gebhart/patrepeval huggingface dataset:
Stability of Cell-Penetrating Peptide−Morpholino Oligomer Conjugates in Human Serum and in Cells (2006)

Cell penetrating peptides (CPPs) have been shown to enhance the cellular uptake of antisense oligonucleotides (AOs). However, the effectiveness of the CPPs for cytoplasmic or nuclear delivery of therapeutic AOs must take into account the possible entrapment of the CPP-AO conjugates in endosomes/lysosomes and the overall stability of the CPP-AO conjugates to enzymes. This includes the stabilities of the CPPs and AOs themselves as well as the linkage between them. In this study, we investigated the effects of several structural features of arginine-rich CPPs on the metabolic stability of CPP conjugated to phosphorodiamidate morpholino oligomers (PMOs) in human serum and in cells. Those structural features include amino acid configurations (d or l), incorporation of non-alpha-amino acids, peptide sequences, and types of linkages between CPPs and PMOs. Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry, we found that the stability of the CPP portion was varied although the PMO portion of the conjugate was completely stable both in cells and in human serum. d-Configuration CPPs were completely stable, while l-CPPs were degraded in both serum and HeLa cells. Insertions of 6-aminohexanoic acid residues (X) into an R8 peptide increased the corresponding CPP's serum stability with the degree of stability being dependent upon the positions of X. However, X-containing CPPs were degraded rapidly intracellularly. Insertions of beta-alanines (B) into the R8 peptide increased its serum stability and intracellular stability. An amide or a maleimide linkage was stable in both serum and cells; however, an unhindered disulfide linkage was not stable in either. By using fluorescent microscopy, flow cytometry, and an antisense splice correction assay, the cellular uptakes of an X-containing conjugate and its fragments were compared to their antisense activities. We found that a large fraction of the conjugate was trapped within vesicles and the degraded fragments cannot escape from the vesicles. This study indicates that the incorporation of non-alpha-amino acids into l-CPPs can increase the metabolic stability of CPP-PMOs without using costly d-CPPs. However, the position and type of non-alpha-amino acids affect the degree of stability extracellularly and intracellularly. In addition, this study reveals that the degradation of an X-containing CPP-PMO conjugate is a more rapid process than degradation of a B-containing conjugate. Last, the endosomal/lysosomal trapping limits the effectiveness of a CPP-PMO conjugate, and the stability of the CPP is one of the factors affecting the ability of the conjugate to escape the endosomes/lysosomes.
Design of a Low-cost Physiological Parameter Measurement and Monitoring Device (2007)

In this paper we present the design of a low-cost system that can be used to monitor physiological parameters, such as temperature and heart rate, of a human subject. The system consists of an electronic device which is worn on the wrist and finger, by an elderly or at-risk person. Using several sensors to measure different vital signs, the person is wirelessly monitored within his own home. An impact sensor has been used to detect falls. The device detects if a person is medically distressed and sends an alarm to a receiver unit that is connected to a computer. This sets off an alarm, allowing help to be provided to the patient. The device is battery powered for use indoors. The device can be easily adapted to monitor athletes and infants. The low cost of the device will help to lower the cost of home monitoring of patients recovering from illness. A prototype of the device has been fabricated and extensively tested with very good results.
Heterogeneity of malignant cells from a human colonic carcinoma. (1981)

Three subpopulations of malignant cells were isolated from a primary cell culture of a single human colonic carcinoma. The variant cells were established as cell lines designated HCT 116, HCT 116a, and HCT 116b, respectively. In vitro characterizations of the variant lines included growth in 0.5% agarose and growth on confluent layers of mouse fibroblasts. HCT 116a showed the highest colony formation in agarose and on confluent fibroblasts, while colony formation by HCT 116 was higher than that of HCT 116b in both of these systems. All of the variant lines were tumorigenic in athymic nude mice given injections of 10 x 10(6) cells, but the time between inoculation and tumor development (latency period) was approximately 10 times longer for HCT 116b as for HCT 116a and 8 times longer than for HCT 116. HCT 116b was not tumorigenic at an inoculum of 5 x 10(6) cells, while both HCT 116 and 116a were tumorgenic at this level. However, HCT 116a was clearly more tumorigenic than was HCT 116 on the basis of the number of animals developing tumors at inoculate of both 10 x 10(6) and 5 x 10(6) cells and on the basis of their differences in latency periods. While all the cell lines had near diploid numbers of chromosomes, each line showed a distinct histological pattern when grown as xenografts in athymic nude mice.
Calcium Channels: Mechanisms Of Selectivity, Permeation, And Block (1987)

Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems employ the dual RNA–guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific ...Read More
Convection-Enhanced Delivery of Targeted Quantum Dot–Immunoliposome Hybrid Nanoparticles to Intracranial Brain Tumor Models (2013)

QD-ILs serve as an effective imaging agent in vitro and in vivo, and the data suggest that ligand-directed liposomal nanoparticles in conjunction with convection-enhanced delivery may offer therapeutic benefits for glioblastoma treatment as a result of specific and efficient uptake by malignant cells.
Construction, expression, and activity of a bivalent bispecific single-chain antibody. (1994)

This report describes the design, construction, and expression of a bivalent bispecific single-chain antibody (SCA) protein in Escherichia coli. The bispecificity of the bivalent protein was based on two previously constructed monovalent single-chain antibody molecules possessing distinct specificities, SCA 4-4-20 (anti-fluorescein) and SCA 04-01 (anti-single-stranded DNA). A flexible linker, modeled after a secreted fungal cellulase protein, was incorporated as the interdomain linker covalently joining the two active sites. Bivalent bispecific SCA protein that accumulated in bacteria as insoluble inclusion bodies was harvested, denatured, refolded, and affinity-purified in vitro. Affinity-purified bivalent bispecific SCA showed nearly identical ligand binding properties at each site relative to the individual monovalent single-chain antibody prototype molecules. In both solid and solution phase binding assays, the bivalent bispecific single-chain antibody simultaneously bound both ligands (fluorescein and (dT)6). Construction of a model bivalent bispecific molecule provides a foundation for future assembly of similar molecules designed to identify parameters involved in enhanced binding of antibodies due to avidity and dual specificity.
Apocynin Derivatives Interrupt Intracellular Signaling Resulting in Decreased Migration in Breast Cancer Cells (2006)

Cancer cells are defined by their ability to divide uncontrollably and metastasize to secondary sites in the body. Consequently, tumor cell migration represents a promising target for anticancer drug development. Using our high-throughput cell migration assay, we have screened several classes of compounds for noncytotoxic tumor cell migration inhibiting activity. One such compound, apocynin (4-acetovanillone), is oxidized by peroxidases to yield a variety of oligophenolic and quinone-type compounds that are recognized inhibitors of NADPH oxidase and may be inhibitors of the small G protein Rac1 that controls cell migration. We report here that while apocynin itself is not effective, apocynin derivatives inhibit migration of the breast cancer cell line MDA-MB-435 at subtoxic concentrations; the migration of nonmalignant MCF10A breast cells is unaffected. These compounds also cause a significant rearrangement of the actin cytoskeleton, cell rounding, and decreased levels of active Rac1 and its related G protein Cdc42. These results may suggest a promising new route to the development of novel anticancer therapeutics.
CP-154,526: a potent and selective nonpeptide antagonist of corticotropin releasing factor receptors. (1996)

Here we describe the properties of CP-154,526, a potent and selective nonpeptide antagonist of corticotropin (ACTH) releasing factor (CRF) receptors. CP-154,526 binds with high affinity to CRF receptors (Ki < 10 nM) and blocks CRF-stimulated adenylate cyclase activity in membranes prepared from rat cortex and pituitary. Systemically administered CP-154,526 antagonizes the stimulatory effects of exogenous CRF on plasma ACTH, locus coeruleus neuronal firing and startle response amplitude. Potential anxiolytic activity of CP-154,526 was revealed in a fearpotentiated startle paradigm. These data are presented in the context of clinical findings, which suggest that CRF is hypersecreted in certain pathological states. We propose that a CRF antagonist such as CP-154,526 could affirm the role of CRF in certain psychiatric diseases and may be of significant value in the treatment of these disorders.
A New Map of Glycosaminoglycan and C3b Binding Sites on Factor H (2008)

Human complement factor H, consisting of 20 complement control protein (CCP) modules, is an abundant plasma glycoprotein. It prevents C3b amplification on self surfaces bearing certain polyanionic carbohydrates, while complement activation progresses on most other, mainly foreign, surfaces. Herein, locations of binding sites for polyanions and C3b are reexamined rigorously by overexpressing factor H segments, structural validation, and binding assays. As anticipated, constructs corresponding to CCPs 7-8 and 19-20 bind well in heparin-affinity chromatography. However, CCPs 8-9, previously reported to bind glycosaminoglycans, bind neither to heparin resin nor to heparin fragments in gel-mobility shift assays. Introduction of nonnative residues N-terminal to a construct containing CCPs 8-9, identical to those in proteins used in the previous report, converted this module pair to an artificially heparin-binding one. The module pair CCPs 12-13 does not bind heparin appreciably, notwithstanding previous suggestions to the contrary. We further checked CCPs 10-12, 11-14, 13-15, 10-15, and 8-15 for ability to bind heparin but found very low affinity or none. As expected, constructs corresponding to CCPs 1-4 and 19-20 bind C3b amine coupled to a CM5 chip (K(d)s of 14 and 3.5 microM, respectively) or a C1 chip (K(d)s of 10 and 4.5 microM, respectively). Constructs CCPs 7-8 and 6-8 exhibit measurable affinities for C3b according to surface plasmon resonance, although they are weak compared with CCPs 19-20. Contrary to expectations, none of several constructs encompassing modules from CCP 9 to 15 exhibited significant C3b binding in this assay. Thus, we propose a new functional map of factor H.
Performance Management of Solar Water Heating Installations (1986)

Study of the results of two sets of year long performance measurements on domestic solar water heating systems led to the conclusion that the data could be treated on a daily basis by a simple linear regression procedure for two variables and that this would provide a satisfactory estimate of annual solar energy used. A much shorter test than one year under outdoor conditions would be adequate provided that certain conditions were satisfied. A comparatively quick and simple procedure was also available to obtain an approximate estimate of performance. The measurement procedures can be applied to systems other than solar.
Super-long photonic nanojet generated from liquid-filled hollow microcylinder (2015)

Photonic nanojet (PNJ) from liquid-filled hollow microcylinder (LFHM) under a liquid immersion condition is numerically investigated based on the finite element method and physically analyzed with ray optics. Simulation and analysis results show that, by simultaneously introducing the immersed liquid and filled liquid, the propagation beam is greatly flattened, and super-long PNJs with decay length more than 100 times the illumination wavelengths are obtained in the outer near-field region of the LFHM. With the variation of the refractive index contrast between the filled and immersed-liquids, the properties of the PNJs, such as the focal distance, decay length, full width at half-maximum, and maximum light intensity can be flexibly tuned.
Cystatin C reduces thein vitroformation of soluble Aβ1‐42 oligomers and protofibrils (2006)

There are an increasing number of genetic and neuropathological observations to suggest that cystatin C, an extracellular protein produced by all nucleated cells, might play a role in the pathophysiology of sporadic Alzheimer's disease (AD). Recent observations indicate that small and large soluble oligomers of the β‐amyloid protein (Aβ) impair synaptic plasticity and induce neurotoxicity in AD. The objective of the present study was to investigate the influence of cystatin C on the production of such oligomers in vitro. Co‐incubation of cystatin C with monomeric Aβ1‐42 significantly attenuated the in vitro formation of Aβ oligomers and protofibrils, as determined using electron microscopy (EM), dodecyl sulphate polyacrylamide gel electrophoresis (SDS‐PAGE), immunoblotting, thioflavin T (ThT) spectrofluorimetry and gel chromatography. However, cystatin C did not dissolve preformed Aβ oligomers. Direct binding of cystatin C to Aβ was demonstrated with the formation of an initial 1:1 molar high‐affinity complex. These observations suggest that cystatin C might be a regulating element in the transformation of monomeric Aβ to larger and perhaps more toxic molecular species in vivo.
Cyclic di‐nucleotides: new era for small molecules as adjuvants (2011)

The implementation of vaccination as an empiric strategy to protect against infectious diseases was introduced even before the advent of hygiene and antimicrobials in the medical practice. Nevertheless, it was not until a few decades ago that we really started understanding the underlying mechanisms of protection triggered by vaccination. Vaccines were initially based on attenuated or inactivated organisms. Subunit vaccines were then introduced as more refined formulations, exhibiting improved safety profiles. However, purified antigens tend to be poorly immunogenic and often require the use of adjuvants to achieve adequate stimulation of the immune system. Vaccination strategies, such as mucosal administration, also require potent adjuvants to improve performance. In the 1990s, immunologists found that pathogens could be sensed as 'danger signals' by receptors recognizing conserved motifs. Although our knowledge is still limited, tremendous advances were made in the understanding of host defence mechanisms regulated by these evolutionary conserved receptors, and the molecular structures which are recognized by them. This opened a new era in adjuvant development. Some of the latest players arrived to this field are the cyclic di-nucleotides, which are ubiquitous prokaryotic intracellular signalling molecules. This review is focused on their potential for the development of vaccines and immunotherapies.
Primary sclerosing cholangitis (1999)

Primary sclerosing cholangitis (PSC) is a chronic cholestatic syndrome of unknown etiology commonly associated with inflammatory bowel disease (IBD) and characterized by fibrosing inflammatory destruction of intra-and/or extrahepatic biliary ducts. Currently, liver transplantation is the only life-extending therapeutic alternative for patients with end-stage PSC.
Low-dose Irinotecan as a Second-line Chemotherapy for Recurrent Small Cell Lung Cancer (2014)

Low-dose irinotecan monotherapy for recurrent small cell lung cancer might be effective with favorable toxicity. Randomized trial of 60 mg/m(2) versus standard dose of irinotecan is warranted.
Update on the use of systemic biologic agents in the treatment of noninfectious uveitis (2014)

Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet's disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine) may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet's disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present work aims to provide a broad and updated review of the current and in-development systemic biologic agents for the treatment of noninfectious uveitis.
Side Effects of Methylphenidate and Dexamphetamine in Children With Attention Deficit Hyperactivity Disorder: A Double-blind, Crossover Trial (1997)

Many symptoms commonly attributed to stimulant medication are actually preexisting characteristics of children with ADHD and improve with stimulant treatment. At the doses investigated, both DEX and MPH caused appetite suppression, and DEX caused insomnia. Negative emotional symptoms were more severe on DEX than MPH.
Quantitative proteome analysis reveals annexin A3 as a novel biomarker in lung adenocarcinoma (2008)

Metastasis is a common phenomenon and the major lethal cause of lung adenocarcinoma (AdC). To discover novel potential biomarkers associated with lymph node metastasis and prognosis in lung AdC, we assessed differences in protein expression between primary lung AdC with (LNM AdC) and without lymph node metastasis (non-LNM AdC) using a quantitative proteomic approach. Laser capture microdissection was performed to purify the cancer cells from primary lung AdC tissues. The differential proteins between the pooled microdissected non-LNM AdC and LNM AdC tissues were identified by two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). In this study, twenty proteins were found to be differentially expressed in two types of lung AdC. ANXA3, significantly up-regulated in LNM AdC compared with non-LNM AdC, was validated by western blotting. Immunohistochemistry showed that ANXA3 over-expression was frequently observed in LNM AdCs and matched lymph node metastases compared with non-LNM AdCs. ANXA3 over-expression was significantly associated with advanced clinical stage (p < 0.001) and lymph node metastasis (p < 0.001) and increased relapse rate (p < 0.001) and decreased overall survival (p < 0.001) in lung AdCs. Cox regression analysis indicated ANXA3 over-expression was an independent prognostic factor. Our results indicate that ANXA3 might serve as a novel biomarker for lymph node metastasis and prognosis in lung AdC, and play an important role in lung AdC progression.
The Crystal Structure of a T Cell Receptor in Complex with Peptide and MHC Class II (1999)

The crystal structure of a complex involving the D10 T cell receptor (TCR), 16-residue foreign peptide antigen, and the I-Ak self major histocompatibility complex (MHC) class II molecule is reported at 3.2 angstrom resolution. The D10 TCR is oriented in an orthogonal mode relative to its peptide-MHC (pMHC) ligand, necessitated by the amino-terminal extension of peptide residues projecting from the MHC class II antigen-binding groove as part of a mini beta sheet. Consequently, the disposition of D10 complementarity-determining region loops is altered relative to that of most pMHCI-specific TCRs; the latter TCRs assume a diagonal orientation, although with substantial variability. Peptide recognition, which involves P-1 to P8 residues, is dominated by the Valpha domain, which also binds to the class II MHC beta1 helix. That docking is limited to one segment of MHC-bound peptide offers an explanation for epitope recognition and altered peptide ligand effects, suggests a structural basis for alloreactivity, and illustrates how bacterial superantigens can span the TCR-pMHCII surface.
Documenting Biospecimen Conditions in Reports of Studies (2008)

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