Miracle-dz/UniFAR-FTUs huggingface dataset:
Oncogenic Activation of c-Myb Correlates with a Loss of Negative Regulation by TIF1β and Ski*[boxs]

The c-myb proto-oncogene product (c-Myb) regulates proliferation of hematopoietic cells by inducing the transcription of a group of target genes. Removal or mutations of the negative regulatory domain (NRD) in the C-terminal half of c-Myb leads to increased transactivating capacity and oncogenic activation. Here we report that TIF1β directly binds to the NRD and negatively regulates the c-Myb-dependent trans-activation. In addition, three corepressors (Ski, N-CoR, and mSin3A) bind to the DNA-binding domain of c-Myb together with TIF1β and recruit the histone deacetylase complex to c-Myb. Furthermore, the Drosophila TIF1β homolog, Bonus, negatively regulates Drosophila Myb activity. The Ski corepressor competes with the coactivator CBP for binding to c-Myb, indicating that the selection of coactivators and corepressors is a key event for c-Myb-dependent transcription. Mutations or deletion of the NRD of c-Myb and the mutations found in the DNA-binding domain of v-Myb decrease the interaction with these corepressors and weaken the corepressor-induced negative regulation of Myb activity. These observations have conceptual implications for understanding how the nuclear oncogene is activated.
Introduction to the Special Issue on Index Number Theory and Price Statistics

Index theory as well as price statistics has undergone a remarkable change in the last twenty years. Some of the influential publications were the System of National Accounts 1993, the famous Reports of the Boskin and Schultze Commissions, the ongoing creation of a number of Manuals and recommendations of best practice, created by international groups of experts and edited by international organisations such as the ILO, IMF, OECD, UNECE, Eurostat, or the World Bank. Thus we now have best practice Manuals for Productivity Measurement, Consumer Prices, Producer Prices, Export and Import Prices, the Measurement of Capital, the Measurement of Non-Market Production, and additional Manuals or Handbooks for House Prices (or Residential Property Prices) and for International and Interregional Comparisons of Consumer Prices are in progress.
Exploring the use of dimethylsulfate for in vivo proteome footprinting

Protein footprinting is a new methodology that is based on probing, typically with the use of MS, of reactivity of different amino acid residues to a modifying reagent. Data thus obtained allow one to make inferences about protein conformations and their intermolecular interactions. Most of the protein footprinting studies so far have been performed on individual proteins in vitro. We explore whether a similar approach is possible with the proteins inside of living cells, employing dimethylsulfate (DMS), a reagent widely used for the in vivo footprinting of nucleic acids. DMS can induce methylation of the lysine, histidine and glutamate residues on proteins. Using models of the histone H2B/H2AZ heterodimer assembled in vitro and from chromatin treated in vivo, we show that the methylation by deuterated DMS allows one to distinguish the accessibility of a particular residue in and out of the protein's environmental/structural context. The detection of changes in protein conformations or their interactions in vivo can provide a new approach to the identification of proteins involved in various intracellular pathways and help in the search for perspective drug targets and biomarkers of diseases.
Macroevolution by transposition: drastic modification of DNA recognition by a type I restriction enzyme following Tn5 transposition.

We have characterized a novel mutant of EcoDXXI, a type IC DNA restriction and modification (R‐M) system, in which the specificity has been altered due to a Tn5 insertion into the middle of hsdS, the gene which encodes the polypeptide that confers DNA sequence specificity to both the restriction and the modification reactions. Like other type I enzymes, the wild type EcoDXXI recognizes a sequence composed of two asymmetrical half sites separated by a spacer region: TCA(N7)RTTC. Purification of the EcoDXXI mutant methylase and subsequent in vitro DNA methylation assays identified the mutant recognition sequence as an interrupted palindrome, TCA(N8)TGA, in which the 5′ half site of the wild type site is repeated in inverse orientation. The additional base pair in the non‐specific spacer of the mutant recognition sequence maintains the proper spacing between the two methylatable adenine groups. Sequencing of both the wild type and mutant EcoDXXI hsdS genes showed that the Tn5 insertion occurred at nucleotide 673 of the 1221 bp gene. This effectively deletes the entire carboxyl‐terminal DNA binding domain which recognizes the 3′ half of the EcoDXXI binding site. The truncated hsdS gene still encodes both the amino‐terminal DNA binding domain and the conserved repeated sequence that defines the length of the recognition site spacer region. We propose that the EcoDXXI mutant methylase utilizes two truncated hsdS subunits to recognize its binding site. The implications of this finding in terms of subunit interactions and the malleability of the type I R‐M systems will be discussed.
Personalized Location Recommendations with Local Feature Awareness

Location-based social networks (LBSNs) make it possible for servers to record users' location histories, mine their life patterns, and infer individual preferences. As an important component of LBSNs, recommender systems gained popularity in recent years. Recommender systems can automatically list candidate locations for users according to their preferences, which is different from traditional search methods. However, making effective recommendations suffers from data sparsity. In order to relieve this problem and achieve high effectiveness, we take context information into consideration and present a personalized location recommender system considering both user preference and local features in this paper. To be specific, we apply Labeled-LDA in user preference learning and local features inference processes, which are denoted as UL-LDA model and CL-LDA model, respectively. Because of this, we can make recommendations even on the condition that users are in a new city and have little information about the city. We evaluate our approach with extensive experiments on a large-scale Foursquare dataset. The experimental results clearly validate the effectiveness of our approach.
Datos y cifras

This paper analyzes the Spanish energy transition’s general situation and its increasing electricity prices in recent years from a free-market environmentalist (FME) approach. We hypothesize and argue that high taxes, high government subsidies, and government industrial access restrictions breach private property rights, hindering Spain’s renewable energy (RE) development. Our paper discovers that Spain’s state-interventionist policies have increased the cost of the energy and power industries, leading to electricity prices remaining relatively high before and after the outbreak of the COVID-19 pandemic. After reviewing the literature on the FME approach and Spain’s case, a Box–Jenkins (ARIMA) model is used to clarify the economic performance of the Spanish electricity industry with a proposal for forecasting electricity prices. It is observed that Spain fails the EU and its national goal of providing an affordable energy price as a part of the green energy transition. Finally, free-market environmental solutions and policy reforms are proposed to facilitate Spain’s
The Relative Efficient Markets Hypothesis: Information Space and Refutable Models

The concept of information is not specified with an information space in the conventional proposition of Efficient Markets Hypothesis (EMH). As a result, due to the “joint-hypothesis problem” (Fama, 1991), the EMH is not well-defined and empirically refutable. Nonetheless, the EMH or its accompanying model of equilibrium becomes well-defined and empirically refutable once the concept of information is confined to some particular information space. The EMH hence can be deciphered either way: the traditional none-refutable way or the information-specified refutable way. The former is what we call the absolute EMH and the later the relative EMH. By virtue of a Hilbert space we demonstrate how an information space alternative to the neoclassical one is characterized and how its relative efficiency is compared against the neoclassical information space in terms of viable price systems or pricing kernels.
Selected Ethical Issues in Research and Publication: Perceptions of Health Education Faculty

A national random sample of 195 university health education faculty at graduate degree–granting programs completed a 31-item survey with regard to their perceptions of ethical issues in research and publishing. Most respondents were male (57%), tenured (75%), had graduate faculty status (92%), had presented original research at conferences (85%), and had published articles in health education journals (89%). Faculty members were requested to assess whether 21 scenarios dealing with ethical issues in research and publishing were ethical, unethical, questionable, or not an ethical issue. Of the scenarios, 3 were considered ethical and 7 unethical by the majority of respondents. The perceptions of how ethical the remaining 11 scenarios were varied considerably. Perceptions of the ethical scenarios did not differ among respondents by sex, academic rank, years taught as a faculty member, whether the department taught units/classes on research ethics, or whether the respondents were from doctoral-level versus master’s-level programs.
Rapid Method for Coextraction of DNA and RNA from Natural Environments for Analysis of Ribosomal DNA- and rRNA-Based Microbial Community Composition

ABSTRACT A rapid protocol for the extraction of total nucleic acids from environmental samples is described. The method facilitates concomitant assessment of microbial 16S rRNA diversity by PCR and reverse transcription-PCR amplification from a single extraction. Denaturing gradient gel electrophoresis microbial community analysis differentiated the active component (rRNA derived) from the total bacterial diversity (ribosomal DNA derived) down the horizons of an established grassland soil.
A privacy-friendly smart metering architecture with few-instance storage

We provide a privacy-friendly cloud-based smart metering storage architecture which provides few-instance storage on encrypted measurements by at the same time allowing SQL queries on them. Our approach is most flexible with respect to two axes: on the one hand it allows to apply filtering rules on encrypted data with respect to various upcoming business cases; on the other hand it provides means for a storage-efficient handling of encrypted measurements by applying server-side deduplication techniques over all incoming smart meter measurements. Although the work at hand is purely dedicated to a smart metering architecture we believe our approach to have value for a broader class of IoT cloud storage solutions. Moreover, it is an example for Privacy-by-design supporting the positive-sum paradigm.
Preserved metabolic reserve capacity in skeletal muscle of post‐infarction heart failure patients

It has been proposed that exercise capacity during whole body exercise in post‐infarction congestive heart failure (CHF) patients is limited by skeletal muscle function. We therefore investigated the balance between cardiopulmonary and muscular metabolic capacity. CHF patients (n=8) and healthy subjects (HS, n=12) were included. Patients with coronary artery disease (CAD, n=8) were included as a control for medication. All subjects performed a stepwise incremental load test during bicycling (∼24 kg muscle mass), two‐legged knee extensor (2‐KE) exercise (∼4 kg muscle mass) and one‐legged knee extensor (1‐KE) exercise (∼2 kg muscle mass). Peak power and peak pulmonary oxygen uptake (VO2peak) increased and muscle‐specific VO2peak decreased with an increasing muscle mass involved in the exercise. Peak power and VO2peak were lower for CHF patients than HS, with values for CAD patients falling between CHF patients and HS. During bicycling, all groups utilized 24–29% of the muscle‐specific VO2peak as measured during 1‐KE exercise, with no difference between the groups. Hence, the muscle metabolic reserve capacity during whole body exercise is not different between CHF patients and HS, indicating that appropriately medicated and stable post‐infarction CHF patients are not more limited by intrinsic skeletal muscle properties during whole body exercise than HS.
Survival and Treatment for Colorectal Cancer Medicare Patients in Two Group/Staff Health Maintenance Organizations and the Fee-for-Service Setting

The current study compares treatment use and long-term survival in colorectal cancer patients between Medicare beneficiaries enrolled in two large prepaid group/staff health maintenance organizations (HMOs) and the fee-for-service (FFS) setting. The study is based on 15,352 colorectal cancer cases diagnosed between 1985 and 1992 and followed through 1995. Survival differences between the HMO and FFS cases were assessed using Cox regression. Treatment differences were evaluated using logistic regression. HMO cases had a lower overall mortality than did FFS cases but not a significantly lower colorectal cancer-specific mortality. Use of surgical resection was similar between HMO and FFS cases. However, rectal cancer cases in the HMOs were more likely to receive postsurgical radiation therapy than FFS cases. Superior overall survival in the HMOs may be the result of increased colorectal cancer screening, greater use of adjuvant therapies, and selection of healthier individuals.
Work-in-Progress: TTI: A Timing ISA for LET Model in Safety-Critical Systems

Safety-critical systems have suffered a complexity growth as the number of services continuously increases in these systems. The Logical Execution Time (LET) model is applied to tackle this issue due to its simple strategies and deterministic timed behaviors. However, existing implementations of LET usually rely on periodic timer interrupts of operating systems, yielding limited time precision and enormous jitter in kernel's executions. In this paper, we propose a time-triggered instruction set – TTI to augment ISA with timing properties. TTI implements as a processor architecture extension using co-processor2 interfaces in standard MIPS32. The extension mainly comprises a task management module, and a timed I/O-behaviors management module. Preliminary results show that our approach can significantly reduce overheads of LET kernel and jitters of the LET-based tasks compared to traditional implementations, which can achieve cycle-level precise timed behaviors as a result.
Primary Total Hip Arthroplasty using 3rd Generation Ceramic-on-Ceramic Articulation

Purpose Ceramic-on-ceramic (CoC) is currently a popular bearing combination in young patients in primary total hip arthroplasty (THA). The purpose of this study was to evaluate clinical and radiographic results and complications of cementless THA with 3rd generation CoC articulation. Materials and methods From April 2001 to January 2008, 310 primary THAs were performed in 300 patients using 3rd generation CoC articulation. The mean follow-up period was 8.9 years and the mean age at index surgery was 54.6 years. Patient clinical outcome was evaluated with the Harris Hip Score. Radiographic evaluations was performed to analyse osteolysis, implant fixation and loosening. Results Mean Harris Hip Score at last follow-up was 95.4 (76-100). Radiographic analysis demonstrated no evidence of stem or cup loosening and there were no cases of osteolysis. Ceramic wear was not detectable on the plain radiograph. Complications requiring revision occurred in 12 cases; 2 ceramic head fractures, 4 dislocations, 2 deep infections and 4 cases of periprosthetic fracture. The cohort had an overall revision rate of 3.9%. Conclusions Clinical outcomes using cementless THA with 3rd generation CoC articulation were satisfactory. Although the mechanical properties of ceramic materials have improved, there are still problems such as ceramic fracture and squeaking. More clinical study and investigation for alternative bearing are necessary to reduce complications. 4th generation CoC or ceramic on cross linked polyethylene may address some of these issues.
Pancreatic cancer microenvironment

Pancreatic ductal adenocarcinoma remains an extremely aggressive malignancy that is virtually therapy‐resistant and has therefore one of the worst prognoses of all human cancers. The focus of research, which had been placed mostly on genetic and epigenetic alterations of the cancer cells themselves, has shifted gradually towards the microenvironment. The cancer microenvironment consists of various components, including fibroblasts, endothelial cells, immune cells, and endocrine cells, that interact with each other and the cancer cells in a complex fashion. This interplay has implications for pancreatic cancer cell growth, migration and invasion, angiogenesis, and immunological recognition of cancer cells. Evidence is accumulating that the cancer microenvironment plays an active role in disease progression, and efforts are being made to target this interplay between cancer cells and host cells to improve the outcome of this deadly disease. © 2007 Wiley‐Liss, Inc.
Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics

The recognition of invading pathogens and endogenous molecules from damaged tissues by toll-like receptors (TLRs) triggers protective self-defense mechanisms. However, excessive TLR activation disrupts the immune homeostasis by sustained pro-inflammatory cytokines and chemokines production and consequently contributes to the development of many inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE), infection-associated sepsis, atherosclerosis, and asthma. Therefore, inhibitors/antagonists targeting TLR signals may be beneficial to treat these disorders. In this article, we first briefly summarize the pathophysiological role of TLRs in the inflammatory diseases. We then focus on reviewing the current knowledge in both preclinical and clinical studies of various TLR antagonists/inhibitors for the prevention and treatment of inflammatory diseases. These compounds range from conventional small molecules to therapeutic biologics and nanodevices. In particular, nanodevices are emerging as a new class of potent TLR inhibitors for their unique properties in desired bio-distribution, sustained circulation, and preferred pharmacodynamic and pharmacokinetic profiles. More interestingly, the inhibitory activity of these nanodevices can be regulated through precise nano-functionalization, making them the next generation therapeutics or “nano-drugs. ” Although, significant efforts have been made in developing different kinds of new TLR inhibitors/antagonists, only limited numbers of them have undergone clinical trials, and none have been approved for clinical uses to date. Nevertheless, these findings and continuous studies of TLR inhibition highlight the pharmacological regulation of TLR signaling, especially on multiple TLR pathways, as future promising therapeutic strategy for various inflammatory and autoimmune diseases.
The Internet profiles of men who have sex with men within bareback websites

The Internet has become a venue for men who have sex with men to search for sexual partners. Some of these men intentionally seek unprotected anal intercourse with other men (‘bareback’ sex). This paper focuses on the creation, use, and content of Internet personal profiles of men who have sex with men in the greater New York City metropolitan area who use bareback sites for sexual networking. We used a mixed-methods approach to examine data from a cybercartography of Internet sites conducted during the first phase of the research (199 personal profiles) and from in-depth interviews conducted during its second phase (120 men who have sex with men who sought partners online for bareback sex). Results indicate that men generally followed offline stereotypical patterns in their online profiles. However, men who disclosed being HIV-positive were more likely to include face and head pictures. Overall, the images they used were heavily sexualised in accordance with group norms perceived and reinforced by the websites' design and imagery. Bottom-identified men tended to be more explicit in the exposition of their sexual and drug use interests online. This paper highlights how certain virtual and social performances play upon and reinforce other, in the flesh, performances.
Color stability and degree of cure of direct composite restoratives after accelerated aging.

PURPOSE This study evaluated the color changes and amount of remaining C = C bonds (%RDB) in three dental composites after hydrothermal- and photoaging. METHODS AND MATERIALS The materials tested were Estelite sigma, Filtek Supreme and Tetric Ceram. Specimens were fabricated from each material and subjected to L* a* b* colorimetry and FTIR spectroscopy before and after aging. Statistical evaluation of the deltaL,* deltaa,* deltab,* deltaE and %deltaRDB data was performed by one-way ANOVA and Tukey's test. The %RDB data before and after aging were statistically analyzed using two-way ANOVA and Student-Newman-Keuls test. In all cases an alpha = 0.05 significance level was used. RESULTS No statistically significant differences were found in deltaL*, deltaa*, deltaE and %deltaRDB among the materials tested. Tetric Ceram demonstrated a significant difference in deltab*. All the materials showed visually perceptible (deltaE >1) but clinically acceptable values (deltaE < 3.3). Within each material group, statistically significant differences in %RDB were noticed before and after aging (p < 0.05). Filtek Supreme presented the lowest %RDB before aging, with Tetric Ceram presenting the lowest %RDB after aging (p < 0.05). The %deltaRDB mean values were statistically significantly different among all the groups tested. No correlation was found between deltaE and %deltaRDB.
Acetylsalicylic Acid Inhibits IL‐18‐Induced Cardiac Fibroblast Migration Through the Induction of RECK

The pathogenesis of cardiac fibrosis and adverse remodeling is thought to involve the ROS‐dependent induction of inflammatory cytokines and matrix metalloproteinases (MMPs), and the activation and migration of cardiac fibroblasts (CF). Here we investigated the role of RECK (reversion‐inducing‐cysteine‐rich protein with Kazal motifs), a unique membrane‐anchored MMP regulator, on IL‐18‐induced CF migration, and the effect of acetylsalicylic acid (ASA) on this response. In a Matrigel invasion assay, IL‐18‐induced migration of primary mouse CF was dependent on both IKK/NF‐κB‐ and JNK/AP‐1‐mediated MMP9 induction and Sp1‐mediated RECK suppression, mechanisms that required Nox4‐dependent H2O2 generation. Notably, forced expression of RECK attenuated IL‐18‐induced MMP9 activation and CF migration. Further, therapeutic concentrations of ASA inhibited IL‐18‐induced H2O2 generation, MMP9 activation, RECK suppression, and CF migration. The salicylic acid moiety of ASA similarly attenuated IL‐18‐induced CF migration. Thus, ASA may exert potential beneficial effect in cardiac fibrosis through multiple protective mechanisms. J. Cell. Physiol. 229: 845–855, 2014. © 2013 Wiley Periodicals, Inc.