gebhart/patrepeval huggingface dataset:
Epidermal Growth Factor Receptor Inhibitors: A New Prospective in the Treatment of Lung Cancer (2004)

Lung cancer is the leading cause of death worldwide. Current treatment modalities, including chemotherapy, radiotherapy and surgery, provide only limited improvement in the natural course of this disease. Therefore, the development of new therapeutic strategies is highly awaited. This review focuses on recent achievements on a novel class of anticancer drugs targeting the EGFR (Epidermal Growth Factor Receptor). The EGFR family is a group of four structurally similar growth factor receptors with tyrosine-kinase activity (EGFR, HER2/neu, ErbB-3, ErbB-4), which dimerize upon binding with a number of ligands, including EGF (Epidermal Growth Factor) and TGF (Transforming Growth Factor), allowing downstream transduction of mitogenic signals. Overexpression of EGFR and HER2 is frequently found in non-small-cell lung cancer (NSCLC), which accounts for over 80% of all malignant lung tumors, and has been associated with a worse clinical outcome. New agents developed to inhibit EGFR function include monoclonal antibodies and small-molecule receptor tyrosine-kinase inhibitors. In this review, results of most recent clinical with EGFR inhibitors including monoclonal antibodies, such as Trastuzumab (Herceptin), IMC-C225 (Cetuximab) and others (ABX-EGF, EMD 72000), and tyrosine-kinase inhibitors, such as ZD1839 (Gefitinib, Iressa), OSI-774 (Erlotinib, Tarceva) and others (CI-1033, GW2016), are summarized. In particular, final results of phase II (IDEAL 1 and 2) and III (INTACT 1 and 2) studies of ZD1839 are reported. In IDEAL trials (ZD1839 single agent in patients pre-treated with chemotherapy) there was clear evidence of tumor regression, symptoms improvement and overall clinical benefit, whereas in the two INTACT trials (ZD1839 in combination with standard platinum-based chemotherapy in chemo-naive patients) ZD1839 did not improve either survival or other clinical endpoints. Possible explanations for these contradictory results and future perspectives are discussed.
The Cc Chemokine Thymus-Derived Chemotactic Agent 4 (Tca-4, Secondary Lymphoid Tissue Chemokine, 6ckine, Exodus-2) Triggers Lymphocyte Function–Associated Antigen 1–Mediated Arrest of Rolling T Lymphocytes in Peripheral Lymph Node High Endothelial Venules (2000)

T cell homing to peripheral lymph nodes (PLNs) is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial tethering and rolling via L-selectin, firm adhesion of T cells requires rapid upregulation of lymphocyte function-associated antigen 1 (LFA-1) adhesiveness by a previously unknown pathway that activates a Galpha(i)-linked receptor. Here, we used intravital microscopy of murine PLNs to study the role of thymus-derived chemotactic agent (TCA)-4 (secondary lymphoid tissue chemokine, 6Ckine, Exodus-2) in homing of adoptively transferred T cells from T-GFP mice, a transgenic strain that expresses green fluorescent protein (GFP) selectively in naive T lymphocytes (T(GFP) cells). TCA-4 was constitutively presented on the luminal surface of HEVs, where it was required for LFA-1 activation on rolling T(GFP) cells. Desensitization of the TCA-4 receptor, CC chemokine receptor 7 (CCR7), blocked T(GFP) cell adherence in wild-type HEVs, whereas desensitization to stromal cell-derived factor (SDF)-1alpha (the ligand for CXC chemokine receptor 4 [CXCR4]) did not affect T(GFP) cell behavior. TCA-4 protein was not detected on the luminal surface of PLN HEVs in plt/plt mice, which have a congenital defect in T cell homing to PLNs. Accordingly, T(GFP) cells rolled but did not arrest in plt/plt HEVs. When TCA-4 was injected intracutaneously into plt/plt mice, the chemokine entered afferent lymph vessels and accumulated in draining PLNs. 2 h after intracutaneous injection, luminal presentation of TCA-4 was detectable in a subset of HEVs, and LFA-1-mediated T(GFP) cell adhesion was restored in these vessels. We conclude that TCA-4 is both required and sufficient for LFA-1 activation on rolling T cells in PLN HEVs. This study also highlights a hitherto undocumented role for chemokines contained in afferent lymph, which may modulate leukocyte recruitment in draining PLNs.
Combining text and image information in content-based retrieval (2002)

This research explores the interaction of textual and photographic information in an integrated text/image database environment. By understanding the caption accompanying a picture, we are able to extract information useful in (i) retrieving the picture and (ii) directing an image interpretation system to identify relevant objects (in this case, faces) in the picture. The latter constitutes a powerful technique for automatically indexing images. In cases where images are not accompanied by text, it is far easier to manually add a line of descriptive text than to manually truth the images. A multi-stage system, PICTION, which uses captions to identify human faces in an accompanying photograph has been developed. We discuss the use of PICTION's output in content-based retrieval of images to satisfy focus of attention in queries.
5. Functional Inverse Problems (2005)

When in doubt, smooth. Sir Harold Jeffreys (Quoted by Moritz, 1980) Many inverse problems involve functions: the data set sometimes consists of recordings as a function of time or space, and the main unknown in the parameter set sometimes consists of a function of the spatial coordinates and/or of time. Quite often, the functions can be approximated by their discretized versions, and an infinite-dimensional problem is then reduced to a finite-dimensional one. In fact, many ‘functions’ are handled and displayed by digital computers, and their discretization is implicit (like, for instance, when dealing with space images of Earth). In spite of this, there are situations where the inverse problem is better formulated using functions (i.e., using the concepts of functional analysis). One may go quite far using the functional formulation, even if, at the end, some sort of discretization is used for the actual computations. Few developments are needed for the general inverse problem (we shall see that the very definition of random function considers successive discretizations). But in the special case where the considered random functions are Gaussian, lots of beautiful mathematics is available that provides efficient methods of resolution. 5.1 Random Functions 5.1.1 Description of a Random Function Looking at Figures 5.1–5.2, we can understand what is generally meant by a random function. Each of the figures represents some realizations of the considered random function, each realization being an ordinary function.
Activating frataxin expression by single-stranded siRNAs targeting the GAA repeat expansion (2018)

Friedreich's ataxia (FRDA) is an incurable neurodegenerative disorder caused by reduced expression of the mitochondrial protein frataxin (FXN). The genetic cause of the disease is an expanded GAA repeat within the FXN gene. Agents that increase expression of FXN protein are a potential approach to therapy. We previously described anti-trinucleotide GAA duplex RNAs (dsRNAs) and antisense oligonucleotides (ASOs) that activate FXN protein expression in multiple patient derived cell lines. Here we test two distinct series of compounds for their ability to increase FXN expression. ASOs with butane linkers showed low potency, which is consistent with the low T<sub>m</sub> values and suggesting that flexible conformation impairs activity. By contrast, single-stranded siRNAs (ss-siRNAs) that combine the strengths of dsRNA and ASO approaches had nanomolar potencies. ss-siRNAs provide an additional option for developing nucleic acid therapeutics to treat FRDA.
Pyrazolo[1,5-a]pyrimidines. Identification of the Privileged Structure and Combinatorial Synthesis of 3-(Hetero)arylpyrazolo[1,5-a]pyrimidine-6-carboxamides (2007)

The pyrazolo[1,5-a]pyrimidine class of compounds has been identified as a privileged structure for library synthesis on the basis of several key characteristics of the core molecule. A chemical set in excess of 400 compounds was synthesized to give 3,6,7-substituted pyrazolo[1,5-a]pyrimidinecarboxamides 9. To facilitate the rapid preparation of this library, a preparative strategy included the synthesis of activated p-nitrophenyl esters, followed by subsequent scavenging of the p-nitrophenol leaving group. Excess reagents were also removed using scavenging reagents that were found to be compatible with the synthetic methodology and that afforded target compounds in acceptable purity and yields.
CFTR, SPINK1, CTRC and PRSS1 variants in chronic pancreatitis: is the role of mutated CFTR overestimated? (2012)

Accumulation of CFTR variants in CP is less pronounced than reported previously, with ORs between 2.7 and 4.5. Only CF-causing variants reached statistical significance. Compound and trans-heterozygosity is an overt risk factor for the development of CP, but the number of CFTR compound heterozygotes in particular is rather low. In summary, the study demonstrates the complexity of genetic interactions in CP and a minor influence of CFTR alterations in CP development.
Numerical Network‐Preserving BCU Method (2010)

This chapter contains sections titled: Introduction Computational Considerations Numerical Scheme to Detect Exit Points Computing the MGP Computation of Equilibrium Points Numerical Examples Large Test Systems Concluding Remarks
Fructose-6-phosphate Aldolase Is a Novel Class I Aldolase from Escherichia coli and Is Related to a Novel Group of Bacterial Transaldolases (2001)

We have cloned an open reading frame from the Escherichia coli K-12 chromosome that had been assumed earlier to be a transaldolase or a transaldolase-related protein, termed MipB. Here we show that instead a novel enzyme activity, fructose-6-phosphate aldolase, is encoded by this open reading frame, which is the first report of an enzyme that catalyzes an aldol cleavage of fructose 6-phosphate from any organism. We propose the name FSA (for fructose-six phosphate aldolase; gene name fsa). The recombinant protein was purified to apparent homogeneity by anion exchange and gel permeation chromatography with a yield of 40 mg of protein from 1 liter of culture. By using electrospray tandem mass spectroscopy, a molecular weight of 22,998 per subunit was determined. From gel filtration a size of 257,000 (+/- 20,000) was calculated. The enzyme most likely forms either a decamer or dodecamer of identical subunits. The purified enzyme displayed a V(max) of 7 units mg(-)1 of protein for fructose 6-phosphate cleavage (at 30 degrees C, pH 8.5 in 50 mm glycylglycine buffer). For the aldolization reaction a V(max) of 45 units mg(-)1 of protein was found; K(m) values for the substrates were 9 mm for fructose 6-phosphate, 35 mm for dihydroxyacetone, and 0.8 mm for glyceraldehyde 3-phosphate. FSA did not utilize fructose, fructose 1-phosphate, fructose 1,6-bisphosphate, or dihydroxyacetone phosphate. FSA is not inhibited by EDTA which points to a metal-independent mode of action. The lysine 85 residue is essential for its action as its exchange to arginine (K85R) resulted in complete loss of activity in line with the assumption that the reaction mechanism involves a Schiff base formation through this lysine residue (class I aldolase). Another fsa-related gene, talC of Escherichia coli, was shown to also encode fructose-6-phosphate aldolase activity and not a transaldolase as proposed earlier.
The role of ataxia-telangiectasia heterozygotes in familial breast cancer. (1998)

The role of ataxia-telangiectasia (AT) heterozygotes in breast cancer has been controversial. We have found previously an overrepresentation (3.4%) of ATM mutations in a subset of 88 selected breast cancer patients with a family history of breast cancer, leukemia, and lymphoma. This prevalence is comparable to the estimated value (3.8%) from epidemiological study. To further examine the possibility that ATM is correlated to breast cancer, we screened for ATM germ-line mutations in another 100 breast cancer patients with a family history of breast cancer. We used the protein truncating test and found one new germ-line mutation. This figure (1%) is consistent with the observed 0.2-1% carrier frequency for AT. We also studied breast tumors from ATM mutants, and three showed retention of both alleles, whereas the fourth showed loss of the mutant allele. We conclude that the contribution of heterozygous ATM mutations to familial breast cancer is minimal. Even if the ATM gene were causative in these cases, it is not likely to act as a tumor suppressor.
A mm-Wave Power-Harvesting RFID Tag in 90 nm CMOS (2010)

A mm-wave power-harvesting RFID tag is implemented in 90 nm CMOS. Operation at mm-wave reduces antenna size and could allow antenna integration on-chip. This, together with power harvesting that can be used in lieu of a battery, can result in a pinless, CMOS-only tag with no package and no off-chip components whatsoever. The tag harvests energy from the incoming mm-wave continuous wave (CW) signal transmitted by the reader and then uses a 60 GHz free-running oscillator to transmit back pulse-width modulated bursts. An in-depth treatment of the voltage multiplier and associated matching network and implications on tag range are presented. With 2 dBm mm-wave input power, the tag achieves a rate of 5 kb/s. The RFIC size is 1.3 × 0.95 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> including pads.
Operational and reliability comparison of discrete-storage nonvolatile memories: advantages of single- and double-layer metal nanocrystals (2004)

Aggressive scaling of EEPROM to below 1,000 nm/sup 2/ bit area will enable more applications as low-power mobile systems. We have performed a critical comparison on discrete charge storage nodes, and established the advantages of metal nanocrystals in terms of programming/retention design trade-off and long-term endurance.
Electrochemical detection of saccharides by the redox cycle of a chiral ferrocenylboronic acid derivative: a novel method for sugar sensing (1995)

A chiral ferrocenylboronic acid 1 bearing an intramolecular tertiary amine binds saccharides at ca. pH 7, the complexation event, which can be conveniently detected by an electrochemical method, shows chiral discrimination for certain linear saccharides.
Electrical and Mechanical Components of Dyssynchrony in Heart Failure Patients With Normal QRS Duration and Left Bundle-Branch Block (2004)

Resynchronization of systole can be achieved for patients with normal QRSd and LBBB during biventricular and LV pacing. The timing of LV free-wall electrical activation correlated with the improvement in synchrony.
Inertial migration of rigid spherical particles in Poiseuille flow (2004)

An experimental study of the migration of dilute suspensions of particles in Poiseuille flow at Reynolds numbers $\hbox{\it Re}\,{=}\,67\hbox{--}1700$ was performed, with a few experiments performed at $\hbox{\it Re}$ up to 2400. The particles used in the majority of the experiments were neutrally buoyant spheres with diameters $d$ yielding a ratio of pipe to particle diameter in the range $D/d \,{=}\, 8\hbox{--}42$ . The volume fraction of solids was less than 1% in all cases studied. The results of G. Segré &amp; A. Silberberg ( J. Fluid Mech. 14 , 136, 1962) have been extended to show that the tubular pinch effect in which particles accumulate on a narrow annulus is moved toward the wall as $\hbox{\it Re}$ increases. A careful comparison with asymptotic theory for Poiseuille flow in a channel was performed. Another inner annulus closer to the centre, and not predicted by this asymptotic theory, was observed at elevated $\hbox{\it Re}$ . As $\hbox{\it Re}$ is increased, the distribution of particles over the cross-section of the tube at the measurement location, lying at a distance $L \doteq 310 D$ from the entrance, changes from one centred at the annulus predicted by the theory to one with the particles primarily on the inner annulus. The case of slightly non-neutrally buoyant particles was also investigated. A particle trajectory simulation based on asymptotic theory was performed to facilitate the comparison of theory and the experimental observations.
Small Ubiquitin-like Modifier (SUMO) Modification of Zinc Finger Protein 131 Potentiates Its Negative Effect on Estrogen Signaling (2012)

Like ubiquitin, small ubiquitin-like modifier (SUMO) covalently attaches to specific target proteins and modulates their functional properties, including subcellular localization, protein dimerization, DNA binding, and transactivation of transcription factors. Diverse transcriptional co-regulator complexes regulate the ability of estrogen receptors to respond to positive and negative acting hormones. Zinc finger protein 131 (ZNF131) is poorly characterized but may act as a repressor of estrogen receptor α (ERα)-mediated trans-activation. Here, we identify ZNF131 as a target for SUMO modification and as a substrate for the SUMO E3 ligase human polycomb protein 2 (hPc2). We report that the SUMO-interacting motif 1 (SIM1) and the C-box of hPc2 are critical regions required for ZNF131 SUMOylation and define the ZNF131 SUMOylation site as lysine 567. We further show that SUMO modification potentiates the negative effect of ZNF131 on estrogen signaling and consequently attenuates estrogen-induced cell growth in a breast cancer cell line. Our findings suggest that SUMOylation is a novel regulator of ZNF131 action in estrogen signaling and breast cancer cell proliferation.
Pressure-induced changes in the conductivity of AlGaN∕GaN high-electron mobility-transistor membranes (2004)

AlGaN ∕ GaN high-electron-mobility transistors (HEMTs) show a strong dependence of source∕drain current on the piezoelectric-polarization-induced two-dimensional electron gas. The spontaneous and piezoelectric-polarization-induced surface and interface charges can be used to develop very sensitive but robust sensors for the detection of pressure changes. The changes in the conductance of the channel of a AlGaN∕GaN high electron mobility transistor (HEMT) membrane structure fabricated on a Si substrate were measured during the application of both tensile and compressive strain through changes in the ambient pressure. The conductivity of the channel shows a linear change of −(+)6.4×10−2mS∕bar for application of compressive (tensile) strain. The AlGaN∕GaN HEMT membrane-based sensors appear to be promising for pressure sensing applications.
A serial-link transceiver based on 8 GSample/s A/D and D/A converters in 0.25 μm CMOS (2002)

On-chip VCOs generate 16 clock phases that drive an 8-way interleaved 4b A/D input receiver and an 8-way interleaved 8b D/A transmitter. 4 GHz bandwidth is achieved by inductors that distribute the I/O capacitance and a transmit equalizer. Digital calibration adjusts the sample timing to 10 ps, the input and output accuracy to <1 LSB and 3 LSBs, respectively.
Ig-Like Transcript 3 Regulates Expression of Proinflammatory Cytokines and Migration of Activated T Cells (2009)

Ig-like transcript 3 (ILT3), an inhibitory receptor expressed by APC is involved in functional shaping of T cell responses toward a tolerant state. We have previously demonstrated that membrane (m) and soluble (s) ILT3 induce allogeneic tolerance to human islet cells in humanized NOD/SCID mice. Recombinant sILT3 induces the differentiation of CD8(+) T suppressor cells both in vivo and in vitro. To better understand the molecular mechanisms by which ILT3 suppresses immune responses, we have generated ILT3 knockdown (ILT3KD) dendritic cells (DC) and analyzed the phenotypic and functional characteristics of these cells. In this study, we report that silencing of ILT3 expression in DC (ILT3KD DC) increases TLR responsiveness to their specific ligands as reflected in increased synthesis and secretion of proinflammatory cytokines such as IL-1alpha, IL-1beta, and IL-6 and type I IFN. ILT3KD-DC also secretes more CXCL10 and CXCL11 chemokines in response to TLR ligation, thus accelerating T cell migration in diffusion chamber experiments. ILT3KD-DC elicit increased T cell proliferation and synthesis of proinflammatory cytokines IFN-gamma and IL-17A both in MLC and in culture with autologous DC pulsed with CMV protein. ILT3 signaling results in inhibition of NF-kappaB and, to a lesser extent, MAPK p38 pathways in DC. Our results suggest that ILT3 plays a critical role in the control of inflammation.
Transition Metal-Promoted Free-Radical Reactions in Organic Synthesis: The Formation of Carbon-Carbon Bonds (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTransition Metal-Promoted Free-Radical Reactions in Organic Synthesis: The Formation of Carbon-Carbon BondsJaved Iqbal, Beena Bhatia, and Naresh K. NayyarCite this: Chem. Rev. 1994, 94, 2, 519–564Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/cr00026a008https://doi.org/10.1021/cr00026a008research-articleACS PublicationsRequest reuse permissionsArticle Views8050Altmetric-Citations639LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Profound, Non-Opioid Analgesia Produced by the High-Efficacy 5-HT<sub>1A</sub> Agonist F 13640 in the Formalin Model of Tonic Nociceptive Pain (2003)

Previously, we have reported that in rat models of chronic pain, in particular, the very-high-efficacy 5-HT(1A) agonist F 13640 induces unprecedented pain relief by novel neuroadaptative mechanisms that involve inverse tolerance and cooperation with nociceptive stimulation in producing analgesia. The present studies detailed the actions of F 13640 and other compounds in the formalin model of tonic nociceptive pain. Intraperitoneal injection of F 13640 (0.01-2.5 mg/kg; t -15 min) caused a dose-dependent and complete inhibition of the paw elevation and paw licking that occurred both early (0-5 min) and late (22.5-27.5 min) after the intraplantar injection of diluted formaldehyde (2.5%) in the rat. The extent to which F 13640 and other 5-HT(1A) receptor ligands inhibited these pain behaviors correlated (p < 0.05) with the extent to which they activated 5-HT(1A) receptors. Under similar conditions, some inhibitory effects were also observed with various agents that are known to produce analgesia by different peripheral and/or central mechanisms (e.g., opioids, NA/5-HT reuptake inhibitors, COX-2 inhibitors and other nonsteroidal anti-inflammatory drugs, gabapentin, and ABT-594). However, with the possible exception of morphine, the effects of all of these agents at nontoxic doses were lower than those of F 13640, in particular in inhibition of early paw elevation. The 5-HT(1A) antagonist WAY 100635, but not naloxone, antagonized the actions of F 13640. These results help to establish large-magnitude 5-HT(1A) receptor activation as a new molecular mechanism of profound, central analgesia and suggest that F 13640 may be particularly effective against pain arising from severe tonic nociceptive stimulation.