gebhart/patrepeval huggingface dataset:
Cool-fetch: a compiler-enabled IPC estimation based framework for energy reduction (2004)

With power consumption becoming an increasingly important factor, it is necessary to reevaluate traditional, power-intensive, architectural techniques and their relative performance benefits. We believe that combined architecture-compiler efforts open up new and efficient ways to retain the performance benefits of modern architectures while addressing their power impact. In this paper, we present Cool-Fetch, an architecture compiler based approach to reduce energy consumption in the processor. While we mainly target the fetch unit, an important side-effect of our approach is that we obtain energy savings in many other parts of the processor. The explanation is that the fetch unit often runs substantially ahead of execution, bringing in instructions to different stages in the processor that may never be executed. We have found that although the degree of instruction level parallelism (ILP) of a program tends to vary over time, it can be statically estimated by the compiler. Our instructions per clock (IPC) estimation scheme uses monotonic dataflow analysis and simple heuristics, to guide a fetch-throttling mechanism. We develop the necessary architecture support and include its power overhead. Using Mediabench and SPEC2000 applications, we obtain up to 15% total energy savings in the processor with generally little performance degradation. We also provide a comparison of Cool-Fetch with previously proposed hardware-only dynamic fetch-throttling schemes.
Cetuximab promotes epithelial to mesenchymal transition and cancer associated fibroblasts in patients with head and neck cancer (2015)

Even if EMT and CAFs are implicated in cetuximab resistance in pre-clinical models, we demonstrate for the first time that these molecular processes may occur clinically early on.
Absorbed fractions for alpha-particles in tissues of trabecular bone: considerations of marrow cellularity within the ICRP reference male. (2005)

Improvements in patient-specific dosimetry of skeletal tissues require explicit consideration of not only changes in target mass with variable patient marrow cellularity (i.e., active marrow) but also corresponding changes in values of the absorbed fraction. The data given in this study provide a more-firm basis for application of the MIRD schema to patient-specific dosimetry for newly developing therapies using alpha-particle emitters.
Tetracycline-controllable Selection of CD4+ T Cells: Half-Life and Survival Signals in the Absence of Major Histocompatibility Complex Class II Molecules (2000)

A system that allows the study, in a gentle fashion, of the role of MHC molecules in naive T cell survival is described. Major histocompatibility complex class II-deficient mice were engineered to express Ealpha chains only in thymic epithelial cells in a tetracycline (tet)-controllable manner. This resulted in tet-responsive display of cell surface E complexes, positive selection of CD4(+)8(-) thymocytes, and generation of a CD4(+) T cell compartment in a class II-barren periphery. Using this system, we have addressed two unresolved issues: the half-life of naive CD4(+) T cells in the absence of class II molecules (3-4 wk) and the early signaling events associated with class II molecule engagement by naive CD4(+) T cells (partial CD3 zeta chain phosphorylation and ZAP-70 association).
Development of smart nanoparticle–aptamer sensing technology (2010)

Quantum dots (QDs) are excellent donors in Förster resonance energy transfer (FRET) based sensors because of their broad absorption and narrow symmetric emission. However, the strict requirement of a short donor-acceptor distance to achieve high FRET (hence sensitivity) has posed a significant challenge for QD-FRET-based sensors due to challenges associated with the preparation of QD conjugates that are both compact and highly stable. Consequently, most robust QD-FRET sensors are often too bulky to produce FRET efficiently, especially at low target-to-QD copy numbers. They have largely relied on increasing the target:QD ratio to achieve high FRET, making them undesirable and inefficient in situations of low target:QD copy numbers. Herein we report our work on the preparation of stable, compact and water-soluble QDs and their subsequent use in making compact, functional QD-DNA-based smart nanoparticle sensors for labelled and label-free DNA and protein detection. We have developed two strategies to prepare QD-DNA sensors: 1) via QD-thiolated DNA self-assembly, and 2) via covalent coupling between DNA and a QD surface ligand functional group. We found that thiolated DNA (fluorophore labelled) can self-assemble onto a 3-mercaptopropionic acid-capped QDs to produce highly efficient FRET (~80%) at a DNA:QD ratio of 1 : 1. However, this system suffers from strong non-specific adsorption and the self-assembled single-stranded (ss) DNA target is unable to hybridise to its complementary probe. More recently, we found that a dihydrolipoic acid-capped QD-ssDNA self-assembled system can hybridise to a labelled complementary probe to produce efficient FRET that can be exploited for labelled DNA probe quantification. Further, incorporating an anti-thrombin DNA aptamer to this system leads to a QD-DNA aptamer sensor that can specifically detect a 10 nM unlabelled protein probe (thrombin). The non-specific adsorption problem can be eliminated by introducing a poly(ethylene glycol) (PEG) linker to the QD capping ligands or by capping the QD with a chelating dendritic ligand. The resulting QD-DNA sensors can specifically detect 1 nM unlabelled or 35 pM labelled DNA probes using QD-sensitised dye FRET signals on a conventional fluorimeter. Extension of the DNA target to other functional DNAs or DNA/RNA aptamers should allow the development of a multi-functional QD-DNA platform suitable for biosensing, disease diagnosis and therapeutic applications.
Enzyme prodrug gene therapy: synergistic use of the herpes simplex virus-cellular thymidine kinase/ganciclovir system and thymidylate synthase inhibitors for the treatment of colon cancer. (1999)

The goal of this study was to improve the therapeutic index of the herpes simplex virus-thymidine kinase/ganciclovir (HSV-tk/GCV) system by the addition of thymidylate synthase (TS) inhibitors. For this, we assessed the potential of GCV to synergistically interact with 5-fluorouracil (5-FU), ZD1694 (Tomudex), and (E)-5-(2-bromovinyl)-2'-deoxyuridine in HSV-tk-expressing murine MC38 STK and human HT-29 STK colon carcinoma cell lines. Synergistic cell killing was observed in a clonogenic assay over most of the cytotoxic dose range by the median-effect principle of Chou and Talalay (T. C. Chou and P. Talalay, Adv. Enzyme Regul., 22: 27-55, 1984). In a s.c. HT-29 STK xenograft tumor model, we demonstrated that the combination of GCV and 5-FU resulted in statistically significant enhanced animal survival over single-agent treatment. Furthermore, we showed that the combination of GCV and ZD1694 in association with the HSV-tk/GCV system was at least as effective as GCV/5-FU in vitro and in vivo. The mechanism for the observed synergy is most likely attributable to the increased GCV phosphorylation in the presence of the tested TS inhibitors. Our data suggest that the HSV-tk/GCV metabolic suicide gene transfer system could serve as an adjuvant of the presently used TS inhibitors, thus potentially improving the efficacy of present cancer gene therapy approaches.
Inflammatory glia mediate delayed neuronal damage after ischemia in the central nervous system. (1993)

Reactive microglia respond within hours to central nervous system ischemic injury as exhibited by increased surface molecules, including the scavenger receptor. It is at least several days after an insult, however, before these activated mononuclear phagocytes reach a peak of secretory activity with the release of neurotoxins. This period of cytotoxin secretion is associated with a delayed neuronal loss seen in tissues neighboring sites of ischemia. Microglia-suppressing drugs reduce tissue production of neurotoxic factors and improve functional outcome after ischemic injury. Immunosuppressive therapy may offer a means to reduce late neuronal damage associated with stroke.
Drug Discovery Toward Antagonists of Methyl-Lysine Binding Proteins (2011)

The recognition of methyl-lysine and -arginine residues on both histone and other proteins by specific "reader" elements is important for chromatin regulation, gene expression, and control of cell-cycle progression. Recently the crucial role of these reader proteins in cancer development and dedifferentiation has emerged, owing to the increased interest among the scientific community. The methyl-lysine and -arginine readers are a large and very diverse set of effector proteins and targeting them with small molecule probes in drug discovery will inevitably require a detailed understanding of their structural biology and mechanism of binding. In the following review, the critical elements of methyl-lysine and -arginine recognition will be summarized with respect to each protein family and initial results in assay development, probe design, and drug discovery will be highlighted.
Flexible-Radio: A General Framework with PHY-layer algorithm-design insights (2005)

This is a tutorial paper on the concept of flexible/reconfigurable radio systems and, especially, on the elements of flexibility residing in the PHY sical layer (PHY). It reviews past research efforts towards flexible radios and introduces the various ways in which a reconfigurable transceiver can be used to provide multi-standard capabilities, link adaptation and user/service personalization. It overviews specific tools developed within two IST projects aiming at such flexible transceiver architectures and presents a specific example of a mode-selection algorithmic architecture which incorporates all the proposed tools. Thus, it serves to illustrate a baseband version of flexibility mechanisms.
Compression of compound images by combining several strategies (2011)

Compound images are combinations of text, graphics and natural images. They possess characteristics different from those of natural images, such as a strong anisotropy, sparse color histograms and repeated patterns. Former research on compressing them has mainly focused on developing certain strategies based on some of these characteristics but has failed so far to fully exploit them simultaneously. In this paper, we investigate the combination of four up-to-date strategies to construct a comprehensive scheme for compound image compression. We have implemented these strategies as four types of modes with variable block sizes. Experimental results show that the proposed scheme achieves significant coding gains for compound image compression at all bitrates.
APSK CODED MODULATION SCHEMES FOR NONLINEAR SATELLITE CHANNELS WITH HIGH POWER AND SPECTRAL EFFICIENCY (2002)

A new class of 16-ary Amplitude Phase Shift Keying (APSK) coded modulations deemed double-ring PSK modulations best suited for (satellite) nonlinear channels is proposed. Constellation parameters optimization has been based on geometric and information-theoretic considerations. Furthermore, pre- and post-compensation techniques to reduce the nonlinearity impact have been examined. Digital timing clock and carrier phase have been derived and analyzed for a Turbo coded version of the same new modulation scheme. Finally, the performance of state-of the art Turbo coded modulation for this new 16-ary digital modulation has been investigated and compared to the known TCM schemes. It is shown that for the same coding scheme, double-ring APSK modulation outperforms classical 16-QAM and 16-PSK over a typical satellite nonlinear channel due to its intrinsic robustness against the High Power Amplifier (HPA) nonlinear characteristics. The new modulation is shown to be power- and spectrally-efficient, with interesting applications to satellite communications. © 2002 by the American Institute of Aeronautics and Astronautics, Inc.
Activation of RhoA by Thrombin in Endothelial Hyperpermeability (2000)

Endothelial cells (ECs) actively regulate the extravasation of blood constituents. On stimulation by vasoactive agents and thrombin, ECs change their cytoskeletal architecture and small gaps are formed between neighboring cells. These changes partly depend on a rise in [Ca(2+)](i) and activation of the Ca(2+)/calmodulin-dependent myosin light chain kinase. In this study, mechanisms that contribute to the thrombin-enhanced endothelial permeability were further investigated. We provide direct evidence that thrombin induces a rapid and transient activation of RhoA in human umbilical vein ECs. Under the same conditions, the activity of the related protein Rac was not affected. This was accompanied by an increase in myosin light chain phosphorylation, the generation of F-actin stress fibers, and a prolonged increase in endothelial permeability. Inhibition of the RhoA target Rho kinase with the specific inhibitor Y-27632 reduced all of these effects markedly. In the presence of Y-27632, the thrombin-enhanced permeability was additionally reduced by chelation of [Ca(2+)](i) by BAPTA. These data indicate that RhoA/Rho kinase and Ca(2+) represent 2 pathways that act on endothelial permeability. In addition, the protein tyrosine kinase inhibitor genistein reduced thrombin-induced endothelial permeability without affecting activation of RhoA by thrombin. Our data support a model of thrombin-induced endothelial permeability that is regulated by 3 cellular signal transduction pathways.
Novel biopolymers for drug discovery (1995)

The solid phase synthesis and generation of libraries of "unnatural biopolymers" is described. These polymers are characterized by novel backbones and building blocks, the properties of which may modify their pharmacological and folding properties.
Adaptive multiple-antenna receiver for CDMA mobile reception (2002)

This paper examines the utilization of multiple antennas for direct-sequence code division multiple access (DS-CDMA) mobile communications at the mobile receiver. A linear single-user multiple-antenna receiver is derived and its performance is compared with that of the conventional matched filter. An adaptive implementation of the receiver is also considered. The results show that the multiple-antenna receiver is insensitive to the interfering powers and can provide room for more users or a smaller number of antennas than the matched filter solution. Using the adaptive algorithm, the performance even with a single antenna is often much better than that of a matched filter with 4 antennas.
Novel cancer therapy by reactivation of the p53 apoptosis pathway (2003)

The p53 transcription factor prevents tumor development through induction of cell cycle arrest and cell death by apoptosis. As many as several hundred genes or more are regulated by p53. Around half of all human tumors carry p53 mutation, mostly point mutations that abrogate p53's specific DNA binding and transactivation activity. p53 mutation is associated with poor therapeutic response and prognosis. Tumors that carry wild type p53 often have other alterations in the p53 pathway that ablate the p53 response. Several strategies have been designed to restore p53 function in human tumors, including p53 gene therapy, reactivation of mutant p53, and activation of wild type p53 by inhibition of the p53 antagonist MDM2. In all cases, the aim is to eliminate the tumor through induction of massive apoptosis.
Exponential growth by cross-catalytic cleavage of deoxyribozymogens (2003)

We have designed an autocatalytic cycle based on the highly efficient 10-23 RNA-cleaving deoxyribozyme that is capable of exponential amplification of catalysis. In this system, complementary 10-23 variants were inactivated by circularization, creating deoxyribozymogens. Upon linearization, the enzymes can act on their complements, creating a cascade in which linearized species accumulate exponentially. Seeding the system with a pool of linear catalysts resulted not only in amplification of function but in sequence selection and represents an in vitro selection experiment conducted in the absence of any protein enzymes.
Virus-like Replicon Particle Co-expression of PRRSV GP5 and M Proteins (2007)

VRP were constructed that co-express porcine reproductive and respiratory syndrome virus (PRRSV) GP5 and M proteins and form a heterodimer. This co-expressing VRP is an attractive candidate for a novel PRRSV vaccine based on previous work with equine arteritis virus (EAV).
Reactions of 4‐Chloromethyl‐1,3‐dioxolan‐2‐one with Phenols as A New Route to Polyols and Cyclic Carbonates (1985)

Abstract Reaction of 4‐chloromethyl‐1,3‐dioxolan‐2one ( 1 ) with phenol in the presence of potassium carbonate was studied and found to yield 4‐phenoxymethyl‐1,3‐dioxolan‐2one ( 2 ) and 3‐phenoxypropan‐1,2‐diol ( 3 ). The latter compound 3 was also found to be formed as the main product in the reaction of 1 , phenol and sodium hydroxide at a temperature higher than 90°C. The effect of various factors on the reaction course and the yield of 2 and 3 was examined. It was found that the reaction studied can be extended to those of difunctional phenols such as 2,2‐di(4‐hydroxyphenyl)‐propane producing the corresponding tetrahydroxyderivative – 2,2‐bis‐[4‐(2,3‐dihydroxypropoxy)phenyl]propane.
A PDA-based sign translator (2003)

We propose an effective approach for a PDA-based sign system and present the sign translator. Its main functions include three parts: detection, recognition and translation. Automatic detection and recognition of text in natural scenes is a prerequisite for the automatic sign translator. In order to make the system robust for text detection in various natural scenes, the detection approach efficiently embeds multi-resolution, adaptive search in a hierarchical framework with different emphases at each layer. We also introduce an intensity-based OCR method to recognize characters in various fonts and lighting conditions, where we employ the Gabor transform to obtain local features, and LDA for selection and classification of features. The recognition rate is 92.4% for the testing set obtained from the natural sign. A sign is different from the normal used sentence. It is brief with a lot of abbreviations and place nouns. We only briefly introduce a rule-based place name translation. We have integrated all these functions in a PDA, which can capture sign images, auto segment and recognize the Chinese sign, and translate it into English.
Subclassification of the RBCC/TRIM Superfamily Reveals a Novel Motif Necessary for Microtubule Binding (2006)

The biological significance of RBCC (N-terminal RING finger/B-box/coiled coil) proteins is increasingly being appreciated following demonstrated roles in disease pathogenesis, tumorigenesis, and retroviral protective activity. Found in all multicellular eukaryotes, RBCC proteins are involved in a vast array of intracellular functions; but as a general rule, they appear to function as part of large protein complexes and possess ubiquitin-protein isopeptide ligase activity. Those members characterized to date have diverse C-terminal domain compositions and equally diverse subcellular localizations and functions. Using a bioinformatics approach, we have identified some new RBCC proteins that help define a subfamily that shares an identical domain arrangement (MID1, MID2, TRIM9, TNL, TRIM36, and TRIFIC). Significantly, we show that all analyzed members of this subfamily associate with the microtubule cytoskeleton, suggesting that subcellular compartmentalization is determined by the unique domain architecture, which may in turn reflect basic functional similarities. We also report a new motif called the COS box, which is found within these proteins, the MURF family, and a distantly related non-RBCC microtubule-binding protein. Notably, we demonstrate that mutations in the COS box abolish microtubule binding ability, whereas its incorporation into a nonmicrotubule-binding RBCC protein redirects it to microtubule structures. Further bioinformatics investigation permitted subclassification of the entire human RBCC complement into nine subfamilies based on their varied C-terminal domain compositions. This classification schema may aid the understanding of the molecular function of members of each subgroup and their potential involvement in both basic cellular processes and human disease.
Duloxetine (LY 248686): an inhibitor of serotonin and noradrenaline uptake and an antidepressant drug candidate (1998)

Duloxetine is a potent inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (NE) uptake in vitro and in vivo and is 3- to 5-times more effective at inhibiting 5-HT uptake. Duloxetine is a weak inhibitor of dopamine (DA) uptake and the binding of radioligands to neurotransmitter receptors. Upon administration of duloxetine in vivo, the inhibitory effects on uptake of 5-HT and NE persist for up to 8 h. Desmethylduloxetine, a potential metabolite, is also an inhibitor of 5-HT and NE uptake. Consistent with the ability to inhibit the uptake of 5-HT, duloxetine blocks p-chloroamphetamine induced depletion of mouse and rat brain 5-HT. Duloxetine also blocks the 6-hydroxydopamine induced depletion of mouse heart NE and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced depletion of NE in frontal cortex but does not block the MPTP induced depletion of DA in rat striatum. Electrophysiological studies show that duloxetine decreases the activity of 5-HT neurones in dorsal raphe and at a 5-times higher dose also decreases the activity of NE neurones in the locus coeruleus. Microdialysis techniques have demonstrated that duloxetine effectively elevates extracellular 5-HT and NE levels in rat frontal cortex and hypothalamus. Antagonists at somatodendritic 5-HT(1A) autoreceptors or at presynaptic alpha(2)-adrenergic receptors could augment the duloxetine induced elevation of extracellular 5-HT, NE and DA levels. Duloxetine produces behavioural responses consistent with the enhancement of 5-HT and NE neurotransmission. Pharmacokinetic studies in healthy human volunteers show that duloxetine has a half-life of 10 - 15 h without the influence of food. In preliminary clinical trials, duloxetine has shown antidepressive effects in patients with major depression. Duloxetine offers an opportunity to utilise combined central 5-HT and NE neuronal pathways to improve the treatment of patients with major depression.
Responsive Cyclohexane‐Based Low‐Molecular‐Weight Hydrogelators with Modular Architecture (2004)

pH-sensitive gels: By using a cyclohexane-based scaffold to which various amino acid based substituents can be connected, low-molecular-weight compounds were obtained that can gelate water at very low concentrations. Their modular design (see picture: AA=amino acid(s), X=hydrophilic substituent, dark purple=hydrophobic region, light purple=hydrophilic region), allows tuning of the thermally and pH-induced reversible gel-to-sol transition of their gels. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z52396_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cluster Headache (2011)

Pharmacotherapy for the treatment of acute attacks and for attack prophylaxis is effective in most patients. For the minority who do not gain adequate relief, newer invasive techniques are available in some referral centers. Definitive conclusions as to their value cannot yet be drawn from the available data.