gebhart/patrepeval huggingface dataset:
Use of Escherichia coli strains containing fad mutations plus a triple plasmid expression system to study the import of myristate, its activation by Saccharomyces cerevisiae acyl-CoA synthetase, and its utilization by S. cerevisiae myristoyl-CoA:protein N-myristoyltransferase. (1993)

A system is described for studying protein N-myristoylation, a eukaryotic protein modification, in Escherichia coli strains containing components of eukaryotic metabolic pathways that regulate metabolism of myristoyl-CoA:protein N-myristoyltransferase (Nmt1p) substrates. Three recombinant plasmids were used to simultaneously direct synthesis of Saccharomyces cerevisiae Nmt1p, a substrate protein (S. cerevisiae ADP-ribosylation factor 1, Arf1p), and one of the acyl-CoA synthetases produced by S. cerevisiae (Faa1p) in isogenic strains of bacteria with wild type or mutant alleles of genes comprising the regulon for fatty acid degradation (FadR, FadE, FadL and FadD). Incorporation of exogenous tritiated myristate into Arf1p and bacterial phospholipid biosynthetic pathways was analyzed. Removal of FadL, a 448-residue protein necessary for efficient transport of fatty acids across the outer membrane, had no detectable effect on Nmt1p-dependent N-myristoylation of Arf1p. This finding is consistent with the notion that permeation of C14:0 across the bacterial inner membrane can occur by simple diffusion. Studies of strains that contain a mutation in FadE which inhibits beta-oxidation of exogenous fatty acids, confirm that Nmt1p retains its specificity for myristoyl-CoA over palmitoyl-CoA in E. coli. A mutation that inactivates FadD, a 580-residue protein which is the only acyl-CoA synthetase produced by this bacterium, completely blocks incorporation of exogenous myristate into Arf1p. This failure to be incorporated indicates that myristoyl-acyl carrier protein, generated by inner membrane acyl-acyl carrier protein synthetase, is not a substrate for Nmt1p. S. cerevisiae Faa1p can partially complement this mutant fadD allele. It can fully "restore" N-myristoylation of Arf1p. Faa1p can also rescue growth at 37 degrees C of fadD- strains on minimal media supplemented with C12:0, although this rescue becomes less efficient as the chain length of the supplemental fatty acid increases. In addition, S. cerevisiae Faa1p is better able to direct myristoyl-CoA to the bacteria's phospholipid biosynthetic pathways than FadD, while FadD is more efficient at directing myristoyl-CoA to the genetically engineered protein N-myristoylation pathway. Since cellular acyl-CoA synthetase activity in S. cerevisiae has been distributed to at least two functionally differentiated proteins, this system should be useful for comparing their structure-activity relationships as well as their interactions with Nmt1p in an organelle-free environment.
Safety and Immunogenicity of a Recombinant Tetravalent Dengue Vaccine in 9–16 Year Olds (2013)

CYD-TDV had a favorable safety profile and elicited antibody responses against all 4 dengue virus serotypes in 9-16 year olds in Latin America. These findings support the continued development of CYD-TDV.
CNN-based Segmentation of Medical Imaging Data (2017)

Convolutional neural networks have been applied to a wide variety of computer vision tasks. Recent advances in semantic segmentation have enabled their application to medical image segmentation. While most CNNs use two-dimensional kernels, recent CNN-based publications on medical image segmentation featured three-dimensional kernels, allowing full access to the three-dimensional structure of medical images. Though closely related to semantic segmentation, medical image segmentation includes specific challenges that need to be addressed, such as the scarcity of labelled data, the high class imbalance found in the ground truth and the high memory demand of three-dimensional images. In this work, a CNN-based method with three-dimensional filters is demonstrated and applied to hand and brain MRI. Two modifications to an existing CNN architecture are discussed, along with methods on addressing the aforementioned challenges. While most of the existing literature on medical image segmentation focuses on soft tissue and the major organs, this work is validated on data both from the central nervous system as well as the bones of the hand.
Principles for Human Gene Therapy Studies (2000)

The recent revelations of problems in gene therapy trials have clearly indicated that the current federal mechanisms for review, regulation, and oversight of human gene transfer studies require modification. This policy forum discusses the basic principles that form the foundation of clinical research, with the most important being patient protection, and makes recommendations for changes in oversight that will ensure that the highest standards are met.
CURRENT CONCEPTS IN INTERVERTEBRAL DISK RESTORATION (2000)

A current focus of treatment for degenerative disk disease is the restoration of the intervertebral disk. This article summarizes the structure and function of the intervertebral disk, the pathogenesis of its degeneration, and the clinical relevance of degenerative disk disease. Current literature relating to intervertebral disk replacement and regeneration is reviewed.
512. Tumor-Associated Macrophages Via Up-Regulation of PD1 Ligands Protect Neuroblastoma from Immunotherapy With NKT Cells Expressing GD2-Specific Chimeric Antigen Receptor (2015)

Immunotherapy with Natural Killer T cells engineered to express a GD2-specific chimeric antigen receptor (CAR.GD2 NKTs) demonstrated potent anti-tumor activity in a metastatic model of neuroblastoma in humanized (hu)NSG mice. However, tumors eventually progressed without the loss of GD2 expression suggesting that tumor escape is due to inhibition of effector function of CAR. GD2 NKTs. Since NKTs co-localize and specifically interact with M2-like tumor-associated macrophages (TAMs), we examined whether TAMs inhibit effector functions of NKT and CAR.GD2 NKT cells. In vitro experiments revealed a reciprocal inhibition of NKTs and M2-polarized macrophages. We found that NKTs selectively kill M2-polarized macrophages or induce their differentiation toward M1-like cells. However, both M2- and M1-macrophages suppressed NKT-cell proliferation and IFNγ production in response to TCR or CAR stimulation. This was associated with rapid up-regulation of PD-L1 and PD-L2 on both M2 and M1 macrophages upon addition of supernatant from activated NKT cells. Moreover, M1 macrophages constitutively expressed PD-L1 and were resistant to NKT-cell cytotoxicity. The analysis of tumor tissues in hu-NSG mice revealed strong up-regulation of PD-L1 expression exclusively on TAMs and not on neuroblastoma cells after treatment with CAR. GD2 NKTs. Neither neuroblastoma cells nor TAMs expressed PD1 ligands in untreated mice or in primary NB tissues from patients with stage 4 disease. Importantly, a combination of CAR.GD2 NKT cell immunotherapy with anti-PD1 blocking mAb produced durable tumor regression. The results provide a rationale for a combined use of CAR-redirected NKT cells with PD1-blocking therapeutics for immunotherapy of neuroblastoma and possibly other solid tumors.
Dead time of an anger camera in dual‐energy‐window‐acquisition mode (1993)

Two side-by-side energy windows are sometimes employed in quantitative single photon emission computed tomography (SPECT) studies. The count-rate losses at high activities for a GE400AT camera were measured in such a dual-window-acquisition mode by imaging a decaying source composed of a hot sphere within a warm cylinder. The data in each window was either kept separate or combined for purposes of dead-time correction and the paralyzable model was assumed. In addition, correction factors were derived from a "monitor" source at the edge of the camera. Finally, energy spectra for only the monitor-source region of interest and for the entire camera were obtained under both low- and high-count conditions and compared. With 99mTc (1) the spectral measurements show no peak shift but reveal pulse-pile-up spectral degradation. (2) The monitor-source corrections do not agree well with those from the model, presumably because of the differential effects of such degradation. For this camera the preferred correction method for patients is one using the model and two, effective, phantom-derived dead times for the separate data from the two windows. The two effective dead times are needed to compensate for pulse pile-up adding more counts to the lower-energy window than to the higher-energy one at high rates.(ABSTRACT TRUNCATED AT 250 WORDS)
Cancer therapy and cardiovascular risk: focus on bevacizumab (2015)

Recognition and management of treatment-related cardiovascular toxicity, defined as either an acute cardiac event or a chronic condition, has been tightly integrated into routine cancer care and has become an important component in treatment selection. Several chemotherapeutic agents, such as anthracyclines, are traditionally characterized as cardiotoxic, but cardiovascular adverse events are also associated with commonly used molecular targeted therapies. In the past decade, bevacizumab, a monoclonal humanized antibody against vascular endothelial growth factor, has been introduced in the treatment of a variety of metastatic malignancies. Despite its efficacy, bevacizumab has been associated with significant risk of cardiovascular complications, such as hypertension, cardiac ischemia, and congestive heart failure. This review will focus on the cardiovascular toxicity of bevacizumab, providing the latest evidence on the incidence, clinical spectrum, risk factors, and responsible mechanisms.
The P2X7 Receptor: A Novel Biomarker of Uterine Epithelial Cancers (2006)

(a) Levels of the P2X(7) are lower in uterine epithelial cancer tissues than in the corresponding normal tissues. (b) The data suggest that tissue P2X(7) mRNA and protein levels could be used as a novel biomarker to differentiate normal and cancer uterine epithelial tissues.
Adaptive/self-tuning PID control by frequency loop-shaping (2002)

Addresses issues arising in the online adaptation of PID controller parameters. With frequency loop-shaping principles as the underlying controller design approach, the PID parameter adaptation can be performed directly by minimizing a suitable estimation error with standard least-squares algorithms. A variant of such an algorithm is also proposed in an effort to approximate the minimization of the H-infinity norm of the error operator. A numerical example is used to illustrate the implementation of the algorithm.
Non-viral amplification systems for gene transfer: vectors based on alphaviruses. (1999)

Non-viral self-replicating vectors based on defective viral genomes have been developed for a number of different alphaviruses including Semliki Forest virus (SFV), Sindbis virus (SIN) and Venezuelan equine encephalitis virus (VEE). These vectors can be used for gene delivery as naked RNA or DNA. Recombinant alphavirus RNA can be synthesized in vitro from plasmids containing the alphavirus replicon under the control of a prokaryotic promoter such as SP6 or T7. These self-replicating RNAs have been able to induce protective immune responses in vivo, probably due to the high level of expression of the recombinant antigen in the transfected cells. However, alphavirus vectors based on the direct delivery DNA are probably a better choice due to their higher stability and lower production cost. In these vectors, the alphavirus replicon is placed under the control of a RNA polymerase II promoter. These vectors are more efficient than conventional plasmids in inducing both humoral and cellular immune responses in small animals, allowing the use of significant smaller amounts of DNA for immunization. In addition, due to the transient nature of the alphavirus replicons, possible problems associated with DNA integration into host chromosomes are eliminated.
Cytomegalovirus induced PMN adherence in relation to an ELAM-1 antigen present on infected endothelial cell monolayers. (1991)

In human umbilical vein endothelial cells infected with cytomegalovirus (CMV), an activation antigen recognized by monoclonal antibody (mAb) ENA1 appeared. mAb ENA1 reacts with an inducible endothelial surface antigen which has characteristics similar to those of ELAM-1. Incubation with anti-IL-1 partly inhibited this appearance and, parallel to this, the virus-induced polymorphonuclear cell (PMN) adhesion was decreased. In addition, the adhesion of PMN to virus-infected endothelial cells could be reduced by F(ab)2 fragments of mAb ENA1 to almost control level. The results obtained after incubation of PMN with mAb IB4 (against CD18) suggest that the adhesion of PMN to uninfected endothelial cells is CD18 glycoprotein dependent, and virus infection up-regulates this glycoprotein-dependent mechanism. These results indicate that the virus-induced PMN adhesion is regulated by the following mechanism: virus infection of endothelial cells induces IL-1 production, and the autocrine IL-1 causes the expression of ELAM-1 on the surface of endothelial cells. In turn this activation antigen ELAM-1 binds with its putative ligand present on the PMN membrane. The virus-induced PMN adhesion occurs also through a CD18 glycoprotein-dependent mechanism.
Self-assembled collagen-like peptide fibers as templates for metallic nanowires (2008)

Inspired by nature's ability to fabricate supramolecular nanostructures from the bottom-up, materials scientist have become increasingly interested in the use of biomolecules like DNA, peptides, or proteins as templates for the creation of novel nanostructures and nanomaterials. Although the advantages of self-assembling biomolecular structures clearly lie in their chemical diversity, spatial control, and numerous geometric architectures, it is challenging to elaborate them into functional hybrid inorganic-bionanomaterials without rendering the biomolecular scaffold damaged or dysfunctional. In this study, attachment of gold nanoparticles to collagen-related self-assembling peptides at L-lysine residues incorportated within the peptides sequence and the N-terminus led to metal nanoparticle-decorated fibers. After electroless silver plating, these fibers were completely metalized, creating electrically conductive nanowires under mild conditions while leaving the peptide fiber core intact. This study demonstrates the bottom-up assembly of synthetic peptidic fibers under mild conditions and their potential as templates for other complex inorganic-organic hybrid nanostructures.
Tailored Glycoproteomics and Glycan Site Mapping Using Saccharide-Selective Bioorthogonal Probes (2007)

Protein glycosylation is an important post-translational modification of proteins that has profound effects on structure and function. However, the complex and non-templated nature of glycans has been a barrier to studying many of their basic features, especially on a proteome-wide scale. Here, we introduce a glycoproteomic method, glycoprotein identification and glycan mapping (GIDmap), that tailors the isolation of specific glycoprotein subpopulations based on display of metabolically inserted alkynyl sugar probes that can be selectively manipulated using the bioorthogonal Cu(I)-catalyzed [3 + 2] azide−alkyne cycloaddition. This saccharide-selective glycoprotein immobilization allows for subsequent manipulation and analysis of peptides and glycopeptides by liquid chromatography-tandem mass spectrometry. The power of GIDmap was demonstrated by mapping over 200 N-linked glycosylation sites from glycoproteins isolated from prostate cancer cells treated with an alkynyl sugar derivative of N-acetylmannosamine. Overall, GIDmap is a robust method that will greatly aid in inventorying glycoproteins and mapping glycosylation sites, in addition to providing specific information about saccharide content and glycan behavior.
Development of an intramuscular xenograft model of canine osteosarcoma in mice for evaluation of the effects of radiation therapy (2009)

A reliable, repeatable, and easily produced IM xenograft model was developed for in vivo assessment of canine osteosarcoma.
Streaming Into the Future: Why Legislation and Technology Have Opened Pandora’s Box for the Recording Industry and the Webcasting Services, 13 J. Marshall Rev. Intell. Prop. L. 649 (2014) (2014)

Today, music is everywhere, but this was not always the case. Listeners are surrounded by endless access to libraries and playlists from the advancement in technology. With the rapid technological advancements, Copyright law has been left behind at a stand still. Since the enactment of the Copyright Act, sound recordings have received less favorable treatment compared to their music counterpart. Sound recording copyrights are afforded digital performance royalties when broadcasted on popular Internet streaming services, like Pandora. In the last few years, music streaming has become more popular among listeners and thus, more sound recording royalties have been distributed; but, at a large cost to the services. The webcasters seek lower royalty rates for playing sound recordings, because they view their service as promotional. The sound recording copyright owners seek equality among all broadcasting services to receive fair compensation for every public performance, not merely digital. Recent bills have been introduced by both sides of this debate, but have yet to become law. The Internet Radio Fairness Act (IRFA), backed by the webcasters, places a higher burden of proof on the sound recording owner to develop a royalty rate the services deem fair, which would undoubtedly lower rates. On the other side, the Free Market Royalty Act (FMRA) seeks a comparable royalty beyond digital transmissions to all broadcast services. Balancing the needs of both parties provide an avenue to create parity within the music industry and the law.
Vascular Endothelial Growth Factor and Diabetic Retinal Disease (2016)

Diabetic retinal disease remains a leading cause of blindness among working-aged adults around the world. Until this decade, laser photocoagulation for both proliferative diabetic retinopathy and diabetic macular edema had been the standard of care for millions of patients. The introduction of vascular endothelial growth factor inhibitors (anti-VEGF) and subsequent clinical trials demonstrating their efficacy for treatment of diabetic eye disease have established a new standard in treatment of center-involved diabetic macular edema that is highly specific to the pathologic process and highly effective in preserving and improving vision. This review focuses on clinically relevant developments that led to the shift from focal/grid laser photocoagulation to anti-VEGF injections in the treatment of center-involved diabetic macular edema (DME), with an overview of the disease pathophysiology, clinical disease course, and available anti-VEGF agents. This article also reviews the scientific evidence exploring the use of anti-VEGF agents in nonproliferative and proliferative diabetic retinopathy.
Enhanced Measles Virus cDNA Rescue and Gene Expression after Heat Shock (1999)

Rescue of negative-stranded RNA viruses from full-length genomic cDNA clones is an essential technology for genetic analysis of this class of viruses. Using this technology in our studies of measles virus (MV), we found that the efficiency of the measles virus rescue procedure (F. Radecke et al., EMBO J. 14:5773-5784, 1995) could be improved by modifying the procedure in two ways. First, we found that coculture of transfected 293-3-46 cells with a monolayer of Vero cells increased the number of virus-producing cultures about 20-fold. Second, we determined that heat shock treatment increased the average number of transfected cultures that produced virus another two- to threefold. In addition, heat shock increased the number of plaques produced by positive cultures. The effect of heat shock on rescue led us to test the effect on transient expression from an MV minireplicon. Heat shock increased the level of reporter gene expression when either minireplicon DNA or RNA was used regardless of whether complementation was provided by cotransfection with expression plasmids or infection with MV helper virus. In addition, we found that MV minireplicon gene expression could be stimulated by cotransfection with an Hsp72 expression plasmid, indicating that hsp72 likely plays a role in the effect of heat shock.
Uncovering Functionally Relevant Signaling Pathways Using Microarray-Based Expression Profiling (2000)

The introduction of microarray technology to the scientific and medical communities has fundamentally altered the way in which we now address basic biomedical questions. Microarrays technology facilitates a more complete and inclusive experimental approach where alterations in the transcript level of entire genomes can be simultaneously assayed in response to a variety of stimuli. Conceptually different approaches to the development of microarray technology have resulted in the generation of two different array formats: oligonucleotide arrays and cDNA arrays. The application of microarray and related technologies to identify specific targets of defined genes that have clearly been implicated in cancer progression requires a specific experimental approach. The objective of this approach is to define changes in transcriptional profile that occur in response to modulating the expression level of the gene to be studied. The resulting altered expression profile can then be viewed as a blueprint by which that gene effects its cellular function. We have used oligonucleotide array-based expression profiling in collaboration with Affymetrix to identify downstream transcriptional targets of the BRCA1 tumor-suppressor gene as a means of defining its function. BRCA1 has been implicated in at least three functional pathways, namely, mediating the cellular response to DNA damage, as a cell cycle checkpoint protein and in the regulation of transcription. The physiological significance of these properties and their implications for the function of BRCA1 as a tumor-suppressor gene remain to be defined.
IPEL-a novel ion-implanted electrically programmable element (1989)

The programmable element consists of a metal/amorphous-silicon/crystalline-silicon structure in which the amorphous-silicon layer is created by high-dose ion implantation. Amorphization by the damage caused by the collisions of the energetic ions with the substrate increases resistivity of a normal contact to single-crystal silicon by many orders of magnitude. The specific resistance of a typical aluminum contact to heavily doped n-type silicon increases from 10/sup -6/-10/sup -5/ to 1-10 Omega -cm/sup 2/ at room temperature. Applying a sufficiently high voltage induces an irreversible transformation of the device into a low-resistance state. The postprogramming resistance can be as low as 100 Omega for a 3*3- mu m/sup 2/ contact at room temperature.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>