gebhart/patrepeval huggingface dataset:
A role for CKII phosphorylation of the Cactus PEST domain in dorsoventral patterning of the Drosophila embryo (1997)

Regulated proteolysis of Cactus, the cytoplasmic inhibitor of the Rel-related transcription factor Dorsal, is an essential step in patterning of the Drosophila embryo. Signal-induced Cactus degradation frees Dorsal for nuclear translocation on the ventral and lateral sides of the embryo, establishing zones of gene expression along the dorsoventral axis. Cactus stability is regulated by amino-terminal serine residues necessary for signal responsiveness, as well as by a carboxy-terminal PEST domain. We have identified Drosophila casein kinase II (CKII) as a Cactus kinase and shown that CKII specifically phosphorylates a set of serine residues within the Cactus PEST domain. These serines are phosphorylated in vivo and are required for wild-type Cactus activity. Conversion of these serines to alanine or glutamic acid residues differentially affects the levels and activity of Cactus in embryos, but does not inhibit the binding of Cactus to Dorsal. Taken together, these data indicate that wild-type axis formation requires CKII-catalyzed phosphorylation of the Cactus PEST domain.
Artificial Riboswitches: Synthetic mRNA‐Based Regulators of Gene Expression (2008)

Genetic RNA switches: An overview of the different concepts that are based on the insertion of ligand-sensing elements into mRNAs that enable the regulation of expression of the respective message is given.
Preparation and partial characterization of hepatic regenerative stimulator substance (SS) from rat liver. (1975)

1. The elucidation of the biochemical controls of growth processes is basic to understanding both normal and malignant growth. The exquisitely sensitive control demonstrated in the regenerating liver provides an excellent model system for growth studies. 2. Intraperitoneal injection of an extract from weanling rat liver into 34% hepatectomized rats stimulates [3H]thymidine incorporation into recipient hepatic DNA 2.5-fold. This stimulation is seen after a 10 hr lag period. 3. Extracts from weanling rat liver contain the highest level of the hepatic regenerative stimulator substance (SS), whereas extracts from adult liver give no significant stimulation. 4. If adult rats are partially hepatectomized, SS is demonstrated in their livers 12-15 hr after hepatectomy. 5. Partial characterization of SS shows that it is a soluble material not sedimented by centrifugation for 2 hr at 145,000 g. The stimulator activity is stable to heating at 65 degrees C and 100 degrees C for 15 min but is lost when treated with 10% perchloric acid.
Ubiquitin‐dependent and ‐independent mitochondrial protein quality controls: implications in ageing and neurodegenerative diseases (2008)

The ubiquitin-independent protein quality control of matrix proteins of the mitochondrion is well characterized and until recently the mitochondrion was considered a 'ubiquitination-free' organelle. However, a number of studies now indicate multiple roles of the ubiquitin-proteasome pathway in the regulation and maintenance of mitochondrial integrity. Of particular interest to this review is the finding of a mitochondrial ubiquitin-dependent protein quality control and that this pathway may share similarity to the endoplasmic reticulum-associated degradation (ERAD) pathway that acts to eliminate misfolded proteins from the lumen of the endoplasmic reticulum. The potential cross-talk between the ubiquitin-dependent and -independent protein quality controls and their implications in ageing and neurodegenerative diseases, notably in Parkinson's disease, are discussed.
Rapid Gelling Chitosan/Polylysine Hydrogel with Enhanced Bulk Cohesive and Interfacial Adhesive Force: Mimicking Features of Epineurial Matrix for Peripheral Nerve Anastomosis (2016)

Prompt and strong reconnection of severed peripheral nerves is crucial to nerve regeneration. The development of biocompatible nerve adhesives that are stronger than commonly used fibrin glue would be extremely beneficial to this field. We designed an in situ forming nerve adhesive hydrogel composed of chitosan and ε-polylysine (PL), which mimics the polysaccharides/protein structure of natural epineurium matrices, thus, enhancing the compatibility with nerves. Michael-type addition between the maleimide and thiol group was employed as a cross-linking reaction to eliminate foreign damage to nerves and to ensure a fast hydrogel formation speed (curing speed). Gelation occurred within 10 s, quick enough to promptly seal the transected nerve. Catechol groups conjugated onto PL molecules were demonstrated to reinforce both the bulk cohesive force of the hydrogel and the interfacial adhesive force between the hydrogel and epineurium. The storage modulus of the hydrogel was elevated to more than 2400 Pa. A superior nerve adhesion property that can tolerate 0.185 N of force (8× higher than fibrin glue) was obtained. After 8 weeks, the morphology of the repaired nerve fiber coapted by our hydrogel was very close to the morphology of normal nerve, and the axon cross ratio of the regenerated nerves coapted using hydrogel (57%) was much higher than employing the suture technique (35%). Thus, the in situ rapid gelling system offers a promising approach to the repair of severed peripheral nerves.
Neutrophil-activating protein 1/interleukin 8 stimulates the binding activity of the leukocyte adhesion receptor CD11b/CD18 on human neutrophils. (1990)

The cytokine NAP-1/IL-8 is produced by a variety of different cells in response to inflammatory stimuli and elicits several biological responses from PMN. Experiments presented here demonstrate that PMN exposed to NAP-1/IL-8 expressed increased amounts of CD11b/CD18, as well as CD11c/CD18 and CR1, on their cell surface, while expression of Fc gamma RIII and HLA-A,B,C remained essentially unchanged. Increased CD11b/CD18 and CD11c/CD18 appears to correspond with the release of specific granules by NAP-1/IL-8. NAP-1/IL-8 was also a potent stimulator of several of the binding activities of CD11b/CD18. Ligation of EC3bi by CD11b/CD18 was rapidly enhanced by NAP-1/IL-8, but phagocytosis of the ligated particles was not induced by the agonist. In addition, enhanced binding of EC3bi was observed in the absence of an increase in receptor expression as shown with PMN cytoplasts. NAP-1/IL-8 promoted additional adhesive interactions between CD11b/CD18 and the biosynthetic precursor of LPS, lipid IVa, fibrinogen, and endothelial cells, suggesting that NAP-1/IL-8 may promote leukocyte adhesion in vivo that could lead to recruitment of PMN to sites of tissue inflammation.
Needle-based refractive index measurement using low-coherence interferometry (2007)

We present a novel needle-based device for the measurement of refractive index and scattering using low-coherence interferometry. Coupled to the sample arm of an optical coherence tomography system, the device detects the scattering response of, and optical path length through, a sample residing in a fixed-width channel. We report use of the device to make near-infrared measurements of tissues and materials with known optical properties. The device could be used to exploit the refractive index variations of tissue for medical and biological diagnostics accessible by needle insertion.
Using iterative dynamic programming to obtain accurate pairwise and multiple alignments of protein structures. (1996)

We show how a basic pairwise alignment procedure can be improved to more accurately align conserved structural regions, by using variable, position-dependent gap penalties that depend on secondary structure and by taking the consensus of a number of suboptimal alignments. These improvements, which are novel for structural alignment, are direct analogs of what is possible with normal sequences alignment. They are feasible for us since our basic structural alignment procedure, unlike others, is so similar to normal sequence alignment. We further present preliminary results that show how our procedure can be generalized to produce a multiple alignment of a family of structures. Our approach is based on finding a "median" structure from doing all possible pairwise alignments and then aligning everything to it.
Rapid self-assembly of DNA on a microfluidic chip (2005)

BACKGROUND: DNA self-assembly methods have played a major role in enabling methods for acquiring genetic information without having to resort to sequencing, a relatively slow and costly procedure. However, even self-assembly processes tend to be very slow when they rely upon diffusion on a large scale. Miniaturisation and integration therefore hold the promise of greatly increasing this speed of operation. RESULTS: We have developed a rapid method for implementing the self-assembly of DNA within a microfluidic system by electrically extracting the DNA from an environment containing an uncharged denaturant. By controlling the parameters of the electrophoretic extraction and subsequent analysis of the DNA we are able to control when the hybridisation occurs as well as the degree of hybridisation. By avoiding off-chip processing or long thermal treatments we are able to perform this hybridisation rapidly and can perform hybridisation, sizing, heteroduplex analysis and single-stranded conformation analysis within a matter of minutes. The rapidity of this analysis allows the sampling of transient effects that may improve the sensitivity of mutation detection. CONCLUSIONS: We believe that this method will aid the integration of self-assembly methods upon microfluidic chips. The speed of this analysis also appears to provide information upon the dynamics of the self-assembly process.
SURFACE MODIFICATION OF POLYTETRAFLUOROETHYLENE WITH ArF EXCIMER LASER IRRADIATION (1994)

PTFE surface property was modified from hydrophobicity to high wetting ability by ArF excimer laser irradiation in Monosodium L- Glutamate Monohydrate (L-Glutamate) solution and in ethyl alcohol solution. The wetting ability of the processed surface was examined by the water contact angle method. The contact angle of the film was improved from 120 degree to 0 degree. By XPS analysis it was shown that amino groups, carbonyl groups, ethylene linkages were substitutionally formed with the release of fluorine atom on the surface. These hydrophilic molecules formed on the processed surface are believed to make the surface hydrophilic. The processed surface showed its original appearance without any stain and physical damage. Spatial resolution of 1μm is obtained with this method.
The Interaction of Neuropilin-1 with Vascular Endothelial Growth Factor and Its Receptor Flt-1 (2000)

Neuropilin-1 (NP-1) was first identified as a semaphorin receptor involved in neuron guidance. Subsequent studies demonstrated that NP-1 also binds an isoform of vascular endothelial growth factor (VEGF) as well as several VEGF homologs, suggesting that NP-1 may also function in angiogenesis. Here we report <i>in vitro</i> binding experiments that shed light on the interaction between VEGF165 and NP-1, as well as a previously unknown interaction between NP-1 and one of the VEGF receptor tyrosine kinases, VEGFR1 or Flt-1. BIAcore analysis demonstrated that, with the extracellular domain (ECD) of NP-1 immobilized at low density, VEGF165 bound with low affinity (<i>K</i> <sub>d</sub> = 2 μm) and fast kinetics. The interaction was dependent on the heparin-binding domain of VEGF165 and increased the affinity of VEGF165 for its signaling receptor VEGFR2 or kinase insert domain-containing receptor. The affinity of VEGF165 for the NP-1 ECD was greatly enhanced either by increasing the density of immobilized NP-1 (<i>K</i> <sub>d</sub> = 113 nm) or by the addition of heparin (<i>K</i> <sub>d</sub> = 25 nm). We attribute these affinity enhancements to avidity effects mediated by the bivalent VEGF165 homodimer or multivalent heparin. We also show that the NP-1 ECD binds with high affinity (<i>K</i> <sub>d</sub> = 1.8 nm) to domains 3 and 4 of Flt-1 and that this interaction inhibits the binding of NP-1 to VEGF165. Based on these results, we propose that NP-1 acts as a coreceptor for various ligands and that these functions are dependent on the density of NP-1 on the cell membrane. Furthermore, Flt-1 may function as a negative regulator of angiogenesis by competing for NP-1.
Primary structure of amyloid fibril protein AA in azocasein-induced amyloidosis of CBA/J mice. (1987)

Secondary amyloidosis was induced in CBA/J mice by subcutaneous injections of azocasein after priming with amyloid-enhancing factor. Amyloid fibrils were isolated from spleens and the subunit amyloid A (AA) protein purified by gel filtration on a column of Sepharose CL6B. The AA protein was fragmented with trypsin, cyanogen bromide, and Staphylococcus protease, and the peptides were purified by reverse-phase high-performance liquid chromatography. This protein is composed of 73 amino acid residues arranged in a single polypeptide chain with homogeneous amino and carboxyl terminals. Sequence homology with protein AA from other species is quite high with near identity for residues 31 through 54. This sequence is identical to the partial structures for CBA/J mouse AA and serum amyloid A (SAA) previously reported. It is also an exact match to a predicted 73-residue segment from one form of mouse SAA complementary DNA.
IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis (2008)

Expression of IL-22 is induced in several human inflammatory conditions, including inflammatory bowel disease (IBD). Expression of the IL-22 receptor is restricted to innate immune cells; however, the role of IL-22 in colitis has not yet been defined. We developed what we believe to be a novel microinjection-based local gene-delivery system that is capable of targeting the inflamed intestine. Using this approach, we demonstrated a therapeutic potency for IL-22-mediated activation of the innate immune pathway in a mouse model of Th2-mediated colitis that induces disease with characteristics similar to that of IBD ulcerative colitis (UC). IL-22 gene delivery enhanced STAT3 activation specifically within colonic epithelial cells and induced both STAT3-dependent expression of mucus-associated molecules and restitution of mucus-producing goblet cells. Importantly, IL-22 gene delivery led to rapid amelioration of local intestinal inflammation. The amelioration of disease by IL-22 was mediated by enhanced mucus production. In addition, local gene delivery was used to inhibit IL-22 activity through overexpression of IL-22-binding protein. Treatment with IL-22-binding protein suppressed goblet cell restitution during the recovery phase of a dextran sulfate sodium-induced model of acute colitis. These data demonstrate what we believe to be a novel function for IL-22 in the intestine and suggest the potency of a local IL-22 gene-delivery system for treating UC.
Different Roles for Nonhomologous End Joining and Homologous Recombination following Replication Arrest in Mammalian Cells (2002)

Homologous recombination (HR) and nonhomologous end joining (NHEJ) play overlapping roles in repair of DNA double-strand breaks (DSBs) generated during the S phase of the cell cycle. Here, we characterized the involvement of HR and NHEJ in the rescue of DNA replication forks arrested or slowed by treatment of hamster cells with hydroxyurea or thymidine. We show that the arrest of replication with hydroxyurea generates DNA fragmentation as a consequence of the formation of DSBs at newly replicated DNA. Both HR and NHEJ protected cells from the lethal effects of hydroxyurea, and this agent also increased the frequency of recombination mediated by both homologous and nonhomologous exchanges. Thymidine induced a less stringent arrest of replication and did not generate detectable DSBs. HR alone rescued cells from the lethal effects of thymidine. Furthermore, thymidine increased the frequency of DNA exchange mediated solely by HR in the absence of detectable DSBs. Our data suggest that both NHEJ and HR are involved in repair of arrested replication forks that include a DSB, while HR alone is required for the repair of slowed replication forks in the absence of detectable DSBs.
Design of refractive-index and rare-earth-dopant distributions for large-mode-area fibers used in coiled high-power amplifiers (2007)

We have numerically compared the performance of various designs for the core refractive-index (RI) and rare-earth-dopant distributions of large-mode-area fibers for use in bend-loss-filtered, high-power amplifiers. We first established quantitative targets for the key parameters that determine fiber-amplifier performance, including effective LP<sub>01</sub> modal area (<i>A<sub>eff</sub></i>, both straight and coiled), bend sensitivity (for handling and packaging), high-order mode discrimination, mode-field displacement upon coiling, and index contrast (manufacturability). We compared design families based on various power-law and hybrid profiles for the RI and evaluated confined rare-earth doping for hybrid profiles. Step-index fibers with straight-fiber <i>A<sub>eff</sub></i> values > 1000 &mgr;m<sup>2</sup> exhibit large decreases in <i>A<sub>eff</sub></i> and transverse mode-field displacements upon coiling, in agreement with recent calculations of Hadley et al. [Proc. of SPIE, Vol. 6102, 61021S (2006)] and Fini [Opt. Exp. 14, 69 (2006)]. Triangular-profile fibers substantially mitigate these effects, but suffer from excessive bend sensitivity at <i>A<sub>eff</sub></i> values of interest. Square-law (parabolic) profile fibers are free of modal distortion but are hampered by high bend sensitivity (although to a lesser degree than triangular profiles) and exhibit the largest mode displacements. We find that hybrid (combined power-law) profiles provide some decoupling of these tradeoffs and allow all design goals to be achieved simultaneously. We present optimized fiber designs based on this analysis.
Reducing energy consumption by dynamic copying of instructions onto onchip memory (2002)

The number of mobile embedded systems is increasing and all of them are limited in their uptime by their battery capacity. Several hardware changes have been introduced during the last years, but the steadily growing functionality still requires further energy reductions, e.g. through software optimizations. A significant amount of energy can be saved in the memory hierarchy where most of the energy is consumed.In this paper, a new software technique is presented which supports the use of an onchip scratchpad memory by dynamically copying program parts into it. The set of selected program parts are determined with an optimal algorithm using integer linear programming.
Suppression of Proinflammatory Cytokines in Functionalized Fullerene‐Exposed Dermal Keratinocytes (2010)

Initial experiments using differentially functionalized fullerenes, CD‐C 60 , hexa‐C 60 , and tris‐C 60 , suggested a properties dependent effect on cytotoxic and proliferative responses in human skin keratinocytes. In the present study we investigated the cytokine secretion profile of dermal epithelial cells exposed to functionalized fullerenes. Keratinocyte‐derived cytokines affect homing and trafficking of normal and malignant epidermal immune as well as nonimmune cells in vivo. These cytokines are critical for regulating activation, proliferation, and differentiation of epidermal cells. Our results indicate that tris‐C 60 (size range &lt;100 nm) significantly reduces inflammatory cytokine release in a dose‐ and time‐dependent manner. In contrast CD‐C 60 demonstrated a relatively pro‐inflammatory cytokine response, while hexa‐C 60 did not significantly perturb cytokine responses. Physical and chemical characterizations of these engineered nanomaterials suggest that the disparate biological responses observed may potentially be a function of the aggregation properties of these fullerenes.
Control Strategies Based on Symmetrical Components for Grid-Connected Converters Under Voltage Dips (2009)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> Low-voltage ride-through (LVRT) requirements demand wind-power plants to remain connected to the network in presence of grid-voltage dips. Most dips present positive-, negative-, and zero-sequence components. Hence, regulators based on symmetrical components are well suited to control grid-connected converters. A neutral-point-clamped topology has been considered as an active front end of a distributed power-generation system, following the trend of increasing power and voltage levels in wind-power systems. Three different current controllers based on symmetrical components and linear quadratic regulator have been considered. The performance of each controller is evaluated on LVRT requirement fulfillment, grid-current balancing, maximum grid-current value control, and oscillating power flow. Simulation and experimental results show that all three controllers meet LVRT requirements, although different system performance is found for each control approach. Therefore, controller selection depends on the system constraints and the type of preferred performance features. </para>
D-RNAi (Messenger RNA-antisense DNA Interference) as a Novel Defense System Against Cancer and Viral Infections. (2001)

D-RNAi (Messenger RNA-antisense DNA interference), a novel posttranscriptional phenomenon of silencing gene expression by transfection of mRNA-aDNA hybrids, was originally observed in the effects of bcl-2 on phorbol ester-induced apoptosis in human prostate cancer LNCaP cells. This phenomenon was also demonstrated in chicken embryos and a human CD4(+) T cell line, H9. The in vivo transduction of beta-catenin D-RNAi was shown to knock out more than 99% endogenous beta-catenin gene expression, while the in cell transfection of HIV-1 D-RNAi homolog rejected viral gene replication completely. D-RNAi was found to have long-term gene knockout effects resulting from a posttranscriptional gene silencing mechanism that may involve the homologous recombination between intracellular mRNA and the mRNA components of a D-RNAi construct. These findings provide a potential intracellular defense system against cancer and viral infections.
DNA sequencing using a four‐color confocal fluorescence capillary array scanner (1996)

The design, construction and operation of a four-color capillary array electrophoresis scanner are presented. The use of sensitive energy transfer primers facilitates four-color detection of the DNA sequencing fragments following excitation at a single laser wavelength (488 nm). This scanner collects fluorescence data from up to 25 capillaries in parallel. The resulting four-color image files are automatically reduced to four-color line plots, and a base-calling program (Sax) is used to call the sequence. The performance of this system for DNA sequencing is demonstrated by examining twelve different motifs of the hypervariable region I of human mitochondrial (mt) DNA obtained from a Sierra Leone population.
Identification and Optimization of Pyrrolo[3,2-d]pyrimidine Toll-like Receptor 7 (TLR7) Selective Agonists for the Treatment of Hepatitis B (2017)

Pyrrolo[3,2-d]pyrimidines were identified as a new series of potent and selective TLR7 agonists. Compounds were optimized for their activity and selectivity over TLR8. This presents an advantage over recently described scaffolds that have residual TLR8 activity, which may be detrimental to the tolerability of the candidate drug. Oral administration of the lead compound 54 effectively induced a transient interferon stimulated gene (ISG) response in mice and cynomolgus monkeys. We aimed for a high first pass effect, limiting cytokine induction systemically, and demonstrated the potential for the immunotherapy of viral hepatitis.