gebhart/patrepeval huggingface dataset:
Differential degradation of calpastatin by μ‐ and m‐calpain in Ca2+‐enriched human neuroblastoma LAN‐5 cells (2000)

In neuroblastoma LAN-5 cells during calpain activation, in addition to the two expressed 70 kDa and 30 kDa calpastatin forms, other inhibitory species are produced, having molecular masses of 50 kDa and 15 kDa. At longer times of incubation, both native and new calpastatin species disappear. The formation of these new calpastatins as well as the decrease in intracellular total calpastatin activity are mediated by calpain itself, as indicated by the effect of the synthetic calpain inhibitor I, which prevents both degradative processes. Analysis of the calcium concentrations required for the two processes indicates that the first conservative proteolytic event is mediated by micro-calpain, whereas the second one is preferentially carried out by m-calpain. The appearance of the 15 kDa form, containing only the calpastatin repetitive inhibitory domain and identified also in red cells of hypertensive rats as the major inhibitor form, can be considered a marker of intracellular calpain activation, and it can be used for the monitoring of the involvement of calpain in pathological situations.
Cerebrovascular smooth muscle cells internalize Alzheimer amyloid beta protein via a lipoprotein pathway: implications for cerebral amyloid angiopathy. (1997)

Cerebral amyloid angiopathy (CAA) is caused by the cerebrovascular deposition of Alzheimer amyloid beta protein (Abeta) and shows an increased incidence in carriers of the apolipoprotein E (APOE) epsilon4 genotype. To study the pathogenesis of CAA, primary cultures of human and canine smooth muscle cells from leptomeningeal vessels were incubated with fluorescein- and biotin-conjugated amyloid beta-protein. In the presence of human serum or cerebrospinal fluid, A beta1-40 and Abeta1-42 were rapidly internalized and appeared within endosomal and lysosomal vesicles. The accumulation of intracellular Abeta was enhanced by chloroquine and blocked by cycloheximide and brefeldin A and pretreatment with trypsin, suggesting that the internalization of Abeta occurs by receptor-mediated endocytosis. The internalization of Abeta was also inhibited by lipoprotein-deficient serum or by incubation with the 39-kd receptor-associated protein, indicating that Abeta is internalized via a receptor of the low-density lipoprotein receptor family. A lipoprotein pathway was confirmed by colocalization of cell surface-bound or internalized Abeta with APOE and low-density lipoprotein receptor-related protein. We propose a pathogenetic model of CAA, in which Abeta-APOE-complexes contained within the cerebrospinal fluid or the extracellular fluid of the brain are internalized and accumulated in cerebrovascular smooth muscle cells. Such a model could explain the preferential localization of CAA to the outer and middle layers of cortical and leptomeningeal arterioles, while indicating a mechanism by which the APOE genotype might determine the risk of CAA.
Resveratrol Enhances Radiosensitivity of Human Non-Small Cell Lung Cancer NCI-H838 Cells Accompanied by Inhibition of Nuclear Factor-Kappa B Activation (2005)

Resveratrol, a polyphenol in red wine, possesses many pharmacological activities including cardioprotection, chemoprevention, anti-tumor effects, and nuclear factor-kappa B (NF-kappaB) inactivation. The present study was designed to evaluate the effects and possible mechanism of resveratrol in enhancing radiosensitivity of lung cancer cells. Human non-small cell lung cancer NCI-H838 cells were irradiated with or without resveratrol pretreatment. The surviving fraction and sensitizer enhancement ratio (SER) were estimated by using a colony formation assay and linear-quadratic model. The cell-cycle distribution was evaluated by using propidium iodide staining and flow cytometry. An ELISA-based assay with immobilized oligonucleotide was performed to assess the DNA binding activity of NF-kappaB. Resveratrol had no direct growth-inhibitory effect on NCI-H838 cells treated for 24 hours with doses up to 25 microM. Pretreatment with resveratrol significantly enhanced cell killing by radiation, with an SER up to 2.2. Radiation activated NF-kappaB, an effect reversed by resveratrol pretreatment. Resveratrol resulted in a decrease of cells in the G0/G1 phase and an increase in the S phase. Our results demonstrate that resveratrol enhances the radiosensitivity of NCI-H838 cells accompanied by NF-kappaB inhibition and S-phase arrest.
Ultrasensitive Scaffold-Dependent Protease Sensors with Large Dynamic Range (2017)

The rational construction of synthetic protein switches with predefined input-output parameters constitutes a key goal of synthetic biology with many potential applications ranging from metabolic engineering to diagnostics. Yet, generally applicable strategies to construct tailor-engineered protein switches have so far remained elusive. Here, we use SpyTag/SpyCatcher-mediated protein ligation to engineer modularly organized, scaffold-dependent protease sensors that exploit a combination of affinity targeting and protease-inducible protein-protein interactions. We use this architecture to create a suite of integrated signal sensing and amplification circuits that can detect the activity of α-thrombin and prostate specific antigen with a dynamic range covering 5 orders of magnitude. We determine the key design features critical for signal transmission between protease-based sensors, transducers, and actuators.
STI571 prevents apoptosis, tau phosphorylation and behavioural impairments induced by Alzheimer's β-amyloid deposits (2008)

There is evidence that amyloid beta-protein (Abeta) deposits or Abeta intermediates trigger pathogenic factors in Alzheimer's disease patients. We have previously reported that c-Abl kinase activation involved in cell signalling regulates the neuronal death response to Abeta fibrils (Abeta(f)). In the present study we investigated the therapeutic potential of the selective c-Abl inhibitor STI571 on both the intrahippocampal injection of Abeta(f) and APPsw/PSEN1DeltaE9 transgenic mice Alzheimer's disease models. Injection of Abeta(f) induced an increase in the numbers of p73 and c-Abl immunoreactive cells in the hippocampal area near to the lesion. Chronic intraperitoneal administration of STI571 reduced the rat behavioural deficit induced by Abeta(f), as well as apoptosis and tau phosphorylation. Our in vitro studies suggest that inhibition of the c-Abl/p73 signalling pathway is the mechanism underlying of the effects of STI571 on Abeta-induced apoptosis for the following reasons: (i) Abeta(f) induces p73 phosphorylation, the TAp73 isoform levels increase so as to enhance its proapoptotic function, and all these effects where reduced by STI571; (ii) c-Abl kinase activity is required for neuronal apoptosis and (iii) STI571 prevents the Abeta-induced increase in the expression of apoptotic genes. Furthermore, in the Abeta-injected area there was a huge increase in phosphorylated p73 and a larger number of TAp73-positive cells, with these changes being prevented by STI571 coinjection. Moreover, the intraperitoneal administration of STI571 rescued the cognitive decline in APPsw/PSEN1DeltaE9 mice, p73 phosphorylation, tau phosphorylation and caspase-3 activation in neurons around Abeta deposits. Besides, we observed a decrease in the number and size of Abeta deposits in the APPsw/PSEN1DeltaE9-STI571-treated mice. These results are consistent with the role of the c-Abl/p73 signalling pathway in Abeta neurodegeneration, and suggest that STI571-like compounds would be effective in therapeutic treatments of Alzheimer disease.
Taking the sting out of carrier sense (2008)

A fundamental problem with unmanaged wireless networks is high packet loss rates and poor spatial reuse, especially with bursty traffic typical of normal use. To address these limitations, we explore the notion of interference cancellation for unmanaged networks - the ability for a single receiver to disambiguate and successfully receive simultaneous overlapping transmissions from multiple unsynchronized sources. We describe a practical algorithm for interference cancellation, and implement it for ZigBee using software radios. In this setting, we find that our techniques can reduce packet loss rate and substantially increase spatial reuse. With carrier sense set to prevent concurrent sends, our approach reduces the packet loss rate during collisions from 14% to 8% due to improved handling of hidden terminals. Conversely, disabling carrier sense reduces performance for only 7% of all pairs of links and increases the delivery rate for the median pair of links in our testbed by a factor of 1.8 due to improved spatial reuse.
Boxing code for stroke-order free handprinted Chinese character recognition (2002)

Many Chinese input methods rely heavily on the dictionary stroke orders of Chinese characters. Any deviation from the standard stroke orders in these methods would result in incorrect inputs. We propose a new coding scheme for handprinted Chinese characters, which allows stroke-order free input methods to be derived. In this scheme, each handprinted Chinese character is assigned an n-or-less-digit boxing code, which is derived from the box-like structure of Chinese characters. Each digit of the boxing code represents a unique stroke type of a given character stroke. Subsequent character recognition is then based on the matching of these boxing codes. Experiments were conducted based on 6 basic stroke types (t=6), and a boxing code length of 10 (n=10). Of the 300 characters we have tested, the boxing codes generated from both the dictionary and random stroke orders were the same for each character. The duplication rate was 5.6%. The results of the test indicate that boxing code is a feasible representation of Chinese characters. Although duplications exist, these could be reduced, if not totally removed, by taking in more stroke types. Further investigation is worthwhile in the fine-tuning of the two parameters t and n so as to obtain a more accurate and wider representation, and in the application of the new coding scheme.
The fatty acids and glycerides of an indian sesame oil (1951)

Abstract The component acids and glycerides in sesame oil (iodine value 114.1) extracted from seed grown in Eastern India have been investigated. The acids included palmitic 9.4, stearic 5.7, arachidic 1.2, oleic 35.0 and linoleic 48.4% (wt.). The glycerides follow the usual seed‐fat distribution: the chief members present are oleodilinoleins (40%), saturated‐oleo‐linoleins (37%) and dioleolinoleins (15%). 43% of the glycerides contain two linoleic groups and 53% contain one linoleic group per triglyceride molecule. The glyceride structure of groundnut, cottonseed, sesame, sunflower seed and soya‐bean oils are compared, with special reference to their respective dilinoleo‐ and monolinoleo‐glycerides.
Enhancing Gelation of Doubly Thermosensitive Hydrophilic ABC Linear Triblock Copolymers in Water by Thermoresponsive Hairy Nanoparticles (2016)

A method is reported for enhancing the gelation of doubly thermosensitive hydrophilic linear ABC triblock copolymers in water using thermoresponsive polymer brush-grafted nanoparticles (hairy NPs). A linear ABC triblock copolymer (ABC-Q) composed of a hydrophilic, charged middle block, and two thermosensitive outer blocks with different LCSTs, LCSTA of the lower LCST A block and LCSTC of the higher LCST C block, and two batches of hairy NPs with distinct thermoresponsive properties were prepared. When the temperature was raised from 0 °C to above the LCSTA but below the LCSTC, ABC-Q self-assembled into micelles in water with the lower LCST A block forming the core; further heating to above the LCSTC triggered the collapse of the C block, producing a two-compartment 3-D network micellar hydrogel when the polymer concentration was sufficiently high. Rheological studies showed that adding thermoresponsive hairy NPs with a LCST similar to the LCSTC of ABC-Q led to a significant increase in dynamic storage modulus (G′). For 6 wt % aqueous solutions of ABC-Q, the maximum value of G′ (G′max) increased with increasing amount of hairy NPs; a 45% increase in G′max was observed at the NP-to-polymer mass ratio of 60:100. It is believed that hairy NPs acted as “seeds” to adsorb the collapsed C block of ABC-Q, promoting the formation of bridging chains among micellar cores and NPs and thus enhancing the gelation. In contrast, no benefit was observed when adding hairy NPs with a LCST much higher than LCSTC; the G′max exhibited little change with increasing NP-to-polymer mass ratio. Our explanations for the rheological observations were supported by fluorescence resonance energy transfer studies.
Enhanced Immunogenicity of Stabilized Trimeric Soluble Influenza Hemagglutinin (2010)

Our data indicate that the recombinant trimeric sHA presents native trimeric epitopes while the unmodified sHA presents epitopes not exposed in the native HA molecule. The epitopes presented in the unmodified sHA constitute a "silent face" which may skew the antibody response to epitopes not accessible in live virus at neutral pH. The results demonstrate that the trimeric sHA is a more effective influenza vaccine candidate and emphasize the importance of structure-based antigen design in improving recombinant HA vaccines.
Recruitment of latent pools of high-avidity CD8+ T cells to the antitumor immune response (2005)

A major barrier to successful antitumor vaccination is tolerance of high-avidity T cells specific to tumor antigens. In keeping with this notion, HER-2/neu (neu)-targeted vaccines, which raise strong CD8(+) T cell responses to a dominant peptide (RNEU(420-429)) in WT FVB/N mice and protect them from a neu-expressing tumor challenge, fail to do so in MMTV-neu (neu-N) transgenic mice. However, treatment of neu-N mice with vaccine and cyclophosphamide-containing chemotherapy resulted in tumor protection in a proportion of mice. This effect was specifically abrogated by the transfer of neu-N-derived CD4(+)CD25(+) T cells. RNEU(420-429)-specific CD8(+) T cells were identified only in neu-N mice given vaccine and cyclophosphamide chemotherapy which rejected tumor challenge. Tetramer-binding studies demonstrated that cyclophosphamide pretreatment allowed the activation of high-avidity RNEU(420-429)-specific CD8(+) T cells comparable to those generated from vaccinated FVB/N mice. Cyclophosphamide seemed to inhibit regulatory T (T reg) cells by selectively depleting the cycling population of CD4(+)CD25(+) T cells in neu-N mice. These findings demonstrate that neu-N mice possess latent pools of high-avidity neu-specific CD8(+) T cells that can be recruited to produce an effective antitumor response if T reg cells are blocked or removed by using approaches such as administration of cyclophosphamide before vaccination.
Analysis of adenovirus early region 4-encoded polypeptides synthesized in productively infected cells (1987)

Peptide-specific antisera were developed to analyze the products encoded by adenovirus type 5 early region 4 (E4) open reading frames 6 and 7. Reading frame 6 previously was shown to encode a 34-kilodalton polypeptide (34K polypeptide) that forms a complex with the early region 1B (E1B)-55K antigen and is required for efficient viral growth in lytic infection. Antisera that were generated recognized the E4-34K protein as well as a family of related polypeptides generated by the fusion of open reading frames 6 and 7. These polypeptides shared amino-terminal sequences with the 34K protein. Short-pulse analysis suggested that the heterogeneity observed with the 6/7 fusion products resulted from differential splicing patterns of related E4 mRNAs. An antiserum directed against the amino terminus of reading frame 6 recognized only the free form of the 34K antigen that was not associated with the E1B-55K protein. This observation allowed the determination of the stability of the free and complexed form of this polypeptide. Pulse-chase analyses demonstrated that both forms of the 34K protein had half-lives greater than 24 h, suggesting that complex formation did not result in stabilization of this gene product. The half-lives of the 6/7 fusion products were approximately 4 h. The 34K protein also was shown to have a nuclear localization within infected cells. Finally, analysis of a mutant carrying deletions in both the E4-34K and E1B-55K polypeptides indicated that the complex formed between these two proteins was a functional unit in lytic infection.
Level set methods and fast marching methods : evolving interfaces in computational geometry, fluid mechanics, computer vision, and materials science (1999)

Introduction 1. Formulations of interface propagation Part I. Theory and Algorithms: 2. Theory of curve and surface evolution 3. Hamilton-Jacobi equations and associated theory 4. Numerical approximations: first attempt 5. Numerical schemes for hyperbolic conservation laws 6. Algorithms for the initial and boundary value formulations 7. Efficient schemes: adaptivity 8. Triangulated versions of level set and fast marching method: extensions and variations 9. Tests of basic methods Part II. Applications: 10. Geometry 11. Grid generation 12 Image denoising 13. Computer vision: shape detection and recognition 14. Fluid mechanics and materials sciences: adding physics 15. Computational geometry and computer-aided-design 16. First arrivals, optimizations, and control 17. Applications to semi-conductor manufacturing 18. Comments, conclusions, future directions References Index.
Sputum Proteomics in Inflammatory and Suppurative Respiratory Diseases (2008)

Proteomic screening of sputum yields potential biomarkers of inflammation. The early development of a clinically relevant assay from such data is demonstrated.
Investigation of ion‐beam‐treated SiO x film surfaces for liquid crystal alignment (2012)

We investigated the liquid crystal (LC) alignment on SiO x film surfaces as a function of ion beam exposure time using scanning probe microscopy and X‐ray photoemission spectroscopy. It was concluded that the LC alignment with high or low pretilt angles did not contribute to the morphological roughness but depended on the roughness in the electric potential of the SiO x surfaces. We also found that SiO x films with vertical LC alignment show relatively low values of stoichiometry parameters (1.42 &lt; x &lt; 1.57), whereas those with homogeneous LC alignment show relatively high values of stoichiometry parameters (1.58 &lt; x &lt; 1.77). All the experimental results showed that the electric dipole–dipole interactions between the LC molecules and the SiO x surfaces played a dominant role in aligning LC molecules on ion‐beam‐treated inorganic surfaces. Copyright © 2012 John Wiley &amp; Sons, Ltd.
Processive cytoskeletal motors studied with single‐molecule fluorescence techniques (2014)

Processive cytoskeletal motors from the myosin, kinesin, and dynein families walk on actin filaments and microtubules to drive cellular transport and organization in eukaryotic cells. These remarkable molecular machines are able to take hundreds of successive steps at speeds of up to several microns per second, allowing them to effectively move vesicles and organelles throughout the cytoplasm. Here, we focus on single-molecule fluorescence techniques and discuss their wide-ranging applications to the field of cytoskeletal motor research. We cover both traditional fluorescence and sub-diffraction imaging of motors, providing examples of how fluorescence data can be used to measure biophysical parameters of motors such as coordination, stepping mechanism, gating, and processivity. We also outline some remaining challenges in the field and suggest future directions.
Dementia and cognitive impairment three months after stroke (2001)

To investigate the cognitive capacities of a cohort of ischaemic or haemorrhagic stroke survivors and to identify the clinical determinants of post-stroke cognitive impairment, we evaluated 237 patients admitted to a Stroke Unit (mean age 59; SD=12.7). Three months after stroke, patients were submitted to a neuropsychological evaluation that included the Mini-Mental State Examination (MMSE), a complementary battery to assess specific cognitive domains, the Hamilton Depression Rating Scale (HDRS) and the Blessed Dementia Scale (BDS). Disturbed performance on at least one domain was detected on 131 (55%) patients: 27% had cognitive deficits other than memory, 7% had focal memory deficit, 9% had memory and other cognitive deficits and 6% had dementia. Dementia was associated with female gender (P=0.01), older age (P=0.01) and lower education level (P=0.04). Patients with memory deficits were older (P=0.01) with lower educational level (P=0.08) and more left sided lesions (P=0.02) than patients without memory deficits. In this middle aged stroke survivors cognitive impairment was common 3 months after stroke, while dementia was infrequent.
Retrograde Cerebral Perfusion with Hypothermic Blood Provides Efficient Protection of the Brain: A Neuropathological Study (1995)

Retrograde cerebral perfusion is a method that is recently being used for protection of the brain during operations on the aortic arch. This method is useful but is said to provide a limited time for protecting the brain. We designed an experiment in dogs to investigate neuropathologically the effect of protecting the brain for 120 minutes under: (1) circulatory arrest (CA); (2) retrograde cerebral perfusion with moderately cooled blood (RCPMC); and (3) retrograde cerebral perfusion with deeply cooled blood (RCPDC). We calculated the number of the abnormal cells of 400 hippocampal neurons per dog light microscopically. The number was 199 +/- 23 (mean +/- 1 SD) in the CA group, 149 +/- 50 in the RCPMC group, and 72 +/- 33 in the RCPDC group. The difference between the CA group and the RCPMC group was not statistically significant (p < 0.05), but there was a significant difference between the RCPMC and RCPDC groups (p < 0.05). The degree of cerebral protection provided by retrograde cerebral perfusion for 120 minutes is not sufficient when using moderately cooled blood. If we use deeply cooled blood at a temperature of about 10 degrees C, we should obtain a sufficient degree of protection of the brain.
Why Target PIM1 for Cancer Diagnosis and Treatment? (2010)

The highly conserved proto-oncogenic protein PIM1 is an unusual serine or threonine kinase, in part because it is constitutively active. Overexpression of PIM1 experimentally leads to tumor formation in mice, while complete knockout of the protein has no observable phenotype. It appears to contribute to cancer development in three major ways when it is overexpressed; by inhibiting apoptosis, by promoting cell proliferation and by promoting genomic instability. Expression in normal tissues is nearly undetectable. However, in hematopoietic malignancies and in a variety of solid tumors, increased PIM1 expression has been shown to correlate with the stage of disease. This characteristic suggests it can serve as a useful biomarker for cancer diagnosis and prognosis. Several specific and potent inhibitors of PIM1&#x2019;s kinase activity have also been shown to induce apoptotic death of cancer cells, to sensitize cancer cells to chemotherapy and to synergize with other anti-tumor agents, thus making it an attractive therapeutic target.