gebhart/patrepeval huggingface dataset:
Pluripotent Stem Cell Model Reveals Essential Roles for miR‐450b‐5p and miR‐184 in Embryonic Corneal Lineage Specification (2012)

Approximately 6 million people worldwide are suffering from severe visual impairments or blindness due to corneal diseases. Corneal allogeneic transplantation is often required to restore vision; however, shortage in corneal grafts and immunorejections remain major challenges. The molecular basis of corneal diseases is poorly understood largely due to lack of appropriate cellular models. Here, we described a robust differentiation of human-induced pluripotent stem cells (hiPSCs) derived from hair follicles or skin fibroblasts into corneal epithelial-like cells. We found that BMP4, coupled with corneal fibroblast-derived conditioned medium and collagen IV allowed efficient corneal epithelial commitment of hiPSCs in a manner that recapitulated corneal epithelial lineage development with high purity. Organotypic reconstitution assays suggested the ability of these cells to stratify into a corneal-like epithelium. This model allowed us identifying miR-450b-5p as a molecular switch of Pax6, a major regulator of eye development. miR-450b-5p and Pax6 were reciprocally distributed at the presumptive epidermis and ocular surface, respectively. miR-450b-5p inhibited Pax6 expression and corneal epithelial fate in vitro, altogether, suggesting that by repressing Pax6, miR-450b-5p triggers epidermal specification of the ectoderm, while its absence allows ocular epithelial development. Additionally, miR-184 was detectable in early eye development and corneal epithelial differentiation of hiPSCs. The knockdown of miR-184 resulted in a decrease in Pax6 and K3, in line with recent findings showing that a point mutation in miR-184 leads to corneal dystrophy. Altogether, these data indicate that hiPSCs are valuable for modeling corneal development and may pave the way for future cell-based therapy.
Performance analysis of dynamic flow setup in ATM networks (2002)

There has been a rapid growth in applications such as World Wide Web browsing, which are characterized by fairly short sessions that transfer substantial amounts of data. Conventional connection-oriented and datagram services are not ideally engineered to handle this kind of traffic. We present a new ATM service, called Dynaflow service, in which virtual circuits are created on a burst-by-burst basis and we evaluate key aspects of its performance. We compare Dynaflow to the fast reservation protocol (FRP) and show that Dynaflow can achieve higher overall throughput due to the elimination of reservation delays, and through the use of shared "burst-stores." We study the queueing performance of the Dynaflow switch and quantify the relationship between the loss ratio and the buffer size.
Public key cryptography (2000)

Key management: In a large network, there are many key pairs to be managed.Moreover, to guarantee security, the key should be changed Key ExchangeKey exchange was the first application of public key cryptography.The requirement is to share a key, which can later be used to encrypt and decrypt messages by a secret key system like DES.The following process can be used:
Predictive Control: A Unified Approach (1992)

Unified predictive controller design analysis of design parameters predictive control with controller output constraints applications conclusions and suggestions.
COVID-19 and the legacy of grief (2020)

As the first wave of this pandemic, effectively unprecedented in all of our lifetimes, begins to subside,1 we find ourselves confronting a legacy of grief and loss, which seems likely to be continually replenished as the disease rolls on. An understanding of the breadth and depth of this legacy will be essential to effective and humane health care over decades to come.

The most immediate and obvious form of grief is felt by those who have lost parents, life partners, children, and dear friends, both young and old, and we must acknowledge that some communities, particularly those subject to the structural violence of poverty and racism, have been significantly more exposed to this than others. Much of this anguish has been compounded by being obliged to let these precious people die alone with a minimal funeral, and no real opportunity to say goodbye and draw a loving relationship to a proper close.2 And too many survivors of the most serious variants of the disease are facing futures marred by chronic …
Identification of the<i>RLBP1</i>Gene Promoter (2007)

The findings presented here suggest that CRALBP transcripts in RPE cells contain a noncoding exon in addition to a newly described promoter and, by definition, an additional intron. This finding sets the stage for a mechanistic understanding of the high degree of cell type-specific expression of RLBP1.
RNA Interference Tolerates 2′‐Fluoro Modifications at the Argonaute2 Cleavage Site (2007)

Abstract Short interfering RNA (siRNA) molecules with good gene‐silencing properties are needed for drug development based on RNA interference (RNAi). An initial step in RNAi is the activation of the RNA‐induced silencing complex RISC, which requires degradation of the sense strand of the siRNA duplex. Although various chemical modifications have been introduced to the antisense strand, modifications to the Argonaute2 (Ago2) cleavage site in the sense strand have, so far, not been described in detail. In this work, novel 2′‐F‐purine modifications were introduced to siRNAs, and their biological efficacies were tested in cells stably expressing human tartrate‐resistant acid phosphatase (TRACP). A validated siRNA that contains both purine and pyrimidine nucleotides at the putative Ago2 cleavage site was chemically modified to contain all possible combinations of 2′‐fluorinated 2′‐deoxypurines and/or 2′‐deoxypyrimidines in the antisense and/or sense strands. The capacity of 2′‐F‐modified siRNAs to knock down their target mRNA and protein was studied, together with monitoring siRNA toxicity. All 2′‐F‐modified siRNAs resulted in target knockdown at nanomolar concentrations, despite their high thermal stability. These experiments provide the first evidence that RISC activation not only allows 2′‐F modifications at the sense‐strand cleavage site, but also increase the biological efficacy of modified siRNAs in vitro.
Technical quality of root fillings in an adult Swedish population (1986)

Abstract The purpose of this investigation was to study the technical quality of root fillings in a sample representative of the Swedish population. The material consisted of radiographs of the mandibular premolar and molar regions from 861 individuals (20–60 years old). Pulpoiomies and root fillings were registered and the periapical status and the technical quality of the root fillings were evaluated. The results showed that more than 60% of the root‐filled teeth were inadequately sealed. The defect most commonly found was incomplete obturation of the root canal. Periapical lesions were observed in 31% of the root‐filled teeth. In teelh with completely obturated root canals, only 7% had a periapical lesion, as compared to 45% of the teeth with inadequately sealed root canals.
Synthesis and shape modification of organo-functionalised silica nanoparticles with ordered mesostructured interiorsElectronic supplementary information (ESI) available: SAXRD data for functionalised and unfunctionalised MCM-41 nanoparticles. See http://www.rsc.org/suppdata/jm/b3/b300851g/ (2003)

Organo-functionalised MCM-41 nanoparticles have been prepared by a dilution/neutralisation method involving the surfactant-templated co-condensation of 3-aminopropyltriethoxysilane, allyltriethoxysilane or 3-mercaptopropyltriethoxysilane with tetraethoxysilane under alkaline conditions. The presence of covalently coupled organic groups within the hexagonally ordered silica mesophase was confirmed by solid-state 13C and 29Si MAS NMR spectroscopy. TEM studies show that amine- and allyl-functionalised nanoparticles are single-domain oblate ellipsoidal crystals, in which the cylindrical micelles are aligned parallel to the morphological minor axis. In contrast, the thiol-functionalised nanoparticles were synthesised in the form of nanofilaments elongated specifically along the channel direction of the MCM-41 hexagonal mesostructure. A mechanism is proposed in which changes in the nanoparticle morphology are attributed predominantly to an increase in surface charge associated with the anionic mercaptopropyl groups that inhibits the side-on attachment of silica–surfactant micelles to partially ordered primary nanoclusters. In contrast, nanoparticles with neutral side chains, such as amino and allyl moieties, as well as unfunctionalised MCM-41, develop by side-on attachment to radially arranged defect sites of a modulated hexagonal mesophase associated with the oblate ellipsoidal morphology.
A double-blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis (2004)

Tumor necrosis factor-α (TNF-α) may contribute to the progression of acute alcoholic hepatitis (AAH). The aim of this study was to evaluate the efficacy of an association of infliximab and prednisolone at reducing the 2-month mortality rate among patients with severe AAH. Patients with severe AAH (Maddrey score ≥32) were randomly assigned to group A receiving intravenous infusions of infliximab (10 mg/kg) in weeks 0, 2, and 4; or group B receiving a placebo at the same times. All patients received prednisolone (40 mg/day) for 28 days. Blood neutrophil functional capacities were monitored over 28 days. After randomization of 36 patients, seven patients from group A and three from group B died within 2 months. The probability of being dead at 2 months was higher (not significant [NS]) in group A (39% ± 11%) than in group B (18% ± 9%). The study was stopped by the follow-up committee and the sponsor (Assistance Publique-Hôpitaux de Paris). The frequency of severe infections within 2 months was higher in group A than in group B ( P < .002). This difference was potentially related to a significantly lower ex vivo stimulation capacity of neutrophils. There were no differences between the two groups in terms of Maddrey scores at any time point. In conclusion, three infusions of 10 mg/kg of infliximab in association with prednisolone may be harmful in patients with severe AAH because of the high prevalence of severe infections. (Hepatology 2004;39:1390-1397.)
The Leukocyte Chemotactic Receptor FPR1 Is Functionally Expressed on Human Lens Epithelial Cells (2012)

This is the first link between non-hematopoietic expression of FPR1 and an ophthalmologic phenotype. Formyl peptide receptor 1 (FPR1) is a G protein-coupled chemoattractant receptor expressed mainly on leukocytes. Surprisingly, aging Fpr1(-/-) mice develop spontaneous lens degeneration without inflammation or infection (J.-L. Gao et al., manuscript in preparation). Therefore, we hypothesized that FPR1 is functionally expressed directly on lens epithelial cells, the only cell type in the lens. Consistent with this, the human fetal lens epithelial cell line FHL 124 expressed FPR1 mRNA and was strongly FPR1 protein-positive by Western blot and FACS. Competition binding using FPR1 ligands N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys (Nle = Norleucine), formylmethionylleucylphenylalanine, and peptide W revealed the same profile for FHL 124 cells, neutrophils, and FPR1-transfected HEK 293 cells. Saturation binding with fluorescein-labeled N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys revealed ~2500 specific binding sites on FHL-124 cells (K(D) ~ 0.5 nm) versus ~40,000 sites on neutrophils (K(D) = 3.2 nm). Moreover, formylmethionylleucylphenylalanine induced pertussis toxin-sensitive Ca(2+) flux in FHL 124 cells, consistent with classic G(i)-mediated FPR1 signaling. FHL 124 cell FPR1 was atypical in that it resisted agonist-induced internalization. Expression of FPR1 was additionally supported by detection of the intact full-length open reading frame in sequenced cDNA from FHL 124 cells. Thus, FHL-124 cells express functional FPR1, which is consistent with a direct functional role for FPR1 in the lens, as suggested by the phenotype of Fpr1 knock-out mice.
Overview of Anticoagulant Activity of Sulfated Polysaccharides from Seaweeds in Relation to their Structures, Focusing on those of Green Seaweeds (2010)

The anticoagulant behavior of sulfated polysaccharides from seaweeds is reviewed based on their chemical structures. Analysis of the literature suggested that the driving force for the formation of the sulfated polysaccharide/protein complex is the non-specific polar interaction between the negatively and positively charged groups in the polysaccharide and protein, respectively and that the complex is further stabilized by short-range interactions. The polysaccharide binding site should be able to go through the following conformational steps in the formation of the complex: random coil-->ordered conformation--> low distortion of this conformation to form a complementary fitting structure with the protein backbone. The sulfated monosaccharide units with the highest potential for anticoagulant activity should have two sulfate groups and a glycosidic linkage on the pyranose ring with C-2, C-3 and C-4 in 2S, 3R, 4R or 2R, 3S, 4S configurations for galactose, fucose and arabinose and 2S, 3S, 4R, for rhamnose. Three distributions of these substituents appear: 3-linked 2,4-disulfated units, 4-linked 2,3-disulfated units and 2-linked 3,4-disulfated residues. These types of units have the possibility, through the equilibrium of the chair conformations, to place their sulfate groups in adequate special positions to interact with basic groups of the protein. The anticoagulant activity is mainly attributed to thrombin inhibition mediated by antithrombin and/or heparin cofactor II, with different effectivenesses depending of the compound. Other mechanisms are also proposed and these differences could be attributed to the diversity of structures of the polysaccharides evaluated and to the fact that one compound may have more than one target protease.
Retinoic acid is required for and potentiates differentiation of acute promyelocytic leukemia cells by nonretinoid agents (1994)

Patients with acute promyelocytic leukemia (APL) associated with the t(15;17) translocation and fusion of the promyelocytic leukemia (PML) and retinoic acid receptor-alpha (RAR-alpha) genes achieve complete remission but not cure with all-trans retinoic acid (RA), NB4, a cell line derived from a patient with t(15;17) APL that undergoes granulocytic differentiation when treated with pharmacologic doses of RA, was used as a model for differentiation therapy of APL. We found that NB4 cells are resistant to differentiation by nonretinoid inducers such as hexamethylene bisacetamide (HMBA), butyrates, vitamin D3, or hypoxanthine, all of which can induce differentiation in the commonly used HL60 leukemia cell line. Preexposure of NB4 cells to low concentrations of RA for a period as short as 30 minutes abolished resistance to nonretinoids and potentiated differentiation. Sequential RA and HMBA treatment yielded maximal differentiation by 3 days of drug exposure, whereas the effect of RA alone peaked after 6 days and yielded a smaller percentage of differentiated cells. RA also reversed NB4 cell resistance to butyrates and allowed for synergistic differentiation by these agents. Pretreatment with HMBA before exposure to RA failed to stimulate differentiation. Sequential RA/HMBA treatment also markedly increased the extent of differentiation of primary cultures of bone marrow and peripheral blood mononuclear cells from three APL patients. In one case RA/HMBA treatment overcame resistance to RA in vitro. Together, these results suggest that intermittent low doses of RA followed by either HMBA or butyrates may be a useful combination in the treatment of APL. This clinical strategy may help prevent or overcome RA resistance in APL.
Design Criteria of an Ergonomic Mouse Computer Input Device (1995)

The rapid growth of graphical user interfaces on personal computers has led to the mouse input device playing a prominent and central role in the control of computer applications. As their use increases, mouse design and comfort issues are becoming more and more critical. This report describes the ergonomic design criteria and resulting product attributes of a commercially successful mouse computer input device. Although well-founded ergonomic principles were incorporated into the design criteria, very little ergonomic research has been published on the design of mice. There is a need for additional research on the ergonomics computer mouse input devices.
Mutation in the M1 Domain of the Acetylcholine Receptor α Subunit Decreases the Rate of Agonist Dissociation (1997)

We describe the kinetic consequences of the mutation N217K in the M1 domain of the acetylcholine receptor (AChR) alpha subunit that causes a slow channel congenital myasthenic syndrome (SCCMS). We previously showed that receptors containing alpha N217K expressed in 293 HEK cells open in prolonged activation episodes strikingly similar to those observed at the SCCMS end plates. Here we use single channel kinetic analysis to show that the prolonged activation episodes result primarily from slowing of the rate of acetylcholine (ACh) dissociation from the binding site. Rate constants for channel opening and closing are also slowed but to much smaller extents. The rate constants derived from kinetic analysis also describe the concentration dependence of receptor activation, revealing a 20-fold shift in the EC50 to lower agonist concentrations for alpha N217K. The apparent affinity of ACh binding, measured by competition against the rate of 125I-alpha-bungarotoxin binding, is also enhanced 20-fold by alpha N217K. Both the slowing of ACh dissociation and enhanced apparent affinity are specific to the lysine substitution, as the glutamine and glutamate substitutions have no effect. Substituting lysine for the equivalent asparagine in the beta, epsilon, or delta subunits does not affect the kinetics of receptor activation or apparent agonist affinity. The results show that a mutation in the amino-terminal portion of the M1 domain produces a localized perturbation that stabilizes agonist bound to the resting state of the AChR.
Clustered pixels analysis for functional MRI activation studies of the human brain (1995)

Abstract Conventional t ‐statistics and cross‐correlation coefficients are commonly used for analysis of functional magnetic resonance images. The sensitivity of these statistics is usually low because severe Bonferroni‐type corrections are required for multiple statistical comparisons to minimize the false‐positive error. In the human brain, most functional areas are larger in size than a single image pixel, and coactivation of numerous contiguous pixels is expected. The probability of occurrence of clusters due to random noise is small and can be modeled. Cluster size and intensity thresholding can be used to assess statistical significance. Previous cluster analysis strategies used Gaussian models, working best with low spatial resolution images (e.g., positron emission tomography). We present a new cluster analysis model applicable to data with little or even no covariance between adjacent pixels. Computer simulations and phantom experiments were used to verify this strategy. Our new method is substantially more sensitive than both the conventional intensity‐only thresholding (IOT) method and the previous cluster method for signal change less than 6%, with maximum significant enhancement in sensitivity of 12.8 and 3.8 times, respectively. The results obtained from normal volunteers with visual stimulation further confirm the effectiveness of our new approach and show an average increase in detected activation area of 3.1 times over the IOT method and of 1.6 times over the previous cluster method using the new approach. ©1996 Wiley‐Liss, Inc.
Gushed light field (2016)

We present a new method to render aerial images by aerosol-based fog screens. Conventional fog screens are easily affected by the air flow and their generator occupy large areas. In this study, we propose to add new tradeoffs between limited display time and payloads. We employ aerosol distribution from off-the-shelf spray as a fog screen that can resist the wind, and has high portability. We present some application example; wearable application, multi-viewpoint display, display embedded in the environment, and aerial imaging with drone or radio-controlled model car. This study will contribute to the exploration of new application areas for fog displays and expand expressions of entertainments and interactivity.
RNA fingerprinting by arbitrarily primed PCR. (1994)

M McClelland and J Welsh California Institute of Biological Research, La Jolla 92037, USA.
A Novel Small Molecule, LLL12, Inhibits STAT3 Phosphorylation and Activities and Exhibits Potent Growth-Suppressive Activity in Human Cancer Cells (2010)

Constitutive activation of signal transducer and activator of transcription 3 (STAT3) signaling is frequently detected in cancer, promoting its emergence as a promising target for cancer treatment. Inhibiting constitutive STAT3 signaling represents a potential therapeutic approach. We used structure-based design to develop a nonpeptide, cell-permeable, small molecule, termed as LLL12, which targets STAT3. LLL12 was found to inhibit STAT3 phosphorylation (tyrosine 705) and induce apoptosis as indicated by the increases of cleaved caspase-3 and poly (ADP-ribose) polymerase in various breast, pancreatic, and glioblastoma cancer cell lines expressing elevated levels of STAT3 phosphorylation. LLL12 could also inhibit STAT3 phosphorylation induced by interleukin-6 in MDA-MB-453 breast cancer cells. The inhibition of STAT3 by LLL12 was confirmed by the inhibition of STAT3 DNA binding activity and STAT3-dependent transcriptional luciferase activity. Downstream targets of STAT3, cyclin D1, Bcl-2, and survivin were also downregulated by LLL12 at both protein and messenger RNA levels. LLL12 is a potent inhibitor of cell viability, with half-maximal inhibitory concentrations values ranging between 0.16 and 3.09 microM, which are lower than the reported JAK2 inhibitor WP1066 and STAT3 inhibitor S3I-201 in six cancer cell lines expressing elevated levels of STAT3 phosphorylation. In addition, LLL12 inhibits colony formation and cell migration and works synergistically with doxorubicin and gemcitabine. Furthermore, LLL12 demonstrated a potent inhibitory activity on breast and glioblastoma tumor growth in a mouse xenograft model. Our results indicate that LLL12 may be a potential therapeutic agent for human cancer cells expressing constitutive STAT3 signaling.
High-level synthesis using genetic algorithm (2002)

This paper reports on a genetic algorithm applied to high-level hardware synthesis. The GA generates a register transfer level circuit from a behavioral specificatioiz of a hardware system. High-Level synthesis is an NP complete and multiple objective problem. This paper describes two methods which were applied to the problem: the jirsd divides high-level synthesis into scheduling and allocation problems and th,e second treats high-leael synthesis as a resource assignment task without dividing it. Both these methods succeed in obtaining optimal soluitions. In particularly, it is shoutn that the latter method is gen.era1 enough to be applied to a class of problems minimizing several objectives such as high-level synthesis.