gebhart/patrepeval huggingface dataset:
Targeted Release of Tobramycin from a pH-Responsive Grafted Bilayer Challenged with S. aureus (2015)

A stimuli-responsive, controlled release bilayer for the prevention of bacterial infection on biomaterials is presented. Drug release is locally controlled by the pH-responsiveness of the bilayer, comprised of an inner poly(acrylic acid) (PAA) monolayer grafted to a biomaterial and cross-linked with an outer chitosan (CH) brush. Tobramycin (TOB) is loaded in the inner PAA in part to minimize bacteria resistance. Because biofilm formation causes a decrease in local pH, TOB is released from PAA and permeates through the CH, which is in contact with the biofilm. Antibiotic capacity is controlled by the PAA thickness, which depends on PAA brush length and the extent of cross-linking between CH and PAA at the bilayer interface. This TOB-loaded, pH-responsive bilayer exhibits significantly enhanced antibacterial activity relative to controls.
Cellular senescence in naevi and immortalisation in melanoma: a role for p16? (2006)

Cellular senescence, the irreversible proliferative arrest seen in somatic cells after a limited number of divisions, is considered a crucial barrier to cancer, but direct evidence for this in vivo was lacking until recently. The best-known form of human cell senescence is attributed to telomere shortening and a DNA-damage response through p53 and p21. There is also a more rapid form of senescence, dependent on the p16-retinoblastoma pathway. p16 (CDKN2A) is a known melanoma susceptibility gene. Here, we use retrovirally mediated gene transfer to confirm that the normal form of senescence in cultured human melanocytes involves p16, since disruption of the p16/retinoblastoma pathway is required as well as telomerase activation for immortalisation. Expression (immunostaining) patterns of senescence mediators and markers in melanocytic lesions provide strong evidence that cell senescence occurs in benign melanocytic naevi (moles) in vivo and does not involve p53 or p21 upregulation, although p16 is widely expressed. In comparison, dysplastic naevi and early (radial growth-phase, RGP) melanomas show less p16 and some p53 and p21 immunostaining. All RGP melanomas expressed p21, suggesting areas of p53-mediated senescence, while most areas of advanced (vertical growth-phase) melanomas lacked both p16 and p21, implying escape from both forms of senescence (immortalisation). Moreover, nuclear p16 but not p21 expression can be induced in human melanocytes by oncogenic BRAF, as found in around 80% of naevi. We conclude that cell senescence can form a barrier to melanoma development. This also provides a potential explanation of why p16 is a melanoma suppressor gene.
Detection of cell free Epstein–Barr virus DNA in sera from patients with nasopharyngeal carcinoma (2002)

This study demonstrated that, by using a 50-cycle PCR-based approach, high sensitivity and high negative predictive value for detecting recurrent disease can be obtained from the detection of the cell free EBV genome in sera from patients with NPC. The 50-cycle PCR analysis, therefore, may provide a simple, clinically useful adjuvant method for monitoring patients with NPC.
Overexpression of glutamine synthetase is associated with beta-catenin-mutations in mouse liver tumors during promotion of hepatocarcinogenesis by phenobarbital. (2002)

Phenobarbital (PB) is an antiepileptic drug that promotes hepatocarcinogenesis in rodents when administered subsequent to an initiating carcinogen like N-nitrosodiethylamine (DEN). In the mouse, the promotional effect of PB on liver tumor development results from a selective stimulation of clonal outgrowth of hepatocytes harboring activating mutations in the beta-catenin gene. Because glutamine synthetase (GS) has recently been shown to be a putative transcriptional target of beta-catenin, expression of GS during PB-mediated promotion of mouse hepatocarcinogenesis was investigated. Preneoplastic and neoplastic liver lesions were induced in 6-week-old male mice by a single injection of 90 micro g/g body weight of DEN, and groups of mice were subsequently kept on PB-containing (0.05%) or control diet for 39 weeks. In PB-treated mice, 46 of 51 lesions ( approximately 90%) were GS-positive in contrast to only 16 of 46 ( approximately 35%) in mice not treated with PB. Approximately 33% of liver was occupied by neoplastic tissue in PB-treated mice, of which >80% was GS positive. By contrast, only approximately 3.5% of liver consisted of neoplastic tissue in mice treated with DEN only, and approximately 25% of this was GS positive. We have previously shown that beta-catenin mutations are present in approximately 80% of liver tumors from PB-treated mice but are absent in liver tumors from mice treated with DEN only. By analyzing a panel of larger liver tumors, we now observed that tumors harboring beta-catenin mutations were GS positive, whereas tumors without beta-catenin mutations were GS negative. Similarly, tumors from an additional mouse carcinogenicity experiment where PB inhibited rather than promoted hepatocarcinogenesis were mostly GS negative. These data suggest that promotion of hepatocarcinogenesis by PB confers beta-catenin-mutated tumor cells with a selective advantage by up-regulation of GS expression.
Kinetics of duplex formation for individual DNA strands within a single protein nanopore (2001)

A single oligonucleotide was covalently attached to a genetically engineered subunit of the heptameric protein pore, alpha-hemolysin, to allow DNA duplex formation inside the pore lumen. Single-channel current recording was used to study the properties of the modified pore. On addition of an oligonucleotide 8 bases in length and with a sequence complementary to the tethered DNA strand, current blockades with durations of hundreds of milliseconds occurred, representing hybridization events of individual oligonucleotides to the tethered DNA strand. Kinetic constants for DNA duplex formation at the single molecule level were derived and found to be consistent with established literature values for macroscopic duplex formation. The resultant equilibrium constant for duplex formation in the nanopore was found to be close to the experimentally derived constant for duplex formation in solution. A good agreement between the equilibrium constants for duplex formation in the nanopore and in solution was also found for two other oligonucleotide pairs. In addition, the nanopore recordings revealed details of the kinetics difficult to obtain by conventional methods, like surface plasmon resonance, which measure ensemble properties. By investigating the temperature dependence of DNA duplex formation at the single molecule level, the standard enthalpy and entropy of the interaction could be obtained.
Overcoming multidrug resistance of small-molecule therapeutics through conjugation with releasable octaarginine transporters (2008)

Many cancer therapeutic agents elicit resistance that renders them ineffective and often produces cross-resistance to other drugs. One of the most common mechanisms of resistance involves P-glycoprotein (Pgp)-mediated drug efflux. To address this problem, new agents have been sought that are less prone to inducing resistance and less likely to serve as substrates for Pgp efflux. An alternative to this approach is to deliver established agents as molecular transporter conjugates into cells through a mechanism that circumvents Pgp-mediated efflux and allows for release of free drug only after cell entry. Here we report that the widely used chemotherapeutic agent Taxol, ineffective against Taxol-resistant human ovarian cancer cell lines, can be incorporated into a releasable octaarginine conjugate that is effective against the same Taxol-resistant cell lines. It is significant that the ability of the Taxol conjugates to overcome Taxol resistance is observed both in cell culture and in animal models of ovarian cancer. The generality and mechanistic basis for this effect were also explored with coelenterazine, a Pgp substrate. Although coelenterazine itself does not enter cells because of Pgp efflux, its octaarginine conjugate does so readily. This approach shows generality for overcoming the multidrug resistance elicited by small-molecule cancer chemotherapeutics and could improve the prognosis for many patients with cancer and fundamentally alter search strategies for novel therapeutic agents that are effective against resistant disease.
Safety and Feasibility of Liver-Directed Ex Vivo Gene Therapy for Homozygous Familial Hypercholesterolemia (1996)

Liver-directed ex vivo gene therapy can be accomplished safely in humans and is appropriate for selected patients.
Age and the Cardiovascular System (1992)

DESPITE the decline in rates of mortality due to heart disease during the past two decades, cardiovascular disease remains the most frequent single cause of death among persons over 65 years of age.1 2 3 It also accounts for a major and growing proportion of hospitalizations and health care costs and is a leading cause of morbidity among older people.2 , 3 In this review, I shall consider age-associated changes that may influence the diagnosis and treatment of cardiac disease in older patients and aspects of evaluation and management that are different for older patients than for younger adults.Morphologic ChangesThe MyocardiumMany . . .
Removal of proteoglycans from the surface of defects in articular cartilage transiently enhances coverage by repair cells (1998)

Lesions within the articular cartilage layer of synovial joints do not heal spontaneously. Some repair cells may appear, but their failure to become established may be related to problems of adhesion to proteoglycan-rich surfaces. We therefore investigated whether controlled enzymatic degradation of surface proteoglycan molecules to a depth of about 1 microm, using chondroitinase ABC, would improve coverage by repair cells. We created superficial lesions (1.0 x 0.2 x 5 mm) in the articular cartilage of mature rabbit knees and treated the surfaces with 1 U/ml of chondroitinase ABC for four minutes. The defects were studied by histomorphometry and electron microscopy at one, three and six months. At one month, untreated lesions were covered to a mean extent of 28% by repair cells; this was enhanced to a mean of 53% after enzyme treatment. By three months, the mean coverage of both control and chondroitinase-ABC-treated defects had diminished dramatically to 0.2% and 13%, respectively, but at six months both untreated and treated lesions had a similar coverage of about 30%, not significantly different from that achieved in untreated knees at one month. These findings suggest that, with time, chondrocytes near the surface of the defect may compensate for the loss of proteoglycans produced by enzyme treatment, thereby restoring the inhibitory properties of the matrix as regards cell adhesion. This supposition was confirmed by electron microscopy. Our results have an important bearing on attempts made to induce healing responses by transplanting chondrogenic cells or by applying growth factors.
Incremental learning methods with retrieving of interfered patterns (1999)

There are many cases that a neural-network-based system must memorize some new patterns incrementally. However, if the network learns the new patterns only by referring to them, it probably forgets old memorized patterns, since parameters in the network usually correlate not only to the old memories but also to the new patterns. A certain way to avoid the loss of memories is to learn the new patterns with all memorized patterns. It needs, however, a large computational power. To solve this problem, we propose incremental learning methods with retrieving interfered patterns (ILRI). In these methods, the system employs a modified version of a resource allocating network (RAN) which is one variation of a generalized radial basis function (GRBF). In ILRI, the RAN learns new patterns with a relearning of a few number of retrieved past patterns that are interfered with the incremental learning. In this paper, we construct ILRI in two steps. In the first step, we construct a system which searches the interfered patterns from past input patterns stored in a database. In the second step, we improve the first system in such a way that the system does not need the database. In this case, the system regenerates the input patterns approximately in a random manner. The simulation results show that these two systems have almost the same ability, and the generalization ability is higher than other similar systems using neural networks and k-nearest neighbors.
High expression of a specific T-cell receptor γ transcript in epithelial cells of the prostate (1999)

We have identified expression of T-cell receptor gamma chain (TCRgamma) mRNA in human prostate and have shown that it originates from epithelial cells of the prostate and not from infiltrating T-lymphocytes. In contrast, the T-cell receptor delta chain (TCRdelta) gene is silent in human prostate. The major TCRgamma transcript in prostate has a different size than the transcript expressed in thymus, spleen, and blood leukocytes. It is expressed in normal prostate epithelium, adenocarcinoma of the prostate, and the prostatic adenocarcinoma cell line LNCaP. The RNA originates from an unrearranged TCRgamma locus, and it is initiated within the intronic sequence directly upstream of the Jgamma1.2 gene segment. The prostate-specific TCRgamma transcript consists of the Jgamma1.2 and Cgamma1 gene segments, and it has an untranslated sequence including a polyadenylation signal and poly(A) sequence at the 3'end. The finding that prostate epithelial cells express a high level of a transcript from a gene that was thought to by exclusively expressed by T-lymphocytes is highly unexpected.
Successive Construction of Cellulase Hyperproducers of Trichoderma Using Hyperpolyploids (2000)

When the swollen conidia of Trichoderma reesei QM 6a are treated with 0.1% (w/v) colchicine solution, huge autopolyploid nuclei can be formed in those swollen conidia. When a mycelial mat derived from such a conidum is treated with a haploidizing reagent, benomyl, many fan-shaped sectors are produced from the colony, and cellulase hyperproducers are selected from conidia on the colony. When colchicine and benomyl treatments are repeated on cellulase hyperproducers, new hyperproducers can be constructed successively and systematically. Moreover, when conidia derived from autopolyp loids are treated with ethylmethanesulf onate solution, another type of cellulase hyperproducers (polyploids) can be obtained.
Inhibition of metastasis of lewis lung carcinoma by a synthetic peptide within growth factor‐like domain of urokinase in the experimental and spontaneous metastasis model (1994)

Four synthetic peptides (residues 20-30 and 17-34) within the growth factor-like domain (GFD) of murine and human urokinase-type plasminogen activator (uPA) were examined to determine whether they inhibit production of experimental and spontaneous lung metastasis by murine Lewis lung carcinoma (3LL) cells. In an in vivo experimental metastasis assay, which determines mainly the later steps of the metastatic migration process (extravasation from the bloodstream and then growth into pulmonary tumor), none of the peptides introduced by i.v. single co-injection into syngeneic C57B1/6 mice inhibited pulmonary metastasis, when 3LL cells were pre-incubated with the peptides followed by i.v. co-injection of the peptide and cells. In addition, none of the peptides, when injected i.p. daily for 7 days after i.v. tumor cell inoculation, reduced the number of lung tumor colonies. In a second in vivo assay that measures metastasis from a primary tumor (spontaneous metastasis model), multiple i.p. injections of the mouse peptide 17-34 for 7 days after s.c. tumor cell inoculation significantly inhibited metastatic lung tumor colonization in a dose-dependent manner, whereas human peptide 17-34 had no effect. Mouse and human peptide 20-30 had no effect either. The inhibition of lung metastasis was not due to direct antitumor effects of mouse peptide 17-34. Our results indicate that occupation of uPA receptors on 3LL cells by the enzymatically inactive mouse peptide 17-34 or prevention of rebinding of uPA synthesized by tumor cells to their receptor specifically reduced tumor cell invasion and formation of metastasis and that uPA may regulate more efficiently the mechanism involved in the entry of tumor cells into vascular circulation than extravasation during the metastatic process.
Transplantation of Engineered Chimeric Liver With Autologous Hepatocytes and Xenobiotic Scaffold (2012)

This is the first report showing that engineered CLs have potential as alternative grafts to replace the use of grafts from human donors.
Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration (2015)

Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.
Image processing system for traffic measurement (2002)

The authors provide details of the system architecture and algorithm of an image processing system applied to traffic measurement. This traffic measurement system is based on an image processing technique for video pictures. This development has achieved good cost-performance systems due to falling costs for image processing hardware with powerful computation. The authors have developed some operational systems for practical use, such as a traffic flow measurement system, an automatic stopped vehicle detection system, an automatic license plate reader for measurement of travel time, and an illegal parking monitoring system. The customized hardware and algorithm which are suitable for each system are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
RNA-Seq gene expression estimation with read mapping uncertainty (2009)

We present a generative statistical model and associated inference methods that handle read mapping uncertainty in a principled manner. Through simulations parameterized by real RNA-Seq data, we show that our method is more accurate than previous methods. Our improved accuracy is the result of handling read mapping uncertainty with a statistical model and the estimation of gene expression levels as the sum of isoform expression levels. Unlike previous methods, our method is capable of modeling non-uniform read distributions. Simulations with our method indicate that a read length of 20-25 bases is optimal for gene-level expression estimation from mouse and maize RNA-Seq data when sequencing throughput is fixed.
A fatal overdose of transdermally administered fentanyl (1998)

We present a case of fentanyl overdose via mucous membrane absorption. A 31-year-old man presented to the emergency department in respiratory arrest. At intubation, a Duragesic transdermal patch (75 micrograms/h) was recovered from the buccal cavity. A second fentanyl transdermal patch (75 micrograms/h) was noted on the right lateral aspect of the thigh. Postmortem blood evaluation returned a venous fentanyl level of 17.2 micrograms/L. The therapeutic range for analgesic use is 1 microgram/L to 3 micrograms/L. Drug screens were positive for benzodiazepines and cocaine. Mass spectrophotometry/gas chromatography was used to determine fentanyl levels and to confirm drug screen results. Case history, findings at intubation, and high fentanyl blood concentration suggest the cause of respiratory arrest and death was fentanyl overdose.
Transport to the cell surface of a peptide sequence attached to the truncated C terminus of an N-terminally anchored integral membrane protein. (1988)

Attempts to construct hybrid proteins that are transported to the plasma membrane are frequently unsuccessful because of perturbations in polypeptide folding. In seeking to minimize this problem, we have used the less common type of integral membrane protein, which has an uncleaved signal-anchor domain and an extracellular carboxyl portion, to transport a peptide sequence of interest to the cell surface. A set of plasmids was constructed that contained the gene encoding respiratory syncytial virus glycoprotein G (RSVG) interrupted immediately after one of several proline codons by a synthetic sequence containing unique restriction endonuclease sites and a stop codon. The shortened RSVG gene was flanked by vaccinia virus DNA to permit cloning and expression in a vaccinia virus vector. An open reading frame encoding four copies of the immunodominant repeating epitope of the circumsporozoite protein of Plasmodium falciparum was inserted into the tails of the truncated RSVG genes. Recombinant vaccinia viruses were isolated and shown to express hybrid proteins that reacted with a monoclonal antibody directed to the repeating circumsporozoite epitope. Moreover, immunofluorescence studies indicated that the peptide was on the external cell surface and available to react with antibodies. Expression of the hybrid protein also occurred in rabbits inoculated with the live recombinant vaccinia virus, as demonstrated by the generation of antibodies that bound to P. falciparum sporozoites in vitro.
Making a Long Video Short: Dynamic Video Synopsis (2006)

The power of video over still images is the ability to represent dynamic activities. But video browsing and retrieval are inconvenient due to inherent spatio-temporal redundancies, where some time intervals may have no activity, or have activities that occur in a small image region. Video synopsis aims to provide a compact video representation, while preserving the essential activities of the original video. We present dynamic video synopsis, where most of the activity in the video is condensed by simultaneously showing several actions, even when they originally occurred at different times. For example, we can create a "stroboscopic movie", where multiple dynamic instances of a moving object are played simultaneously. This is an extension of the still stroboscopic picture. Previous approaches for video abstraction addressed mostly the temporal redundancy by selecting representative key-frames or time intervals. In dynamic video synopsis the activity is shifted into a significantly shorter period, in which the activity is much denser. Video examples can be found online in http://www.vision.huji.ac.il/synopsis