gebhart/patrepeval huggingface dataset:
Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia (2013)

Acute myeloid leukemia (AML) continues to be extremely difficult to treat successfully, and the unacceptably low overall survival rates mandate that we assess new potential therapies to ameliorate poor clinical response to conventional therapy. Abnormal tyrosine kinase activation in AML has been associated with poor prognosis and provides strategic targets for novel therapy development. We found that Mer receptor tyrosine kinase was over-expressed in a majority of pediatric (29/36, 80%) and adult (10/10, 100%) primary AML patient blasts at the time of diagnosis, and 100% of patient samples at the time of relapse. Mer was also found to be expressed in 12 of 14 AML cell lines (86%). In contrast, normal bone marrow myeloid precursors expressed little to no Mer. Following AML cell line stimulation with Gas6, a Mer ligand, we observed activation of prosurvival and proliferative signaling pathways, including phosphorylation of ERK1/2, p38, MSK1, CREB, ATF1, AKT and STAT6. To assess the phenotypic role of Mer in AML, two independent short-hairpin RNA (shRNA) constructs were used to decrease Mer expression in the AML cell lines Nomo-1 and Kasumi-1. Reduction of Mer protein levels significantly increased rates of myeloblast apoptosis two to threefold in response to serum starvation. Furthermore, myeloblasts with knocked-down Mer demonstrated decreased colony formation by 67-87%, relative to control cell lines (P<0.01). NOD-SCID-gamma mice transplanted with Nomo-1 myeloblasts with reduced levels of Mer had a significant prolongation in survival compared with mice transplanted with the parental or control cell lines (median survival 17 days in parental and control cell lines, versus 32-36 days in Mer knockdown cell lines, P<0.0001). These data suggest a role for Mer in acute myeloid leukemogenesis and indicate that targeted inhibition of Mer may be an effective therapeutic strategy in pediatric and adult AML.
Long-Range Photoinduced Electron Transfer Through a DNA Helix (1993)

Rapid photoinduced electron transfer is demonstrated over a distance of greater than 40 angstroms between metallointercalators that are tethered to the 5' termini of a 15-base pair DNA duplex. An oligomeric assembly was synthesized in which the donor is Ru(phen)2dppz2+ (phen, phenanthroline, and dppz, dipyridophenazine) and the acceptor is Rh(phi)2phen3+ (phi, phenanthrenequinone diimine). These metal complexes are intercalated either one or two base steps in from the helix termini. Although the ruthenium-modified oligonucleotide hybridized to an unmodified complement luminesces intensely, the ruthenium-modified oligomer hybridized to the rhodium-modified oligomer shows no detectable luminescence. Time-resolved studies point to a lower limit of 10(9) per second for the quenching rate. No quenching was observed upon metallation of two complementary octamers by Ru(phen)3(2+) and Rh(phen)3(3+) under conditions where the phen complexes do not intercalate. The stacked aromatic heterocycles of the DNA duplex therefore serve as an efficient medium for coupling electron donors and acceptors over very long distances.
Unbleachable rhodopsin with an 11-cis-locked eight-membered ring retinal: The visual transduction process (1994)

Visual transduction occurs through photorhodopsin, the primary photoproduct of rhodopsin, which relaxes to bathorhodopsin and a series of other intermediates until it reaches the metarhodopsin II stage, upon which the enzymatic cascade leading to vision is activated. Despite advances in areas related to visual transduction, the triggering process itself, a key problem in the chemistry of rhodopsin, has remained unsolved. In order to clarify the extent of involvement of the chromophoric excited state versus the 11-cis to trans isomerization, and as an extension of past studies with 11-cis-locked seven-membered ring rhodopsin (Rh7), 11-cis eight- and nine-membered ring retinal analogs, ret8 and ret9, respectively, have been synthesized. The bulkiness of the tetramethylene bridge in ret8 led to numerous unexpected obstacles in attempts to reconstitute a ret8-containing rhodopsin (Rh8) embedded in lipid bilayer membranes. These obstacles were solved by using methylated rhodopsin which gave MeRh8 containing 11-cis-ret8 as its chromophore. MeRh8 exhibited UV-vis and CD spectra very similar to those of native rhodopsin (Rh); furthermore, the quantum efficiency of photorhodopsin formation was comparable to that of Rh.(ABSTRACT TRUNCATED AT 250 WORDS)
Two Distributed-State Models For Generating High-Dimensional Time Series (2011)

In this paper we develop a class of nonlinear generative models for high-dimensional time series. We first propose a model based on the restricted Boltzmann machine (RBM) that uses an undirected model with binary latent variables and real-valued variables. The latent and visible variables at each time step receive directed connections from the visible variables at the last few time-steps. This conditional RBM (CRBM) makes on-line inference efficient and allows us to use a simple approximate learning procedure. We demonstrate the power of our approach by synthesizing various sequences from a model trained on motion capture data and by performing on-line filling in of data lost during capture. We extend the CRBM in a way that preserves its most important computational properties and introduces multiplicative three-way interactions that allow the effective interaction weight between two variables to be modulated by the dynamic state of a third variable. We introduce a factoring of the implied three-way weight tensor to permit a more compact parameterization. The resulting model can capture diverse styles of motion with a single set of parameters, and the three-way interactions greatly improve its ability to blend motion styles or to transition smoothly among them. Videos and source code can be found at http://www.cs.nyu.edu/~gwtaylor/publications/jmlr2011.
Recent advances in amperometric glucose biosensors for in vivo monitoring (1995)

Electrochemical biosensors for glucose, based on the specific glucose oxidizing enzyme glucose oxidase, have generated considerable interest. Several commercial devices based on this principle have been developed and are widely used for in vitro monitoring of glucose e.g. in hospitals, doctors surgeries and for home monitoring by patients themselves. A significant advance in the application of biosensor technology would be the development of portable, implantable sensors which could continuously indicate the blood glucose concentration, enabling swift corrective action to be taken by the patient. This review highlights recent developments in amperometric glucose biosensors for in vivo monitoring and also considers the remaining barrier which need to be overcome to enable successful introduction of an implantable sensor.
Relationship between Exogenous Polyamines and Nitric Oxide and Their Induced Effects on Lettuce Seed Germination (2009)

Normal lettuce seeds(Lactuca sativa L.cv Guasihong) were used to understand the relationship between polyamines and nitric oxide(NO) in the process of seed germination after treatments with exogenous polyamines and NO donor SNP(sodium nitroprusside) together with NO specific scavenger cPTIO.The results showed that exogenous polyamines,especially Spd,had a certain role in promoting early germination and the optimal concentration was 0.5 mmol·L-1.Their effect was more significant before 48 h after seed imbibition.Consistent with the result,1.0 mmol·L-1 cyclohexylamine(CHA,spermidine synthase inhibitor) had a strong inhibitory effect on the germination of lettuce seeds.Like Spd,exogenous NO donor SNP also promoted seed early germination of lettuce,but in a concentration-dependent way,its function disappeared after 48 h.When treated with SNP and Spd,application of NO scavenger cPTIO could markedly reduce the SNP-or Spd-promoted effect on lettuce seed germination.Fluorescent detection using the DAQ,a NO-sensitive fluorescent probe,showed that there was strong NO fluorescence near seed embryo treated with Spd or SNP.The fluorescence could be eliminated by cPTIO concomitantly with its inhibitory effect on the early germination promoted by Spd or SNP.In this paper,we preliminarily approve that polyamines-,especially spermidine-induced early germination of lettuce seeds may be relevant to the NO induction.
Two different pathogenic mechanisms, dying-back axonal neuropathy and pancreatic senescence, are present in the YG8R mouse model of Friedreich’s ataxia (2016)

Frataxin (FXN) deficiency causes Friedreich's ataxia (FRDA), a multisystem disorder with neurological and non-neurological symptoms. FRDA pathophysiology combines developmental and degenerative processes of dorsal root ganglia (DRG), sensory nerves, dorsal columns and other central nervous structures. A dying-back mechanism has been proposed to explain the peripheral neuropathy and neuropathology. In addition, affected individuals have non-neuronal symptoms such as diabetes mellitus or glucose intolerance. To go further in the understanding of the pathogenic mechanisms of neuropathy and diabetes associated with the disease, we have investigated the humanized mouse YG8R model of FRDA. By biochemical and histopathological studies, we observed abnormal changes involving muscle spindles, dorsal root axons and DRG neurons, but normal findings in the posterior columns and brain, which agree with the existence of a dying-back process similar to that described in individuals with FRDA. In YG8R mice, we observed a large number of degenerated axons surrounded by a sheath exhibiting enlarged adaxonal compartments or by a thin disrupted myelin sheath. Thus, both axonal damage and defects in Schwann cells might underlie the nerve pathology. In the pancreas, we found a high proportion of senescent islets of Langerhans in YG8R mice, which decreases the β-cell number and islet mass to pathological levels, being unable to maintain normoglycemia. As a whole, these results confirm that the lack of FXN induces different pathogenic mechanisms in the nervous system and pancreas in the mouse model of FRDA: dying back of the sensory nerves, and pancreatic senescence.
A novel affinity protein selection system based on staphylococcal cell surface display and flow cytometry (2008)

Here we describe the first reported use of a Gram-positive bacterial system for the selection of affinity proteins from large combinatorial libraries displayed on the surface of Staphylococcus carnosus. An affibody library of 3 x 10(9) variants, based on a 58 residue domain from staphylococcal protein A, was pre-enriched for binding to human tumor necrosis factor-alpha (TNF-alpha) using one cycle of phage display and thereafter transferred to the staphylococcal host ( approximately 10(6) variants). The staphylococcal-displayed library was subjected to three rounds of flow-cytometric sorting, and the selected clones were screened and ranked by on-cell analysis for binding to TNF-alpha and further characterized using biosensor analysis and circular dichroism spectroscopy. The successful sorting yielded three different high-affinity binders (ranging from 95 pM to 2.2 nM) and constitutes the first selection of a novel affinity protein using Gram-positive bacterial display. The method combines the simplicity of working with a bacterial host with the advantages of displaying recombinant proteins on robust Gram-positive bacteria as well as using powerful flow cytometry in the selection and characterization process.
Anti-CD40L Immune Complexes Potently Activate Platelets In Vitro and Cause Thrombosis in FCGR2A Transgenic Mice (2010)

Anti-CD40L immunotherapy in systemic lupus erythematosus patients was associated with thromboembolism of unknown cause. We previously showed that monoclonal anti-CD40L immune complexes (ICs) activated platelets in vitro via the IgG receptor (FcgammaRIIa). In this study, we examined the prothrombotic effects of anti-CD40L ICs in vivo. Because mouse platelets lack FcgammaRIIa, we used FCGR2A transgenic mice. FCGR2A mice were injected i.v. with preformed ICs consisting of either anti-human CD40L mAb (M90) plus human CD40L, or a chimerized anti-mouse CD40L mAb (hMR1) plus mouse CD40L. ICs containing an aglycosylated form of hMR1, which does not bind FcgammaRIIa, were also injected. M90 IC caused shock and thrombocytopenia in FCGR2A but not in wild-type mice. Animals injected with hMR1 IC also experienced these effects, whereas those injected with aglycosylated-hMR1 IC did not, demonstrating that anti-CD40L IC-induced platelet activation in vivo is FcgammaRIIa-dependent. Sequential injections of individual IC components caused similar effects, suggesting that ICs were able to assemble in circulation. Analysis of IC-injected mice revealed pulmonary thrombi consisting of platelet aggregates and fibrin. Mice pretreated with a thrombin inhibitor became moderately thrombocytopenic in response to anti-CD40L ICs and had pulmonary platelet-thrombi devoid of fibrin. In conclusion, we have shown for the first time that anti-CD40L IC-induced thrombosis can be replicated in mice transgenic for FcgammaRIIa. This molecular mechanism may be important for understanding thrombosis associated with CD40L immunotherapy. The FCGR2A mouse model may also be useful for assessing the hemostatic safety of other therapeutic Abs.
Decoherence-Free Subspaces for Quantum Computation (1998)

Decoherence in quantum computers is formulated within the semigroup approach. The error generators are identified with the generators of a Lie algebra. This allows for a comprehensive description which includes as a special case the frequently assumed spin-boson model. A generic condition is presented for errorless quantum computation: decoherence-free subspaces are spanned by those states which are annihilated by all the generators. It is shown that these subspaces are stable to perturbations and, moreover, that universal quantum computation is possible within them.
American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee (2012)

These recommendations are based on the consensus judgment of clinical experts from a wide range of disciplines, informed by available evidence, balancing the benefits and harms of both nonpharmacologic and pharmacologic modalities, and incorporating their preferences and values. It is hoped that these recommendations will be utilized by health care providers involved in the management of patients with OA.
Studies of water-in-oil emulsions : stability and oil properties (1998)

The stability of water-in-oil emulsions were studied by examining the asphaltene and resin content of oils. The visco-elastic properties of 82 oils from Environment Canada`s Emergencies Science Division were also examined to determine which factors are responsible for the stability regimes. The stability of emulsions were grouped into three categories: (1) stable, (2) unstable, and (3) meso-stable. It was shown that there is a range of compositions and viscosities in which each type of water-in-oil state exists. It was also shown that the viscosity of a stable emulsion at a shear rate of one reciprocal second is about three times greater than that of the starting oil. An unstable emulsion typically had a viscosity of 20 times greater than that of the starting oil. A stable emulsion had pronounced elasticity, but an unstable emulsion did not. A meso-stable emulsion had properties between stable and unstable, but broke down after a few days of standing. It was concluded that the formation of both stable and meso-stable emulsions is due to the combination of surface-active forces from resins and asphaltenes from viscous forces. Only a small difference was detected between stable and meso-stable emulsions. Stable emulsions were found to have more asphaltenes and less resins and a narrow viscosity window. Instability results when the oil has either a high viscosity or a very low viscosity and when the resins and asphaltenes are less than about 3 per cent. In highly viscous oils, the migration of asphaltenes and resins is too low to permit droplet stabilization, therefore the formation of stable or meso-stable emulsions does not occur in highly viscous oils. 18 refs., 8 tabs., 8 figs.
Expression of αvβ6integrin in oral leukoplakia (2000)

The distribution of alpha(v)beta6 integrin was examined in oral leukoplakia, lichen planus and squamous cell carcinomas using immunohistochemistry. Controls included oral mucosal wounds, chronically inflamed and normal oral mucosa. Integrins beta1, beta3, beta4, beta5, fibronectin and tenascin were also studied. The integrin alpha(v)beta6 was highly expressed throughout the whole lesion of 90% of the squamous cell carcinomas but was not present in any of the normal specimens. alpha(v)beta6 integrin was also expressed in 41% of the leukoplakia specimens, and 85% of the lichen planus samples, but in none of the tissues with inflammatory hyperplasia or chronic inflammation. The expression of beta1 integrins was localized in the basal layer, and that of the beta4 at the cell surface facing the basement membrane of all specimens. The integrins beta3 and beta5 were absent from all normal and leukoplakia specimens. Fibronectin and tenascin were present in the connective tissue underneath the epithelium of all the sections, and their expression was similar in both alpha(v)beta6-positive and alpha(v)beta6-negative tissues. A group of 28 leukoplakia patients were followed 1-4 years after first diagnosis. In this group, initially alpha(v)beta6 integrin-positive leukoplakia specimens had high tendency for disease progression while alpha(v)beta6-negative specimens did not progress. These results suggest that the expression of alpha(v)beta6 integrin could be associated in the malignant transformation of oral leukoplakias.
Purification and characterization of a novel lactonohydrolase, catalyzing the hydrolysis of aldonate lactones and aromatic lactones, from Fusarium oxysporum (1992)

A novel lactonohydrolase, an enzyme that catalyzes the hydrolysis of aldonate lactones to the corresponding aldonic acids, was purified 10-fold to apparent homogeneity, with a 61% overall recovery, from Fusarium oxysporum AKU 3702, through a purification procedure comprising DEAE-Sephacel, octyl-Sepharose CL-4B and hydroxyapatite chromatographies and crystallization. The molecular mass of the native enzyme, as estimated by high-performance gel-permeation chromatography, is 125 kDa, and the subunit molecular mass is 60 kDa. The enzyme contains 15.4% (by mass) glucose equivalent of carbohydrate, and about 1 mol calcium/subunit. The enzyme hydrolyzes aldonate lactones, such as D-galactono-gamma-lactone and L-mannono-gamma-lactone, stereospecifically. Furthermore, it can catalyze the asymmetric hydrolysis of D-pantoyl lactone, which is a promising chiral building block for the chemical synthesis of D-pantothenate. These reactions are reversible, and the reaction equilibrium at pH 6.0 has a molar ratio of nearly 1:1 with D-pantoyl lactone and D-pantoic acid. The Km and Vmax for D-galactono-gamma-lactone are 3.6 mM and 1440 U/mg, respectively, and those for D-galactonate are 52.6 mM and 216 U/mg, respectively. The enzyme also irreversibly hydrolyzes several aromatic lactones, such as dihydrocoumarin and homogentisic-acid lactone.
Overlap Extension PCR Cloning: A Simple and Reliable Way to Create Recombinant Plasmids (2010)

Here we describe a straightforward, efficient, and reliable way to clone an insert of choice into a plasmid of choice without restriction endonucleases or T4 DNA ligase. Chimeric primers containing plasmid sequence at the 5' ends and insert sequence at the 3' ends were used to PCR-amplify insertion sequences of various sizes, namely the genes for GFP (gfp), beta-d-glucuronidase (gusA), and beta-galactosidase (lacZ), as well as the entire luxABCDE operon. These inserts were employed as mega-primers in a second PCR with a circular plasmid template. The original plasmid templates were then destroyed in restriction digests with DpnI, and the overlap extension PCR products were used to transform competent Escherichia coli cells. Phusion DNA polymerase was used for the amplification and fusion reactions, so both reactions were easy to monitor and optimize.
Rapid Perfusion and Network Remodeling in a Microvascular Construct After Implantation (2004)

With this model, we reproduce the important aspects of vascularization, angiogenesis, inosculation, and network remodeling. Furthermore, we demonstrate that the model accommodates human-derived vessel fragments, enabling the construction of human-mouse vascular chimeras.
Chondrocyte transplantation and experimental treatment options for articular cartilage defects. (1997)

Current treatment options for injured articular cartilage have resulted in temporary improvements in clinical symptoms and functional levels. None of these modalities, however, has resulted in restoration of an articular surface that is able to withstand long-term joint loading and function. As a result, numerous investigators have attempted to devise alternative therapies. The limited regnerative potential of articular cartilage has led investigators to attempt using cells with the potential for differentiation and proliferation to repair chondral defects. Chondrocyte transplantation, both allogeneic and autogenous, has shown early promising results in regenrating hyaline-like tissue in both animals and humans. Encouraging results in animals have also been demonstrated with alternative sources of osteoprogenitor cells as grafts, as well as with natural/synthetic implants and the use of growth factors and cytokines. However, despite encouraging short-term results, long-term data concerning the regenerate tissue are still needed. As more research is being conducted to understand the processes of cartilage maintenance and healing, there is hope that cartilage regeneration and neochondrogenesis will be possible in the future.
Local delivery of chemotherapy and concurrent external beam radiotherapy prolongs survival in metastatic brain tumor models. (1996)

Local chemotherapy with biodegradable polymers prolongs survival with minimal morbidity in patients with intracranial high-grade gliomas. However, use of local chemotherapy for metastatic brain tumors has not been defined. We studied the safety and the efficacy of locally delivered chemotherapy with and without concurrent radiation therapy in treating tumors that frequently metastasize to the brain. The chemotherapeutic agents 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), carboplatin, and camptothecin were incorporated into controlled-release polymers and tested individually against intracranial challenges with one of four tumors (lung carcinoma, renal cell carcinoma, colon carcinoma, and melanoma). For each combination of drug and tumor type, four groups were tested: (a) empty polymer (no drug); (b) external beam radiotherapy (XRT) alone; (c) local chemotherapy from biodegradable polymer alone; and (d) local chemotherapy and XRT together. Polymers were implanted 5 days after tumor inoculation; XRT was given on days 7-9 (300 cGy/day). BCNU and XRT together were effective against all four tumors. BCNU polymer alone significantly prolonged survival in mice with intracranial melanoma or renal cell carcinoma. Carboplatin alone was effective against both melanoma and colon carcinoma and in combination with XRT against colon and renal cell carcinomas. Camptothecin was effective only with XRT against melanoma. These studies demonstrate that local delivery of chemotherapy with concurrent radiation therapy is safe and can significantly prolong survival in models of common intracranial metastatic tumors. Concurrent use of local chemotherapy with standard XRT appears to be more effective than either treatment alone. Local chemotherapy may also be of benefit to patients who have previously received maximal cranial irradiation but suffer an intracranial recurrence.