gebhart/patrepeval huggingface dataset:
Concise Review: Hitting the Right Spot with Mesenchymal Stromal Cells (2010)

Mesenchymal stromal cells or mesenchymal stem cells (MSCs) have captured considerable scientific and public interest because of their potential to limit physical and immune injury, to produce bioactive molecules and to regenerate tissues. MSCs are phenotypically heterogeneous and distinct subpopulations within MSC cultures are presumed to contribute to tissue repair and the modulation of allogeneic immune responses. As the first example of efficacy, clinical trials for prevention and treatment of graft-versus-host disease after hematopoietic cell transplantation show that MSCs can effectively treat human disease. The view of the mechanisms whereby MSCs function as immunomodulatory and reparative cells has evolved simultaneously. Initially, donor MSCs were thought to replace damaged cells in injured tissues of the recipient. More recently, however, it has become increasingly clear that even transient MSC engraftment may exert favorable effects through the secretion of cytokines and other paracrine factors, which engage and recruit recipient cells in productive tissue repair. Thus, an important reason to investigate MSCs in mechanistic preclinical models and in clinical trials with well-defined end points and controls is to better understand the therapeutic potential of these multifunctional cells. Here, we review the controversies and recent insights into MSC biology, the regulation of alloresponses by MSCs in preclinical models, as well as clinical experience with MSC infusions (Table 1) and the challenges of manufacturing a ready supply of highly defined transplantable MSCs.
Insulin Kinetics, Models, and Delivery Schedules (1980)

Several insulin models are examined as to their responses to various insulin inputs and glucose utilization and production control. It is shown that the action of insulin on glucose utilization correlates best with model compartments having a 30--50-min delay compared with plasma, whereas glucose production control is rapid. It is further shown that whereas the predicted plasma insulin response curves are nearly the same for various models, the responses at possible sites of action (e.g., receptors or slowly exchanging tissues) can differ considerably for the different models. By determining the parameter values for the glucose-insulin system in a patient through isotope kinetics studies, it is possible to use the patient's model either as a direct algorithm for insulin delivery or as a tool for studying glucose control under various conditions and thus aid in the design of appropriate algorithms or schedules for insulin delivery.
Graphene-based quantum capacitance wireless vapor sensors (2013)

A wireless vapor sensor based upon the quantum capacitance effect in graphene is demonstrated. The sensor consists of a metal-oxide-graphene variable capacitor (varactor) coupled to an inductor, creating a resonant oscillator circuit. The resonant frequency is found to shift in proportion to water vapor concentration for relative humidity (RH) values ranging from 1% to 97% with a linear frequency shift of 5.7 +- 0.3 kHz / RH%. The capacitance values extracted from the wireless measurements agree with those determined from capacitance-voltage measurements, providing strong evidence that the sensing arises from the variable quantum capacitance in graphene. These results represent a new sensor transduction mechanism and pave the way for graphene quantum capacitance sensors to be studied for a wide range of chemical and biological sensing applications.
Deepwater Drilling Riser System (1986)

Summary The principal focus of this paper is to discuss and summarize, from the manufacturer's perspective, the primary milestones in the development of the marine riser system used to drill in record water depths off the U.S. east coast. This riser system is unique in that it used advanced designs, material technology, and quality control to enable safe operation in water depths beyond the capability of conventional drilling riser systems. Experience and research have led to design improvements that are now being incorporated in new riser systems that have the potential of expanding the frontiers to increasingly deeper water.
Mammalian end binding proteins control persistent microtubule growth (2009)

End binding proteins (EBs) are highly conserved core components of microtubule plus-end tracking protein networks. Here we investigated the roles of the three mammalian EBs in controlling microtubule dynamics and analyzed the domains involved. Protein depletion and rescue experiments showed that EB1 and EB3, but not EB2, promote persistent microtubule growth by suppressing catastrophes. Furthermore, we demonstrated in vitro and in cells that the EB plus-end tracking behavior depends on the calponin homology domain but does not require dimer formation. In contrast, dimerization is necessary for the EB anti-catastrophe activity in cells; this explains why the EB1 dimerization domain, which disrupts native EB dimers, exhibits a dominant-negative effect. When microtubule dynamics is reconstituted with purified tubulin, EBs promote rather than inhibit catastrophes, suggesting that in cells EBs prevent catastrophes by counteracting other microtubule regulators. This probably occurs through their action on microtubule ends, because catastrophe suppression does not require the EB domains needed for binding to known EB partners.
Phosphorylation of DNA topoisomerase II by casein kinase II: modulation of eukaryotic topoisomerase II activity in vitro. (1985)

The phosphorylation of Drosophila melanogaster DNA topoisomerase II by purified casein kinase II was characterized in vitro. Under the conditions used, the kinase incorporated a maximum of 2-3 molecules of phosphate per homodimer of topoisomerase II. No autophosphorylation of the topoisomerase was observed. The only amino acid residue modified by casein kinase II was serine. Apparent Km and Vmax values for the phosphorylation reaction were 0.4 microM topoisomerase II and 3.3 mumol of phosphate incorporated per min per mg of kinase, respectively. Phosphorylation stimulated the DNA relaxation activity of topoisomerase II by 3-fold over that of the dephosphorylated enzyme, and the effects of modification could be reversed by treatment with alkaline phosphatase. Therefore, this study demonstrates that post-translational enzymatic modifications can be used to modulate the interaction between topoisomerase II and DNA.
The pinned photodiode for an interline-transfer CCD image sensor (1984)

A pinned photodiode has been developed for use in an interline-transfer CCD. This photoelement has excellent blue response and high charge capacity. Both modeling and experimental results will be presented, including process considerations necessary to avoid unwanted barriers at the diode/transfer-gate edge.
Multiple Splice Variants of the Human Calcium-independent Phospholipase A2 and Their Effect on Enzyme Activity (1998)

Recently, the cloning of a novel Ca2+-independent phospholipase A2 (iPLA2) from Chinese hamster ovary cells as well as from mouse and rat sources containing a C-terminal lipase motif and eight N-terminal ankyrin repeats has been described. In this report we describe the cloning of the human iPLA2 cDNA and its expression in B-cells and show that the iPLA2 gene undergoes extensive alternative splicing generating multiple isoforms that contribute to a novel mechanism to control iPLA2 activity. The full-length cDNA clone encodes a 806-amino acid protein with a calculated molecular mass of 88 kDa. The protein contains a lipase motif, GXSXG, and ankyrin repeats, as described for the hamster and rodent forms of the enzyme but has an additional 54-amino acid proline-rich insertion in the last of the eight ankyrin repeats (residues 395-449). Furthermore, at least three additional isoforms most likely due to alternative splicing were identified. One that is present as a partial cDNA in the expressed sequence tag data base is similar to iPLA2 but terminates just after the lipase active site, and two other isoforms contain only the iPLA2 ankyrin repeat sequence (ankyrin-iPLA2-1 and -2). Ankyrin repeats are involved in protein-protein interactions and because the purified iPLA2 enzyme exists as a multimeric complex of 270-350 kDa, the expression of just the ankyrin-iPLA2 sequence suggested that these may also interact with the iPLA2 oligomeric complexes and perhaps modulate PLA2 activity. Transfection of the human iPLA2 cDNA into COS cells resulted in a substantial increase in calcium-independent PLA2 activity in cell lysate. No activity above background was observed following ankyrin-iPLA2-1 cDNA transfection. However, co-transfection of the ankyrin-iPLA2-1 and the iPLA2 cDNAs resulted in a 2-fold reduction in activity compared with iPLA2 alone. A similar co-transfection of ankyrin-iPLA2-1 cDNA with the cPLA2 cDNA had no effect on PLA2 activity. These results suggest that the ankyrin-iPLA2 sequence can function as a negative regulator of iPLA2 activity and that the alternative splicing of the iPLA2 gene can have a direct effect on the attenuation of enzyme activity.
Hereditary and acquired angioedema: experience with patients in Puerto Rico. (2004)

Hereditary (HAE) and acquired (AAE) angioedema are vascular reactions involving the sub mucosal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries. HAE and AAE are clinical disorders characterized by angioedema that require prompt differentiation from other causes of angioedema in order to receive the most pertinent and effective therapeutic interventions. The aim of this report is to describe the clinical characteristics of patients with both HAE and AAE identified and followed at the Immunology Clinic of the University Hospital at the Puerto Rico Medical Center, their response and side effects to danazol therapy and their comparison with other series of similar patients reported in the literature. Overall, the patients in this sample presented a similar clinical profile compared to other reported series in the literature.
Detection of Specific Sequences in RNA Using Differential Adsorption of Single-Stranded Oligonucleotides on Gold Nanoparticles (2005)

We have used the disparity in adsorption rates for single- and double-stranded RNA on ionically coated gold nanoparticles suspended in a colloid to design a rapid sequence identification assay. Unlabeled target RNA and a probe sequence are mixed prior to exposure to the gold nanoparticles to enable efficient hybridization. We have designed assays based on either color changes or fluorescence that are sensitive to a few picomoles of target. Single-base mutations on RNA sequences can be detected even in complex oligonucleotide mixtures. The assay requires less than 10 min so that RNA degradation problems are avoided.
Urinary dysfunction in early and untreated Parkinson's disease (2011)

Urinary dysfunction, manifested primarily as storage disorders with subclinical voiding disorders and normal anal-sphincter electromyography, occurs in early and untreated PD patients. In cases with severe voiding disorder and/or abnormal anal-sphincter electromyography, other diagnoses should be considered.
Synthesis, photophysical, electrochemical, and electrochemiluminescent properties of 5,15-bis(9-anthracenyl)porphyrin derivatives (2009)

Novel 5,15-bis(9-anthracenyl)porphyrin derivatives (, ) were synthesized by stepwise Suzuki-type coupling reactions using anthracenyl-boronates bearing various electronically active moieties. Absorption spectra of these porphyrin conjugates reveal some degree of delocalisation with the directly linked chromophores, particularly in the case of anthracenyl-porphyrin bearing dimethylanilino moieties at the two extremities. Fluorescence and 77 K phosphorescence properties indicate that the excitation energy is invariably funnelled to the lowest singlet and triplet states of the porphyrin chromophore. The latter levels have been probed also by transient absorption spectroscopy, showing the typical triplet features detected in meso-substituted porphyrins. Extensive electrochemical studies have been performed to unravel the electronic properties of the newly synthesized porphyrins. Low-temperature cyclic voltammetry investigations showed that the anthracenyl-porphyrins are capable of undergoing as many as four electron transfer processes. In particular, by means of UV-Vis-NIR spectroelectrochemical measurements, a NIR-centred intramolecular photoinduced intervalence charge transfer (IV-CT) from a neutral N,N-dimethylanilino moiety to the N,N-dimethylanilino radical cation has been observed for the doubly-oxidised porphyrin (2+). The molecules also showed unexpected electrogenerated chemiluminescence properties, which revealed to be largely controlled by the electronic characteristics of the peripheral anthracenyl substituents. The structural and the electronic properties of these complexes have been also characterised by DFT calculations, as well as by X-ray crystallographic analyses.
Identification and Functional Analysis of a Novel Cyclin E/Cdk2 Substrate Ankrd17 (2009)

Cyclin E/Cdk2 is a key regulator in G(1)-S transition. We have identified a novel cyclin E/Cdk2 substrate called Ankrd17 (ankyrin repeat protein 17) using the TAP tag purification technique. Ankrd17 protein contains two clusters of a total 25 ankyrin repeats at its N terminus, one NES (nuclear exporting signal) and one NLS (nuclear localization signal) in the middle, and one RXL motif at its C terminus. Ankrd17 is expressed in various tissues and associates with cyclin E/Cdk2 in an RXL-dependent manner. It can be phosphorylated by cyclin E/Cdk2 at 3 phosphorylation sites (Ser(1791), Ser(1794), and Ser(2150)). Overexpression of Ankrd17 promotes S phase entry, whereas depletion of Ankrd17 expression by small interfering RNA inhibits DNA replication and blocks cell cycle progression as well as up-regulates the expression of p53 and p21. Ankrd17 is localized to the nucleus and interacts with DNA replication factors including MCM family members, Cdc6 and PCNA. Depletion of Ankrd17 results in decreased loading of Cdc6 and PCNA onto DNA suggesting that Ankrd17 may be directly involved in the DNA replication process. Taken together, these data indicate that Ankrd17 is an important downstream effector of cyclin E/Cdk2 and positively regulates G(1)/S transition.
Met protein expression level correlates with survival in patients with late-stage nasopharyngeal carcinoma. (2002)

Met tyrosine kinase, the receptor for HGF/SF, is important in various cellular functions, including proliferation, mitogenesis, formation of branching tubules, angiogenesis, and tumor cell invasion and metastasis. However, the role of Met/HGF signaling pathway in nasopharyngeal carcinoma (NPC) has not been evaluated. In this study, we determined the expression profile and clinical correlation of Met/HGF in 66 cases of advanced NPC and the activation mechanisms of Met receptor in five NPC cell lines. Immunofluorescent staining and quantitative image analysis showed that the Met protein was expressed throughout the tumors and normal nasopharyngeal epithelia. Compared with NPC, the Met expression level was higher in columnar nasopharyngeal epithelium but lower in squamous nasopharyngeal epithelium. The normal interstitial stromal tissue expressed the lowest level of Met protein. HGF was detected mainly in the normal interstitial tissue surrounding the tumor. Met protein expression level was inversely correlated with patients' survival time; the correlation coefficient was -0.319 (P = 0.009). The mean survival time was 118 months in low Met expression group versus 52 months in high expression group (P = 0.0004). The cumulative 5-year survival rate was 77.68% in low expression group versus 38.24% in high expression group. The clinical stage was also significantly more advanced in high Met expression group. In the multivariate analysis, both clinical stage and Met protein expression level were independent prognostic indicators for patient survival. All of the five NPC cell lines tested did not express hgf mRNA but expressed met mRNA, and tyrosine phosphorylation of Met protein was mainly induced by exogenous HGF stimulation in these cells. No mutation was found in the tyrosine kinase and the juxtamembrane domains of Met receptor in the five NPC cell lines tested. These results indicate that: (a) high Met protein expression level correlates with poorer survival in late-stage NPC and serves as an independent prognostic indicator; and (b) the Met receptor in NPC is activated by its paracrine ligand HGF from the interstitial tissues rather than by an autocrine loop or its activating mutation.
Simultaneous detection of microsatellite repeats and SNPs in the macrophage migration inhibitory factor (MIF) gene by thin-film biosensor chips and application to rural field studies (2005)

Microsatellite repeat and single nucleotide polymorphisms (SNPs) are abundant sources of genetic variation, but existing methodologies cannot simultaneously detect these variants in a facile or inexpensive way. We describe herein a thin-film biosensor chip based on an allele-discriminating oligonucleotide array that enables genotyping for both microsatellite repeats and SNPs in a single analysis. We validated this methodology for the functionally polymorphic -794 CATT(5-8) repeat and -173 G/C SNP present in the promoter of the human gene for macrophage migration inhibitory factor (MIF). In a comparison of 30 samples collected at a rural hospital in Zambia, we observed a 100% concordance for both the CATT repeat and G/C SNP between the biosensor methodology and the conventional capillary electrophoresis. The biosensor chips are low in cost and once printed, they are robust and require no instrumentation for analysis. When combined with multiple displacement amplification, this methodology can be utilized in primitive settings for the genotyping of nanogram quantities of DNA present in blood, dried and stored on filter paper samples. We applied this methodology to a field study of MIF genotype in children with malaria, and provide first evidence for a potential association between MIF alleles and malaria infection. We also present data supporting significant population stratification of the low- versus high-expression forms of MIF that may bear on the role of this gene in infectious diseases.
Tip-Techniques for Microcharacterization of Materials (1987)

The invention of the Scanning Tunneling Microscope has stimulated the development of new techniques for microcharacterization of materials, which are based on the use of a very fine tip. Two of these techniques have emerged about one year ago, the Thermal Profiler and the Atomic Force Microscope. Both techniques have recently demonstrated the capability to profile and image conductors and insulators. The resolution attained varies from approximately 50 nm by the Thermal Profiler to a few nanometers with the Atomic Force Microscope, therefore competing with the resolution obtained with electron beam microscopy. We shall describe the principle of these techniques, and present recent results obtained for surface profiling, as well as for temperature mapping, force measurement and mapping of magnetic field on a nanometer scale.
D-periodic distribution of collagen type IX along cartilage fibrils. (1988)

It has recently become apparent that collagen fibrils may be composed of more than one kind of macromolecule. To explore this possibility, we developed a procedure to purify fibril fragments from 17-d embryonic chicken sternal cartilage. The fibril population obtained shows, after negative staining, a uniformity in the banding pattern and diameter similar to the fibrils in situ. Pepsin digestion of this fibril preparation releases collagen types II, IX, and XI in the proportion of 8:1:1. Rotary shadowing of the fibrils reveals a d-periodic distribution of 35-40-nm long projections, each capped with a globular domain, which resemble in form and dimensions the aminoterminal globular and collagenous domains, NC4 and COL3, of type IX collagen. The monoclonal antibody (4D6) specific for an epitope close to the amino terminal of the COL3 domain of type IX collagen bound to these projections, thus confirming their identity. Type IX collagen is therefore distributed in a regular d-periodic arrangement along cartilage fibrils, with the chondroitin sulfate chain of type IX collagen in intimate contact with the fibril.
Current-dependent Block of Rabbit Sino-Atrial Node If Channels by Ivabradine (2002)

"Funny" (f-) channels have a key role in generation of spontaneous activity of pacemaker cells and mediate autonomic control of cardiac rate; f-channels and the related neuronal h-channels are composed of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel subunits. We have investigated the block of f-channels of rabbit cardiac sino-atrial node cells by ivabradine, a novel heart rate-reducing agent. Ivabradine is an open-channel blocker; however, block is exerted preferentially when channels deactivate on depolarization, and is relieved by long hyperpolarizing steps. These features give rise to use-dependent behavior. In this, the action of ivabradine on f-channels is similar to that reported of other rate-reducing agents such as UL-FS49 and ZD7288. However, other features of ivabradine-induced block are peculiar and do not comply with the hypothesis that the voltage-dependence of block is entirely attributable to either the sensitivity of ivabradine-charged molecules to the electrical field in the channel pore, or to differential affinity to different channel states, as has been proposed for UL-FS49 (DiFrancesco, D. 1994. Pflugers Arch. 427:64-70) and ZD7288 (Shin, S.K., B.S. Rotheberg, and G. Yellen. 2001. J. Gen. Physiol. 117:91-101), respectively. Experiments where current flows through channels is modified without changing membrane voltage reveal that the ivabradine block depends on the current driving force, rather than voltage alone, a feature typical of block induced in inwardly rectifying K(+) channels by intracellular cations. Bound drug molecules do not detach from the binding site in the absence of inward current through channels, even if channels are open and the drug is therefore not "trapped" by closed gates. Our data suggest that permeation through f-channel pores occurs according to a multiion, single-file mechanism, and that block/unblock by ivabradine is coupled to ionic flow. The use-dependence resulting from specific features of I(f) block by ivabradine amplifies its rate-reducing ability at high spontaneous rates and may be useful to clinical applications.
A novel drug delivery system for osteomyelitis using porous hydroxyapatite blocks loaded by centrifugation (1995)

A novel drug delivery system for osteomyelitis was developed using porous hydroxyapatite blocks (HA-b) loaded with antibiotics by centrifugation. In the study, 10 mm3 HA-b was placed in a container and mixed with antibiotic solution; the antibiotic was then loaded into the pores of the HA-b by centrifuging at 1500 rpm for 15 min. Slow release of HA-b in both moist form and dried form (by heating at 160 degrees C) was tested after loading with the antibiotic arbekacin sulfate (ABK), 1-N-(S)-4 amino-2-hydroxybutyryl dibekacin. To estimate the concentration of antibiotic, both forms of HA-b were placed in 3 mL of phosphate buffered saline (PBS), which was replaced every 48 h. In both groups, which were loaded with 70 mg ABK per one block of HA (concn 0.5 microgram/mL) which is sufficiently high to control most pathogens, was maintained for 21 exchanges of PBS (after 42 days). Minimum inhibitory concentration for methicillin-resistant Staphylococcus aureus (MRSA), 3.13 micrograms/mL, was maintained until nine exchanges took place (after 18 days). The centrifugation method is simple, and dried ABK produced by heating loaded HA-b is particularly useful in clinical applications for osteomyelitis.