gebhart/patrepeval huggingface dataset:
PKC412--a protein kinase inhibitor with a broad therapeutic potential. (2000)

The staurosporine derivative PKC412 was originally identified as an inhibitor of protein kinase C (PKC) and subsequently shown to inhibit other kinases including the kinase insert domain receptor (KDR) (vascular endothelial growth factor receptor, VEGF-R2), the receptor of platelet-derived growth factor, and the receptor for the stem cell factor, c-kit. PKC412 showed a broad antiproliferative activity against various tumor and normal cell lines in vitro, and was able to reverse the Pgp-mediated multidrug resistance of tumor cells in vitro. Exposure of cells to PKC412 resulted in a dose-dependent increase in the G2/M phase of the cell cycle concomitant with increased polyploidy, apoptosis and enhanced sensitivity to ionizing radiation. PKC412 displayed a potent antitumor activity as single agent and was able to potentiate the antitumor activity of some of the clinically used cytotoxins (Taxol and doxorubicin) in vivo. The combined treatment of PKC412 with loco-regional ionizing irradiation showed significant antitumor activity against tumors which are resistant to both ionizing radiation and chemotherapeutic agents (dysfunctional p53). The finding that PKC412 is an inhibitor of the VEGF-mediated cellular signaling via inhibition of KDR and PKC in vitro is consistent with the in vivo inhibition of VEGF-dependent angiogenesis in a growth factor implant model. Orally administered PKC412 also strongly inhibited retinal neovascularization as well as laser-induced choroidal neovascularization in murine models. In summary, PKC412 may suppress tumor growth by inhibiting tumor angiogenesis in addition to directly-inhibiting tumor cell proliferation via its effects on PKC and/or other protein kinases. PKC412 is currently in Phase I clinical trials for treatment of advanced cancer as well as for the treatment of ischemic retinopathy.
Production of High-Titer Epstein-Barr Virus Recombinants Derived from Akata Cells by Using a Bacterial Artificial Chromosome System (2004)

An Epstein-Barr virus (EBV) genome in Burkitt's lymphoma-derived cell line Akata was cloned into a bacterial artificial chromosome (BAC) vector. The BAC clone, designated AK-BAC, was rapidly and precisely modified by means of efficient homologous recombination in Escherichia coli. This system was used to produce recombinant EBVs with transgenes. An expression cassette of green fluorescent protein (GFP) was inserted into AK-BAC, and the resultant BAC clone, AK-BAC-GFP, was transfected into Akata cells. We found that transfected BAC plasmids efficiently formed episomes in EBV-positive Akata cells. Mixtures of wild-type and AK-BAC-GFP viruses were then produced and used to infect EBV-negative Akata cells. We obtained cell clones that harbored only AK-BAC-GFP but no wild-type episome. These cell clones produced infectious viruses after stimulating virus production, and the recombinant viruses of AK-BAC-GFP efficiently immortalized primary B lymphocytes. We further revised the method so that any kind of cDNA could be rapidly inserted into the unique I-PpoI site that had been artificially introduced into AK-BAC. The AK-BAC system will have a broad range of applications, such as genetic analyses of various viral gene products and development of viral vectors for human gene therapy.
En-face optical coherence imaging for three-dimensional microscopy (2002)

En-face optical coherence tomography (OCT) employing parallel heterodyne detection technique is demonstrated for three-dimensional microscopy. To enable the use of commercially available CCD cameras as two-dimensional heterodyne detector arrays in OCT imaging, a frequency synchronous detection method is employed. Depth-resolved, full-field images are acquired at 30 Hz video-rate without lateral scanning.
Livestock's long shadow: environmental issues and options. (2006)

Présentation de l'éditeur : This report aims to assess the full impact of the livestock sector on environmental problems, along with potential technical and policy approaches to mitigation. The assessment takes into account direct impacts, along with the impacts of feed crop agriculture required for livestock production. The livestock sector emerges as one of the top two or three most significant contributors to the most serious environmental problems, at every scale from local to global. The findings of this report suggest that it should be a major policy focus when dealing with problems of land degradation, climate change and air pollution, water shortage and water pollution, and loss of biodiversity. Livestock's contribution to environmental problems is on a massive scale and its potential contribution to their solution is equally large. The impact is so significant that it needs to be addressed with urgency. Major reductions in impact could be achieved at reasonable cost
LEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8 (2000)

Liver-expressed chemokine (LEC) is an unusually large CC chemokine, which is also known as LMC, HCC-4, NCC-4, and CCL16. Previously, LEC was shown to induce leukocyte migration but the responsible signaling receptors were not characterized. We report chemotaxis and competitive binding studies that show LEC binds to and activates CCR1 and CCR8 transfected HEK-293 cells. LEC induced maximal migration of CCR1 and CCR8 transfected cells at 89.3 nmol/L and cell adhesion at 5.6 nmol/L. The molar concentration of LEC required to induce maximum cell migration is 20- to 200-fold greater than that required for RANTES or I309, respectively. All 3 chemokines induced maximal static adhesion at 5 to 7 nmol/L. A neutralizing polyclonal antibody to LEC was developed to demonstrate that the unusually high concentration of LEC required to induce chemotaxis was a property of LEC and not as a result of an irrelevant protein contamination. This study suggests that LEC may be a more effective inducer of cell adhesion than cell migration.
Dual exon skipping in myostatin and dystrophin for Duchenne muscular dystrophy (2011)

We conclude that two AONs can be used to target two different genes, MSTN and DMD, in a straightforward manner. Targeting multiple ligands of TGF-beta family will be more promising as adjuvant therapies for DMD.
Pyruvate formate-lyase mechanism involving the protein-based glycyl radical (1993)

Conference Article| August 01 1993 Pyruvate formate-lyase mechanism involving the protein-based glycyl radical J. Knappe; J. Knappe 1Institut für Biologische Chemie, Universität Heidelberg, D-6900 Heidelberg, Germany Search for other works by this author on: This Site PubMed Google Scholar S. Elbert; S. Elbert 1Institut für Biologische Chemie, Universität Heidelberg, D-6900 Heidelberg, Germany Search for other works by this author on: This Site PubMed Google Scholar M. Frey; M. Frey 1Institut für Biologische Chemie, Universität Heidelberg, D-6900 Heidelberg, Germany Search for other works by this author on: This Site PubMed Google Scholar A. F. V. Wagner A. F. V. Wagner 1Institut für Biologische Chemie, Universität Heidelberg, D-6900 Heidelberg, Germany Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1993) 21 (3): 731–734. https://doi.org/10.1042/bst0210731 Article history Received: April 01 1993 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation J. Knappe, S. Elbert, M. Frey, A. F. V. Wagner; Pyruvate formate-lyase mechanism involving the protein-based glycyl radical. Biochem Soc Trans 1 August 1993; 21 (3): 731–734. doi: https://doi.org/10.1042/bst0210731 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: AdoMet, adenosyl methionine, E, inactive, non-radical form of PFL, E*, radical form of PFL, PFL, pyruvate formate-lyase This content is only available as a PDF. © 1993 Biochemical Society1993 Article PDF first page preview Close Modal You do not currently have access to this content.
Catalytic Asymmetric Epoxidation of α,β-Unsaturated Esters Using an Yttrium-Biphenyldiol Complex (2005)

We succeeded in a catalytic asymmetric epoxidation reaction of alpha,beta-unsaturated esters via a conjugate addition of an oxidant using 2-10 mol % of the yttirium-chiral biphenyldiol catalyst. A variety of substrates with beta-aryl and beta-alkyl substituents were epoxidized efficiently, yielding the corresponding alpha,beta-epoxy esters in up to 97% yield and 99% ee.
Rheumatoid arthritis and the complement system (2007)

Complement activation contributes to a pathological process in a number of autoimmune and inflammatory diseases, including rheumatoid arthritis (RA). In this review we summarize current knowledge of complement contribution to RA, based on clinical observations in patients and in vivo animal models, as well as on experiments in vitro aiming at elucidation of underlying molecular mechanisms. There is strong evidence that both the classical and the alternative pathways of complement are pathologically activated during RA as well as in animal models for RA. The classical pathway can be initiated by several triggers present in the inflamed joint such as deposited autoantibodies, dying cells, and exposed cartilage proteins such as fibromodulin. B cells producing autoantibodies, which in turn form immune complexes, contribute to RA pathogenesis partly via activation of complement. It appears that anaphylatoxin C5a is the main product of complement activation responsible for tissue damage in RA although deposition of membrane attack complex as well as opsonization with fragments of C3b are also important. Success of complement inhibition in the experimental models described so far encourages novel therapeutic approaches to the treatment of human RA.
Contribution of Human FcÎ³Rs to Disease with Evidence from Human Polymorphisms and Transgenic Animal Studies (2014)

The biological activities of human IgG antibodies predominantly rely on a family of receptors for the Fc portion of IgG, FcγRs: FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, FcγRIIIB, FcRL5, FcRn, and TRIM21. All FcγRs bind IgG at the cell surface, except FcRn and TRIM21 that bind IgG once internalized. The affinity of FcγRs for IgG is determined by polymorphisms of human FcγRs and ranges from 2 × 10(4) to 8 × 10(7) M(-1). The biological functions of FcγRs extend from cellular activation or inhibition, IgG-internalization/endocytosis/phagocytosis to IgG transport and recycling. This review focuses on human FcγRs and intends to present an overview of the current understanding of how these receptors may contribute to various pathologies. It will define FcγRs and their polymorphic variants, their affinity for human IgG subclasses, and review the associations found between FcγR polymorphisms and human pathologies. It will also describe the human FcγR-transgenic mice that have been used to study the role of these receptors in autoimmune, inflammatory, and allergic disease models.
Nerve growth factor induces mechanical allodynia associated with novel A fibre-evoked spinal reflex activity and enhanced neurokinin-1 receptor activation in the rat (1995)

A single dose of nerve growth factor (NGF, 1 microgram/g, i.p.) administered to rats aged between postnatal days (PND) 12 and 14 resulted in a behavioural hypersensitivity of the hindlimb flexion withdrawal reflex to mechanical stimuli which developed 2 h after NGF and remained significant for 24 h. Heat hyperalgesia occurred some 4 h following NGF injection and lasted for 24 h. Isolated spinal cords were prepared from animals treated with NGF and were maintained in vitro for physiological and pharmacological analysis of lumbar spinal reflex activity. Repetitive, low-frequency group I/II A beta-fibre stimulation evoked a novel wind-up response after NGF injection similar to that produced by C-fiber group III/IV stimulation in normal animals. The neurokinin-1 (NK1) receptor antagonist RP67580 reduced the C fiber-evoked responses following NGF treatment but not in naive preparations. The novel A beta fiber-evoked wind-up response was also reduced by RP67580. The NGF-induced changes in NK1 receptor responses occurred in the absence of any detectable changes in either spinal cord NK1 receptor dose-response relationships or NK1 receptor mRNA levels. These findings are likely to be related to the behavioural allodynia observed in the present study and to central excitability changes observed after chronic inflammation where NGF levels are increased.
Multislice double inversion pulse sequence for efficient black‐blood MRI (2002)

Over the last several years there has been a rapidly growing interest in high-resolution MRI of the vascular wall to assess the extent of atherosclerotic lesions. Vessels of particular clinical relevance are the carotid and coronary arteries. Currently, the preferred imaging sequence for these studies is a "black-blood" technique based on the double-inversion scheme to null the blood signal. A critical drawback of the black-blood technique, however, has been its single-slice nature, as there is only one point in time during the recovery of the blood magnetization from inversion at which the signal is completely nulled. Consequently, the total scan time can become prohibitively long, particularly when an imaging protocol includes several series of these datasets. In this work, a multiple-slice double-inversion technique is described that can reduce the scan time by a factor of two or more. It is demonstrated in vivo with examples from carotid and coronary arteries that one can acquire multiple slices with sufficient nulling of blood, following a single set of inversion pulses.
Synthesis of cis -Bicyclo[4,4,0]deca-2,8-dien-4-one (1973)

A synthesis of cis-bicyclo[4,4,0]deca-2,8-dien-4-one is described, starting from the Diels-Alder adduct of methoxybenzo-1,4-quinone and 1,3-butadiene.
Lumbar Laminectomy Alone or With Instrumented or Noninstrumented Arthrodesis in Degenerative Lumbar Spinal Stenosis (1997)

Findings were limited by the small number of participating surgeons, modest sample size that produced P values of borderline significance, and nonrandomized design. With these caveats in mind, the authors conclude: (1) The individual surgeon was a more important correlate of the decision to perform arthrodesis than clinical variables such as spondylolisthesis. (2) Noninstrumented arthrodesis resulted in superior relief of back pain after 6 and 24 months. (3) Instrumented arthrodesis was the most costly option. These results highlight the need for randomized controlled trials and cost effectiveness analyses of lumbar arthrodesis and instrumentation in patients with degenerative lumbar spinal stenosis.
The Human Agonistic CD40 Antibody ADC-1013 Eradicates Bladder Tumors and Generates T-cell–Dependent Tumor Immunity (2014)

Our data demonstrate that ADC-1013 induces long-lasting antitumor responses and immunologic memory mediated by CD40 stimulation. To the best of our knowledge, ADC-1013 represents the first immunomodulatory antibody developed for local immunotherapy of cancer.
GAN-based synthetic brain PET image generation (2020)

In recent days, deep learning technologies have achieved tremendous success in computer vision-related tasks with the help of large-scale annotated dataset. Obtaining such dataset for medical image analysis is very challenging. Working with the limited dataset and small amount of annotated samples makes it difficult to develop a robust automated disease diagnosis model. We propose a novel approach to generate synthetic medical images using generative adversarial networks (GANs). Our proposed model can create brain PET images for three different stages of Alzheimer's disease-normal control (NC), mild cognitive impairment (MCI), and Alzheimer's disease (AD).
PAM recognition by miniature CRISPR nucleases triggers programmable double-stranded DNA target cleavage (2019)

ABSTRACT In recent years, CRISPR-associated (Cas) nucleases have revolutionized the genome editing field. Being guided by an RNA to cleave double-stranded (ds) DNA targets near a short sequence termed a protospacer adjacent motif (PAM), Cas9 and Cas12 offer unprecedented flexibility, however, more compact versions would simplify delivery and extend application. Here, we present a collection of 10 exceptionally compact (422-603 amino acids) CRISPR-Cas nucleases that recognize and cleave dsDNA in PAM dependent manner. Categorized as class 2 type V-F they come from the Cas14 family and distantly related type V-U3 Cas proteins found in bacteria. Using biochemical methods, we demonstrate that a 5’ T- or C-rich PAM sequence triggers double stranded (ds) DNA target cleavage. Based on this discovery, we evaluated whether they can protect against invading dsDNA in E. coli and find that some but not all can. Altogether, our findings show that miniature Cas nucleases are functional CRISPR-Cas defense systems and have the potential to be harnessed as programmable nucleases for genome editing.
Combined Screening With Ultrasound and Mammography vs Mammography Alone in Women at Elevated Risk of Breast Cancer (2008)

clinicaltrials.gov Identifier: NCT00072501.
Expansion of rat oligodendrocyte progenitors into proliferative ?oligospheres? that retain differentiation potential (1996)

The limited availability of enriched populations of oligodendroglial progenitors has impeded the exploration of the complex spatio-temporal mechanisms which dictate the chemical "language" of their biology. We have developed a technique to prepare homotypic aggregates of oligodendrocyte progenitors called "oligospheres." These were obtained using various approaches (sieving, Percoll gradient separation and differential adhesion) to purify oligodendroglial progenitors from newborn rat brain. Culturing cells in a mixture of N1 defined medium and conditioned medium from the B104 neuronal cell line in the absence of adhesive substrate allowed to expand routinely and extensively for several months, the oligodendrocyte progenitor population. Under these conditions, the resulting population consisted of 98% GD3-positive/GFAP-negative cells. After dissociation and plating on polyornithine coated substrates, in the presence of low (2%) or high (20%) serum, oligosphere-derived oligodendrocyte progenitors were induced to differentiate into GalC-positive oligodendrocytes or GFAP-positive astrocytes, respectively. When transplanted into the newborn shiverer mouse brain, oligospheres were able to provide a focal reservoir of migrating and myelinating cells. Oligospheres are thus ideal tools for exploring the biological and molecular events of the oligodendrocyte lineage both in vitro and in vivo.
Comparison of a generic and a disease-specific measure of pain and physical function after knee replacement surgery. (1995)

Generic and disease-specific health status instruments are commonly used to assess patients' outcomes. The hypothesis that they measure distinct but complementary aspects of patients' quality of life was tested using a sample of patients aged 67 to 99 years who had undergone knee replacement surgery 2 to 7 years previously. Patients' scores on a generic health-related quality-of-life (HRQOL) measure, the SF-36, were compared to those of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index; the WOMAC was developed specifically for patients with lower extremity arthritis, whereas the SF-36 is aimed at all conditions. A stratified sample of 1,750 Medicare beneficiaries was surveyed and an overall response rate of 80.3% achieved, resulting in 1,193 usable surveys (after adjustment for ineligible, incapacitated, and deceased individuals). The distribution of scores on the three dimensions common to both instruments (i.e., pain, physical function, and overall score) showed consistently higher scores on the WOMAC, on a scale of 0 (worst) to 100 (best), than on the SF-36, indicating less disability from arthritis than from other conditions after knee surgery in this elderly population. Statistically significant differences in the number of people with perfectly healthy scores were detected between the instruments; with regard to pain, 32.2% of the sample reported no pain due to arthritis on the WOMAC, compared with only 13.6% reporting no pain due to any conditions on the SF-36. The figures for physical function and overall score were 9.6% versus 1.4%, and 6.9% versus 0.2%, respectively. Examination for discriminant validity showed that the scores on the two scales followed hypothesized patterns: the WOMAC discriminated better among subjects with varying severity of knee problems, whereas the SF-36 discriminated better among subjects with varying levels of self-reported health status and comorbidity. The results of this study support the inclusion of both a generic and a disease-specific HRQOL measure to assess patient outcomes fully.
Preliminary testing of the contraceptive collagen sponge. (1980)

The results of 3 years of developing the collagen sponge as an intravaginal contraceptive are presented. Postcoital tests were used to evaluate the efficacy of the sponge as a mechanical barrier. Results with the collagen sponge alone were compared to those of the sponge with spermicidal cream or spermicidal solution (acid buffer and zinc) and of spermicidal cream alone. The presence of any motile spermatozoa in the cervical mucus was considered a failure of the barrier method. The collagen sponge alone or with acid and zinc and spermicidal cream alone had failure rates of 22, 20, and 14%, respectively, whereas the collagen sponge with spermicidal cream had a 6% failure rate. The authors conclude that the combination of a mechanical and a chemical barrier is a more effective contraceptive method than a mechanical barrier or chemical agent alone.
The Byzantine Generals Problem (1982)

Reliable computer systems must handle malfunctioning components that give conflicting information to different parts of the system. This situation can be expressed abstractly in terms of a group of generals of the Byzantine army camped with their troops around an enemy city. Communicating only by messenger, the generals must agree upon a common battle plan. However, one or more of them may be traitors who will try to confuse the others. The problem is to find an algorithm to ensure that the loyal generals will reach agreement. It is shown that, using only oral messages, this problem is solvable if and only if more than two-thirds of the generals are loyal; so a single traitor can confound two loyal generals. With unforgeable written messages, the problem is solvable for any number of generals and possible traitors. Applications of the solutions to reliable computer systems are then discussed.
Dielectric Thin Films through rf Sputtering (1966)

Insulators cannot be sputtered with standard dc glow discharge techniques, because the accelerating potential cannot be directly applied and because the positive charge which accumulates on the surface during ion bombardment cannot be neutralized. Direct sputtering of insulators can be achieved by applying a high-frequency potential to a metal electrode behind the dielectric target. This technique was used to deposit thin insulating films. With a properly optimized electrode configuration and a superimposed magnetic field, deposition rates up to 2000 Å/min were obtained. Electrode potentials between 700 and 5500 V peak-to-peak were used. In all experiments described herein, the frequency was 13.56 Mc/sec and the pressure was 5×10−3 Torr. It was found that the introduction of oxygen into the argon sputtering atmosphere greatly reduced the deposition rate. Most experiments were carried out with borosilicate glass (Corning Pyrex 7740) and fused quartz. Without any special measures, films with a low pinhole density were obtained.