gebhart/patrepeval huggingface dataset:
The influence of particle size and multiple apoprotein E-receptor interactions on the endocytic targeting of beta-VLDL in mouse peritoneal macrophages. (1991)

Low density lipoprotein (LDL) and beta-very low density lipoprotein (beta-VLDL) are internalized by the same receptor in mouse peritoneal macrophages and yet their endocytic patterns differ; beta-VLDL is targeted to both widely distributed and perinuclear vesicles, whereas LDL is targeted almost entirely to perinuclear lysosomes. This endocytic divergence may have important metabolic consequences since beta-VLDL is catabolized slower than LDL and is a more potent stimulator of acyl-CoA/cholesterol acyl transferase (ACAT) than LDL. The goal of this study was to explore the determinants of beta-VLDL responsible for its pattern of endocytic targeting. Fluorescence microscopy experiments revealed that large, intestinally derived, apoprotein (Apo) E-rich beta-VLDL was targeted mostly to widely distributed vesicles, whereas small, hepatically derived beta-VLDL was targeted more centrally (like LDL). Furthermore, the large beta-VLDL had a higher ACAT-stimulatory potential than the smaller beta-VLDL. The basis for these differences was not due to fundamental differences in the means of uptake; both large and small beta-VLDL were internalized by receptor-mediated endocytosis (i.e., not phagocytosis) involving the interaction of Apo E of the beta-VLDL with the macrophage LDL receptor. However, large beta-VLDL was much more resistant to acid-mediated release from LDL receptors than small beta-VLDL. Furthermore, partial neutralization of the multiple Apo Es on these particles by immunotitration resulted in a more perinuclear endocytic pattern, a lower ACAT-stimulatory potential, and an increased sensitivity to acid-mediated receptor release. These data are consistent with the hypothesis that the interaction of the multivalent Apo Es of large beta-VLDL with multiple macrophage LDL receptors leads to a diminished or retarded release of the beta-VLDL from its receptor in the acidic sorting endosome which, in turn, may lead to the widely distributed endocytic pattern of large beta-VLDL. These findings may represent a physiologically relevant example of a previously described laboratory phenomenon whereby receptor cross-linking by multivalent ligands leads to a change in receptor targeting.
Site-specific inversion sequence of the herpes simplex virus genome: Domain and structural features (1981)

The genome of herpes simplex virus-1 consists of two covalently linked components, L and S, that invert relative to each other. The L and S components consist of unique DNA sequences bracketed by inverted repeats. The inverted repeats of the L component are designated ab and b' a' and those of the S component are designated a' c' and ca. The number of a sequences at the termini and at the L-S component junction varies from one to several copies. Insertion into the middle of the L component of a DNA fragment consisting of 156 base pairs (bp) of the b sequence, an entire a sequence of 501 bp, and 618 bp of the c sequence created a new site through which additional inversions in the genome occurred. Comparison of the nucleotide sequences of DNA fragments containing one and two a sequences defined the domain of the a sequence. The single a sequence consists of two 20-bp direct repeats (designated as DR1) bracketing a region that contains 19 tandem direct repeats of a 12-bp sequence (DR2) adjacent to three direct repeats of a 37-bp sequence (DR4), in addition to short stretches of unique sequences. The fragment with two tandem a sequences contained three copies of DR1-i.e., the intervening DR1 was shared by the two a sequences. Furthermore, one a sequence contained 22 copies of DR2 and two copies of DR4 whereas the second a sequence contained 19 copies of DR2 and two copies of DR4. These observations suggest that (i) amplification of the number of terminal and internal a sequences is the consequence of intramolecular or intermolecular recombination through DR1, (ii) the number of copies of DR2 and DR4 within the a sequence is not fixed and may vary as a consequence of unequal crossing over or slippage, and (iii) inversion results from intramolecular recombination between terminal and inverted a sequences.
On the linkage of impact damage to modeling of ballistic performance (2014)

Welcome to the WIT Press eLibrary - the home of the Transactions of the Wessex Institute collection, providing on-line access to papers presented at the Institute's prestigious international conferences and from its State-of-the-Art in Science & Engineering publications.
Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. (1992)

An understanding of the differences and similarities of the retinoid X receptor (RXR) and retinoic acid receptor (RAR) systems requires knowledge of the diversity of their family members, their patterns of expression, and their pharmacological response to ligands. In this paper we report the isolation of a family of mouse RXR genes encoding three distinct receptors (RXR alpha, beta, and gamma). They are closely related to each other in their DNA- and ligand-binding domains but are quite divergent from the RAR subfamily in both structure and ligand specificity. Recently, we demonstrated that all-trans retinoic acid (RA) serves as a "pro-hormone" to the isomer 9-cis RA, which is a high-affinity ligand for the human RXR alpha. We extend those findings to show that 9-cis RA is also "retinoid X" for mouse RXR alpha, beta, and gamma. Trans-activation analyses show that although all three RXRs respond to a variety of endogenous retinoids, 9-cis RA is their most potent ligand and is up to 40-fold more active than all-trans RA. Northern blot and in situ hybridization analyses define a broad spectrum of expression for the RXRs, which display unique patterns and only partially overlap themselves and the RARs. This study suggests that the RXR family plays critical roles in diverse aspects of development, from embryo implantation to organogenesis and central nervous system differentiation, as well as in adult physiology.
The role of HER-2 oncoprotein in drug-sensitivity in breast cancer (Review) (2002)

Overexpression of human epidermal growth factor receptor-2 (HER-2) oncoprotein is an important prognostic factor associated with a poor prognosis in breast cancer. Although treatment with trastuzumab, an anti-HER-2 antibody, increases drug-sensitivity in vitro and in vivo, the role of HER-2 oncoprotein in drug-sensitivity is still uncertain. The present work discusses the clinical significance of the HER-2 oncoprotein in drug-sensitivity in breast cancer based on previous clinical and basic results and reviews the current concept of HER-2 oncoprotein in drug-sensitivity. Introduction of HER-2 oncoprotein in vitro induces resistance to several anticancer drugs, including taxanes, cisplatin (CDDP) and 5-fluorouracil (5-FU) in breast cancer cells. The acquisition of drug-resistance by introduction of the HER-2 gene, however, depends on the cell type, because transfection of the HER-2 gene per se does not necessarily induce resistance to the same drugs in all types of breast cancer cells. In clinical studies, patients with HER-2 overexpression responded better to an anthracycline-based regimen than patients with low HER-2 expression, and their overall survival was also superior. In contrast, a correlation between the response to a cyclophosphamide + methotrexate + 5-FU regimen and overexpression of HER-2 is not certain. Taxanes responsiveness in patients with HER-2 oncoprotein overexpression was superior in patients with low HER-2 expression. Treatment with trastuzumab increased drug-sensitivity to anthracyclines, CDDP, and taxanes, but not to 5-FU, in breast cancer cells. Although the mechanism(s) by which trastuzumab enhances drug-sensitivity is not fully understood, modulation of the signal transduction pathways leading to apoptosis, such as down-regulation of the anti-apoptotic protein, Bcl-2, might be an important target to increase drug-sensitivity in breast cancer. HER-2 overexpression can be a good indicator for the selection of aniticancer drugs, especially for anthracycline containing regimens. To modulate HER-2-targeting therapy, the mechanism(s) by which trastuzumab enhances drug-sensitivity requires elucidation at the molecular level, including determination of other factors that influence drug-sensitivity, leading to a more promising treatment for individual patients receiving combination therapy with trastuzumab and anticancer drugs for breast cancer.
Prefetch-aware shared resource management for multi-core systems (2011)

Chip multiprocessors (CMPs) share a large portion of the memory subsystem among multiple cores. Recent proposals have addressed high-performance and fair management of these shared resources; however, none of them take into account prefetch requests. Without prefetching, significant performance is lost, which is why existing systems prefetch. By not taking into account prefetch requests, recent shared-resource management proposals often significantly degrade both performance and fairness, rather than improve them in the presence of prefetching. This paper is the first to propose mechanisms that both manage the shared resources of a multi-core chip to obtain high-performance and fairness, and also exploit prefetching. We apply our proposed mechanisms to two resource-based management techniques for memory scheduling and one source-throttling-based management technique for the entire shared memory system. We show that our mechanisms improve the performance of a 4-core system that uses network fair queuing, parallelism-aware batch scheduling, and fairness via source throttling by 11.0%, 10.9%, and 11.3% respectively, while also significantly improving fairness.
Human β-cell Precursors Mature Into Functional Insulin-producing Cells in an Immunoisolation Device: Implications for Diabetes Cell Therapies (2009)

We demonstrate for the first time that human beta-cells function is compatible with encapsulation in a durable, immunoprotective device. Moreover, our study suggests that encapsulation of beta-cells before terminal differentiation will be a successful approach for new cell-based therapies for diabetes, such as those derived from stem cells.
Influence of the strain on the energy levels of semiconductor quantum dots (2005)

We systematically investigate a strain of self-assembled InAs/GaAs quantum dots (QDs) for the case of growth on a (001) substrate. The dependence of the biaxial and hydrostatic components of the strain on the quantum dot aspect ratio is studied using a finite element method. The dependence of the carrier's confining potentials is then calculated in the framework of eight-band kp theory. The shifts of the energy level in three shapes of QDs are investigated. By comparing the results, the influence of the strain on the QDs are given.
How Do PCSK9 Inhibitors Stack Up to Statins for Low-Density Lipoprotein Cholesterol Control? (2015)

Despite advances in the approach toward treating hypercholesterolemia and widespread access to statin medications, not all people are able to reach target low-density lipoprotein cholesterol (LDL-C) levels to reduce their cardiovascular risk. Some of the reasons include the inability to tolerate statin therapy, LDL-C levels that remain high even in the presence of statin therapy, and a familial disorder that is characterized by extremely high levels of LDL-C. A new therapeutic class, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, represents a novel and promising approach to reducing LDL-C levels using a mechanism at the LDL receptor level. The recent approval of the first 2 PCSK9 inhibitors and the anticipated approval of the third agent in this class within approximately 1 year may provide clinicians powerful new weapons to lower LDL-C levels in patients who are not satisfactorily managed with statins. However, the results of long-term studies of the ability of these new medications to influence cardiovascular outcomes will not be known for several years.
Efficient string matching (1975)

This paper describes a simple, efficient algorithm to locate all occurrences of any of a finite number of keywords in a string of text. The algorithm consists of constructing a finite state pattern matching machine from the keywords and then using the pattern matching machine to process the text string in a single pass. Construction of the pattern matching machine takes time proportional to the sum of the lengths of the keywords. The number of state transitions made by the pattern matching machine in processing the text string is independent of the number of keywords. The algorithm has been used to improve the speed of a library bibliographic search program by a factor of 5 to 10.
A study in interactive 3-D rotation using 2-D control devices (1988)

This paper describes and evaluates the design of four virtual controllers for use in rotating three-dimensional objects using the mouse. Three of four of these controllers are "new" in that they extend traditional direct manipulation techniques to a 3-D environment. User performance is compared during simple and complex rotation tasks. The results indicate faster performance for complex rotations using the new continuous axes controllers compared to more traditional slider approaches. No significant differences in accuracy for complex rotations were found across the virtual controllers.A second study compared the best of these four virtual controllers (the Virtual Sphere) to a control device by Evans, Tanner and Wein. No significant differences either in time to complete rotation task or accuracy of performance were found. All but one subject indicated they preferred the Virtual Sphere because it seemed more "natural".
Cellular DNA amounts of squamous cell carcinomas of the head and neck region in relation to prognosis (1982)

Cytophotometric measurements of Feulgen DNA content were made in individual tumor cells from 45 patients with squamous cell carcinomas of the head and neck region. Eleven carcinomas were found to have a predominantly diploid distribution of DNA values, while the remaining 34 carcinomas were non-diploid. In 11 of the tumors--not entirely identical with the diploid tumors--50% or less of the malignant cells had DNA values exceeding the modal diploid value (DNA G1 + 2 S.D.), whereas 34 had higher DNA values. The non-diploid carcinomas and those where greater than 50% of the cells had DNA values greater than DNA G1 + 2 S.D. showed more advanced clinical stage, due to the presence of regional metastases. They were also associated with a poorer prognosis than the diploid carcinomas or those with less than or equal to 50% of the cells with DNA values greater than DNA G1 + 2 S.D. Cellular DNA amounts seemed to be of greater prognostic value than type of ploidy. The study indicates that DNA analysis may contribute important information of the biological behavior and prognosis of squamous cell carcinomas of the head and neck region.
Photonic band gap templating using optical interference lithography (2005)

We describe the properties of three families of inversion-symmetric, large photonic band-gap (PBG) template architectures defined by iso-intensity surfaces in four beam laser interference patterns. These templates can be fabricated by optical interference (holographic) lithography in a suitable polymer photo-resist. PBG materials can be synthesized from these templates using two stages of infiltration and inversion, first with silica and second with silicon. By considering point and space group symmetries to produce laser interference patterns with the smallest possible irreducible Brillouin zones, we obtain laser beam intensities, directions, and polarizations which generate a diamond-like (fcc) crystal, a novel body-centered cubic (bcc) architecture, and a simple-cubic (sc) structure. We obtain laser beam parameters that maximize the intensity contrasts of the interference patterns. This optimizes the robustness of the holographic lithography to inhomogeneity in the polymer photo-resist. When the optimized iso-intensity surface defines a silicon to air boundary (dielectric contrast of 11.9 to 1), the fcc, bcc, and sc crystals have PBG to center frequency ratios of 25%, 21%, and 11%, respectively. A full PBG forms for the diamond-like crystal when the refractive index contrast exceeds 1.97 to 1. We illustrate a non-inversion symmetric PBG architecture that interpolates between a simple fcc structure and a diamond network structure. This crystal exhibits two distinct and complete photonic band gaps. We also describe a generalized class of tetragonal photonic crystals that interpolate between and extrapolate beyond the diamond-like crystal and the optimized bcc crystal. We demonstrate the extent to which the resulting PBG materials are robust against perturbations to the laser beam amplitudes and polarizations, and template inhomogeneity. The body centered cubic structure exhibits the maximum robustness overall.
Mechanics of ostraciiform propulsion (1981)

Two hydromechanical models are employed to analyse the motions of the caudal fin of a small specimen of Ostracion lentiginosum (Ostraciidae). Values of the drag coefficient of the body of the fish are inferred by equating the impulse of the thrust force produced over the tail beat cycle with the impulse of the drag force acting on the body over the same period of time. On average, the inferred values for the drag coefficient are within 15% of experimentally determined values. Drag coefficients for ostraciiform fish are an order of magnitude greater than those for streamlined fish. The hydromechanical efficiency of the caudal fin propeller of O. lentiginosum is calculated to be of the order of 0.5. This result is predicted by the hydromechanical theory.
Kit signaling inhibits the sphingomyelin-ceramide pathway through PLCγ1: implication in stem cell factor radioprotective effect (2002)

Previous studies demonstrated that Kit activation confers radioprotection. However, the mechanism by which Kit signaling interferes with cellular response to ionizing radiation (IR) has not been firmly established. Based on the role of the sphingomyelin (SM) cycle apoptotic pathway in IR-induced apoptosis, we hypothesized that one of the Kit signaling components might inhibit IR-induced ceramide production or ceramide-induced apoptosis. Results show that, in both Ba/F3 and 32D murine cell lines transfected with wild-type c-kit, stem cell factor (SCF) stimulation resulted in a significant reduction of IR-induced apoptosis and cytotoxicity, whereas DNA repair remained unaffected. Moreover, SCF stimulation inhibited IR-induced neutral sphingomyelinase (N-SMase) stimulation and ceramide production. The SCF inhibitory effect on SM cycle was not influenced by wortmannin, a phosphoinositide-3 kinase (PI3K) inhibitor. The SCF protective effect was maintained in 32D-KitYF719 cells in which the PI3K/Akt signaling pathway is abolished due to mutation in Kit docking site for PI3K. In contrast, phospholipase C gamma (PLC gamma) inhibition by U73122 totally restored IR-induced N-SMase stimulation, ceramide production, and apoptosis in Kit-activated cells. Moreover, SCF did not protect 32D-KitYF728 cells (lacking a functional docking site for PLC gamma 1), from IR-induced SM cycle. Finally, SCF-induced radioprotection of human CD34(+) bone marrow cells was also inhibited by U73122. Altogether, these results suggest that SCF radioprotection is due to PLC gamma 1-dependent negative regulation of IR-induced N-SMase stimulation. Beyond the scope of Kit-expressing cells, it suggests that PLC gamma 1 status could greatly influence the post-DNA damage cellular response to IR, and perhaps, to other genotoxic agents.
The protein translocation machinery of the endoplasmic reticulum (1982)

The rough endoplasmic reticulum (r.e.r.) has been postulated to possess a single translation-coupled translocation system (in multiple copies) that effects signal sequence-mediated translocation of all secretory and lysosomal proteins and integration of all integral membrane proteins whose port of entry is the rough endoplasmic reticulum (G. Blobel 1980 Proc. natn. Acad. Sci. U.S.A. 77, 1496-1500). Two proteins have been isolated that are components of the r.e.r. translocation system. Their properties and function in protein translocation across and integration into membranes are discussed.
Nitrates in the human diet - good or bad? (2000)

Although the nitrate and nitrite have been used for centuries, it has only recently been discovered that nitrate is manufactured in mammals by the oxidation of nitric oxide and that the nitrate formed also has the potential for disinfecting the food we eat. The mechanisms by which nitric oxide and other nitrogen oxides provide selective toxicity towards pathogens is not yet completely understood, and it is likely that the mechanisms will be different with different organisms. Whereas it is clear that acidified nitrite is produced on mucosal surfaces, and that this combination is effective in killing a variety of human gut and skin pathogens, there is no definite evidence as yet that this mechanism is truly protective in humans exposed to a contaminated environment. Further understanding of the complex chemistry of nitrogen oxides may also help develop new antimicrobial therapies based on augmenting what seems to be a simple and effective host defence system.
WFSBP Guidelines on Brain Stimulation Treatments in Psychiatry (2010)

Chittaranjan Andrade (India), Andreas Conca (Austria), Delcir da Costa (Brazil), Gerhard Eschweiler (Germany), Max Fink (USA), Paul Fitzgerald (Australia), Loes Gabriels (Belgium), Christian Geretsegger (Austria), Benjamin Greenberg (USA), Paul Holtzheimer (USA), Mindaugas Jasulaitis (Lithuania), Andy Krystal (USA), Yechiel Levkovitz (Israel), Daniel Lijtenstein (Uruguay), Sarah H. Lisanby (USA), Philip Mitchell (Australia), Nobutaka Motohashi (Japan), Angela Naderi-Heiden (Austria), Jose Otegui (Uruguay), Harold Sackeim (USA), E. Tsukarzi (Russia), Ioannis Zervas (Greece).
The Cross-sectional and Longitudinal Associations of Diabetic Retinopathy With Cognitive Function and Brain MRI Findings: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial (2014)

Diabetic retinopathy is associated with future cognitive decline in people with type 2 diabetes. Although diabetic retinopathy is not a perfect proxy for diabetes-related brain and cognitive decline, patients with type 2 diabetes and retinopathy represent a subgroup at higher risk for future cognitive decline.
Evidence for two DNA repair enzymes for 8-hydroxyguanine (7,8-dihydro-8-oxoguanine) in human cells. (1993)

Two DNA repair enzymes for 8-hydroxyguanine (also known as 7,8-dihydro-8-oxoguanine; OH8Gua, oxo8Gua) have been identified in human HeLa cell nuclear extract. One is OH8Gua-glycosylase and the other is OH8Gua-endonuclease that lacks OH8Gua-glycosylase activity. They were separated by heparin-Sepharose column chromatography and characterized by endonuclease nicking assay or by measuring the OH8Gua released from substrate DNA using high pressure liquid chromatography-electrochemical detection. Both OH8Gua repair enzymes act only on the OH8Gua-containing strand of the duplex substrate DNA containing OH8Gua/C, OH8Gua/T, or OH8Gua/G. DNA containing OH8Gua/A base pair was very poor substrate for either enzymes. OH8Gua-endonuclease simultaneously cleaves phosphodiester bonds on both sides of the OH8Gua residue, leaving 5'-hydroxy and 3'-hydroxy groups.