Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential expression of G1 cyclins and cyclin-dependent kinase inhibitors in normal and transformed melanocytes.

PURPOSE To investigate the levels of the different regulatory proteins involved in the G1 progression and G1/S transition in normal and transformed human choroidal melanocytes (CM). METHODS Three choroidal melanoma cell lines and three CM cultures were used. The purity of the CM cultures was assessed by different approaches, including morphologic study, specific immunostaining, cell proliferation behavior, and transforming growth factor-beta1 responsiveness. The cell cycle protein levels were evaluated by specific immunoblotting of total extracts obtained from the different cell lines. RESULTS Alterations were observed in the expression of cylins D1 and E in the transformed cells, whereas the amounts of the cyclin-dependent kinases (CDKs) CDK2 and CDK4 were almost identical in both cell types. Although the expression of cyclin H was slightly increased in transformed cells, neither the CDK7 level nor the CDK7 and cyclin H localizations were altered when compared with those in normal CM. The results suggest the absence of the CDK inhibitor (CKI) p21 in two of the three melanoma cell lines and, as a main feature, a striking underexpression of p27 in the three transformed cell lines. Finally, although the p16 level was almost the same in normal and transformed cells, a loss of p16-CDK4 interaction was observed in two of the three melanoma cell lines. CONCLUSIONS Deregulated expression of G1 cyclins and CKIs and alteration in the interaction of CKIs with CDKs may be implicated in the neoplastic transformation of human ocular melanocytes to malignant melanoma cells.
NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification of Vitamin C and CAPE as natural products targeting “stemness”

Here, we assembled a broad molecular “tool-kit” to interrogate the role of metabolic heterogeneity in the propagation of cancer stem-like cells (CSCs). First, we subjected MCF7 cells to “metabolic fractionation” by flow cytometry, using fluorescent mitochondrial probes to detect PCG1α activity, as well ROS and hydrogen-peroxide (H2O2) production; NADH levels were also monitored by auto-fluorescence. Then, the various cell populations were functionally assessed for “stem cell activity”, using the mammosphere assay (3D-spheroids). Our results indicate that a sub-population of MCF7 cells, with increased PGC1α activity, high mitochondrial ROS/H2O2 production and high NADH levels, all form mammospheres with a higher efficiency. Thus, it appears that mitochondrial oxidative stress and the anti-oxidant response both contribute to the promotion of mitochondrial biogenesis and oxidative metabolism in CSCs. Further validation was provided by using specific inhibitors to target metabolic processes (the NAD+ salvage pathway, glycolysis, mitochondrial protein synthesis and OXPHOS), significantly reducing CSC propagation. As a consequence, we have now identified a variety of clinically-approved drugs (stiripentol), natural products (caffeic acid phenyl ester (CAPE), ascorbic acid, silibinin) and experimental pharmaceuticals (actinonin, FK866, 2-DG), that can be used to effectively inhibit CSC activity. We discuss the use of CAPE (derived from honey-bee propolis) and Vitamin C, as potential natural therapeutic modalities. In this context, Vitamin C was ∼10 times more potent than 2-DG for the targeting of CSCs. Similarly, stiripentol was between 50 to 100 times more potent than 2-DG.
Comparative Genomic Analysis of Two Novel Sporadic Shiga Toxin-Producing Escherichia coli O104:H4 Strains Isolated 2011 in Germany

A large outbreak of gastrointestinal disease occurred in 2011 in Germany which resulted in almost 4000 patients with acute gastroenteritis or hemorrhagic colitis, 855 cases of a hemolytic uremic syndrome and 53 deaths. The pathogen was an uncommon, multiresistant Escherichia coli strain of serotype O104:H4 which expressed a Shiga toxin characteristic of enterohemorrhagic E. coli and in addition virulence factors common to enteroaggregative E. coli. During post-epidemic surveillance of Shiga toxin-producing E. coli (STEC) all but two of O104:H4 isolates were indistinguishable from the epidemic strain. Here we describe two novel STEC O104:H4 strains isolated in close spatiotemporal proximity to the outbreak which show a virulence gene panel, a Shiga toxin-mediated cytotoxicity towards Vero cells and aggregative adherence to Hep-2 cells comparable to the outbreak strain. They differ however both from the epidemic strain and from each other, by their antibiotic resistance phenotypes and some other features as determined by routine epidemiological subtyping methods. Whole genome sequencing of these two strains, of ten outbreak strain isolates originating from different time points of the outbreak and of one historical sporadic EHEC O104:H4 isolate was performed. Sequence analysis revealed a clear phylogenetic distance between the two variant strains and the outbreak strain finally identifying them as epidemiologically unrelated isolates from sporadic cases. These findings add to the knowledge about this emerging pathogen, illustrating a certain diversity within the bacterial core genome as well as loss and gain of accessory elements. Our results do also support the view that distinct new variants of STEC O104:H4 repeatedly might originate from yet unknown reservoirs, rather than that there would be a continuous diversification of a single epidemic strain established and circulating in Germany after the large outbreak in 2011.
A Long-Wavelength Fluorescent Squarylium Cyanine Dye Possessing Boronic Acid for Sensing Monosaccharides and Glycoproteins with High Enhancement in Aqueous Solution

Fluorescence sensing of saccharides and glycoproteins using a boronic acid functionalized squarylium cyanine dye (“SQ-BA”) is characterized in terms of synthetic, fluorometric, thermodynamic and kinetic parameters. In our previous work, this newly synthesized dye was successfully applied to the separation and quantification of Gram-positive bacteria by capillary electrophoresis with laser-induced fluorescence detection (CE-LIF); however, the fundamental properties of the dye and its saccharide complexes still required elucidation, as presented in this paper. The dye itself forms nonemissive, soluble aggregates in aqueous solution. With the addition of a monosaccharide, the dye aggregate dissociates to form an emissive monomer accompanied by the formation of a cyclic cis-diol ester with long-wavelength emission (λex = 630 nm, λem = 660 nm). A very large fluorescence enhancement factor of 18× was observed for the sensing dye as a fructose complex at pH 10, yielding a limit of detection of 10 μM fructose. The relative order of fluorescence enhancement of SQ-BA with other monosaccharides was found to be: fructose > ribose > arabinose ≈ galactose > xylose > mannose > rhamnose > fucose ≈ glucose; and apparent affinity constants of 102.80, 102.08 and 100.86 M−1 were determined for fructose, ribose and glucose, respectively. Formation of the emissive complexes occurred within minutes, proving the kinetics of the sugar-dye interactions to be suitable for on-column labeling methods in CE-LIF. Furthermore, the sensing dye was successfully applied to glycoproteins, mucin type I–S and type III, which were detected with high sensitivity in batch aqueous solution as a result of the sugar-selective boronic acid-diol esterification as well as hydrophobic interactions.
Want to, need to, ought to: employee commitment to organizational change

Purpose – This study aims to focus on the role of employee commitment in the success of organizational change initiatives. The authors seek to propose and test a model that delineates antecedents and consequences of affective, normative, and continuance commitment to organizational change.Design/methodology/approach – Data were collected via online survey from employees working in a large not‐for‐profit organization. A total of 191 responses (32 per cent) were obtained. The hypothesized model relationships were tested using structural equation modeling.Findings – The results demonstrate that the antecedents: fit with vision, employee‐manager relationship quality, job motivation, and role autonomy all influence commitment to change (C2C). Notably, affective commitment, which in turn influences employee perceptions about improved performance, implementation success, and individual learning regarding the change, had the greatest impact.Research limitations/implications – Limitations that could lead to future.
SINFONI-HiZELS: the dynamics, merger rates and metallicity gradients of ‘typical’ star-forming galaxies at z = 0.8–2.2

We present adaptive optics (AO) assisted SINFONI integral field unit (IFU) spectroscopy of 11 Hα emitting galaxies selected from the High-Z Emission Line Survey (HiZELS). We obtain spatially resolved dynamics on ∼kpc-scales of star-forming galaxies [stellar mass M⋆ = 109.5 − 10.5 M⊙ and star formation rate (SFR) = 2–30 M⊙ yr−1] near the peak of the cosmic star formation rate history. Combining these observations with our previous SINFONI-HiZELS campaign, we construct a sample of 20 homogeneously selected galaxies with IFU AO-aided observations – the ‘SHiZELS’ survey, with roughly equal number of galaxies per redshift slice, at z = 0.8, 1.47 and 2.23. We measure the dynamics and identify the major kinematic axis by modelling their velocity fields to extract rotational curves and infer their inclination-corrected rotational velocities. We explore the stellar mass Tully–Fisher relationship, finding that galaxies with higher velocity dispersions tend to deviate from this relation. Using kinemetry analyses, we find that galaxy interactions might be the dominant mechanism controlling the star formation activity at z = 2.23 but they become gradually less important down to z = 0.8. Metallicity gradients derived from the [N ii]/Hα emission line ratio show a median negative gradient for the SHiZELS survey of Δlog(O/H)/ΔR = −0.026 ± 0.008 dex kpc−1. We find that metal-rich galaxies tend to show negative gradients, whereas metal-poor galaxies tend to exhibit positive metallicity gradients. This result suggests that the accretion of pristine gas in the periphery of galaxies plays an important role in replenishing the gas in ‘typical’ star-forming galaxies.
Tamoxifen in the Mouse Brain: Implications for Fate-Mapping Studies Using the Tamoxifen-Inducible Cre-loxP System

The tamoxifen-inducible Cre-loxP system is widely used to overcome gene targeting pre-adult lethality, to modify a specific cell population at desired time-points, and to visualize and trace cells in fate-mapping studies. In this study we focused on tamoxifen degradation kinetics, because for all genetic fate-mapping studies, the period during which tamoxifen or its metabolites remain active in the CNS, is essential. Additionally, we aimed to define the tamoxifen administration scheme, enabling the maximal recombination rate together with minimal animal mortality. The time window between tamoxifen injection and the beginning of experiments should be large enough to allow complete degradation of tamoxifen and its metabolites. Otherwise, these substances could promote an undesired recombination, leading to data misinterpretation. We defined the optimal time window, allowing the complete degradation of tamoxifen and its metabolites, such as 4-hydroxytamoxifen, N-desmethyltamoxifen, endoxifen and norendoxifen, in the mouse brain after intraperitoneal tamoxifen injection. We determined the biological activity of these substances in vitro, as well as a minimal effective concentration of the most potent metabolite 4-hydroxytamoxifen causing recombination in vivo. For this purpose, we analyzed the recombination rate in double transgenic Cspg4-cre/Esr1/ROSA26Sortm14(CAG-tdTomato) mice, in which tamoxifen administration triggers the expression of red fluorescent protein in NG2-expressing cells, and employed a liquid chromatography, coupled with mass spectrometry, to determine the concentration of studied substances in the brain. We determined the degradation kinetics of these substances, and revealed that this process is influenced by mouse strains, age of animals, and dosage. Our results revealed that tamoxifen and its metabolites were completely degraded within 8 days in young adult C57BL/6J mice, while the age-matched FVB/NJ male mice displayed more effective degradation. Moreover, aged C57BL/6J mice were unable to metabolize all substances within 8 days. The lowering of initial tamoxifen dose leads to a significantly faster degradation of all studied substances. A disruption of the blood-brain barrier caused no concentration changes of any tamoxifen metabolites in the ipsilateral hemisphere. Taken together, we showed that tamoxifen metabolism in mouse brains is age-, strain- and dose-dependent, and these factors should be taken into account in the experimental design.
Communication network activity: Network attributes of the young and elderly

This manuscript details a study aimed at preliminary exploration of the relationship between aging and changes in communication network composition and quality. Two age groups (young and elderly) were asked to recall their interpersonal communication for two days. Subjects also completed a relational assessment instrument for each person they communicated with. The results suggest that the elderly, as compared to the young, engage in greater communicative contact with their families and that the level of contact with non‐family network members is less. In addition, the elderly's level of solidarity with non‐family members is lower than that for the young. However, levels of family solidarity do not differ between these groups. Positive relationships exist between communication network contact and solidarity for both groups. However, inverse relationships were found when network composition was considered. As contact with family increased, friendship contact and solidarity declined. On the basis of these f.
Orthodontic Bracket Manufacturing Tolerances and Dimensional Differences between Select Self-Ligating Brackets

In all manufacturing processes there are tolerances; however, orthodontic bracket manufacturers seldom state the slot dimensional tolerances. This experiment develops a novel method of analyzing slot profile dimensions using photographs of the slot. Five points are selected along each wall, and lines are fitted to define a trapezoidal slot shape. This investigation measures slot height at the slot's top and bottom, angles between walls, slot taper, and the linearity of each wall. Slot dimensions for 30 upper right central incisor self-ligating stainless steel brackets from three manufacturers were evaluated. Speed brackets have a slot height 2% smaller than the nominal 0.559 mm size and have a slightly convergent taper. In-Ovation brackets have a divergent taper at an average angle of 1.47 degrees. In-Ovation is closest to the nominal value of slot height at the slot base and has the smallest manufacturing tolerances. Damon Q brackets are the most rectangular in shape, with nearly 90-degree corners between the slot bottom and walls. Damon slot height is on average 3% oversized.
Biological and therapeutic aspects of infant leukemia.

Leukemias diagnosed in the first 12 months of life are characterized by an equal distribution of lymphoid and myeloid subtypes and account for 2.5% to 5% of acute lymphoblastic leukemias (ALLs) and 6% to 14% of acute myeloid leukemias (AMLs) of childhood. [1][1] [2][2] In contrast to an excess of
Comparison of propofol and methohexitone as anaesthetic agents for electroconvulsive therapy

Propofol was compared to methohexitone for induction of anaesthesia for electroconvulsive therapy. Seizures were significantly shorter after the use of propofol, in respect of both visible seizures and duration of cerebral electrical seizure activity. This suggests the possibility that additional treatments may be needed for the same clinical effect in psychiatric illness when propofol is used as the induction agent. Propofol was more effective than methohexitone at obtunding the hypertensive response to electroconvulsive therapy without causing significant hypotension.
The minority identity and the idea of the ‘unity’ of the nation: the case of Hungarian minorities from Romania, Slovakia, Serbia and Ukraine

A comparison analysis of the ethno-national identity of Hungarian minorities living in Romania, Slovakia, Serbia and Ukraine is performed in the paper, including the identifications to majority community and the relationship with Hungary, respectively. According to the empirical results in every country, the community with the pan-Hungarian ethnocultural nation, and the identification with actual Hungary, is less important than regional Hungarianness in the minority identity of Hungarian minority members from outside the borders of Hungary. The primary in-group is the self-minority community in every country. This may be empirically grasped both on the level of the perceptions of social distances and on stereotypes toward Hungarians from Hungary and toward majority populations (Romanians, Slovaks, etc.).
Role of Dot1 in the Response to Alkylating DNA Damage in Saccharomyces cerevisiae: Regulation of DNA Damage Tolerance by the Error-Prone Polymerases Polζ/Rev1

Maintenance of genomic integrity relies on a proper response to DNA injuries integrated by the DNA damage checkpoint; histone modifications play an important role in this response. Dot1 methylates lysine 79 of histone H3. In Saccharomyces cerevisiae, Dot1 is required for the meiotic recombination checkpoint as well as for chromatin silencing and the G1/S and intra-S DNA damage checkpoints in vegetative cells. Here, we report the analysis of the function of Dot1 in the response to alkylating damage. Unexpectedly, deletion of DOT1 results in increased resistance to the alkylating agent methyl methanesulfonate (MMS). This phenotype is independent of the dot1 silencing defect and does not result from reduced levels of DNA damage. Deletion of DOT1 partially or totally suppresses the MMS sensitivity of various DNA repair mutants (rad52, rad54, yku80, rad1, rad14, apn1, rad5, rad30). However, the rev1 dot1 and rev3 dot1 mutants show enhanced MMS sensitivity and dot1 does not attenuate the MMS sensitivity of rad52 rev3 or rad52 rev1. In addition, Rev3-dependent MMS-induced mutagenesis is increased in dot1 cells. We propose that Dot1 inhibits translesion synthesis (TLS) by Polζ/Rev1 and that the MMS resistance observed in the dot1 mutant results from the enhanced TLS activity.
Access to talker-specific representations is dependent on word frequency

Determining the precise circumstances under which nonlinguistic information such as talker identity influences spoken-word recognition is critical for models that postulate both abstract and detailed representations. In this study, we used the long-term repetition priming paradigm and manipulated both talker identity and word frequency. The results showed that change in the talker identity diminishes the magnitude of the repetition priming effect when words are of low frequency but not when they are of high frequency. Our results support the time-course hypothesis which posits that talker-specificity effects take time to develop, and thus are more likely to emerge when lexical identification requires time to be accomplished.
Interference Alignment-Based Sum Capacity Bounds for Random Dense Gaussian Interference Networks

We consider a dense K user Gaussian interference network formed by paired transmitters and receivers placed independently at random in a fixed spatial region. Under natural conditions on the node position distributions and signal attenuation, we prove convergence in probability of the average per-user capacity CΣ/K to 1/2E log(1 + 2SNR). The achievability result follows directly from results based on an interference alignment scheme presented in recent work of Nazer et al. Our main contribution comes through an upper bound, motivated by ideas of "bottleneck capacity" developed in recent work of Jafar. By controlling the physical location of transmitter-receiver pairs, we can match a large proportion of these pairs to form so-called ε-bottleneck links, with consequent control of the sum capacity.
Efficient reconstruction of haplotype structure via perfect phylogeny.

Each person's genome contains two copies of each chromosome, one inherited from the father and the other from the mother. A person's genotype specifies the pair of bases at each site, but does not specify which base occurs on which chromosome. The sequence of each chromosome separately is called a haplotype. The determination of the haplotypes within a population is essential for understanding genetic variation and the inheritance of complex diseases. The haplotype mapping project, a successor to the human genome project, seeks to determine the common haplotypes in the human population. Since experimental determination of a person's genotype is less expensive than determining its component haplotypes, algorithms are required for computing haplotypes from genotypes. Two observations aid in this process: first, the human genome contains short blocks within which only a few different haplotypes occur; second, as suggested by Gusfield, it is reasonable to assume that the haplotypes observed within a block have evolved according to a perfect phylogeny, in which at most one mutation event has occurred at any site, and no recombination occurred at the given region. We present a simple and efficient polynomial-time algorithm for inferring haplotypes from the genotypes of a set of individuals assuming a perfect phylogeny. Using a reduction to 2-SAT we extend this algorithm to handle constraints that apply when we have genotypes from both parents and child. We also present a hardness result for the problem of removing the minimum number of individuals from a population to ensure that the genotypes of the remaining individuals are consistent with a perfect phylogeny. Our algorithms have been tested on real data and give biologically meaningful results. Our webserver (http://www.cs.columbia.edu/compbio/hap/) is publicly available for predicting haplotypes from genotype data and partitioning genotype data into blocks.
Technical and tactical analysis of women’s volleyball

Summary Introduction: The study aim was to construct a technical and tactical analysis of women’s volleyball based on notational analysis in top-level and junior women’s European volleyball matches, to compare these two levels, and to clarify the differences between the winners and losers of a set. Material and Methods: Four matches from the 2010 FIVB Women’s Volleyball World Championships and 2010 CEV Junior Women’s European Championship 2010 were analyzed using Data Volley software. The number and performance level of different skills were recorded in total and were grouped according to the role of the players. Methods of scoring and attacking zones were also analyzed. Results: There were only slight differences between the two levels in terms of success in different skills. When the skill executions were compared between the winning and losing teams of a set within the levels, less successful skill executions and more errors in different skills were found for the losing teams. Conclusions: The results seem to indicate that there are only minor differences between adult and junior women’s volleyball at the highest level. Attacking seems to be the most important skill concerning winning in both levels. The efficiency of attacking seems to depend upon the quality and versatility of the setting and also from the physical abilities of the players.