gebhart/patrepeval huggingface dataset:
Hierarchical Responsive Nanoplatform with Two-Photon Aggregation-Induced Emission Imaging for Efficient Cancer Theranostics (2019)

Theranostic nanoplatforms haev been proven to be a feasible strategy against cancer for convenient diagnosis, efficient drug release, and reduced side effects. However, the drug leakage during blood circulation, poor cellular uptake of drug-loaded nanoparticles, and insufficient drug release still remain to be overcome. Herein, a hierarchical pH and reactive oxygen species (ROS)-responsive nanoplatform is constructed labeling with a two-photon fluorophore developed by us, aiming for a programmed drug delivery and an intensive two-photon bioimaging. With the capecitabine (Cap) conjugated, the prodrug polymer PMPC-<i>b</i>-P[MPA(Cap)-<i>co</i>-TPMA]-PAEMA (PMMTA<sub><i>b</i></sub>-Cap) can be self-assembled into the core-shell structured micelles, which can stay stable in the blood stream. Once the micelles accumulate at the tumor tissue, the outside PMPC shell can be desquamated while the inner PAEMA become hydrophilic and electropositive under the acidic extracellular tumor microenvironment, leading to a shrunken micellar size for the better penetration along with enhanced endocytosis. After cellular internalization, the overexpressed intracellular ROS can eventually trigger the drug delivery for an accurate tumor therapy, which is confirmed by the in vivo antitumor experiments. Furthermore, the in vivo micellar biodistribution can be traced by a deep tissue imaging up to 150 μm because of the aggregation-induced emission active two-photon fluorophore. As a theranostic nanoplatform with two-photon bioimaging and hierarchical responsiveness, these PMMTA<sub><i>b</i></sub>-Cap micelles can be a potential candidate for tumor theranostical applications.
A novel approach for nasopharyngeal carcinoma treatment uses phenylbutyrate as a protein kinase C modulator: implications for radiosensitization and EBV-targeted therapy. (2000)

Sodium phenylbutyrate (NaPB) represent a new non-toxic class of compounds with antiproliferative activities to different tumors and has been shown to modulate many gene expressions by inhibiting histone deacetylation and DNA methylation as the major mechanism. Butyrate and other protein kinase C (PKC) activators have been reported to be able to activate virus enzymes. The present work investigates whether NaPB has an antiproliferative effect or modulatory effects on EBV-associated nasopharyngeal carcinoma (NPC) and whether EBV thymidine kinase gene can be activated to make cells susceptible to ganciclovir (GCV) therapy. NaPB treatment displayed a dose- and time-dependent antiproliferative effect on the NPC cell line CNE2. Cell cycle analysis revealed an inhibitory effect of NaPB on G1-S-phase progression. Shortly after NaPB treatment, we found that PKC activity was activated rapidly but also decreased rapidly. Down-regulation of PKC-alpha and translocation of PKC-alpha from the cytosol to membrane were seen by Western blot. The decrease in PKC activity by NaPB corresponds to an enhanced response to radiation on CEN2 cells. Moreover, NaPB up-regulated EBV thymidine kinase activity to render EBV-associated Daudi cells susceptible to killing by GCV. Based on the observations of NaPB as a PKC modulator, the combination of NaPB, GCV, and radiation may provide a potential novel approach for treatment of EBV-associated NPC.
Comparative stability of ethanol production by Escherichia coli KO11 in batch and chemostat culture (1999)

Differing claims regarding the stability of the recombinant ethanologen E. coli KO11 are addressed here in batch and chemostat culture. In repeat batch culture, the organism was stable on glucose, mannose, xylose and galactose for at least three serial transfers, even in the absence of a selective antibiotic. Chemostat cultures on glucose were remarkably stable, but on mannose, xylose and a xylose/glucose mixture, they progressively lost their hyperethanologenicity. On xylose, the loss was irreversible, indicating genetic instability. The loss of hyperethanologenicity was accompanied by the production of high concentrations of acetic acid and by increasing biomass yields, suggesting that the higher ATP yield associated with acetate production may foster the growth of acetate-producing revertant strains. Plate counts on high chloramphenicol-containing medium, whether directly, or following preliminary growth on non-selective medium, were not a reliable indicator of high ethanologenicity during chemostat culture. In batch culture, the organism appeared to retain its promise for ethanol production from lignocellulosics and concerns that antibiotics may need to be included in all media appear unfounded.
Structural Mechanism of ER Retrieval of MHC Class I by Cowpox (2012)

One of the hallmarks of viral immune evasion is the capacity to disrupt major histocompatibility complex class I (MHCI) antigen presentation to evade T-cell detection. Cowpox virus encoded protein CPXV203 blocks MHCI surface expression by exploiting the KDEL-receptor recycling pathway, and here we show that CPXV203 directly binds a wide array of fully assembled MHCI proteins, both classical and non-classical. Further, the stability of CPXV203/MHCI complexes is highly pH dependent, with dramatically increased affinities at the lower pH of the Golgi relative to the endoplasmic reticulum (ER). Crystallographic studies reveal that CPXV203 adopts a beta-sandwich fold similar to poxvirus chemokine binding proteins, and binds the same highly conserved MHCI determinants located under the peptide-binding platform that tapasin, CD8, and natural killer (NK)-receptors engage. Mutagenesis of the CPXV203/MHCI interface identified the importance of two CPXV203 His residues that confer low pH stabilization of the complex and are critical to ER retrieval of MHCI. These studies clarify mechanistically how CPXV203 coordinates with other cowpox proteins to thwart antigen presentation.
Small Molecule Neurotrophin Receptor Ligands: Novel Strategies for Targeting Alzheimers Disease Mechanisms (2007)

A number of factors limit the therapeutic application of neurotrophin proteins, such as nerve growth factor (NGF) and brain-derived growth factor (BDNF), for Alzheimer's and other neurodegenerative diseases. These factors include unfavorable pharmacological properties typical of proteins and the pleiotropic effects mediated by protein-ligand interactions with p75(NTR), Trk, and sortilin neurotrophin receptors. Targeted modulation of p75(NTR) provides a strategy for preventing degeneration without promoting TrkA-mediated deleterious effects, and targeted activation of TrkB might achieve more favorable neurotrophic effects than those achieved by concomitant activation of p75(NTR) and TrkB. The discovery of small molecules functioning as ligands at specific neurotrophin receptors has made possible for the first time approaches for modulating selected components of neurotrophin signaling processes for the purpose of modulating underlying Alzheimer's disease mechanisms.
Conformal airborne arrays (1997)

Many of the latest developments in airborne conformal arrays are reviewed. Array packaging is dependent on the frequency band and amount of radiated power. From microwave through millimeter-wave bands, various configurations are shown and discussed.
Intravitreal invading cells contribute to vitreal cytokine milieu in proliferative vitreoretinopathy (2001)

Levels of both protein and mRNA encoding IL-6, IL-8, IL-1beta, and IFNgamma is significantly increased in vitreous samples from patients with PVR. The strong correlation between ELISA detectable cytokines (protein products) and their respective mRNA levels suggest that intravitreal, invasive cells are the major source of these cytokines, with the exception of IL-12. Cells invading the vitreous do not appear to locally produce IL-12 mRNA. This would appear to implicate cells peripheral to the vitreal mass as the major source of this cytokine.
Occurrence of a Bacterial Watermelon Fruit Blotch in Florida (1991)

Mature watermelon fruit with large, firm, dark green, water-soaked lesions were observed in spring 1989. Losses of up to 50% in marketable fruit occurred in some fields in Florida. A gram-negative, aerobic, rod-shaped, nonfluorescent, oxidase-positive, arginine dihydrolase-negative bacterium was isolated from diseased tissues. In pathogenicity tests, the bacterium produced symptoms in foliage and fruit. Morphological, physiological, and biochemical properties of the bacterium related it to a previously described pathogen of watermelon, Pseudomonas pseudoalcaligenes subsp. citrulli
Imaginary phone (2011)

We propose a method for learning how to use an imaginary interface (i.e., a spatial non-visual interface) that we call "transfer learning". By using a physical device (e.g. an iPhone) a user inadvertently learns the interface and can then transfer that knowledge to an imaginary interface. We illustrate this concept with our Imaginary Phone prototype. With it users interact by mimicking the use of a physical iPhone by tapping and sliding on their empty non-dominant hand without visual feedback. Pointing on the hand is tracked using a depth camera and touch events are sent wirelessly to an actual iPhone, where they invoke the corresponding actions. Our prototype allows the user to perform everyday task such as picking up a phone call or launching the timer app and setting an alarm. Imaginary Phone thereby serves as a shortcut that frees users from the necessity of retrieving the actual physical device. We present two user studies that validate the three assumptions underlying the transfer learning method. (1) Users build up spatial memory automatically while using a physical device: participants knew the correct location of 68% of their own iPhone home screen apps by heart. (2) Spatial memory transfers from a physical to an imaginary inter-face: participants recalled 61% of their home screen apps when recalling app location on the palm of their hand. (3) Palm interaction is precise enough to operate a typical mobile phone: Participants could reliably acquire 0.95cm wide iPhone targets on their palm-sufficiently large to operate any iPhone standard widget.
Common Protective and Diverse Smooth Muscle Cell Effects of AAV-Mediated Angiopoietin-1 and -2 Expression in Rat Cardiac Allograft Vasculopathy (2006)

Angiopoietin-1 (Ang1) and Ang2 regulate the maintenance of normal vasculature by direct endothelial and indirect smooth muscle cell (SMC) effects. Dysfunction of vascular wall cells is considered central in cardiac allograft vasculopathy (CAV), where inflammation and arterial injury initiate subsequent intimal SMC proliferation. In this study, we investigated the effect of exogenous Ang1 and Ang2 in chronically rejecting rat cardiac allografts by intracoronary adeno-associated virus (AAV)-mediated gene transfer. Bioluminescent imaging of AAV-transfected syngeneic grafts revealed gradual and stable transgene expression in graft cardiomyocytes. In cardiac allografts, both AAV-Ang1 and AAV-Ang2 decreased inflammation and increased antiapoptotic Bcl-2 mRNA and Bcl-2/Bax ratio at 8 weeks. Only AAV-Ang2 decreased the development of CAV, whereas AAV-Ang1 activated arterial SMC and increased PDGF-A mRNA in the allograft. Collectively, our results show that exogenous Ang1 and Ang2 have similar antiinflammatory and antiapoptotic effects in cardiac allografts. Prolonged AAV-mediated Ang1 transgene expression also induced SMC activation, whereas AAV-Ang2 lacked the SMC activating effects and decreased CAV. Our results thus highlight the common protective and diverse SMC effects of Ang1 and Ang2 in cardiac allograft microenvironment and the importance of timing of angiopoietins to achieve therapeutic effects.
Gate-Tunable Conducting Oxide Metasurfaces (2016)

Metasurfaces composed of planar arrays of subwavelength artificial structures show promise for extraordinary light manipulation. They have yielded novel ultrathin optical components such as flat lenses, wave plates, holographic surfaces, and orbital angular momentum manipulation and detection over a broad range of the electromagnetic spectrum. However, the optical properties of metasurfaces developed to date do not allow for versatile tunability of reflected or transmitted wave amplitude and phase after their fabrication, thus limiting their use in a wide range of applications. Here, we experimentally demonstrate a gate-tunable metasurface that enables dynamic electrical control of the phase and amplitude of the plane wave reflected from the metasurface. Tunability arises from field-effect modulation of the complex refractive index of conducting oxide layers incorporated into metasurface antenna elements which are configured in reflectarray geometry. We measure a phase shift of 180° and ∼30% change in the reflectance by applying 2.5 V gate bias. Additionally, we demonstrate modulation at frequencies exceeding 10 MHz and electrical switching of ±1 order diffracted beams by electrical control over subgroups of metasurface elements, a basic requirement for electrically tunable beam-steering phased array metasurfaces. In principle, electrically gated phase and amplitude control allows for electrical addressability of individual metasurface elements and opens the path to applications in ultrathin optical components for imaging and sensing technologies, such as reconfigurable beam steering devices, dynamic holograms, tunable ultrathin lenses, nanoprojectors, and nanoscale spatial light modulators.
An Ultra-specific Avian Antibody to Phosphorylated Tau Protein Reveals a Unique Mechanism for Phosphoepitope Recognition (2012)

Highly specific antibodies to phosphoepitopes are valuable tools to study phosphorylation in disease states, but their discovery is largely empirical, and the molecular mechanisms mediating phosphospecific binding are poorly understood. Here, we report the generation and characterization of extremely specific recombinant chicken antibodies to three phosphoepitopes on the Alzheimer disease-associated protein tau. Each antibody shows full specificity for a single phosphopeptide. The chimeric IgG pT231/pS235_1 exhibits a K(D) of 0.35 nm in 1:1 binding to its cognate phosphopeptide. This IgG is murine ortholog-cross-reactive, specifically recognizing the pathological form of tau in brain samples from Alzheimer patients and a mouse model of tauopathy. To better understand the underlying binding mechanisms allowing such remarkable specificity, we determined the structure of pT231/pS235_1 Fab in complex with its cognate phosphopeptide at 1.9 Å resolution. The Fab fragment exhibits novel complementarity determining region (CDR) structures with a "bowl-like" conformation in CDR-H2 that tightly and specifically interacts with the phospho-Thr-231 phosphate group, as well as a long, disulfide-constrained CDR-H3 that mediates peptide recognition. This binding mechanism differs distinctly from either peptide- or hapten-specific antibodies described to date. Surface plasmon resonance analyses showed that pT231/pS235_1 binds a truly compound epitope, as neither phosphorylated Ser-235 nor free peptide shows any measurable binding affinity.
Pathogenesis of Preeclampsia (2010)

Preeclampsia is a systemic syndrome that occurs in 3 to 5% of pregnant women and classically manifests as new-onset hypertension and proteinuria after 20 weeks of gestation. Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality. The only known cure is delivery of the placenta. Recent discoveries, however, have led to important advances in understanding the pathogenesis of the condition. Placental antiangiogenic factors are upregulated and disrupt the maternal endothelium. This change in the normal angiogenic balance toward an antiangiogenic state can result in hypertension, proteinuria, glomerular endotheliosis, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and cerebral edema-the clinical signs of preeclampsia and eclampsia. The regulation of these antiangiogenic factors in the placenta is unknown. The recent discoveries of upregulated antiangiogenic factors provide promise for future testing to predict and diagnose preeclampsia as well as therapeutic targets for amelioration of the clinical disease.
Hope for Treatment of Thrombocytopenia (1994)

Thrombocytopenia has been a major problem in the treatment of patients undergoing bone marrow transplantation or chemotherapy for cancer. Thrombopoietin, the hormone thought to stimulate the production and maturation of megakaryocytes (Figure 1), which in turn produce platelets, has recently been purified and cloned14. This discovery may lead to advances in the treatment of thrombocytopenia caused by deficient production of platelets.The recovery of platelets after bone marrow transplantation or chemotherapy often occurs later (23 to 60 days after transplantation) than the recovery of other hematopoietic lineages. Treatment has relied on the administration of many units of platelet . . .
[Achalasia: report of two cases]. (1990)

The first case, a two-month-old female infant, had frequent vomiting since 5 days of age. Dilated esophagus with narrowed distal end was noted on barium meal study. Panendoscopic examination revealed dilated esophagus and a pin-head sized, stenotic lumen at 15 cm from the incisor. Under the impression of esophageal stenosis, gastrostomy was performed for feeding. Esophagogram made at 6 months of age demonstrated good patency of the esophagus without stenosis and gastrostomy was subsequently closed at the age of 1 year. Unfortunately, swallowing disturbance had bothered her intermittently since. Barium esophagogram and panendoscopy made 8 years later again revealed distal esophageal obstruction with dilated proximal esophagus. The second case was a two and half year old boy who suffered from frequent regurgitation of undigested food for 6 months. Dilated esophagus with narrowing of the lower end of esophagus was noted on barium meal study. After admission, panendoscopic examination revealed the esophagus was very narrow at 25 cm from incisor and the proximal esophagus was dilated. The esophageal dilatation with mercury-weighted bougies was performed intermittently. At present he is doing well, and a barium meal study showed adequate esophageal emptying.
Oblimersen Bcl-2 Antisense: Facilitating Apoptosis in Anticancer Treatment (2002)

The components of the apoptotic program are targets for anticancer therapy. Bcl-2 protein inhibits apoptosis and confers resistance to treatment with traditional cytotoxic chemotherapy, radiotherapy, and monoclonal antibodies (mAb). Oblimersen sodium (G3139, Genasense, Genta Inc., Berkeley Heights, NJ) is an antisense oligonucleotide (AS-ON) compound designed to specifically bind to the first 6 codons of the human bcl-2 mRNA sequence, resulting in degradation of bcl-2 mRNA and subsequent decrease in Bcl-2 protein translation. Oblimersen is the first oligonucleotide to demonstrate proof of principle of an antisense effect in human tumors by the documented downregulation of the target Bcl-2 protein. A growing body of preclinical and clinical evidence suggests that oblimersen synergizes with many cytotoxic and biologic/immunotherapeutic agents against a variety of hematologic malignancies and solid tumors. Randomized clinical trials are currently underway to evaluate the efficacy and tolerability of oblimersen in combination with cytotoxic chemotherapy in chronic lymphocytic leukemia, multiple myeloma, malignant melanoma, and non-small cell lung cancer. In addition, nonrandomized trials are under way to evaluate oblimersen in non-Hodgkin's lymphoma, acute myeloid leukemia, and hormone-refractory prostate cancer. Preclinical data also support the clinical evaluation of oblimersen in additional tumor types, including chronic myelogenous leukemia and breast, small cell lung, gastric, colon, bladder, and Merkel cell cancers. Enhancement of the efficacy of anticancer treatments with oblimersen Bcl-2 antisense therapy represents a promising new apoptosis-modulating strategy, and ongoing clinical trials will test this therapeutic approach.
Induction of Heart Valve Lesions by Small-Molecule ALK5 Inhibitors (2011)

Aberrant signaling by transforming growth factor-β (TGF-β) and its type I (ALK5) receptor has been implicated in a number of human diseases and this pathway is considered a potential target for therapeutic intervention. Transforming growth factor-β signaling via ALK5 plays a critical role during heart development, but the role of ALK5 in the adult heart is poorly understood. In the current study, the preclinical toxicology of ALK5 inhibitors from two different chemistry scaffolds was explored. Ten-week-old female Han Wistar rats received test compounds by the oral route for three to seven days. Both compounds induced histopathologic heart valve lesions characterized by hemorrhage, inflammation, degeneration, and proliferation of valvular interstitial cells. The pathology was observed in all animals, at all doses tested, and occurred in all four heart valves. Immunohistochemical analysis of ALK5 in rat hearts revealed expression in the valves, but not in the myocardium. Compared to control animals, protein levels of ALK5 were unchanged in the heart valves of treated animals. We also observed a physeal dysplasia in the femoro-tibial joint of rats treated with ALK5 inhibitors, a finding consistent with a pharmacological effect described previously with ALK5 inhibitors. Overall, these findings suggest that TGF-β signaling via ALK5 plays a critical role in maintaining heart valve integrity.
A general extension system for event processing languages (2011)

Event processing languages (EPLs) for Complex Event Processing (CEP) systems are descriptive in nature. This allows the authoring of event processing applications at a higher level of abstraction. However, they are less suitable for dealing with low- level tasks, such as String manipulation, and other programming- in-the-small problems. In addition, current EPL implementations lack the richness of other programming language libraries (e.g. Java), which have been built over several years of usage. We present an architecture whereby providers can integrate existing programming languages into CQL, our EPL language of choice, leveraging the advantages of other languages, while still retaining the expressiveness and conciseness of EPL. We also demonstrate how the architecture avoids the awkwardness of previous integration solutions, which generally were focused only at the function-level (e.g. User-Defined Functions, Java call outs). Rather, the outlined solution is realized at the language level, through the extension of language implementation artifacts, such as type systems; thus resulting in a seamless, precise, and naturally blended environment for developing CEP applications. The architecture is based upon the concept of extension cartridges, which are modules that provide metadata describing the extensions. Finally, we show how these extension cartridges may be used in real-world CEP scenarios.
Randomized clinical trial of sacral versus percutaneous tibial nerve stimulation in patients with faecal incontinence (2015)

In the short term, both SNS and PTNS provide some clinical benefit to patients with FI. Registration numbers: 2010-018728-15 and 10479 (http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=10479).
An Asymptotic Equivalence of Choice of Model by Cross-Validation and Akaike's Criterion (1977)

Summary A logarithmic assessment of the performance of a predicting density is found to lead to asymptotic equivalence of choice of model by cross-validation and Akaike's criterion, when maximum likelihood estimation is used within each model.