gebhart/patrepeval huggingface dataset:
Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy (2011)

Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.
Characterization of InAs quantum dots in strained InxGa1−xAs quantum wells (2000)

The properties of InAs quantum dots placed in a strained InGaAs quantum well are investigated. The structures are grown by solid-source molecular beam epitaxy on GaAs substrates and are characterized using photoluminescence and atomic force microscopy. Emission wavelength and the optical quality of the quantum dots vary with growth temperature and also depend on the position of the dots in the well. A strong dependence of the dot properties on the capping conditions is established. A postgrowth anneal similar to a typical laser cladding growth results in a large photoluminescence (PL) blueshift and reduces the PL intensity by more than two orders of magnitude. It is shown that these dots-in-a-well structures have superior optical properties as compared to conventional InAs dots in a GaAs matrix, and their emission wavelength can be tuned past the technologically important wavelength of 1.3 μm.
Modulation of dendritic differentiation by corticotropin-releasing factor in the developing hippocampus (2004)

The interplay of environmental and genetic factors in the developmental organization of the hippocampus has not been fully elucidated. The neuropeptide corticotropin-releasing factor (CRF) is released from hippocampal interneurons by environmental signals, including stress, to increase synaptic efficacy. In the early postnatal hippocampus, we have previously characterized a transient population of CRF-expressing Cajal-Retzius-like cells. Here we queried whether this stress-activated neuromodulator influences connectivity in the developing hippocampal network. Using mice deficient in the principal hippocampal CRF receptor [CRF(1)(-/-)] and organotypic cultures grown in the presence of synthetic CRF, or CRF receptor antagonists, we found robust effects of CRF on dendritic differentiation in hippocampal neurons. In CRF(1)(-/-) mice, the dendritic trees of hippocampal principal cells were exuberant, an effect that was induced in normal hippocampi in vitro by the presence of CRF(1) antagonists. In both cases, total dendritic length and dendritic branching were significantly increased. In contrast, exogenous synthetic CRF blunted the dendritic growth in hippocampal organotypic cultures. Taken together, these findings suggest that endogenous CRF, if released excessively by previous early postnatal stress, might influence neuronal connectivity and thus function of the immature hippocampus.
A ferroelectric capacitor over bit-line (F-COB) cell for high density nonvolatile ferroelectric memories (2002)

A ferroelectric capacitor over bit-line (F-COB) cell is proposed for high density nonvolatile ferroelectric memories (NVFRAMs). This memory cell with 0.7 /spl mu/m design rule was successfully fabricated using a newly-developed fabrication process, combining CMP and MOCVD techniques. Good ferroelectric properties of storage capacitor, having a remanent polarization of 15 /spl mu/C/cm/sup 2/ and leakage current density of 10/sup -6/ A/cm/sup 2/, have been realized without degradation in CMOS characteristics.
Covalently-Functionalized Single-Walled Carbon Nanotube Probe Tips for Chemical Force Microscopy (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTCovalently-Functionalized Single-Walled Carbon Nanotube Probe Tips for Chemical Force MicroscopyStanislaus S. Wong, Adam T. Woolley, Ernesto Joselevich, Chin Li Cheung, and Charles M. LieberView Author Information Department of Chemistry and Chemical Biology Harvard University, 12 Oxford Street Cambridge, Massachusetts 02138 Cite this: J. Am. Chem. Soc. 1998, 120, 33, 8557–8558Publication Date (Web):August 5, 1998Publication History Received22 May 1998Published online5 August 1998Published inissue 1 August 1998https://pubs.acs.org/doi/10.1021/ja9817803https://doi.org/10.1021/ja9817803rapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views1694Altmetric-Citations218LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Carbon nanotubes,Functionalization,Probes,Surface interactions,Titration Get e-Alerts
Kinetics of cellulose conversion at 25 MPa in sub‐ and supercritical water (2004)

Abstract Experiments of microcrystalline cellulose conversion in subcritical and supercritical water were conducted at temperatures between 290 and 400°C, a pressure of 25 MPa, and residence times of 0.02–13.1 s using a continuous‐flow‐type microreactor. First, the reaction mechanism of microcrystalline cellulose in subcritical and supercritical water was proposed on the basis of detailed product analyses. Next, the kinetic description of this reaction in subcritical and supercritical water using a grain model was carried out to verify the proposed reaction mechanism and consequently found that the reaction‐rate models were able to express the reaction of microcrystalline cellulose at identical conditions. © 2004 American Institute of Chemical Engineers AIChE J , 50: 192–202, 2004
A Phase 1 Clinical Study of the Retinoid X Receptor (RXR) Selective Agonist IRX4204 in Patients with Early Parkinson’s Disease (PD) (P2.342) (2016)

Objective: To evaluate the safety, tolerability, and effects on dopamine transporter binding (DAT), UPDRS Total and Motor Score, of short term administration of IRX4204 to patients with early PD. Background: IRX4204 is a highly selective and potent agonist of the RXR nuclear receptors, and of RXR-Nurr1 and RXR-Nur77 heterodimers. IRX4204 and other RXR agonists previously have been reported to promote dopaminergic neuron survival and functions in vitro, and to be effective in vivo in a 6-OH induced rat model of PD. Design: This study was a single center, open-label clinical trial. IRX4204 was administered orally, once daily, at 5, 10, or 20 mg/day, for up to 30 days. Three cohorts of 5 early PD patients were enrolled. Patients were evaluated for safety, UPDRS, and DAT binding using [123I]β-CIT SPECT. Results: Few adverse events, all non-serious, were observed. Safety laboratory side effects, including known RXR agonist class related reductions in TSH, T4, and circulating leukocytes; and elevations of circulating triglycerides, occurred at all dose levels. Treatment was suspended in the 20 mg/day cohort for decreased leukocytes; and in one patient in the 10 mg/day cohort for elevated triglycerides. No effect on DAT expression was observed by SPECT. There was a trend toward reduction of UPDRS total scores by 4.6 (SD 3.9). Conclusions: IRX4204 was safe and well tolerated by early PD patients at 5 and 10 mg/day for 30 days. No short-term effect on DAT binding was observed by SPECT. There was a trend towards improvements in UPDRS in this open label study. More definitive assessment of UPDRS change after treatment with IRX4204, will require future blinded, controlled clinical trials. These are the first human clinical data to support RXR agonists may be effective for treatment of PD.
PTHrP and Skeletal Development (2006)

Parathyroid hormone-related protein (PTHrP) participates in the regulation of endochondral bone development. After the cartilage mold is established in fetal life, perichondrial cells and chondrocytes at the ends of the mold synthesize PTHrP. This ligand then acts on PTH/PTHrP receptors on chondrocytes. As chondrocytes go through a program of proliferation and then further differentiation into post-mitotic, hypertrophic chondrocytes, PTHrP action keeps chondrocytes proliferating and delays their further differentiation. Indian hedgehog (Ihh) is synthesized by chondrocytes that have just stopped proliferating and is required for synthesis of PTHrP. The feedback loop between PTHrP and Ihh serves to regulate the pace of chondrocyte differentiation and the sites at which perichondrial cells first differentiate into osteoblasts. Activation of the PTH/PTHrP receptor leads to stimulation of both Gs and Gq family heterotrimeric G proteins. Genetic analyses demonstrate that Gs activation mediates the action of PTHrP to keep chondrocytes proliferating, while Gq activation opposes this action. Downstream from Gs activation, synthesis of the cyclin-cdk inhibitor, p57, is suppressed, thereby increasing the pool of proliferating chondrocytes. PTHrP's actions to delay chondrocyte differentiation are mediated by the phosphorylation of the transcription factor, SOX9, and by suppression of synthesis of mRNA encoding the transcription factor, Runx2. These pathways and undoubtedly others cooperate to regulate the pace of differentiation of growth plate chondrocytes in response to PTHrP.
Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. (1993)

Specific CD44 variant glycoproteins are overexpressed at particular stages of colorectal tumor progression. Some variants of the CD44 glycoprotein without exon v6 sequences appear at the earliest stage of tumorigenesis, i.e., in early adenomas. Expression of variants containing exon v6 sequences is largely restricted to the advanced stages of tumor development and in addition is more prevalent and intense in metastatic (Dukes C/D) than in nonmetastatic (Dukes A/B) carcinomas. The observation that CD44 variants containing a protein domain of CD44 that confers full metastatic potential to rat carcinoma and sarcoma cell lines is increasingly expressed during colorectal tumor progression indicates that this domain may have an important role in tumor progression and metastasis in humans. Information on v6 expression, which can be obtained by routine immunohistochemistry, may prove of important prognostic value, particularly in carcinomas (Dukes A and B) that have not yet given rise to detectable metastases.
FeCl2-CatalyzedAminobromination of Alkenes Using Amides or Sulfonamidesand NBS as the Nitrogen and Bromine Sources (2008)

We have developed a convenient and efficient iron-catalyzed aminobromination of the alkenes using inexpensive FeCl2 as the catalyst, amides/sulfonamides and NBS as the nitrogen and bromine sources, respectively, under mild conditions.
Naturally Occurring Human Glutathione S‐transferase GSTP1‐1 Isoforms with Isoleucine and Valine in Position 104 Differ in Enzymic Properties (1994)

Glutathione S-transferase P1-1 isoforms, differing in a single amino acid residue (Ile104 or Val104), have been previously identified in human placenta [Ahmad, H., Wilson, D. E., Fritz, R. R., Singh, S. V., Medh, R. D., Nagle, G. T., Awasthi, Y. C. & Kurosky, A. (1990) Arch. Biochem. Biophys. 278, 398-408]. In the present report, the enzymic properties of these two proteins are compared. [I104]glutathione S-transferase P1-1 has been expressed from its cDNA in Escherichia coli and purified to homogeneity by affinity chromatography; the cDNA has been mutated to replace Ile104 by Val104, and [V104]glutathione S-transferase P1-1 was expressed and isolated as described for [I104]glutathione S-transferase P1-1. The two enzymes differed in their specific activity and affinity for electrophilic substrates (KM values for 1-chloro-2,4-dinitrobenzene were 0.8 mM and 3.0 mM for [I-104]glutathione S-transferase P1-1 and [V-104]glutathione S-transferase P1-1, respectively), but were identical in their affinity for glutathione. In addition, the two enzymes were distinguishable by their heat stability, with half-lives at 45 degrees C of 19 min and 51 min, respectively. The resistance to heat denaturation was differentially modulated by the presence of substrates. These data, in conjunction with molecular modeling, indicate that the residue in position 104 helps to define the geometry of the hydrophobic substrate-binding site, and may also influence activity by interacting with residues directly involved in substrate binding.
Ultra-rapid opiate detoxification using dexmedetomidine under general anesthesia (2011)

Dexmedetomidine had shown to decrease markedly the withdrawal symptoms when used during ultra-rapid opiate detoxification under GA, and the patients in this group were more satisfied.
Inwardly rectifying potassium channels (Kir) in central nervous system glia: a special role for Kir4.1 in glial functions (2006)

Glia in the central nervous system (CNS) express diverse inward rectifying potassium channels (Kir). The major function of Kir is in establishing the high potassium (K+) selectivity of the glial cell membrane and strongly negative resting membrane potential (RMP), which are characteristic physiological properties of glia. The classical property of Kir is that K+ flows inwards when the RMP is negative to the equilibrium potential for K+ (E(K)), but at more positive potentials outward currents are inhibited. This provides the driving force for glial uptake of K+ released during neuronal activity, by the processes of "K+ spatial buffering" and "K+ siphoning", considered a key function of astrocytes, the main glial cell type in the CNS. Glia express multiple Kir channel subtypes, which are likely to have distinct functional roles related to their differences in conductance, and sensitivity to intracellular and extracellular factors, including pH, ATP, G-proteins, neurotransmitters and hormones. A feature of CNS glia is their specific expression of the Kir4.1 subtype, which is a major K+ conductance in glial cell membranes and has a key role in setting the glial RMP. It is proposed that Kir4.1 have a primary function in K+ regulation, both as homomeric channels and as heteromeric channels by co-assembly with Kir5.1 and probably Kir2.0 subtypes. Significantly, Kir4.1 are also expressed by oligodendrocytes, the myelin-forming cells of the CNS, and the genetic ablation of Kir4.1 results in severe hypomyelination. Hence, Kir, and in particular Kir4.1, are key regulators of glial functions, which in turn determine neuronal excitability and axonal conduction.
Active Immunization against Pneumocystis carinii with a Recombinant P. carinii Antigen (2006)

Mice immunized with recombinant mouse Pneumocystis carinii antigen A12-thioredoxin fusion protein developed an antibody response that recognized P. carinii antigens, as determined by Western blotting and immunofluorescence analysis. Compared to mice immunized with thioredoxin alone, mice immunized with A12-thioredoxin had significantly reduced lung P. carinii burdens after CD4+ T-cell depletion and challenge with P. carinii.
Treatment of Refractory Disseminated Nontuberculous Mycobacterial Infection With Interferon Gamma: A Preliminary Report (1994)

Interferon gamma in combination with conventional therapy may be effective for some cases of refractory disseminated nontuberculous mycobacterial infection.
Laminectomy versus Percutaneous Electrode Placement for Spinal Cord Stimulation (2000)

Spinal cord stimulation is an effective treatment for chronic pain in the lower back and lower extremities that is refractory to conservative therapy. Electrodes placed via laminectomy in the thoracic region appear to be associated with significantly better long-term effectiveness than are electrodes placed percutaneously.
The dissociation constants and stoichiometries of the interactions of Lys-plasminogen and chloromethyl ketone derivatives of tissue plasminogen activator and the variant delta FEIX with intact fibrin. (1990)

Active-site-blocked, fluorescent derivatives of tPA (Activase) and a variant (delta FEIX) which lacks the finger and epidermal growth factor-like domains and possesses Asn to Gln and Val to Met mutations at residues 117 and 245, respectively, were prepared. The binding of these to fibrin was studied by adding them at systematically varying concentrations to fibrinogen, at a fixed concentration, inducing clotting with thrombin, separating free and bound tPA or delta FEIX by centrifugation, and measuring the concentration of unbound material by extrinsic fluorescence. Similar studies were performed with Glu and Lys-plasminogen, using intrinsic fluorescence. epsilon-amino caproic acid (EACA) was utilized to distinguish kringle-dependent from finger-dependent binding. In the absence of EACA, delta FEIX-bound fibrin through a single class of sites with Kd = 0.69 microM and n = 1.34 delta FEIX/fibrin. The binding of delta FEIX was completely inhibited by EACA and 50% displacement occurred at [EACA] = 300 microM. Fibrin-bound tPA was only partially displaced with EACA. In the presence of 30 mM EACA, tPA binding reflected a single class of sites with Kd = 0.26 microM and n = 0.60 tPA/fibrin. In the absence of EACA, tPA binding was complex, typified by downwardly curved Scatchard plots, and was consistent with interactions of the two classes of sites, characterized by Kd = 0.13 microM, n = 0.60 and Kd = 0.61 microM, n = 1.23. These were attributed to finger and kringle-dependent interactions, respectively. Under the experimental conditions employed, Glu-plasminogen exhibited no binding to fibrin, whereas Lys-plasminogen bound to a single class of sites with Kd = 0.25 microM and n = 1.02 plasminogen/fibrin. This binding was completely inhibited by EACA and 50% displacement occurred at [EACA] = 28 microM. Competition experiments indicated that Lys-plasminogen does not displace either tPA or delta FEIX from fibrin. From these results the conclusions are drawn that tPA can interact with intact fibrin by two different and independent modes, involving, respectively, the finger and kringle 2 domains, and neither of these modes are competitive with the kringle-dependent binding of Lys-plasminogen.
A statistical approach to background subtraction for surveillance systems (2002)

Background subtraction is a commonly used process in surveillance systems. One difficult problem when using the process is maintaining a correct background image against changing illumination conditions. Most methods for maintaining the background image are based on intuitive definitions about the illumination change and are implemented as somewhat ad hoc algorithms. In contrast, we first define mathematical models representing the relation between the illumination intensity, a reflection index of objects and a pixel value. We also mathematically define an assumption about illumination, which requires that the distribution of the illumination intensity in a small region does not change. Then we formalize the background subtraction problem as a statistical test (/spl chi//sup 2/ test) based on the models and assumption. The experiments show that our models appropriately express the imaging process of a camera and our method provides stable detection performance for foreground objects.
Payment-Based Email. (2004)

Spam is a major problem facing email today, and current solutions are ine#ective. This paper presents our progress towards defining and implementing a payment-based email delivery system that solves the problem of spam. We present an extension to the email delivery protocol for specifying and collecting payments, explain its security requirements, and illustrate the use of the Lightweight Currency Protocol as an underlying currency system for payment-based email. We discuss the various ways payment requirements can be presented to the end user, and explain our prototyping e#orts and how they fit into the larger picture of a peer-to-peer service market based on micro-payments.
Effects of processing and storage on walnut (Juglans regia L) tannins (2001)

Abstract Walnut tannins were maximally extracted with absolute methanol and an extraction time of 60 min. Storage (21 days at 25 °C) significantly reduced (20–40% reduction) the assayable tannin content in walnuts. The ranges of tannin content in freshly cracked inshell and shelled walnuts were respectively 372–1095 and 363–667 mg catechin equivalent per 100 g dry weight. The assayable tannin content in inshell and shelled walnuts was 10–20% higher when the particle size was reduced from 2‐ to 8‐mesh. Using 0.5 as compared to 2% (w/v) vanillin as colour development reagent yielded 15–20% higher assayable tannin contents. The assay colour development reached a maximum after 20 min of incubation at 25 °C. Roasting (204 °C for 5 min) caused a small (14%) but significant reduction in assayable tannins. Soaking in aqueous alkali solutions was more effective (44–100% reduction) than soaking in aqueous acid solutions (6–76% reduction) in decreasing the assayable tannin content in walnuts. Microwave heating in distilled deionised water resulted in 93–98% reduction in walnut assayable tannins. Blanching at 100 °C for 2 min was as effective as alkali soaking in significantly reducing the amount of extractable walnut tannins (98% reduction). The tannin content in blanched walnuts was positively related to astringency scores ( r = 0.92). © 2001 Society of Chemical Industry
ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers (2012)

ROS1 rearrangement defines a molecular subset of NSCLC with distinct clinical characteristics that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib shows in vitro activity and early evidence of clinical activity in ROS1-rearranged NSCLC.
Reciprocal regulation by TLR4 and TGF-β in tumor-initiating stem-like cells (2013)

Tumor-initiating stem-like cells (TICs) are resistant to chemotherapy and associated with hepatocellular carcinoma (HCC) caused by HCV and/or alcohol-related chronic liver injury. Using HCV Tg mouse models and patients with HCC, we isolated CD133(+) TICs and identified the pluripotency marker NANOG as a direct target of TLR4, which drives the tumor-initiating activity of TICs. These TLR4/NANOG-dependent TICs were defective in the TGF-β tumor suppressor pathway. Functional oncogene screening of a TIC cDNA library identified Yap1 and Igf2bp3 as NANOG-dependent genes that inactivate TGF-β signaling. Mechanistically, we determined that YAP1 mediates cytoplasmic retention of phosphorylated SMAD3 and suppresses SMAD3 phosphorylation/activation by the IGF2BP3/AKT/mTOR pathway. Silencing of both YAP1 and IGF2BP3 restored TGF-β signaling, inhibited pluripotency genes and tumorigenesis, and abrogated chemoresistance of TICs. Mice with defective TGF-β signaling (Spnb2(+/-) mice) exhibited enhanced liver TLR4 expression and developed HCC in a TLR4-dependent manner. Taken together, these results suggest that the activated TLR4/NANOG oncogenic pathway is linked to suppression of cytostatic TGF-β signaling and could potentially serve as a therapeutic target for HCV-related HCC.