gebhart/patrepeval huggingface dataset:
Derivation of Functional Retinal Pigmented Epithelium from Induced Pluripotent Stem Cells (2009)

Abstract Human induced pluripotent stem cells (iPSCs) have great promise for cellular therapy, but it is unclear if they have the same potential as human embryonic stem cells (hESCs) to differentiate into specialized cell types. Ocular cells such as the retinal pigmented epithelium (RPE) are of particular interest because they could be used to treat degenerative eye diseases, including age-related macular degeneration and retinitis pigmentosa. We show here that iPSCs generated using Oct4, Sox2, Nanog, and Lin28 can spontaneously differentiate into RPE cells, which can then be isolated and cultured to form highly differentiated RPE monolayers. RPE derived from iPSCs (iPS-RPE) were analyzed with respect to gene expression, protein expression, and rod outer segment phagocytosis, and compared with cultured fetal human RPE (fRPE) and RPE derived from hESCs (hESC-RPE). iPS-RPE expression of marker mRNAs was quantitatively similar to that of fRPE and hESC-RPE, and marker proteins were appropriately expressed and localized in polarized monolayers. Levels of rod outer segment phagocytosis by iPS-RPE, fRPE, and hESC-RPE were likewise similar and dependent on integrin αvβ5. This work shows that iPSCs can differentiate into functional RPE that are quantitatively similar to fRPE and hESC-RPE and further supports the finding that iPSCs are similar to hESCs in their differentiation potential.
Recovery of SiO₂ and Al₂O₃ from coal fly ash (2016)

Most of the world's energy production is still mainly achieved by the combustion of coal in power stations.Coal fly ash is the inevitable waste product that accumulates to metric ton volumes each year.These vast volumes pose a problem in the disposal of the coal fly ash which conventionally is loaded onto ash dumps located near the coal power stations.Alternatives need to be investigated for the use of the coal fly ash in applications that would make the coal fly ash useful and thereby help to mitigate the environmental strain imposed by conventional ash dump disposal.This study focussed on investigating the extraction of Si and Al from CFA.The investigation into the removal of the magnetic iron oxide content and calcium content from coal fly ash was also carried out to enhance the extraction of the Si and Al from CFA e.g. the removal of calcium was attempted to promote the leaching of aluminium from the ash.The rationale for this process was that by removing and recovering these major constituent elements from the ash, it would be easier to concentrate and isolate the trace elements especially the rare earth elements that are present in the CFA.Coal fly ash sourced from Matla coal power station was characterised using x-ray diffraction to determine the mineral phases present in the raw coal fly ash and elemental composition determined by x-ray fluorescence and laser ablation ICP-MS.The main mineral phases in coal fly ash were determined to be quartz, mullite, magnetite and lime (CaO).Magnetic extraction was initially carried out on the coal fly ash to remove the iron rich magnetic material.Extraction tests were then performed on the coal fly ash using alkaline and acidic media namely; NaOH, HCl and H 2 SO 4. The extraction tests were assessed and a sequential extraction experimental procedure developed to achieve the highest extraction yield for Si, Al, Fe, Ca, and Mg from the coal fly ash.Lastly the rare earth element content in ABSTRACT ii coal fly ash was tracked from the beginning till the end of the sequential extraction procedure to ascertain whether the rare earth elements partitioned to the leachates or the solid residues.The total element recoveries for Al, Si, Ca Fe, Mg were 53.36 %, 39.96 %, 93.8 %, 25.6 % and 67.3 % respectively using the sequential extraction procedure developed in this study.The rare earth elements contents were not affected by the sequential extraction procedure and on the whole remained in the solid residues at the completion of the sequential extraction, resulting in a residue with enriched levels of recoverable or extractable REE content after the removal of the major oxides from the CFA.The lowest enrichment being approximately 5 % for Thulium and the highest being approximately 76 % for Erbium
Pertussis toxin-sensitive G proteins influence nitric oxide synthase III activity and protein levels in rat heart. (1998)

Inhibitory G protein activity (Gi) and nitric oxide (NO) modulate muscarinic-cholinergic (MC) inhibition of cardiac beta-adrenergic inotropic responses. We hypothesized that Gi mediates MC-NO synthase (NOS) signal transduction. Isoproterenol (0.2-0.8 microg/min) and acetylcholine (1 microM) were administered to isolated perfused rat hearts pretreated with saline (controls; n = 8) or pertussis toxin (PT; 30 microg/kg intraperitoneally 3 d before study; n = 20). PT abrogated in vitro ADP-ribosylation of Gi protein alpha subunit(s) indicating near-total decrease in Gi protein function. Isoproterenol increased peak +dP/dt in both control (peak isoproterenol effect: +2, 589+/-293 mmHg/s, P < 0.0001) and PT hearts (+3,879+/-474 mmHg/s, P < 0.0001). Acetylcholine reversed isoproterenol inotropy in controls (108+/-21% reduction of +dP/dt response, P = 0.001), but had no effect in PT hearts. In controls, NG-monomethyl-L-arginine (100 microM) reduced basal +dP/dt, augmented isoproterenol +dP/dt (peak effect: +4,634+/-690 mmHg/s, P < 0.0001), and reduced the MC inhibitory effect to 69+/-8% (P < 0.03 vs. baseline). L-arginine (100 M) had no effect in controls but in PT hearts decreased basal +dP/dt by 1, 426+/-456 mmHg/s (P < 0.005), downward-shifted the isoproterenol concentration-effect curve, and produced a small MC inhibitory effect (27+/-4% reduction, P < 0.05). This enhanced response to NO substrate was associated with increased NOS III protein abundance, and a three- to fivefold increase in in vitro calcium-dependent NOS activity. Neomycin (1 microM) inhibition of phospholipase C did not reverse L-arginine enhancement of MC inhibitory effects. These data support a primary role for Gi in MC receptor signal transduction with NOS in rat heart, and demonstrate regulatory linkage between Gi and NOS III protein levels.
Inter- and Intra-Host Viral Diversity in a Large Seasonal DENV2 Outbreak (2013)

Despite the error-prone nature of RNA-dependent RNA-polymerase, dengue viruses maintain low levels of intra-host variability.
NB1, a new neutrophil-specific antigen involved in the pathogenesis of neonatal neutropenia (1971)

A new human antigen is reported which is present only on blood neutrophils. A neutrophil-specific antigen, designated NA1, has previously been identified in two unrelated families, and was shown to be involved in fetomaternal incompatibility and the development of isoimmune neonatal neutropenia in five newborns. In the present paper, a second antigen, designated NB1, is identified in four families with seven affected children. Antibodies that react with this second antigen are shown to produce selective agglutination of neutrophils but not other blood cells. They are neither absorbed by cells prepared from solid tissues nor by non-neutrophilic blood cells. By family and population studies, NB is shown to be distinct from NA, representing an independent genetic locus. 68% of the New York population are homozygous for NB1, 29% heterozygous, and 3% negative. The NB locus is shown to be independent from those of HL-A and other known leukocyte antigens. No evidence for linkage between NA, NB, and red cell antigens was obtained.
Design, Synthesis and X-ray Structure of Protein−Ligand Complexes:  Important Insight into Selectivity of Memapsin 2 (β-Secretase) Inhibitors (2006)

Structure-based design, synthesis, and X-ray structure of protein-ligand complexes of memapsin 2 are described. The inhibitors are designed specifically to interact with S2- and S3-active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 6 has exhibited exceedingly potent inhibitory activity against memapsin 2 and selectivity over memapsin 1 (>3800-fold) and cathepsin D (>2500-fold). A protein-ligand crystal structure revealed cooperative interactions in the S2- and S3-active sites of memapsin 2. These interactions may serve as an important guide to design selectivity over memapsin 1 and cathepsin D.
Angiopoietin‐2 enhances retinal vessel sensitivity to vascular endothelial growth factor (2004)

Increased expression of vascular endothelial growth factor (VEGF) in the retina starting after postnatal day (P)7 results in neovascularization originating from deep retinal capillaries, but not those in the superficial capillary bed. Doxycycline was administered starting P0 to double transgenic mice with inducible expression of VEGF in the retina. These mice showed proliferation and dilation of superficial retinal capillaries, indicating that at this stage of development, the superficial capillaries are sensitive to the effects of VEGF. Angiopoietin-2 (Ang2) is expressed along the surface of the retina for several days after birth, but by P7 and later, Ang2 is only expressed in the region of the deep capillary bed. In mice with ubiquitous doxycycline-inducible expression of Ang2, in the absence of doxycycline, intravitreous injection of a gutless adenoviral vector expressing VEGF (AGV.VEGF) resulted in neovascularization of the cornea and iris, but no retinal neovascularization. After treatment with doxycycline to induce Ang2 expression, intravitreous injection of AGV.VEGF caused retinal neovascularization in addition to corneal and iris neovascularization. The retinal neovascularization originated from both the superficial and deep capillary beds. These data suggest that Ang2 promotes sensitivity to the angiogenic effects of VEGF in retinal vessels.
Successful Use of High-Frequency Spinal Cord Stimulation Following Traditional Treatment Failure (2015)

HFSCS at the frequency of 1 kHz offers a new tool for treatment of chronic pain in patients with traditional stimulation settings. Furthermore, most standard SCS batteries are capable of delivering stimulation in this frequency range.
Photoaffinity labeling of the T cell receptor on living cytotoxic T lymphocytes (1993)

Using a direct binding assay based on photoaffinity labeling, we have studied the interaction of an antigenic peptide with MHC class I molecules and the TCR on living cells. Two photoreactive derivatives of the H-2Kd (Kd) restricted Plasmodium berghei circumsporozoite (PbCS) peptide 253-260 (YIPSAEKI) were used. The first derivative contained an N-terminal photoreactive iodo, 4-azido salicyloyl (IASA) group and biotin on the TCR contact residue Lys259 [IASA-YIPSAEK(biotin)I]. As previously described, this derivative selectively bound to and labeled the Kd molecule. The second photoreactive compound, the isomeric biotin-YIPSAEK(IASA)I, also efficiently bound to the Kd molecule, but failed to label this protein. A CTL clone derived from a mouse immunized with this derivative recognized this conjugate but not the parental P. berghei circumsporozoite peptide or the [IASA-YIPSAEK-(biotin)I] derivative in an Kd-restricted manner. Incubation of the cloned CTL cells with biotin-YIPSAEK(IASA)I, but not its isomer, followed by UV irradiation resulted in photoaffinity labeling of the TCR-alpha chain that was dependent on the conjugate binding to the Kd molecule. The TCR labeling was partially inhibited by anti-LFA 1 and anti-ICAM1 mAb, but was increased by addition of beta 2m or soluble KdQ10. The exquisite labeling selectivity of the two photoprobes opens a new, direct approach to the molecular analysis of antigen presentation and recognition by living CTL.
New tools for rapid clinical and bioagent diagnostics: microwaves and plasmonic nanostructures (2008)

In this timely review, we summarize recent work on ultra-fast and sensitive bioassays based on microwave heating, and provide our current interpretation of the role of the combined use of microwave energy and plasmonic nanostructures for applications in rapid clinical and bioagent diagnostics. The incorporation of microwave heating into plasmonic nanostructure-based bioassays brings new advancements to diagnostic tests. A temperature gradient, created by the selective heating of water in the presence of plasmonic nanostructures, results in an increased mass transfer of target biomolecules towards the biorecognition partners placed on the plasmonic nanostructures, enabling diagnostic tests to be completed in less than a minute, and in some cases only a few seconds, by further microwave heating. The diagnostic tests can also be run in complex biological samples, such as human serum and whole blood.
A fibrin sealant for perforated and preperforated corneal ulcers. (1989)

Fibrin sealant is used to close perforated or preperforated corneal ulcers. In addition to the usual advantages of cyanoacrylates it is degraded physiologically and provides a good support for corneal healing. Corneal grafting can be avoided when contraindicated or postponed when conditions allow. This technique has been successful in nine eyes of eight patients.
Construction of recombinant plasmids containing Xenopus immunoglobulin heavy chain DNA sequences. (1981)

A recombinant cDNA plasmid containing Xenopus immunoglobulin heavy chain sequence has been constructed from Xenopus spleen poly(A)-containing RNA. The plasmid was identified by colony hybridization and a hybridization-translation assay and its identity was confirmed by DNA sequence analysis. The portion of the heavy chain sequence contained in the plasmid is 35% homologous to mammalian mu and gamma sequences. The mRNA corresponding to this plasmid is 2.5 kilobases, in close agreement with the size of mouse mu mRNA. RNA sequences complementary to the cloned sequence appear in embryos about 24 hr after fertilization, which corresponds to 24 hr before the first detectable immunoglobulin.
The role of oxidative stress in the genesis of heart disease (1998)

Although researchers in radiation and cancer biology have known about the existence of free radicals and their potential role in pathobiology for several decades, cardiac biologists only began to take notice of these noxious species in the 1970s. Exponential growth of free radical research occurred after the discovery of superoxide dismutase in 1969. This antioxidant enzyme is responsible for the dismutation of superoxide radical--a free radical chain initiator. A fine balance between free radicals and a variety of endogenous antioxidants is believed to exist. Any disturbance in this equilibrium in favour of free radicals causes an increase in oxidative stress and initiates subcellular changes leading to cardiomyopathy and heart failure. Our knowledge about the role of free radicals in the pathogenesis of cardiac dysfunction is fast approaching the point where newer therapies employing antioxidants are in sight.
A Small-Angle Neutron Scattering Study of the Structure of Gelatin at the Surface of Polystyrene Latex Particles (1998)

Small-angle neutron scattering has been employed to investigate the effects of salt and pH on the structure of gelatin at the surface of negatively charged polystyrene latex particles. Measurements were made with the scattering length density of the particles matched with the solvent. The data have been fitted to a combination of the scattering due to the average volume fraction profile of the layer and scattering from spatial concentration fluctuations. It has been shown that the scattering from the bare latex particles, the gelatin in solution, and the adsorbed layer have very different forms. The difference in the gelatin scattering indicates a significant change in the structure of the polymer on adsorption. The volume fraction profiles derived from the fits show that, on increasing the pH, the concentration of chains at the interface decreased but the extension of the chains from the surface increased. Varying the ionic strength of the continuous phase gave unexpected results.
Posttranscriptional control of inflammation by an RNase Regnase-1 (2015)

自然免疫は，肺傷害の原因となる細菌やウイルス感染認識を介して，その発症，重症化に深く関わっている．中でも自然免疫受容体として重要なToll-like receptor（TLR）は，インフルエンザウイルスなどの感染に対する急性肺傷害に重要であることが報告されている．一方で，TLRを介した認識は，感染防御に必須であり，生理的な条件下では，TLRにより惹起される炎症応答は適切に調節を受けることで，過剰な応答を起こさずに病原体感染を排除している．サイトカインをはじめとした炎症関連遺伝子発現は，転写調節のみではなく，転写後のmRNA分解速度や翻訳などによって緻密に制御され，適切な炎症応答を保っている．microRNAだけではなく，mRNA不安定化を促すTristetraprolinやRNA分解酵素であるRegnase-1といったmRNAの3′UTRに結合するRNA結合タンパク質が炎症制御に重要であることが明らかになってきた．シグナル伝達経路によりRegnase-1の発現が直接制御されることから，mRNA安定性は，転写に加えた新たな外的シグナル受容システムであると考えられる．本総説では，Regnase-1を切り口に炎症の転写後調節の分子メカニズムに焦点を当て，紹介したい．
Acute myeloid leukaemia in the elderly: a review (2011)

The majority of patients with acute myeloid leukaemia (AML) are elderly. Advancements in supportive care and regimen intensification have resulted in improvements in clinical outcomes for younger AML patients, but analogous improvements in older patients have not been realized. While outcomes are compromised by increased comorbidities and susceptibility to toxicity from therapy, it is now recognized that elderly AML represents a biologically distinct disease that is more aggressive and less responsive to therapy. Some patients tolerate and benefit from intensive remission-induction approaches, while others are best managed with less aggressive strategies. The challenge is to differentiate these groups based on host-related and biological features, in order to maximize the therapeutic benefit and minimize toxicity. As more is understood about the complicated pathogenesis and molecular basis of AML, there are more opportunities to develop and test targeted therapies. Elderly patients, with their narrow therapeutic window, are well positioned to derive a benefit from these novel agents, and therefore, despite a difficult past, there are reasons to be optimistic about the future of elderly AML.
O‐Mannosylation of Pichia pastoris cellular and recombinant proteins (1998)

O-linked saccharides were released from a major cell wall glycoprotein and from cellular mannan-protein complexes obtained from Pichia pastoris cells. Analysis by a variety of chromatographic methods and exoglycosidase digestions revealed the presence of mannose and (alpha1-2)-linked dimer, trimer and tetramer saccharides of mannose. The recombinant kringle 1-4 domain of human plasminogen expressed in P. pastoris was subjected to hydrazinolysis of both O- and N-linked saccharides. Only a very small quantity of N-linked oligosaccharides was present on the Asn289 consensus site. The major products were O-linked (alpha1-2)-linked mannans, containing dimeric, trimeric, tetrameric and pentameric oligosaccharides with the major amount of the total saccharides being distributed approximately equally between the dimer and trimer components. These results show that short O-linked saccharides of mannose containing (alpha1-2) glycosidic linkages are present in P. pastoris cells and expressed proteins.
An Introduction to Lithography (1983)

1.1 Historical Perspective Soon after the invention of the point contact transistor over three decades ago, several important technological trends were rapidly established. First, a technology known as planar junction technology (1) was developed; the development of this technology permitted the construction of p-n junctions in a semiconductor material without the use of bulky, three-dimensional contact devices. Within a few years, silicon had become the dominant material for semiconductor fabrication, and photolithography was established as the technique of choice in fabricating planar, silicon devices. Numerous volumes have been written about the chemistry and physics of semiconductor devices and of materials for semiconductor manufacturing (2-4). Much less information has been compiled concerning the processing steps involved in semiconductor device fabrication, especially in the area of lithography. Another important innovation in semiconductor devices was the invention of the monolithic integrated circuit. This technology provides a means for the internal interconnection of many
Fine-tuning citrate synthase flux potentiates and refines metabolic innovation in the Lenski evolution experiment (2015)

Evolutionary innovations that enable organisms to colonize new ecological niches are rare compared to gradual evolutionary changes in existing traits. We discovered that key mutations in the gltA gene, which encodes citrate synthase (CS), occurred both before and after Escherichia coli gained the ability to grow aerobically on citrate (Cit(+) phenotype) during the Lenski long-term evolution experiment. The first gltA mutation, which increases CS activity by disrupting NADH-inhibition of this enzyme, is beneficial for growth on the acetate and contributed to preserving the rudimentary Cit(+) trait from extinction when it first evolved. However, after Cit(+) was refined by further mutations, this potentiating gltA mutation became deleterious to fitness. A second wave of beneficial gltA mutations then evolved that reduced CS activity to below the ancestral level. Thus, dynamic reorganization of central metabolism made colonizing this new nutrient niche contingent on both co-opting and overcoming a history of prior adaptation.
Patterns-Oriented Design Applied to Cross-Platform Web-based Interactive Systems (2007)

Design pattern suggests that developers must be able to reuse proven solutions emerging from the best design practices to solve common design problems while composing patterns to create reusable designs that can be mapped to different platforms. Without this, cross-platform Web applications designers are not properly applying design solutions or take full benefit of the power of patterns as reuse blocks, resulting in poor performance, poor scalability, and poor usability. Furthermore, the designer may "reinvent the wheel" when attempting to implement the same design for different platform. In this paper, we first introduce different types of Web design patterns as a vehicle for capturing and reusing good designs while detailing a motivating exemplar on how Web design patterns can be composed to create a generic Web application design. Then, we discuss why patterns are a suitable means for mapping a Web design to new platforms while maintaining its intrinsic quality attributes.
A cone beam filtered backprojection (CB‐FBP) reconstruction algorithm for a circle‐plus‐two‐arc orbit (2001)

The circle-plus-arc orbit possesses advantages over other "circle-plus" orbits for the application of x-ray cone beam (CB) volume CT in image-guided interventional procedures requiring intraoperative imaging, in which movement of the patient table is to be avoided. A CB circle-plus-two-arc orbit satisfying the data sufficiency condition and a filtered backprojection (FBP) algorithm to reconstruct longitudinally unbounded objects is presented here. In the circle suborbit, the algorithm employs Feldkamp's formula and another FBP implementation. In the arc suborbits, an FBP solution is obtained originating from Grangeat's formula, and the reconstruction computation is significantly reduced using a window function to exclude redundancy in Radon domain. The performance of the algorithm has been thoroughly evaluated through computer-simulated phantoms and preliminarily evaluated through experimental data, revealing that the algorithm can regionally reconstruct longitudinally unbounded objects exactly and efficiently, is insensitive to the variation of the angle sampling interval along the arc suborbits, and is robust over practical x-ray quantum noise. The algorithm's merits include: only 1D filtering is implemented even in a 3D reconstruction, only separable 2D interpolation is required to accomplish the CB backprojection, and the algorithm structure is appropriate for parallel computation.