gebhart/patrepeval huggingface dataset:
Crystal structure of the ALK (anaplastic lymphoma kinase) catalytic domain (2010)

ALK (anaplastic lymphoma kinase) is an RTK (receptor tyrosine kinase) of the IRK (insulin receptor kinase) superfamily, which share an YXXXYY autophosphorylation motif within their A-loops (activation loops). A common activation and regulatory mechanism is believed to exist for members of this superfamily typified by IRK and IGF1RK (insulin-like growth factor receptor kinase-1). Chromosomal translocations involving ALK were first identified in anaplastic large-cell lymphoma, a subtype of non-Hodgkin's lymphoma, where aberrant fusion of the ALK kinase domain with the NPM (nucleophosmin) dimerization domain results in autophosphosphorylation and ligand-independent activation. Activating mutations within the full-length ALK kinase domain, most commonly R1275Q and F1174L, which play a major role in neuroblastoma, were recently identified. To provide a structural framework for understanding these mutations and to guide structure-assisted drug discovery efforts, the X-ray crystal structure of the unphosphorylated ALK catalytic domain was determined in the apo, ADP- and staurosporine-bound forms. The structures reveal a partially inactive protein kinase conformation distinct from, and lacking, many of the negative regulatory features observed in inactive IGF1RK/IRK structures in their unphosphorylated forms. The A-loop adopts an inhibitory pose where a short proximal A-loop helix (alphaAL) packs against the alphaC helix and a novel N-terminal beta-turn motif, whereas the distal portion obstructs part of the predicted peptide-binding region. The structure helps explain the reported unique peptide substrate specificity and the importance of phosphorylation of the first A-loop Tyr1278 for kinase activity and NPM-ALK transforming potential. A single amino acid difference in the ALK substrate peptide binding P-1 site (where the P-site is the phosphoacceptor site) was identified that, in conjunction with A-loop sequence variation including the RAS (Arg-Ala-Ser)-motif, rationalizes the difference in the A-loop tyrosine autophosphorylation preference between ALK and IGF1RK/IRK. Enzymatic analysis of recombinant R1275Q and F1174L ALK mutant catalytic domains confirms the enhanced activity and transforming potential of these mutants. The transforming ability of the full-length ALK mutants in soft agar colony growth assays corroborates these findings. The availability of a three-dimensional structure for ALK will facilitate future structure-function and rational drug design efforts targeting this receptor tyrosine kinase.
Examples of Effective Data Sharing in Scientific Publishing (2015)

We present a perspective on an approach to data sharing in scientific publications we have been developing in our group. The essence of the approach is that data can be embedded in a human-readable and machine-addressable way within the traditional publishing environment. We show this by example for both computational and experimental data. We articulate a need for new authoring tools to facilitate data sharing, and we discuss the tools we have been developing for this purpose. With these tools, data generation, analysis, and manuscript preparation can be deeply integrated, resulting in easier and better data sharing in scientific publications.
Inhibition of Inflammatory Hyperalgesia by Activation of Peripheral CB2Cannabinoid Receptors (2003)

Local, peripheral CB2 receptor activation inhibits inflammation and inflammatory hyperalgesia. These results suggest that peripheral CB2 receptors may be an appropriate target for eliciting relief of inflammatory pain without the CNS effects of nonselective cannabinoid receptor agonists.
The function of hairy-related bHLH repressor proteins in cell fate decisions (1998)

Hairy-related proteins are a distinct subfamily of basic helix-loop-helix (bHLH) proteins that generally function as DNA-binding transcriptional repressors. These proteins act in opposition to bHLH transcriptional activator proteins such as the proneural and myogenic proteins; together, the activator and repressor genes that encode these proteins have co-evolved as a regulatory gene "cassette" or "module" for controlling cell fate decisions. In the development of the Drosophila peripheral nervous system, Hairy-related genes function at multiple steps during neurogenesis, for example, as positional information genes that establish the "prepattern" that controls where "proneural cluster" equivalence groups will form, and later as nuclear effectors of the Notch signaling pathway to "single out" individual precursor cells within the equivalence group. Hairy-related genes also function in the establishment and restriction of other types of equivalence groups, such as those for muscle and Malphigian tubule precursors. This general function in cell fate specification has been conserved from Drosophila to vertebrates and has implications for human disease pathogenesis.
Investigation of Defects and Polarity in GaN Using Hot Wet Etching, Atomic Force and Transmission Electron Microscopy and Convergent Beam Electron Diffraction (2001)

Availability of reliable and quick methods to investigate defects and polarity in GaN films is of great interest. We have used photo-electrochemical (PEC) and hot wet etching to determine the defect density. We found the density of whiskers formed by the PEC process to be similar to the density of hexagonal pits formed by wet etching and to the dislocation density obtained by transmission electron microscopy (TEM). Hot wet etching was used also to investigate the polarity of MBE-grown GaN films together with convergent beam electron diffraction (CBED) and atomic force microscopy (AFM). We have found that hot H3PO4 etches N-polarity GaN films very quickly resulting in the complete removal or a drastic change of surface morphology. On the contrary, the acid attacks only the defect sites in Ga-polar films leaving the defect-free GaN intact and the morphology unchanged. The polarity assignments, confirmed by CBED experiments, were related to the as-grown surface morphology and to the growth conditions.
The Thrombospondin Receptor CD47 (IAP) Modulates and Associates with α2β1 Integrin in Vascular Smooth Muscle Cells (1998)

The carboxyl-terminal domain of thrombospondin-1 enhances the migration and proliferation of smooth muscle cells. Integrin-associated protein (IAP or CD47) is a receptor for the thrombospondin-1 carboxyl-terminal cell-binding domain and binds the agonist peptide 4N1K (kRFYVVMWKk) from this domain. 4N1K peptide stimulates chemotaxis of both human and rat aortic smooth muscle cells on gelatin-coated filters. The migration on gelatin is specifically blocked by monoclonal antibodies against IAP and a beta1 integrin, rather than alphav beta3 as found previously for 4N1K-stimulated chemotaxis of endothelial cells on gelatin. Both human and rat smooth muscle cells displayed a weak migratory response to soluble type I collagen; however, the presence of 4N1K peptide or intact thrombospondin-1 provoked a synergistic chemotactic response that was partially blocked by antibodies to alpha2 and beta1 integrin subunits and to IAP. A combination of antialpha2 and IAP monoclonal antibodies completely blocked chemotaxis. RGD peptide and antialphav beta3 mAb were without effect. 4N1K and thrombospondin-1 did not augment the chemotactic response of smooth muscle cells to fibronectin, vitronectin, or collagenase-digested type I collagen. Complex formation between alpha2 beta1 and IAP was detected by the coimmunoprecipitation of both alpha2 and beta1 integrin subunits with IAP. These data suggest that IAP can associate with alpha2 beta1 integrin and modulate its function.
Breaching Biological Barriers: Protein Translocation Domains as Tools for Molecular Imaging and Therapy (2003)

The lipid bilayer of a cell presents a significant barrier for the delivery of many molecular imaging reagents into cells at target sites in the body. Protein translocation domains (PTDs) are peptides that breach this barrier. Conjugation of PTDs to imaging agents can be utilized to facilitate the delivery of these agents through the cell wall, and in some cases, into the cell nucleus, and have potential for in vitro and in vivo applications. PTD imaging conjugates have included small molecules, peptides, proteins, DNA, metal chelates, and magnetic nanoparticles. The full potential of the use of PTDs in novel in vivo molecular probes is currently under investigation. Cells have been labeled in culture using magnetic nanoparticles derivatized with a PTD and monitored in vivo to assess trafficking patterns relative to cells expressing a target antigen. In vivo imaging of PTD-mediated gene transfer to cells of the skin has been demonstrated in living animals. Here we review several natural and synthetic PTDs that have evolved in the quest for easier translocation across biological barriers and the application of these peptide domains to in vivo delivery of imaging agents.
Role of host microenvironment in angiogenesis and microvascular functions in human breast cancer xenografts: mammary fat pad versus cranial tumors. (2002)

The primary breast cancer exhibited higher vascular permeability, but the cranial tumor showed more angiogenesis, suggesting that the cranial environment is leakage resistant but proangiogenic. Collectively, host microenvironment is an important determinant of tumor gene expression and microvascular functions, and, thus, orthotopic breast tumor models should be useful for obtaining clinically relevant information.
Flood, Gavin. El hinduismo. (1999)

advierten los autores en las primeras pginas con una cita de Nebrija: Planta de nuevo aquellas dos
Content-adaptive parallax barriers (2010)

We optimize automultiscopic displays built by stacking a pair of modified LCD panels. To date, such dual-stacked LCDs have used heuristic parallax barriers for view-dependent imagery: the front LCD shows a fixed array of slits or pinholes, independent of the multi-view content. While prior works adapt the spacing between slits or pinholes, depending on viewer position, we show both layers can also be adapted to the multi-view content, increasing brightness and refresh rate. Unlike conventional barriers, both masks are allowed to exhibit non-binary opacities. It is shown that any 4D light field emitted by a dual-stacked LCD is the tensor product of two 2D masks. Thus, any pair of 1D masks only achieves a rank-1 approximation of a 2D light field. Temporal multiplexing of masks is shown to achieve higher-rank approximations. Non-negative matrix factorization (NMF) minimizes the weighted Euclidean distance between a target light field and that emitted by the display. Simulations and experiments characterize the resulting content-adaptive parallax barriers for low-rank light field approximation.
SMRT compounds correct nonsense mutations in primary immunodeficiency and other genetic models (2012)

Within less than 10 years after the realization of the double helix of DNA, the ability of aminoglycosides to influence the misreading or readthrough of premature termination codons was discovered. It took another three decades to clone and sequence disease genes and appreciate the similarity of mutation spectra for most inborn errors. Nonsense mutations once again have become the target of readthrough compounds. In this brief review, we trace the development in our laboratory of the next generation of readthrough agents, small molecule readthrough (SMRT) drug-like chemicals, and assays for comparing their in vitro activity. Possible mechanisms of action and potential clinical applications are considered.
Design and cloning strategies for constructing shRNA expression vectors (2006)

In this study we detail simple improvements for constructing and sequencing shRNA that overcome current limitations. We also compare the advantages of our solutions against proposed alternatives. Our technical modifications will be of tangible benefit to researchers looking for a more efficient and reliable shRNA construction process.
Oligomerisation of G-protein-coupled receptors (2001)

A range of approaches have recently provided evidence that G-protein-coupled receptors can exist as oligomeric complexes. Both homo-oligomers, comprising multiple copies of the same gene product, and hetero-oligomers containing more than one receptor have been detected. In several, but not all, examples, the extent of oligomerisation is regulated by the presence of agonist ligands, and emerging evidence indicates that receptor hetero-oligomers can display distinct pharmacological characteristics. A chaperonin-like role for receptor oligomerisation in effective delivery of newly synthesised receptors to the cell surface is a developing concept, and recent studies have employed a series of energy-transfer techniques to explore the presence and regulation of receptor oligomerisation in living cells. However, the majority of studies have relied largely on co-immunoprecipitation techniques, and there is still little direct information on the fraction of receptors existing as oligomers in intact cells.
Laser Drilling: Drilling with the Power of Light Phase 1: Feasibility Study (2001)

A laser drilling research team was formed from members of academia, industry and national laboratory to explore the feasibility of using modern high-powered lasers to drill and complete oil and gas wells. The one-year Phase 1 study discussed in this report had the goals of quantifying the amount of pulsed infrared laser energy needed to spall and melt rock of varying lithologies and to investigate the possibility of accomplishing the same task in water under atmospheric conditions. Previous work by some members of this team determined that continuous wave lasers of varying wavelengths have more than enough power to cut, melt and vaporize rock. Samples of sandstone, limestone, and shale were prepared for laser beam interaction with a 1.6 kW pulsed Nd:YAG laser beam to determine how the beam's size, power, repetition rate, pulse width, exposure time and energy can affect the amount of energy transferred to the rock for the purposes of spallation, melting and vaporization. The purpose of the laser rock interaction experiment was to determine the threshold parameters required to remove a maximum rock volume from the samples while minimizing energy input. Absorption of radiant energy from the laser beam gives rise to the thermal energy transfer required for the destruction and removal of the rock matrix. Results from the tests indicate that each rock type has a set of optimal laser parameters to minimize specific energy (SE) values as observed in a set of linear track and spot tests. In addition, it was observed that the rates of heat diffusion in rocks are easily and quickly overrun by absorbed energy transfer rates from the laser beam to the rock. As absorbed energy outpaces heat diffusion by the rock matrix, local temperatures can rise to the melting points of the minerals and quickly increase observed SE values. The lowest SE values are obtained in the spalling zone just prior to the onset of mineral melt. The current study determined that using pulsed lasers could accomplish removing material from rock more efficiently than continuous wave lasers. The study also determined that reducing the effect of secondary energy absorbing mechanisms resulted in lower energy requirements in shale and, to some extent, in sandstones. These secondary mechanisms are defined as physical processes that divert beam energy from directly removing rock, and may include thermally-induced phase behavior changes of rock minerals (i.e., melting, vaporization, and dissociation) and fractures created by thermal expansion. Limestone is spalled by a different mechanism and does not seem to be as affected by secondary mechanisms. It was also shown that the efficiency of the cutting mechanism improved by saturating porous rock samples with water, and that a laser beam injected directly through a water layer at a sandstone sample was able to spall and melt the sample.
Antigen-independent processes in antigen-specific immunity. A role for alpha 4 integrin (1993)

It has been proposed that the migration of immune T cells out of blood vessels through connective tissue to the site of antigenic challenge is facilitated by the interaction of VLA integrins on lymphocytes with endothelial cell adhesion molecules and matrix proteins. Indeed, we have recently demonstrated that peptides derived from sequences in fibronectin abrogate the T cell-mediated contact hypersensitivity (CHS) reactions in vivo. These peptides blocked the interaction of the integrins VLA-4 and VLA-5 with fibronectin (FN), and our results suggested that by preventing the interaction of T cell integrins with FN, we successfully prevented the migration of T cells to sites of antigenic challenge. To further explore the role of integrins in T cell migration, we have used an antibody (R1-2) specific for the alpha-chain of alpha 4 integrins. Our data show that this antibody stains more than 90% of CD3+ T cells, and this percentage does not change after the mice have been immunized with a contact sensitizer. We also show that this antibody blocks the interaction of cells with immobilized FN and vascular cell adhesion molecule-1 on activated endothelial cells. Although R1-2 identifies alpha 4 integrin on a large number of T cells, it does not discriminate between activated and resting forms of this integrin, because very few T cells from immune or nonimmune mice actually bind FN or activated endothelium. In vivo, antibody R1-2 effectively blocks Ag-specific CHS, but has little effect on the non-Ag-specific cells that localize to the site of antigenic challenge. The population of cells that adoptively transfer CHS exits with the population of cells that bind to FN or to activated endothelial cells. Our data demonstrate that a small number of Ag-specific T cells use alpha 4 integrin to enter sites of inflammation and mediate effector immune responses. Ag-independent accumulation of T cells near sites of inflammation does not appear to be mediated by alpha 4 integrin.
Remington's pharmaceutical sciences (2016)

Remington's pharmaceutical sciences , Remington's pharmaceutical sciences , کتابخانه دیجیتالی دانشگاه علوم پزشکی و خدمات درمانی شهید بهشتی
Accurate sperm morphology assessment predicts sperm function (2011)

Sperm morphology has been associated with in vitro as well as in vivo fertilisation. The study aimed to evaluate the possible relation between the percentage of spermatozoa with normal morphology and the following sperm functional assays: (i) zona-induced acrosome reaction (ZIAR); (ii) DNA integrity; (iii) chromatin condensation; (iv) sperm apoptosis; and (v) fertilisation rates. Regression analysis was employed to calculate the association between morphology and different functional tests. Normal sperm morphology correlated significantly with the percentages of live acrosome-reacted spermatozoa in the ZIAR (r = 0.518; P < 0.0001; n = 92), DNA integrity (r = -0.515; P = 0.0018; n = 34), CMA(3) -positive spermatozoa (r = -0.745; P < 0.0001; n = 92), sperm apoptosis (r = -0.395; P = 0.0206; n = 34) and necrosis (r = -0.545; P = 0.0009; n = 34). Negative correlations existed between for the acrosome reaction, and DNA integrity, while negative associations were recorded with the percentages of CMA(3) -positive spermatozoa, apoptotic and necrotic spermatozoa. Sperm morphology is related to sperm dysfunction such as poor chromatin condensation, acrosome reaction and DNA integrity. Negative and significant correlations existed between normal sperm morphology and chromatin condensation, the percentage of spermatozoa with abnormal DNA and spermatozoa with apoptotic activity. The authors do not regard sperm morphology as the only test for the diagnosis of male fertility, but sperm morphology can serve as a valuable indicator of underlying dysfunction.
Thermal Breakdown by the Retro Diels–Alder Reaction of Crosslinking in Poly[styrene‐co‐(furfuryl methacrylate)] (2003)

Abstract Crosslinked poly[styrene‐ co ‐(furfuryl methacrylate)] has been produced by the Diels–Alder (D‐A) reaction between the furan ring (within the copolymer) and the maleimide (MI) group (within the other reactant, bismaleimide). The retro D‐A reaction was followed by the analysis of MI groups produced at different times at five constant temperatures. The process was shown to follow first‐order kinetics, and the rate constants were determined. The findings are believed to be the first to provide quantitative information on the breakdown by a retro D‐A reaction of crosslinking in a polymer system. The D‐A and retro D‐A processes constitute a thermoreversible gelling system with respect to the formation and breakdown of crosslinks. First‐order rate plot for the retro D‐A breakdown of crosslinked poly(ST‐ co ‐FM). magnified image First‐order rate plot for the retro D‐A breakdown of crosslinked poly(ST‐ co ‐FM).
The Action of Bean Leaves Against the Bedbug (1943)

Journal Article The Action of Bean Leaves Against the Bedbug Get access Henry H. Richardson Henry H. Richardson U. S. D. A., Agr. Res. Adm., Bureau of Entomology and Plant Quarantine Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Economic Entomology, Volume 36, Issue 4, 1 August 1943, Pages 543–545, https://doi.org/10.1093/jee/36.4.543 Published: 01 August 1943
Neural stem cells and the regulation of adult neurogenesis (2003)

Presumably, the 'hard-wired' neuronal circuitry of the adult brain dissuades addition of new neurons, which could potentially disrupt existing circuits. This is borne out by the fact that, in general, new neurons are not produced in the mature brain. However, recent studies have established that the adult brain does maintain discrete regions of neurogenesis from which new neurons migrate and become incorporated into the functional circuitry of the brain. These neurogenic zones appear to be vestiges of the original developmental program that initiates brain formation. The largest of these germinal regions in the adult brain is the subventricular zone (SVZ), which lines the lateral walls of the lateral ventricles. Neural stem cells produce neuroblasts that migrate from the SVZ along a discrete pathway, the rostral migratory stream, into the olfactory bulb where they form mature neurons involved in the sense of smell. The subgranular layer (SGL) of the hippocampal dentate gyrus is another neurogenic region; new SGL neurons migrate only a short distance and differentiate into hippocampal granule cells. Here, we discuss the surprising finding of neural stem cells in the adult brain and the molecular mechanisms that regulate adult neurogenesis.
Distributed Blinding for Distributed ElGamal Re-Encryption (2005)

A protocol is given to take an ElGamal ciphertext encrypted under the key of one distributed service and produce the corresponding ciphertext encrypted under the key of another distributed service, but without the plaintext ever becoming available. Each distributed service comprises a set of servers and employs threshold cryptography to maintain its service private key. Unlike prior work, the protocol requires no assumptions about execution speeds or message delivery delays. The protocol also imposes fewer constraints on where and when various steps are performed, which can bring improvements in end-to-end performance for some applications (e.g., a trusted publish/subscribe infrastructure.) Two new building blocks employed — a distributed blinding protocol and verifiable dual encryption proofs — could have uses beyond re-encryption protocols.