Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor-specific silencing of COPZ2 gene encoding coatomer protein complex subunit ζ2 renders tumor cells dependent on its paralogous gene COPZ1

Anticancer drugs are effective against tumors that depend on the molecular target of the drug. Known targets of cytotoxic anticancer drugs are involved in cell proliferation; drugs acting on such targets are ineffective against nonproliferating tumor cells, survival of which leads to eventual therapy failure. Function-based genomic screening identified the coatomer protein complex ζ1 (COPZ1) gene as essential for different tumor cell types but not for normal cells. COPZ1 encodes a subunit of coatomer protein complex 1 (COPI) involved in intracellular traffic and autophagy. The knockdown of COPZ1, but not of COPZ2 encoding isoform coatomer protein complex ζ2, caused Golgi apparatus collapse, blocked autophagy, and induced apoptosis in both proliferating and nondividing tumor cells. In contrast, inhibition of normal cell growth required simultaneous knockdown of both COPZ1 and COPZ2. COPZ2 (but not COPZ1) was down-regulated in the majority of tumor cell lines and in clinical samples of different cancer types. Reexpression of COPZ2 protected tumor cells from killing by COPZ1 knockdown, indicating that tumor cell dependence on COPZ1 is the result of COPZ2 silencing. COPZ2 displays no tumor-suppressive activities, but it harbors microRNA 152, which is silenced in tumor cells concurrently with COPZ2 and acts as a tumor suppressor in vitro and in vivo. Silencing of microRNA 152 in different cancers and the ensuing down-regulation of its host gene COPZ2 offer a therapeutic opportunity for proliferation-independent selective killing of tumor cells by COPZ1-targeting agents.
Attitudes and Satisfaction of Nurses with the Work Environment in Turkey

www.internationaljournalofcaringsciences. org Original Article Attitudes and Satisfaction of Nurses with the Work Environment in Turkey Guler Duru Asiret, PhD Assistant Professor, Nursing Department, Faculty of Health Science, Aksaray University, Aksaray, Turkey Sevgisun Kapucu, PhD Associate Professor, Internal Medicine Nursing Department, Faculty of Nursing, Hacettepe University, Ankara, Turkey Tekmile Kurnaz Kose, MSc Ankara University, Ibnı Sina Hospital, Nursing Services Director, Ankara, Turkey Berna Kurt, MSc Research Assistant, Internal Medicine Nursing Depar tment, Faculty of Nursing, Hacettepe University, Ankara, Turkey Neşe Altınok Ersoy, MSc Research Assistant, Internal Medicine Nursing Depar tment, Faculty of Nursing, Hacettepe University, Ankara, Turkey Correspondence: Assist. Prof. Guler Duru A şiret, Aksaray University, Nursing Department, Faculty of Health Science, 68100, Aksaray, Turkey E -mail: gulerduru@gmail.com Abstract Background: The satisfaction of the nurses can be influenced b y factors affecting the working environment and working environment. Aim: The aim of this study was to determine the effect of the factors affecting nurses' work environment and the work environment itself on the satisfaction of nurses. Methods: A total of 327 nurses were administered an introdu ctory questionnaire, the Practice Environment Scale of the Nursing Work Index (PES-NW I) and the Employee Satisfaction Scale (ESS) in our descriptive study. Results: The mean PES-NWI score was 2.6 ±0.4 and the mean ESS score was 79.69. The highest mean score among the PES-NWI sub-dimensions was for staffing and resource adequacy (3.0±0.5) while the lowest mean score was for nursing foundat ions for quality of care (2.3±0.5). The ESS increased as the PES-NWI score increased (r =-.772, p=0.000). Conclusions: We found that the attitudes of the nurses regarding the work environment and their vocational satisfaction were moderate and the age, educational level and work duration affected the attitude regarding the work environment.
The Effect of Various Durations of Noise Exposure on Auditory Brainstem Response, Distortion Product Otoacoustic Emissions and Transient Evoked Otoacoustic Emissions in Rats

This study was designed to investigate the effect of various durations of noise exposure in animals on physiological responses from the cochlea which are also used clinically in humans: auditory brainstem response (ABR), transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs). Rats were exposed to 113 dB SPL broad-band noise (12 h on/12 h off) for durations of 3, 6, 9, 12, 15 and 21 days, and tested 24 h after cessation of the noise and again after a period of 6 weeks. ABR threshold to click stimuli and to a 2-kHz tone burst (TB), TEOAE energy content and DPOAE amplitude in the exposed rats were compared to those in a group of control rats not exposed to noise. ABR thresholds (click and TB) were significantly elevated in all exposure duration groups compared to control rats. DPOAE amplitudes and TEOAE energy content were significantly reduced. The mean ABR thresholds following 21 days exposure were significantly greater (click = 100 dB pe SPL; TB = 115 dB pe SPL) than those following 3 days exposure (click = 86 dB pe SPL; TB = 91 dB pe SPL). Linear regression analysis between recorded responses and duration of noise exposure (days) showed a significant increase in ABR thresholds of approximately 0.8– 1.4 dB/day. TEOAE and DPOAE responses showed no such dependence on noise duration and were already maximally reduced after only 3 days of exposure. This can be explained by the possibility that short noise exposures may cause damage to the early, more active stages of cochlear transduction (as shown by TEOAEs and DPOAEs). As the noise exposure continues, further damage may be induced at additional, later stages of the cochlear transduction cascade (as shown by ABR). Thus, ABR seems more sensitive to noise duration than OAE measures.
Dichotic-listening performance and intracarotid injections of amobarbital in children and adolescents. Preoperative and postoperative comparisons.

BACKGROUND Dichotic listening (DL) to consonant-vowel syllables is frequently used in clinical and experimental studies of brain laterality. However, the paradigm of consonant-vowel syllables has not been thoroughly validated through a comparison with injections of amobarbital sodium (Amytal). OBJECTIVE To validate the DL test for hemisphere dominance preoperatively vs postoperatively with the results from intracarotid injections of amobarbital (i.e., the Wada test) in epileptic children and adolescents. DESIGN AND MAIN OUTCOME MEASURES Patients were tested with DL preoperatively and at 6-month follow-up. Correct reports in the DL tests were entered in a stepwise discriminant analysis for calculation of correct classification of hemisphere dominance with the results from the injections of amobarbital as the grouping variable. Correct reports from the right and left ears on the consonant-vowel DL test were compared preoperatively and postoperatively, separated for the subjects with regard to language dominance in the left and right hemispheres. SETTING The Department of Pediatrics, Ostra Hospital, University of Göteborg, Göteborg, Sweden. PATIENTS Thirteen children and adolescents between the ages of 10 and 19 years, who were surgically treated for resistant epilepsy, were included in the study. The operated area corresponded with morphological changes and functional dysfunctions according to findings from computed tomography, magnetic resonance imaging, single photon emission computed tomography, and electroencephalography. RESULTS The results of the Wada tests revealed that 10 subjects had left hemisphere language dominance, with 3 subjects having right hemisphere language dominance. All 3 subjects with right hemisphere language dominance showed a left ear advantage on the DL test preoperatively and postoperatively, with 8 and 7 of the 10 subjects with left hemisphere dominance showing a right ear advantage, preoperatively and postoperatively, respectively. However, according to discriminant analysis, knowledge of the DL performance led to a correct classification according to the Wada test results in 12 (92%) of the 13 subjects. CONCLUSIONS A quantitative classification procedure like discriminant analysis may be more sensitive when predicting hemisphere speech dominance from DL data than a qualitative procedure based on the ear advantage dichotomy. The ear advantage dichotomy may actually introduce arbitrary left-right categories that do not correspond to the actual clustering of the data.
γ-H2AX in Cancer Cells: A Potential Biomarker for Cancer Diagnostics, Prediction and Recurrence

Current advances in cancer biology have identified major pathways involved in tumorigenesis. The association of DNA damage with premalignant stages of tumor progression, genome instability and further oncogenic transformation opens the possibility of using common DNA damage markers for early cancer detection, prediction, prognosis, therapeutics and possibly for cancer prevention. Perhaps the most sensitive DNA damage marker is γ-H2AX formation in the chromatin flanking the free DNA double-stranded ends in double-strand breaks (DSBs) and eroded telomeres, both present during oncogenic transformation. Our group and others found elevated endogenous levels of γ-H2AX in various human cancer cell lines, premalignant lesions and solid tumors. These data suggest that increased DNA damage is a general characteristic of cancer development. γ-H2AX-based assay can be applied to human biopsies, aspirates and, possibly, to mononuclear cells of the peripheral blood. We propose that detection of γ-H2AX could benefit for the early cancer screening and to ascertain the efficiency of clinical treatment involving chemo- and radiotherapeutic protocols.
Asymmetric structure and domain binding interfaces of human tyrosyl‐tRNA synthetase studied by molecular dynamics simulations

Human tyrosyl‐tRNA synthetase (HsTyrRS) is composed of two structural modules: N‐terminal catalytic core and an EMAP II‐like C‐terminal domain. The structures of these modules are known, but no crystal structure of the full‐length HsTyrRS is currently available. An all‐atom model of the full‐length HsTyrRS was developed in this work. The structure, dynamics, and domain binding interfaces of HsTyrRS were investigated by extensive molecular dynamics (MD) simulations. Our data suggest that HsTyrRS in solution consists of a number of compact asymmetric conformations, which differ significantly by their rigidity, internal mobility, orientation of C‐terminal modules, and the strength of interdomain binding. Interfaces of domain binding obtained in MD simulations are in perfect agreement with our previous coarse‐grained hierarchical rotations technique simulations. Formation of the hydrogen bonds between R93 residue of the ELR cytokine motif and the residues A340 and E479 in the C‐module was observed. This observation supports the idea that the lack of cytokine activity in the full‐length HsTyrRS is explained by interactions between N‐modules and C‐modules, which block the ELR motif. Copyright © 2013 John Wiley & Sons, Ltd.
An association of the MCP-1 and CCR2 single nucleotide polymorphisms with colorectal cancer prevalence.

THE AIM OF THE STUDY We evaluated the connection between the presence of the -2518 A/G MCP-1 as well as 190 G/A CCR2 polymorphic variants and colorectal cancer (CRC) occurrence. MATERIAL AND METHODS Study group consisted of subjects with different stages of CRC as well as healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS W observed an association between the colorectal cancer and the GG genotype of the -2518 A/G MCP-1 single nucleotide polymorphism. No statistically significant correlation was found between CRC and the 190 G/A CCR2 polymorphism. CONCLUSION The results of this study support the hypothesis that polymorphism in the MCP-1 gene may contribute to the etiology of colorectal cancer.
Clonal propagation of Epstein-Barr virus (EBV) recombinants in EBV-negative Akata cells

We lack a host cell supporting an efficient lytic replication of Epstein-Barr virus (EBV). Recently, we isolated EBV-negative cell clones from the Akata cell line (referred as Akata- [N. Shimizu, A. Tanabe-Tochikura, Y. Kuroiwa, and K. Takada, J. Virol. 68:6069-6073, 1994). Since the parental Akata line is one of the highest EBV producers, we examined whether Akata- cells had become a good host for EBV propagation. The parental Akata cells have about 20 copies of EBV plasmid per cell. A drug resistance gene was inserted into one of them by homologous recombination. The resultant virus preparation, a mixture of wild-type and recombinant EBV, was used to infect Akata- cells. After incubation in the selective medium, drug-resistant Akata- cell clones were isolated and proved to be infected with recombinant EBV only. By treatment of the cells with antiimmunoglobulin antibodies, a large amount of recombinant EBV (i.e., more than 10 microg/1-liter culture) was produced. In contrast, three other B-lymphoma lines, BJAB, Ramos, and Louckes, were nonpermissive for virus replication. These results indicate that Akata- cells are suitable for propagation of recombinant EBV clonally, which becomes a powerful tool for determining EBV genetics and which makes it possible to use EBV as a vector for gene therapy.
SUMOylation substrates in neuronal intranuclear inclusion disease

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized pathologically by the presence of ubiquitinated intranuclear inclusions (NII) in neuronal cells. We demonstrate that NIIs in both sporadic and familial NIID contained the small ubiquitin modifier‐1 (SUMO‐1) and the SUMOylation substrates promyelocytic leukaemia protein (PML) and histone deacetylase 4 (HDAC4). Both PML and SUMO‐1 are major components of nuclear bodies (NBs), suggesting that the NIIs in NIID, as well as the intranuclear inclusions in polyglutamine diseases, might derive from these intranuclear functional domains that serve as sites for ubiquitin‐related protein degradation. HDAC4 was also a major component of the NIIs. HDACs are transcriptional corepressors that regulate histone remodelling, and NBs are thought to be sites at which the level of histone acetylation is controlled. The presence of PML, SUMO‐1 and HDAC4 in NIIs suggests that transcriptional activity regulated by histone acetylation might contribute to the disease process in NIID. In addition, we showed that another SUMOylation substrate, RanGAP1 is associated with NIIs only in the familial NIID patient. This might be explained by different pathogenetic mechanisms underlying subcategories of NIID, which is very heterogeneous.
Salivary gland scintigraphy in Sjögren’s syndrome

Summary The aim of this study was to compare the diagnostic utility of visual versus semiquantitative analysis of salivary gland scintigraphy in the diagnosis of Sjögren’s syndrome (SS). Patients, methods: 99mTc-pertech- netate salivary gland scintigraphy was performed in 145 patients (133 women, 12 men) with clinically suspicious SS. The images were interpreted with visual and semiquantitative methods and the diagnostic performances for SS were compared using uptake and excretory functional parameters. Results: In total, 76 patients (52.4%) were finally diagnosed with SS. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of visual analysis for the diagnosis of SS were 88.2%, 48.6%, 65.1%, 79.1%, and 69.2%, respectively. Semiquantitative values, the area under the ROC curve for uptake ratio and percentage excretion in the right salivary glands were significantly greater than 0.5 (p < 0.05). However, the percentage excretion in the left salivary glands did not show a statistically significant diagnostic ability for SS. The diagnostic ability of visual assessment was greater than that of the semiquantitative method in terms of evaluating uptake and excretory function in the sub- mandibular glands. Conclusion: Visual analysis of salivary gland scintigraphy showed greater diagnostic utility than semiquantitative assessment in the diagnosis of SS, especially in the submandibular glands.
Efficacy of turkey herpesvirus vaccine against Marek's disease in broilers.

Abstract In three different broiler producing areas in Georgia, a total of 2,500,000, broilers were vaccinated at one day of age with various doses of turkey herpesvirus (HVT) vaccine ranging from 200 to 2600 plaque forming units (PFU) per bird. Approximately 600,000 broilers reared in separate houses on the same farms served as unvaccinated controls. All groups were identified and processed separately. Very little effect on reduction of condemnations for Marek’s disease was realized with doses of vaccine greater than 1000 PFU per bird. If the advantages of weight gains of vaccinated birds were not taken into consideration, 500 PFU per bird gave the best return on money invested for vaccine when the vaccine cost was $50 per thousand doses. However, when the cost of vaccine was reduced to ten dollars per 1000 doses the 1000 PFU dose was more advantageous. A dose of approximately 1000 PFU per bird also yielded a better return on money spent for the HVT vaccine because of the advantages of increased body weight and livability.
Interviewers' perceptions of persons-organization fit and organizational selection decisions.

A model of person-organization fit and organizational hiring decisions is developed and tested, using data from 38 interviewers making hiring decisions about 93 applicants. Results suggest that interviewers can assess applicant-organization values congruence with significant levels of accuracy and that interviewers compare their perceptions of applicants' values with their organizations' values to assess person-organization fit. Results also suggested that interviewers' subjective person-organization fit assessments have large effects on their hiring recommendations relative to competing applicant characteristics, and that interviewers' hiring recommendations directly affect organizations' hiring decisions (e.g., job offers).
Authenticity of pronunciation in naturalistic second language acquisition: The case of very advanced late learners of Dutch as a second language

The article reports on the fourth study in a series of four designed to test the prediction that a nativelike accent is unattainable for those who start to acquire an SL after the close of the critical period. Sentences read out by late learners, who acquired Dutch in an immersion setting, were rated for accent by native speakers of Dutch. The results from this study, in combination with those from three previous studies, suggest that, in spite of the claims of the critical period hypothesis, late learners can achieve a nativelike accent in an SL, and that a combination of input, motivational, and instructional factors may compensate for the neurological disadvantages of a late start.
Earlier Treatment May Explain Diabetes Data

In the News Focus story “Paradoxical effects of tightly controlled blood sugar” (17 October 2008, p. [365][1]), G. Taubes reported that tight glucose control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD), ADVANCE, and Veterans Affairs Diabetes Trial (VADT) trials failed to
Deficiency of regulatory T cells in children with autoimmune neutropenia

CD4+ 25+ regulatory T cells (Tregs) play a role in controlling the development and progression of autoimmunity. The transcription factors Foxp3 and NFATC2 (NFAT1) play key roles in regulating the development and function of Tregs. The present study examined the involvement of Tregs in the pathophysiology of autoimmune neutropenia in children. Tregs were analysed by flow cytometry, based on the expressions of CD4, CD25, and intracellular Foxp3. The expressions of FOXP3 and NFATC2 mRNA in the CD4+ 25+ cells were determined by quantitative real‐time polymerase chain reaction. The percentage of CD4+ 25high Tregs in patients with autoimmune neutropenia was significantly lower than that in age‐matched healthy subjects. The intracellular expression of Foxp3 of CD4+ 25+ cells in patients similarly decreased in comparison to that in healthy subjects. The expression of FOXP3 and NFATC2 mRNA of CD4+ 25+ cells in patients also significantly decreased in comparison to that in healthy subjects. These results suggest that the deficiency of Tregs might thus play an important role in the immunopathophysiology of autoimmune neutropenia in children.
Permutation decoding for codes from designs, finite geometries and graphs

Permutation decoding was introduced by MacWilliams [Mac64] in the early 60’s. It can be used when a linear code has a sufficiently large automorphism group to ensure the existence of a set of automorphisms, called a PD-set, that has some specifed properties. This series of talks will describe the method and some recent developments in finding PD-sets for codes defined through the row-span over finite fields of incidence matrices of classes of designs or graphs, and adjacency matrices of classes of regular graphs. These codes have many properties that can be deduced from the combinatorial properties of the designs or graphs, and often have a great deal of symmetry and large automorphism groups. J.D. Key (keyj@clemson.edu) Permutation decoding ASI Croatia June 2010 2 / 81
Comparison of techniques for detecting antigens of Giardia lamblia and Cryptosporidium parvum in faeces.

AIM--To compare the use of commercial monoclonal antibody test systems--the Giardia CEL IF test and the Crypto CEL IF test--for the detection of Giardia lamblia and Cryptosporidium parvum antigens in faeces with conventional techniques. METHODS--Sensitivity and specificity were evaluated using preparations of cysts of G lamblia and purified oocysts of C parvum. Evaluation of 59 random faecal samples passing through the Department of Clinical Parasitology, Hospital for Tropical Diseases, London, was carried out for both organisms. RESULTS--The fluorescence staining techniques proved more sensitive than other tests routinely used for diagnosis.
Avoiding false positive diagnoses of motor neuron disease: lessons from the Scottish Motor Neuron Disease Register.

OBJECTIVES--To describe the frequency and characteristics of those patients initially registered with the Scottish Motor Neuron Disease Register (SMNDR) but who subsequently had a diagnosis other than MND made (false positives), to analyse the features which led to a revised diagnosis, and to draw conclusions which might improve routine neurological practice. METHODS--The Scottish Motor Neuron Disease Register is a community based, prospective disease register to identify and follow up all incident cases of motor neuron disease in Scotland. Fifty three patients out of a total of 552 registered are presented, who, after initial registration, were later excluded because they failed to satisfy the register's diagnostic criteria. RESULTS--Seven of these patients were labelled as "MND plus" syndromes and may represent a distinct subset of MND. The remaining 46 patients had an alternative diagnosis made (false positive group), accounting for 8% of the total. In half of these cases, potentially beneficial therapies are available. The predominant reasons which lead to a diagnostic revision were: failure of symptom progression, development of atypical clinical features for MND, and investigation results. CONCLUSIONS--Patients with MND should undergo thorough and relevant investigations at presentation with the emphasis on neuroradiological imaging and neurophysiology; all patients should be followed up by an experienced neurologist, particularly those in whom symptoms and signs are restricted to either the bulbar or spinal muscles; failure of symptom progression or development of atypical features should lead to an early reassessment; finally, patients should be informed of the diagnosis only when it is secure.