gebhart/patrepeval huggingface dataset:
miR-99a/100∼125b tricistrons regulate hematopoietic stem and progenitor cell homeostasis by shifting the balance between TGFβ and Wnt signaling (2014)

Although regulation of stem cell homeostasis by microRNAs (miRNAs) is well studied, it is unclear how individual miRNAs genomically encoded within an organized polycistron can interact to induce an integrated phenotype. miR-99a/100, let-7, and miR-125b paralogs are encoded in two tricistrons on human chromosomes 11 and 21. They are highly expressed in hematopoietic stem cells (HSCs) and acute megakaryoblastic leukemia (AMKL), an aggressive form of leukemia with poor prognosis. Here, we show that miR-99a/100∼125b tricistrons are transcribed as a polycistronic message transactivated by the homeobox transcription factor HOXA10. Integrative analysis of global gene expression profiling, miRNA target prediction, and pathway architecture revealed that miR-99a/100, let-7, and miR-125b functionally converge at the combinatorial block of the transforming growth factor β (TGFβ) pathway by targeting four receptor subunits and two SMAD signaling transducers. In addition, down-regulation of tumor suppressor genes adenomatous polyposis coli (APC)/APC2 stabilizes active β-catenin and enhances Wnt signaling. By switching the balance between Wnt and TGFβ signaling, the concerted action of these tricistronic miRNAs promoted sustained expansion of murine and human HSCs in vitro or in vivo while favoring megakaryocytic differentiation. Hence, our study explains the high phylogenetic conservation of the miR-99a/100∼125b tricistrons controlling stem cell homeostasis, the deregulation of which contributes to the development of AMKL.
Approaching Nanoxerography: The Use of Electrostatic Forces to Position Nanoparticles with 100 nm Scale Resolution (2002)

Nanoparticles have been self-assembled using a novel technique described as nanoxerography (see cover). A method has been developed by the authors to pattern charge with 100 nm resolution. These charge patterns act as “receptors” for nanoparticles (see Figure), enabling the directed self-assembly of nanoparticles from a powder, gas phase (aerosol), and liquid phase (suspension).
Experimental Investigation of a 2D Supercritical Circulation-Control Airfoil Using Particle Image Velocimetry (2006)

Recent efforts in extreme short takeoff and landing aircraft configurations have renewed the interest in circulation control wing design and optimization. The key to accurately designing and optimizing these configurations rests in the modeling of the complex physics of these flows. This paper will highlight the physics of the stagnation and separation regions on two typical circulation control airfoil sections.
Abstract 2322: The Hippo signaling pathway mediates BMP inhibition of cancer stem cells (2015)

Abstract Multiple developmental signaling pathways cooperatively regulate cancer stem cell (CSC) function. Among them, the BMP pathway has been implicated in brain CSC tumorigenicity. To examine whether BMP is a general regulator of CSCs across diverse organ systems we utilized lentivirus-mediated BMP4 expression in patient-derived xenograft models in NOD/SCID mice. The prevention of tumor growth was observed in breast, colon, ovarian, and melanoma models. Similarly, adenovirus-mediated systemic delivery of BMP4 inhibited tumor growth, dramatically affected CSC-specific cell surface markers and decreased CSC frequency. Microarray analysis of BMP4-treated tumors showed that a set of genes encoding for components of the actin cytoskeleton was significantly enriched amongst regulated genes and identified Hippo pathway genes as potential mediators of the BMP4 anti-tumor response with up-regulation of SAV1 and LATS2 and down-regulation of BIRC5. Hippo signaling regulates organ size, stem cell biology and cancer through a protein kinase complex including MST1/2, SAV1, and LATS1/2, which phosphorylates the downstream nuclear effector YAP/TAZ. Phosphorylated YAP/TAZ is unable to induce the expression of cell proliferation and anti-apoptotic genes through interaction with transcriptional co-activators such as TEAD. The Hippo pathway, known to cross-talk with BMP signaling at multiple levels, recently emerged as a cellular sensor of the physical environment through the actin cytoskeleton. We thus asked whether modulating Hippo signaling affected tumor growth. YAP1 overexpression resulted in tumor growth decrease. A deletion variant of YAP, YAP1-291, possessing a deletion of the transactivation domain has been shown to act as a dominant-negative through binding to TEAD. Intriguingly YAP1-291 was also sufficient to strongly attenuate growth of diverse BMP4-sensitive and BMP4-insensitive tumor models suggesting that transactivation through TEAD is not the only route by which YAP modulates tumor growth. YAP anti-proliferative properties were reported before. In order to reconcile the dual function of YAP in cancer, we propose that the transcriptional co-activator's TEAD-mediated oncogenic function may be counter-balanced by its potentiation of SMAD signaling in response to BMP. Citation Format: Cecile Chartier, Shirley Ma, Dragana Antic, Elsa Quintana, Janak Raval, Min Wang, Cristina Dee-Hoskins, Ann Kapoun, Tim Hoey, John Lewicki, Austin Gurney. The Hippo signaling pathway mediates BMP inhibition of cancer stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2322. doi:10.1158/1538-7445.AM2015-2322
Including Group-By in Query Optimization (1994)

In existing relational database systems, processing of group-by and computation of aggregate functions are always postponed until all joins are performed. In this paper, we present transformations that make it possible to push group-by operation past one or more joins and can potentially reduce the cost of processing a query significantly. Therefore, the placement of group-by should be decided based on cost estimation. We explain how the traditional System-R style optimizers can be modified by incorporating the greedy conservative heuristic that we developed. We prove that applications of greedy conservative heuristic produce plans that are better (or no worse) than the plans generated by a traditional optimizer. Our experimental study shows that the extent of improvement in the quality of plans is significant with only a modest increase in optimization cost. Our technique also applies to optimization of Select Distinct queries by pushing down duplicate elimination in a cost-based fas...
Chlorpromazine in combination with nitrosourea inhibits experimental glioma growth (1994)

Modern cancer therapy has improved the prognosis for several tumour types. This, however, does not apply to the largest group of brain tumours, the malignant astrocytomas grades III-IV. Hence, there is need for new ideas to improve treatment. Ca2+ and the Ca(2+)-binding protein calmodulin have been shown to be involved in the processes conferring stability to DNA in proliferating neoplastic cells. We have combined the calmodulin-inhibiting neuroleptic drug chlorpromazine (CPZ), with the anti-neoplastic drug 1,3-bis(2-chloroethyl-1)-nitrosourea (BCNU) in a treatment regime for rats with glioma cells implanted in the brain. A highly significant inhibiting effect upon the tumour growth was noticed, not by CPZ or BCNU as single drugs, but with their combination.
Micro-component survey of residential water consumption in Hanoi (2013)

Daily total water consumption per capita has been used as a basic unit for the future planning of water supply for domestic use. However, for innovative water utilization designs that consider various scenarios, including the effects of policy direction and global warming, and more strategic and efficient water use, it is absolutely essential to consider water usage divided by residential activities, such as toilet flushing, cooking, clothes washing, and bathing. We collected micro-component data by direct measurement from each household outlet, and developed small accumulative meters. Measurements were conducted at 56 households for 2 months in Hanoi, Vietnam, and the average consumption was 18.6 L/p/d for toilet, 16.2 L/p/d for laundry, 10.4 L/p/d for bath, and 15.7 L/p/d for kitchen. We then analyzed the representative values and the distribution of water consumption for every usage from social and economic perspectives. In addition, we compared the results in Hanoi with those in Chiang Mai, Thailand, where we investigated water consumption a few years ago, and their value seemed similar except for bathroom use, but the substance was different. One distinct outcome of our investigation was the recognition of the cultural and methodological challenges to end-use assessment of water consumption in modernizing Asian communities.
Complement inhibition by anti-C5 antibodies - from bench to bedside and back again (2007)

The complement system is an important part of the innate immune system with pro-inflammatory and regulatory functions. Although many experimental studies have demonstrated that complement inhibition might be advantageous in a number of different human diseases, complement inhibition is still not part of the clinical treatment routine. With blocking antibodies against complement C5 a new generation of therapeutic complement inhibitors has now been investigated in some human diseases. This review gives an overview on the new complement inhibitors and the results obtained in clinical studies thus far.
Pharmacological inhibitors of the ERK signaling pathway: application as anticancer drugs. (2003)

The ERK signaling pathway, also known as the p42/p44 MAP kinase pathway, is a major determinant in the control of cell growth, cell differentiation and cell survival. This pathway, which operates downstream of Ras, is often up-regulated in human tumors and as such represents an attractive target for anticancer therapy. In this chapter we review the rationale for targeting the components of the ERK pathway, either alone or in association with cytotoxic anticancer agents. We present the most advanced inhibitors of this pathway and discuss their specificity and mechanism of action.
Light-water interaction using backward beam tracing (1990)

A new two pass approach is presented based on a variation of backward ray tracing backward beam tracing. Advantages include its capability of rendering complex, hitherto unattainable, specular to diffuse phenomenon and its easy insertion into standard renderers. The algorithm is applied to aspects of the interaction of light with water. Within this context a variety of first generation effects, including shadowing and light scattering, are both rendered and animated. Results taken from the treatment of caustics within classical optics are included as they provide valuable insights into the precise nature of specular to diffuse transfer.
Selectivity in a barren landscape: the P450BioI–ACP complex (2010)

The cytochromes P450 (P450s) are a superfamily of oxidative haemoproteins that are capable of catalysing a vast range of oxidative transformations, including the oxidation of unactivated alkanes, often with high stereo- and regio-selectivity. Fatty acid hydroxylation by P450s is widespread across both bacteria and higher organisms, with the sites of oxidation and specificity of oxidation varying from system to system. Several key examples are discussed in the present article, with the focus on P450(BioI) (CYP107H1), a biosynthetic P450 found in the biotin operon of Bacillus subtilis. The biosynthetic function of P450(BioI) is the formation of pimelic acid, a biotin precursor, via a multiple-step oxidative cleavage of long-chain fatty acids. P450(BioI) is a member of an important subgroup of P450s that accept their substrates not free in solution, but rather presented by a separate carrier protein. Structural characterization of the P450(BioI)-ACP (acyl-carrier protein) complex has recently been performed, which has revealed the basis for the oxidation of the centre of the fatty acid chain. The P450(BioI)-ACP structure is the first such P450-carrier protein complex to be characterized structurally, with important implications for other biosynthetically intriguing P450-carrier protein complexes.
Shoot meristem: an ideal explant for Zea mays L. transformation (2003)

We report on a rapid high-frequency somatic embryogenesis and plant regeneration protocol for Zea mays. Maize plants were regenerated from complete shoot meristem (3-4 mm) explants via organogenesis and somatic embryogenesis. In organogenesis, the shoot meristems were directly cultured on a high-cytokinin medium comprising 5-10 mg x L(-1) 6-benzylaminopurine (BAP). The number of multiple shoots produced per meristem varied from six to eight Plantlet regeneration through organogenesis resulted in just four weeks. Callus was induced in five days of incubation on an auxin-modified Murashige and Skoog (MS) medium. Prolific callus, with numerous somatic embryos, developed within 3-4 weeks when cultured on an auxin medium containing 5 mg 2,4-dichlorophenoxyacetic acid x L(-1). The number of multiple shoots varied from three to six per callus. Using R23 (Pioneer, Hi-Bred, Johnston, Iowa), the frequency of callus induction was consistently in excess of 80% and plant regeneration ranged between 47 and 64%. All regenerated plantlets survived in the greenhouse and produced normal plants. Each transgenic plant produced leaves, glumes, and anthers that uniformly expressed green fluorescent protein (GFP). The GFP gene segregated in the pollen. Based on this data it is concluded that the transgenics arose from single-cell somatic embryos. The rate of transfer DNA (T-DNA) transfer to complete shoot meristems of Zea mays was high on the auxin medium and was independent of using super-virulent strains of Agrobacterium.
LAB ON A CD (2006)

In this paper, centrifuge-based microfluidic platforms are reviewed and compared with other popular microfluidic propulsion methods. The underlying physical principles of centrifugal pumping in microfluidic systems are presented and the various centrifuge fluidic functions, such as valving, decanting, calibration, mixing, metering, heating, sample splitting, and separation, are introduced. Those fluidic functions have been combined with analytical measurement techniques, such as optical imaging, absorbance, and fluorescence spectroscopy and mass spectrometry, to make the centrifugal platform a powerful solution for medical and clinical diagnostics and high throughput screening (HTS) in drug discovery. Applications of a compact disc (CD)-based centrifuge platform analyzed in this review include two-point calibration of an optode-based ion sensor, an automated immunoassay platform, multiple parallel screening assays, and cellular-based assays. The use of modified commercial CD drives for high-resolution optical imaging is discussed as well. From a broader perspective, we compare technical barriers involved in applying microfluidics for sensing and diagnostic use and applying such techniques to HTS. The latter poses less challenges and explains why HTS products based on a CD fluidic platform are already commercially available, whereas we might have to wait longer to see commercial CD-based diagnostics.
Strategies for developing effective radioimmunotherapy for solid tumors. (1999)

Single-agent radioimmunotherapy (RIT) has proven efficacy as a treatment for hematological malignancies, particularly non-Hodgkin's lymphoma. Although promising, RIT has been less effective for solid tumors, in part because they are less radiosensitive. Bone marrow transplantation permits the administration of larger radiopharmaceutical doses, but the results of bone marrow transplantation-supported RIT for solid tumors have been marginal. The purpose of this publication is to provide an overview of promising RIT strategies for solid tumors. It is apparent that combination therapy is required, but optimization of the radiopharmaceutical should be the first step. Metallic radionuclides provide higher tumor radiation doses but not necessarily an improved therapeutic index, that is, the ratio of tumor:normal tissue radiation doses. Biodegradable peptide linkers between the chelated metal and the antibody improve the therapeutic index. Further improvements depend on identification of synergistic therapies which recognize that: (a) continuous, low-dose radionuclide therapy acts through apoptosis; and (b) apoptosis is often blocked because most tumors have ineffective p53 and increased Bcl-2. Taxanes are particularly attractive as synergistic agents for RIT because they induce cell cycle arrest in the radiosensitive G2-M phase and p53-independent apoptosis. Optimal sequence and timing for combined modality RIT are critical to achieve synergy. Data from preclinical and clinical studies will be reviewed to illustrate the potential of these strategies.
RNA location and modeling of a WD40 repeat domain within the vault (2000)

The vault complex is a ubiquitous 13-MDa ribonucleoprotein assembly, composed of three proteins (TEP1, 240 kDa; VPARP, 193 kDa; and MVP, 100 kDa) that are highly conserved in eukaryotes and an untranslated RNA (vRNA). The vault has been shown to affect multidrug resistance in cancer cells, and one particular component, MVP, is thought to play a role in the transport of drug from the nucleus. To locate the position of the vRNA, vaults were treated with RNases, and cryo-electron microscopy (cryo-EM) was performed on the resulting complexes. Using single-particle reconstruction techniques, 3,476 particle images were combined to generate a 22-A-resolution structure. Difference mapping between the RNase-treated vault and the previously calculated intact vault reconstructions reveals the vRNA to be at the ends of the vault caps. In this position, the vRNA may interact with both the interior and exterior environments of the vault. The finding of a 16-fold density ring at the top of the cap has allowed modeling of the WD40 repeat domain of the vault TEP1 protein within the cryo-EM vault density. Both stoichiometric considerations and the finding of higher resolution for the computationally selected and refined "barrel only" images indicate a possible symmetry mismatch between the barrel and the caps. The molecular architecture of the complex is emerging, with 96 copies of MVP composing the eightfold symmetric barrel, and the vRNA together with one copy of TEP1 and four predicted copies of VPARP comprising each cap.
Synthesis and Characterization of a New Fluorine‐Containing Polybenzimidazole (PBI) for Proton‐Conducting Membranes in Fuel Cells (2013)

Abstract A new type of fluorine‐containing polybenzimidazole, namely poly(2,2′‐(2,2′‐bis(trifluoromethyl)‐4,4′‐biphenylene)‐5,5′‐bibenzimidazole) (BTBP‐PBI), was developed as a candidate for proton‐conducting membranes in fuel cells. Polymerization conditions were experimentally investigated to achieve high molecular weight polymers with an inherent viscosity (IV) up to 1.60 dl g –1 . The introduction of the highly twisted 2,2′‐disubstituted biphenyl moiety into the polymer backbone suppressed the polymer chain packing efficiency and improved polymer solubility in certain polar organic solvents. The polymer also exhibited excellent thermal and oxidative stability. Phosphoric acid (PA)‐doped BTBP‐PBI membranes were prepared by the conventional acid imbibing procedure and their corresponding properties such as mechanical properties and proton conductivity were carefully studied. The maximum membrane proton conductivity was approximately 0.02 S cm –1 at 180 °C with a PA doping level of 7.08 PA/RU. The fuel cell performance of BTBP‐PBI membranes was also evaluated in membrane electrode assemblies (MEA) in single cells at elevated temperatures. The testing results showed reliable performance at 180 °C and confirmed the material as a candidate for high‐temperature polymer electrolyte membrane fuel cell (PEMFC) applications.
Expression of complete chicken thymidine kinase gene inserted in a retrovirus vector. (1984)

The chicken thymidine kinase (tk) gene was inserted into spleen necrosis virus. Thymidine kinase activity was expressed even when the promoter and terminator sequences for tk RNA synthesis were retained. When the promoter was present in the same orientation as the promoter in the long terminal repeat of the virus, deletions occurred both in the virus and in the tk gene, and the thymidine kinase-transforming activity of the recovered virus was low. Splicing of apparent intervening sequences in the tk gene was also observed. When the orientation of the tk promoter was opposite to the promoter in the long terminal repeat, virus synthesis was diminished, whereas thymidine kinase activity was expressed at an elevated level compared with virus in which the promoter was in the same orientation. However, when the apparent tk promoter was deleted from virus with the tk gene in the opposite orientation, a high level of virus synthesis was observed, probably as a result of absence of interference of RNA synthesis from converging promoters. The intervening sequences in the virus in which the promoters were in opposite orientation were not spliced.
Laminar MoS2 membranes for molecule separation (2013)

For the first time, a laminar separation membrane was assembled from atom-thick MoS2 sheets and exhibited a water permeance of 245 L h(-1) m(-2) bar(-1), which was 3-5 times higher than that of graphene oxide membranes without degradation of the rejection ratio (89%) for Evans blue molecules.