gebhart/patrepeval huggingface dataset:
Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) in human osteoarthritic chondrocytes (2002)

Objective. We aimed to investigate the expression of nerve growth factor (NGF) and high&#13;\naffinity NGF receptor (p140 TrkA) on chondrocytes from human healthy and osteoarthritic&#13;\ncartilage.&#13;\nMethods. We recruited 12 patients with osteoarthritis (OA) undergoing surgical knee&#13;\nreplacement. Articular cartilage was split into two zones showing macroscopically and&#13;\nhistologically the lowest (MIN) and highest (MAX) degree of osteoarthritic damage. Additional&#13;\nspecimens of cartilage were obtained from three healthy donors. Chondrocytes were isolated by&#13;\nenzymatic digestion and freshly processed for NGF protein, Trk A detection and mRNA&#13;\nextraction. NGF-b mRNA was determined by a reverse transcriptase–polymerase chain reaction&#13;\n(RT–PCR). NGF-b and TrkA expression was evaluated by immunofluorescence and flow&#13;\ncytometry analysis.&#13;\nResults. NGF-b-specific mRNA was detected in normal and osteoarthritic chondrocytes.&#13;\nNGF-b protein levels were low in normal chondrocytes, increased in MIN osteoarthritic cartilage&#13;\nand further enhanced in MAX osteoarthritic cartilage. Likewise, TrkA was scarcely expressed on&#13;\nnormal chondrocytes and progressively increased on osteoarthritic chondrocytes based on the&#13;\nextent of anatomic damage.&#13;\nConclusions. This is the first study showing that human chondrocytes synthesize NFG-b and&#13;\nexpress on their surface the high affinity NGFR (p140 TrkA). Of note, NGF-b and TrkA were&#13;\nupregulated in osteoarthritic chondrocytes suggesting a role of NGF in the pathophysiology of&#13;\nOA. We can speculate that NGF, like other growth factors, stimulates chondrocyte metabolism&#13;\nin the osteoarthritic process
Total Syntheses of [17]- and [18]Dehydrodesoxyepothilones B via a Concise Ring-Closing Metathesis-Based Strategy:  Correlation of Ring Size with Biological Activity in the Epothilone Series (2002)

A convergent ring-closing metathesis strategy has been employed for the highly concise syntheses of 10,11-dehydro-13,14-[17]desoxyepothilone B ([17]ddEpoB) and 10,11-dehydro-14,15-[18]desoxyepothilone B ([18]ddEpoB), which are 17- and 18-membered ring homologues of 10,11-dehydro-12,13-desoxyepothilone B ([16]ddEpoB or epothilone 490). We have demonstrated that the ring-closing metathesis (RCM) provides [17]ddEpoB or [18]ddEpoB with a high level of stereocontrol in the generation of the desired olefin in the products. These analogues were evaluated for antitumor activity. The results from the in vitro assays revealed that the [17]ddEpoB analogue is highly active against various tumor cell lines with a potency comparable to that of [16]ddEpoB. This is the first example of a 17-membered ring macrolactone epothilone that has retained its antitumor activity. In contrast, the biological data revealed that [18]ddEpoB is significantly less active than either [17]ddEpoB or the parent [16]ddEpoB.
Structure and Regulation of the Gene Encoding the Neuron-specific Protein Kinase C Substrate Neurogranin (RC3 Protein) (1995)

A 13-kilobase pair genomic DNA encoding a 78-amino acid brain-specific calmodulin-binding protein kinase C (PKC) substrate, neurogranin (Ng/RC3; also known as RC3 or p17), has been sequenced. The Ng/RC3 gene is composed of four exons and three introns, with the protein-coding region located in the first and second exons. This gene was found to have multiple transcriptional start sites clustered within 20 base pairs (bp); it lacks the TATA, GC, and CCAAT boxes in the proximal upstream region of the start sites. The promoter activity was characterized by transfection of 293 cells with nested deletion mutants of the 5'-flanking region fused to the luciferase reporter gene. A minimal construct containing bp +11 to +256 was nearly as active as that covering bp -1508 to +256, whereas a shorter one covering bp +40 to +256 had a greatly reduced activity. Between bp +11 and +40 lies a 12-nucleotide sequence (CCCCGCCCACCC) containing overlapping binding sites for AP2 (CCGCCCACCC) and SP1 (CCCGCC); this region may be important for conferring the basal transcriptional activity of the Ng/RC3 gene. The expression of a Ng/RC3-luciferase fusion construct (-1508/+256) in transfected 293 cells was stimulated by phorbol 12-myristate 13-acetate (PMA), but not by cAMP, arachidonic acid, vitamin D, retinoic acid, or thyroxines T3 and T4. PMA caused a 2-4-fold stimulation of all the reporter gene constructs ranging from +11/+256 to -1508/+256. The stimulatory effects of PMA could be magnified by cotransfection with both Ca(2+)-dependent and -independent phorbol ester-binding PKC-alpha, -beta I, -beta II, -gamma, -delta, and -epsilon cDNAs, but not by non-phorbol ester-binding PKC-zeta cDNA. The Ng/RC3 and PKC-gamma genes have a similar expression pattern in the brain during development. These two genes share at least four conserved sequence segments 1.5 kilobase pair upstream from their transcriptional start sites and a gross similarity in that they possess several AT-rich segments within bp -550 to -950. A near homogeneous 20-kDa DNA-binding protein purified from rat brain was able to bind to these AT-rich regions of both Ng/RC3 and PKC-gamma genes with footprints containing ATTA, ATAA, and AATA sequences.
Therapeutic approaches to inflammation in neurodegenerative disease (2007)

It can be anticipated that a more detailed understanding of neuroinflammatory mechanisms in Parkinson's disease will lead to new cellular and molecular targets, which may, in turn, permit design of Parkinson's disease modifying drugs. Future treatment may involve combination therapies with drugs directed at both inflammatory and non-inflammatory mechanisms.
N,O-Chelating Four-Membered Metallacyclic Titanium(IV) Complexes for Atom-Economic Catalytic Reactions (2015)

Titanium, as the second most abundant transition metal in the earth's crust, lends itself as a sustainable and inexpensive resource in catalysis. Its nontoxicity and biocompatibility are also attractive features for handling and disposal. Titanium has excelled as a catalyst for a broad range of transformations, including ethylene and α-olefin polymerizations. However, many reactions relevant to fine chemical synthesis have preferrentially employed late transition metals, and reactive, inexpensive early transition metals have been largely overlooked. In addition to promising reactivity, titanium complexes feature more robust character compared with some other highly Lewis-acidic metals such as those found in the lanthanide series. Since the advent of modulating ligand scaffolds, titanium has found use in a growing variety of reactions as a versatile homogeneous catalyst. These catalytic transformations include hydrofunctionalization reactions (adding an element-hydrogen (E-H) bond across a C-C multiple bond), as well as the ring-opening polymerization of cyclic esters, all of which are atom-economic transformations. Our investigations have focused on tight bite angle monoanionic N,O-chelating ligands, forming four-membered metallacycles. These ligand sets, including amidates, ureates, pyridonates, and sulfonamidates, have flexible binding modes offering a range of stable and reactive intermediates necessary for catalytic activity. Additionally, the simple form of these ligands leads to easily prepared proligands, along with facile tuning of steric and electronic factors. A sterically bulky titanium amidate complex has proven to be a leading catalyst for the selective formation of anti-Markovnikov addition products via intermolecular hydroamination of terminal alkynes, while sterically less demanding titanium pyridonates have opened the path to the selective formation of amine substituted cycloalkanes via the intramolecular hydroaminoalkylation of aminoalkenes over the competing hydroamination pathway. Sulfonamidates have boosted reactivity for hydrofunctionalization and polymerization reactions compared with amide ligands not bearing a sulfonyl group. N,O-Chelated titanium complexes have been used to synthesize ultrahigh molecular weight polyethylene and have been utilized in the challenging task of realizing equal incorporation of two different cyclic esters in a random ring-opening copolymerization. These discrete complexes have allowed for careful study of fundamental coordination chemistry and stoichiometric organometallic investigations. With inexpensive starting materials and modular ligands, titanium N,O-chelated complexes are well-suited to address the challenges of achieving greener chemical processes while accessing useful reaction manifolds for sustainable synthesis.
Investigation of photoplethysmography and arterial blood oxygen saturation from the ear-canal and the finger under conditions of artificially induced hypothermia (2015)

Pulse oximeters relay on the technique of photoplethysmography (PPG) to estimate arterial oxygen saturation (SpO2). In conditions of poor peripheral perfusion such as hypotension, hypothermia, and vasoconstriction, pulse oximeters become inaccurate or provide no reading. This is due to the poor quality of the PPG signals detected at that instance. In order to overcome this problem, the ear canal has been proposed as a alternative measurement site for measuring reliable SpO2. Hence, an ear canal PPG sensor was developed along with a PPG processing system. The performance of the sensor was evaluated by measuring the red and infrared PPGs and SpO2 from 10 healthy volunteers undergoing artificially induced hypothermia. The results from the ear canal sensor were compared with simultaneously acquired results from the finger. Hypothermia was induced by exposing the volunteers to cold temperatures of 10 ± 1°C. The results acquired suggest that the ear canal pulse oximeter endures more in estimating SpO2 values accurately when compared with the more common finger pulse oximeter.
Dose-Dependent Sustained Release of Dexamethasone in Inner Ear Cochlear Fluids Using a Novel Local Delivery Approach (2009)

The thermo-reversible triblock copolymer poloxamer 407 was investigated as a drug delivery vehicle for micronized dexamethasone into the middle and inner ears of guinea pigs. The study characterized the gelation and in vitro release kinetics of poloxamer formulations. In vivo, the pharmacokinetic profile of formulations containing varying concentrations of poloxamer and dexamethasone was examined following intratympanic administration. Significant drug levels within the perilymph were observed for at least 10 days, while systemic exposure was minimal. The sustained-release kinetics profile could be significantly modulated by varying the concentrations of both poloxamer and dexamethasone. Assessment of auditory function revealed a small transient shift in hearing threshold, most probably of conductive nature, which resolved itself within a week. No significant histological changes of the round window membrane or cochlea could be noted. Poloxamer 407 thus represents an effective and safe delivery system to achieve sustained release of dexamethasone to the inner ear.
Enhanced thermal stability of silica-coated  gold nanorods for photoacoustic imaging and image-guided therapy (2010)

Photothermal stability and, therefore, consistency of both optical absorption and photoacoustic response of the plasmonic nanoabsorbers is critical for successful photoacoustic image-guided photothermal therapy. In this study, silica-coated gold nanorods were developed as a multifunctional molecular imaging and therapeutic agent suitable for image-guided photothermal therapy. The optical properties and photothermal stability of silica-coated gold nanorods under intense irradiation with nanosecond laser pulses were investigated by UV-Vis spectroscopy and transmission electron microscopy. Silica-coated gold nanorods showed increased photothermal stability and retained their superior optical properties under much higher fluences. The changes in photoacoustic response of PEGylated and silica-coated nanorods under laser pulses of various fluences were compared. The silica-coated gold nanorods provide a stable photoacoustic signal, which implies better imaging capabilities and make silica-coated gold nanorods a promising imaging and therapeutic nano-agent for photoacoustic imaging and image-guided photothermal therapy.
Silk-based resorbable electronic devices for remotely controlled therapy and in vivo infection abatement (2014)

Significance We present the demonstration of in vivo operation of a subcutaneously implanted, resorbable electronic device. The remotely controlled device was wirelessly activated after implantation, successfully eliminating infection, and subsequently dissolving in the surrounding tissue. This approach is a first step for the development of a class of implantable, technological, biomedical devices that resorb harmlessly, eliminating the need for retrieval after use.
SCF E3 Ubiquitin Ligases as Anticancer Targets (2011)

The SCF multisubunit complex (Skp1, Cullins, F-box proteins) E3 ubiquitin ligase, also known as CRL (Cullin-RING ubiquitin Ligase) is the largest E3 ubiquitin ligase family that promotes the ubiquitination of various regulatory proteins for targeted degradation, thus regulating many biological processes, including cell cycle progression, signal transduction, and DNA replication. The efforts to discover small molecule inhibitors of a SCF-type ligase or its components were expedited by the FDA approval of Bortezomib (also known as Velcade or PS-341), the first (and only) class of general proteasome inhibitor, for the treatment of relapsed/refractory multiple myeloma and mantle cell lymphoma. Although Bortezomib has demonstrated a certain degree of cancer cell selectivity with measurable therapeutic index, the drug is, in general, cytotoxic due to its inhibition of overall protein degradation. An alternative and ideal approach is to target a specific E3 ligase, known to be activated in human cancer, for a high level of specificity and selectivity with less associated toxicity, since such inhibitors would selectively stabilize a specific set of cellular proteins regulated by this E3. Here, we review recent advances in validation of SCF E3 ubiquitin ligase complex as an attractive anti-cancer target and discuss how MLN4924, a small molecule inhibitor of NEDD8-activating enzyme, can be developed as a novel class of anticancer agents by inhibiting SCF E3 ligase complex via removal of cullin neddylation. Finally, we discuss under future perspective how basic research on SCF biology will direct the drug discovery efforts surrounding this target.
Information pathways in a disordered lattice (2014)

The maximum entropy random walk in a disordered lattice is obtained as a consequence of the principle of maximum entropy for a particular type of prior information without restriction on the number of steps. This novel result demonstrates that transition probabilities defining the random walk represent a general characterization of information on a defective lattice and does not necessarily reflect a physical process. The localization phenomenon is shown to be a consequence of solution of the Laplacian on the lattice-hence it contradicts the previous interpretation as a spherical Lifshitz state-and naturally generalizes to multiple modes, whose order reflects the significance of information. The dynamics of information flow on the microscale is related to the macroscopic structure of the lattice through a Fokker-Planck formalism. This newly derived theoretical framework is opening doors for a wide range of applications in analysis of (information) flow in disordered systems. That includes potentially breakthrough resolution of the outstanding problem of inferring connectivity from discrete imaging (i.e., neural) data.
Fetal membrane collagens: identification of two new collagen alpha chains. (1976)

Human fetal membranes contain two new genetically distinct collagen polypeptide chains which are subunits of one (or two) new molecular species of collagen. These new polypeptide chains, which we have tentatively named alphaA and alphaB, have been directly compared with the polypeptide chain subunits of Types I, II, and III human collagen and Type IV collagen from bovine lens capsule. Both alphaA and alphaB exhibit characteristic profiles on carboxymethyl-cellulose chromatography and sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The distribution of methionine residues along both new chains is different from known collagen chains as manifest by distinctly different cyanogen bromide peptide profiles on carboxymethyl-cellulose chromatography and/or sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Both alphaA and alphaB exhibit contents of amino acids and glycine typical of collagens, and comparison with the observed and reported compositions of collagen chains of Types I-IV collagens reveals notable differences, particularly in the content of alanine, leucine, isoleucine, and the basic amino acids, lysine, hydroxylysine, and arginine. The new collagen species containing both alphaA and alphaB may be separated in the native (triple-helical) state from other native collagen species by differential salt precipitation. The observations that both chains coprecipitate in the same narrow NaCl range, and that the ratio of alphaA:alphaB is constant, suggest the possibility of a single new species of collagen with a subunit structure alphaA [alphaB]2.
Regional localization of a glioma-associated antigen defined by monoclonal antibody 81C6 in vivo: kinetics and implications for diagnosis and therapy. (1987)

The pharmacokinetics and regional tissue distribution of two IgG2b immunoglobulins were studied in athymic mice with D54MG human glioma xenografts. Monoclonal antibody (Mab) 81C6, an antiglioma antibody, had a plasma half-life of 2.7 +/- 0.3 (SE) days; 45.6, a control immunoglobulin, had a plasma half-life of 3.3 +/- 0.4 days. The immunoreactive fraction of 81C6 in plasma fell slowly from 0.37 to 0.23 over 9 days. The blood-to-tissue transfer constant (K1) of Mab was 0.11 +/- 0.05 ml/g/h in brain xenografts and 0.07 +/- 0.02 ml/g/h in s.c. xenografts. In contrast, K1 in muscle (0.005 +/- 0.002) and brain (0.0004 +/- 0.0001 ml/g/h) was much lower. The equilibration half-time of Mab in extracellular space was 1.1 +/- 0.2 h in the brain xenografts, 3.6 +/- 1.4 h in s.c. xenografts, and 8.1 and 24 h in muscle and brain, respectively. Distribution and binding of 81C6 was heterogeneous in the xenografts. A binding potential of 5-14 was found centrally and a binding potential of 0.8-1.0 was found peripherally in the brain xenografts. In the s.c. xenografts, the binding potential was higher peripherally than centrally. The exposure of D54MG xenograft tissue to Mab 81C6 was not significantly limited by the permeability of the blood vessels or blood flow due to the long plasma half-life of the immunoglobulin. A comparison of Mab and alpha-aminoisobutyric acid influx constants suggests that Mab entry into intracerebral xenografts occurs through large pores without significant sieving or steric restriction. Under such conditions the differences in influx constants between immunoglobulin and smaller immunoglobulin fragments will be proportional to the differences in their aqueous diffusion constants.
Object tracking (2006)

The goal of this article is to review the state-of-the-art tracking methods, classify them into different categories, and identify new trends. Object tracking, in general, is a challenging problem. Difficulties in tracking objects can arise due to abrupt object motion, changing appearance patterns of both the object and the scene, nonrigid object structures, object-to-object and object-to-scene occlusions, and camera motion. Tracking is usually performed in the context of higher-level applications that require the location and/or shape of the object in every frame. Typically, assumptions are made to constrain the tracking problem in the context of a particular application. In this survey, we categorize the tracking methods on the basis of the object and motion representations used, provide detailed descriptions of representative methods in each category, and examine their pros and cons. Moreover, we discuss the important issues related to tracking including the use of appropriate image features, selection of motion models, and detection of objects.
Class analyses as abstract interpretations of trace semantics (2003)

We use abstract interpretation to abstract a compositional trace semantics for a simple imperative object-oriented language into its projection over a set of program points called watchpoints . We say that the resulting watchpoint semantics is focused on the watchpoints. Every abstraction of the computational domain of this semantics induces an abstract, still compositional, and focused watchpoint semantics. This establishes a basis for developing static analyses obtaining information pertaining only to the watchpoints. As an example, we consider three domains for class analysis of object-oriented programs derived from three techniques present in the literature, namely, rapid type analysis, a simple dataflow analysis, and a constraint-based analysis. We obtain three static analyses which are provably correct and whose abstract operations are provably optimal. Moreover, we prove that our formalization of the constraint-based analysis is more precise than that of the other two analyses. We have implemented our watchpoint semantics and our three domains for class analysis. This implementation shows that the time and space costs of the analysis are actually proportional to the number of watchpoints, as a consequence of the focused nature of the watchpoint semantics.
In Vivo Lysogenic Conversion of Tox − Streptococcus pyogenes to Tox + with Lysogenic Streptococci or Free Phage (2003)

Temperate bacteriophage can transfer toxin-encoding genes between bacteria, often resulting in acquired pathogenicity. However, little is known regarding the effects of the eukaryotic host on the phage-pathogen interaction. Using Streptococcus pyogenes as a model, we demonstrate, both in vitro and in vivo, that the eukaryote mediates the efficient induction of toxin-encoding temperate phage and the resultant conversion of Tox(-) flora to Tox(+). Furthermore, we show that both phage induction and subsequent conversion need not happen in the same mammalian host, as host-to-host phage transmission can result in toxigenic conversion within the secondary host. Ultimately, our findings demonstrate that the eukaryotic host serves as an essential component in the phage-mediated evolution of virulence within the microbial population.
An Efficient Model-Free Setting for Longitudinal and Lateral Vehicle Control: Validation Through the Interconnected Pro-SiVIC/RTMaps Prototyping Platform (2017)

In this paper, the problem of tracking desired longitudinal and lateral motions for a vehicle is addressed here. Let us point out that a “good” modeling is often quite difficult or even impossible to obtain. It is due for example to parametric uncertainties, for the vehicle mass, inertia or for the interaction forces between the wheels and the road pavement. To overcome this type of difficulties, we consider a model-free control approach leading to “intelligent” controllers. The longitudinal and the lateral motions, on one hand, and the driving/braking torques and the steering wheel angle, on the other hand, are respectively the output and the input variables. An important part of this paper is dedicated to present simulation results with actual data. Actual data, used in MATLAB as reference trajectories, have been previously recorded with an instrumented Peugeot 406 experimental car. The simulation results show the efficiency of our approach. Some comparisons with a nonlinear flatness-based control in one hand, and with a classical PID control in another hand confirm this analysis. Other virtual data have been generated through the interconnected platform SiVIC/RTMaps, which is a virtual simulation platform for prototyping and validation of advanced driving assistance systems.