Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and chromosomal localization of murine ORC3, a new member of the mouse origin recognition complex

A new member of the murine origin recognition complex (ORC) related to Saccharomyces cerevisiae ORC3 has been cloned. Transcription of ORC3 is not suppressed in mouse NIH3T3 fibroblasts made quiescent by serum starvation. The transcription level of the ORC3 gene is constantly high in all phases of the cell cycle. Murine ORC3 protein contains a putative nuclear localization signal and a non-basic helix-loop-helix motif. Both motifs are conserved in eukaryotes. A potential dimerization partner of ORC3p in the murine ORC complex is ORC1p which also contains an HLH motif. This HLH motif is also highly conserved in all eukaryotic ORC1 proteins. Comparison of murine ORC3p with other ORC3-related proteins shows high amino acid homology and motif conservation leading to the conclusion that ORC3p is part of the initiation machinery conserved in eukaryotes. The mouse ORC3 gene Orc3 was assigned to mouse chromosome 4A3 by fluorescence in situ hybridization (FISH) analysis.
Does Income Smoothing Make Stock Prices More Informative?

This paper presents a new approach to studying the effects of earnings management, by testing whether income smoothing, a particular form of earnings management, is associated with more informative stock prices. Stock price informativeness is defined as the amount of information about future earnings and cash flows reflected in current period stock returns, and is measured as the coefficient on future earnings (cash flows) in a regression of current stock return against current and future earnings (cash flows and accruals). I find that firms with greater smoothing have more informative stock prices, implying that managers use income smoothing to reveal their private information about the firm's future profitability.
Preservation and expansion of the primate keratocyte phenotype by downregulating TGF-beta signaling in a low-calcium, serum-free medium.

PURPOSE To demonstrate whether the original keratocyte phenotype is maintained with proliferative activity by suppressing TGF-beta signaling in rhesus monkey keratocytes expanded in a serum-free and low-[Ca2+] medium. METHODS Rhesus monkey keratocytes were isolated from central corneal buttons by collagenase digestion for 16 hours, seeded on plastic in Dulbecco's modified Eagle's medium (DMEM) containing insulin-transferrin-sodium selenite (ITS) supplement (DMEM/ITS) or 10% fetal bovine serum (DMEM/10% FBS), or in a defined keratinocyte serum-free medium (KSFM). After confluence, cells in KSFM were continuously subcultured at a 1-to-3 split. Cellular proliferation was analyzed by immunostaining for Ki67 and the MTT assay. The cellular phenotype was determined by immunostaining for aldehyde dehydrogenase (ALDH), keratocan, and CD34 and by the expression of keratocan promoter-driven enhanced cyan fluorescent protein (ECFP). The stability of the keratocyte phenotype was examined by switching KSFM to DMEM/ITS and DMEM/10% FBS. TGF-beta signaling was monitored by measuring the promoter activity of TGF-beta1, -beta2, and -beta RII after transient adenoviral transfection, and cytolocalization of Smad2 and Smad4. RESULTS In KSFM, monkey keratocytes proliferated while maintaining the expression of keratocan, CD34, and ALDH proteins and keratocan promoter-driven ECFP for at least 15 passages. The nuclear accumulation of Smad2 and Smad4 and the promoter activities of TGF-beta1 and -beta RII were significantly downregulated in KSFM compared with DMEM/10% FBS. In KSFM, an increase of [Ca2+] to 1.8 mM and addition of 10% FBS synergistically downregulated the keratocan promoter activity, facilitated Smad2 and Smad4 nuclear translocation, and upregulated TGF-beta1 and -beta RII promoter activities. CONCLUSIONS The normal monkey keratocyte phenotype can be maintained in a low-calcium, serum-free medium by downregulating Smad-mediated TGF-beta signaling.
Comparative effectiveness of prostate cancer treatments for patient-centered outcomes

Background: In the context of prostate cancer (PCa) characterized by the multiple alternative treatment strategies, comparative effectiveness analysis is essential for informed decision-making. We analyzed the comparative effectiveness of PCa treatments through systematic review and meta-analysis with a focus on outcomes that matter most to newly diagnosed localized PCa patients. Methods: We performed a systematic review of literature published in English from 1995 to October 2016. A search strategy was employed using terms “prostate cancer,” “localized,” “outcomes,” “mortality,” “health related quality of life,” and “complications” to identify relevant randomized controlled trials (RCTs), prospective, and retrospective studies. For observational studies, only those adjusting for selection bias using propensity-score or instrumental-variables approaches were included. Multivariable adjusted hazard ratio was used to assess all-cause and disease-specific mortality. Funnel plots were used to assess the level of bias. Results: Our search strategy yielded 58 articles, of which 29 were RCTs, 6 were prospective studies, and 23 were retrospective studies. The studies provided moderate data for the patient-centered outcome of mortality. Radical prostatectomy demonstrated mortality benefit compared to watchful waiting (all-cause HR = 0.63 CI = 0.45, 0.87; disease-specific HR = 0.48 CI = 0.40, 0.58), and radiation therapy (all-cause HR = 0.65 CI = 0.57, 0.74; disease-specific HR = 0.51 CI = 0.40, 0.65). However, we had minimal comparative information about tradeoffs between and within treatment for other patient-centered outcomes in the short and long-term. Conclusion: Lack of patient-centered outcomes in comparative effectiveness research in localized PCa is a major hurdle to informed and shared decision-making. More rigorous studies that can integrate patient-centered and intermediate outcomes in addition to mortality are needed.
Analysis and design of singular linear systems under actuator saturation and L2/L∞ disturbances

This paper carries out an analysis of the L2 gain and Linfin performance for singular linear systems under actuator saturation. The notion of bounded state stability (BSS) with respect to the influence of L2 or Linfin disturbances is introduced and conditions under which a system is bounded state stable are established in terms of linear matrix inequalities (LMIs). The disturbance tolerance capability of the system is then measured as the bound on the L2 or Linfin norm of the disturbances under which the system remains bounded state stable and the disturbance rejection capability is measured by the restricted L2 gain from the disturbance to the system output or Linfin norm of the system output. Based on the BSS conditions, the assessment of the disturbance tolerance and rejection capabilities of the system under a given state feedback law is formulated and solved as LMI constrained optimization problems. By viewing the feedback gain as an additional variable, these optimization problems can be readily adapted for control design. Our analysis and design reduce to the existing results for regular linear systems in the degenerate case where the singular linear system reduces to a regular system, and to the existing results for singular systems in the absence of actuator saturation or when the disturbance is weak enough to not cause saturation.
Disentangling the Role of the MEC and LEC in the Processing of Spatial and Non-Spatial Information: Contribution of Lesion Studies

It is now widely accepted that the entorhinal cortex (EC) plays a pivotal role in the processing of spatial information and episodic memory. The EC is segregated into two sub-regions, the medial EC (MEC) and the lateral EC (LEC) but a comprehensive understanding of their roles across multiple behavioral contexts remains unclear. Considering that it is still useful to investigate the impact of lesions of EC on behavior, we review the contribution of lesion approach to our knowledge of EC functions. We show that the MEC and LEC play different roles in the processing of spatial and non-spatial information. The MEC is necessary to the use of distal but not proximal landmarks during navigation and is crucial for path integration, in particular integration of linear movements. Consistent with predominant hypothesis, the LEC is important for combining the spatial and non-spatial aspects of the environment. However, object exploration studies suggest that the functional segregation between the MEC and the LEC is not as clearly delineated and is dependent on environmental and behavioral factors. Manipulation of environmental complexity and therefore of cognitive demand shows that the MEC and the LEC are not strictly necessary to the processing of spatial and non-spatial information. In addition we suggest that the involvement of these sub-regions can depend on the kind of behavior, i.e., navigation or exploration, exhibited by the animals. Thus, the MEC and the LEC work in a flexible manner to integrate the “what” and “where” information in episodic memory upstream the hippocampus.
New Traces of an Inland Neolithic Culture in the Chukotsk (Chukchi) Peninsula

Abstract The El'gytkhyn site consists of a cache of stone artifacts and a nearby campsite on the shores of Lake El'gytkhyn on the central Anadyr plateau. The cache contained some 50 artifacts, both knives and points made on large flake-blades and carefully retouched by pressure flaking, and blanks from which they were made. Similar points were found at the campsite along with scrapers and other tools, many retouched chips, prismatic nuclei, and the blades struck from them. Previously, similar artifacts had been found at the Amguema site about 300 km. to the east and the Chirovoe site about 100 km. to the south. The latter is a settlement with pottery as well as stone artifacts. The inland Neolithic culture is compared to the Caribou Eskimo and the Yukaghir, and the El'gytkhyn site is interpreted as the summer hunting camp of people following reindeer to the north from permanent winter villages like the Chirovoe site. The presence of blades removed from prismatic cores, retouched points and other artifacts, tools with graver facets, and pottery in both the Chukchi inland Neolithic and the Paleo-Eskimo cultures suggests movements from the Asiatic to the American Arctic by 4000 years ago.
Influence of the Availability of Laser Transmyocardial Revascularisation on Surgical Strategy in Patients with Advanced Coronary Artery Disease

Objective: To compare the planned and actual revascularisation techniques used in patients undergoing cardiac surgery for refractory angina when excimer transmyocardial laser revascularisation (TMR) is available. Methods: Observational series of 31 patients (mean age 65 years) with severe angina [mean CCS score (SD) 3.8 (0.4)] and three-vessel coronary artery disease judged unsuitable for conventional bypass surgery alone. All patients underwent cardiac surgery: revascularisation techniques were determined by the operative findings. Results: Pre-operative strategy was altered by the intra-operative findings in 13 patients (42%). In 5 (16%), the coronary vessels proved graftable and TMR was unnecessary. Conversely, in 6 patients (19%) an anticipated graft could not be performed and TMR was used as an alternative. In 2 patients (7%), neither strategy was possible. Overall, TMR was performed as a stand-alone procedure in 9 (29%) and combined with CABG in 17 (55%). Operative mortality was low: 0% at 30 days and 6% at 6 months. Mean CCS class (SD) improved post-operatively from 3.8 (0.4) to 1.7 (1.1) (p < 0.01). Conclusions: The pre-operative coronary angiogram is an imperfect predictor of which coronary vessels are suitable for grafting. The availability of laser TMR allows the cardiac surgeon to accept cases which would otherwise be considered inoperable and to respond better to intraoperative findings. The combination of laser TMR and bypass grafts provides good short- and medium-term symptomatic improvement with a low post-operative mortality.
Comprehensive Analysis of Glycosylphosphatidylinositol-Anchored Proteins in Candida albicans

There are two types of membrane proteins: the integral membrane proteins and the lipid-anchored proteins. Integral membrane proteins contain one or several transmembrane domains that allow for the formation of hydrophobic -helices, which ultimately embed the protein in a lipid bilayer. We count four types of lipid-anchored proteins divided into two groups: one group generally links the proteins to the internal side of the plasma membrane and the other generally links them to the outside. In the first group are found the amide-linked myristoyl anchors (calcineurin B) (6), the (thio)ester-linked fatty acyl anchors, and the thioether-linked prenyl anchors (G protein alpha subunits) (13). The second group is composed only of the proteins that contain a C-terminal signal sequence that allows for linkage to a glycosylphosphatidylinositol (GPI) anchor. The anchor of the GPI-anchored proteins (GpiPs) can be removed by the action of specific phospholipases (24), converting the protein into a water-soluble form. GpiPs are thought to associate with lipid rafts, specialized regions of the membrane containing elevated levels of cholesterol and sphingolipids, common to human cells, for example (48). Proteins destined to be GPI anchored share conserved features: an N-terminal signal sequence for localization to the endoplasmic reticulum (ER), a C-terminal hydrophobic domain (9 to 24 residues) for transient attachment to the ER membrane, and the so-called site, where the protein is cleaved to be ligated to the GPI anchor (57). The site is localized 9 to 10 amino acids before the C-terminal hydrophobic domain, and its amino acid environment determines whether the protein has a high probability to be GPI anchored. Amino acids at positions -1 to -11 form a linker region usually with no charge and no secondary structure (-helix or -sheet). The site region is composed of small amino acids to fit the transamidase protease catalytic pocket, and finally, the spacer region ( 3t o9) is comparable to the linker, having no charge and being flexible (16). Shortly after protein synthesis in the ER, the preformed GPI anchor replaces the C-terminal transmembrane region. The core GPI anchor consists of a lipid group (serving as the membrane anchor), a myoinositol group, an N-acetylglucosamine group, three mannose groups, and a phosphoethanol
Strategic Bias Shifting: Herding as a Behaviorally Rational Response to Regret Aversion

In this article, we show experimentally that individuals can adapt their decision making to social environments, like markets, and respond strategically to biases, such as regret aversion. We find they can employ herding as a behaviorally rational strategy to improve their expected outcomes and shift anticipated regret when regret would otherwise bias them towards a suboptimal status quo. Herding can improve decision making when people observe the choices of professionals and businesses, who are less likely to be biased by regret. Focusing on others’ choices can allow decision makers to shift their reference point, and their bias, to favor their optimal choice. We find that decision makers exploit this process to shift their bias strategically. They seek information when their reference point is not optimal, but block it otherwise. They also strategically select among different types of decision makers and focus on those that made the better decision. Our research suggests that decision makers employ strategies to reduce the welfare effects of biases in certain domains. Policy responses may support private ordering by seeking to complement, rather than substitute for, these strategies.
What’s My Style? The Influence of Top Managers on Voluntary Corporate Financial Disclosure

ABSTRACT: Financial economics has posited a limited role for idiosyncratic noneconomic manager-specific influences, but the strategic management literature suggests such individual influences can affect corporate outcomes. We investigate whether individual managers play an economically significant role in their firms’ voluntary financial disclosure choices. Tracking managers across firms over time, we find top executives exert unique and economically significant influence (manager-specific fixed effects) on their firms’ voluntary disclosures, incremental to known economic determinants of disclosure, and firm- and time-specific effects. Managers’ unique disclosure styles are associated with observable demographic characteristics of their personal backgrounds: managers promoted from finance, accounting, and legal career tracks, managers born before World War II, and those with military experience develop disclosure styles displaying certain conservative characteristics; and managers from finance and account.
Homodimerization of adenosine A2A receptors: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer

The results presented in this paper show that adenosine A2A receptor (A2AR) form homodimers and that homodimers but not monomers are the functional species at the cell surface. Fluorescence resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET) techniques have been used to demonstrate in transfected HEK293 cells homodimerization of A2AR, which are heptaspanning membrane receptors with enriched expression in striatum. The existence of homodimers at the cell surface was demonstrated by time‐resolved FRET. Although agonist activation of the receptor leads to the formation of receptor clusters, it did not affect the degree of A2AR–A2AR dimerization. Both monomers and dimers were detected by immunoblotting in cell extracts. However, cell surface biotinylation of proteins has made evident that more than 90% of the cell surface receptor is in its dimeric form. Thus, it seems that homodimers are the functional form of the receptor present on the plasma membrane. A deletion mutant version of the A2A receptor, lacking its C‐terminal domain, was also able to form both monomeric and dimeric species when cell extracts from transfected cells were analyzed by immunoblotting. This suggests that the C‐terminal tail does not participate in the dimerization. This is relevant as the C‐terminal tail of A2AR is involved in heteromers formed by A2AR and dopamine D2 receptors. BRET ratios corresponding to A2AR–A2AR homodimers were higher than those encountered for heterodimers formed by A2AR and dopamine D2 receptors. As A2AR and dopamine D2 receptors do indeed interact, these results indicate that A2AR homodimers are the functional species at the cell surface and that they coexist with A2AR/D2 receptor heterodimers.
The lgtABCDE Gene Cluster, Involved in Lipooligosaccharide Biosynthesis in Neisseria gonorrhoeae, Contains Multiple Promoter Sequences

ABSTRACT Biosynthesis of the variable core domain of lipooligosaccharide (LOS) in Neisseria gonorrhoeae is mediated by glycosyl transferases encoded by lgtABCDE. Changes within homopolymeric runs within lgtA, lgtC, and lgtD affect the expression state of these genes, with the nature of the LOS expressed determined by the functionality of these genes. However, the mechanism for modulating the amount of multiple LOS chemotypes expressed in a single cell is not understood. Using mutants containing polar disruptions within the lgtABCDE locus, we determined that the expression of this locus is mediated by multiple promoters and that disruption of transcription from these promoters alters the relative levels of simultaneously expressed LOS chemotypes. Expression of the lgtABCDE locus was quantified by using xylE transcriptional fusions, and the data indicate that this locus is transcribed in trace amounts and that subtle changes in transcription result in phenotypic changes. By using rapid amplification of 5′ cDNA ends, transcriptional start sites and promoter sequences were identified within lgtABCDE. Most of these promoters possessed 50 to 67% homology with the consensus gearbox promoter sequence of Escherichia coli.
EEG-Based Estimation and Classification of Mental Fatigue

Mental fatigue was associated with increased power in frontal theta (θ) and parietal alpha (α) EEG rhythms. A statistical classifier can use these effects to model EEG-fatigue relationships accurately. Participants (n = 22) solved math problems on a computer until either they felt exhausted or 3 h had elapsed. Pre- and post-task mood scales showed that fatigue increased and energy decreased. Mean response times rose from 6.7 s to 7.9 s but accuracy did not change significantly. Mean pow- er spectral densities or PSDs of θ and α bands rose by 29% and 44%, respectively. A kernel partial least squares classifier trained to classify PSD coefficients (1 - 18 Hz) of single 13-s EEG segments from alert or fatigued task periods was 91% to 100% accurate. For EEG segments from other task periods, the classifier outputs tracked the time course of the development of mental fatigue. By this measure, most subjects became substantially fatigued after 60 min of task performance. However, the trajectories of individual classifier outputs showed that EEG signs of developing fa- tigue were present in all subjects after 15 - 30 minutes of task performance. The results show that EEG can track the development of mental fatigue over time with accurate updates on a time scale a short as 13 seconds. In addition, the results agree with the notion that growing mental fatigue produces a shift away from executive and attention networks to default mode and is accompanied by a shift in alpha frequency to the lower alpha band.
A Quantified Industrial Performance Measurement System Based on a Choquet Fuzzy Integral

This study deals with the aggregation of performance expressions in a manufacturing context, Le. the mechanism which allows the computation of a global performance knowing the elementary ones. In this kind of aggregation the elementary performances to be combined are, on the one hand, information, often of a heterogeneous nature (cost, quality, delay .), on the other hand, they are associated to diversified and numerous objectives which interact in different ways. In this context, the conventional approaches based on the Weighted Arithmetic Mean and the Analytic Hierarchy Process show their limitations. Thus, we propose an approach based on the fuzzy Choquet integral and on a MACBETH inspired method. This approach satisfies measurement theory requirements thanks to performance expressions defined according interval scales. The proposed procedure for quantifying performance measurement is illustrated on a case study submitted by a company that manufactures bathrooms and kitchens.