gebhart/patrepeval huggingface dataset:
Preparation, Microscopy, and Flow Cytometry with Excitation into Surface Plasmon Resonance Bands of Gold or Silver Nanoparticles on Aminodextran-Coated Polystyrene Beads (2000)

Spherical polystyrene latex beads of about 2.0 μm diameter were coated with islands of silver or gold metal, about 5−200 nm in diameter, by reduction of aqueous silver or gold ions in the presence of sugar-coated polystyrene latex beads. The metal islands are held on the bead surface by a polymeric sugar derivative, aminodextran, covalently bound to the polystyrene aldehyde/sulfate bead. Images of the gold or silver nanoparticle-coated polystyrene beads, obtained with an optical microscope, show that gold, silver, and uncoated polystyrene beads can be distinguished by their different colors, red-purple, black, and colorless, respectively. Also, scanning electron micrographs of coated versus uncoated polystyrene beads show a distinct granular bead surface when metal nanostructures are present versus a smooth bead surface when they are absent. Nanoparticles of gold greater than about 50 nm in diameter on polystyrene beads showed enhanced 90° or side light scatter (resonant Rayleigh scattering) with excitation at 633 nm but no enhancement (same light scatter intensity as uncoated polystyrene beads) at excitation wavelengths of 544, 488, and 458 nm. On the other hand, nanoparticles of silver greater than about 50 nm in diameter on polystyrene beads showed enhanced 90° or side light scatter with excitation wavelengths of 458, 488, 544, and 633 nm but no enhancement with 351−365 nm excitation. Amplification of elastic scatter from both silver and gold colloids was maximally achieved with structures of 50−200 nm diameter, as shown in forward versus side scatter histograms obtained by flow cytometry. Side scatter enhancements of 2- to 10-fold were observed for gold- or silver-coated polystyrene beads over uncoated polystyrene beads of the same diameter. The origin of this wavelength-dependent, light scattering amplification that was observed by flow cytometry has been identified with excitation into surface plasmon resonance bands of gold and silver nanoparticles on polystyrene latex beads.
Influence of l -dopa and pramipexole on striatal dopamine transporter in early PD (2001)

Short-term therapy with L-dopa and, to a lesser extent, pramipexole can modestly down-regulate striatal DAT in patients with early PD. Decreased striatal DAT could increase dopaminergic neurotransmission with potential benefit, but might also play a role in the development of dopamine-related response fluctuations in patients with advanced disease. Our data also suggest caution in interpretation of longitudinal imaging studies employing DAT to assess disease progression and the efficacy of neuroprotective agents.
Advances in Therapeutics for Neurodegenerative Tauopathies: Moving toward the Specific Targeting of the Most Toxic Tau Species (2014)

Neurodegenerative disease is one of the greatest health concerns today and with no effective treatment in sight, it is crucial that researchers find a safe and successful therapeutic. While neurofibrillary tangles are considered the primary tauopathy hallmark, more evidence continues to come to light to suggest that soluble, intermediate tau aggregates--tau oligomers--are the most toxic species in disease. These intermediate tau species may also be responsible for the spread of pathology, suggesting that oligomeric tau may be the best therapeutic target. Here, we summarize results for the modulation of tau by molecular chaperones, small molecules and aggregation inhibitors, post-translational modifications, immunotherapy, other techniques, and future directions.
PROTAMINE INSULINATE (1936)

When treating diabetes with insulin, one has to replace the regulated continuous secretion from the normal pancreas into the portal vein by a few daily injections into the subcutaneous tissue. This method is of course only a poor imitation of nature's own mechanism. Serious disturbances are avoided only because the organism has other means of regulating the blood sugar than to vary the rate of insulin secretion. This is the reason why treatment with one or two injections daily is found to give fairly good results in many cases. In more severe cases, however, very pronounced oscillations of the blood sugar may occur. During the last few hours before the injection metabolic disturbances develop, which tend to minimize the available deposits of carbohydrate, strongly needed when the blood sugar runs low after the injection. It is obvious that the insulin hydrochloride will rapidly become absorbed into the blood after the
Identification of Specific Nucleotide Sequences within the Conserved 3′-SL in the Dengue Type 2 Virus Genome Required for Replication (1998)

The flavivirus genome is a positive-stranded approximately 11-kb RNA including 5' and 3' noncoding regions (NCR) of approximately 100 and 400 to 600 nucleotides (nt), respectively. The 3' NCR contains adjacent, thermodynamically stable, conserved short and long stem-and-loop structures (the 3'-SL), formed by the 3'-terminal approximately 100 nt. The nucleotide sequences within the 3'-SL are not well conserved among species. We examined the requirement for the 3'-SL in the context of dengue virus type 2 (DEN2) replication by mutagenesis of an infectious cDNA copy of a DEN2 genome. Genomic full-length RNA was transcribed in vitro and used to transfect monkey kidney cells. A substitution mutation, in which the 3'-terminal 93 nt constituting the wild-type (wt) DEN2 3'-SL sequence were replaced by the 96-nt sequence of the West Nile virus (WN) 3'-SL, was sublethal for virus replication. An analysis of the growth phenotypes of additional mutant viruses derived from RNAs containing DEN2-WN chimeric 3'-SL structures suggested that the wt DEN2 nucleotide sequence forming the bottom half of the long stem and loop in the 3'-SL was required for viability. One 7-bp substitution mutation in this domain resulted in a mutant virus that grew well in monkey kidney cells but was severely restricted in cultured mosquito cells. In contrast, transpositions of and/or substitutions in the wt DEN2 nucleotide sequence in the top half of the long stem and in the short stem and loop were relatively well tolerated, provided the stem-loop secondary structure was conserved.
Nrf2 is essential for protection against acute pulmonary injury in mice (1999)

Nrf2 is a member of the "cap 'n' collar" family of transcription factors. These transcription factors bind to the NF-E2 binding sites (GCTGAGTCA) that are essential for the regulation of erythroid-specific genes. Nrf2 is expressed in a wide range of tissues, many of which are sites of expression for phase 2 detoxification genes. Nrf2(-/-) mice are viable and have a normal phenotype under normal laboratory conditions. The NF-E2 binding site is a subset of the antioxidant response elements that have the sequence GCNNNGTCA. The antioxidant response elements are regulatory sequences found on promoters of several phase 2 detoxification genes that are inducible by xenobiotics and antioxidants. We report here that Nrf2(-/-) mice are extremely susceptible to the administration of the antioxidant butylated hydroxytoluene. With doses of butylated hydroxytoluene that are tolerated by wild-type mice, the Nrf2(-/-) mice succumb from acute respiratory distress syndrome. Gene expression studies show that the expression of several detoxification enzymes is altered in the Nrf2(-/-) mice. The Nrf2(-/-) mice may prove to be a good in vivo model for toxicological studies. As oxidative damage causes DNA breakage, these mice may also be useful for testing carcinogenic agents.
Progress in research on ligands, nuclides and techniques for labeling monoclonal antibodies (1991)

This paper reviews the current methods for radiolabelling monoclonal antibodies with particular emphasis on radiometals useful for radioimmunoscintigraphy. The discussion, however, is equally applicable to therapeutic radionuclides. The advantages and the pitfalls of the various techniques are critically evaluated. Both direct labeling methods, as well as indirect methods using the bifunctional chelating agent approach, are covered. Recent work on the development and synthesis of new and more specific chelating agents, including the approach of utilizing rigid polyaminocarboxylates, is described. Preliminary promising results with these newer generation chelating agents are presented.
Ferrous Iron Is a Significant Component of Bioavailable Iron in Cystic Fibrosis Airways (2013)

Iron is an important environmental parameter that helps pathogens thrive in sites of infection, including those of cystic fibrosis (CF) patients. Ferric iron chelation therapy has been proposed as a novel therapeutic strategy for CF lung infections, yet until now, the iron oxidation state has not been measured in the host. In studying mucus from the infected lungs of multiple CF patients from Europe and the United States, we found that ferric and ferrous iron change in concentration and relative proportion as infections progress; over time, ferrous iron comes to dominate the iron pool. This information is relevant to the design of novel CF therapeutics and, more broadly, to developing accurate models of chronic CF infections.
Immortalization of osteoclast precursors by targeting Bcl -XL and Simian virus 40 large T antigen to the osteoclast lineage in transgenic mice. (1998)

Cellular and molecular characterization of osteoclasts (OCL) has been extremely difficult since OCL are rare cells, and are difficult to isolate in large numbers. We used the tartrate-resistant acid phosphatase promoter to target the bcl-XL and/or Simian Virus 40 large T antigen (Tag) genes to cells in the OCL lineage in transgenic mice as a means of immortalizing OCL precursors. Immunocytochemical studies confirmed that we had targeted Bcl-XL and/or Tag to OCL, and transformed and mitotic OCL were readily apparent in bones from both Tag and bcl-XL/Tag mice. OCL formation in primary bone marrow cultures from bcl-XL, Tag, or bcl-XL/Tag mice was twofold greater compared with that of nontransgenic littermates. Bone marrow cells from bcl-XL/Tag mice, but not from singly transgenic bcl-XL or Tag mice, have survived in continuous culture for more than a year. These cells form high numbers of bone-resorbing OCL when cultured using standard conditions for inducing OCL formation, with approximately 50% of the mononuclear cells incorporated into OCL. The OCL that form express calcitonin receptors and contract in response to calcitonin. Studies examining the proliferative capacity and the resistance of OCL precursors from these transgenic mice to apoptosis demonstrated that the increased numbers of OCL precursors in marrow from bcl-XL/Tag mice was due to their increased survival rather than an increased proliferative capacity compared with Tag, bcl-XL, or normal mice. Histomorphometric studies of bones from bcl-XL/Tag mice also confirmed that there were increased numbers of OCL precursors (TRAP + mononuclear cells) present in vivo. These data demonstrate that by targeting both bcl-XL and Tag to cells in the OCL lineage, we have immortalized OCL precursors that form bone-resorbing OCL with an efficiency that is 300-500 times greater than that of normal marrow.
Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole (2001)

Aggregation greatly boosts emission efficiency of the silole, turning it from a weak luminophor into a strong emitter.
Persistence of mild, early inflammatory arthritis: The importance of disease duration, rheumatoid factor, and the shared epitope (1999)

The strongest predictor of persistent disease was a disease duration of >12 weeks. Rheumatoid factor and SE were also predictors to a lesser extent. Patients who both fulfilled the ACR classification criteria for rheumatoid arthritis (RA) and had a short disease duration included some with an excellent prognosis. Therefore, 12 weeks may be a more appropriate disease duration to use for the RA classification criteria. Administering a bolus of corticosteroids may be a useful diagnostic/therapeutic approach.
Effects of Oxidative Stress on Mesenchymal Stem Cell Biology (2016)

Mesenchymal stromal/stem cells (MSCs) are multipotent stem cells present in most fetal and adult tissues. Ex vivo culture-expanded MSCs are being investigated for tissue repair and immune modulation, but their full clinical potential is far from realization. Here we review the role of oxidative stress in MSC biology, as their longevity and functions are affected by oxidative stress. In general, increased reactive oxygen species (ROS) inhibit MSC proliferation, increase senescence, enhance adipogenic but reduce osteogenic differentiation, and inhibit MSC immunomodulation. Furthermore, aging, senescence, and oxidative stress reduce their ex vivo expansion, which is critical for their clinical applications. Modulation of sirtuin expression and activity may represent a method to reduce oxidative stress in MSCs. These findings have important implications in the clinical utility of MSCs for degenerative and immunological based conditions. Further study of oxidative stress in MSCs is imperative in order to enhance MSC ex vivo expansion and in vivo engraftment, function, and longevity.
Ensuring privacy in presence awareness (2000)

Providing information about other users and their activites is a central function of many collaborative applications. The data that provide this "presence awareness" are usually automatically generated and highly dynamic. For example, services such as AOL Instant Messenger allow users to observe the status of one another and to initiate and participate in chat sessions. As such services become more powerful, privacy and security issues regarding access to sensitive user data become critical. Two key software engineering challenges arise in this context:
The Development of the Antitumour Benzothiazole Prodrug, Phortress, as a Clinical Candidate (2004)

This review traces the development of a series of potent and selective antitumour benzothiazoles from the discovery of the initial lead compound, 2-(4-amino-3-methylphenyl)benzothiazole (DF 203) in 1995 to the identification of a clinical candidate, Phortress, scheduled to enter Phase 1 trials in Q1 2004 under the auspices of Cancer Research U.K. Advances in our understanding of the mechanism of action of this unique series of agents are described and can be summarised as follows: selective uptake into sensitive cells followed by Arylhydrocarbon Receptor (AhR) binding and translocation into the nucleus, induction of the cytochrome P450 isoform (CYP) 1A1, conversion of the drug into an electrophilic reactive intermediate and formation of extensive DNA adducts resulting in cell death. Our understanding of this mechanistic scenario has played a crucial role in the drug development process, most notably in the synthesis of fluorinated DF 203 analogues to thwart deactivating oxidative metabolism (5F 203) and water-soluble prodrug design for parenteral administration. Aspects of mechanism of action studies, in vitro and in vivo screening, synthetic chemistry and pharmacokinetics are reviewed here.
Highly Pathogenic Avian Influenza Outbreaks in Europe, Asia, and Africa Since 1959, Excluding the Asian H5N1 Virus Outbreaks (2008)

This chapter contains sections titled: Introduction Great Britain South Africa Germany 1979 (H7N7) Ireland 1983 (H5N8) Italy The Netherlands, Belgium, and Germany 2003 (H7N7) Democratic People's Republic of Korea (North Korea) 2005 (H7N7) Conclusions References
Signaling in stem cell niches: lessons from theDrosophilagermline (2005)

Stem cells are cells that, upon division, can produce new stem cells as well as daughter cells that initiate differentiation along a specific lineage. Studies using the Drosophila germline as a model system have demonstrated that signaling from the stem cell niche plays a crucial role in controlling stem cell behavior. Surrounding support cells secrete growth factors that activate signaling within adjacent stem cells to specify stem cell self-renewal and block differentiation. In addition, cell-cell adhesion between stem cells and surrounding support cells is important for holding stem cells close to self-renewal signals. Furthermore, a combination of localized signaling and autonomously acting proteins might polarize stem cells in such a way as to ensure asymmetric stem cell divisions. Recent results describing stem cell niches in other adult stem cells, including hematopoietic and neural stem cells, have demonstrated that the features characteristic of stem cell niches in Drosophila gonads might be conserved.
Application REQuested IP over ATM (AREQUIPA) (1997)

This document specifies a method for allowing ATM-attached hosts that have direct ATM connectivity to set up end-to-end IP over ATM connections within the reachable ATM cloud, on request from applications, and for the exclusive use by the requesting applications. This allows the requesting applications to benefit in a straightforward way from ATM's inherent ability to guarantee the quality of service (QoS).
Acute dialysis and continuous renal replacement: the emergence of new technology involving the nephrologist in the intensive care setting. (1997)

The emergence of dialytic support for patients with reversible renal failure was one of the most significant advances in critical care medicine. Supporting a patient with a failed organ till organ recovery has not had the same success with other organ failures. Despite the indispensable nature of the support, dialysis was intermittent at best, and carried its own morbidity. The emergence of a "continuous" dialysis delivery system, originally through an arteriovenous access and later through veno-venous methodology, began to simulate the continuity of the natural kidney, and lifted much of the fluid and drug restrictions imposed by the intermittent nature of standard dialytic therapies. Components of the system were next reviewed for improvement and biocompatability. Differences in patient outcome were documented with various component comparisons, and disparate patient tolerance of delivery modality was also clearly proven. The hemodynamic stability of continuous treatment created utilization to be focused on the more unstable, the more severely compromised patient group. In this context, comparative studies with intermittent delivery methods showed improved hemodynamic stability among patients treated with continuous renal replacement therapies (CRRT), but no clear difference in patient mortality. Patient characteristics and severity scoring have recently been undertaken to better describe the population, and attempts at dialysis dosing is currently being developed for ARF dialysis recipients. Early results seem to point toward a dialysis dose effect on mortality in certain groups of ICU acute renal failure patients. However, the dialytic process is only depurative and artificial. Plastic membrane bio-incompatibility, human physiological responses to foreign material exposure, either in the circuit material itself or introduced from therapy methodology, pose practical and theoretical problems. Recent advances in the field of bio-artificial technology have allowed the development of functioning hybrid "blood processors," which function as a renal tubule and may be able to not only "clean" blood, but also allow for other cellular functions not currently possible with dead membrane technology. Combining living cells with a continuous delivery method may be the next significant step toward a fully functional renal replacement therapy.
Transdermal peptide delivery (1989)

The transdermal delivery of peptide drugs, though ill-favoured by their hydrophilicity and high molecular mass, would seem very attractive from the pharmacotherapeutical and patient compliance point of view. In some cases, effective transdermal dosing has been achieved in vivo, especially with the aid of iontophoresis. This paper deals with a dodecapeptide, des-enkephalin-gamma-endorphin, of which the transepidermal permeation and the intra(epi-)dermal biotransformation were both studied in vitro. Small, though measurable, fluxes through human stratum corneum were obtained in vitro, which could be enhanced by using a skin lipid fluidizer. The half-life of the peptide, both in the epidermis and in the dermis, was surprisingly long as compared with that in human plasma. Hence, improvement of the transdermal bioavailability of the peptide will most likely be obtained chiefly by enhancing its flux (possibly through iontophoresis), intra(epi-)dermal degradation being a problem of only minor importance.
The GARP modelling system: problems and solutions to automated spatial prediction (1999)

This paper is concerned with the problems and solutions to reliable analysis of arbitrary datasets. Our approach is to describe components of a system called the GARP Modelling System (GMS) which we have developed for automating predictive spatial modelling of the distribution of species of plants and animals. The essence of the system is an underlying generic spatial modelling method which filters out potential sources of errors. The approach is generally applicable however, as the statistical problems arising in arbitrary spatial data analysis potentially apply to any domain. For ease of development, GMS is integrated with the facilities of existing database and visualization tools, and Internet browsers. The GMS is an example of a class of application which has been very successful for providing spatial data analysis in a simple to use way via the Internet.
Sequential Use of lndium-111 Labeled Monoclonal Antibodies 96.5 and ZME-018 does not Increase Detection Sensitivity for Metastatic Melanoma (1989)

Two indium-111 labeled anti-melanoma murine monoclonal antibodies (MAb), 96.5 and ZME-018, each recognizing separate antigens on melanoma cells, were administered intravenously to 17 patients with melanoma in a sequential fashion to determine whether: 1) additional tumor sites could be imaged with the combination compared to a single Mab; 2) the first MAb influenced the biodistribution and tumor localization of the second; and 3) significantly toxicity occurred with the combination. Patients were randomized to receive either 96.5, followed by ZME-018, ZME-018 followed by 96.5, or each MAb followed by itself (controls). Infusions of the second MAb occurred 10 days after the first infusion. Gamma camera images were obtained 72 hours after each antibody infusion. There were 139 known metastatic sites of which 72 lesions were localized by either MAb for an overall sensitivity of 52%. The detection rate was higher when lesions only greater than 1.5 cm were considered. Imaging results were independent of MAb administration sequence. When ZME-018 was given as the first infusion, when ZME-018 was given as a second infusion (p = NS). However, mean sensitivities using 96.5 as the first or second infusion were 48% and 66% respectively (p = NS). There was not a significant number of sites detected by MAb 2 that were missed by MAb 1. Human anti-murine antibody (HAMA) response occurred in seven of eight patients studied; two patients who experienced toxicity had levels of HAMA greater than 2000 ng/ml. We conclude that the use of these two murine anti-melanoma monoclonal antibodies given in sequential fashion did not significantly change the imaging sensitivity from that seen with each individual antibody. Moreover, with the exception of one patient, mean plasma half-life of the MAb did not change significantly, suggesting that overall clearance mechanisms were not saturated by the consecutive doses of monoclonal antibody or significantly altered by the presence of HAMA.