gebhart/patrepeval huggingface dataset:
Inhibition of Ataxia Telangiectasia- and Rad3 -Related Function Abrogates the In Vitro and In Vivo Tumorigenicity of Human Colon Cancer Cells Through Depletion of the CD133+ Tumor-Initiating Cell Fraction (2011)

The identification of novel approaches to specifically target the DNA-damage checkpoint response in chemotherapy-resistant cancer stem cells (CSC) of solid tumors has recently attracted great interest. We show here in colon cancer cell lines and primary colon cancer cells that inhibition of checkpoint-modulating phosphoinositide 3-kinase-related (PIK) kinases preferentially depletes the chemoresistant and exclusively tumorigenic CD133(+) cell fraction. We observed a time- and dose-dependent disproportionally pronounced loss of CD133(+) cells and the consecutive lack of in vitro and in vivo tumorigenicity of the remaining cells. Depletion of CD133(+) cells was initiated through apoptosis of cycling CD133(+) cells and further substantiated through subsequent recruitment of quiescent CD133(+) cells into the cell cycle followed by their elimination. Models using specific PIK kinase inhibitors, somatic cell gene targeting, and RNA interference demonstrated that the observed detrimental effects of caffeine on CSC were attributable specifically to the inhibition of the PIK kinase ataxia telangiectasia- and Rad3-related (ATR). Mechanistically, phosphorylation of CHK1 checkpoint homolog (S. pombe; CHK1) was significantly enhanced in CD133(+) as compared with CD133(-) cells on treatment with DNA interstrand-crosslinking (ICL) agents, indicating a preferential activation of the ATR/CHK1-dependent DNA-damage response in tumorigenic CD133(+) cells. Consistently, the chemoresistance of CD133(+) cells toward DNA ICL agents was overcome through inhibition of ATR/CHK1-signaling. In conclusion, our study illustrates a novel target to eliminate the tumorigenic CD133(+) cell population in colon cancer and provides another rationale for the development of specific ATR-inhibitors.
Leveraging RFID in hospitals: Patient life cycle and mobility perspectives (2007)

The application of Radio Frequency Identification (RFID) to patient care in hospitals and healthcare facilities has only just begun to be accepted. This article develops a set of frameworks based on patient life cycle and time-and-motion perspectives for how RFID can be leveraged atop existing information systems to offer many benefits for patient care and hospital operations. It examines how patients are processed from admission to discharge, and considers where RFID can be applied. From a time-and-motion perspective, it shows how hospitals can apply RFID in three ways: fixed RFID readers interrogate mobile objects; mobile, handheld readers interrogate fixed objects; and mobile, handheld readers interrogate mobile objects. Implemented properly, RFID can significantly aid the medical staff in performing their duties. It can greatly reduce the need for manual entry of records, increase security for both patient and hospital, and reduce errors in administering medication. Hospitals are likely to encounter challenges, however, when integrating the technology into their day-to-day operations. What we present here can help hospital administrators determine where RFID can be deployed to add the most value.
Intrathecal delivery of frataxin mRNA encapsulated in lipid nanoparticles to dorsal root ganglia as a potential therapeutic for Friedreich’s ataxia (2016)

In Friedreich's ataxia (FRDA) patients, diminished frataxin (FXN) in sensory neurons is thought to yield the predominant pathology associated with disease. In this study, we demonstrate successful usage of RNA transcript therapy (RTT) as an exogenous human FXN supplementation strategy in vitro and in vivo, specifically to dorsal root ganglia (DRG). Initially, 293 T cells were transfected with codon optimized human FXN mRNA, which was translated to yield FXN protein. Importantly, FXN was rapidly processed into the mature functional form of FXN (mFXN). Next, FXN mRNA, in the form of lipid nanoparticles (LNPs), was administered intravenously in adult mice. Examination of liver homogenates demonstrated efficient FXN LNP uptake in hepatocytes and revealed that the mitochondrial maturation machinery had efficiently processed all FXN protein to mFXN in ~24 h in vivo. Remarkably, greater than 50% mFXN protein derived from LNPs was detected seven days after intravenous administration of FXN LNPs, suggesting that the half-life of mFXN in vivo exceeds one week. Moreover, when FXN LNPs were delivered by intrathecal administration, we detected recombinant human FXN protein in DRG. These observations provide the first demonstration that RTT can be used for the delivery of therapeutic mRNA to DRG.
Fidelity and Predominant Mutations Produced by Deep Vent Wild-Type and Exonuclease-Deficient DNA Polymerases During In Vitro DNA Amplification (1996)

Denaturing gradient gel electrophoresis (DGGE) was used to examine error rates and mutations induced by native (wt) and exonuclease-deficient (exo-) Deep Vent DNA polymerases during DNA amplification by polymerase chain reaction (PCR), in the presence or absence of the T4 bacteriophage gene 32 protein (gp32).gp32 was found to decrease the error rate of the wt, but not that of the exo-, Deep Vent. The average errors per base duplication for the native form were 8.0 x 10(-5) and 6.0 x 10(-5) in the absence and presence of gp32, respectively. For the exo- form, the error rates were 2.0 x 10(-4) and 2.2 x 10(-4) errors per base duplication in the absence and presence of gp32, respectively. Examination of mutations produced by native Deep Vent showed that A/T to G/C transition predominated, consistent with the results of our earlier studies with DNA polymerases derived from other thermophilic bacteria. These results indicate that PCR with high fidelity can be achieved by using wt Deep Vent in combination with gp32.
HER3 and downstream pathways are involved in colonization of brain metastases from breast cancer (2010)

Deregulated HER family receptors, particularly HER3, and their downstream pathways are implicated in colonization of brain metastasis. The need for HER family receptors to dimerize for activation suggests that tumors may be susceptible to combinations of anti-HER family inhibitors, and may even be effective in the absence of HER2 amplification (that is, in triple negative/basal cancers). However, the presence of activating mutations in PIK3CA, HRAS, KRAS and NRAS suggests the necessity for also specifically targeting downstream molecules.
Eremophilane Sesquiterpenes from Capsidiol (2004)

A series of eremophilane sesquiterpene alcohols and hydrocarbons was prepared from the phytoalexin capsidiol (1) for mechanistic studies with epiaristolochene synthase and epiaristolochene dihydroxylase. Among them, 3-deoxycapsidiol (10) was obtained through selective derivatization and reductive cleavage of the equatorial 3 alpha hydroxyl group. Two novel isomers of aristolochene and eremophilene were accessed from the 1- and 3-deoxycapsidiol isomers. 4-Epieremophilene (17) was obtained by conjugate reduction of epiaristolochen-1-one tosylhydrazone with catecholborane followed by sulfinate elimination and diimide rearrangement. Epimerization of epiaristolochen-3-one (27a) at the C4 methyl followed by reductions led to the previously unknown aristolochene isomer, eremophila-9(10),11(12)-diene (30). Optical rotations and characteristic (1)H NMR data for the related eremophilenols and dienes are collected in Tables 1 and 2. Finally, bioassays were used to assess the antifungal potencies of capsidiol and its synthetic derivatives. The minimum inhibitory concentration for capsidiol (3-10 ng) was at least 1 order of magnitude lower than that of any of the derivatives and considerably lower than those previously reported for ketoconazole, nystatin, and propiconazole.
Applying Location-Aware Computing for Electronic Commerce: Mobile Guide (1998)

Location-Aware applications for supporting the mobile user have proven significant relevance for future telecommunication and computing. Based on the state-of-the-art analysis and the business view, the paper evaluates the outcome of the labs and the requirements of commercial usage. A system architecture is proposed from the technical perspective. The required support of heterogeneous resources leads to the necessity of an adequate middleware platform. Merging data from different sources and constraints in the transmission and presentation capabilities of the mobile side require sophisticated media scaling and conversion capabilities. The envisaged service architecture leads finally to the discussion of the prototype developed on our Mobile Guide test-bed.
Toward Biocompatible Nuclear Hyperpolarization Using Signal Amplification by Reversible Exchange: Quantitative in Situ Spectroscopy and High-Field Imaging (2014)

Signal amplification by reversible exchange (SABRE) of a substrate and parahydrogen at a catalytic center promises to overcome the inherent insensitivity of magnetic resonance. In order to apply the new approach to biomedical applications, there is a need to develop experimental equipment, in situ quantification methods, and a biocompatible solvent. We present results detailing a low-field SABRE polarizer which provides well-controlled experimental conditions, defined spins manipulations, and which allows in situ detection of thermally polarized and hyperpolarized samples. We introduce a method for absolute quantification of hyperpolarization yield in situ by means of a thermally polarized reference. A maximum signal-to-noise ratio of ∼10(3) for 148 μmol of substance, a signal enhancement of 10(6) with respect to polarization transfer field of SABRE, or an absolute (1)H-polarization level of ≈10(-2) is achieved. In an important step toward biomedical application, we demonstrate (1)H in situ NMR as well as (1)H and (13)C high-field MRI using hyperpolarized pyridine (d3) and (13)C nicotinamide in pure and 11% ethanol in aqueous solution. Further increase of hyperpolarization yield, implications of in situ detection, and in vivo application are discussed.
Poly-γ-Glutamate Capsule-Degrading Enzyme Treatment Enhances Phagocytosis and Killing of EncapsulatedBacillus anthracis (2006)

The poly-gamma-d-glutamic acid capsule confers antiphagocytic properties on Bacillus anthracis and is essential for virulence. In this study, we showed that CapD, a gamma-polyglutamic acid depolymerase encoded on the B. anthracis capsule plasmid, degraded purified capsule and removed the capsule from the surface of anthrax bacilli. Treatment with CapD induced macrophage phagocytosis of encapsulated B. anthracis and enabled human neutrophils to kill encapsulated organisms. A second glutamylase, PghP, a gamma-polyglutamic acid hydrolase encoded by Bacillus subtilis bacteriophage PhiNIT1, had minimal activity in degrading B. anthracis capsule, no effect on macrophage phagocytosis, and only minimal enhancement of neutrophil killing. Thus, the levels of both phagocytosis and killing corresponded to the degree of enzyme-mediated capsule degradation. The use of enzymes to degrade the capsule and enable phagocytic killing of B. anthracis offers a new approach to the therapy of anthrax.
Optimizing loss functions through multi-variate taylor polynomial parameterization (2021)

Metalearning of deep neural network (DNN) architectures and hyperparameters has become an increasingly important area of research. Loss functions are a type of metaknowledge that is crucial to effective training of DNNs, however, their potential role in metalearning has not yet been fully explored. Whereas early work focused on genetic programming (GP) on tree representations, this paper proposes continuous CMA-ES optimization of multivariate Taylor polynomial parameterizations. This approach, TaylorGLO, makes it possible to represent and search useful loss functions more effectively. In MNIST, CIFAR-10, and SVHN benchmark tasks, TaylorGLO finds new loss functions that outperform the standard cross-entropy loss as well as novel loss functions previously discovered through GP, in fewer generations. These functions serve to regularize the learning task by discouraging overfitting to the labels, which is particularly useful in tasks where limited training data is available. The results thus demonstrate that loss function optimization is a productive new avenue for metalearning.
Boosting adaptive linear weak classifiers for online learning and tracking (2008)

Online boosting methods have recently been used successfully for tracking, background subtraction etc. Conventional online boosting algorithms emphasize on interchanging new weak classifiers/features to adapt with the change over time. We are proposing a new online boosting algorithm where the form of the weak classifiers themselves are modified to cope with scene changes. Instead of replacement, the parameters of the weak classifiers are altered in accordance with the new data subset presented to the online boosting process at each time step. Thus we may avoid altogether the issue of how many weak classifiers to be replaced to capture the change in the data or which efficient search algorithm to use for a fast retrieval of weak classifiers. A computationally efficient method has been used in this paper for the adaptation of linear weak classifiers. The proposed algorithm has been implemented to be used both as an online learning and a tracking method. We show quantitative and qualitative results on both UCI datasets and several video sequences to demonstrate improved performance of our algorithm.
Highly efficient gene replacements in Neurospora strains deficient for nonhomologous end-joining (2004)

Gene disruption and overexpression play central roles in the analysis of gene function. Homologous recombination is, in principle, the most efficient method of disrupting, modifying, or replacing a target gene. Although homologous integration of exogenous DNA into the genome occurs readily in Saccharomyces cerevisiae, it is rare in many other organisms. We identified and disrupted Neurospora crassa genes homologous to human KU70 and KU80, which encode proteins that function in nonhomologous end-joining of double-stranded DNA breaks. The resulting mutants, named mus-51 and mus-52, showed higher sensitivity to methyl methanesulfonate, ethyl methanesulfonate, and bleomycin than wild type, but not to UV, 4-nitroquinoline 1-oxide, camptothecin, or hydroxyurea. Vegetative growth, conidiation, and ascospore production in homozygous crosses were normal. The frequency of integration of exogenous DNA into homologous sequences of the genome in the KU disruption strains of N. crassa was compared with that in wild type, mei-3, and mus-11. In mei-3 and mus-11, which are defective in homologous recombination, none or few homologous integration events were observed under any conditions. When mtr target DNA with approximately 2-kb 5' and 3' flanking regions was used for transformation of the KU disruption strains, 100% of transformants exhibited integration at the homologous site, compared to 10 to 30% for a wild-type recipient. Similar results were obtained when the ad-3A gene was targeted for disruption. These results indicate that KU disruption strains are efficient recipients for gene targeting.
Artificial Molecular Clamp: A Novel Device for Synthetic Polymerases (2011)

Synthetic polymerases composed of a cyclodextrin (CD) dimer yield high-molecular-weight polymers of cyclic esters without using solvents and co-catalysts. One CD moiety is attached to the active site of a supramolecular catalyst and propagates the polymerization by serving as artificial molecular clamp (see picture). The other CD moiety initiates the ring-opening polymerization. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Antimicrobial peptides: therapeutic potential (2006)

A significant component of the innate immune system of a wide variety of animals and plants is arbitrated by cationic host defence peptides. In man, these peptides, in addition to exhibiting a direct antimicrobial activity, seems to provide a range of non-antimicrobial bioactivities related to defence, inflammation and wound healing. Despite the fact that such peptides have so far failed to reach the market, there are continued initiatives to advance such potential therapeutics to, and through, the clinic. The reasons behind such initiatives include: reduced manufacturing costs for peptides; allowing entry into therapeutic areas previously inaccessible due to cost; the continued identification of previously unknown bioactivities of such peptides; and the resurgence of interest in peptide therapeutics. As a result, clinical programmes based on cationic host defence peptides exist in the areas of infection, dermatology, cancer and inflammation. The probability of clinical success for host defence peptide-based therapeutics is on the rise as options for a wider range of clinical indications emerge.
Solutions able to reproduce in vivo surface‐structure changes in bioactive glass‐ceramic A‐W3 (1990)

High-strength bioactive glass-ceramic A-W was soaked in various acellular aqueous solutions different in ion concentrations and pH. After soaking for 7 and 30 days, surface structural changes of the glass-ceramic were investigated by means of Fourier transform infrared reflection spectroscopy, thin-film x-ray diffraction, and scanning electronmicroscopic observations, in comparison with in vivo surface structural changes. So-called Tris buffer solution, pure water buffered with trishydroxymethyl-aminomethane, which had been used by various workers as a "simulated body fluid," did not reproduce the in vivo surface structural changes, i.e., apatite formation on the surface. A solution, ion concentrations and pH of which are almost equal to those of the human blood plasma--i.e., Na+ 142.0, K+ 5.0, Mg2+ 1.5, Ca2+ 2.5, Cl- 148.8, HCO3- 4.2 and PO4(2-) 1.0 mM and buffered at pH 7.25 with the trishydroxymethyl-aminomethane--most precisely reproduced in vivo surface structure change. This shows that careful selection of simulated body fluid is required for in vitro experiments. The results also support the concept that the apatite phase on the surface of glass-ceramic A-W is formed by a chemical reaction of the glass-ceramic with the Ca2+, HPO4(2-), and OH- ions in the body fluid.
The Dynamic Expression of Extracellular Matrix in the Bovine Endometrium at Implantation. (2002)

Remodeling of uterine endometrial extracellular matrix (ECM) is pivotal to successful implantation and placentation, and has been well described in the rodents and humans. However, bovine endometrial ECM remodeling is still vaguely defined, especially at the time of implantation. Therefore, this study investigated the distribution of four ECMs namely, types I and IV collagen, laminin and fibronectin, from days 0 to 30 of gestation in bovine endometrium by immunofluorescence microscopy. A change in the distribution pattern of ECMs was evident by day 14 of gestation as features at this stage were clearly different from those of day 14 of the estrous cycle. The immunoreactivity of type I collagen, fibronectin and laminin decreased from day 14 of gestation and was obscured by day 24 of gestation. The type I collagen fibers formed were of thinner consistency than those of the estrous cycle and showed a coarser meshwork within the epithelium sites during the implantation period. In addition, the type IV collagen and laminin immunoreactivities of epithelial basement membrane also remarkably declined at exactly the same time. By day 30 of gestation, the four ECMs had regenerated with the formation of the placentome. In conclusion, this study reveals that remodeling of ECM is essential for the successful establishment of pregnancy in the bovine.
Side effects of antiglaucomatous drugs on the ocular surface (1996)

An increasing number of studies, both experimental and epidemiologic, have shown that filtering glaucoma surgery has progressively become less effective than initially described. Of a number of risk factors for failure, duration and number of antiglaucoma drugs before surgery seem to play a critical role, and high accumulated antiglaucoma topical treatments significantly reduce success rates. Histopathologic studies have confirmed that topically applied drugs may exert toxic effects to the corneoconjunctival surface and induce chronic infraclinical inflammation, as shown by the presence of immunologic changes and inflammatory infiltrates in multitreated eyes. The origin of topical inflammation has not yet been clearly determined, but benzalkonium chloride, which is used as a preservative in almost all antiglaucoma preparations, has shown strong evidence of toxicity to the ocular surface. A number of questions remain to be investigated, but suppression of preservatives from chronically applied drugs should be a critical issue in the near future.
B Cells and Antibody Play Critical Roles in the Immediate Defense of Disseminated Infection by West Nile Encephalitis Virus (2003)

West Nile virus (WNV) causes severe central nervous system (CNS) infection primarily in humans who are immunocompromised or elderly. In this study, we addressed the mechanism by which the immune system limits dissemination of WNV infection by infecting wild-type and immunodeficient inbred C57BL/6J mice with a low-passage WNV isolate from the recent epidemic in New York state. Wild-type mice replicated virus extraneuronally in the draining lymph nodes and spleen during the first 4 days of infection. Subsequently, virus spread to the spinal cord and the brain at virtually the same time. Congenic mice that were genetically deficient in B cells and antibody (microMT mice) developed increased CNS viral burdens and were vulnerable to lethal infection at low doses of virus. Notably, an approximately 500-fold difference in serum viral load was detected in micro MT mice as early as 4 days after infection, a point in the infection when low levels of neutralizing immunoglobulin M antibody were detected in wild-type mice. Passive transfer of heat-inactivated serum from infected and immune wild-type mice protected micro MT mice against morbidity and mortality. We conclude that antibodies and B cells play a critical early role in the defense against disseminated infection by WNV.
A 1 Mb EEPROM with MONOS memory cell for semiconductor disk application (1991)

A 1 Mb 5 V-only EEPROM (electrically erasable programmable ROM) with metal-oxide-nitride-oxide-semiconductor (MONOS) memory cells specifically designed for a semiconductor disk application is described. The memory has high endurance to write/erase cycles and a relatively low programming voltage of +or-9 V. These advantages result from the structure and the characteristics of the MONOS memory cell. A newly developed dual-gate-type MONOS memory cell has a small unit cell area of 18.4 mu m/sup 2/ with 1.2 mu m lithography, and the die size of the fabricated chip is 5.3 mm*6.3 mm. A new programming scheme called multiblock erase solved the problem of slow programming speed. A programming speed of up to 1.1 mu s/B equivalent (140 ms/chip) was obtained.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Medical Device Accidents With Illustrative Cases (1998)

Medical device accidents: with illustrative cases , Medical device accidents: with illustrative cases , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی