gebhart/patrepeval huggingface dataset:
Auto-silencing by the retinoid X receptor (1998)

Gene transcription is often regulated by small ligands, enabling cells to respond to external and metabolic stimuli. Of particular interest are the mechanisms by which hydrophobic hormones modulate the transcriptional activities of proteins of the nuclear receptor superfamily. It was previously shown that, in the absence of ligand, the retinoid X receptor (RXRalpha) forms tetramers with a high affinity and a pronounced positive co-operativity such that tetramers become the receptor's predominant species tat concentrations as low as 60-70 nM. It was shown further that while RXR tetramers are remarkably stable in the absence of ligand, ligand-binding induces their rapid dissociation into smaller species, dimers and monomers. Here, the functional consequences of the self-association properties of RXR were studied by examining two point mutants of RXR that displayed aberrant oligomerization behaviors. One mutant, mRXRalpha-R321A, was found to form tetramers with a wild-type affinity, but these tetramers failed to dissociate upon ligand-binding. This mutant was found to be impaired in its ability to associate with the nuclear receptor co-activator p/CIP and to activate transcription in response to the RXR ligand 9-cis-retinoic acid. The other mutant, mRXRalpha-F318A, self-associated into dimers with a wild-type affinity, but was unable to form tetramers. This mutant displayed substantial transcriptional activity even in the absence of ligand. We previously proposed, based on in vitro studies that RXR acts as an auto-silencer by sequestering itself into tetramers, and that an important role for the ligand in activating this receptor is to release active species, dimers and monomers, from the transcriptionally inactive tetrameric pool. The observations reported here provide in-cell evidence in support of this model and indicate that ligand induced dissociation of tetramers is the first step in signalling by RXR.
Tid1, a Cochaperone of the Heat Shock 70 Protein and the Mammalian Counterpart of the Drosophila Tumor Suppressor l(2)tid, Is Critical for Early Embryonic Development and Cell Survival (2004)

Tid1 is the mammalian counterpart of the Drosophila tumor suppressor Tid56 and is also a DnaJ protein containing a conserved J domain through which it interacts with the heat shock protein 70 (Hsp70) family of chaperone proteins. We generated a Tid1 conditional mutation in mice, and the subsequent global removal of the Tid1 protein was achieved by crossing these conditional knockout mice with general deletor mice. No Tid1(-/-) embryos were detected as early as embryonic day 7.5 (E7.5). Nonetheless, Tid1-deficient blastocysts were viable, hatched, formed an inner cell mass and trophectoderm, and implanted (E4.5), suggesting that the homozygous mutant embryos die between E4.5 and E7.5. To assess the function of Tid1 in embryonic cells, mouse embryonic fibroblasts with the homologous Tid1 floxed allele were produced. Tid1 removal in these cells led to massive cell death. The death of Tid1-deficient cells could be rescued by ectopic expression of wild-type Tid1 but not by expression of the Tid1 protein that had a mutated J domain and was thus incapable of binding to Hsp70. We propose that Tid1 is critical for early mammalian development, most likely for its function in sustaining embryonic-cell survival, which requires its association with Hsp70.
Active damping of the scanner for high-speed atomic force microscopy (2005)

The scanner that moves the sample stage in three dimensions is a crucial device that limits the imaging rate of atomic force microscopy. This limitation derives mainly from the resonant vibrations of the scanner in the z direction (the most frequent scanning direction). Resonance originates in the scanner’s mechanical structure as well as in the z piezoactuator itself. We previously demonstrated that the resonance originating in the structure can be minimized by a counterbalancing method. Here we report that the latter resonance from the actuator can be eliminated by an active damping method, with the result the bandwidth of the z scanner nearly reaches the first resonant frequency (150kHz) of the z piezoactuator.
Enormous catalyses of lanthanide metal ions for unprecedentedly fast hydrolysis of 3',5'-cyclic adenosine monophosphate. (1992)

3',5'-cyclic adenosine monophosphate (cAMP) is efficiently hydrolyzed by use of lanthanide metal(III) ions as catalysts. The acceleration by 10(-2) M of Ce(III) is remarkable (more than 10(11) fold) at pH 8.0, 30 degrees C, decreasing the half-life from a half million years to 35 seconds. The catalytic activity is in the following order: Ce >> Pr > Nd, La > Y, Sm, Dy > others. The catalysis is ascribed to cooperation of three or four lanthanide metal ions.
A clinicopathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria (2013)

The independent prognostic significance of Ang-2 and the Ang-2/Ang-1 ratio in severe malaria was confirmed, although immunohistochemistry in fatal cases did not reveal increased expression on brain endothelium in cerebral versus non-cerebral cases. Activation of the Ang-Tie-2 pathway in severe malaria is therefore related to acidosis, number of severity criteria and outcome, but is not a specific event in the brain during cerebral malaria.
Permanent dipole moment and charges in colloidal semiconductor quantum dots (1999)

The presence of a large permanent dipole moment has important implications on our understanding of nanocrystalline materials. We report the results of dielectric dispersion studies of CdSe, ZnSe, and metal nanocrystals. Due to the polar nature of the wurtzite lattice, a permanent dipole moment may be expected for CdSe nanocrystals. However, dielectric dispersion studies reveal a similar magnitude of the dipole moment, as well as its dependence on size, in zinc-blende ZnSe nanocrystals. These dipole moments may be intrinsic attributes to all nonmetal nanoparticles with surface localized charges. We show evidence for thermally induced charging of both semiconductor and metal nanocrystals and present a simple picture to describe the linear dependence of dipole moment on the size in semiconductor nanocrystals.
Stimulation of Irritable Tissues by Means of an Alternating Magnetic Field. (1959)

Stimulation of frog nerves and of excised frog muscles submerged in Ringer's solution has been obtained without the use of electrodes by means of sinusoidal alternating magnetic fields. This effect is due to eddy currents induced in conductive tissues and their surroundings. Visual and non-visual sensations have been induced in human subjects by non-homogeneous alternating magnetic fields adjacent to the brain.
New Combinations with Herceptin<sup>®</sup> in Metastatic Breast Cancer (2001)

Preclinical data indicate that trastuzumab (Herceptin) has the potential for synergistic or additive effects in combination with therapies including chemotherapy and hormonal agents, providing the rationale for a number of clinical trials in women with HER2-positive metastatic breast cancer. A recently reported phase II trial has demonstrated that trastuzumab plus vinorelbine is both effective (overall response rate 75%) and well tolerated, with the major side effects being typical of single-agent vinorelbine. Other combinations of trastuzumab with a variety of other chemotherapeutic and hormonal agents are also being assessed. In an effort to overcome the cardiotoxicity observed with trastuzumab plus doxorubicin in the pivotal phase III trial, combination regimens involving potentially less toxic anthracyclines such as epirubicin and liposomal formulations of doxorubicin are ongoing. In addition, trials are investigating whether trastuzumab can reverse the resistance to hormonal therapy that develops in most women with metastatic breast cancer. These and other studies will identify the regimens that produce the best outcomes with the fewest possible side effects in women with HER2-positive breast cancer.
Ferroelectric negative capacitance MOSFET: Capacitance tuning &amp; antiferroelectric operation (2011)

A design methodology of ferroelectric (FE) negative capacitance FETs (NCFETs) based on the concept of capacitance matching is presented. A new mode of NCFET operation, called the “antiferroelectric mode” is proposed, which, besides achieving sub-60mV/dec subthreshold swing, can significantly boost the on-current in exchange for a nominal hysteresis. Design considerations for different device parameters (FE thickness, EOT, source/drain overlap & gate length) are explored. It is suggested that relative improvement in device performance due to FE negative capacitance becomes more significant in very short channel length devices because of the increased drain-to-channel coupling.
Molecular cloning and partial characterization of unintegrated linear DNA from gibbon ape leukemia virus. (1981)

We have cloned the complete genome of an oncogenic primate retrovirus, the San Francisco isolate of gibbon ape leukemia virus, in a lambda phage vector. DNA sequence analysis and restriction endonuclease mapping of the inserted linear provirus demonstrated 9-base pair inverted repeats at its ends, flanking direct terminal repeats 470 base pairs in length. The (-) strong stop region of this DNA showed surprisingly low sequence homology to that of another gibbon ape leukemia virus isolate from an animal with similar disease. Analysis of the clone also revealed the terminal phosphate configuration of the linear provirus. The recombinant phage is suitable for direct use as a hybridization probe to detect homologous retroviral sequences in human cell lines.
The NASA Astrophysics Data System: The searchengine and its user interface (2000)

The ADS Abstract and Article Services provide access to the astronomical literature through the World Wide Web (WWW). The forms based user interface provides access to sophisticated searching capabilities that allow our users to find references in the fields of Astronomy, Physics/Geophysics, and astronomical Instrumentation and Engineering. The returned information includes links to other on-line information sources, creating an extensive astronomical digital library. Other interfaces to the ADS databases provide direct access to the ADS data to allow developers of other data systems to integrate our data into their system. The search engine is a custom-built software system that is specifically tailored to search astronomical references. It includes an extensive synonym list that contains discipline specific knowledge about search term equivalences. Search request logs show the usage pattern of the various search system capabilities. Access logs show the world-wide distribution of ADS users. The ADS can be accessed at: http://adswww.harvard.edu
Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells (2000)

Adult T-cell leukemia (ATL) is characterized by infiltration of various tissues by circulating ATL cells, a finding often associated with a poor prognosis. Leukocyte migration from the circulation into tissues depends on integrin-mediated adhesion to the endothelium, and integrins are tightly regulated by several factors, such as chemokines. In this study, we focused on the interaction between chemokines and chemokine receptors on ATL cells to understand factors involved in ATL cell infiltration of lymphoid organs. We compared freshly isolated ATL cells from patients with and without lymphoid organ involvement for the expression of the chemokine receptor CCR7/EBI1, the functional receptor for secondary lymphoid-tissue chemokine (SLC), which is expressed at high levels by high endothelial venules of lymph nodes and Peyer's patches. Reverse transcriptase-polymerase chain reaction and flow cytometric analysis, using anti-CCR7 monoclonal antibody (CCR7.6B3), revealed that ATL cells from patients with lymphoid organ involvement expressed significantly more CCR7/EBI1 than control CD4(+)CD45RO(+) T cells and ATL cells from patients without lymphoid organ involvement. Consequently, significantly more ATL cells from patients with lymphoid organ involvement than control CD4(+)CD45RO(+) T cells and ATL cells from patients without lymphoid organ involvement adhered to surfaces coated with ICAM-1 and SLC or EBI1-ligand chemokine (ELC), another ligand for CCR7/EBI1, under static and flow conditions and migrated toward SLC or ELC at a low concentration (30 ng/ml). These findings suggest that increased CCR7/EBI1 expression plays a role in lymphoid organ infiltration of ATL cells. (Blood. 2000; 30-38)
A critical role of placental growth factor in the induction of inflammation and edema formation (2002)

Angiogenesis is a prominent feature of a number of inflammatory human diseases, including rheumatoid arthritis, psoriasis, and cutaneous delayed-type hypersensitivity (DTH) reactions. Up-regulation of placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, has been found in several conditions associated with pathologic angiogenesis; however, its distinct role in the control of angiogenesis has remained unclear. To directly investigate the biologic function of PlGF in cutaneous inflammation and angiogenesis, DTH reactions were investigated in the ear skin of wild-type mice, of PlGF-deficient mice, and of transgenic mice with targeted overexpression of human PlGF-2 in epidermal keratinocytes, driven by a keratin 14 promoter expression construct. Chronic transgenic delivery of PlGF-2 to murine epidermis resulted in a significantly increased inflammatory response, associated with more pronounced vascular enlargement, edema, and inflammatory cell infiltration than seen in wild-type mice. Conversely, PlGF deficiency resulted in a diminished and abbreviated inflammatory response, together with a reduction of inflammatory angiogenesis and edema formation. VEGF expression was up-regulated at a comparable level in the inflamed skin of all genotypes. These findings reveal that placental growth factor plays a critical role in the control of cutaneous inflammation, and they suggest inhibition of PlGF bioactivity as a potential new approach for anti-inflammatory therapy.
Insulin and Insulin-Like Growth Factor-I Receptors Differentially Mediate Insulin-Stimulated Adhesion Molecule Production by Endothelial Cells (2009)

Patients with type 2 diabetes are hyperinsulinemic and insulin resistant and develop premature atherosclerosis. High concentrations of insulin stimulate the production of adhesion molecules by endothelial cells (ECs). ECs express abundant IGF-I receptors as well as insulin receptors. Whether IGF-I receptors contribute to insulin-induced endothelial production of adhesion molecules is unknown. Bovine aortic ECs (BAECs) were incubated with insulin (100 nm) for 24 h. The cellular content of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was measured, and monocyte adhesion to ECs was quantified. Insulin increased both VCAM-1 (P < 0.001) and ICAM-1 (P < 0.0002) content, which was accompanied by an increased number of monocytes adherent to BAECs (P = 0.0001). Inhibition of either MAPK kinase-1 or p38 MAPK but not phosphatidylinositol 3-kinase abolished insulin-mediated production of adhesion molecules. Insulin receptor small interfering RNA knockdown abolished insulin-stimulated increases of ICAM-1 but not VCAM-1. Conversely, IGF-I receptor blockade with either a neutralizing antibody or specific small interfering RNA eliminated insulin-induced VCAM-1 but not ICAM-1 production. Blockade of signaling via either the insulin or IGF-I receptors decreased monocyte adherence to BAECs (P < 0.01 for each). We conclude that insulin and IGF-I receptors differentially mediate the production of adhesion molecules by ECs and monocyte adhesion onto the vascular endothelium in response to the hyperinsulinemic state. Dual-receptor activation may most effectively contribute to the pathogenesis of atherosclerotic disease in diabetes.
Using genetic algorithms to select and create features for pattern classification (1990)

Genetic algorithms were used for feature selection and creation in two pattern-classification problems. On a machine-version inspection task, it was found that genetic algorithms performed no better than conventional approaches to feature selection but required much more computation. On a difficult artificial machine-vision task, genetic algorithms were able to create new features (polynomial functions of the original features) which dramatically reduced classification error rates. Neural network and nearest-neighbor classifiers were unable to provide such low error rates using only the original features
Human papillomavirus-specific cytotoxic T lymphocytes in patients with cervical intraepithelial neoplasia grade III. (1997)

Human papillomaviruses (HPVs), especially types 16 and 18, are strongly associated with the development of cervical intraepithelial neoplasia (CIN) and invasive carcinoma. The HPV E6 and E7 proteins are expressed constitutively in the majority of CIN lesions and carcinomas. Therefore, they are targets for the immune response against HPV and candidates for active immunotherapy. We have previously detected HPV-specific CTLs from the peripheral blood mononuclear cells from a cervical cancer patient following immunization with a recombinant vaccinia using in vitro restimulation with adenovirus recombinants expressing HPV16 or HPV18 E6/E7 fusion proteins. In this study, we used a similar protocol to determine the prevalence of CTL responses against HPV16 and HPV18 E6/E7 in the peripheral blood mononuclear cells from 10 CIN III and 10 normal subjects. HPV-specific CTL responses were detected in 6 of 10 CIN III subjects. These CTL lines recognized HPV16 E6/E7 proteins presented by at least three MHC class 1 HLA alleles and by HPV-transformed CaSki cells. No HPV-specific CTLs were detected in normal subjects. This study demonstrates the presence of naturally occurring HPV-specific memory CTLs in a majority of CIN III patients and provides an approach for further study of their role in modulating cervical malignancy.
Quantum cryptography and long distance Bell experiments: How to control decoherence (1999)

Several mechanisms that affect one and two photon coherence in optical fibers and their remedies are discussed. The results are illustrated on quantum cryptography experiments and on long distance Bell inequality tests.
The Handbook of Forecasting: A Manager's Guide. (1983)

ROLE AND APPLICATION OF FORECASTING IN ORGANIZATIONS: Introduction to Management Forecasting Sales Forecasting Requirements Forecasting Requirements for Operations Planning and Control Capacity Planning Forecasting Requirements Forecasting and Strategic Planning Forecasting in the Electric Utility Industry State and Local Government Revenue Forecasting Forecasting: The Issues APPROACHES TO FORECASTING: Smoothing Methods for Short-Term Planning and Control A Practical Overview of ARIMA MODELS for Time Series Forecasting Decomposition Methods for Medium-Term Planning and Budgeting FORECASTING CHALLENGES: Forecasting and the Environment: The Challenges of Rapid Change Life-Cycle Forecasting Forecasting Recessions MANAGING THE FORECASTING FUNCTION: Forecasting and Planning: An Evaluation Integrating Forecasting and Decision Making The Forecasting Audit Index.
Systematic Profiling and Novel Targets of the Bcr-Abl Kinase Inhibitors Imatinib, Nilotinib and Dasatinib. (2007)

Abstract The BCR-ABL tyrosine kinase inhibitor imatinib represents the current frontline therapy in chronic myeloid leukemia (CML). Since imatinib resistance has become a major clinical problem in recent years, two second-generation drugs, nilotinib and dasatinib, displaying increased potency against BCR-ABL and targeting imatinib-resistant CML clones were developed. To predict potential side effects and novel medical uses we generated comprehensive drug-protein interaction profiles for all three drugs. We have used an unbiased chemical proteomics approach to detect drug-binding proteins directly from lysates of CML cells. Our studies yielded four major findings: The interaction profiles of the three drugs displayed strong differences and only a small overlap covering the ABL kinases. Dasatinib bound in excess of thirty Tyr− and Ser−/Thr−kinases, including major regulators of the immune system suggesting that dasatinib might have a particular impact on immune function. Despite the high specificity of nilotinib the receptor tyrosine kinase DDR1 was identified and validated as an additional major target. The oxidoreductase NQO2 was bound and inhibited by imatinib and nilotinib at physiologically relevant drug concentrations representing the first non-kinase target of these drugs. In addition, we have concentrated on the promiscuous binding profile of dasatinib: Besides Abl and Src kinases, we have identified the Tec kinases Btk and Tec, but not Itk, as major binders of dasatinib. The kinase activity of Btk and Tec, but not of Itk, was inhibited by nanomolar concentrations of dasatinib in vitro and in cultured cells. We identified the gatekeeper residue as the critical determinant of dasatinib susceptibility. Mutation of Thr-474 in Btk to Ile and Thr-442 in Tec to Ile conferred resistance to dasatinib, while mutation of the corresponding residue in Itk (Phe-435) to Thr sensitized the otherwise insensitive Itk to dasatinib. The configuration of this residue may be a predictor for dasatinib sensitivity across the kinome. Analysis of mast cells derived from Btk-deficient mice suggested that inhibition of Btk by dasatinib may be responsible for the observed reduction in histamine release upon dasatinib treatment. Furthermore, dasatinib inhibited histamine release in primary human basophils and secretion of pro-inflammatory cytokines in immune cells. The observed inhibition of Tec kinases by dasatinib predicts immunosuppressive (side) effects of this drug and may offer new therapeutic opportunities for inflammatory and immunological disorders.
Studies on Spiro Azetidinones and Spiro Thiazolidinones, III Synthesis of Some New Spiro Azetidinones, Spiro Thiazolidinones, Bis-azetidinones and Bis-thiazolidinones (1979)

Abstract Cyclocondensation reaction of 3-isatylideneoxime (1a), -hydrazone (1b), -phenyl-hydrazone (1c), semicarbazone (1d) and -thiosemicarbazone (1e) with chloroacetyl chloride (and thioglycolic acid) gave the corresponding spiro azetidinones (2) and spiro thiazolidinones (3). 3-Isatylidenehydrazone (1b) was condensed easily with aromatic aldehydes afforded a new 3-isatylidene azomethines (4) which submitted for cyclocondensation reaction with chloroacetyl chloride (and thioglycolic acid) giving bis-azetidinones (5) and bis-thiazolidinones (6), respectively.