Miracle-dz/UniFAR-FTUs huggingface dataset:
Progress and pitfalls of using isobaric mass tags for proteome profiling

ABSTRACT Introduction: Quantitative proteomics using mass spectrometry is performed via label-free or label-based approaches. Labeling strategies rely on the incorporation of stable heavy isotopes by metabolic, enzymatic, or chemical routes. Isobaric labeling uses chemical labels of identical masses but of different fragmentation behaviors to allow the relative quantitative comparison of peptide/protein abundances between biological samples. Areas covered: We have carried out a systematic review on the use of isobaric mass tags in proteomic research since their inception in 2003. We focused on their quantitative performances, their multiplexing evolution, as well as their broad use for relative quantification of proteins in pre-clinical models and clinical studies. Current limitations, primarily linked to the quantitative ratio distortion, as well as state-of-the-art and emerging solutions to improve their quantitative readouts are discussed. Expert opinion: The isobaric mass tag technology offers a unique opportunity to compare multiple protein samples simultaneously, allowing higher sample throughput and internal relative quantification for improved trueness and precision. Large studies can be performed when shared reference samples are introduced in multiple experiments. The technology is well suited for proteome profiling in the context of proteomic discovery studies.
Deciphering Patterns of Adaptation and Acclimation in the Transcriptome of Phaeocystis antarctica to Changing Iron Conditions1

The haptophyte Phaeocystis antarctica is endemic to the Southern Ocean, where iron supply is sporadic and its availability limits primary production. In iron fertilization experiments, P. antarctica showed a prompt and steady increase in cell abundance compared to heavily silicified diatoms along with enhanced colony formation. Here we utilized a transcriptomic approach to investigate molecular responses to alleviation of iron limitation in P. antarctica. We analyzed the transcriptomic response before and after (14 h, 24 h and 72 h) iron addition to a low‐iron acclimated culture. After iron addition, we observed indicators of a quick reorganization of cellular energetics, from carbohydrate catabolism and mitochondrial energy production to anabolism. In addition to typical substitution responses from an iron‐economic toward an iron‐sufficient state for flavodoxin (ferredoxin) and plastocyanin (cytochrome c6), we found other genes utilizing the same strategy involved in nitrogen assimilation and fatty acid desaturation. Our results shed light on a number of adaptive mechanisms that P. antarctica uses under low iron, including the utilization of a Cu‐dependent ferric reductase system and indication of mixotrophic growth. The gene expression patterns underpin P. antarctica as a quick responder to iron addition.
FOXM1: a potential therapeutic target in human solid cancers

ABSTRACT Introduction: FOXM1 is one of the most frequently overexpressed proteins in human solid cancers. Here, we discuss novel direct targets of FOXM1 as well as new pathways involving FOXM1, through which this protein exerts its oncogenic activity. Areas covered: We give a detailed review of FOXM1 transcriptional targets involved in 16 different types of human cancer as published in the literature in the last 5 years. We also discuss a novel positive feedback loop between FOXM1 and AKT – both well-established master regulators of cancer. Expert opinion: Despite the discovery of several FOXM1 inhibitors over the years (by our team and others), their therapeutic use is limited by their adverse off-target effects. Newly-discovered proteins regulated by FOXM1 present a promising alternative approach to target its pro-cancer activity. In addition, targeting regulating proteins that take part in the positive feedback loop between FOXM1/AKT has the double advantage of suppressing both, and can lead to developing novel anti-cancer drugs.
Pervasive Suicidal Integrases in Deep-Sea Archaea

Abstract Mobile genetic elements (MGEs) often encode integrases which catalyze the site-specific insertion of their genetic information into the host genome and the reverse reaction of excision. Hyperthermophilic archaea harbor integrases belonging to the SSV-family which carry the MGE recombination site within their open reading frame. Upon integration into the host genome, SSV integrases disrupt their own gene into two inactive pseudogenes and are termed suicidal for this reason. The evolutionary maintenance of suicidal integrases, concurring with the high prevalence and multiples recruitments of these recombinases by archaeal MGEs, is highly paradoxical. To elucidate this phenomenon, we analyzed the wide phylogenomic distribution of a prominent class of suicidal integrases which revealed a highly variable integration site specificity. Our results highlighted the remarkable hybrid nature of these enzymes encoded from the assembly of inactive pseudogenes of different origins. The characterization of the biological properties of one of these integrases, IntpT26-2 showed that this enzyme was active over a wide range of temperatures up to 99 °C and displayed a less-stringent site specificity requirement than comparable integrases. These observations concurred in explaining the pervasiveness of these suicidal integrases in the most hyperthermophilic organisms. The biochemical and phylogenomic data presented here revealed a target site switching system operating on highly thermostable integrases and suggested a new model for split gene reconstitution. By generating fast-evolving pseudogenes at high frequency, suicidal integrases constitute a powerful model to approach the molecular mechanisms involved in the generation of active genes variants by the recombination of proto-genes.
Issues with cancer spheroid models in therapeutic drug screening.

In vitro screening for anti-cancer agents currently uses mainly cell lines in 2D culture. It is generally assumed that 3D culture, namely spheroids, represent physiologically more relevant models for tumors. Unfortunately, drug testing in spheroids is not as easy and reproducible as in 2D culture because there are factors that limit the universal use of spheroids as screening platforms. Technical problems in the generation of uniform spheroids, cell/tumor-specific differences in the ability to form spheroids, and more complex readout parameters are main reasons for differences between spheroid data. The review discusses requirements for cancer spheroids to be representative models, suitable methodologies to generate spheroids for the screening, and readout parameters for the evaluation of anti-cancer agents.
Sildenafil as a vasodilatatory madiator in the treatment of abdominal sepsis

Objective: To analyse the effects of previous treatment with sildenafil in rats with abdominal sepsis induced by cecal ligation and puncture (CLP). Methods: Wistar rats were randomly allocated in 3 groups of 6 each. Sham group (SG): rats were subjected to laparotomy and no induction of sepsis; CLP/sil: rats subjected to cecal ligation and puncture, treated with sildenafil 1mg/Kg via gavage, 60 min before sepsis induction; CLP group: rats with sepsis, no sildenafil. After anesthesia under aseptic technique, we underwent a laparotomy and CLP. Postoperative pain was controlled with tenoxicam 3mg/Kg, i.m. The rats were observed for 24 hs, and examined on the late stage of polymicrobial abdominal sepsis. Body weight, leukogram, C-reactive protein, TNF-α, IL-1β, IL-6, IL-10. Statistical analysis was done by ANOVA and Tukey test, with significance p<0.05. Results: Group CLP rats had their weight reduced in 12% when compared with sham rats (p<0.05). However, comparing the sham and CLP/sil rats the diference on weight loss was not significant. Leukocytes and neutrophils counts were significantly elevated in group CLP rats compared with sham (p<0.05). In CLP/sil group rats a decreased total leukocyte and neutrophil counts were detected, compared with the CLP group (p<0.05). Reduced levels of C-reactive protein in the LPC/sil group were observed, compared with CLP rats (p<0.05). Serum levels of TNF-α, IL-1β and IL-6 were lower in the CLP/sil rats, compared with untreated CLP animals (p<0.05). Increased IL-10 in the CLP/sil rats, compared with CLP rats, demonstrated a protective effect on the vasodilatory sepsis. Conclusion: The data revealed that the pretreatment of abdominal sepsis with the vasodilator sildenafil favorably influenced the evolution of inflammation and immune response in rats.
Roux-en-Y Gastric Bypass and Antipsychotic Therapeutic Drug Monitoring: Two Cases

Many patients with psychiatric conditions undergo bariatric surgery. The Roux-en-Y gastric bypass (RYGB) procedure alters medication pharmacokinetic properties and may have significant impact on drug response. Our report is the first to describe atypical antipsychotic therapeutic drug monitoring in patients who have undergone RYGB. The first patient is a 53-year-old female with a stable psychiatric condition undergoing a laparoscopic RYGB. Her medications prior and following the procedure include bupropion, fluvoxamine, lurasidone, methylphenidate, oxcarbazepine, and verapamil. A concentration steady-state lurasidone concentration obtained prior to the procedure was 20 ng/mL and returned at 8.1 ng/mL, 29 days after surgery. The second patient is a 42-year-old female psychiatric inpatient who had previously undergone an RYGB procedure. Medications on admission included phenytoin, oxcarbazepine, risperidone, and venlafaxine. The patient was believed to be a good candidate for a long-acting antipsychotic and paliperidone was chosen. After concentration-steady-state on 6 mg oral paliperidone, a 23.5-hour trough level was drawn. The patient was noted to be improved on the oral paliperidone, the paliperidone long-acting injection was given, and the patient was discharged. After discharge, the paliperidone concentration returned very low at 1.1 ng/mL. We describe the contributions of drug–drug interactions, medication release mechanisms, and food coadministration that may have affected our therapeutic drug monitoring. Our therapeutic drug monitoring results need to be replicated prior to use in the general population but suggest that oral extended-release drug formulations are particularly poor choices and that nonoral antipsychotic formulations may be preferred in some patients who have undergone RYBG.
Screening for Lifetime History of Traumatic Brain Injury Among Older American and Irish Adults at Risk for Dementia: Development and Validation of a Web-Based Survey.

BACKGROUND Traumatic brain injury (TBI) is an established risk factor for dementia but mechanisms are uncertain. Accurate TBI exposure classification is critical for cognitive aging research studies seeking to discover mechanisms and treatments of post-TBI dementia. Brief TBI screens, commonly used in epidemiological studies of cognitive aging, are insensitive, leading to exposure mis-classification. Comprehensive TBI interviews, while more sensitive, may be impractical. OBJECTIVE We aimed to develop and validate a scalable, self-administered, comprehensive, web-based, TBI exposure survey for use in international cognitive aging research. METHODS We adapted a gold-standard comprehensive TBI interview (the Ohio State University TBI Identification Method; OSU TBI-ID) into a self-administered web-based survey for older adults (Older Adult modification of the OSU TBI-ID; OA OSU TBI-ID). We assessed reliability of our web-based survey versus the gold-standard interview among 97 older adults with normal cognition and mild cognitive impairment (MCI). In addition, we assessed sensitivity of the National Alzheimer's Coordinating Center Uniform Data Set (NACC UDS) brief TBI screen versus the interview among 70 older adults with normal cognition. RESULTS Our OA OSU TBI-ID web-based survey had good to excellent reliability versus the interview (κ 0.66-0.73; ICCs 0.68-0.81) even among the sub-set with MCI (κ 0.74-0.88; ICCs 0.76-0.85), except for several age-at-injury variables. The NACC UDS brief TBI screen missed 50% of TBI exposures identified using the OSU TBI-ID interview. CONCLUSION The OSU TBI-ID interview and web-based survey may facilitate more accurate TBI exposure classification in cognitive aging research thereby accelerating discovery of targetable mechanisms of post-TBI dementia.
The Relation Between the Phase Transition in Ising Type Agent Model and Its Implication to the Growth Curve

It has been said that many ICT related services such as SNS have network externality. It has also been said that the network externality has the chilling effect and a service cannot gain many users at the start-up stage, which means that the service providing firm must keep investing even if it does not have enough income at its start-up. This chilling effect can be explained by agent models. It is also known that agent model has the feature of phase transition. In this paper, we investigate the effect of the phase transition and its relation to the chilling effect. It is shown that there is no chilling effect under the process of phase transition while keeping other features of externality such as fixed shares. This implies that a service providing firm can obtain large number of users at the start-up stage with taking the advantage of the fixed share.
ADRRI JOURNAL OF AGRICULTURE AND FOOD SCIENCES

The study sought to examine the relevance of food tourism in national development, determine the factors which influence the participation in food tourism and promote interest in local dishes. Questionnaires were administered to 200 respondents who were purposively selected tourists and 20 restaurant operators were interviewed from the Kintampo, Brong Ahafo region. The results revealed that most 104(52%) tourists travel from far and near to enjoy the culture of other regions and countries of which food is part. Factors influencing participation in food tourism are that tourists look for quality food to enjoy and also are attracted by food Bazaars and local delicacies. It was also agreed (100%) that food tourism is relevant to national development. It is therefore recommended that Food tourism be part of the government’s tourism agenda and should be properly organized to meet the current changes and challenges. Also hoteliers should from time to time organize food bazaar and conferences showcasing Ghanaian indigenous dishes. There is the need for the Ministry of Tourism to organize food fairs to showcase local delicacies by both chop bar operators and other food vendors to market the industry.
Application of metabolomics in the diagnosis of breast cancer: a systematic review

Breast cancer (BC) remains the most frequent type of cancer in females worldwide. However, the pathogenesis of BC is still under the cloud, along with the huge challenge of early diagnosis, which is widely acknowledged as the key to a successful therapy. Metabolomics, a newborn innovative technique in recent years, has demonstrated great potential in cancer-related researches. The aim of this review is to look back on clinical and cellular metabolomic studies in the diagnosis of BC over the past decade, and provide a systematic summary of metabolic biomarkers and pathways related to BC diagnosis.
Ultra-Dense Networks: A Holistic Analysis of Multi-Piece Path Loss, Antenna Heights, Finite Users and BS Idle Modes

We discover a new capacity scaling law in ultra-dense networks under practical system assumptions, such as a general multi-piece path loss model, a non-zero base station to user equipment antenna height difference, and a finite user equipment density. The intuition and implication of this new capacity scaling law are completely different from those found in the year 2011. That law indicated that the increase of the interference power caused by a denser network would be exactly compensated by the increase of the signal power due to the reduced distance between transmitters and receivers, and thus, network capacity should grow linearly with network densification. However, we find that both the signal and interference powers become bounded in practical ultra-dense networks, which leads to a constant capacity scaling law. Moreover, our new discovery on the constant capacity scaling law indicates three network optimization problems respectively for base station deployment, user equipment scheduling and base station coordination. These three optimization problems are justified and solved in this paper, shedding new light on the deployment and optimization of ultra-dense networks.
BIFUERCATION OF PERPENDICULAR ROTATION AND FIELD PENETRATION AT THE TRANSITION TO RMP-INDUCED ELM-CRASH SUPPRESSION

The bifurcation of perpendicular rotation (v⊥) at the transition of ELM-crash suppression has been measured using electron cyclotron emission imaging (ECEI) system on KSTAR. The ECEI revealed that the ELM crashes are suppressed along with a rapid reduction of v⊥, which synchronizes with the transition into and out of the ELM-crash suppression. The v⊥ bifurcation is mainly attributed to the rapid change of E × B velocity and the v⊥ magnitude is maintained the smallest near the normalized flux surface ψN~0.95 during the ELM-crash suppression. The plasma response to the RMP, normalized by v⊥ changes, is strongest in the vicinity of ψN~0.95 during the ELM-crash suppression.
Motion Magnified Video Application to Machinery Diagnosis

Vibration detection can be performed by a meter, or a single channel spectrum analyzer. The former has quantified vibration amplitude levels since the 1950’s, while the latter was able to implement the Fast Fourier Transform (FFT) since the 1960’s to break vibration down into its frequency components. Multiple channel FFT analyzers enabled the process of Operating Deflection Shape (ODS) determination, which has been an important tool in visualizing the vibration of the machine and its system, including the foundation and piping networks. The input for ODS is the phase-linked signal set from a group of accelerometers, moved over often hundreds of test points. The data is superimposed onto a CAD model, and then scaled-up vibrations are animated at frequencies of interest. This process provides valuable insights, but is time-consuming and therefore expensive each time it is applied by experts, and it is error-prone. An alternative method has been developed that is based on evaluation of high resolution/ high speed videos. The method provides information equivalent to a high-sensor-count ODS, by treating each pixel as an accelerometer, using the pixel’s light intensity modulation to translate information embedded in the video into vibration motion able to be observed and interpreted by human investigators. This method is known by some as Motion-Magnified Video (MMV).
Chromosome Maintenance

Maintenance of chromosomal organization is critical for stable chromosome function. Two aspects of maintenance annotated in Reactome are centromeric chromatin assembly outside the context of DNA replication, involving nucleosome assembly with the histone H3 variant CenH3 (also called CENP-A), and the maintenance of telomeres , protein-DNA complexes at the ends of linear chromosomes that are important for genome stability.
Epistemic and Root Modals in Chinese Students’ English Argumentative Writings

The role of learners’L1 in L2 collaborative activities has been of great interest to researchers and teachers. Much effort has been devoted to examining learners’ interactions during collaborative work. However, little attention has been paid to how the shared L1 may affect the text features of the written production in collaborative writing. The present study examined this issue by comparing the complexity, accuracy, and fluency of the essays by students who share the same L1s with those by students who had different L1s. Ten pairs of intermediate-low ESL learners formed two groups: the group of shared L1s and the group of different L1s. Each pair wrote a cause-effect essay on a topic of their own choice. The essays were analyzed in terms of complexity, accuracy, and fluency. The results indicated that learners’ shared the L1s have beneficial effects on the complexity of their essays. Also, sharing L1s in collaborative writing did not result in lower accuracy and fluency of learners’ written production. Reasons accounting for the results and pedagogical implications were discussed.
Urographic changes in homozygous sickle cell disease.

: A prospective urographic study of 40 Nigerian homozygous sickle cell patients is presented. The age range was 13-51 years with a mean of 20. The excretory urogram was normal in 30% of the patients. There is a very high incidence of renal papillary necrosis (40%). The other abnormalities observed are non-obstructive caliectasis (47.5%), poor excretion of contrast medium (40%) and renal enlargement. The incidence of urographic abnormality was neither age- or sex-related. There is also no relationship between abnormality and urinary symptoms.
Decision-making of Adjuvant Chemotherapy for Breast Cancer Patients with Discordant Risk Classifications between Clinical-Pathological Factors and 21-gene Recurrence Score

Background: Clinical-pathological factors and 21-gene recurrence score (RS) influence adjuvant chemotherapy (ACT) decision for early breast cancer patients. We investigated the decision-making of ACT in patients with discordant risk classifications of clinical-pathological factors and RS. Methods: Patients with hormonal receptor (HR)+/ human epidermal growth factor receptor 2 (HER2)-, early breast cancer, who underwent 21-gene RS testing were identified from Ruijin Hospital (RJBC) and the Surveillance, Epidemiology, and End Results (SEER) database. According to Adjuvant! Online and RS (≤25 or >25), discordant risk classifications were defined as: clinical low-risk/ RS high-risk (C-low/ RS-high) and clinical high-risk/ RS low-risk (C-high/RS-low). McNemar's test was used to assess the changes between pre- and post-RS recommendations. Breast cancer-specific survival (BCSS) was estimated using the Kaplan-Meier methods. Results: Among 727 RJBC patients, the C-low/RS-high group and the C-high/RS-low group represented 19.7% and 21.3% of the cohort. After receiving 21-gene RS results, treatment recommendations were changed for 22.1% patients with discordant risk classifications: ACT rate increased from 41.9% to 75.5% in the C-low/RS-high group and decreased from 63.9% to 60.0% in the C-high/RS-low group. Among 2958 patients from the SEER cohort, 18.4% of the C-high/RS-low group and 59.2% of the C-low/RS-high group received ACT. There was no significant difference in the estimated 3-year BCSS between ACT or not among the C-low/RS-high group (p=0.708) and the C-high/RS-low groups (p=0.391). Conclusion: For patients with discordant risk classifications, physicians were apt to adopt the 21-gene RS rather than routine clinical-pathological factors to guide ACT selection.