gebhart/patrepeval huggingface dataset:
Pseudomonas aeruginosa binds to neoglycoconjugates bearing mucin carbohydrate determinants and predominantly to sialyl-Lewis x conjugates (1999)

Pseudomonas aeruginosa plays an important role in the colonization of the airways of patients suffering from cystic fibrosis. It binds to the carbohydrate part of respiratory and salivary mucins and its binding to cystic fibrosis mucins is even higher, suggesting that qualitative or/and quantitative modifications of the carbohydrate chains may be involved in this process. In order to find out the best carbohydrate receptors for P.aeruginosa, a flow cytometry technique using a panel of polyacrylamide based glycoconjugates labeled with fluorescein was developed. The neoglycoconjugates contained neutral, sialylated or sulfated chains analogous to carbohydrate determinants found at the periphery of respiratory mucins (Le(a), Le(y), Le(x), sialyl- and 3'-sulfo-Le(x), and blood group A determinants). We used also neoglycoconjugates containing Gal(alpha1-2)Galbeta and sialyl- N -acetyllactosamine determinants. The interaction of these glycoconjugates with the nonpiliated strain of P.aeruginosa, 1244-NP, was saturable except for the glycoconjugates containing blood group A or sialyl- N -acetyllactosamine epitopes. The measure of Kd indicated that strain 1244-NP had a higher affinity for the glycoconjugate bearing the sialyl-Le(x)determinant than for all the other glycoconjugates studied. The role of sialic acid was confirmed by competition assay using mainly sialylated mucin glycopeptides. In order to find out if this behavior was the same for pathological strains as for the 1244-NP mutant, four mucoid strains of P.aeruginosa isolated from cystic fibrosis patients were analyzed with the Le(x)neoglycoconjugate, its sialylated and its sulfated derivatives. Individual variations in the binding of these strains to the three glycoconjugates were observed. However, three strains out of four had a higher affinity for the sialyl-Le(x)than for the 3'-sulfo-Le(x)derivative.
The effects of chemical doping with F4TCNQ in carbon nanotube field-effect transistors studied by the transmission-line-model technique (2007)

We have studied the effects of p-type chemical doping with F4TCNQ (tetrafluorotetracyano-p-quinodimethane) in carbon nanotube field-effect transistors (CNFETs). The transmission-line-model technique using multi-probe CNFETs has been employed to investigate the effects of chemical doping on the channel resistance and contact resistance. It has been found that chemical doping is effective in the reduction of the contact resistance as well as the channel resistance. The device performances of top-gate CNFETs such as transconductance, on-resistance, and on/off ratio were improved by the F4TCNQ chemical doping on the access regions.
Gene therapy for bone formation: In vitro and in vivo osteogenic activity of an adenovirus expressing BMP7 (2000)

Bone morphogenetic proteins (BMPs) are well-established agents for inducing orthotopic and ectopic bone formation. However, their clinical usefulness as regenerative agents may be limited by a short in vivo half-life and low specific activity. BMP gene therapy is an alternative route for exploiting the bone-inductive activity of this class of molecules. To test the feasibility of this approach, we examined the osteogenic activity of AdCMV-BMP7, an adenovirus containing BMP7 cDNA under control of the CMV promoter that was constructed using Cre/lox recombination (Hardy et al. [1997] J. Virol. 71:1842-1849). Adenovirus vectors were shown to readily infect a wide variety of cell types in vitro including osteoblasts, fibroblasts, and myoblasts. COS7 cells transduced with AdCMV-BMP7 produced high levels of BMP-7 (approximately 0.5 microg/10(6) cells). Furthermore, transduction of C2C12 murine myoblast cells with AdCMVBMP-7 suppressed the muscle phenotype and induced in vitro osteoblast differentiation. To test its in vivo biological activity, AdCMV-BMP7 was mixed with a bovine bone-derived collagen carrier (10(8) plaque-forming units virus/site) and was implanted into mouse muscle and dermal pouches. In both cases, an ossicle containing cortical and trabecular bone and a clearly defined marrow cavity formed at the site of virus implantation within 4 weeks. These data demonstrate that AdCMV-BMP7 transduced cells produce biologically active BMP-7 both in vitro and in vivo and show that gene therapy by direct viral transduction using a virus/matrix implant may be a viable route for stimulating bone regeneration.
An Antifibrinolytic Mechanism Describing the Prothrombotic Effect Associated with Factor VLeiden (1996)

Factor Va is the essential cofactor in prothrombinase-dependent activation of prothrombin. Resistance of Factor VaLeiden to inactivation by activated protein C (APC) contributes to thrombotic tendencies in subjects with the variant due, in part, to the inability to terminate thrombin production which increases both fibrin accretion and the frequency of thrombus formation. A reduced ability to inhibit thrombin generation, however, may lead to the stabilization of a clot through the activation of thrombin activatable fibrinolysis inhibitor (TAFI). This hypothesis was tested by determining the profibrinolytic effect of APC on lysis time using clots formed with plasma from either homozygous normal (n = 4) or homozygous factor VLeiden (n = 4) subjects. Clots were formed in the presence of tissue-type plasminogen activator, thrombin, phosphatidylcholine/phosphatidylserine vesicles, Ca2+, and various concentrations of APC. Approximately 10-fold more APC was required to reduce lysis time from 140 to 50 min in clots containing factor VLeiden compared to normal factor V. This effect was specific to the form of factor V present in plasma since identical results were obtained in an appropriately reconstituted purified system, which included both TAFI and either form of factor V purified from pooled plasma. In the absence of TAFI, APC did not affect clot lysis in experiments with either normal factor V or factor VLeiden. During the various lysis assays performed with purified components, clots were solubilized and the proteolytic alterations in factor V/Va were assessed by Western blotting using a specific factor Va heavy chain monoclonal antibody. The heavy chain of factor VaLeiden persisted for as long as 60 min, in the presence of 6.3 n APC indicating sustained activity of factor VaLeiden during the lysis assay. In contrast, no factor Va heavy chain was present after the first 5.0 min in clots formed in the presence of normal factor V and 6.3 n APC. These combined data indicate that factor VaLeiden specifically attenuates the profibrinolytic effect of APC. Thus, an impaired TAFI-dependent profibrinolytic response to APC in APC-resistant individuals appears to be an additional factor contributing to the prothrombotic tendencies in subjects with factor VLeiden.
Tandem stenting of crossed renal arteries with ostial stenosis. (2000)

Ostial stenosis of renal arteries has been shown to respond favorably to stenting. Heterogeneity of renal artery anatomy is very common and often increases the technical difficulty of percutaneous treatment of stenotic lesions. We present the case of a 69-year-old man with severe hypertension who had 2 right renal arteries, both of which had ostial stenosis. We treated these stenoses with simultaneous stenting of both renal ostia. Since the procedure, the patient has had significantly improved control of his hypertension.
A Unique Substrate Recognition Profile for Matrix Metalloproteinase-2 (2002)

The catalytic domains of the matrix metalloproteinases (MMPs) are structurally homologous, raising questions as to the degree of distinction, or overlap, in substrate recognition. The primary objective of the present study was to define the substrate recognition profile of MMP-2, a protease that was historically referred to as gelatinase A. By cleaving a phage peptide library with recombinant MMP-2, four distinct sets of substrates were identified. The first set is structurally related to substrates previously reported for other MMPs. These substrates contain the PXX/X(Hy) consensus motif (where X(Hy) is a hydrophobic residue) and are not generally selective for MMP-2 over the other MMPs tested. Two other groups of substrates were selected from the phage library with similar frequency. Substrates in group II contain the L/IXX/X(Hy) consensus motif. Substrates in group III contain a consensus motif with a sequence of X(Hy)SX/L, and the fourth set of substrates contain the HXX/X(Hy) sequence. Substrates in Group II, III, and IV were found to be 8- to almost 200-fold more selective for MMP-2 over MMP-9. To gain an understanding of the structural basis for substrate selectivity, individual residues within substrates were mutated, revealing that the P(2) residue is a key element in conferring selectivity. These findings indicate that MMP-2 and MMP-9 exhibit different substrate recognition profiles and point to the P(2) subsite as a primary determinant in substrate distinction.
Development of Plant Promoter Expression Vectors and Their Use for Analysis of Differential Activity of Nopaline Synthase Promoter in Transformed Tobacco Cells (1986)

I have developed promoter expression binary vectors based on the tumor-inducing plasmid of Agrobacterium tumefaciens to facilitate elucidation of plant gene regulation. Promoter activity can be determined by inserting DNA fragments into the multiple cloning sites of the vectors forming transcriptional and/or translational fusions between the cat structural gene and an inserted promoter region. The activity of the nopaline synthase (nos) promoter was demonstrated with the vector. However, three animal promoters tested with this system showed no measurable activity in plant cells. Examination of 40 independently derived transformed tissues revealed a 200-fold difference in the nos promoter activity. Furthermore, there is no apparent correlation between the neomycin phosphotransferase and chloramphenicol acetyltransferase activities, although both genes are closely linked and under control of identical nos promoters. These results indicate that vast differences in promoter activity of transferred genes can occur within the same cell, as well as in independently derived cell lines.
Multi-user wireless access to a digital cable system (2004)

We describe a system, a wireless overlay on existing hybrid fiber/coax digital packet-based networks, for high-speed, short-range wireless access to video programming services, to the Internet, and to the telephone, cellular mobile, and other communication networks. Wireless access may be provided to both fixed (residential) users and to passersby with portable devices. Smart transponder nodes and antennas are densely distributed along the access cable line for wireless communication with user nodes. The antennas along a cable access line form an adaptive "superantenna" that is excited, for downstream transmission, by short sequences of vector signals that cancel radio interference. These excitations can be derived from a stable adaptive process. Upstream transmission from a subscriber node is designed so that the vector received by the superantenna can be used to separate this signal from that of other users' transmitters. Cooperation among end users is not necessary but is possible. Antenna excitation signals are controlled from the system headend, based on processing that uses measured channel parameters between the sets of access line and user antennas. A program controller in the headend, responding to end user requests, manages delivery of selected program streams and other customer services through generation of superimposed superantenna excitation signals that target multiple end users. This model offers opportunities for flexible capacity allocations and a wide range of programming and customized private.
Evaluation of a Quantitative Magnetic Resonance Method for Mouse Whole Body Composition Analysis (2004)

QMR and DXA detected similar fat content, but the improved precision afforded by QMR compared with DXA and chemical analysis allowed detection of a significant difference in body fat after 7 days of consuming a diet rich in fat even though average body weight did not significantly change. QMR provides a very precise, accurate, fast, and easy-to-use method for determining fat and lean tissue of mice without the need for anesthesia. Its ability to detect differences with great precision should be of value when characterizing phenotype and studying regulation of body composition brought about by pharmacological and dietary interventions in energy homeostasis.
Neural spike sorting under nearly 0-dB signal-to-noise ratio using nonlinear energy operator and artificial neural-network classifier (2000)

We report a result on neural spike sorting under conditions where the signal-to-noise ratio is very low. The use of nonlinear energy operator enables the detection of an action potential, even when the SNR is so poor that a typical amplitude thresholding method cannot be applied. The superior detection ability facilitates the collection of a training set under lower SNR than that of the methods which employ simple amplitude thresholding. Thus, the statistical characteristics of the input vectors can be better represented in the neural-network classifier. The trained neural-network classifiers yield the correct classification ratio higher than 90% when the SNR is as low as 1.2 (0.8 dB) when applied to data obtained from extracellular recording from Aplysia abdominal ganglia using a semiconductor microelectrode array.
A case of squamous-cell carcinoma with a suspected cervical cyst. (1993)

臨床的に嚢胞と診断された頸部皮下腫瘤性病変の一例を種々の画像診断法 (コンピュータ断層撮影法, 超音波診断法および唾液腺造影法) によって検討した。コンピュータ断層撮影法と唾液腺造影法では腫瘤と唾液腺およびその周辺組織の関係を知ることができた。超音波診断法では病変の内部構造を把握することができた。その結果, 病変は唾液腺外に存在する悪性腫瘍と診断した。病理組織診断は扁平上皮癌であった。
An aromatic effector specificity mutant of the transcriptional regulator DmpR overcomes the growth constraints of Pseudomonas sp. strain CF600 on para-substituted methylphenols (1994)

The pVI150 catabolic plasmid of Pseudomonas sp. strain CF600 carries the dmp system, which comprises the divergently transcribed dmpR gene and the dmp operon coding for the catabolic enzymes required for growth on (methyl)phenols. The constitutively expressed DmpR transcriptional activator positively controls the expression of the RpoN-dependent dmp operon promoter in the presence of the aromatic effector in the growth medium. However, the magnitude of the transcriptional response differs depending on the position of the methyl substituent on the aromatic ring. Experiments involving an elevated copy number of the dmp system demonstrate that growth on para-substituted methylphenols is limited by the level of the catabolic enzymes. An effector specificity mutant of DmpR, DmpR-E135K, that responded to the presence of 4-ethylphenol, a noneffector of the wild-type protein, was isolated by genetic selection. The single point mutation in DmpR-E135K, which results in a Glu-to-Lys change in residue 135, also results in a regulator with enhanced recognition of para-substituted methylphenols. The DmpR-E135K mutation, when introduced into the wild-type strain, confers enhanced utilization of the para-substituted methylphenols. These experiments demonstrate that the aromatic effector activation of wild-type DmpR by the para-substituted methylphenols is a major factor limiting the catabolism of these compounds.
Anatomic heterogeneity of the rat amygdaloid complex. (2000)

The amygdala is a nuclear complex composed of 13 nuclei and cortical areas and their subdivisions. Tract-tracing studies performed over the past 20 years demonstrate that each nucleus is uniquely connected with other brain areas. Consistent with anatomic heterogeneity, the functions of the amygdala vary from attention to memory to formation of emotional responses to sensory stimuli. Here, we briefly review the principles of amygdaloid neuronal wiring that underlie the computations necessary to perform such complex behavioural functions.
eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR (2005)

The eukaryotic translation initiation factor eIF4E is a critical modulator of cellular growth with functions in the nucleus and cytoplasm. In the cytoplasm, recognition of the 5' m(7)G cap moiety on all mRNAs is sufficient for their functional interaction with eIF4E. In contrast, we have shown that in the nucleus eIF4E associates and promotes the nuclear export of cyclin D1, but not GAPDH or actin mRNAs. We determined that the basis of this discriminatory interaction is an approximately 100-nt sequence in the 3' untranslated region (UTR) of cyclin D1 mRNA, we refer to as an eIF4E sensitivity element (4E-SE). We found that cyclin D1 mRNA is enriched at eIF4E nuclear bodies, suggesting these are functional sites for organization of specific ribonucleoproteins. The 4E-SE is required for eIF4E to efficiently transform cells, thereby linking recognition of this element to eIF4E mediated oncogenic transformation. Our studies demonstrate previously uncharacterized fundamental differences in eIF4E-mRNA recognition between the nuclear and cytoplasmic compartments and further a novel level of regulation of cellular proliferation.
Image Charge and Dipole Combination Model for the Schottky Barrier Tuning at the Dopant Segregated Metal/Semiconductor Interface (2009)

First-principle-based calculations are given to explain the Schottky barrier height (SBH) modifications of nickel silicide/silicon contacts by dopant atoms. Dopant atoms, including B, Al, In, Mg, P, As, Sb, and S, are placed near the NiSi <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> /Si interface, and a systematic study of their effects on the band structure is considered. A new image charge and dipole combination model is proposed to explain the SBH tuning by these atoms, which is in good agreement with experimental observations. Both image charge and dipole moment provide the same p-SBH lowering direction for B atom and the same n-SBH lowering direction for Sb atom. Therefore, the total lowering of the SBH is enhanced for B and Sb; thus, they are good candidates for SBH modifications of nickel silicide/silicon contacts in CMOS applications.
Abstract 5596: Enhanced anti-tumor effect of combination therapy with anti-CD40 antibody and the mTOR kinase inhibitor AZD8055 (2010)

Abstract mTOR signaling, which plays a central role in controlling cell cell proliferation, survival, mobility and angiogenesis, is considered an important target for new anticancer drugs development. The involvement of the CD40/CD154 signaling pathway has also been reported to play an important role in regulating anti-tumor immune responses. In this study, using a first-in-class orally bioavailable mTOR kinase inhibitor, AZD8055, which, unlike rapamycin, can inhibit both mTORC1 and mTORC2, we evaluated the anti-tumor efficacy of mTOR kinase inhibitor treatment alone in a murine model of metastatic renal cell carcinoma (Renca) and compared biological responses achieved by administering AZD8055 as a single agent to those obtained in combination with agonistic anti-CD40 antibody. In vitro survival assays showed that Renca cell apoptosis could be induced by AZD8055. In vivo, although both agents administered alone had some anti-tumor efficacy, the combination of AZD8055 and CD40 Ab induced a significant anti-tumor response in both intra-renal and intra-splenic inoculations model of renal cell carcinoma, as compared to single agent treatments. The combination treatment, also resulted in an increase and activation of tumor- and liver-associated macrophages, NK cells and CD8 T cells in vivo. AZD8055/anti-CD40 treatment also increased the level of systemic Th1 cytokines, including IL-12, IFN-γ, TNFα. IFN-γ production by CD8+ T cells and TNFα production by macrophages were also found to be elevated in the AZD8055/anti-CD40 combination treated-group, compared with any single treatment group. Furthermore, the expression of Th1-associated chemokines, RANTES and IP10, were significantly induced in the combination treated-group. These data suggest that the combination of mTOR kinase targeting agents with immunotherapy could be an area of further development in renal cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5596.
Integrin‐nucleated Toll‐like receptor (TLR) dimerization reveals subcellular targeting of TLRs and distinct mechanisms of TLR4 activation and signaling (2002)

Toll-like receptors (TLRs) are activated by microbial structures. To investigate the mechanisms of TLR activation, the 10 human TLRs were expressed as chimeras with the integrin alphav and beta5 subunits. Co-expression of the alphav-TLR and beta5-TLR chimeras in 293T cells generated 10 TLR homodimers, but only TLR4/4 could effectively activate NF-kappaB. TLR4 monomers also activated NF-kappaB but it was enhanced upon homodimerization. The TLR homodimers showed differential surface/intracellular expression. In TLR heterodimers, only TLR2/1 and TLR2/6 were potent in NF-kappaB activation. NF-kappaB activation by TLR2/1, TLR2/6 and the TLR4 monomer, but not TLR4/4, was completely inhibited by dominant negative MyD88, suggesting that TLR4 homodimers and monomers could activate NF-kappaB through different mechanisms.
Substrate flexibility regulates growth and apoptosis of normal but not transformed cells (2000)

One of the hallmarks of oncogenic transformation is anchorage-independent growth (27). Here we demonstrate that responses to substrate rigidity play a major role in distinguishing the growth behavior of normal cells from that of transformed cells. We cultured normal or H-ras-transformed NIH 3T3 cells on flexible collagen-coated polyacrylamide substrates with similar chemical properties but different rigidity. Compared with cells cultured on stiff substrates, nontransformed cells on flexible substrates showed a decrease in the rate of DNA synthesis and an increase in the rate of apoptosis. These responses on flexible substrates are coupled to decreases in cell spreading area and traction forces. In contrast, transformed cells maintained their growth and apoptotic characteristics regardless of substrate flexibility. The responses in cell spreading area and traction forces to substrate flexibility were similarly diminished. Our results suggest that normal cells are capable of probing substrate rigidity and that proper mechanical feedback is required for regulating cell shape, cell growth, and survival. The loss of this response can explain the unregulated growth of transformed cells.
NF-Y and Sp1 Cooperate for the Transcriptional Activation and cAMP Response of Human Tissue Inhibitor of Metalloproteinases-2 (2000)

The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) is a key determinant in the homeostasis of the extracellular matrix. We have identified two cis-acting elements involved in the transcriptional regulation of TIMP-2. The first is an inverted CCAAT box located at position -73 to -69 in the TIMP-2 promoter that binds the transcription factor NF-Y. The second is a GAGGAGGGGG motif located at position -107 to -98, that binds the transcription factors Sp1 and Sp3. NF-Y and Sp1 cooperate for the basal transcription activity of the promoter. We then determined that TIMP-2 is transcriptionally up-regulated by cAMP analogs. Up-regulation of TIMP-2 by dibutyryl cAMP is a delayed response that requires de novo protein synthesis and does not affect RNA stability. The NF-Y and the Sp1 binding site are both involved in cAMP-dependent up-regulation of TIMP-2. Whereas NF-Y is essential for cAMP mediated regulation, Sp1 alone is not sufficient but enhances the activity of NF-Y. Dibutyryl cAMP has no effect on the expression of MMP-2 and MMP-9 and switches the MMP-TIMP balance in favor of the inhibitor.