4+ T cell function. Thirdly, mesenchymal stem cells induce a suppressive local microenvironment through the production of prostaglandins and interleukin-10 as well as by the expression of indoleamine 2,3,-dioxygenase, which depletes the local milieu of tryptophan. Comparison is made to maternal tolerance of the fetal allograft, and contrasted with the immune evasion mechanisms of tumor cells. Mesenchymal stem cells are a highly regulated self-renewing population of cells with potent mechanisms to avoid allogeneic rejection.
Synthesis of High-Mannose Type Neoglycolipids: Active Targeting of Liposomes to Macrophages in Gene Therapy (2000)

The concise synthesis of five biantennary oligomannose neoglycolipids is presented. Employing a strategy based on the principles of reactivity tuning and orthogonal activation, the oligomannose moieties, isolated from the glycoprotein 63 of the parasite Leishmania mexicana amazonensis, were rapidly assembled taking advantage of common structural motifs found in these N-glycans. Deprotection of all structures was achieved in high yield by hydrogenolysis. The deprotected glycoconjugates were subsequently coupled to a cholesteroldiamine derivative using diethylsquarate as a linker. The resulting neoglycolipids will be used as additives to cationic liposome formulations in the active targeting of liposomes to macrophages.
The 11q23 breakpoint in acute leukemia with t(11;19)(q23;p13) is distal to those of t(4;11), t(6;11) and t(9;11) (1992)

Thirteen cosmid probes were mapped on the long arm of chromosome 11 between 11q22 and 11q24 by nonradioactive in situ hybridization. Starting with these localizations and those of other probes mapped to 11q23, four acute leukemias with translocations involving 11q23 were studied with the same method. The translocation breakpoints of the t(4;11)(q21;q23), t(6;11)(q27;q23), t(9;11)(p21-p22;q23), and t(11;19)(q23;p13) were confirmed to be distal to CD3D. The probe cC111-304 was proximal to the t(11;19) breakpoint while distal to the breakpoints of the other rearrangements. In view of the diversity of chromosomal abnormalities involving band 11q23, our finding extends the molecular heterogeneity of the breakpoint localization in leukemias with rearrangements involving 11q23.
Tailoring the Lasing Modes in Semiconductor Nanowire Cavities Using Intrinsic Self-Absorption (2013)

Understanding the optical gain and mode-selection mechanisms in semiconductor nanowire (NW) lasers is key to the development of high-performance nanoscale oscillators, amplified semiconductor/plasmon lasers and single photon emitters, and so forth. Modification of semiconductor band structure/bandgap through electric field modulation, elemental doping, or alloying semiconductors has so far gained limited success in achieving output mode tunability of the NW laser. One stifling issue is the considerable optical losses induced in the NW cavities by these extrinsic methods that limit their applicability. Herein we demonstrate a new optical self-feedback mechanism based on the intrinsic self-absorption of the gain media to achieve low-loss, room-temperature NW lasing with a high degree of mode selectivity (over 30 nm). The cadmium sulfide (CdS) NW lasing wavelength is continuously tunable from 489 to 520 nm as the length of the NWs increases from 4 to 25 μm. Our straightforward approach is widely applicable in most semiconductor or semiconductor/plasmonic NW cavities.
Mechanisms of Liver and Muscle Insulin Resistance Induced by Chronic High-Fat Feeding (1997)

To elucidate cellular mechanisms of insulin resistance induced by excess dietary fat, we studied conscious chronically high-fat-fed (HFF) and control chow diet-fed rats during euglycemic-hyperinsulinemic (560 pmol/l plasma insulin) clamps. Compared with chow diet feeding, fat feeding significantly impaired insulin action (reduced whole body glucose disposal rate, reduced skeletal muscle glucose metabolism, and decreased insulin suppressibility of hepatic glucose production [HGP]). In HFF rats, hyperinsulinemia significantly suppressed circulating free fatty acids but not the intracellular availability of fatty acid in skeletal muscle (long chain fatty acyl-CoA esters remained at 230% above control levels). In HFF animals, acute blockade of beta-oxidation using etomoxir increased insulin-stimulated muscle glucose uptake, via a selective increase in the component directed to glycolysis, but did not reverse the defect in net glycogen synthesis or glycogen synthase. In clamp HFF animals, etomoxir did not significantly alter the reduced ability of insulin to suppress HGP, but induced substantial depletion of hepatic glycogen content. This implied that gluconeogenesis was reduced by inhibition of hepatic fatty acid oxidation and that an alternative mechanism was involved in the elevated HGP in HFF rats. Evidence was then obtained suggesting that this involves a reduction in hepatic glucokinase (GK) activity and an inability of insulin to acutely lower glucose-6-phosphatase (G-6-Pase) activity. Overall, a 76% increase in the activity ratio G-6-Pase/GK was observed, which would favor net hepatic glucose release and elevated HGP in HFF rats. Thus in the insulin-resistant HFF rat 1) acute hyperinsulinemia fails to quench elevated muscle and liver lipid availability, 2) elevated lipid oxidation opposes insulin stimulation of muscle glucose oxidation (perhaps via the glucose-fatty acid cycle) and suppression of hepatic gluconeogenesis, and 3) mechanisms of impaired insulin-stimulated glucose storage and HGP suppressibility are not dependent on concomitant lipid oxidation; in the case of HGP we provide evidence for pivotal involvement of G-6-Pase and GK in the regulation of HGP by insulin, independent of the glucose source.
Impact of Gate Metal on the Performance of p-GaN/AlGaN/GaN High Electron Mobility Transistors (2015)

For conventional GaN-based high electron mobility transistors (HEMTs), the work function of gate metal is critical to electrical parameters, such as OFF-state leakage current, forward operating current, and threshold voltage. A high work function is thus required to maintain Schottky gate contact. In this letter, an enhancement-mode HEMT composed of p-type GaN/AlGaN/GaN was fabricated. Unlike typical HEMTs that the Schottky barrier height is determined by the energy difference between gate metal work function and semiconductor (AlGaN, or GaN) conduction band, the insertion of the p-GaN relieves the constraint of gate metal. In addition, the gate Schottky barrier now correlates to the valence band of the semiconductor. Here we compare the HEMT performance of different gate metals-Ni/Au, Ti/Au, and Mo/Ti/Au. The results reveal that a tradeoff between V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">TH</sub> and output drain current.
Bottom-Up Synthetic Biology: Engineering in a Tinkerer’s World (2011)

How synthetic can "synthetic biology" be? A literal interpretation of the name of this new life science discipline invokes expectations of the systematic construction of biological systems with cells being built module by module--from the bottom up. But can this possibly be achieved, taking into account the enormous complexity and redundancy of living systems, which distinguish them quite remarkably from design features that characterize human inventions? There are several recent developments in biology, in tight conjunction with quantitative disciplines, that may bring this literal perspective into the realm of the possible. However, such bottom-up engineering requires tools that were originally designed by nature's greatest tinkerer: evolution.
Pharmaceutical nanotechnology: polymeric vesicles for drug and gene delivery (2006)

Improving the therapeutic index of medicines is a goal of drug delivery. Employing nanosystems that control drug biodistribution is one way of achieving therapeutic improvements, and polymeric bilayer vesicles are one such nanosystem. Polymeric vesicles, with the ability to transport drugs or genes, are prepared in one of two ways: i) the self-assembly of amphiphilic polymers and ii) the polymerisation of monomers, following self-assembly (polymerised vesicles). There are two types of self-assembling amphiphilic polymers: water-soluble polymers derivatised with hydrophobic pendant groups and amphiphilic block copolymers. Amphiphilic alkenes and alkynes are the main compounds that are used to make polymerised vesicles. This review discusses polymer architecture fundamentals that govern the self-assembly of polymers into vesicles, the fine control on vesicle size that is achievable with polymeric vesicles and the application of the vesicles to drug delivery.