Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative PCR – new diagnostic tool for quantifying specific mRNA and DNA molecules: HER2/neu DNA quantification with LightCycler real‐time PCR in comparison with immunohistochemistry and fluorescence in situ hybridization

Previously, polymerase chain reaction (PCR) technology has been hampered by its inability to generate quantitative results, a drawback inherent to the high degree of amplification taking place in the reaction. Recently, PCR techniques have been described with the potential of quantifying the amount of mRNA or DNA in biological samples. In this study quantitative PCR was used to investigate the role of the EGF (epidermal growth factor) system in cancer both for measurements of mRNA concentrations and for measurements of the number of copies of specific genes. It is shown that the mRNA expression of a subset of ligands from the EGF system is increased in bladder cancer. Furthermore, measurement of the mRNA concentration gives important information such as the expression of these ligands correlated to the survival of the patients. In addition to the alterations at the mRNA level, changes also can occur at the DNA level in the EGF system. Thus, it has been demonstrated that the number of genes coding for the human epidermal growth factor receptor 2 (HER2) is increased in a number of breast tumors. It is now possible to treat breast cancer patients with a humanized antibody reacting with HER2, and the treatment is considered to be justified if the tumor displays an increased amount of HER2. For this reason there is a need for techniques suitable for HER2 measurements. A LightCycler real‐time PCR method used for HER2/neu DNA quantification was evaluated and the results compared with those obtained by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Tumor biopsies were collected from 112 patients diagnosed with early breast cancer from January 1990 to March 1994. The samples were analyzed for HER2 DNA amplification by real‐time PCR on LightCycler and by FISH and for HER2 protein expression by IHC. Inter‐assay variation for HER2 measured by LightCycler was 10% (×=3.1; n=17). Amplification ≥2 was observed in 19% of the patients. Concordance rates between real‐time PCR and the other methods were 91% (IHC) and 92% (FISH). The correlation between real‐time PCR and FISH was highly significant (p<0.001). The “LightCycler‐HER2/neu DNA quantification kit” produces results with a high level of reproducibility and its ease of use allows rapid screening for amplification of HER2. In this paper useful information is given on how real‐time PCR compares with FISH and IHC. The data show that results obtained for amplification of HER2 by real‐time PCR on the LightCycler instrument are comparable to results obtained by IHC and FISH.
Long non‐coding RNAs in nuclear bodies

High‐throughput analyses of mammalian transcriptomes have revealed that more than half of the transcripts produced by RNA polymerase II are non‐protein‐coding. One class of these non‐coding transcripts is the long non‐coding RNAs (lncRNAs), which are more than 200 nucleotides in length and are molecularly indistinguishable from other protein‐coding mRNAs. Although the molecular functions of these lncRNAs have long remained unknown, emerging evidence implicates the functional involvement of lncRNAs in the regulation of gene expression through the modification of chromatin, maintenance of subnuclear structures, transport of specific mRNAs, and control of pre‐mRNA splicing. Here, we discuss the functions of a distinct group of vertebrate‐specific lncRNAs, NEAT1/MENε/β/VINC, MALAT1/NEAT2, and Gomafu/RNCR2/MIAT, which accumulate abundantly within the nucleus as RNA components of specific nuclear bodies.
Electrical Control of Epileptic Seizures

Summary: Epilepsy is among the most common neurologic disorders, yet it is estimated that about one third of patients do not respond favorably to currently available drug treatments and up to 50% experience major side effects of these treatments. Although surgical resection of seizure foci can provide reduction or cessation of seizure incidents, a significant fraction of pharmacologically intractable seizure patients are not considered viable candidates for such procedures. Research advances in applying electrical stimulation as an alternative treatment for intractable epilepsy have been reported. The primary focus of these studies has been the search for optimized stimulation protocols by which to electrically suppress, revert or prevent seizures. In this review, the authors discuss some of the promising results that have been achieved. These results are organized in three broad categories based on how such protocols are generated. They focus on how information of the electrical activity in the brain is incorporated in the control schemes, namely: open loop, semiclosed loop, and closed loop protocols. Benefits, potential promises, and challenges of these different control techniques are discussed.
The Hidden Costs and Returns of Incentives - Trust and Trustworthiness Among CEOS

We examine experimentally how Chief Executive Officers (CEOs) respond to incentives and how they provide incentives in situations requiring trust and trustworthiness. As a control we compare the behavior of CEOs with the behavior of students. We find that CEOs are considerably more trusting and exhibit more trustworthiness than students—thus reaching substantially higher efficiency levels than students. Moreover, we find that, for CEOs as well as for students, incentives based on explicit threats to penalize shirking backfire by inducing less trustworthy behavior—giving rise to hidden costs of incentives. However, the availability of penalizing incentives also creates hidden returns: if a principal expresses trust by voluntarily refraining fromimplementingthepunishmentthreat, theagentexhibitssignificantlymoretrustworthiness than if the punishment threat is not available. Thus trust seems to reinforce trustworthy behavior. Overall, trustworthiness is highest if the threat to punish is available but not used, while it is lowest if the threat to punish is used. Paradoxically, however, most CEOs and students use the punishment threat, although CEOs use it significantly less. (JEL: C91, C92, J30, J41)
Acute exposure to apolipoprotein A1 inhibits macrophage chemotaxis in vitro and monocyte recruitment in vivo

Apolipoprotein A1 (apoA1) is the major protein component of high-density lipoprotein (HDL) and has well documented anti-inflammatory properties. To better understand the cellular and molecular basis of the anti-inflammatory actions of apoA1, we explored the effect of acute human apoA1 exposure on the migratory capacity of monocyte-derived cells in vitro and in vivo. Acute (20–60 min) apoA1 treatment induced a substantial (50–90%) reduction in macrophage chemotaxis to a range of chemoattractants. This acute treatment was anti-inflammatory in vivo as shown by pre-treatment of monocytes prior to adoptive transfer into an on-going murine peritonitis model. We find that apoA1 rapidly disrupts membrane lipid rafts, and as a consequence, dampens the PI3K/Akt signalling pathway that coordinates reorganization of the actin cytoskeleton and cell migration. Our data strengthen the evidence base for therapeutic apoA1 infusions in situations where reduced monocyte recruitment to sites of inflammation could have beneficial outcomes. DOI: http://dx.doi. org/10.7554/eLife.15190. 001
Evaluation of the RIM-N, Gonochek II, and Phadebact systems for the identification of pathogenic Neisseria spp. and Branhamella catarrhalis

Methods for identifying Neisseria spp. include conventional and modified carbohydrate degradation procedures, chromogenic enzyme substrate tests, and immunologic coagglutination tests for Neisseria gonorrhoeae. In this study, we evaluated the abilities of the RIM-N carbohydrate degradation system (American MicroScan, Campbell, Calif.), the Gonochek II enzymatic identification system (Du Pont Co., Wilmington, Del.), and the Phadebact Gonococcus coagglutination test (Pharmacia Diagnostics, Piscataway, N.J.) to identify pathogenic Neisseria spp. and Branhamella catarrhalis. Both stock strains and clinical isolates, including 176 N. gonorrhoeae, 173 Neisseria meningitidis, 48 Neisseria lactamica, and 12 B. catarrhalis strains, were tested. The RIM-N identified 98% of the gonococci, 99% of the meningococci, 94% of the N. lactamica strains, and 100% of the B. catarrhalis strains within 1 h. The Gonochek II system identified 99% of the gonococci, 97% of the meningococci, 100% of the N. lactamica strains, and 100% of the B. catarrhalis strains within 30 min. Phadebact coagglutination provided clearly positive results for only 77% of the N. gonorrhoeae strains, producing negative or equivocal results with 23% of the strains. The RIM-N and Gonocheck II tests generally produced clear-cut reactions. An additional advantage of the Gonocheck II system was the small inoculum required for the performance of the test compared with the other systems, thus allowing the identification of N. gonorrhoeae directly from the primary isolation medium.
Examining the effects of brief training on the attitudes and future use of behavioral methods by teachers

Teachers from government and independent schools anonymously completed a measure of attitudes towards applied behavior analysis (ABA) before and after participation in a short seminar on ABA. A total of 187 primary teachers provided data on professional qualifications, years of teaching, school type, number of students in the classroom, and prior knowledge of ABA. Data were also collected on the number of students with a disability the teacher had instructed. Survey results suggested that, before and after the seminar, teachers held negative attitudes towards ABA. These attitudes, however, significantly and positively shifted after attending the seminar. Neither the number of students taught with a disability over the last 5 years nor teacher type (e.g., specialist or classroom) nor school type (e.g., independent or government) was significantly related to the attitude measure. The findings have implications for ongoing teacher education and professional development, as well as for school psychologists tailoring interventions and framing recommendations for teachers in mainstream primary settings. Copyright © 2014 John Wiley & Sons, Ltd.
Screening for Lynch Syndrome in Cases with Colorectal Carcinoma from Mashhad.

INTRODUCTION Lynch Syndrome (LS) is a genetically inherited autosomal disorder that increases the risk of many types of cancer, especially colorectal cancer (CRC). Identifying these subjects improves morbidity and mortality. We aimed to assess the prevalence of LS with both clinical criteria and universal strategy in Mashhad, Iran. METHODS In this retrospective study, we screened 322 patients with CRC between 2013 and 2016 in Mashhad, Iran. CRCs were screened based on Amsterdam II criteria, revised Bethesda guideline, and universal strategy. Information regarding the clinical criteria was obtained by interviewing the patients or, their families. Tumors were screened by pathologists with IHC staining of four Mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, and PMS2). Tumors with absent IHC staining of MLH1 were tested for BRAF mutations to exclude sporadic CRCs. RESULTS Of 322 CRCs, 33 cases were found to be deficient-MMR; 22 of these had concurrent loss of MLH1 and PMS2, followed by concurrent loss of MSH2 and MSH6 in 8 CRCs. Twenty-two cases with a loss of MLH1 underwent testing for the BRAF mutation, 4 of which were recognized as a positive BRAF mutation. Finally, 29 CRCs were found as being positive screen for LS. Poor sensitivity (21.74%) was found for the Amsterdam II criteria and a poor positive predictive value (15.39%) for the revised Bethesda. CONCLUSION Application of clinical criteria may not be effective enough to identify LS and at least 2-antibody panel (PMS2, MSH6) should be conducted for newly diagnosed CRCs.
Dynamic Metabolite Profiling in an Archaeon Connects Transcriptional Regulation to Metabolic Consequences

Previous work demonstrated that the TrmB transcription factor is responsible for regulating the expression of many enzyme-coding genes in the hypersaline-adapted archaeon Halobacterium salinarum via a direct interaction with a cis-regulatory sequence in their promoters. This interaction is abolished in the presence of glucose. Although much is known about the effects of TrmB at the transcriptional level, it remains unclear whether and to what extent changes in mRNA levels directly affect metabolite levels. In order to address this question, here we performed a high-resolution metabolite profiling time course during a change in nutrients using a combination of targeted and untargeted methods in wild-type and ΔtrmB strain backgrounds. We found that TrmB-mediated transcriptional changes resulted in widespread and significant changes to metabolite levels across the metabolic network. Additionally, the pattern of growth complementation using various purines suggests that the mis-regulation of gluconeogenesis in the ΔtrmB mutant strain in the absence of glucose results in low phosphoribosylpyrophosphate (PRPP) levels. We confirmed these low PRPP levels using a quantitative mass spectrometric technique and found that they are associated with a metabolic block in de novo purine synthesis, which is partially responsible for the growth defect of the ΔtrmB mutant strain in the absence of glucose. In conclusion, we show how transcriptional regulation of metabolism affects metabolite levels and ultimately, phenotypes.
When Subcategorization Facilitates Group Cohesion

This paper analyzes the conditions under which groups composed of two opposing factions are able to preserve group cohesion and subgroup opinion divisions simultaneously. Results from two experimental studies conducted with small interactive groups showed that groups with opposing factions were able to preserve subgroup divergence without jeopardizing superordinate group cohesion. A process termed relational regulation of ingroup opinion divisions explains these findings: The more group members perceived the group as promoting good relations, the more they maintained or even radicalized their initial opinions. In contrast, in an experimental context in which opinion divergences were not reinforced by subcategorization, we observed convergence toward a unique group position destined to maintain group cohesion that was independent of the perceived relational norm.
How Can We Plan for Progression in Primary School History

This paper addresses issues concerning planning for and assessing progression in children’s thinking in primary school history. It argues that it is necessary to assess progression within the framework of constructivist learning theories, applied to the processes of historical enquiry. First, it discusses early research into children’s ability to understand concepts of time, historical sources and interpretations. Next, it describes the structure of the English National Curriculum, introduced in 1989, in which pupils are required to apply the processes of historical enquiry to content, in increasingly complex ways. The problem of what is meant by progression in history led to a large-scale research project attempting to identify patterns of development. It is argued that this proved problematic, and the level descriptors for the English History Curriculum have subsequently been removed. The article concludes that, at the moment, progression can be best planned for based on small-scale case studies, which apply constructivist theories to historical enquiries. Finally, suggestions are given for how teachers can plan and evaluate both their own practice and their pupils’ progress.
Long-term survival after surgery for primary hepatic sarcoma in adults.

HYPOTHESIS Patients with primary hepatic sarcomas benefit from resection, with possible long-term cure. DESIGN Retrospective and prospective cohort study. SETTING University hospitals of Hamburg-Eppendorf and Düsseldorf, Germany. PATIENTS Between 1985 and 2006, 22 patients (8 men and 14 women; median age at initial diagnosis, 54 years [range, 19-80 years]) were surgically treated for primary hepatic sarcomas. INTERVENTION Tumor resection with curative intent ranging from nonanatomical resection to liver transplant. MAIN OUTCOME MEASURES Effects on overall survival were analyzed using the log-rank test. RESULTS The majority of tumors were more than 5 cm (n = 19), with a median tumor size of 7 cm (range, 4-14 cm); of intermediate differentiation (G2; n = 15); and classified as leiomyosarcoma (n = 7). Ten patients received a hemihepatectomy. In 4 patients, a bisegmentectomy was performed and in 2 patients, a segmentectomy, while 4 patients received a nonanatomical resection. Liver transplant was performed in 2 patients. In 18 patients, complete tumor resection (R0) was achieved. Perioperative mortality was 0%. Median follow-up was 88 months (range, 6-246 months). Local recurrence occurred in 6 patients. Distant metastases were diagnosed in 10 patients, predominantly in the lung (n = 6). The 5-year survival after surgery was 65%, with 41% of the patients living more than 10 years without disease. Patients with angiosarcoma had a poor prognosis (P = .03). CONCLUSIONS Although primary hepatic sarcoma is a rare malignant tumor, no standard treatment is established. A long-term survival is possible after complete tumor resection in a preselected population with early-stage disease.
Developing Cultural Awareness: The Text-Driven Approach as Evidence of a Good Language Teaching Practice

The present article reports a descriptive and explanatory case study, whose objective was to identify and describe to what extend students develop cultural awareness through activities designed under the principles of the Text-Driven Approach (TDA). This approach, presented by Brian Tomlinson, answers the question of how a second language can be learned or acquired in the most effective way in the classroom, and also aims to design interesting materials for students which lead them to think, reflect, and communicate. The research deals with developing cultural awareness in Elementary English students in the Modern Languages Degree at Pontificia Universidad Javeriana. Basically, the research development comprised 3 stages. The first one consisted of the identification of the problem, which was intended to figure out if students develop cultural awareness in their English classes; the second stage was intended to design a set of activities following the TDA principles. Said design became the core of the pedagogical intervention to give answers to the problem found. The third stage was featured by the implementation of the activities in two different classrooms for a period of three months. During such implementation of the activities, data were collected by using 3 important instruments: the observation sheets, which were helpful in order to gather information about observable students’ behaviors (what students do). The second instrument was a questionnaire, in which students had the opportunity to express what they thought and learned during the implementation of the activities (what students say they do) and finally, we count on artifacts from students (what students really do), regarding the activities designed in order to develop cultural awareness; such artifacts were found by means of the teacher’s guide, the document in which the activities were presented. Therefore, the same phenomenon was observed from 3 different perspectives obtaining a triangulation, a technique, which was considered the most appropriate to do the analysis of the data. The information collected led researchers to 4 important categories through which answers were given to the research question: knowledge (savoir), socio-cultural competence (savoir fare), attitude (savoir etre), understanding ‘’the other’’. Such categories allowed researchers to classify the information gathered and obtain the preliminary findings, which showed that the activities designed definitely developed cultural awareness to some extend in Elementary English students.
Comorbidity and age are both independent predictors of length of hospitalization in trauma patients.

BACKGROUND Length of hospitalization is a good indicator of resource utilization. Older patients are increasingly suffering trauma, and comorbid medical conditions are also increasing. Our objective was to determine the separate and combined effect of these 2 factors on length of hospital stay for trauma patients in a tertiary trauma centre. METHODS All 994 consecutive trauma patients surviving to hospital discharge between Apr. 1, 2000, and Mar. 31, 2001, were identified. Patient characteristics, injury severity and length of hospitalization were obtained from the hospital trauma registry. Each medical record was then reviewed for completeness of information and assessment of comorbid conditions. A multivariate linear regression model was developed to predict logarithmic length of stay from age and presence of a cormorbid condition while adjusting for the Injury Severity Score (ISS). RESULTS The mean age of the patients was 49.7 (range from 14-100) years and median ISS was 9 (range from 1-50). At least 1 comorbid condition was present in 321 (32%) patients. Mean length of hospital stay was 15.3 days. The proportion of patients with a comorbid condition increased steadily with age, from 8.7% before the age of 55 years to 92% at 85 or more years of age (p < 0.001). According to the multivariate model, the presence of comorbidity, age and ISS were all independent predictors of hospital stay (p < 0.001). When applied to patients with the mean ISS value of 9, the model showed an increase in length of hospitalization for patients with a comorbid condition over those without; (3.6 v. 13.1 d for patients < 55 and > or = 85 yr respectively). Length of hospital stay increased particularly with neurologic and pulmonary problems. CONCLUSIONS Comorbidity and age were both independently significant predictors of length of hospitalization over and beyond that which is expected based on the severity of the injuries. With an aging population, this phenomenon should severely affect resource utilization in trauma centres in the near future. Researchers should take account of both age and comorbidity in order to compare trauma populations.
Postprandial Plasma ApoB-48 Levels Are Influenced by a Polymorphism in the Promoter of the Microsomal Triglyceride Transfer Protein Gene

The microsomal triglyceride transfer protein (MTP) plays a key role in the secretion of apolipoprotein B (apoB)-containing lipoproteins. The rare variant of a functional polymorphism in the promoter region of the MTP gene has been associated with elevated transcriptional activity of the gene in vitro (MTP−493G/T). With use of a “recruit-by-genotype” approach, we investigated one of the potentially complex phenotypes of this polymorphism, the appearance in plasma of apoB-48 after a meal intake. A total of 12 homozygous carriers of the rare MTP−493T variant were identified from a population-based screening of 50-year-old healthy white men. All subjects were of the apoE3/3 genotype. Along with 48 baseline well-matched heterozygotes (n=24) plus homozygotes (n=24) for the common variant, they were given a standardized oral fat meal. Postprandial plasma concentrations of apoB-48 were determined by the combination of density gradient ultracentrifugation and analytical SDS-PAGE. The postprandial plasma concentrations of triglycerides did not differ between the groups, but homozygous carriers of the rare MTP−493T variant showed a >100% greater increase in apoB-48 in the smallest (Svedberg flotation rate constant 20 to 60) triglyceride-rich lipoprotein fraction (P =0.005). These data support the notion that elevated transcriptional activity of MTP leads to an increased generation of the smallest triglyceride-rich lipoprotein from the intestine.