gebhart/patrepeval huggingface dataset:
Notch signaling pathway and tissue engineering (2007)

The Notch pathway is a signaling network essential for proper organ development in an embryo, and is indispensable for tissue regeneration in the adult. This key regulatory signaling network is evolutionarily conserved in all metazoans and is continually utilized for the building, maintenance and repair of diverse organs and tissues. Importantly, dysfunctions in the Notch pathway have been demonstrated to result in oncogenic transformation, such as in lymphoid cancers, and have been linked to the pathogenesis of several inherited human diseases. Therefore, the ability to regulate Notch signaling intensity both positively and negatively has a very high therapeutic relevance. Adapting this pathway for tissue engineering applications has great potential to spear-head the development of smart biomaterials to deliberately control cell-fate decisions and lead to designer ex vivo morphogenesis. This review describes the components of Notch-specific signal transduction, presents the role of the Notch signaling network in constructing and repairing multiple organ systems, summarizes the Notch-related pathologies, outlines current advances in the deliberate modulation of the Notch pathway in bioengineering applications, and introduces future perspectives on the use of Notch pathway manipulations as a powerful universal tool in tissue engineering and in the orchestration of stem cell responses. This review also summarizes the existing bioengineering methods most suitable for the deliberate manipulation of Notch signaling, such as smart biomaterials able to pattern Notch ligands or to create gradients of Notch agonists and antagonists. Such methods will likely facilitate the engineering and dynamic remodeling of tissues composed of stem, progenitor and differentiated cells derived from an initially equivalent cell population.
Practical and Highly Enantioselective Ring Opening of Cyclic Meso-Anhydrides Mediated by Cinchona Alkaloids (2000)

The cinchona alkaloid-mediated opening of prochiral cyclic anhydrides in the presence of methanol leading to optically active hemiesters is described. Very structurally diverse anhydrides are converted into their corresponding methyl monoesters, and either enantiomer can be obtained with up to 99% ee by using quinine or quinidine as directing additive. After the reaction, the alkaloids can be recovered almost quantitatively and reused without loss of enantioselectivity. Additionally, a catalytic protocol which permits the substoichiometric use of quinidine in the presence of easily accessible pentamethylpiperidine (pempidine) is presented.
Tolerability of Crisaborole Ointment for Application on Sensitive Skin Areas: A Randomized, Double-Blind, Vehicle-Controlled Study in Healthy Volunteers (2016)

Crisaborole ointment application to sensitive skin areas was well tolerated in healthy volunteers, supporting its potential role as a topical treatment alternative for patients with AD or psoriasis.
Patterned growth of pentacene (2004)

We propose a way of patterning organic small molecule thin films without requiring a hardmask and therefore more compatible with printing technologies. Active and passive areas for transistors are predefined by different surface chemistries. The subsequent growth takes place under conditions that cause the formation of a high mobility two-dimensional film in the active area and a disconnected three-dimensional film or no film in the passive area. This concept is founded on the basic theory of nucleation of organic small molecules on inert substrates and applied to the growth of patterned pentacene layers.
InP/InGaAs resonant tunneling diode with six-route negative differential resistances (2005)

Sequential tunneling behavior of p-n resonant tunneling diode with four-period InP/InGaAs superlattice is demonstrated. Theoretical calculation shows three split quantized energies in the four-period InP (50Å)/InGaAs (25Å) superlattice structure. For the increase of more negative differential resistance (NDR) routes, high-field domain is formed in the superlattice under sufficiently large operation biases. Experimentally, an interesting six-route NDR characteristic, resulting from the form of split miniband structures and the extension of high-field domain in the InP/InGaAs superlattice, is observed at room temperature.
The POLARIS Gene of Arabidopsis Encodes a Predicted Peptide Required for Correct Root Growth and Leaf Vascular Patterning (2002)

The POLARIS (PLS) gene of Arabidopsis was identified as a promoter trap transgenic line, showing beta-glucuronidase fusion gene expression predominantly in the embryonic and seedling root, with low expression in aerial parts. Cloning of the PLS locus revealed that the promoter trap T-DNA had inserted into a short open reading frame (ORF). Rapid amplification of cDNA ends PCR, RNA gel blot analysis, and RNase protection assays showed that the PLS ORF is located within a short ( approximately 500 nucleotides) auxin-inducible transcript and encodes a predicted polypeptide of 36 amino acid residues. pls mutants exhibit a short-root phenotype and reduced vascularization of leaves. pls roots are hyperresponsive to exogenous cytokinins and show increased expression of the cytokinin-inducible gene ARR5/IBC6 compared with the wild type. pls seedlings also are less responsive to the growth-inhibitory effects of exogenous auxin and show reduced expression of the auxin-inducible gene IAA1 compared with the wild type. The PLS peptide-encoding region of the cDNA partially complements the pls mutation and requires the PLS ORF ATG for activity, demonstrating the functionality of the peptide-encoding ORF. Ectopic expression of the PLS ORF reduces root growth inhibition by exogenous cytokinins and increases leaf vascularization. We propose that PLS is required for correct auxin-cytokinin homeostasis to modulate root growth and leaf vascular patterning.
Gene expression profiling of minor salivary glands clearly distinguishes primary Sjögren's syndrome patients from healthy control subjects (2005)

We have identified distinct gene expression profiles in MSGs from patients with primary SS that provide new knowledge about groups of genes that are up-regulated or down-regulated during disease, constituting an excellent platform for forthcoming functional studies.
Identification of multiple genes in bovine retinal pericytes altered by exposure to elevated levels of glucose by using mRNA differential display. (1994)

Loss of capillary pericytes, a characteristic finding in diabetic retinopathy, is strongly associated with hyperglycemia. The pathologic aberrations associated with diabetic retinopathy are localized primarily in the retinal capillaries and are only poorly reversed by subsequent euglycemic control. Since hyperglycemia significantly inhibits pericyte growth in culture, we investigated the regulation of gene expression in retinal pericytes exposed to physiologic (5.5mM) and pathologic (20 mM) glucose concentrations. By utilizing modifications of the mRNA differential display technique, over 14,000 mRNA species were screened, and 35 candidate clones were obtained. Partial DNA sequence demonstrated that 25 of these were distinct genes, including 7 known, 16 previously unreported, and 2 sequences with known homologues. Northern blot analysis demonstrated altered gene expression in 10 (40%), undetectable signals in 12 (48%), and nonregulation in 3 (12%). Genes with glucose-regulated expression included those encoding fibronectin (51% +/- 15%, P = 0.003; mean percentage of control +/- SD), caldesmon (68% +/- 18%; P = 0.026), two ribosomal proteins (201% +/- 72%, P = 0.011; 136% +/- 16%, P = 0.036), Rieske FeS reductase (66% +/- 17%; P = 0.029), three previously unreported sequences (57%, 167%, 271%), and molecules homologous to autoantigens (213%) and tyrosine kinases (down 16- to 33-fold). Caldesmon protein concentrations in pericytes and smooth muscle cells demonstrated decreases by Western blot analysis concordant with mRNA levels. These studies identify genes whose expression is significantly altered after 7 days of exposure to elevated glucose levels and provide new targets for understanding the adverse effects of hyperglycemia on vascular cells. In addition, this study provides strong support for the use of differential mRNA display as a method to rapidly isolate differentially expressed genes in metabolic systems.
Pentoxifylline and severe acute respiratory syndrome (SARS): a drug to be considered. (2003)

The antiinflammatory, antiviral, immunomodulatory and bronchodilatory effects of PTX, along with its low cost and toxicity, make it a promising drug to be considered for SARS treatment, alone or as an adjuvant therapy in combination with other drugs. The classical antiviral approach as single treatment for viral diseases should be reviewed in this occasion; immunomodulatory therapies could play an important role in SARS therapy.
Arterial-Venous Segregation by Selective Cell Sprouting: An Alternative Mode of Blood Vessel Formation (2009)

Blood vessels form de novo (vasculogenesis) or upon sprouting of capillaries from preexisting vessels (angiogenesis). With high-resolution imaging of zebrafish vascular development, we uncovered a third mode of blood vessel formation whereby the first embryonic artery and vein, two unconnected blood vessels, arise from a common precursor vessel. The first embryonic vein formed by selective sprouting of progenitor cells from the precursor vessel, followed by vessel segregation. These processes were regulated by the ligand EphrinB2 and its receptor EphB4, which are expressed in arterial-fated and venous-fated progenitors, respectively, and interact to orient the direction of progenitor migration. Thus, directional control of progenitor migration drives arterial-venous segregation and generation of separate parallel vessels from a single precursor vessel, a process essential for vascular development.
DNA Vaccines. (2000)

DNA vaccination or genetic immunization is a rapidly developing technology that offers new approaches for the prevention and therapy of disease. Regarding the inoculation method of DNA vaccine, we recommend the gene gun delivery system, which is a highly reliable method compared to intramuscular inoculation. DNA vaccines could have potential advantages over other types of vaccines in that these vaccines can induce strong cellular immune responses, cytotoxic T lymphocytes and type 1 helper T cells, without resorting to live organisms or complicated protein formulation. The cellular immune responses are especially required for the protection against infections with intracellular pathogens such as viruses and Mycobacterium tuberculosis and protection against cancers, suggesting that they seem to be suitable targets of DNA vaccines. We describe here that their application to bacterial infections requires optimization of codon usage in the DNA vaccines to the host animal to improve translational efficiencies of the bacteria genes. DNA vaccines for a variety of pathogens and cancers have now entered phase I/II human clinical trials.
On the mechanism of CD47 targeting in cancer (2012)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Crystal Structure of HLA-DR2 (DRA*0101, DRB1*1501) Complexed with a Peptide from Human Myelin Basic Protein (1998)

Susceptibility to multiple sclerosis is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 (DRB1*1501) haplotype. The structure of HLA-DR2 was determined with a bound peptide from human myelin basic protein (MBP) that is immunodominant for human MBP-specific T cells. Residues of MBP peptide that are important for T cell receptor recognition are prominent, solvent exposed residues in the crystal structure. A distinguishing feature of the HLA-DR2 peptide binding site is a large, primarily hydrophobic P4 pocket that accommodates a phenylalanine of the MBP peptide. The necessary space for this aromatic side chain is created by an alanine at the polymorphic DRbeta 71 position. These features make the P4 pocket of HLA-DR2 distinct from DR molecules associated with other autoimmune diseases.
Suppression of arterial intimal hyperplasia by cilostamide, a cyclic nucleotide phosphodiesterase 3 inhibitor, in a rat balloon double‐injury model (2000)

The effects of cilostamide, a cyclic nucleotide phosphodiesterase 3 (PDE3) selective inhibitor, on vascular intimal hyperplasia were evaluated using a single-balloon injury model and a double-injury model in which the rat common carotid artery was subjected to a second injury at a site injured 14 days previously. In the double-injury model, the second balloon injury caused more severe intimal hyperplasia (intima/media (IM) ratio, 1.88+/-0.10) than in the single-injury model (1.09+/-0.08). Histopathological study revealed that vascular smooth muscle cells (VSMC) were the predominant cell-type in the affected neointimal area. Oral administration of cilostamide for 2 weeks after the second injury suppressed intimal hyperplasia in the double-injury model (30 mg kg(-1) bid, 83% inhibition in terms of the IM ratio, P<0.05; 100 mg kg(-1) bid, 69% inhibition, P<0.05). Similar effects were also observed in the single-injury model with oral administration of cilostamide for 2 weeks (100 mg kg(-1) bid, 36% inhibition, P<0.01). Cilostamide inhibited DNA synthesis of cultured VSMC stimulated by foetal calf serum or different kinds of growth factors, but did not affect their migration stimulated by platelet-derived growth factor (PDGF)-BB. Cilostamide significantly increased the cyclic AMP concentration of VSMC dose-dependently. These results indicate that cilostamide suppresses intimal hyperplasia both in the single- and double-injury models of rat, presumably by inhibiting proliferation rather than migration of VSMC. It is suggested that PDE3 inhibitors might find application in preventing intimal hyperplasia following angioplasty such as percutaneous transluminal coronary angioplasty (PTCA) or stent.
Parallel Algorithms for Digital Image Processing, Computer Vision and Neural Networks (1993)

Low Level Parallel Image Processing Parallel FFT-like Transform Algorithms on Transputers Parallel Edge Detection and Related Algorithms Parallel Segmentation Algorithms MIMD and SIMD Parallel Range Data Segmentation Parallel Stereo and Motion Estimation Parallel Implementations of the Backpropagation Learning Algorithm Based on Network Topology Parallel Neural Computation Based on Algebraic Partitioning Parallel Neural Computing Based on Network Duplicating PARALLEL EIKONA: A Parallel Digital Image Processing Package Parallel Architectures and Algorithms for Real Time Computer Vision Index.
The role of monoamine oxidase A, MAOA , in the aetiology of antisocial behaviour: the importance of gene–environment interactions (2005)

Reports from both human studies and animal models suggest that MAOA may have a key role in aggression. Differences in the copy number of a repeat motif in the promoter of MAOA appear to regulate its activity. We review the evidence that suggests activity levels of this enzyme may play a key role in modulating antisocial/aggressive behavioural outcomes. Two common alleles in the human population have been identified which confer either high or low transcriptional functionality. The gene is X-linked and males can, therefore, be typed as 'low' or 'high' types. A key feature that has emerged from both our own studies and replicated recently by others, is that high activity variants of the gene appear to confer a protective influence against maltreatment, such that maltreated males with a high-MAOA activity genotype were less likely to develop antisocial problems, an observation that may explain part of the variability in developmental outcomes associated with maltreatment.
Scandium Ion-Promoted Reduction of Heterocyclic NN Double Bond. Hydride Transfer vs Electron Transfer (2002)

Hydride transfer from 10-methyl-9,10-dihydroacridine (AcrH(2)) to 3,6-diphenyl-1,2,4,5-tetrazine (Ph(2)Tz), which contains a N=N double bond, occurs efficiently in the presence of Sc(OTf)(3) (OTf = OSO(2)CF(3)) in deaerated acetonitrile (MeCN) at 298 K, whereas no reaction occurs in the absence of Sc(3+). The observed second-order rate constant (k(obs)) increases with increasing Sc(3+) concentration to approach a limited value. When AcrH(2) is replaced by the dideuterated compound (AcrD(2)), the rate of Sc(3+)-promoted hydride transfer exhibits the same primary kinetic isotope effect (k(H)/k(D) = 5.2+/-0.2), irrespective of Sc(3+) concentration. Scandium ion also promotes an electron transfer from CoTPP (TPP(2)(-) = tetraphenylporphyrin dianion) and 10,10'-dimethyl-9,9'-biacridine [(AcrH)(2)] to Ph(2)Tz, whereas no electron transfer from CoTPP or (AcrH)(2) to Ph(2)Tz occurs in the absence of Sc(3+). In each case, the observed second-order rate constant of electron transfer (k(et)) shows a first-order dependence on [Sc(3+)] at low concentrations and a second-order dependence at higher concentrations. Such dependence of k(et) on [Sc(3+)] is ascribed to formation of 1:1 and 1:2 complexes between Ph(2)Tz(*)(-) and Sc(3+) at the low and high concentrations of Sc(3+), respectively, which results in acceleration of the rate of electron transfer. The formation of 1:2 complex has been confirmed by the ESR spectrum in which the hyperfine structure is different from that of free Ph(2)Tz(*)(-). The 1:2 complex formation results in the saturated kinetic dependence of k(obs) on [Sc(3+)] for the Sc(3+)-promoted hydride transfer, which proceeds via Sc(3+)-promoted electron transfer from AcrH(2) to Ph(2)Tz, followed by proton transfer from AcrH(2)(*)(+) to the 1:1 Ph(2)Tz(*)(-)-Sc(3+) complex and the subsequent facile electron transfer from AcrH(*) to Ph(2)TzH(*). The effects of counteranions on the Sc(3+)-promoted electron transfer and hydride transfer reactions are also reported.
Neural Person Search Machines (2017)

We investigate the problem of person search in the wild in this work. Instead of comparing the query against all candidate regions generated in a query-blind manner, we propose to recursively shrink the search area from the whole image till achieving precise localization of the target person, by fully exploiting information from the query and contextual cues in every recursive search step. We develop the Neural Person Search Machines (NPSM) to implement such recursive localization for person search. Benefiting from its neural search mechanism, NPSM is able to selectively shrink its focus from a loose region to a tighter one containing the target automatically. In this process, NPSM employs an internal primitive memory component to memorize the query representation which modulates the attention and augments its robustness to other distracting regions. Evaluations on two benchmark datasets, CUHK-SYSU Person Search dataset and PRW dataset, have demonstrated that our method can outperform current state-of-the-arts in both mAP and top-1 evaluation protocols.
Design, Synthesis, and Biological Evaluation of 2-Oxo-3,4-dihydropyrimido[4,5-d]pyrimidinyl Derivatives as New Irreversible Epidermal Growth Factor Receptor Inhibitors with Improved Pharmacokinetic Properties (2013)

Structural optimization of a series of 2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidinyl compounds, potential new irreversible EGFR inhibitors, was performed to improve pharmacokinetic properties of the compounds. This led to compound 2v with improved aqueous solubility and good pharmacokinetic properties which at the nanomolar level potently inhibits gefitinib-resistant EGFR(L858R/T790M) kinase and displays strong antiproliferative activity against H1975 nonsmall cell lung cancer cells. The new inhibitor also shows promising antitumor efficacy in a murine EGFR(L858R/T790M)-driven H1975 xenograft model without effect on body weight. These studies provide new lead compounds for further development of drugs for treatment of gefitinib-resistant nonsmall cell lung cancer patients.
Endovascular versus Open Repair of Abdominal Aortic Aneurysm (2010)

In this large, randomized trial, endovascular repair of abdominal aortic aneurysm was associated with a significantly lower operative mortality than open surgical repair. However, no differences were seen in total mortality or aneurysm-related mortality in the long term. Endovascular repair was associated with increased rates of graft-related complications and reinterventions and was more costly. (Current Controlled Trials number, ISRCTN55703451.)
Searching for Efficient Multi-Scale Architectures for Dense Image Prediction (2018)

The design of neural network architectures is an important component for achieving state-of-the-art performance with machine learning systems across a broad array of tasks. Much work has endeavored to design and build architectures automatically through clever construction of a search space paired with simple learning algorithms. Recent progress has demonstrated that such meta-learning methods may exceed scalable human-invented architectures on image classification tasks. An open question is the degree to which such methods may generalize to new domains. In this work we explore the construction of meta-learning techniques for dense image prediction focused on the tasks of scene parsing, person-part segmentation, and semantic image segmentation. Constructing viable search spaces in this domain is challenging because of the multi-scale representation of visual information and the necessity to operate on high resolution imagery. Based on a survey of techniques in dense image prediction, we construct a recursive search space and demonstrate that even with efficient random search, we can identify architectures that outperform human-invented architectures and achieve state-of-the-art performance on three dense prediction tasks including 82.7\% on Cityscapes (street scene parsing), 71.3\% on PASCAL-Person-Part (person-part segmentation), and 87.9\% on PASCAL VOC 2012 (semantic image segmentation). Additionally, the resulting architecture is more computationally efficient, requiring half the parameters and half the computational cost as previous state of the art systems.