Miracle-dz/UniFAR-FTUs huggingface dataset:
Degrons in cancer

Understanding protein degradation signals and systems reveals targets for cancer therapy. Gloss There are many cellular proteins that need to be eliminated quickly in response to changing conditions in or around the cells. Most of these proteins carry a short functional element in their sequence, called a degron. Degrons are typically composed of 6 to 10 amino acids and are generally located within flexible regions of proteins so that the degrons can easily interact with other proteins. E3 ubiquitin ligases bind to specific degrons, enabling the attachment of multiple copies of ubiquitin to target proteins. The ubiquitin chains are a molecular signal that directs the proteins to the proteasome, where the tagged proteins are chopped up into pieces and recycled. The correct removal of proteins is important for many biological processes, such as regulating transcription and controlling the major steps during cell division. Regulated protein degradation also turns off the activity of some proteins that are activated by transient external signals. The encounter between the E3 ligase and the degron determines whether a protein lives or dies. There are ~600 different E3 ligases that are encoded in the human genome. Each of these E3 ligases targets a different set of proteins and operates under a different condition. This ubiquitin-mediated protein degradation process is regulated at multiple levels. Defects in this system can cause systemic diseases, including cancer. This Review with 8 figures, 1 table, and 360 references describes how mutations that affect ubiquitin-mediated protein degradation system contribute to cancer. Degrons are the elements that are used by E3 ubiquitin ligases to target proteins for degradation. Most degrons are short linear motifs embedded within the sequences of modular proteins. As regulatory sites for protein abundance, they are important for many different cellular processes, such as progression through the cell cycle and monitoring cellular hypoxia. Degrons enable the elimination of proteins that are no longer required, preventing their possible dysfunction. Although the human genome encodes ~600 E3 ubiquitin ligases, only a fraction of these enzymes have well-defined target degrons. Thus, for most cellular proteins, the destruction mechanisms are poorly understood. This is important for many diseases, especially for cancer, a disease that involves the enhanced expression of oncogenes and the persistence of encoded oncoproteins coupled with reduced abundance of tumor suppressors. Loss-of-function mutations occur in the degrons of several oncoproteins, such as the transcription factors MYC and NRF2, and in various mitogenic receptors, such as NOTCH1 and several receptor tyrosine kinases. Mutations eliminating the function of the β-catenin degron are found in many cancers and are considered one of the most abundant mutations driving carcinogenesis. In this Review, we describe the current knowledge of degrons in cancer and suggest that increased research on the “dark degrome” (unknown degron-E3 relationships) would enhance progress in cancer research.
CYP2A13 expressed in human bladder metabolically activates 4‐aminobiphenyl

Cigarette smoking is the predominant risk factor for bladder cancer. Aromatic amines such as 4‐aminobiphenyl (ABP) is the major carcinogens found in tobacco smoke. Although it is generally accepted that ABP is metabolically activated via N‐hydroxylation by CYP1A2 in human liver, previous studies using Cyp1a2‐null mice indicated the involvement of other enzyme(s). Here we found that CYP2A13 can metabolically activate ABP to show genotoxicity by Umu assay. The Km and Vmax values for ABP N‐hydroxylation by recombinant CYP2A13 in E. coli were 38.5 ± 0.6 μM and 7.8 ± 0.0 pmol/min/pmol CYP, respectively. The Km and Vmax values by recombinant CYP1A2 were 9.9 ± 0.9 μM and 39.6 ± 0.9 pmol/min/pmol CYP, respectively, showing 20‐fold higher intrinsic clearance than CYP2A13. In human bladder, CYP2A13 mRNA, but not CYP1A2, is expressed at a relatively high level. Human bladder microsomes showed ABP N‐hydroxylase activity (Km = 34.9 ± 4.7 μM and Vmax = 57.5 ± 1.9 pmol/min/mg protein), although the intrinsic clearance was 5‐fold lower than that in human liver microsomes (Km = 33.2 ± 2.0 μM and Vmax = 293.9 ± 5.8 pmol/min/mg protein). The activity in human bladder microsomes was prominently inhibited by 8‐methoxypsoralen, but not by fluvoxamine, anti‐CYP1A2 or anti‐CYP2A6 antibodies. CYP2S1, which is expressed in human bladder and has relatively high amino acid identities with CYP2As, did not show detectable ABP N‐hydroxylase activity. In conclusion, although the enzyme responsible for ABP N‐hydroxylation in human bladder microsomes could not be determined, we found that CYP2A13 metabolically activates ABP. © 2006 Wiley‐Liss, Inc.
Evaluation and Optimization of Battery-Energy-Aware PPM Schemes for Wireless Sensor Networks

Nodes in wireless sensor networks (WSNs) are typically powered by batteries. Hence, their energy conservation is a critical problem. In this paper, pulse position modulation (PPM), one of the orthogonal signaling formats, is tailored for WSNs into two schemes: mono-mode PPM and multi-mode PPM. Resorting to an idealized system model and a practical system model, which combine the power consumptions in transmission and reception modules of nodes with the idealized and realistic battery characteristics, the energy efficiencies of mono- and multi-mode PPM are evaluated and compared. To minimize the battery energy consumption (BEC), these schemes are further optimized for a link in path-loss channels. Our analytical and numerical results show that considerable energy can be saved by multi-mode PPM, and/or by the parameter optimization in terms of constellation size M, at various communication distances
Pro‐Girl Bias in Intra‐Household Allocation in the Rural Philippines: Revisiting the 'Adult Goods' Approach

This paper detects pro-girl (age 5-15) bias in intrahousehold allocation of consumption budget in the rural Philippines using Deaton’s “adult goods” method. Based on additional checks (including those for endogeneity), the results appear to be robust. The paper also finds that a larger share of girls among household members is positively associated with a larger budget share on transportation, suggesting that parents pay more for girls’ transportation, possibly due to safety concerns. The results also suggest that, despite some earlier results in the literature, the adult goods method is capable of detecting gender bias, although alcohol and tobacco may not be suitable for detecting gender bias.
Evaluation of the effect of diet composition and B-group vitamins supplementation on selected calcium metabolism parameters in female rats.

BACKGROUND The aim of the study was to observe the effects of a modified diet, in which whole grains of cereals had been isocalorically substituted with wheat flour (type "500") and saccharose, and supplementation with B-group vitamins, on selected calcium metabolism parameters in female rats. MATERIAL AND METHODS The experiment was carried out on 36 female rats aged 6 months. Animals were fed two different diets. Groups I and II received clean tap water to drink, while group III had water solution of group-B vitamins. RESULTS An analysis of the outcomes of the diet modifications allowed concluding that the females fed on the modified feed, either supplemented or non-supplemented, excreted more calcium with urine and exhibited its lower concentrations in blood plasma, as compared with the females fed on the standard feed. No significant differences, however, were observed in plasma ionized calcium concentrations in the studied animals, which implies that the regulation mechanism of its bio-active form concentrations is preserved. It has been found that the applied supplementation of the modified diet promoted bone calcium release inducing plasma alkaline phosphatase activity in this group of animals. Supplementation was also accompanied by a shift in calcium distribution manifested by its increased concentrations in erythrocytes. CONCLUSIONS Change in diet composition and supplementation were found to significantly affect calcium metabolism of the rats examined. Observed intracellular calcium accumulation may have been an underlying cause of an increased adipose tissue accumulation in B-group vitamin supplemented animals, which had been observed in previous studies.
Forecasting turbulence in the Asian and European stock market using regime-switching models

An early warning system to timely forecast turbulences in the Asian and European stockmarket is proposed. To ensure comparability, the model is constructed analogously to the early warningsystem for the US stock market presented by Hauptmann et al. (2014). Based on the time series ofdiscrete monthly returns of the Nikkei 225 and the EuroStoxx 50, filtered probabilities are estimated bytwo successive Markov-switching models with two regimes each. The market is thus separated in threestates: calm, turbulent positive and turbulent negative. Subsequently, a forecasting model using logisticregression and economic input factors is selected. In an empirical asset management case study it isillustrated that the investment performance is improved when considering the signals of the establishedwarning system. Moreover, the US, Asian and European model are compared and interdependenciesare highlighted.
Use of Subgenic 18S Ribosomal DNA PCR and Sequencing for Genus and Genotype Identification of Acanthamoebae from Humans with Keratitis and from Sewage Sludge

ABSTRACT This study identified subgenic PCR amplimers from 18S rDNA that were (i) highly specific for the genus Acanthamoeba, (ii) obtainable from all known genotypes, and (iii) useful for identification of individual genotypes. A 423- to 551-bpAcanthamoeba-specific amplimer ASA.S1 obtained with primers JDP1 and JDP2 was the most reliable for purposes i and ii. A variable region within this amplimer also identified genotype clusters, but purpose iii was best achieved with sequencing of the genotype-specific amplimer GTSA.B1. Because this amplimer could be obtained from any eukaryote, axenic Acanthamoeba cultures were required for its study. GTSA.B1, produced with primers CRN5 and 1137, extended between reference bp 1 and 1475. Genotypic identification relied on three segments: bp 178 to 355, 705 to 926, and 1175 to 1379. ASA.S1 was obtained from single amoeba, from cultures of all known 18S rDNA genotypes, and from corneal scrapings of Scottish patients with suspected Acanthamoeba keratitis (AK). The AK PCR findings were consistent with culture results for 11 of 15 culture-positive specimens and detected Acanthamoeba in one of nine culture-negative specimens. ASA.S1 sequences were examined for 6 of the 11 culture-positive isolates and were most closely associated with genotypic cluster T3-T4-T11. A similar distance analysis using GTSA.B1 sequences identified nine South African AK-associated isolates as genotype T4 and three isolates from sewage sludge as genotype T5. Our results demonstrate the usefulness of 18S ribosomal DNA PCR amplimers ASA.S1 and GTSA.B1 for Acanthamoeba-specific detection and reliable genotyping, respectively, and provide further evidence that T4 is the predominant genotype in AK.
Real-time dynamics of methyl-CpG-binding domain protein 3 and its role in DNA demethylation by fluorescence correlation spectroscopy

With unprecedented development in technology, epigenetics is recognized as a substantial and flexible regulatory pathway for phenotyping. Cytosine methylation and its subsequent oxidization have attracted significant attention due to their direct impact on gene regulation, in association with methyl-CpG-binding domain proteins (MBDs) and transcription related factors. In this study we record the dynamics of DNA demethylation using the recombinant MBD3-GFP protein in living cells under hypoxia and Decitabine treatment using Fluorescence Correlation Spectroscopy (FCS) by monitoring the diffusion dynamics of MBD3. Our study shows a DNA-replication-independent decrease of 5-methylcytosine (5mC)/5-hydroxymethylcytosine (5hmC) under hypoxia vs. a dependent decrease under Decitabine treatment. Further, we define a significantly faster diffusion of MBD3 in the nucleus as a precursory event for active demethylation rather than the Decitabine induced passive demethylation. By monitoring the diffusion of bound and unbound MBD3 in the nucleus we were able to identify and characterize hypoxia-sensitive cells from insensitive/tolerant cells, as well as the respective contribution to active demethylation in a time-dependent manner. Last, we quantitatively describe the concurrent decreasing trend in all of the three oxidized products of 5mC, which points to the potential involvement of ten-eleven-translocation proteins (TETs) in hypoxia induced active demethylation. Overall, for the first time we correlate the dynamic process of DNA demethylation with the biophysical properties of the corresponding DNA binding proteins in live single cells by single molecule spectroscopy.
Phase I trial of preoperative cetuximab with concurrent continuous infusion 5-fluorouracil and pelvic radiation in patients with local-regionally advanced rectal cancer.

3560 Background: Cetuximab, a chimeric anti-EGFR monoclonal antibody, has clinical activity in colorectal cancer with demonstrated safety, efficacy and additive synergy with radiation in solid tumors (head & neck, lung). A pilot trial was therefore designed to investigate the safety of cetuximab in combination with standard neoadjuvant protracted infusion 5-FU and radiation therapy in ultrasound T3-4 (uT3-4) or clinical T4 (cT4) or locally recurrent rectal adenocarcinoma. Secondary objectives of clinical activity were assessed by R0 resection and pathologic complete response (CR) rates. METHODS uT3-4 or cT4 or locally recurrent rectal adenocarcinoma patients received cetuximab 400mg/m2 day 1 (250mg/m2 weekly thereafter) and 5-FU IVCI (225mg/m2) over 5.5 weeks with concurrent pelvic radiation (5040cGy), and cetuximab (250mg/m2 Qweek) for 4 additional weeks, followed by surgical resection 1-3 weeks later. RESULTS Total Treated: 20 patients (ages 27 - 72), 19 uT3 patients, 1 Local Recurrence patient. Cetuximab Therapy (10 planned treatments): Too early 2 pts, ≥ 8 doses 12 pts, 5 - 8 doses 2 pts, < 5 total doses 4pts* (*cetuximab not given due to: 1 pt - acute cholecystitis from cholelithiasis; 1 pt - Grade 3 radiation perineal toxicity; 2 pts - treatment non-compliance). Radiation Therapy - 18 pts completed, 2 pts too early. Grade 3/4 Toxicities: Diarrhea 10%, Acneiform Rash (outside RT field) 15%, Stomatitis 5%, Radiation Field Dermatitis 5%, Transaminitis 5%. Surgical Outcomes: (17 pts completed surgery): R0 Resection 100%, Pathologic CR 12%. CONCLUSIONS Cetuximab in combination with protracted infusion 5-FU and concurrent radiation is feasible without synergistic or unexpected toxicities. Further randomized investigation of this regimen in the neoadjuvant setting for rectal cancer is warranted. No significant financial relationships to disclose.
Retrenchment Strategies and Family Involvement: The Role of Survival Risk

This article analyzes retrenchment strategies that family businesses adopt during periods of crisis. From a socioemotional wealth perspective, we propose that the influence of family board members and family CEOs on retrenchment depends on survival risk. We collected empirical data from companies on the Spanish Stock Exchange (2008-2012). Our findings reveal that family involvement intensifies retrenchment when performance is declining, and that retrenchment intensifies when survival is at risk. We also demonstrate that family firms are able to implement retrenchment measures when required to improve their performance.
TERLIPRESSIN VERSUS NORADRENALINE FOR HEPATORENAL SYNDROME. Economic evaluation under the perspective of the Brazilian Public Health System.

BACKGROUND - Terlipressin and noradrenaline are the best studied treatments for hepatorenal syndrome, and there is no evidence of superiority of one over the other regarding to efficacy. While the former drug is more costly, the latter requires admission into an intensive care unit. OBJECTIVE - The aim of this study was to perform an economic evaluation, comparing treatments for hepatorenal syndrome with terlipressin and noradrenaline. METHODS - For the economic evaluation, a cost-minimization analysis was performed. Direct medical costs of the two treatment strategies were compared under the perspective of the Brazilian Public Health System as the third-party payer. A probabilistic sensitivity analysis was performed. RESULTS - The costs of treatments with terlipressin or noradrenaline were 287.77 and 2,960.45 International Dollars (Int$) respectively. Treatment using terlipressin would save Int$2,672.68 for the Public Health System for each hospital admission related to hepatorenal syndrome. In the probabilistic sensitivity analysis, it was verified that the cost of the treatment with noradrenaline could vary between Int$2,326.53 and Int$3,644.16, while costs related to the treatment using terlipressin are not variable. CONCLUSION - The treatment strategy using terlipressin was more economical than that using noradrenaline under the perspective of the Brazilian Public Health System as the third-party payer.
Predictors of proximal tibia anterior shear force during a vertical stop‐jump

Anterior cruciate ligament (ACL) continues to be a significant medical issue for athletes participating in sports and recreational activities. Biomechanical analyses have determined that anterior shear force is the most direct loading mechanism of the ACL and a probable component of noncontact ACL injury. The purpose of this study was to examine the biomechanical predictors of proximal tibia anterior shear force during a stop‐jump task. A biomechanical and electromyographic (EMG) analysis of the knee was conducted while subjects performed a vertical stop‐jump task. The task was chosen to simulate an athletic maneuver that included a landing with a sharp deceleration and a change in direction. The final regression model indicated that posterior ground reaction force, external knee flexion moment, knee flexion angle, integrated EMG activity of the vastus lateralis, and sex (female) would significantly predict proximal tibia anterior shear force (p < 0.0001, R2 = 0.8609). Knee flexion moment had the greatest influence on proximal tibia anterior shear force. The mathematical relationships elucidated in the current study support previous clinical and basic science research examining noncontact ACL injuries. This data provides important evidence for clinicians who are examining the risk factors for these injuries and developing/validating training programs to reduce the incidence of injury. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1589–1597, 2007
Forecasting the Demand for Petroleum Products: A Guide to Long Term National Strategic Planning in Ghana

Forecasting is the process of using the patterns contained in past data to predict future values. Forecasts are numerical estimates of the future levels of sales, demand, inventories costs, imports, exports and prices among others; for a firm, an industry, a sector of the economy, or the total economy. The objective of forecasting is to assist management to plan requirements for marketing efforts, materials, personnel, production, services, capital acquisition, construction and finances. The data for the petroleum products were obtained from National Petroleum Authority (NPA) and that of inflation rates as well as the exchange rates were obtained from Ghana Statistical Service (GSS). The data were analysed using statistical software such as Minitab, Excel or SPSS. The main approach to the analysis was exploratory data analysis. Various techniques in times series such as moving averages, exponential smoothing etc were used to model and forecast the demand for Petroleum Products from 1999 â€“ 2007 and also how inflation, Â exchange rates, population etc may impact on the economy of Ghana. Two Econometric models were actually developed and comparison with regard to their R2, Adjusted R2, t-statistics were made using non-natural and natural logarithms for the models. Based on the analysis carried out it was found out that, the best model to be used in forecasting was the model without the natural logarithms. Another finding that came to light was that, some of the independent variables were not quite significant which might impact on the demand for the various petroleum products when analysing with respect to the their R2 and t-statistics values. The results of the R2, Adjusted R2, Predicted values clearly again showed that LPG was the petroleum product which was more demanded, followed by the Gasoil etc. The study also revealed that, Inflation, Exchange Rate, Expump Price and Urban Population could affect the demand for the various product and consequently on the Economy of Ghana. From the study, the irregular nature of the variation of the demand for the petroleum products may be attributed to the problem of under production therefore; there is the need to step up production in order to ensure constant supply of the products for economic activities to be pursued.
MINISYMPOSIUM : POST MORTEM IMAGING Normal pediatric postmortem CT appearances

Postmortem radiology is a rapidly developing specialty that is increasingly used as an adjunct to or substitute for conventional autopsy. The goal is to find patterns of disease and possibly the cause of death. Postmortem CT images bring to light processes of decomposition most radiologists are unfamiliar with. These postmortem changes, such as the formation of gas and edema, should not be mistaken for pathological processes that occur in living persons. In this reviewwe discuss the normal postmortem thoraco-abdominal changes and how these appear on CT images, as well as how to differentiate these findings from those of pathological processes.