Miracle-dz/UniFAR-FTUs huggingface dataset:
Endoscopic Endonasal Approach for Nonvestibular Schwannomas

BACKGROUND Nonvestibular schwannomas of the skull base often represent a challenge owing to their anatomic location. With improved techniques in endoscopic endonasal skull base surgery, resection of various ventral skull base tumors, including schwannomas, has become possible. OBJECTIVE To assess the outcomes of using endoscopic endonasal approach (EEA) for nonvestibular schwannomas of the skull base. METHODS Seventeen patients operated on for skull base schwannomas by EEA at the University of Pittsburgh Medical Center from 2003 to 2009 were reviewed. RESULTS Three patients underwent combined approaches with retromastoid craniectomy (n = 2) and orbitopterional craniotomy (n = 1). Three patients underwent multistage EEA. The rest received a single EEA operation. Data on degree of resection were found for 15 patients. Gross total resection (n = 9) and near-total (>90%) resection (n = 3) were achieved in 12 patients (80%). There were no tumor recurrences or postoperative cerebrospinal fluid leaks. In 3 of 7 patients with preoperative sensory deficits of trigeminal nerve distribution, there were partial improvements. Patients with preoperative reduced vision (n = 1) and cranial nerve VI or III palsies (n = 3) also showed improvement. Five patients had new postoperative trigeminal nerve deficits: 2 had sensory deficits only, 1 had motor deficit only, and 2 had both motor and sensory deficits. Three of these patients had partial improvement, but 3 developed corneal neurotrophic keratopathy. CONCLUSION An EEA provides adequate access for nonvestibular schwannomas invading the skull base, allowing a high degree of resection with a low rate of complications. ABBREVIATIONS CN: cranial nerve EEA: endoscopic endonasal approach ICA: internal carotid artery RMC: retromastoid craniectomy
A Multiparent Advanced Generation Inter-Cross to Fine-Map Quantitative Traits in Arabidopsis thaliana

Identifying natural allelic variation that underlies quantitative trait variation remains a fundamental problem in genetics. Most studies have employed either simple synthetic populations with restricted allelic variation or performed association mapping on a sample of naturally occurring haplotypes. Both of these approaches have some limitations, therefore alternative resources for the genetic dissection of complex traits continue to be sought. Here we describe one such alternative, the Multiparent Advanced Generation Inter-Cross (MAGIC). This approach is expected to improve the precision with which QTL can be mapped, improving the outlook for QTL cloning. Here, we present the first panel of MAGIC lines developed: a set of 527 recombinant inbred lines (RILs) descended from a heterogeneous stock of 19 intermated accessions of the plant Arabidopsis thaliana. These lines and the 19 founders were genotyped with 1,260 single nucleotide polymorphisms and phenotyped for development-related traits. Analytical methods were developed to fine-map quantitative trait loci (QTL) in the MAGIC lines by reconstructing the genome of each line as a mosaic of the founders. We show by simulation that QTL explaining 10% of the phenotypic variance will be detected in most situations with an average mapping error of about 300 kb, and that if the number of lines were doubled the mapping error would be under 200 kb. We also show how the power to detect a QTL and the mapping accuracy vary, depending on QTL location. We demonstrate the utility of this new mapping population by mapping several known QTL with high precision and by finding novel QTL for germination data and bolting time. Our results provide strong support for similar ongoing efforts to produce MAGIC lines in other organisms.
The Effect of Authentic Leadership, Person-Job Fit, and Civility Norms on New Graduate Nurses’ Experiences of Coworker Incivility and Burnout

OBJECTIVE:This study examined the influence of authentic leadership, person-job fit with 6 areas of worklife, and civility norms on coworker incivility and burnout among new graduate nurses. BACKGROUND:New graduate nurses report experiencing high levels of workplace incivility from coworkers, which has been found to negatively impact their job and career satisfaction and increase their intention to leave. The role of civility norms in preventing burnout and subsequent exposure to incivility from coworkers has yet to be examined among new graduate nurses. METHODS:A cross-sectional mail survey of 993 new graduate nurses across Canada was conducted. RESULTS:The results supported the hypothesized relationships between study variables. CONCLUSIONS:Civility norms play a key role in preventing early career burnout and coworker incivility experienced by new graduate nurses. Leaders can influence civility norms by engaging in authentic leadership behaviors and optimizing person-job fit.
Apatinib for the treatment of gastric cancer

Introduction: Antiangiogenesis therapy plays an important role in cancer treatment. Apatinib mesylate, a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, has been recommended as third-line treatment for metastatic gastric cancer patients. Areas covered: The current review summarizes the publications and conference reports relating to apatinib from preclinical and clinical research in gastric cancer. Apatinib showed good safety, tolerance and treatment efficacy in Phase I/II studies. In a Phase III study, apatinib prolonged the median overall survival of patients with chemotherapy-refractory metastatic gastric cancer by 55 days and the median progression-free survival by 25 days compared with placebo. Expert opinion: Apatinib is a new treatment option for advanced gastric cancer. Apatinib is expected to have a broader application when it has been evaluated worldwide. The key issues are to find biomarkers and overcome drug resistance.
Inductive Sparse Subspace Clustering

Sparse subspace clustering (SSC) has achieved state-of-the-art clustering quality by performing spectral clustering over an l1-norm based similarity graph. However, SSC is a transductive method, i.e. it cannot handle out-of-sample data that is not used to construct the graph. For each new datum, SSC requires solving n optimisation problems in O(n) variables, where n is the number of data points. Therefore, it is inefficient to apply SSC in fast online clustering and scalable grouping. An inductive spectral clustering algorithm called inductive SSC (iSSC) is proposed, which makes SSC feasible to cluster out-of-sample data. iSSC adopts the assumption that high-dimensional data actually lie on the low-dimensional manifold such that out-of-sample data could be grouped in the embedding space learned from in-sample data. Experimental results show that iSSC is promising in clustering out-of-sample data.
Revisiting the JDL Data Fusion Model II

Abstract : This paper suggests refinements and extensions of the JDL Data Fusion Model, the standard process model used for a multiplicity of community purposes. However, this Model has not been reviewed in accordance with (a) the dynamics of world events and (b) the changes, discoveries, and new methods in both the data fusion research and development community and related IT technologies. This paper suggests ways to revise and extend this important model. Proposals are made regarding (a) improvements in the understanding of internal processing within a fusion node and (b) extending the model to include (1) remarks on issues related to quality control, reliability, and consistency in DF processing, (2) assertions about the need for co-processing of abductive/ inductive and deductive inferencing processes, (3) remarks about the need for and exploitation of an onto logically-based approach to DF process design, and (4) extensions to account for the case of Distributed Data Fusion (DDF).
Anomalous slip in Mo-5 at.% Nb and Mo-5 at.% Re alloy single crystals

Abstract Single crystals of Mo-5 at. % Nb and Mo-5 at. % Re have been deformed in compression at 77 K. Anomalous slip was observed to occur for orientations X≲0° in the case of the niobium alloy and for orientations X≲-10° for the rhenium alloy. These results are in direct contrast to those found for other body-centred cubic metals where anomalous slip is observed. Here both substitutional and interstitial alloying are found to destroy anomalous slip.
Cleavage of Automodified Poly(ADP-ribose) Polymerase during Apoptosis

The abundant nuclear enzyme poly(ADP-ribose) polymerase (PARP) synthesizes poly(ADP-ribose) in response to DNA strand breaks. During almost all forms of apoptosis, PARP is cleaved by caspases, suggesting the crucial role of its inactivation. A few studies have also reported a stimulation of PARP during apoptosis. However, the role of PARP stimulation and cleavage during this cell death process remains poorly understood. Here, we measured the stimulation of endogenous poly(ADP-ribose) synthesis during VP-16-induced apoptosis in HL60 cells and found that PARP was cleaved by caspases at the time of its poly(ADP-ribosyl)ation. In vitro experiments showed that PARP cleavage by caspase-7, but not by caspase-3, was stimulated by its automodification by long and branched poly(ADP-ribose). Consistently, caspase-7 exhibited an affinity for poly(ADP-ribose), whereas caspase-3 did not. In addition, caspase-7 was activated and accumulated in the nucleus of HL60 cells in response to the VP-16 treatment. Furthermore, caspase-7 activation was concommitant with PARP cleavage in the caspase-3-deficient cell line MCF-7 in response to staurosporine treatment. These results strongly suggest that, in vivo, it is caspase-7 that is responsible for PARP cleavage and that poly(ADP-ribosyl)ation of PARP accelerates its proteolysis. Cleavage of the active form of caspase substrates could be a general feature of the apoptotic process, ensuring the rapid inactivation of stress signaling proteins.
Immunofluorescence evidence for the absence of histone H1 in a mitotically dividing, genetically inactive nucleus

Antibodies directed against whole histone and purified lysine-rich histone H1 extracted from isolated macronuclei of the ciliate Tetrahymena were obtained and conjugated to fluorescein isothiocyanate. The fluorescein-antibody conjugates were used to directly label Tetrahymena cells. Both macro- and micronuclei were visibly fluorescent in cells stained with anti-whole histone conjugate. However, the anti- H1 conjugate only labeled macronuclei. This in situ demonstration of the lack of positive immunofluorescent staining of micronuclei with anti-H1 conjugate provide further evidence for the absence of H1 in the genetically inactive, mitotically dividing Tetrahymena micronucleus.
Ischemia and gangrene of the penis.

Penile ischemia and gangrene can be caused by penile prostheses, severe diabetes, thrombolic phenomena and a buildup of calcium deposits in patients on dialysis. Acute ischemia of the penis is rarely seen because of the excellent collateral circulation of the perineum and lower abdomen.1 There are at least 3 mechanisms for acute ischemia of the male genitalia—widespread ligation of collateral circulation to the penis, spontaneous embolism and operative embolism. Other forms of venous infarction can occur from priapism and intracorporeal injection of pharmacotherpeutic agents. Gradual necrosis has been seen with low cardiac output and renal failure.1 We report 3 cases of penile ischemia and discuss their management, as well as review the literature. CASE REPORTS Case 1. A 52-year-old male with type I diabetes mellitus and on hemodialysis presented with increased glucose levels. The distal one-third of the glans penis was necrotic, and the rest of the shaft was mildly indurated. The patient was offered observation initially, with partial penectomy if the disease progressed. He underwent circumcision for better
Title: Notch Pathway Inhibition Significantly Reduces Rhabdomyosarcoma Invasiveness and Mobility in Vitro

Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. ACKNOWLEDGMENTS The authors wish to thank Ms Marta Valeri for technical support with the in vivo wound-healing assay, Ms Paqui Gallego for technical support with the real-time PCR assays and Ms Christine O'Hara for help with the English version of this manuscript. Carlos III (RTICC, RD06/0020/1021), Asociación Española contra el cáncer-Catalunya contra el càncer, Fundació SMALL and Fundació FADAM. RMS patients with metastatic disease continue to have very poor prognosis, despite the indication of aggressive therapies. Moreover, the major cause of death in these patients is the formation of distant metastases. This work states that the Notch pathway is broadly expressed in RMS tumors and its inhibition in vitro using γ-secretase inhibitors clearly impairs the mobility and invasiveness of RMS cells. This work proposes the Notch pathway as a candidate for the development of targeted therapies focused on reducing metastases in this neoplasia. Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. ABSTRACT Purpose: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and can be divided into two main subtypes: embryonal and alveolar RMS. Patients with metastatic disease continue to have very poor prognosis although aggressive therapies and recurrences are common in advanced localized disease. The oncogenic potential of the Notch pathway has been established in some cancers of the adult and in some pediatric malignancies. Experimental Design: A real-time PCR assay was used to ascertain the expression of several Notch pathway components in a wide panel of RMS and cell lines. Four γ-secretase inhibitors (GSIs) were tested for pathway inhibition and the degree of inhibition was assessed by analysis of Hes1 and Hey1 expression. The putative effects of Notch pathway inhibition were evaluated by wound-healing, matrigel/transwell invasion, cell-cycle and apoptosis assays. Results: The Notch pathway was widely expressed and activated in RMS and underwent substantial inhibition when treated with GSIs or transfected with a dominant negative form of MAML1. RMS cells showed a significant decrease in its mobility and invasiveness when the Notch pathway was properly inhibited; conversely, its inhibition had no noticeable effect on cell cycle or apoptosis. …
Mapping the conformation of a client protein through the Hsp70 functional cycle

Significance Hsp70 chaperones are key components of the cellular proteostasis network. The ATP-dependent interaction of Hsp70 with its substrates prevents aggregation and promotes their correct folding and maturation. Here we investigate the impact of Hsp70 binding on the conformation of a client substrate using nuclear magnetic resonance spectroscopy. Our experiments provide a model for Hsp70 action in which the substrate can adopt substantial amounts of secondary structure even in the globally unfolded Hsp70-bound state. Moreover, the substrate conformation does not evolve as a function of the Hsp70 nucleotide state, demonstrating that the large structural changes in Hsp70 resulting from ATP binding and hydrolysis do not perform conformational work on the bound substrate or lead to changes in client protein conformation. The 70 kDa heat shock protein (Hsp70) chaperone system is ubiquitous, highly conserved, and involved in a myriad of diverse cellular processes. Its function relies on nucleotide-dependent interactions with client proteins, yet the structural features of folding-competent substrates in their Hsp70-bound state remain poorly understood. Here we use NMR spectroscopy to study the human telomere repeat binding factor 1 (hTRF1) in complex with Escherichia coli Hsp70 (DnaK). In the complex, hTRF1 is globally unfolded with up to 40% helical secondary structure in regions distal to the binding site. Very similar conformational ensembles are observed for hTRF1 bound to ATP-, ADP- and nucleotide-free DnaK. The patterns in substrate helicity mirror those found in the unfolded state in the absence of denaturants except near the site of chaperone binding, demonstrating that DnaK-bound hTRF1 retains its intrinsic structural preferences. To our knowledge, our study presents the first atomic resolution structural characterization of a client protein bound to each of the three nucleotide states of DnaK and establishes that the large structural changes in DnaK and the associated energy that accompanies ATP binding and hydrolysis do not affect the overall conformation of the bound substrate protein.
Max- and sum-separable Lyapunov functions for monotone systems and their level sets

For interconnected systems and systems of large size, aggregating information of subsystems studied individually is useful for addressing the overall stability. In the Lyapunov-based analysis, summation and maximization of separately constructed functions are two typical approaches in such a philosophy. This paper focuses on monotone systems which are common in control applications and elucidates some fundamental limitations of max-separable Lyapunov functions in estimating domains of attractions. This paper presents several methods of constructing sum- and max-separable Lyapunov functions for second order monotone systems, and some comparative discussions are given through illustrative examples.
Knockdown of FLOT1 Impairs Cell Proliferation and Tumorigenicity in Breast Cancer through Upregulation of FOXO3a

Purpose: Lipid rafts, specialized domains in cell membranes, function as physical platforms for various molecules to coordinate a variety of signal transduction processes. Flotinllin-1 (FLOT1), a marker of lipid rafts, is involved in the progression of cancer, but the precise mechanism remains unclear. The aim of the present study was to examine the role of FLOT1 on the tumorigenesis of breast cancer cells and its clinical significance in progression of the disease. Experimental Design: FLOT1 expression was analyzed in 212 paraffin-embedded, archived clinical breast cancer samples by using immunohistochemistry (IHC). The effect of FLOT1 on cell proliferation and tumorigenesis was examined in vitro and in vivo. Western blotting and luciferase reporter analyses were carried out to identify the effects of downregulating FLOT1 on expression of cell cycle regulators and transcriptional activity of FOXO3a. Results: IHC analysis revealed high expression of FLOT1 in 129 of the 212 (60.8%) paraffin-embedded archived breast cancer specimens. The overall expression level of FLOT1 significantly correlated with clinical staging and poor patient survival of breast cancer. Strikingly, we found that silencing FLOT1 inhibited proliferation and tumorigenicity of breast cancer cells both in vitro and in vivo, which was further shown to be mechanistically associated with suppression of Akt activity, enhanced transcriptional activity of FOXO3a, upregulation of cyclin-dependent kinase inhibitor p21Cip1 and p27Kip1, and downregulation of the CDK regulator cyclin D1. Conclusions: FLOT1 plays an important role in promoting proliferation and tumorigenesis of human breast cancer and may represent a novel prognostic biomarker and therapeutic target for the disease. Clin Cancer Res; 17(10); 3089–99. ©2011 AACR.
MEMS-based dispenser array for selective immobilization of molecular recognition elements on bio-image sensor

Selective immobilization of molecular recognition elements on bio-image sensor permits detection of different type of target analytes in a single chip. For the selective immobilization, we designed two types of MEMS-based dispenser array, 2D and 3D dispenser arrays. 2D dispenser embedding microchannels is placed on a senor substrate contacting the sensor elements to introduce biomolecules. Fabrication of a 2D dispenser array requires multi-layer architecture and through holes. PDMS through holes were formed via replication from a two-layer SU-8 mold. We measured transportation of particles through a via-hole. We fabricated top and bottom layer structures of 2D dispenser array. Attachment of a probe array to a microchip enables dispensing multiple droplets containing biomolecules from the probe array. We fabricated probe tips of a 3D dispenser array having 32 × 32 of SiO2 tapered probes with aperture diameters of 37.2 μm by MEMS fabrication technology.
Application of immunoassay for detection of Helicobacter pylori antigens in the dental plaque.

PURPOSE The aim of this study was to determine the viability of the commercial test currently used for detection of H. pylori antigens in the stool for detection of H. pylori antigens in dental plaque. MATERIALS AND METHODS A total of 164 dyspeptic patients entered the study; 95 H. pylori infected (positive result of at least 4 of 5 diagnostic tests: Campylobacter-like organisms test (CLO test), histology, culture, stool antigens, serology) and 69 noninfected (negative results of 4 diagnostic tests: CLO test, histology, culture, stool antigens). Dental plaque was collected from natural teeth of the patients and incubated in microaerophilic conditions for 72 hours before immunoassay. RESULTS Experimental findings included that optimal dental plaque weight to perform the examination was over 2 mg and that preliminary incubation increased significantly the number of positive results (p<0.002). It was also found that H. pylori antigens in the dental plaque were positive in 81.2% of infected and only 17.7% of non-infected subjects (p<0.001), while the reproducibility of results was 95%. CONCLUSIONS The immunoassay for detection of H. pylori antigens in the stool may be used, after minor adaptations (specifically pre-incubation in microaerophilic conditions) for H. pylori antigen detection in dental plaque.
Fibrinolysis is essential for fracture repair and prevention of heterotopic ossification.

Bone formation during fracture repair inevitably initiates within or around extravascular deposits of a fibrin-rich matrix. In addition to a central role in hemostasis, fibrin is thought to enhance bone repair by supporting inflammatory and mesenchymal progenitor egress into the zone of injury. However, given that a failure of efficient fibrin clearance can impede normal wound repair, the precise contribution of fibrin to bone fracture repair, whether supportive or detrimental, is unknown. Here, we employed mice with genetically and pharmacologically imposed deficits in the fibrin precursor fibrinogen and fibrin-degrading plasminogen to explore the hypothesis that fibrin is vital to the initiation of fracture repair, but impaired fibrin clearance results in derangements in bone fracture repair. In contrast to our hypothesis, fibrin was entirely dispensable for long-bone fracture repair, as healing fractures in fibrinogen-deficient mice were indistinguishable from those in control animals. However, failure to clear fibrin from the fracture site in plasminogen-deficient mice severely impaired fracture vascularization, precluded bone union, and resulted in robust heterotopic ossification. Pharmacological fibrinogen depletion in plasminogen-deficient animals restored a normal pattern of fracture repair and substantially limited heterotopic ossification. Fibrin is therefore not essential for [. ] Research Article Bone biology