gebhart/patrepeval huggingface dataset:
Isolation And Purification Of Collagen And α1 Receptor From Platelet Membrane (1981)

We have previously demonstrated that chick skin type I collagen and the α1(I) chain mediate platelet aggregation. Aggregation is associated with specific binding of these substances by platelet membranes. We now describe the isolation and purification of the receptor. Platelet membranes were prepared as described previously and isolated membranes were solubilized in 0.5% Triton. The receptor was then purified by a combination of gel filtration, affinity chromatography on α1(I)-sepharose or type I collagen-sepharose and preparative polyacrylamide gel electrophoresis. The receptor activity was assayed either directly by a binding assay using (14C)-glycine-labeled α1(I) or indirectly by an adhesion inhibition assay on Sepharose 2B with (14C)-sero- tinin-labeled platelets. The results show that the α1(I) receptor can be purified to a single band on SDS-gel electrophoresis with a recovery of 2.5%. Its activity is destroyed by preincubation with trypsin or pronase indicating it is a protein. The apparent molecular weight as estimated by gel filtration and SDS-gel electrophoresis is 95,000 daltons. The binding of (14C)- labeled α1(I) is specifically displaced by unlabeled α1(I), and the bound radioactivity can be removed by treatment with purified bacterial collagenase. The binding of (14C)- labeled α1(I) by the purified α1(I) receptor can also be inhibited by the receptor isolated from collagen-sepharose affinity chromatography. These data suggest that the α1(I) binding site is identical to the collagen binding site.
Genome-Editing Technologies: Principles and Applications (2016)

Targeted nucleases have provided researchers with the ability to manipulate virtually any genomic sequence, enabling the facile creation of isogenic cell lines and animal models for the study of human disease, and promoting exciting new possibilities for human gene therapy. Here we review three foundational technologies-clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs). We discuss the engineering advances that facilitated their development and highlight several achievements in genome engineering that were made possible by these tools. We also consider artificial transcription factors, illustrating how this technology can complement targeted nucleases for synthetic biology and gene therapy.
Central nervous system DNA fragmentation induced by the inhibition of nuclear factor kappa B (1998)

Ageing of the central nervous system (CNS) is characterized by a progressive apoptotic loss of neurons that may be in part due to impaired neurotrophin signaling mediated by such elements as the transcription factor nuclear factor kappa B (NFkappaB). To support this hypothesis, we inhibited nuclear translocation of NFkappaB in vivo by injecting a proteasome inhibitor (PSI) directly in the CNS lateral ventricle of rats and then measured fragmented DNA in various CNS areas as an index of ongoing apoptosis. Our results show that after PSI injection there was a significant inhibition of NFkappaB activity in vivo that resulted in the appearance of fragmented (apoptotic) DNA in the CNS of rats. These results suggest that alteration of NFkappaB may cause apoptotic cell death in the rat CNS during ageing.
Abuse of law in European tax law: an overview and some recent trends in the direct and indirect tax case law of the ECJ — part 2 (2013)

This paper examines the right of the EU Member States to combat abuse, as defined in the case law of the European Court, in particular, the balance between enforcement of the principle of legal certainty, the right to choose the most favourable fiscal route and the right of states to combat tax avoidance. Part 2 analyses, inter alia, how specific an anti-abuse provisions should be, the burden of proof, tax jurisdiction shopping and the consequences of abuse
miR2Disease: a manually curated database for microRNA deregulation in human disease (2008)

'miR2Disease', a manually curated database, aims at providing a comprehensive resource of microRNA deregulation in various human diseases. The current version of miR2Disease documents 1939 curated relationships between 299 human microRNAs and 94 human diseases by reviewing more than 600 published papers. Around one-seventh of the microRNA-disease relationships represent the pathogenic roles of deregulated microRNA in human disease. Each entry in the miR2Disease contains detailed information on a microRNA-disease relationship, including a microRNA ID, the disease name, a brief description of the microRNA-disease relationship, an expression pattern of the microRNA, the detection method for microRNA expression, experimentally verified target gene(s) of the microRNA and a literature reference. miR2Disease provides a user-friendly interface for a convenient retrieval of each entry by microRNA ID, disease name, or target gene. In addition, miR2Disease offers a submission page that allows researchers to submit established microRNA-disease relationships that are not documented. Once approved by the submission review committee, the submitted records will be included in the database. miR2Disease is freely available at http://www.miR2Disease.org.
Novel cellulose derivatives. IV. Preparation and thermal analysis of waxy esters of cellulose (1996)

Cellulose esters with linear aliphatic acyl substituents ranging in size from C12 (lauric acid) to C20 (eicosanoic acid) were prepared in homogeneous solution (DMAc/LiCl) using a novel synthetic method based on the use of a mixed p-toluenesulfonic/carboxylic acid anhydride. The resulting waxy cellulose esters had a high degree of substitution (DS), between 2.8 and 2.9, and showed little degradation. Thermal analysis of these cellulose derivatives by differential scanning calorimetry (DSC) and dynamic mechanical thermal analysis (DMTA) revealed a series of transitions that represented motion by both ester substituents and cellulosic main chain. Broad crystallization and melting transitions attributed to side-chain crystallinity were observed in the range between −19 and +55°C; these side-chain Tm and Tc transition temperatures increased by 10°C per carbon atom of the ester substituent. The Tg of these derivatives increased linearly with increasing substituent size from 94°C for C12 (cellulose laurate) to 134°C for C20 (cellulose eicosanoate). Evidence of “main-chain” crystallization was not observed for these samples, except in the case of peracetylated C12 and C14 esters, which had Tm values of 96°C and 107°C, respectively. © 1996 John Wiley & Sons, Inc.
Mitochondrial DNA Damage Level Determines Neural Stem Cell Differentiation Fate (2011)

The mitochondrial DNA (mtDNA) of neural stem cells (NSCs) is vulnerable to oxidation damage. Subtle manipulations of the cellular redox state affect mtDNA integrity in addition to regulating the NSC differentiation lineage, suggesting a molecular link between mtDNA integrity and regulation of differentiation. Here we show that 8-oxoguanine DNA glycosylase (OGG1) is essential for repair of mtDNA damage and NSC viability during mitochondrial oxidative stress. Differentiating neural cells from ogg1(-/-) knock-out mice spontaneously accumulate mtDNA damage and concomitantly shift their differentiation direction toward an astrocytic lineage, similar to wt NSCs subjected to mtDNA damaging insults. Antioxidant treatments reversed mtDNA damage accumulation and separately increased neurogenesis in ogg1(-/-) cells. NSCs from a transgenic ogg1(-/-) mouse expressing mitochondrially targeted human OGG1 were protected from mtDNA damage during differentiation, and displayed elevated neurogenesis. The underlying mechanisms for this shift in differentiation direction involve the astrogenesis promoting Sirt1 via an increased NAD/NADH ratio in ogg1(-/-) cells. Redox manipulations to alter mtDNA damage level correspondingly activated Sirt1 in both cell types. Our results demonstrate for the first time the interdependence between mtDNA integrity and NSC differentiation fate, suggesting that mtDNA damage is the primary signal for the elevated astrogliosis and lack of neurogenesis seen during repair of neuronal injury.
Asymmetric dual quantum well laser—wavelength switching controlled by injection current (1989)

We have performed the first experiment on a novel laser diode, the lasing wavelength of which can be switched with increasing current. Wavelength switching over 13 nm under continuous operation, as well as lasing at dual wavelengths, has been achieved for the first time.
Pharmacologic and potential biologic interventions to restore bladder function after spinal cord injury (2000)

Spinal cord injury disrupts voluntary control of voiding and the normal reflex pathways that coordinate bladder and urethral sphincter function. The present review addresses studies in animals and humans that have evaluated various therapeutic approaches for normalizing lower urinary tract function after spinal cord injury.
α-Lipoic Acid as a Directly Binding Activator of the Insulin Receptor:  Protection from Hepatocyte Apoptosis (2007)

Alpha-lipoic acid mediates its antiapoptotic action via activation of the insulin receptor/PI3-kinase/Akt pathway. We show for the first time a direct binding site for alpha-lipoic acid at the insulin receptor tyrosine kinase domain, which might make alpha-lipoic acid a model substance for the development of insulin mimetics.
Host migration transparency in IP networks (1993)

Increasing portability of computers will require users in the future to access the network regardless of location. Host migration transparency will be an essential feature of wide area network environments. We proposed the concept of virtual network and the propagating cache method to achieve host migration transparency [12]. We also established the feasibility of Virtual Internet Protocol (VIP), derived from Internet Protocol (IP), as an example of a virtual network protocol. In this paper, we define VIP in detail and describe how VIP achieves host migration transparency in IP networks. We also show two VIP implementation approaches: 1) VIP as a sublayer; and 2) VIP as an IP option. By modifying an operating systems kernel in each case, we implement VIP using both approaches. We then compare both implementations in terms of overhead, backward compatibility, and other metrics. The measured performance indicates that VIP can provide host migration transparency in IP networks with negligible overhead.
Dermcidin expression in hepatic cells improves survival without N-glycosylation, but requires asparagine residues (2006)

Proteolysis-inducing factor, a cachexia-inducing tumour product, is an N-glycosylated peptide with homology to the unglycosylated neuronal survival peptide Y-P30 and a predicted product of the dermcidin gene, a pro-survival oncogene in breast cancer. We aimed to investigate whether dermcidin is pro-survival in liver cells, in which proteolysis-inducing factor induces catabolism, and to determine the role of potentially glycosylated asparagine residues in this function. Reverse cloning of proteolysis-inducing factor demonstrated approximately 100% homology with the dermcidin cDNA. This cDNA was cloned into pcDNA3.1+ and both asparagine residues removed using site-directed mutagenesis. In vitro translation demonstrated signal peptide production, but no difference in molecular weight between the products of native and mutant vectors. Immunocytochemistry of HuH7 cells transiently transfected with V5-His-tagged dermcidin confirmed targeting to the secretory pathway. Stable transfection conferred protection against oxidative stress. This was abrogated by mutation of both asparagines in combination, but not by mutation of either asparagine alone. These findings suggest that dermcidin may function as an oncogene in hepatic as well as breast cells. Glycosylation does not appear to be required, but the importance of asparagine residues suggests a role for the proteolysis-inducing factor core peptide domain.
The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2. (1996)

CD2, a cell surface glycoprotein expressed on T cells and natural killer cells, can couple to signaling pathways that result in T cell proliferation. An Src-like protein tyrosine kinase, p56lck, coprecipitates with CD2, and perturbation of CD2 by monoclonal antibodies results in an increase in the activity of p56lck, suggesting that an interaction with p56lck contributes to CD2-mediated signaling. Herein, we investigate the mechanism by which CD2 associates with p56lck. We demonstrate that CD2 and p56lck associate when coexpressed in nonlymphoid cells, that this association requires the cytoplasmic domain of CD2, and that the SH3 domain of p56lck mediates its interactions with CD2. Using truncation mutants of CD2, we identify two regions in the cytoplasmic domain of CD2 involved in binding p56lck. Each region contains a proline-rich sequence that, in the form of a synthetic peptide, directly binds p56lck. Thus, proline-rich sequences in the cytoplasmic domain of CD2 allow this transmembrane receptor to bind to the SH3 domain of p56lck.
Microscope-integrated intraoperative OCT with electrically tunable focus and heads-up display for imaging of ophthalmic surgical maneuvers (2014)

We present novel optical and mechanical designs for a microscope-integrated intraoperative optical coherence tomography (iOCT) system with enhanced function and ergonomics for visualization of ophthalmic surgical maneuvers. Integration of an electrically tunable lens allows rapid focal plane adjustment and iOCT imaging of both anterior and posterior segment tissue microstructures while maintaining parfocality with the ophthalmic surgical microscope. We demonstrate novel visualization of instrument positions relative to tissue layers of interest as colormap overlays onto en face OCT data, which may provide integrative display of volumetric information during surgical maneuvers. Finally, we implement a heads-up display system to provide real-time feedback as proof-of-principle for iOCT-guided ophthalmic surgery.
Kinetic and Structural Studies of Specific Protein−Protein Interactions in Substrate Catalysis by Cdc25B Phosphatase (2006)

Using a combination of steady-state and single-turnover kinetics, we probe substrate association, dissociation, and chemistry for the reaction of Cdc25B phosphatase with its Cdk2-pTpY/CycA protein substrate. The rate constant for substrate association for the wild-type enzyme is 1.3 x 10(6) M(-1) s(-1). The rate constant for dissociation is slow compared to the rate constant for phosphate transfer to form the phospho-enzyme intermediate (k2 = 1.1 s(-1)), making Cdk2-pTpY/CycA a sticky substrate. Compared to the wild type, all hotspot mutants of residues at the remote docking site that specifically affect catalysis with the protein substrate (Arg488, Arg492, and Tyr497 on Cdc25B and Asp206 on Cdk2) have greatly slowed rate constants of association (70- to 4500-fold), and some mutants have decreased k2 values compared to that of the wild type. Most dramatically, R492L, despite showing no significant changes in a crystal structure at 2.0 A resolution, has an approximately 100-fold decrease in k2 compared to that of wild-type Cdc25B. The active site C473S mutant binds tightly to and dissociates slowly from Cdk2-pTpY/CycA (Kd = 10 nM, k(off) = 0.01 s(-1)). In contrast, the C473D mutant, despite showing only localized perturbations in the active site at 1.6 A resolution, has a much weaker affinity and dissociates rapidly (Kd of 2 microM, k(off) > 2 s(-1)) from the protein substrate. Overall, we demonstrate that the association of Cdc25B with its Cdk2-pTpY/CycA substrate is governed to a significant extent by the interactions of the remote hotspot residues, whereas dissociation is governed by interactions at the active site.
Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1. (1992)

The clinical complications associated with severe and cerebral malaria occur as a result of the intravascular mechanical obstruction of erythrocytes infected with the asexual stages of the parasite, Plasmodium falciparum. We now report that a primary P. falciparum-infected erythrocyte (parasitized red blood cell [PRBC]) isolate from a patient with severe complicated malaria binds to cytokine-induced human vascular endothelial cells, and that this adhesion is in part mediated by endothelial leukocyte adhesion molecule 1 (ELAM-1) and vascular cell adhesion molecule 1 (VCAM-1). PRBC binding to tumor necrosis factor alpha (TNF-alpha)-activated human vascular endothelial cells is partially inhibited by antibodies to ELAM-1 and ICAM-1 and the inhibitory effects of these antibodies is additive. PRBCs selected in vitro by sequential panning on purified adhesion molecules bind concurrently to recombinant soluble ELAM-1 and VCAM-1, and to two previously identified endothelial cell receptors for PRBCs, ICAM-1, and CD36. Post-mortem brain tissue from patients who died from cerebral malaria expressed multiple cell adhesion molecules including ELAM-1 and VCAM-1 on cerebral microvascular endothelium not expressed in brains of individuals who died from other causes. These results ascribe novel pathological functions for both ELAM-1 and VCAM-1 and may help delineate alternative adhesion pathways PRBCs use to modify malaria pathology.
Medical Pharmacology at a Glance (1987)

Introduction: Principles of Drug Action Drug-Receptor Interactions Drug Absorption, Distribution and Excretion Drug Metabolism Local Anaesthetics Drugs Acting at the Neuromuscular junction Autonomic nervous system Autonomic drugs acting at cholinergic synapses Drugs acting on the symphathetic system Ocular Pharmacology Asthma, Hay Fever and Anaphylaxis Drugs Acting on the Gastrointestinal Tract. I: Peptic Ulcer Drugs Acting on the Gastrointestinal Tract. II: Motility and Secretions Drugs Acting on the Kidney - Diuretics Drugs used in Hypertension Drugs used in Angina Anti-Arrhythmic Drugs Drugs used in Heart Failure Drugs used to Affect Blood Coagulation Lipid-Lowering Drugs Agents used in Anaemias Central Transmitter Substances General Anaesthetics Anxiolytics and Hypnotics Antiepileptic Drugs Drugs used in Parkinsonism Drugs used in Psychosis - Neuroleptics Drugs used in Affective Disorders - Antidepressants Opioid Analgesics Drugs used in Nausea and Vertigo (Anti-emetics) Drug Misuse and Dependence Non-Steroidal Anti-inflammatory Drugs (NSAIDs) Corticosteroids Sex Hormones and Drugs Thyroid and Antithyroid Drugs Antidiabetic Agents Antimicrobial Drugs that Inhibit Nucleic Acid Synthesis: Sulphonamides, Trimethoprim, Quinolones and Nitroimidazoles Antimicrobial Drugs that Inhibit Cell Wall Synthesis: Penicillins, Cephalosporins and Vancomycin Antimicrobial Drugs that Inhibit Protein Synthesis: Aminoglycosides, Tetracyclines, macrolides and chloramphenicol Antifungal and Antiviral Drugs Drugs Acting on Parasites. I: Helminths (Worms) Drugs Acting on Parasites. II: Protozoa Drugs used in Cancer Poisoning Adverse Drug Reactions Index
Automated TEM Sample Preparation (2000)

Abstract The rising demand in the semiconductor industry for higher spatial resolution in the analysis of device defects has focused attention on the use of transmission electron microscopy (TEM). However, conventional TEM sample preparation can be difficult and time-consuming, and, depending on the operator, may result in a low yield of quality specimens. One solution to this problem is the use of focused ion beam (FIB) milling for the final stage of TEM sample preparation. However, specimens have to be mechanically thinned prior to FIB and the need to characterize specific devices requires a pre-FIB preparation method that can target specific features on the wafer. We will discuss an innovative and automated solution that isolates specific devices and prepares TEM specimens for subsequent FIB thinning. The complete pre-FIB preparation takes less than 30 minutes and yields a sample in which the targeted feature is positioned a specific distance from the sample edge, thereby minimizing final FIB milling time. The output specimen is automatically packaged for FIB milling and TEM analysis. We also present drawings of the process flow and examples showing TEM results from tungsten filled vias.
Intermittent sacral neuromodulation for idiopathic urgency urinary incontinence in women (2015)

Compared to pre-SNM parameters, iSNM shows an improvement in both objective and subjective outcomes. Specifically no difference was found between iSNM and cSNM, indicating that iSNM could be a feasible and cost-effective alternative. Neurourol. Urodynam. 36:385-389, 2017. © 2015 Wiley Periodicals, Inc.
An efficient NAND flash file system for flash memory storage (2006)

In this paper, we present an efficient flash file system for flash memory storage. Flash memory, especially NAND flash memory, has become a major method for data storage. Currently, a block level translation interface is required between an existing file system and flash memory chips due to its physical characteristics. However, the approach of existing file systems on top of the emulating block interface has many restrictions and is, thus, inefficient because existing file systems are designed for disk-based storage systems. The flash file system proposed in this paper is designed for NAND flash memory storage while considering the existing file system characteristics. Our target performance metrics are the system booting time and garbage collection overheads, which are important issues in flash memory. In our experiments, the proposed flash file system outperformed other flash file systems both in booting time and garbage collection overheads.
Expression of the erbB-2 family of growth factor receptors and their ligands in breast cancers. Implication for tumor biology and clinical behavior. (1994)

Transmembrane receptor tyrosine kinases that bind to growth factors transmit signals that are essential to growth and differentiation. These receptors can be classified into groups based on their structure. One group implicated in the pathogenesis of breast cancer contains receptors belonging to the erbB family. This group includes the epidermal growth factor receptors, the HER-2/neu (erbB-2), HER-3, and HER-4. Despite the structural similarity of these receptors, HER-2/neu, HER-4, and HER-3 do not bind to any ligand of the epidermal growth factor receptor. However, a 44-kD glycoprotein called neu differentiation factor (neu differentiation factor/heregulin) has been isolated. This ligand phosphorylates the HER-2/neu receptor and binds directly to HER-4 and HER-3. The abundance of erbB receptors and their ligands in breast cancers points to their functional importance in the pathogenesis and biological behavior of breast cancers. Furthermore, these receptors and ligands may hold a promise for targeted therapy for breast cancer in the future.
A Gold Nanoparticle Based Approach for Screening Triplex DNA Binders (2006)

Nanoparticle assemblies interconnected with DNA triple helixes can be used to colorimetrically screen for triplex DNA binding molecules and simultaneously determine their relative binding affinities based on melting temperatures. Nanoparticles assemble only when DNA triple helixes form between DNA from two different particles and a third strand of free DNA. In addition, the triple helix structure is unstable at room temperature and only forms in the presence of triplex DNA binding molecules which stabilize the triple helix. The resulting melting transition of the nanoparticle assembly is much sharper and at a significantly higher Tm than the analogous triplex structure without nanoparticles. Upon nanoparticle assembly, a concomitant red-to-blue color change occurs. The assembly process and color change do not occur in the presence of duplex DNA binders and therefore provide a significantly better screening process for triplex DNA binding molecules compared to standard methods.