Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Receptor Dimerization as a Novel Negative Feedback Mechanism of EGFR Signaling

Dimerization of the epidermal growth factor receptor (EGFR) is crucial for initiating signal transduction. We employed raster image correlation spectroscopy to continuously monitor the EGFR monomer-dimer equilibrium in living cells. EGFR dimer formation upon addition of EGF showed oscillatory behavior with a periodicity of about 2.5 min, suggesting the presence of a negative feedback loop to monomerize the receptor. We demonstrated that monomerization of EGFR relies on phospholipase Cγ, protein kinase C, and protein kinase D (PKD), while being independent of Ca2+ signaling and endocytosis. Phosphorylation of the juxtamembrane threonine residues of EGFR (T654/T669) by PKD was identified as the factor that shifts the monomer-dimer equilibrium of ligand bound EGFR towards the monomeric state. The dimerization state of the receptor correlated with the activity of an extracellular signal-regulated kinase, downstream of the EGFR. Based on these observations, we propose a novel, negative feedback mechanism that regulates EGFR signaling via receptor monomerization.
Constraints on alternatives to supermassive black holes

Observations of the centres of galaxies continue to evolve, and it is useful to take a fresh look at the constraints that exist on alternatives to supermassive black holes at their centres. We discuss constraints complementary to those of Maoz and demonstrate that an extremely wide range of other possibilities can be excluded. In particular, we present the new argument that for the velocity dispersions inferred for many galactic nuclei, even binaries made of point masses cannot stave off core collapse because hard binaries are so tight that they merge via emission of gravitational radiation before they can engage in three-body or four-body interactions. We also show that under these conditions core collapse leads inevitably to runaway growth of a central black hole with a significant fraction of the initial mass, regardless of the masses of the individual stars. For clusters of non-interacting low-mass objects (from low-mass stars to elementary particles), the relaxation of stars and compact objects that pass inside the dark region will be accelerated by interactions with the dark mass. If the dark region is instead a self-supported object, such as a fermion ball, then if stellar-mass black holes exist they will collide with the object, settle, and consume it. The net result is that the keyhole through which alternatives to supermassive black holes must pass is substantially smaller and more contrived than it was even a few years ago.
Adaptive Control for the Systems Preceded by Hysteresis

Hysteresis hinders the effectiveness of smart materials in sensors and actuators. It is a challenging task to control the systems with hysteresis. This note discusses the adaptive control for discrete time linear dynamical systems preceded with hysteresis described by the Prandtl-Ishlinskii model. The time delay and the order of the linear dynamical system are assumed to be known. The contribution of the note is the fusion of the hysteresis model with adaptive control techniques without constructing the inverse hysteresis nonlinearity. Only the parameters (which are generated from the parameters of the linear system and the density function of the hysteresis) directly needed in the formulation of the controller are adaptively estimated online. The proposed control law ensures the global stability of the closed-loop system, and the output tracking error can be controlled to be as small as required by choosing the design parameters. Simulation results show the effectiveness of the proposed algorithm.
Stochastic Resonance in Simple Electrical Circuits Driven by Quadratic Gaussian Noise

In this brief, we report exact analytical and numerical evidence of the occurrence of the stochastic resonance (SR) phenomenon in simple electrical circuits driven by a quadratic Gaussian colored noise and by a Gaussian white noise. As an example, we have used an RL configuration. However, it is clear that the phenomenon occurs in any other configuration governed by the same type of evolution equation. The main result is that the phenomenon occurs with a quadratic colored noise. When noise enters only linearly we have verified that the SR occurs both with colored noise and white noise. The robustness of our results were verified by calculating the variance as a function of time in each case. We believe that the results obtained could be observed in a laboratory experiment using some kind of digital resistance. The white noise limit with quadratic noise was excluded.
Oncogenic fusion protein EWS-FLI1 is a network hub that regulates alternative splicing

Significance Alternative splicing of RNA allows a limited number of coding regions in the human genome to produce proteins with diverse functionality. Alternative splicing has also been implicated as an oncogenic process. Identifying aspects of cancer cells that differentiate them from noncancer cells remains an ongoing challenge, and our research suggests that alternatively spliced mRNA and subsequent protein isoforms will provide new anticancer targets. We determined that the key oncoprotein of Ewing sarcoma (ES), EWS-FLI1, regulates alternative splicing in multiple cell line models. These experiments establish oncogenic aspects of splicing that are specific to cancer cells and thereby illuminate potentially oncogenic splicing shifts as well as provide a useful stratification mechanism for ES patients. The synthesis and processing of mRNA, from transcription to translation initiation, often requires splicing of intragenic material. The final mRNA composition varies based on proteins that modulate splice site selection. EWS-FLI1 is an Ewing sarcoma (ES) oncoprotein with an interactome that we demonstrate to have multiple partners in spliceosomal complexes. We evaluate the effect of EWS-FLI1 on posttranscriptional gene regulation using both exon array and RNA-seq. Genes that potentially regulate oncogenesis, including CLK1, CASP3, PPFIBP1, and TERT, validate as alternatively spliced by EWS-FLI1. In a CLIP-seq experiment, we find that EWS-FLI1 RNA-binding motifs most frequently occur adjacent to intron–exon boundaries. EWS-FLI1 also alters splicing by directly binding to known splicing factors including DDX5, hnRNP K, and PRPF6. Reduction of EWS-FLI1 produces an isoform of γ-TERT that has increased telomerase activity compared with wild-type (WT) TERT. The small molecule YK-4–279 is an inhibitor of EWS-FLI1 oncogenic function that disrupts specific protein interactions, including helicases DDX5 and RNA helicase A (RHA) that alters RNA-splicing ratios. As such, YK-4–279 validates the splicing mechanism of EWS-FLI1, showing alternatively spliced gene patterns that significantly overlap with EWS-FLI1 reduction and WT human mesenchymal stem cells (hMSC). Exon array analysis of 75 ES patient samples shows similar isoform expression patterns to cell line models expressing EWS-FLI1, supporting the clinical relevance of our findings. These experiments establish systemic alternative splicing as an oncogenic process modulated by EWS-FLI1. EWS-FLI1 modulation of mRNA splicing may provide insight into the contribution of splicing toward oncogenesis, and, reciprocally, EWS-FLI1 interactions with splicing proteins may inform the splicing code.
Brachypodium distachyon grain: identification and subcellular localization of storage proteins

Seed storage proteins are of great importance in nutrition and in industrial transformation because of their functional properties. Brachypodium distachyon has been proposed as a new model plant to study temperate cereals. The protein composition of Brachypodium grain was investigated by separating the proteins on the basis of their solubility combined with a proteomic approach. Salt-soluble proteins as well as salt-insoluble proteins separated by two-dimensional gel electrophoresis revealed 284 and 120 spots, respectively. Proteins from the major spots were sequenced by mass spectrometry and identified by searching against a Brachypodium putative protein database. Our analysis detected globulins and prolamins but no albumins. Globulins were represented mainly by the 11S type and their solubility properties corresponded to the glutelin found in rice. An in silico search for storage proteins returned more translated genes than expressed products identified by mass spectrometry, particularly in the case of prolamin type proteins, reflecting a strong expression of globulins at the expense of prolamins. Microscopic examination of endosperm cells revealed scarce small-size starch granules surrounded by protein bodies containing 11S globulins. The presence of protein bodies containing glutelins makes B. distachyon closer to rice or oat than to wheat endosperm.
Origin of chordoid glioma of the third ventricle.

CONTEXT Chordoid glioma is a relatively recently described unique glial neoplasm that has been formally codified by the World Health Organization in Pathology and Genetics of Tumours of the Nervous System, in which it is included along with astroblastoma and gliomatosis cerebri under the rubric "Tumors of Uncertain Origin. " Many examples of chordoid glioma come to clinical attention only at a relatively large size and occupy a large portion of the third ventricle. Accordingly, the anatomic origin of chordoid glioma has been unclear and debated. OBJECTIVE To examine the regional anatomic origin of chordoid glioma. DATA SOURCES The clinical, imaging, histologic, immunophenotypic, and ultrastructural data in previously published case series and individual case reports of chordoid glioma were reviewed in conjunction with the study of a new case of chordoid glioma that presented at a relatively small size, thereby facilitating neuroanatomic localization. CONCLUSIONS Chordoid glioma exhibits features of specialized ependymal differentiation on ultrastructural examination, and all examples reported in the literature to date have displayed a highly stereotypical suprasellar anatomic localization and an ovoid shape, as seen on neuroimaging studies and gross anatomy. Neuroanatomic, radiologic, and clinical evidence supports an anatomic origin for chordoid glioma from the vicinity of the lamina terminalis.
Elevated atmospheric carbon dioxide effects on sorghum and soybean nutrient status 1

Abstract Increasing atmospheric carbon dioxide (CO2) concentration could have significant implications on technologies for managing plant nutrition to sustain crop productivity in the future. Soybean (Glycine max [L.] Merr.) (C3 species) and grain sorghum (Sorghum bicolor [L.] Moench) (C4 species) were grown in a replicated split‐plot design using open‐top field chambers under ambient (357 μmol/mol) and elevated (705 μmol/mol) atmospheric CO2. At anthesis, leaf disks were taken from upper mature leaves of soybean and from the third leaf below the head of sorghum for analysis of plant nutrients. Leaf greenness was measured with a Minolta SPAD‐502 chlorophyll meter. Concentrations of chlorophylls a and b and specific leaf weight were also measured. Above‐ground dry matter and seed yield were determined at maturiry. Seed yield of sorghum increased 17.5% and soybean seed yield increased 34.7% with elevated CO2. There were no differences in extractable chlorophyll concentration or chlorophyll meter readings du.
SMART: Stroke-Like Migraine Attacks After Radiation Therapy

We describe two adults with stroke-like migraine attacks after radiation therapy (SMART syndrome), propose revised diagnostic criteria, and review the previously reported patients. ‘SMART’ is an acronym for a newly recognized syndrome which occurs as a delayed consequence of cerebral irradiation and consists of prolonged, unilateral, migrainous neurological symptoms with transient, dramatic cortical gadolinium enhancement of the affected cerebral hemisphere and is sometimes punctuated by generalized seizures and ipsilateral EEG slowing. Although the neurological symptoms can last for weeks, full recovery occurs. An appropriate evaluation should exclude alternative explanations.
SOI single-electron transistor with low RC delay for logic cells and SET/FET hybrid ICs

We report on a successful fabrication of silicon-based single-electron transistors (SETs) with low RC time constant and their applications to complementary logic cells and SET/field-effect transistor (FET) hybrid integrated circuit. The SETs were fabricated on a silicon-on-insulator (SOI) structure by a pattern-dependent oxidation (PADOX) technique, combined with e-beam lithography. Drain conductances measured at 4.2 K approach large values of the order of microsiemens, exhibiting Coulomb oscillations with peak-to-valley current ratios /spl Gt/1000. Data analysis with a probable mechanism of PADOX yields their intrinsic speeds of /spl sim/ 2 THz, which is within an order of magnitude of the theoretical quantum limit. Incorporating these SETs as basic elements, in-plane side gate-controlled complementary logic cells and SET/FET hybrid integrated circuits were fabricated on an SOI chip. Such an in-plane structure is very efficient in the Si fabrication process, and the side gates adjacent to the electron island could easily control the phase of Coulomb oscillations. The input-output voltage transfer, characteristic of the logic cell, shows an inverting behavior where the output voltage gain is estimated to be about 1.2 at 4.2 K. The SET/FET hybrid integrated circuit consisting of one SET and three FETs yields a high-voltage gain and power amplification with a wide-range output window for driving the next circuit. The small SET input gate voltage of 30 mV is finally converted to 400 mV, corresponding to an amplification ratio of 13.
Keratin 8 phosphorylation regulates keratin reorganization and migration of epithelial tumor cells

Cell migration and invasion are largely dependent on the complex organization of the various cytoskeletal components. Whereas the role of actin filaments and microtubules in cell motility is well established, the role of intermediate filaments in this process is incompletely understood. Organization and structure of the keratin cytoskeleton, which consists of heteropolymers of at least one type 1 and one type 2 intermediate filament, are in part regulated by post-translational modifications. In particular, phosphorylation events influence the properties of the keratin network. Sphingosylphosphorylcholine (SPC) is a bioactive lipid with the exceptional ability to change the organization of the keratin cytoskeleton, leading to reorganization of keratin filaments, increased elasticity, and subsequently increased migration of epithelial tumor cells. Here we investigate the signaling pathways that mediate SPC-induced keratin reorganization and the role of keratin phosphorylation in this process. We establish that the MEK–ERK signaling cascade regulates both SPC-induced keratin phosphorylation and reorganization in human pancreatic and gastric cancer cells and identify Ser431 in keratin 8 as the crucial residue whose phosphorylation is required and sufficient to induce keratin reorganization and consequently enhanced migration of human epithelial tumor cells.
Coping with Interpersonal Conflicts at Work: An Examination of the Goodness of Fit Hypothesis Among Nurses

This Dissertation is brought to you for free and open access. It has been accepted for inclusion in Dissertations and Theses by an authorized administrator of PDXScholar. For more information, please contact pdxscholar@pdx.edu. Recommended Citation Wright, Robert Randon, "Coping with Interpersonal Conflicts at Work: An Examination of the Goodness of Fit Hypothesis Among Nurses" (2012). Dissertations and Theses. Paper 610.
Thread clustering: sharing-aware scheduling on SMP-CMP-SMT multiprocessors

The major chip manufacturers have all introduced chip multiprocessing (CMP) and simultaneous multithreading (SMT) technology into their processing units. As a result, even low-end computing systems and game consoles have become shared memory multiprocessors with L1 and L2 cache sharing within a chip. Mid- and large-scale systems will have multiple processing chips and hence consist of an SMP-CMP-SMT configuration with non-uniform data sharing overheads. Current operating system schedulers are not aware of these new cache organizations, and as a result, distribute threads across processors in a way that causes many unnecessary, long-latency cross-chip cache accesses. In this paper we describe the design and implementation of a scheme to schedule threads based on sharing patterns detected online using features of standard performance monitoring units (PMUs) available in today's processing units. The primary advantage of using the PMU infrastructure is that it is fine-grained (down to the cache line) and has relatively low overhead. We have implemented our scheme in Linux running on an 8-way Power5 SMP-CMP-SMT multi-processor. For commercial multithreaded server workloads (VolanoMark, SPECjbb, and RUBiS), we are able to demonstrate reductions in cross-chip cache accesses of up to 70%. These reductions lead to application-reported performance improvements of up to 7%.
Eliciting design requirements for maintenance-oriented IDEs: a detailed study of corrective and perfective maintenance tasks

Several innovative tools have found their way into mainstream use in modern development environments. However, most of these tools have focused on creating and modifying code, despite evidence that most of programmers' time is spent understanding code as part of maintenance tasks. If new tools were designed to directly support these maintenance tasks, what types would be most helpful? To find out, a study of expert Java programmers using Eclipse was performed. The study suggests that maintenance work consists of three activities: (1) forming a working set of task-relevant code fragments; (2) navigating the dependencies within this working set; and (3) repairing or creating the necessary code. The study identified several trends in these activities, as well as many opportunities for new tools that could save programmers up to 35% of the time they currently spend on maintenance tasks.
Collection depots facility location problems in trees

We consider a generalization of the median and center facility location problem called the collection depots facility location (CDFL) problem. We are given a set of client locations and a set of collection depots and we are required to find the placement for a certain number of facilities, so that the cost of dispatching a vehicle from a facility, to a client, to a collection depot, and back, is optimized for all clients. The CDFL center problem minimizes the cost of the most expensive vehicle tour among all clients, and the CDFL median problem minimizes the sum of the tour costs for all clients. We provide the first polynomial time algorithms to solve the 1 and k median problems in trees with time complexities O(n log n) and O(kn3), respectively, where n is the number of vertices in the tree. In contrast, a restricted version of the k‐median problem, where clients are given lists of allowed collection depots, is NP‐complete even for star graphs. We also give an optimal linear time algorithm to solve the discrete and continuous weighted 1‐center problem, improving on the O(n log n) result of Tamir and Halman [Discrete Optimization 2(2005), 168–184]. © 2008 Wiley Periodicals, Inc. NETWORKS, 2009
H19 non coding RNA-derived miR-675 enhances tumorigenesis and metastasis of breast cancer cells by downregulating c-Cbl and Cbl-b

H19 is a long non-coding RNA precursor of miR-675microRNA. H19 is increasingly described to play key roles in the progression and metastasis of cancers from different tissue origins. We have previously shown that the H19 gene is activated by growth factors and increases breast cancer cell invasion. In this study, we established H19/miR-675 ectopic expression models of MDA-MB-231 breast cancer cells to further investigate the underlying mechanisms of H19 oncogenic action. We showed that overexpression of H19/miR-675 enhanced the aggressive phenotype of breast cancer cells including increased cell proliferation and migration in vitro, and increased tumor growth and metastasis in vivo. Moreover, we identified ubiquitin ligase E3 family (c-Cbl and Cbl-b) as direct targets of miR-675 in breast cancer cells. Using a luciferase assay, we demonstrated that H19, through its microRNA, decreased both c-Cbl and Cbl-b expression in all breast cancer cell lines tested. Thus, by directly binding c-Cbl and Cbl-b mRNA, miR-675 increased the stability and the activation of EGFR and c-Met, leading to sustained activation of Akt and Erk as well as enhanced cell proliferation and migration. Our data describe a novel mechanism of protumoral action of H19 in breast cancer.
LIN28 Is Involved in Glioma Carcinogenesis and Predicts Outcomes of Glioblastoma Multiforme Patients

LIN28, an evolutionarily conversed RNA binding protein which can bind to the terminal loops of let-7 family microRNA precursors and block their processing to maturation, is highly expressed in several subsets of tumors that carry poor prognoses, such as ovarian carcinoma, hepatocellular carcinoma, colon carcinoma and germ cell carcinoma. However, there has been no study on the expression of LIN28 in glioma tissues or their importance as a prognostic predictor of glioma patients. This study aimed to examine the expression of LIN28 in glioma and correlate the results to patient outcome. We found that LIN28 expression was significantly higher in the group of patients with a poor prognosis compared to patients with a good prognosis by gene microarray. Log-rank analysis showed patients with higher LIN28 expression level in tumor had a shorter progression-free survival and overall survival times compared to those with lower LIN28 expression level. Similar results were also obtained from the tissue microarray analysis. Univariate and multivariate analyses showed high LIN28 expression was an independent prognostic factor for a shorter progression-free survival and overall survival in GBM patients. Furthermore in vitro experiments showed that down-regulation of LIN28 in U251 and U373 cells caused cell cycle arrest in the G1 phase, delayed cell proliferation, increased apoptosis, and resulted in fewer colonies compared to controls. Summarily, our data provides a potential target for cancer therapy as an approach to overcome the poor options currently available for GBM patients.