Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells

Breast cancer is the most common type of malignancy among females. Previous studies examining breast cancer tissue have demonstrated the presence of stem cells, and have detected octamer-binding protein 4 (Oct4) and Nanog transcription factor expression. In the present study, breast cancer stem cells (CSCs) were isolated and enriched from MDA-MB-231 breast cancer cell lines, and were defined as MDA-MB-231 stem cells using flow cytometry. The expression of Oct4 and Nanog in breast CSCs were detected by quantitative polymerase chain reaction and western blotting. RNA interference (RNAi) was used in order to downregulate the expression of Oct4 and Nanog. Drug resistance and tumor-initiating capability following in vivo injection of MDA-MB-231 stem cells transduced with negative RNAi, Oct4 RNAi and Nanog RNAi were compared with that of MDA-MB-231 stem cells without siRNA transfection as a control group. In addition the capability of MDA-MB-231 breast cancer cells to initiate tumor formation in mice was compared with that of MDA-MB-231 stem cells. A paclitaxel inhibition test was also conducted in order to detect resistance of MDA-MB-231 breast cancer stem cells to this treatment. The MDA-MB-231 stem cells were revealed to exhibit elevated percentages of the cluster of differentiation (CD)44+CD24−/low subset, high tumorigenicity and resistance to chemotherapy, all of which are characteristic stem cell properties. In addition, the MDA-MB-231 stem cells were more tumorigenic in vivo. Furthermore, the breast CSCs also expressed high levels of the Oct4 and Nanog transcription factors. Therefore, downregulation of Oct4 or Nanog expression may reduce chemotherapeutic drug resistance and tumorigenicity in breast CSCs. In conclusion, Oct4 and Nanog expression may be a key factor in the development of resistance to chemotherapy and tumor growth of breast CSCs. This finding indicates that Oct4 or Nanog-targeted therapy may be a promising means of overcoming resistance to chemotherapy and inhibiting tumor growth in breast cancer treatment.
Characterizing the Spatio-temporal Dynamics of the Neural Events Occurring prior to and up to Overt Recognition of Famous Faces

Although it is generally acknowledged that familiar face recognition is fast, mandatory, and proceeds outside conscious control, it is still unclear whether processes leading to familiar face recognition occur in a linear (i.e., gradual) or a nonlinear (i.e., all-or-none) manner. To test these two alternative accounts, we recorded scalp ERPs while participants indicated whether they recognize as familiar the faces of famous and unfamiliar persons gradually revealed in a descending sequence of frames, from the noisier to the least noisy. This presentation procedure allowed us to characterize the changes in scalp ERP responses occurring prior to and up to overt recognition. Our main finding is that gradual and all-or-none processes are possibly involved during overt recognition of familiar faces. Although the N170 and the N250 face-sensitive responses displayed an abrupt activity change at the moment of overt recognition of famous faces, later ERPs encompassing the N400 and late positive component exhibited an incremental increase in amplitude as the point of recognition approached. In addition, famous faces that were not overtly recognized at one trial before recognition elicited larger ERP potentials than unfamiliar faces, probably reflecting a covert recognition process. Overall, these findings present evidence that recognition of familiar faces implicates spatio-temporally complex neural processes exhibiting differential pattern activity changes as a function of recognition state.
Natural Selection on Coding and Noncoding DNA Sequences Is Associated with Virulence Genes in a Plant Pathogenic Fungus

Natural selection leaves imprints on DNA, offering the opportunity to identify functionally important regions of the genome. Identifying the genomic regions affected by natural selection within pathogens can aid in the pursuit of effective strategies to control diseases. In this study, we analyzed genome-wide patterns of selection acting on different classes of sequences in a worldwide sample of eight strains of the model plant-pathogenic fungus Colletotrichum graminicola. We found evidence of selective sweeps, balancing selection, and positive selection affecting both protein-coding and noncoding DNA of pathogenicity-related sequences. Genes encoding putative effector proteins and secondary metabolite biosynthetic enzymes show evidence of positive selection acting on the coding sequence, consistent with an Arms Race model of evolution. The 5′ untranslated regions (UTRs) of genes coding for effector proteins and genes upregulated during infection show an excess of high-frequency polymorphisms likely the consequence of balancing selection and consistent with the Red Queen hypothesis of evolution acting on these putative regulatory sequences. Based on the findings of this work, we propose that even though adaptive substitutions on coding sequences are important for proteins that interact directly with the host, polymorphisms in the regulatory sequences may confer flexibility of gene expression in the virulence processes of this important plant pathogen.
A distinct clinical phenotype in a German kindred with motor neuron disease carrying a CHCHD10 mutation.

Sir, Emerging data provide evidence for CHCHD10 as a new candidate gene in familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (Bannwarth et al., 2014; Johnson et al., 2014; Müller et al., 2014). This gene encodes a mitochondrial protein located in the intermembrane space (Bannwarth et al., 2014). Mutant CHCHD10 may lead to altered mitochondrial genome stability and maintenance of cristae junctions (Bannwarth et al., 2014; Chaussenot et al., 2014). So far, three different mutations located either in the non-structured N-terminal region or in the -helix of the CHCHD10 gene have been attributed to cause both ALS and ALS-FTD phenotypes. Here we report another large German family with a history suggestive of autosomal-dominant motor neuron disorder (Fig. 1). After excluding a repeat expansion in C9orf72 and mutations in 25 other known ALS genes in parallel by next-generation sequencing we performed whole-exome sequencing of three affected individuals (Patients III.1, III.2 and III.9). This identified a heterozygous c.44G4T variant (p.Arg15Leu) in exon 2 of the CHCHD10 gene which has recently been reported by Müller et al. (2014) as the likely cause of pure ALS in two German families and was also identified in three families with familial motor neuron disease in the USA (Johnson et al., 2014). The mutation segregated with disease in another cousin (Patient III.5) of our index patient (Patient III.1) and could not be identified in his 41-year-old son (Patient IV.1) and an 85-year-old aunt (Patient II.7), who are both unaffected. No DNA samples were available from the deceased Patients I.1, II.3, II.6 and II.9, as well as from further to-date unaffected family members. However, because of the variable age of onset ranging from 41 to 73 years (59.5 11.2 years; mean SD) only such individuals without clinical signs of a motor neuron disorder clearly after the latest disease onset within the family may really be regarded healthy. In our case, only individuals from the second generation (Fig. 1) would now have fulfilled this criterion with all other unaffected family members still being at risk. Of note, seven of eight affected patients were males. All of them were diagnosed with motor neuron disease/ALS. Similar to the German families carrying the p.Arg15Leu mutation described by Müller et al. (2014), all of our patients exhibited upper limb onset exclusively, presenting with progressive, mostly atonic paresis, muscle wasting and fasciculations in either proximal (Patients II.6 and III.1 with symmetrical onset) or distal muscles (Patients III.2, III.5 and III.9 with a more asymmetrical distribution at onset), spreading out slowly and leading to severe disability of the upper extremities as disease progressed. At least three patients developed bulbar symptoms, however, not requiring supplemental tube feeding. None showed emotional instability. Patients III.1, III.2, III.5 and III.9 doi:10.1093/brain/awv014 BRAIN 2015: 138; 1–3 | e376
Maternal periconceptional vitamin use, genetic variation of infant reduced folate carrier (A80G), and risk of spina bifida.

Women who consume folic acid in early pregnancy reduced their risks for delivering offspring with neural tube defects (NTDs). The underlying process by which folic acid facilitated this risk reduction is unknown. Investigating genetic variation that influences cellular absorption, transport, and metabolism of folate will help fill this data gap. We focused our studies on a candidate gene that is involved in folate transport, the reduced folate carrier 1 (RFC1). Using data from a California population-based case control interview study (1989-1991 birth cohorts), we investigated whether spina bifida risk was influenced by an interaction between a polymorphism of infant RFC1 at nucleotide 80 (A80G) and maternal periconceptional use of vitamins containing folic acid. Allelic variants of RFC1 were determined by genotyping 133 live-born spina bifida case infants and 188 control infants. The percentages of case infants with the A80/A80, G80/G80, and G80/A80 genotypes were 27.2%, 28.0%, and 44.7%, respectively. The percentages of control infants were similar: 26.1%, 29.3%, and 44.7%. Odds ratios of 1.0 (95% confidence interval 0.5-2.0) for the G80/G80 genotype and 1.1 (0.6-2.0) for the G80/A80 genotype were observed relative to the A80/A80 genotype. Among mothers who did not use vitamins, spina bifida risk was 2.4 (0.8-6.9) for infants with genotype G80/G80 compared to those with A80/A80 genotype. Among mothers who did use vitamins, the risk was 0.5 (0.1-3.1) for infants with the G80/G80 genotype. Although this study did not find an increased spina bifida risk for infants who were heterozygous or homozygous for RFC1 A80G, it did reveal modest evidence for a gene-nutrient interaction between infant homozygosity for the RFC1 G80/G80 genotype and maternal periconceptional intake of vitamins containing folic acid on the risk of spina bifida.
For the Commander

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Meta-Analysis of Studies on Cause and Effects of Runaway Girls in Iran

At the first look, Girls running away from home seems to be personal issue but according to its effects on social order it is the basis of many abnormal social behaviors such as prostitution, alcoholic and narcotic addiction, drug distribution, organizing of gangs, deceiving other women and girls, spreading prostitution, out breaking of sexual diseases and. It also expose them to the serious mental and physical disorders and if we couldn’t solve this problem, we will lose part of work and production force and mental & physical health of considerable amount of future mothers of society. Method of this study is Meta-analysis and consider 26 essays on runaway girls. In the beginning questions from previous studies were asked and then we compared findings and researches. Then we descriptively analyzed the quantity of previous researches and also analyzed the quality of basic concepts and relation between variables. Results showed that there is a meaningful relation between occurrence of girls running from their homes and variables such as age, previous record, marital status, narcotic addiction, interpersonal relation problems, parents’ life style, mental or physical abuse by parents or other members of family, presence of punishment without acclaim, social confidence, economic situation, modelling from groups and having sexual relations. DOI: 10.5901/mjss.2014. v5n23p2006
Community Engagement in Genetic Research: Results of the First Public Consultation for the Quebec CARTaGENE Project

Objective: This paper presents the results of the first public consultation for the creation of a large-scale genetic database, the Quebec CARTaGENE project. A consultation has been undertaken in order to gauge whether the general public is receptive to the project. An integral part of the approach of the researchers is to establish a dialogue with the public. Methods: Two independent expert groups have carried out qualitative and quantitative studies measuring knowledge of and interest in genetics, incentives and obstacles to CARTaGENE participation and comprehension and evaluation of the communication tools. Results: CARTaGENE is seen to hold promise for the greater population. However, reported across qualitative and quantitative studies is the concern for confidentiality and respect for the individual, transparency, the donor’s right to feedback and governance. Participation would be conditional on a response to those concerns and a greater dissemination of information. Conclusion: Community engagement in genetic research requires targeted communications, with an appropriate proportioning of information and communication, and a consideration of the ‘values and personal interests’ of individuals according to different societal segments.
‘They Were Very Threatening about Do-Gooding Bastards’: Probation's Changing Relationships with the Police and Prison Services in England and Wales

In recent decades the probation service has been encouraged to work closely with a range of public and voluntary sector agencies. This article examines probation's changing relationships with the police and prison services drawing on sixty interviews with current and former probation workers. Analysing probation-prison and probation-police relationships pre- and post-1998 and drawing on Davidson's (1976) typology of inter-organisational relationships, the article argues that, despite both structural and cultural transformations, there remain cultural continuities in each organisation that create tensions, the significance (both positive and negative) of which should not be under-estimated.
Involvement of Transforming Growth Factor α in the Regulation of Rat Ovarian X-Linked Inhibitor of Apoptosis Protein Expression and Follicular Growth by Follicle-Stimulating Hormone1

Abstract The expression of X-linked inhibitor of apoptosis protein (XIAP), a member of a family of intracellular antiapoptotic proteins, is induced by FSH during follicular development in vivo. Whether the XIAP up-regulation by FSH (100 ng/ml) is a direct action of the gonadotropin and is important in the control of granulosa cell proliferation during follicular growth is unclear. The overall objective of the present study was to examine whether the FSH-induced XIAP expression and granulosa cell proliferation during follicular development is mediated by the secretion and action of intraovarian transforming growth factor α (TGFα). In rat follicles cultured for 2 and 4 days, FSH stimulated estradiol production, TGFα secretion, XIAP expression, and follicular growth. The theca cells are the primary follicular source of FSH-induced TGFα, as indicated by in situ hybridization. Intrafollicular injection of a neutralizing anti-TGFα antibody (50–200 ng/ml; immunoglobulin G as control) or addition of estradiol-antagonist ICI 182780 (0.5–100 nM) to the culture media suppressed FSH-induced XIAP expression and follicular growth. The effect of ICI 182780 could be partially reversed by high concentrations of estrogen (250 and 500 nM). Whereas TGFα (10–20 ng/ml) significantly increased granulosa cell XIAP content and proliferation in primary granulosa cell cultures, FSH alone was ineffective in eliciting the mitogenic response. Our results support the hypothesis that FSH stimulates granulosa cell proliferation via theca TGFα secretion and action in response to increased granulosa cell estradiol synthesis, and that XIAP up-regulation in response to FSH suppresses granulosa cell apoptosis and facilitates FSH-induced follicular growth.
Designing a Framework for Problem Posing: Young Children Generating Open-Ended Tasks

This article describes the type of problems young children (aged six) generated in problem-posing contexts. With support, the children began to generate increasingly sophisticated problems that were open-ended in nature. The problem-solving situations provided opportunities for the children to pose problems they enjoyed solving and promoted both a more complex and motivating learning environment. The results indicate that the problem-posing actions of students can be nurtured by teachers' actions.
Occlusion-aware interfaces

We define occlusion-aware interfaces as interaction techniques which know what area of the display is currently occluded, and use this knowledge to counteract potential problems and/or utilize the hidden area. As a case study, we describe the Occlusion-Aware Viewer, which identifies important regions hidden beneath the hand and displays them in a non-occluded area using a bubble-like callout. To determine what is important, we use an application agnostic image processing layer. For the occluded area, we use a user configurable, real-time version of Vogel et al.'s [21] geometric model. In an evaluation with a simultaneous monitoring task, we find the technique can successfully mitigate the effects of occlusion, although issues with ambiguity and stability suggest further refinements. Finally, we present designs for three other occlusion-aware techniques for pop-ups, dragging, and a hidden widget.
Acute bacterial meningitis in adults. A review of 493 episodes.

BACKGROUND AND METHODS To characterize acute bacterial meningitis in adults, we reviewed the charts of all persons 16 years of age or older in whom acute bacterial meningitis was diagnosed at Massachusetts General Hospital from 1962 through 1988. We included patients who were admitted after initial treatment at other hospitals. RESULTS During the 27-year period, 445 adults were treated for 493 episodes of acute bacterial meningitis, of which 197 (40 percent) were nosocomial. Gram-negative bacilli (other than Haemophilus influenzae) caused 33 percent of the nosocomial episodes but only 3 percent of the community-acquired episodes. In the 296 episodes of community-acquired meningitis, the most common pathogens were Streptococcus pneumoniae (37 percent), Neisseria meningitidis (13 percent), and Listeria monocytogenes (10 percent); these organisms accounted for only 8 percent of the nosocomial episodes. Only 19 of the 493 episodes of meningitis (4 percent) were due to H. influenzae. Nine percent of all patients had recurrent meningitis; many had a cerebrospinal fluid leak. Seizures occurred in 23 percent of patients with community-acquired meningitis, and 28 percent had focal central nervous system findings. Risk factors for death among those with single episodes of community-acquired meningitis included older age (> or = 60 years), obtunded mental state on admission, and seizures within the first 24 hours. Among those with single episodes, the in-hospital mortality rate was 25 percent for community-acquired and 35 percent for nosocomial meningitis. The overall case fatality rate was 25 percent and did not vary significantly over the 27 years. CONCLUSIONS In our large urban hospital, a major proportion of cases of acute bacterial meningitis in adults were nosocomial. Recurrent episodes of meningitis were frequent. The overall mortality rate remained high.
Early word formation in German language acquisition: A study on word formation growth during the second and third years

This study investigates the development of German word formation as an important step in mastering complex lexical items for the language learning child. Thirty mother— child dyads participated. Means of word formation and resulting word categories were analyzed in children’s spontaneous speech at ages 1;9, 1;11, 2;6, and 3;0. In contrast to the acquisition of English, the results show simultaneous development of compounds and derivations. German toddlers produce more verbal than nominal derivations and more compounds based on verbs than on nouns. The findings suggest that (1) there are cross-linguistic differences in the development of word formation devices, and (2) children rely heavily on verbs in word formation.
The Clinical Character of Local Anesthetics: A Function of Frequency‐Dependent Conduction Block

It is a clinically recognized fact that some local anesthetics have a proclivity for inhibition of motor nerves, while others preferentially affect sensory and sympathetic fibers. On the basis that sensory fibers have a frequency threshold for transmission of nociceptive stimuli and that somatic motor fibers have no such frequency threshold, we hypothesized that this variation may be due to differences in the effect of local anesthetics on axonal refractory period. Frog sciatic nerves were partially blocked with lidocaine, bupivacaine, tetracaine and etidocaine, and then stimulated in trains of 17 pulses, at frequencies between 3 and 100 Hz. The height and area of the last action potential in a train were measured. At a comparable level of partial block (50% at 100 Hz), tetracaine and etidocaine showed only a 10% difference between 3 and 100 Hz, while with bupivacaine and lidocaine there was a 30% drop between these two frequencies. This excellent correlation between the laboratory and clinical phenomenon supports our hypothesis. Local anesthetics which have a minimal effect on the refractory period yield enhanced motor block; whereas local anesthetics with a large effect on the refractory period are relatively more potent blockers of sensory and sympathetic transmission.
Advanced Image Fusion to Overlay Coronary Sinus Anatomy with Real‐Time Fluoroscopy to Facilitate Left Ventricular Lead Implantation in CRT

Background: Failure rate for left ventricular (LV) lead implantation in cardiac resynchronization therapy (CRT) is up to 12%. The use of segmentation tools, advanced image registration software, and high‐fidelity images from computerized tomography (CT) and cardiac magnetic resonance (CMR) of the coronary sinus (CS) can guide LV lead implantation. We evaluated the feasibility of advanced image registration onto live fluoroscopic images to allow successful LV lead placement.