gebhart/patrepeval huggingface dataset:
Antisense Targeting of Thymidylate Synthase (TS) mRNA Increases TS Gene Transcription and TS Protein: Effects on Human Tumor Cell Sensitivity to TS Enzyme-Inhibiting Drugs (2006)

Thymidylate synthase (TS) catalyses the only de novo pathway to produce thymidylate for DNA replication and repair and is an important target for cancer chemotherapy. Preexisting or acquired drug resistance in tumor cells limits clinical efficacy of TS-targeting drugs. Cells selected for higher TS protein activity have decreased sensitivity to TS-targeting chemotherapeutic agents (5-FUdR and raltitrexed). New therapeutic strategies are required to overcome treatment resistance. Among these, upregulation of drug resistance mediators in normal, nontarget cells and/or antisense downregulation of those mediators (alone or in combination with protein-targeting drugs) are candidate strategies. We have targeted human TS mRNA with antisense oligodeoxynucleotides (AS ODNs), complementary to the translation start site (TSS), the coding region, and the 3' untranslated region. We report here that, in response to treatment with a novel TSS-targeting AS ODN 791, TS gene transcription in a human cervical carcinoma cell line (HeLa) was unexpectedly increased by 70%. Interestingly, the increased TS gene transcription and nuclear TS RNA did not elevate levels of total cellular TS mRNA, but did increase TS protein activity by 35% and TS protein level by 150%. Increased TS protein activity and level did not alter proliferation rate or sensitivity to TS-targeting drugs (5-FUdR or raltitrexed). To assess concentration-dependent effects of TS on sensitivity to TS-targeting drugs, incremental increases of TS protein levels were generated by transfection of a mammalian TS expression vector. Increases in TS protein of less than approximately 400% did not significantly affect sensitivity to TS-targeting drugs, while greater TS protein levels did. These data indicate that AS ODNs targeting TS mRNA can upregulate TS expression and activity in a manner dependent on the sequence being targeted, and that there exists a threshold increase (greater than approximately 400-700% in HeLa cells), required to initiate resistance to TS-targeting drugs.
AASLD practice guidelines (2005)

These recommendations provide a data-supported approach. They are based on the following: (1) formal review and analysis of the recently published world literature on the topic [Medline search]; (2) American College of Physicians Manual for Assessing Health Practices and Designing Practice Guidelines 1 ; (3) guideline policies, including the AASLD Policy on the Development and Use of Practice Guidelines and the AGA Policy Statement on Guidelines 2 ; (4) the experience of the authors in the specified topic.
High-Temperature Operation of AlGaN/GaN HEMTs Direct-Coupled FET Logic (DCFL) Integrated Circuits (2007)

This letter presents the high-temperature performance of AlGaN/GaN HEMT direct-coupled FET logic (DCFL) integrated circuits. At 375 degC, enhancement-mode (E-mode) AlGaN/GaN HEMTs which are used as drivers in DCFL circuits exhibit proper E-mode operation with a threshold voltage (V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">TH</sub> ) of 0.24 V and a peak current density of 56 mA/mm. The monolithically integrated E/D-mode AlGaN/GaN HEMTs DCFL circuits deliver stable operations at 375 degC: An E/D-HEMT inverter with a drive/load ratio of 10 exhibits 0.1 V for logic-low noise margin (NM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">L</sub> ) and 0.3 V for logic-high-noise margin (NM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">H</sub> ) at a supply voltage (V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DD</sub> ) of 3.0 V; a 17-stage ring oscillator exhibits a maximum oscillation frequency of 66 MHz, corresponding to a minimum propagation delay ( tau <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">pd</sub> ) of 446 ps/stage at V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DD</sub> of 3.0 V
Human Extenders (1993)

A human’s ability to perform physical tasks is limited by physical strength, not by intelligence. We coined the word “extenders” as a class of robot manipulators worn by humans to augment human mechanical strength, while the wearer’s intellect remains the central control system for manipulating the extender. Our research objective is to determine the ground rules for the control of robotic systems worn by humans through the design, construction, and control of several prototype experimental direct-drive/non-direct-drive multi-degree-of-freedom hydraulic/electric extenders. The design of extenders is different from the design of conventional robots because the extender interfaces with the human on a physical level. The work discussed in this article involves the dynamics and control of a prototype hydraulic six-degree-of-freedom extender. This extender’s architecture is a direct drive system with all revolue joints. Its linkage consists of two identical subsystems, the arm and the hand, each having three degrees of freedom. Two sets of force sensors measure the forces imposed on the extender by the human and by the environment (i.e., the load). The extender’s compliances in response to such contact forces were designed by selecting appropriate force compensators. The stability of the system of human, extender, and object being manipulated was analyzed. A mathematical expression for the extender performance was determined to quantify the force augmentation. Experimental studies on the control and performance of the experimental extender were conducted to verify the theoretical predictions.
Bank Applications Fuel Optical Storage Market (1991)

Empyema necessitans (EN) is a rare complication of empyema, in which pus accumulates within the pleural space and spreads through the chest wall, leading to the formation of a subcutaneous abscess. This condition presents significant diagnostic and therapeutic challenges due to its rarity and potential for serious complications. Here, we present the case of an 8-year-old boy with a history of parapneumonic effusion that was incompletely treated due to a lack of fibrinolytic agent injection. He presented with fever, chills, a productive cough, and left-sided chest pain with yellowish purulent secretions from the left chest wall. The patient was diagnosed with EN caused by <i>Staphylococcus aureus</i>, which has occurred due to inadequate treatment and the lack of administration of a fibrinolytic agent injection for the patient. He was treated with broad-spectrum antibiotics, video-assisted thoracic surgery, and a chest tube for complete drainage. The patient showed a smooth and uneventful recovery, highlighting the importance of early diagnosis and prompt treatment of EN to avoid further complications. This case report aims to increase awareness among clinicians about the importance of early recognition and appropriate management of EN to improve patient outcomes.
Critical configurations for n-view projective reconstruction (2005)

In this paper we give a characterization of critical configurations for projective reconstruction with any number of points and views. A set of cameras and points is said to be critical if the projected image points are insufficient to determine the placement of the points and the cameras uniquely, up to a projective transformation. For two views, the critical configurations are well-known. In this paper it is shown that a configuration of n 3 cameras and in points all lying on the intersection of two distinct ruled quadrics is critical. In distinction to the two-view case, which in general allows two alternative solutions, there is a family of ambiguous reconstructions for the n-view case. As a partial converse, it Is shown that for any critical configuration, all the points lie on the intersection of two ruled quadrics.
Astringency - A Molecular Model for Polyphenol/Protein Binding (2004)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Hemodynamic Modulation of Endocardial Thromboresistance (2006)

These findings suggest that increased hemodynamic load adversely affects endocardial function and is a potentially important contributor to thromboembolus formation in heart failure.
Recombinant Platelet Factor 4: A Therapeutic, Anti-Neoplastic Chimera? (2010)

Angiogenesis plays a pivotal role in many serious and life-threatening disorders (e.g., cancer, atherosclerosis, diabetes, arthritis, psoriasis, nephropathy, and retinopathy) and is regulated by a delicate equilibrium between a variety of pro- and anti-angiogenic factors. Although recombinant platelet factor 4 (PF4) was originally developed and evaluated as a clinical alternative to protamine for heparin neutralization, the current scientific evidence supports a role for this protein and derivative peptides in inhibiting tumor growth and spread, by suppression of tumor-induced neovascularization in many different types of solid tumors. As a heparin-binding tetramer, recombinant PF4 interferes with several steps of endothelial cell proliferation, migration, and angiogenesis, regulates apoptotic death through activation of distinct signal transduction pathways, inhibits growth factor receptor binding, amplifies the inflammatory response of natural killer cells through regulation of cytokines production, and induces and maintains a nonspecific immune response to cancer cells. These biological evidences paved the way for the development and marketing of novel PF4-based angiostatic agents characterized by reduced toxicity and improved bioavailability, thus raising the possibility of an alternative approach for preventing and treating growth and metastasis of tumors. Some PF4-derived molecules such as carboxyl-terminal fragments of recombinant human PF4 and modified and chimeric peptides have already been developed that exhibit stronger anti-angiogenic properties than the parent molecule and may serve as leads for further therapeutic developments. Newer means of delivering of this anti-angiogenic agent are also being attempted, including PF4-bearing polymeric microspheres, vector-mediated PF4 transduction, transgene transfection into oncolytic viruses, and molecular targeting therapy against PF4 and rHuPF4 conjugates. These delivery systems aim to produce high concentrations of the therapeutic agent in a local area for a sustained period, thereby avoiding the typical problems encountered with long-term administration of recombinant proteins.
Expression of matrix metalloproteinase 9 (MMP-9/gelatinase B) in adenocarcinomas strongly correlated with expression of immune response genes. (2003)

Matrix metalloproteinases (MMPs) are endopeptidases considered to be important regulators of the microenvironment of cancer. While MMPs are traditionally associated with the extracellular matrix (ECM), here we provide new evidence from an analysis of gene expression profiles from human tumor tissue that MMP-9 (gelatinase B) is associated with elements of the immune system in a way analogous to the association of other MMPs, such as MMP-2 (gelatinase A), with components of the ECM. An analysis of three independent microarray datasets of lung adenocarcinomas from previous studies [Nat. Med. 8, 816-824 (2002); Proc. Natl. Acad. Sci. USA 98, 13790-13795 (2001); Proc. Natl. Acad. Sci. USA, 98, 13784-13789 (2001)] showed that, in each dataset, out of the set of genes with significant correlations in mRNA expression to the expression of MMP9 (P < 0.005), a highly disproportionate number were found to be annotated in the Locuslink database as having a role in the anti-pathogen response. By comparison, out of the set of genes significantly correlated with the expression of MMP2, a highly disproportionate number were known components of the ECM. The same patterns observed in the lung data for both MMP2 and MMP9 were found as well in an additional published dataset of colon and ovarian adenocarcinomas [Am. J. Pathol. 159, 1231-1238 (2001)]. The results of this study suggest a greater functional role for MMP-9 in the immune response to cancer than what may previously have been thought.
Differential timing of nuclear lamin A/C expression in the various organs of the mouse embryo and the young animal: a developmental study (1989)

In mouse embryos, acquisition of the nuclear lamin polypeptides A/C varies according to developmental stage and tissue type. In order to determine the precise time points and cell types in which lamin A/C are first observed, we have used two monoclonal antibodies in immunofluorescence studies of different tissues of developing mouse embryos and of young mice. One antibody (mAB346) is specific for lamins A and C, while the other (PKB8) detects lamins A, B and C. Dividing uterine development into three phases--germ layer formation, organogenesis and tissue differentiation--our results show that lamin A/C expression in the embryo proper is not observed until the third phase of development. Lamin A/C first appears at embryonic day 12 in muscle cells of the trunk, head and the appendages. Three days later it is also seen in cells of the epidermis where its appearance coincides with the time of stratification. In the simple epithelial of lung, liver, kidney and intestine, as well as in heart and brain, lamins A/C do not appear until well after birth. Embryonal carcinoma (EC) cells express lamin B but not lamin A/C. Lamin A/C expression is noted in some EC cells after they are induced to differentiate and in several differentiated teratocarcinoma cell lines. Our results suggest that commitment of a cell to a particular pathway of differentiation (assayed by cell-type-specific expression of intermediate filament proteins) usually occurs prior to the time that lamin A/C can be detected. Thus lamin A/C expression may serve as a limit on the plasticity of cells for further developmental events.
Measurements and modelling of noise in DC-erased thin-film media (1990)

Experimental and theoretical results are given for the noise produced in thin-film media after reverse DC erasure. The noise spectra produced at high bit densities and at reverse DC erasure around the remanent coercivity look identical. A theoretical spectral model based on Poisson statistics shows a good fit with the measured noise spectra. A novel technique for measuring the medium noise in the spatial domain has been developed. The results obtained in the spatial domain through autocorrelation of the read flux agree well with the noise results obtained in the spectral domain.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Fibroblast growth factor 2 retargeted adenovirus has redirected cellular tropism: evidence for reduced toxicity and enhanced antitumor activity in mice. (1999)

Adenovirus (Ad) have been used as vectors to deliver genes to a wide variety of tissues. Despite achieving high expression levels in vivo, Ad vectors display normal tissue toxicity, transient expression, and antivector immune responses that limit therapeutic potential. To circumvent these problems, several retargeting strategies to abrogate native tropism and redirect Ad uptake through defined receptors have been attempted. Despite success in cell culture, in vivo results have generally not shown sufficient selectivity for target tissues. We have previously identified (C. K. Goldman et al., Cancer Res., 57: 1447-1451, 1997) the fibroblast growth factor (FGF) ligand and receptor families as conferring sufficient specificity and binding affinity to be useful for targeting DNA in vivo. In the present studies, we retargeted Ad using basic FGF (FGF2) as a targeting ligand. Cellular uptake is redirected through high-affinity FGF receptors (FGFRs) and not the more ubiquitous lower-affinity Ad receptors. Initial in vitro experiments demonstrated a 10- to 100-fold increase in gene expression in numerous FGFR positive (FGFR+) cell lines using FGF2-Ad when compared with Ad. To determine whether increased selectivity could be detected in vivo, FGF2-Ad was administered i.v. to normal mice. FGF2-Ad demonstrates markedly decreased hepatic toxicity and liver transgene expression compared with Ad treatment. Importantly, FGF2-Ad encoding the herpes simplex virus thymidine kinase (TK) gene transduces Ad-resistant FGFR+ tumor cells both ex vivo and in vivo, which results in substantially enhanced survival (180-260%) when the prodrug ganciclovir is administered. Because FGFRs are up-regulated on many types of malignant or injured cells, this broadly useful method to redirect native Ad tropism and to increase the potency of gene expression may offer significant therapeutic advantages.
Single-Step Synthesis of Cell-Permeable Protein Dimerizers That Activate Signal Transduction and Gene Expression (1997)

The one-step “dimerization” (with loss of ethylene) of the immunosuppressant FK506 by olefin metathesis has been used to create new chemical inducers of dimerization (CIDs). These small-molecule protein dimerizers are shown to activate signal transduction pathways and gene transcription at low concentrations in mammalian cells. Their ease of synthesis provides ready access to reagents of widespread utility in studies of the cellular functions of proteins.
Interaction of guanosine cyclic 3',5'-phosphate dependent protein kinase with lin-benzoadenine nucleotides (1985)

Using the activated cGMP-dependent protein kinase in the presence of the phosphorylatable peptide [[Ala34]histone H2B-(29-35)], we found that lin-benzoadenosine 5'-diphosphate (lin-benzo-ADP) was a competitive inhibitor of the enzyme with respect to ATP with a Ki (22 microM) similar to the Kd (20 microM) determined by fluorescence polarization titrations. The Kd for lin-benzo-ADP determined in the absence of the phosphorylatable peptide, however, was only 12 microM. ADP bound with lower affinity (Ki = 169 microM; Kd = 114 microM). With [Ala34]histone H2B-(29-35) as phosphoryl acceptor, the Km for lin-benzo-ATP was 29 microM, and that for ATP was 32 microM. The Vmax with lin-benzo-ATP, however, was only 0.06% of that with ATP as substrate [0.00623 +/- 0.00035 vs. 11.1 +/- 0.17 mumol (min.mg)-1]. Binding of lin-benzo-ADP to the kinase was dependent upon a divalent cation. Fluorescence polarization revealed that Mg2+, Mn2+, Co2+, Ni2+, Ca2+, Sr2+, and Ba2+ supported nucleotide binding to the enzyme; Ca2+, Sr2+, and Ba2+, however, did not support any measurable phosphotransferase activity. The rank order of metal ion effectiveness in mediating phosphotransferase activity was Mg2+ greater than Ni2+ greater than Co2+ greater than Mn2+. Although these results were similar to those observed with the cAMP-dependent protein kinase [Hartl, F. T., Roskoski, R., Jr., Rosendahl, M. S., & Leonard, N. J. (1983) Biochemistry 22, 2347], major differences in the Vmax with lin-benzo-ATP as substrate and the effect of peptide substrates on nucleotide (both lin-benzo-ADP and ADP) binding were observed.
Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis (2007)

Hepatorenal syndrome (HRS) is a serious complication of end-stage liver disease, occurring mainly in patients with advanced cirrhosis and ascites, who have marked circulatory dysfunction,1 as well as in patients with acute liver failure.2 In spite of its functional nature, HRS is associated with a poor prognosis,3 4 and the only effective treatment is liver transplantation. During the 56th Meeting of the American Association for the Study of Liver Diseases, the International Ascites Club held a Focused Study Group (FSG) on HRS for the purpose of reporting the results of an international workshop and to reach a consensus on a new definition, criteria for diagnosis and recommendations on HRS treatment. A similar workshop was held in Chicago in 1994 in which standardised nomenclature and diagnostic criteria for refractory ascites and HRS were established.5 The introduction of innovative treatments and improvements in our understanding of the pathogenesis of HRS during the previous decade led to an increasing need to undertake a new consensus meeting. This paper reports the scientific rationale behind the new definitions and recommendations. The international workshop included four issues debated by four panels of experts (see Acknowledgements). The issues were: (1) evidence-based HRS pathogenesis; (2) treatment of HRS using vasoconstrictors; (3) other HRS treatments using transjugular intrahepatic portosystemic stent-shunt (TIPS) and extracorporeal albumin dialysis (ECAD); and (4) new definitions and diagnostic criteria for HRS and recommendations for its treatment.
Heparin-Induced Thrombocytopenia (2006)

A 63-year-old man with coronary artery disease who has recently undergone bypass surgery presents with dyspnea. Laboratory testing reveals a platelet count of 86,000 per cubic millimeter, as compared with 225,000 per cubic millimeter at the time of discharge nine days earlier. Findings on chest radiography are unremarkable; spiral computed tomography of the chest shows a pulmonary embolism. Heparin-induced thrombocytopenia is suspected. What diagnostic studies are warranted, and how should this patient be treated?
Synthesis and Luminescent Properties of New Oligofluorene Derivatives Containing Various Comonomers (2011)

Two kinds of oligofluorenes containing acetylene units are synthesized by Sonogashira coupling reaction. naphthalene and anthracene are co-polymerized with ethynylfluorene, respectively. The structure and properties are characterized using NMR, UV-vis spectroscopy, elemental analysis, DSC and photoluminescence. The oligomers are soluble in common organic solvents such as benzene and easily spin-coated onto glass substrates. The products yield strong emission differing from blue to green-yellow, and red-shift are suppressed with the growth in size of co-monomers.
SH3 — an abundant protein domain in search of a function (1992)

Src-homology 3 is a small protein domain of about 60 amino acid residues. It is probably made of beta-sheets. SH3 is present in a large number of eukaryotic proteins which are involved in signal transduction, cell polarization and membrane-cytoskeleton interactions. Here we review its occurrence and discuss possible functions of this domain.
Structural basis for nucleotide exchange in heterotrimeric G proteins (2015)

G protein-coupled receptors (GPCRs) relay diverse extracellular signals into cells by catalyzing nucleotide release from heterotrimeric G proteins, but the mechanism underlying this quintessential molecular signaling event has remained unclear. Here we use atomic-level simulations to elucidate the nucleotide-release mechanism. We find that the G protein α subunit Ras and helical domains-previously observed to separate widely upon receptor binding to expose the nucleotide-binding site-separate spontaneously and frequently even in the absence of a receptor. Domain separation is necessary but not sufficient for rapid nucleotide release. Rather, receptors catalyze nucleotide release by favoring an internal structural rearrangement of the Ras domain that weakens its nucleotide affinity. We use double electron-electron resonance spectroscopy and protein engineering to confirm predictions of our computationally determined mechanism.