gebhart/patrepeval huggingface dataset:
Bone marrow-derived stromal cells prevent apoptotic cell death in B- lineage acute lymphoblastic leukemia (1992)

Establishing requirements for the survival of human immature B cells in vitro has proved elusive. In this article, we report prolonged survival of B-lineage leukemic cells on ‘feeder layers’ of bone marrow (BM)- derived stromal cells in a serum-free environment. In 15 of 18 cases of B-lineage acute lymphoblastic leukemia (ALL), there was a greater than 50% decrease in the number of viable cells after 72 hours of culture in medium alone. Cell loss was preceded by molecular and cellular changes characteristic of programmed cell death, or apoptosis, and was not suppressed by adding interleukin-7 to the tissue culture medium. By contrast, the use of allogeneic BM stromal cells as feeder layers prevented apoptosis in 10 of 12 cases of ALL, leading to extended survival of the blast cells. This method was not successful when the allogeneic marrow cells were replaced with established cell lines. In six of eight cases in which the numbers of intact CD19+ lymphoblasts were counted by flow cytometry after 7 days of culture, the proportion of such cells recovered in the presence of BM stromal cells was 68.8% to 124.7% (median, 95.3%) of that originally seeded, as opposed to the 0.3% to 15.9% fraction (median, 0.7%) obtained in the absence of stromal cells. Survival requirements of the B-lineage lymphoblasts appeared to be heterogeneous, as cells from 3 of the 18 cases studied showed no signs of apoptosis in serum-free tissue culture medium that lacked BM stromal cells. The only cells not giving rise to viable cultures were from two hyperdiploid (greater than 50 chromosomes) cases with identical karyotypes. The serum-free assay described here can be used to compare the survival requirements of normal and leukemic B-cell progenitors as well as to identify the molecules involved in the interaction between BM stroma and immature B cells.
A novel 4‐kb interleukin‐13 receptor α mRNA expressed in human B, T, and endothelial cells encoding an alternate type‐II interleukin‐4/ interleukin‐13 receptor (1997)

A 4 kb human interleukin-13 receptor (IL-13R) chain cDNA was cloned from a B cell cDNA library using expressed sequence tags homologous to mouse IL-13R as probes. The deduced protein sequence shows a significant level of sequence identity with the IL-5R and the human IL-13R identified recently by expression cloning. The cytoplasmic region is very highly conserved between human and mouse homologs and contains a consensus binding motif for a signal transducer and activator of transcription. The cDNA encodes a protein binding IL-13 when expressed alone which participates in a receptor complex for both IL-4 and IL-13 when expressed in conjunction with the IL-4R alpha chain. Transcripts for this IL-13R chain could be detected in most tissues and organs studied and in T, B, endothelial cells, basophilic, immature mast cell, and monocytic cell lines. The pattern of expression is different from the other recently cloned IL-13R molecule, and correlates with sites where IL-4 and IL-13 signaling is known to occur. This novel receptor is therefore likely to be implicated in reactions involved in IgE responses, T helper 2 differentiation, adhesion of leukocytes to endothelium, and therefore in pathological phenomena such as allergy, atopy, and asthma.
Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau (tau) (1986)

The relationship of the neurofibrillary tangle, found in Alzheimer disease and aged brains, to normal or abnormal cytoskeletal proteins remains elusive. Although immunohistochemical studies have yielded disparate results, most antigenic determinants localized to neurofibrillary tangles are cytoskeletal constituents normally present in neuronal perikarya or dendrites. We report light and electron microscopic immunolabeling of neurofibrillary tangles by a monoclonal antibody to the microtubule-associated protein tau (tau). Dephosphorylation of tissue slices not only increased the number of tau-positive tangles but also produced marked positive immunoreactivity of neuritic plaques. The localization of tau, an axonal protein, to neurofibrillary tangles in the perikaryon in particular suggests that abnormal synthesis, modification, or aggregation of tau may induce aberrant cytoskeletal--cell organelle interactions, subsequent interference with axonal flow, and resultant tangle formation.
GCPII Variants, Paralogs and Orthologs (2012)

Glutamate carboxypeptidase II (GCPII) and its splice variants, paralogs and human homologs represent a family of proteins with diverse tissue distribution, cellular localization and largely unknown function which have been explored only recently. While GCPII itself has been thoroughly studied from different perspectives, as clearly documented in this series of reviews, very little is known about other members of its family, even though they might be biologically relevant. Differential expression of individual GCPII splice variants is associated with tumor progression and prognosis of prostate cancer. The best studied GCPII homolog, GCPIII or NAALADase II, may be a valid pharmaceutical target for itself since it may compensate for a lack of normal GCPII enzymatic activity. Detailed molecular characterization of this family of proteins is thus very important not only with respect to the potential therapeutic use of GCPII inhibitors, but also for better understanding of the biological role of GCPII within as well as outside the nervous system.
Opposite roles of apolipoprotein E in normal brains and in Alzheimer’s disease (1998)

We have characterized the interaction between apolipoprotein E (apoE) and amyloid beta peptide (Abeta) in the soluble fraction of the cerebral cortex of Alzheimer's disease (AD) and control subjects. Western blot analysis with specific antibodies identified in both groups a complex composed of the full-length apoE and Abeta peptides ending at residues 40 and 42. The apoE-Abeta soluble aggregate is less stable in AD brains than in controls, when treated with the anionic detergent SDS. The complex is present in significantly higher quantity in control than in AD brains, whereas in the insoluble fraction an inverse correlation has previously been reported. Moreover, in the AD subjects the Abeta bound to apoE is more sensitive to protease digestion than is the unbound Abeta. Taken together, our results indicate that in normal brains apoE efficiently binds and sequesters Abeta, preventing its aggregation. In AD, the impaired apoE-Abeta binding leads to the critical accumulation of Abeta, facilitating plaque formation.
Cloning and disruption of the Pichia pastoris ARG1, ARG2, ARG3, HIS1, HIS2, HIS5, HIS6 genes and their use as auxotrophic markers (2005)

Screening of a partial genomic database of Pichia pastoris allowed us to identify the ARG1, ARG2, ARG3, HIS1, HIS2, HIS5 and HIS6 genes, based on homology to their Saccharomyces cerevisiae counterparts. Based on the cloned sequences, a set of disruption vectors was constructed, using the previously described PpURA5-blaster as a selectable marker, and the cloned genes were individually disrupted. All disruptants exhibited the expected auxotrophic phenotypes, with only the his2 knockouts displaying a bradytroph phenotype. To allow their use as auxotrophic markers, we amplified the open reading frames and respective promoters and terminator regions of PpARG1, PpARG2, PpARG3, PpHIS1, PpHIS2 and PpHIS5. We then designed a set of integration vectors harbouring cassettes of the ARG pathway as selectable markers, to disrupt the genes of the HIS pathway and vice versa. Employing this strategy, we devised a scheme allowing for the rapid and stable introduction of several heterologous genes into the genome of P. pastoris without the need for recyclable markers or strains with multiple auxotrophies. Furthermore, simple replica-plating, instead of cost-consuming and labour-intensive colony PCR or Southern analysis, can be used to identify positive transformants, making this approach amendable for initial high-throughput applications, which can then be followed up by a more careful analysis of the selected transformants.
Activation of Mitochondrial ATP-Dependent Potassium Channels Protects Neurons against Ischemia-Induced Death by a Mechanism Involving Suppression of Bax Translocation and Cytochrome c Release (2002)

Neurons express a variety of plasma-membrane potassium channels that play important roles in regulating neuronal excitability and synaptic transmission, but also contain mitochondrial ATP-sensitive potassium channels, the functions of which are unknown. Studies of cardiac cells suggest that similar mitochondrial ATP-sensitive potassium channels are involved in the process of ischemic preconditioning, suggesting a role in regulating cell survival. The authors report that mice given diazoxide, an activator of mitochondrial ATP-sensitive potassium channels, exhibited a large (60% to 70%) decrease in cortical infarct size after permanent occlusion of the middle cerebral artery. Diazoxide decreases neuronal apoptosis and increases astrocyte survival and activation in the penumbral region of the ischemic cortex. The neuroprotective effect of diazoxide is abolished by 5-hydroxydecanoate, a selective antagonist of mitochondrial ATP-sensitive potassium channels. Studies of cultured hippocampal neurons reveal that diazoxide depolarizes mitochondria, prevents cytochrome c release, and protects cells against death induced by staurosporine and chemical hypoxia. Diazoxide increased the levels of Bcl2 and inhibited the association of Bax with mitochondria in neurons exposed to an apoptotic insult, suggesting that activation of mitochondrial ATP-sensitive potassium channels may stabilize mitochondrial function by differentially modulating proapoptotic and antiapoptotic proteins. Collectively, the data suggest that mitochondrial ATP-sensitive potassium channels play a key role in modulating neuronal survival under ischemic conditions, and identify agents that activate mitochondrial ATP-sensitive potassium channels as potential therapeutics for stroke and related neurodegenerative conditions.
Synthetic Nanomotors in Microchannel Networks: Directional Microchip Motion and Controlled Manipulation of Cargo (2008)

We illustrate the use of catalytic nanowire motors for directional motion and microscale transport of cargo within microfluidic channel networks. The CNT-based synthetic nanomotor can propel a large cargo load at high speeds through predetermined paths and junctions of the microchannel network. The magnetic properties of the nickel-containing nanomotors offer controlled cargo manipulations, including en-route load, drag, and release. Such use of synthetic nanomachines can lead to chemically powered versatile laboratory-on-a-chip devices performing a series of tasks simultaneously or sequentially.
Papilledema in the Assessment of Ventriculomegaly (2006)

To determine whether ventriculomegaly is associated with ongoing increased intracranial pressure (ICP), physicians often rely on corroborative imaging features such as altered periependymal signal, distortion of ventricular shape, subarachnoid space flattening, and an increase in ventricular size over time. In 2 patients with new headache and altered mental status, symptoms and ventriculomegaly were dismissed as long-standing and not reflective of current ICP elevation. In the first patient, ICP was considered normal because there were no corroborative imaging features of elevated ICP. In the second patient, ICP was considered normal because ventricular size was stable over a 1-year period. The diagnosis of ICP elevation was finally made by ICP monitoring after papilledema was recognized. Ventriculoperitoneal shunting rapidly resolved the papilledema and markedly improved mentation. Brain imaging may often be an unreliable guide to the presence of elevated ICP. In such patients, the finding of papilledema is a critical determinant of management.
Improvement of Encryption Processing Speed for a User Attestation System Using a Cellular Phone (2011)

For accessing Internet, a reusable password method is frequently used because of its simplicity. This reusable password method is very vulnerable. In recent years, with the explosive growth of the Internet user, user passwords are often incorrect handled and this attestation system is very dangerous. To solve these vulnerability problems of the attestation system, the one-time password, biometric system, and other methods using IC or LSI chips have been developed to build more complex authentication systems. But, still remain many problems such as system complexity and certification costs. In order to provide a low-cost and simple user attestation method, in our previous work, we proposed a method with strong authentication by using digital camera of cellular phone. But, this method used 2D color code, thus there are some process costs such as create and decode 2D color code. In this paper, we present an improved attestation system using a cellular phone and 2D color code. The efficiency of the proposed attestation method is confirmed by an experimental prototype system.
Neuro-evolutionary topology optimization of structures by utilizing local state features (2014)

In this paper we propose a novel method for the topology optimization of mechanical structures, based on a hybrid combination of a neuro-evolution with a gradient-based optimizer. Conventional gradient-based topology optimization requires problem-specific sensitivity information, however this is not available in the general case. The proposed method substitutes the analytical gradient by an artificial neural network approximation model, whose parameters are learned by an evolutionary algorithm. Advantageous is that the number of parameters in the evolutionary search is not directly coupled to the mesh of the discretized design, potentially enabling the optimization of fine discretizations. Concretely, the network maps features, obtained for each element of the discretized design, to an update signal, that is used to determine a new design. A new network is learned for every iteration of the topology optimization. The proposed method is evaluated on the minimum compliance design problem, with two different sets of features. Feasible designs are obtained, showing that the neural network is able to successfully replace analytical sensitivity information. In concluding remarks, we discuss the significant improvement that is achieved when including the strain energy as feature.
A rigid molecular tweezers with an active site carboxylic acid: exceptionally efficient receptor for adenine in an organic solvent (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA rigid molecular tweezers with an active site carboxylic acid: exceptionally efficient receptor for adenine in an organic solventSteven C. Zimmerman and Weiming WuCite this: J. Am. Chem. Soc. 1989, 111, 20, 8054–8055Publication Date (Print):September 1, 1989Publication History Published online1 May 2002Published inissue 1 September 1989https://pubs.acs.org/doi/10.1021/ja00202a077https://doi.org/10.1021/ja00202a077research-articleACS PublicationsRequest reuse permissionsArticle Views643Altmetric-Citations115LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Nanofiber Scaffolds with Gradations in Mineral Content for Mimicking the Tendon-to-Bone Insertion Site (2009)

We have demonstrated a simple and versatile method for generating a continuously graded, bonelike calcium phosphate coating on a nonwoven mat of electrospun nanofibers. A linear gradient in calcium phosphate content could be achieved across the surface of the nanofiber mat. The gradient had functional consequences with regard to stiffness and biological activity. Specifically, the gradient in mineral content resulted in a gradient in the stiffness of the scaffold and further influenced the activity of mouse preosteoblast MC3T3 cells. This new class of nanofiber-based scaffolds can potentially be employed for repairing the tendon-to-bone insertion site via a tissue engineering approach.
Frontline Science: Functionally impaired geriatric CAR-T cells rescued by increased α5β1 integrin expression (2017)

Chimeric antigen receptor expressing T cells (CAR-T) are a promising form of immunotherapy, but the influence of age-related immune changes on CAR-T production remains poorly understood. We showed that CAR-T cells from geriatric donors (gCAR-T) are functionally impaired relative to CAR-T from younger donors (yCAR-T). Higher transduction efficiencies and improved cell expansion were observed in yCAR-T cells compared with gCAR-T. yCAR-T demonstrated significantly increased levels of proliferation and signaling activation of phosphorylated (p)Erk, pAkt, pStat3, and pStat5. Furthermore, yCAR-T contained higher proportions of CD4 and CD8 effector memory (EM) cells, which are known to have enhanced cytolytic capabilities. Accordingly, yCAR-T demonstrated higher levels of tumor antigen-specific cytotoxicity compared with gCAR-T. Enhanced tumor killing by yCAR-T correlated with increased levels of perforin and granzyme B. yCAR-T had increased α5β1 integrin expression, a known mediator of retroviral transduction. We found that treatment with M-CSF or TGF-β1 rescued the impaired transduction efficiency of the gCAR-T by increasing the α5β1 integrin expression. Neutralization of α5β1 confirmed that this integrin was indispensable for CAR expression. Our study suggests that the increase of α5β1 integrin expression levels enhances CAR expression and thereby improves tumor killing by gCAR-T.
Synthesis of 7-Oxo-5-deoxystrigol, a 7-Oxygenated Strigolactone Analog (2013)

A straightforward synthesis of 7-oxo-5-deoxystrigol, a 7-oxygenated strigolactone analog, was achieved by starting from 2,2-dimethylcyclohexane-1,3-dione.
Functional fetal nigral grafts in a patient with Parkinson's disease: Chemoanatomic, ultrastructural, and metabolic studies (1996)

A patient with Parkinson's disease received bilateral fetal human nigral implants from six donors aged 6.5 to 9 weeks post-conception. Eighteen months following a post-operative clinical course characterized by marked improvement in clinical function, this patient died from events unrelated to the grafting procedure. Post-mortem histological analyses revealed the presence of viable grafts in all 12 implant sites, each containing a heterogeneous population of neurons and glia. Approximately 210,146 implanted tyrosine hydroxylase-immunoreactive (TH-ir) neurons were found. A greater number of TH-ir grafted neurons were observed in the right (128,162) than the left (81,905) putamen. Grafted TH-ir neurons were organized in an organotypic fashion. These cells provided extensive TH-ir and dopamine transporter-ir innervation to the host striatum which occurred in a patch-matrix fashion. Quantitative evaluations revealed that fetal nigral grafts reinnervated 53% and 28% of the post-commissural putamen on the right and left side, respectively. Grafts on the left side innervated a lesser area of the striatum, but optical density measurements were similar on both sides. There was no evidence that the implants induced sprouting of host TH-ir systems. Electron microscopic analyses revealed axo-dendritic and occasional axo-axonic synapses between graft and host. In contrast, axo-somatic synapses were not observed. In situ hybridization for TH mRNA revealed intensely hybridized grafted neurons which far exceeded TH mRNA expression within residual host nigral cells. In addition, gamma-amino butyric acid (GABA)-ergic neurons were observed within the graft that formed a dense local neuropil which was confined to the implant site. Serotonergic neurons were not observed within the graft. Cytochrome oxidase activity was increased bilaterally within the grafted post-commissural putamen, suggesting increased metabolic activity. In this regard, a doubling of cytochrome oxidase activity was observed within the grafted post-commissural putamen bilaterally relative to the non-grafted anterior putamen. The grafts were hypovascular relative to the surrounding striatum and host substantia nigra. Blood vessels within the graft stained intensely for GLUT-1, suggesting that this marker of blood--brain barrier function is present within human nigral allografts. Taken together, these data indicate that fetal nigral neurons can survive transplantation, functionally reinnervate the host putamen, establish synaptic contacts with host neurons, and sustain many of the morphological and functional characteristics of normal nigral neurons following grafting into a patient with PD.
Repression of interleukin‐6 gene expression by 17β‐estradiol: (1997)

The cytokine interleukin-6 (IL-6), a key mediator of immune and acute phase responses of the liver, has also been implicated in uterine functions. Estrogens are potent repressors of IL-6 production by uterine stromal cells. In the endometrial adenocarcinoma cell line Ishikawa, phorbol ester-induced activation of the IL-6 promoter was inhibited to basal levels by 17 beta-estradiol (E2) in a wild-type receptor-dependent fashion. Although tamoxifen has been shown to have estrogenic effects on the endometrium, it did not inhibit induction of the IL-6 promoter. We previously showed that inhibition of IL-6 gene expression by E2 does not involve high-affinity binding of the estrogen receptor (ER) to IL-6 DNA. We now report that the ER can directly interact with the transcription factors NF-IL6 and NF-kappa B and can inhibit their ability to bind DNA which might be the molecular basis for repression of IL-6 gene expression by estrogens.