gebhart/patrepeval huggingface dataset:
Tauopathy with paired helical filaments in an aged chimpanzee (2008)

An enigmatic feature of age-related neurodegenerative diseases is that they seldom, if ever, are fully manifested in nonhuman species under natural conditions. The neurodegenerative tauopathies are typified by the intracellular aggregation of hyperphosphorylated microtubule-associated protein tau (MAPT) and the dysfunction and death of affected neurons. We document the first case of tauopathy with paired helical filaments in an aged chimpanzee (Pan troglodytes). Pathologic forms of tau in neuronal somata, neuropil threads, and plaque-like clusters of neurites were histologically identified throughout the neocortex and, to a lesser degree, in allocortical and subcortical structures. Ultrastructurally, the neurofibrillary tangles consisted of tau-immunoreactive paired helical filaments with a diameter and helical periodicity indistinguishable from those seen in Alzheimer's disease. A moderate degree of Abeta deposition was present in the cerebral vasculature and, less frequently, in senile plaques. Sequencing of the exons and flanking intronic regions in the genomic MAPT locus disclosed no mutations that are associated with the known human hereditary tauopathies, nor any polymorphisms of obvious functional significance. Although the lesion profile in this chimpanzee differed somewhat from that in Alzheimer's disease, the copresence of paired helical filaments and Abeta-amyloidosis indicates that the molecular mechanisms for the pathogenesis of the two canonical Alzheimer lesions--neurofibrillary tangles and senile plaques--are present in aged chimpanzees.
Reduced resolution update video coding with interblock filtering of prediction error residuals (2005)

This paper describes a new improvement upon a video coding tool known as reduced-resolution update (RRU). In RRU, as described in Annex Q of the H.263 standard, full resolution prediction error residuals are downsampled and coded at a reduced spatial resolution. During RRU coding, as previously proposed, each block of prediction errors is downsampled and interpolated without reference to any of its neighboring blocks. This can lead to severe blockiness in the decoded picture. In H.263 Annex Q RRU, the deblocking filter strength is increased to the maximum value to reduce this blockiness. In the new technique presented here, referred to as RRU+, the downsampling and interpolation filters use residuals from neighboring blocks to prevent the blockiness that results from RRU. Experimental results show that RRU+ provides better PSNR versus bitrate performance than RRU with maximum deblocking filter strength.
A modified adaptive hill climbing maximum power point tracking (MPPT) control method for photovoltaic power systems (2009)

A powerful attraction of photovoltaic (PV) power systems is that they produce electric power without harming the environment, by directly transforming a free inexhaustible source of energy, solar irradiation, into electricity. This fact, together with the continuing decrease in PV array cost and increase in efficiency, implies a promising role for PV generation systems in the near future. The study started with the requirement that photovoltaic power systems should be integrated with specific control algorithms to deliver maximum possible power. In this thesis, the PV power system was introduced at the beginning, and a simple maximum power point tracking (MPPT) system was presented and analyzed. Next, different existing MPPT control approaches were discussed and a proposed control algorithm, namely modified adaptive hill climbing (MAHC) method, was introduced. Then, the results of simulation proved that the performance could be improved in both transient and steady state of the suggested control system. Finally, a simple test bed system with digital signal processor (DSP) was designed and implemented with optimized control software to verify the proposals.
Thalamotomy for Parkinsonian Tremor (1997)

Thalamotomy for parkinsonian tremor was performed in 25 patients. A good outcome was achieved in 66% of cases. Three patients sustained a significant new deficit. Stimulation through the lesioning electrode provided an adequate means of corroboration of target localisation.
Efficient, stable silicon tandem cells enabled by anion-engineered wide-bandgap perovskites (2020)

Maximizing the power conversion efficiency (PCE) of perovskite/silicon tandem solar cells that can exceed the Shockley-Queisser single-cell limit requires a high-performing, stable perovskite top cell with a wide bandgap. We developed a stable perovskite solar cell with a bandgap of ~1.7 electron volts that retained more than 80% of its initial PCE of 20.7% after 1000 hours of continuous illumination. Anion engineering of phenethylammonium-based two-dimensional (2D) additives was critical for controlling the structural and electrical properties of the 2D passivation layers based on a lead iodide framework. The high PCE of 26.7% of a monolithic two-terminal wide-bandgap perovskite/silicon tandem solar cell was made possible by the ideal combination of spectral responses of the top and bottom cells.
The Nucleus Accumbens and Pavlovian Reward Learning (2007)

The ability to form associations between predictive environmental events and rewarding outcomes is a fundamental aspect of learned behavior. This apparently simple ability likely requires complex neural processing evolved to identify, seek, and use natural rewards and redirect these activities based on updated sensory information. Emerging evidence from both animal and human research suggests that this type of processing is mediated in part by the nucleus accumbens (NAc) and a closely associated network of brain structures. The NAc is required for a number of reward-related behaviors and processes specific information about reward availability, value, and context. In addition, this structure is critical for the acquisition and expression of most Pavlovian stimulus-reward relationships, and cues that predict rewards produce robust changes in neural activity in the NAc. Although processing within the NAc may enable or promote Pavlovian reward learning in natural situations, it has also been implicated in aspects of human drug addiction, including the ability of drug-paired cues to control behavior. This article provides a critical review of the existing animal and human literature concerning the role of the NAc in Pavlovian learning with nondrug rewards and considers some clinical ture concerning the role of the NAc in Pavlovian learning with nondrug implications of these findings.
Advances in planar lipid bilayers and liposomes (2006)

Advances in Planar Lipid Bilayers and Liposomes volumes cover a broad range of topics, including main arrangements of the reconstituted system, namely planar lipid bilayers as well as spherical liposomes. The invited authors present the latest results of their own research groups in this exciting multidisciplinary field. It incorporates contributions from newcomers and established and experienced researchers. It explores the planar lipid bilayer systems and spherical liposomes from both theoretical and experimental perspectives. It serves as an indispensable source of information for new scientists.
Proteinases in Connective Tissue Breakdown (1980)

Lysosomal cathepsins B and N complete the depolymerization of native fibrillar collagen in the phagolysosome after prior extracellular fragmentation by collagenase and other neutral proteinases. In vitro studies have confirmed that cathepsins B and N cleave native collagen only at the short non-helical telopeptides, which generate the intermolecular cross-links. This action occurs maximally at pH 3.5 and at 37 degrees C the released monomers denature spontaneously and are susceptible to further breakdown. In the phagolysosome the collagenous debris is already weakened and probably therefore, more easily disrupted by these cathepsins. Complete digestion would then be undertaken by the whole complement of proteases. The lysosomal glycosidases may assist this breakdown by degrading ground substance components which are normally tightly bound to collagen. In certain situations cells may instead generate an acidic pericellular environment that could permit the direct action of secreted lysosomal enzymes. This extracellular action may supersede the action of collagenase and the activity of these different enzymes would thus be regulated by changes in the nature of this microenvironment.
Oral Candidiasis: Pathogenesis and Host Defense (1984)

Oral candidiasis is a common problem, frequently presenting as a chronic recurring infection. Oral infection is a potential reservoir of organisms for severe, spreading, local disease and systemic disease in the compromised host. Nonspecific local oral factors in host defense include the epithelial barrier, flow or saliva, microbial interactions, antimicrobial constituents of saliva, lysozyme, lactoferrin, the lactoperoxidase system, levels of iron, and salivary glycoproteins. Immunoglobins are present in saliva, but their role is poorly understood. The activity of antibody against Candida on oral mucosal surfaces may not be mediated by complement and phagocyte activity. Specific antibodies against Candida may function by aggregating the organisms and preventing mucosal adherence of the fungi.
Kinetics of Escherichia coli B D-Lactate Dehydrogenase and Evidence for Pyruvate-controlled Change in Conformation (1968)

Abstract Kinetic properties of d(-)-specific lactate dehydrogenase (d-lactate:diphosphopyridine nucleotide oxidoreductase, EC 1.1.1.28) from Escherichia coli B indicate the following. 1. The reaction catalyzed is essentially unidirectional, the oxidation of d(-)-lactate with diphosphopyridine nucleotide as coenzyme proceeding at only about 0.01% of the rate of pyruvate reduction. 2. The enzyme shows Michaelis-Menten kinetics for reduced diphosphopyridine nucleotide, but pyruvate activates it. 3. A lag in the rate of oxidation of the reduced diphosphopyridine nucleotide is eliminated by prior incubation with pyruvate. The duration of this lag is independent of enzyme concentration, suggesting that pyruvate causes a change in the conformation of the enzyme rather than in its state of aggregation. The identity of the molecular weight of the enzyme at a very low concentration in the absence and in the presence of the substrate confirms this finding. 4. Two lines of evidence indicate that there are two types of binding sites for pyruvate. The variation of Hill plots with pH is interpretable only in terms of two sites with different binding properties. Furthermore, the two sites bind different substrate analogues. Oxamate is an inhibitor of this enzyme, but does not substitute for pyruvate as an activator. On the other hand, α-ketobutyrate does not inhibit the catalysis but activates the enzyme, converting the substrate saturation curve from sigmoidal to hyperbolic. 5. The kinetic properties of the catalytic site appear to be similar to those of vertebrate l-lactate dehydrogenases, although the dissociation constants for both pyruvate and reduced diphosphopyridine nucleotide are considerably larger for the E. coli d-lactate dehydrogenase. 6. The kinetic properties of this enzyme are consistent with the course and regulation in vivo of pyruvate metabolism.
Remote control grubbs catalysts that modulate ring‐opening metathesis polymerizations (2017)

ABSTRACT A broad range of stimuli, including light, heat, mechanical force, or changes in chemical potential, may be used to toggle Ru‐based catalysts between multiple distinct states of activity. Catalysts with such features offer a means to temporally‐ and, in some cases, spatially‐control a variety of polymerizations, and thus should facilitate access to synthetic macromolecular materials with tunable structures and properties. Due to the intrinsic versatility and robustness of the Grubbs‐type catalyst platforms, numerous remotely controlled ring‐opening metathesis polymerizations have been introduced. Herein, selected examples of stimuli‐responsive catalysts that have been recently used for such purposes are surveyed and discussed. Perspectives on potential opportunities for development and growth as well as an outlook for the field are also provided. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55 , 2949–2960
NF-kappaB activation contributes to anthracycline resistance pathway in human ovarian carcinoma cell line A2780. (2005)

The development of chemoresistance is a major obstacle for successful anticancer therapy. Understanding the molecular mechanisms leading to chemoresistance is a rational step to improve the therapeutic efficacy of cytotoxic drugs. Since anthracyclines play an important role in cancer chemotherapy, we have generated a human ovarian tumor cell line resistant to sabarubicin (MEN 10755), the newest anthracycline molecule in clinical development. Expression of the transporter protein MRP that affected sabarubicin uptake, and a reduced DNA topoisomerase II content in A2780/saba cells was observed. Since the poisoning of DNA topoisomerase II results in DNA damage, which is a critical signal for NF-kappaB activation, we explored if this transcription factor has a role in the chemoresistance to anthracyclines. We showed a reduced NF-kappaB activation in the resistant cell line. Moreover, qualitative changes in NF-kappaB dimer formation between the two cell lines were observed. In agreement with the hypothesis of a role of NF-kappaB in mediating drug resistance, we showed that the pharmacological inhibition of NF-kappaB activation attenuated drug resistance in A2780/saba cells whereas it had no effect in A2780 cells. Altogether, these findings show that anthracycline resistance in A2780 cell lines is due to the coexpression of several molecular mechanisms.
A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients (2005)

Engagement of the TCR triggers sustained Ca(2+) entry through Ca(2+) release-activated Ca(2+) (CRAC) channels, which helps drive gene expression underlying the T cell response to pathogens. The identity and activation mechanism of CRAC channels at a molecular level are unknown. We have analyzed ion channel expression and function in T cells from SCID patients which display 1-2% of the normal level of Ca(2+) influx and severely impaired T cell activation. The lack of Ca(2+) influx is not due to deficient regulation of Ca(2+) stores or expression of several genes implicated in controlling Ca(2+) entry in lymphocytes (kcna3/Kv1.3, kcnn4/IKCa1, trpc1, trpc3, trpv6, stim1). Instead, electrophysiologic measurements show that the influx defect is due to a nearly complete absence of functional CRAC channels. The lack of CRAC channel activity is correlated with diminished voltage sensitivity and slowed activation kinetics of the voltage-dependent Kv1.3 channel. These results demonstrate that CRAC channels provide the major, if not sole, pathway for Ca(2+) entry activated by the TCR in human T cells. They also offer evidence for a functional link between CRAC and Kv1.3 channels, and establish a model system for molecular genetic studies of the CRAC channel.
Design and characterization of a lumped element single-ended superconducting microwave parametric amplifier with on-chip flux bias line (2013)

We demonstrate a lumped-element Josephson parametric amplifier, using a single-ended design that includes an on-chip, high-bandwidth flux bias line. The amplifier can be pumped into its region of parametric gain through either the input port or through the flux bias line. Broadband amplification is achieved at a tunable frequency ω/2π between 5 and 7 GHz with quantum-limited noise performance, a gain-bandwidth product greater than 500 MHz, and an input saturation power in excess of −120 dBm. The bias line allows fast frequency tuning of the amplifier, with variations of hundreds of MHz over time scales shorter than 10 ns.
Induction of Thyroid Gene Expression and Radioiodine Uptake in Melanoma Cells: Novel Therapeutic Implications (2009)

Both the MAP kinase and PI3K/Akt pathways play an important role in the pathogenesis of melanoma. We conducted the present study to test the hypothesis that targeting the two pathways to potently induce cell inhibition accompanied with thyroid iodide-handling gene expression for adjunct radioiodine ablation could be a novel effective therapeutic strategy for melanoma. We used specific shRNA approaches and inhibitors to individually or dually suppress the MAP kinase and PI3K/Akt pathways and examined the effects on a variety of molecular and cellular responses of melanoma cells that harbored activating genetic alterations in the two pathways. Suppression of the MAP kinase and PI3K/Akt pathways showed potent anti-melanoma cell effects, including the inhibition of cell proliferation, transformation and invasion, induction of G(0)/G(1) cell cycle arrest and, when the two pathways were dually suppressed, cell apoptosis. Remarkably, suppression of the two pathways, particularly simultaneous suppression of them, also induced expression of genes that are normally expressed in the thyroid gland, such as the genes for sodium/iodide symporter and thyroid-stimulating hormone receptor. Melanoma cells were consequently conferred the ability to take up radioiodide. We conclude that dually targeting the MAP kinase and PI3K/Akt pathways for potent cell inhibition coupled with induction of thyroid gene expression for adjunct radioiodine ablation therapy may prove to be a novel and effective therapeutic strategy for melanoma.
Common and distinctive features of GNRA tetraloops based on a GUAA tetraloop structure at 1.4 Å resolution (2003)

GNRA tetraloops (N is A, C, G, or U; R is A or G) are basic building blocks of RNA structure that often interact with proteins or other RNA structural elements. Understanding sequence-dependent structural variation among different GNRA tetraloops is an important step toward elucidating the molecular basis of specific GNRA tetraloop recognition by proteins and RNAs. Details of the geometry and hydration of this motif have been based on high-resolution crystallographic structures of the GRRA subset of tetraloops; less is known about the GYRA subset (Y is C or U). We report here the structure of a GUAA tetraloop determined to 1.4 A resolution to better define these details and any distinctive features of GYRA tetraloops. The tetraloop is part of a 27-nt structure that mimics the universal sarcin/ricin loop from Escherichia coli 23S ribosomal RNA in which a GUAA tetraloop replaces the conserved GAGA tetraloop. The adenosines of the GUAA tetraloop form an intermolecular contact that is a commonplace RNA tertiary interaction called an A-minor motif. This is the first structure to reveal in great detail the geometry and hydration of a GUAA tetraloop and an A-minor motif. Comparison of tetraloop structures shows a common backbone geometry for each of the eight possible tetraloop sequences and suggests a common hydration. After backbone atom superposition, equivalent bases from different tetraloops unexpectedly depart from coplanarity by as much as 48 degrees. This variation displaces the functional groups of tetraloops implicated in protein and RNA binding, providing a recognition feature.
The PDZ domain protein CAL interacts with mGluR5a and modulates receptor expression (2009)

In this study, we investigated the association of metabotropic glutamate receptor subtype-5a (mGluR5a) with cystic fibrosis transmembrane conductance regulator-associated ligand (CAL). Using glutathione-S-transferase pull-down techniques, we found that mGluR5a directly interacted with CAL, with the C-terminus of the receptor binding to the PSD95/Discslarge/ZO-1 homology domain of CAL. The last four amino acids (S-S-S-L) of the C-terminus of the receptor were essential determinants for the interaction. Co-immunoprecipitation experiments and immunofluorescence assays revealed that full-length mGluR5a also associated with intact CAL in vivo, an observation consistent with the results from studies on fragment interactions in vitro. Functionally, upon co-expression with mGluR5a, CAL profoundly inhibited the ubiquitination of mGluR5a and enhanced receptor expression at the protein level but not at the mRNA level. These findings reveal that mGluR5a protein expression is physiologically regulated via its interaction with CAL. These results also suggest a molecular mechanism by which mGluR5a protein expression may be regulated at the post-translational level by the CAL protein, possibly by blocking ubiquitination-dependent receptor degradation.
Phosphorylated MAP1b, alias MAP5 and MAP1x, is involved in axonal growth and neuronal mitosis (1993)

Microtubule-associated protein 1b, also named MAP5 and MAP1x, is essential for neuronal differentiation. In kitten cerebellum, this protein is partially phosphorylated. During early postnatal development, a phosphorylated form was localized prominently in growing parallel fibres and in mitotic spindles of neuroblasts in the germinal layer, whereas a non-phosphorylated MAP1b form was found in dendrites, perikarya and axons. The MAP1x epitope showed the same immunohistochemical distribution, as seen for phosphorylated MAP1b, while its recognition on immunoblots was independent of phosphorylation. It is concluded that post-translational modifications and conformation of MAP1b influence the immunological detection of MAP1b, and are essential in the neuronal growth processes and mitosis. The antibody against the phosphorylated MAP1b may represent a good marker to identify dividing neurones.
Building better T‐cell‐inducing malaria vaccines (2005)

Since malaria continues to account for millions of deaths annually in endemic regions, the development of an effective vaccine remains highly desirable. The life cycle of malaria poses a number of challenges to the immune response since phases of the cycle express varying antigen profiles and have different locations, thus requiring differing antigenic targets and effector mechanisms. To confer sterile immunity, a vaccine would have to target the pre-erythrocytic stages of infection. Since at this stage the parasite is hidden within liver cells, the host defence predominantly requires cell-mediated immunity, chiefly T cells, to eliminate infected hepatocytes. The development of such vaccines has progressed from irradiated sporozoites, through recombinant proteins, to recombinant DNA and viral vectors. Some of the experimental vaccination regimens that explore various combinations of vaccines for priming and boosting, together with numbers of vaccinations, interval between them, and the vaccination site, are revealing strong immunogenicity and evidence of efficacy in human challenge studies and in field trials. Such approaches should lead to deployable vaccines that protect against malarial disease.
Potentiation of antitumor effects of IL-12 in combination with paclitaxel in murine melanoma model in vivo. (1999)

The early clinical trials with interleukin-12 (IL-12) have demonstrated substantial toxicity of this cytokine. One way to resolve this problem would be to find other antitumor agents, e.g. chemotherapeutics, synergistically interacting with IL-12. However, analysis of the recent reports on this topic leads to the conclusion that the antitumor effects achieved in such combination treatments are dependent not only on the drug applied but also on the tumor model used. We described previously lack of the potentiation of antitumor effects in combination treatment with IL-12 and paclitaxel in a murine leukemia L1210 model. We investigated whether such treatment could bring therapeutical benefit by using the murine melanoma MmB16 model. significant potentiation of antitumor effects in combination treatment with IL-12 and paclitaxel was observed. These results suggest that combination of IL-12 and paclitaxel could be beneficial in the treatment of certain types of tumors.