Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of Ca2+/Calmodulin Dependent Protein Kinase Kinase 2 Leads to Aberrant Transferrin Phosphorylation and Trafficking: A Potential Biomarker for Alzheimer's Disease

Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a serine/threonine kinase that is activated following an increase in the intracellular Ca2+ concentration and activates multiple signaling cascades that control physiologically important neuronal processes. CaMKK2 has been implicated in schizophrenia, bipolar disease, neurodegeneration, and cancer. Using isoelectric focusing (IEF) and mass spectrometry-based proteomic analysis, it was found that knockdown (KD) of CaMKK2 in cultured adult primary dorsal root ganglion (DRG) neurons resulted in the reduction of transferrin (TF) phosphorylation at multiple functionally relevant residues which corresponded to loss of an acidic fraction (pH~3-4) of TF. In vitro studies using CRISPR/Cas9 based CaMKK2 knockout (KO) HEK293 and HepG2 cells lines validated previous findings and revealed that loss of CaMKK2 interfered with TF trafficking and turnover. TF is an iron transporter glycoprotein. Abnormal accumulation of iron and/or deregulated Ca2+ homeostasis leads to neurodegeneration in Alzheimer's disease (AD). Therefore, it was hypothesized that aberrant CaMKK2 in AD may lead to aberrant phosphorylated transferrin (P-TF: pH~3-4 fraction) which may serve as a hallmark biomarker for AD. A significant reduction of P-TF in the brain and serum of CaMKK2 KO mice and a triple-transgenic mouse model of AD (3xTg-AD) supported this hypothesis. In addition, analysis of early (< 65 years) and late-stage (>65 years) postmortem human AD cerebrospinal fluid (CSF) and serum samples revealed that aberrant P-TF (pH~3-4 fraction) profile was associated with both early and late-stage AD compared to age-matched controls. This indicates P-TF (pH~3-4 fraction) profile may be useful as a minimally invasive biomarker for AD. In addition, this study provides a link between aberrant CaMKK2 with TF trafficking and turnover which provides a novel insight into the neurodegeneration process.
Interferon‐γ Receptor 1 and GluR1 upregulated in motor neurons of symptomatic hSOD1G93A mice

Motor neurons are markedly vulnerable to excitotoxicity mostly by alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic receptor (AMPAR) stimulation and are principal targets in the neurodegenerative disease Amyotrophic Lateral Sclerosis. Interferon‐gamma (IFN‐γ), a pro‐inflammatory cytokine, can independently cause neuronal dysfunction by triggering calcium influx through a calcium‐permeable complex of IFN‐γ receptor 1(IFNGR1) subunit and AMPAR subunit GluR1. This receptor complex is formed via a non‐canonical neuron‐specific IFN‐γ pathway that involves Jak1/Stat1 and Protein Kinase A. In this study, we explore the expression of the pathway's participants for the first time in the hSOD1G93A Amyotrophic Lateral Sclerosis mouse model. Elevated IFNGR1 and GluR1 are detected in motor neurons of hSOD1G93A symptomatic mice ex vivo, unlike the downstream targets ‐ Jak1, Stat1, and Protein Kinase A. We, also, determine effects of IFN‐γ alone or in the presence of an excitotoxic agent, kainate, on motor neuron survival in vitro. IFN‐γ induces neuronal damage, but does not influence kainate‐mediated excitotoxicity. Increased IFNGR1 can most likely sensitize motor neurons to excitotoxic insults involving GluR1 and/or pathways mediated by IFN‐γ, thus, serving as a potential direct link between neurodegeneration and inflammation in Amyotrophic Lateral Sclerosis.
Evaluating Automatic Polyphonic Music Transcription

Automatic Music Transcription (AMT) is an important task in music information retrieval. Prior work has focused on multiple fundamental frequency estimation (multi-pitch detection), the conversion of an audio signal into a timefrequency representation such as a MIDI file. It is less common to annotate this output with musical features such as voicing information, metrical structure, and harmonic information, though these are important aspects of a complete transcription. Evaluation of these features is most often performed separately and independent of multi-pitch detection; however, these features are non-independent. We therefore introduce MV 2H , a quantitative, automatic, joint evaluation metric based on musicological principles, and show its effectiveness through the use of specific examples. The metric is modularised in such a way that it can still be used with partially performed annotation— for example, when the transcription process has been applied to some transduced format such as MIDI (which may itself be the result of multi-pitch detection). The code for the evaluation metric described here is available at https://www.github. com/apmcleod/MV2H.
Analysis of Lipid Metabolism, Immune Function, and Neurobehavior in Adult C57BL/6JxFVB Mice After Developmental Exposure to di (2-ethylhexyl) Phthalate

Background: Developmental exposure to di (2-ethylhexyl) phthalate (DEHP) has been implicated in the onset of metabolic syndrome later in life. Alterations in neurobehavior and immune functions are also affected by phthalate exposure and may be linked to the metabolic changes caused by developmental exposure to DEHP. Objectives: Our goal was to study the effects of developmental exposure to DEHP in the context of metabolic syndrome by integrating different parameters to assess metabolic, neurobehavioral, and immune functions in one model. Methods: Female C57BL/6J mice were exposed to DEHP through the diet during gestation and lactation at doses ranging from 3.3 to 100,000 μg/kg body weight/day (μkd). During a 1-year follow-up period, a wide set of metabolic parameters was assessed in the F1 offspring, including weekly body weight measurements, food consumption, physical activity, glucose homeostasis, serum lipids, and endocrine profile. In addition, neurobehavioral and immune functions were assessed by sweet preference test, object recognition test, acute phase protein, and cytokines production. Animals were challenged with a high fat diet (HFD) in the last 9 weeks of the study. Results: Increased free fatty acids (FFA) and, high density lipoprotein (HDL-C) were observed in serum, together with a decrease in glycated hemoglobin levels in blood of 1-year old male DEHP-exposed offspring after HFD challenge. For the most sensitive endpoint measured (FFA), a lower bound of the 90%-confidence interval for benchmark dose (BMD) at a critical effect size of 5% (BMDL) of 2,160 μkd was calculated. No persistent changes in body weight or fat mass were observed. At 33,000 μkd altered performance was found in the object recognition test in males and changes in interferon (IFN)γ production were observed in females. Conclusions: Developmental exposure to DEHP combined with HFD in adulthood led to changes in lipid metabolism and neurobehavior in male offspring and cytokine production in female offspring. Our findings contribute to the evidence that DEHP is a developmental dyslipidemic chemical, however, more research is needed to further characterize adverse health outcomes and the mechanisms of action associated with the observed sex-specific effects.
Using Point-of-Choice Prompts to Reduce Sedentary Behavior in Sit-Stand Workstation Users

Introduction: Desk-based office workers are at occupational risk for poor health outcomes from excessive time spent sitting. Sit-stand workstations are used to mitigate sitting, but lack of workstation usage has been observed. Point-of-choice (PoC) prompts offer a complementary strategy for office workers to break up their sitting time. Study purpose: The purpose of this study was to examine the preliminary efficacy, preference, and acceptability of a theory-driven (i.e., 40 unique prompts encompassing social cognitive theory; TD-PoC) and an atheoretical basic reminder PoC prompt intervention (R-PoC) on reducing sedentary behavior in office workers with self-reported low sit-stand workstation usage (≤4 h per day). Methods: In a cross-over design, participants (N = 19, 78.9% female, 39.4 ± 10.7 years of age) completed a 5-days no-prompt control condition followed by a random and counterbalanced assignment to one of the TD-PoC and R-PoC active conditions with a 1-week washout period between. Preliminary efficacy was assessed during work hours with the activPAL micro accelerometer. Preference was assessed prior to each active condition and acceptability was assessed following each active condition via questionnaire. Results: The R-PoC prompt condition significantly decreased sitting time (b[se] = −49.0 [20.8], p = 0.03) and increased standing time (b[se] = 49.8 [19.7], p = 0.02) and displayed a significant increase in sit-stand transitions (b[se] = 2.3 [1.1], p = 0.04), relative to no-prompt control. Both the R-PoC and TD-PoC prompt conditions significantly decreased time spent in prolonged sitting bouts at b[se] = −68.1 [27.8], (p = 0.02), (b[se] = −76.7 [27.1], p = 0.008) relative to no-prompt control. Overall, the TD-PoC prompt condition displayed higher preference and acceptability ratings; however, these differences were not significant (p's > 0.05). Conclusion: While the R-PoC prompt condition was slightly more efficacious than the TD-PoC prompt condition, the TD-PoC prompt condition was rated with higher preference and acceptability scores. Large variations between participants in preference, acceptability, and intervention feedback may indicate need for tailored messaging which may facilitate sustained use in the long-term.
Dosing Recommendations for Quetiapine When Coadministered With HIV Protease Inhibitors

Although current quetiapine labeling recommends that its dosage should be lowered 6‐fold when coadministered with strong cytochrome P450 (CYP)3A inhibitors, a reported case of coma in a patient receiving quetiapine with lopinavir and ritonavir prompted the reevaluation of labeling recommendations for the dosing of quetiapine when coadministered with human immunodeficiency virus (HIV) protease inhibitors. Literature and database (FDA Adverse Event Reporting System and United States Symphony Health Solutions’ Integrated Dataverse Database) searches allowed us to identify cases of coma and related adverse events involving the coadministration of quetiapine and HIV protease inhibitors and to estimate the frequency of concomitant use. Literature review and physiologically based pharmacokinetic modeling allowed us to estimate the potential for CYP3A inhibition to contribute to adverse events related to HIV protease inhibitor–quetiapine coadministration. We identified excess sedation following coadministration of quetiapine and an HIV protease inhibitor in 3 reports without obvious confounders. In prescription claims data, 0.4% of quetiapine patients were dispensed a concurrent ritonavir prescription. The quetiapine dose was not reduced on ritonavir initiation in 90% of therapy episodes. Available data indicate to us that all HIV protease inhibitors combined with ritonavir are likely to be strong CYP3A inhibitors. We predicted that ritonavir would increase quetiapine exposure comparable to the strong CYP3A inhibitor ketoconazole. The current dosing recommendations for use of quetiapine with strong CYP3A inhibitors (ie, 6‐fold lower quetiapine dose) are appropriate and should be followed when quetiapine is coadministered with HIV protease inhibitors.
The use of non-adapted anaerobic consortium in batch reactors enable to couple polychlorinated biphenyl degradation and community adaptation

ABSTRACT The removal of polychlorinated biphenyls (PCBs) and PCB biosorption was investigated in anaerobic batch reactors with non-adapted sludge fed with 1.5 mg L−1 of six PCB congener (PCB 10, 28, 52, 153, 138 and 180), mineral medium and co-substrates. PCBs were analyzed by gas chromatography using headspace solid-phase microextraction (HS-SPME). In the methanogenic reactor the methane production, COD (Carbon Organic Demand) removal (90% of initial 2292.60 mg L−1) and consumption of volatile organic acids were verified. Nevertheless, anaerobic activity was not observed in the reactor with inactivated biomass and biosorption range of 38% to 89% was measured for distinct PCB congeners in this reactor. The PCB removal was calculated from the PCB bioavailable (not biosorbed) and reached 76% of total PCBs. The selection of some representatives of the Thermotogaceae family, Sedimentibacter and Pseudomonas at 101 days of operation in the methanogenic reactor was correlated with PCB degradation. In addition, the various removal rates for each PCB congener indicate that the removal depends on bioavailability. The selection of the former non-adapted microbiota in the methanogenic reactor combined with PCB degradation occurred at 101 days. These results allow to assert that it is possible to simultaneously couple PCB degradation and community selection, without the previous adaptation step, which is a time-consuming stage. GRAPHICAL ABSTRACT
Systemic Design Engineering

The Concept Phase of Systems Engineering, also known as Design, is most critical for it determines most of the cost, complexity and value of a system. Given the interdisciplinary nature of Design, it is no wonder that a wide variety of tools and approaches have been developed to aid in addressing design problems. Even within the engineering community, designers from different disciplines working on different types of problems have devised their own frameworks to demystify the design process. This paper describes several major paradigms in designing complex products: design thinking, systems thinking, systemic design, engineering design, and systems engineering. The commonalities and differences, as well as the strengths and weaknesses, of each approach are outlined and discussed, and a unified approach is proposed for designers who seek to leverage the strengths of each of these existing paradigms.
Stability Analysis of Biological Networks’ Diffusion State

Computational knowledge acquired from noisy networks is not reliable and the network topology determines the reliability. Protein-protein interaction networks have uncertain topologies and noise that contain false positive and false negative edges at high rates. In this study, we analyze effects of the existing mutations in a network topology to the diffusion state of that network. To evaluate the sensitivity of the diffusion state, we derive the fitness measures based on the mathematically defined stability of a network. Searching for an influential set of edges in a network is a difficult problem. We handle the computational challenge by developing a novel metaheuristic optimization method and we find influential mutations time-efficiently. Our experiments, conducted on both synthetic and real networks from public databases, demonstrated that our method obtained better results than competitors for all types of network topologies. This is the first-time that the diffusion has been evaluated under topological mutations. Our analysis identifies significant biological results about the stability of biological - synthetic networks and diffusion state. In this manner, mutations in protein-protein interaction network topologies have a significant influence on the diffusion state of the network. Network stability is more affected by the network model than the network size.
On the Relationships between Music-induced Emotion and Physiological Signals

Emotion-aware music information retrieval (MIR) has been difficult due to the subjectivity and temporality of emotion responses to music. Physiological signals are regarded as related to emotion and thus could potentially be exploited in emotion-aware music discovery. This study explored the possibility of using physiological signals to detect users’ emotion responses to music, with consideration of individual characteristics (personality, music preferences, etc.). A user experiment was conducted with 23 participants who searched for music in a novel MIR sys-tem. Users’ listening behaviors and self-reported emotion responses to a total of 628 music pieces were collected. During music listening, a series of peripheral physiological signals (e.g., heart rate, skin conductance) were recorded from participants unobtrusively using a research-grade wearable wristband. A set of features in the time-and frequency-domains were extracted from the physiological signals and analyzed using statistical and machine learning methods. Results reveal 1) significant differences in some physiological features between positive and negative arousal and mood categories, and 2) effective classification of emotion responses based on physiological signals for some individuals. The findings can contribute to further improvement of emotion-aware intelligent MIR systems exploiting physiological signals as an objective and personalized input.
Zero-Mean Convolutions for Level-Invariant Singing Voice Detection

State-of-the-art singing voice detectors are based on clas-siﬁers trained on annotated examples. As recently shown, such detectors have an important weakness: Since singing voice is correlated with sound level in training data, clas-siﬁers learn to become sensitive to input magnitude, and give different predictions for the same signal at different sound levels. Starting from a Convolutional Neural Network (CNN) trained on logarithmic-magnitude mel spectrogram excerpts, we eliminate this dependency by forcing each ﬁrst-layer convolutional ﬁlter to be zero-mean – that is, to have its coefﬁcients sum to zero. In contrast to four other methods – data augmentation, instance normalization, spectral delta features, and per-channel energy normalization (PCEN) – that we evaluated on a large-scale public dataset, zero-mean convolutions achieve perfect sound level invariance without any impact on prediction accuracy or computational requirements. We assume that zero-mean convolutions would be useful for other machine listening tasks requiring robustness to level changes.
Mango Firmness Modeling as Affected by Transport and Ethylene Treatments

More and more, tropical fruit are subjected to accelerated ripening at receiving markets until “ready to eat. ” We propose a kinetic model that incorporates the effects of temperature and ethylene on the firmness behavior of “Keitt” and “Kent” mangoes. Stiffness of individual mangoes, as measured by the acoustic firmness tester, was measured repeatedly over time. The firmness model assumes fixed levels of ethylene, established after the climacteric peak, that steadily induces production of softening enzymes that subsequently denaturalize. The initial level of these enzymes is assumed to be zero due to either the tree factor for freshly harvested mangoes, or due to chilling injury for reefer transported mangoes. The kinetic parameter set for “Keitt” mangoes was estimated based on a Spanish batch, freshly harvested and ripened under dynamic temperature scenarios, combined with a reefer transported Brazilian batch stored at four constant temperatures. Firmness data from reefer transported batches, from Brazil, Ivory Coast and Mali, stored at four constant temperatures were used to estimate a set of kinetic parameters for the “Kent” mangoes. Only a partial set of “Kent” kinetic parameters could be established due to the often already advanced stage of softening at the time of arrival. The effect of ethylene was investigated by applying external ethylene levels, varying from 0 to 100 μL L−1. The effect of external application of ethylene was modeled by estimating EF, the ethylene factor, being a reflection of the internal ethylene level and ethylene sensitivity. The effect of ethylene application on softening was sometimes huge. For an Israeli “Keitt” batch a fifty times higher EF was found when the firmness behavior of low- (without ethylene application) and high temperature (with ethylene application) stored sub-batches were compared. However, this effect was sometimes also small, especially for reefer transported mangoes. For commercial application, a reliable prediction of the time until “ready to eat” is not possible because of the current inability to assess EF. Nevertheless, the proposed model described mango softening accurately, irrespective of the sourcing area and includes the effects of storage temperature and ethylene application.
Cross cultural adaptation of the Greek sarcopenia quality of life (SarQoL) questionnaire

Abstract Purpose: To translate and validate into the Greek language and setting the Sarcopenia Quality of Life (SarQoL®) questionnaire. Methods: A convenience sample of 176 Greek elderly people (136 females, 40 males; aged 71.19 ± 7.95 years) was recruited, 50 of which (36 females, 14 males) were diagnosed sarcopenic. Questionnaire was back-translated and culturally adapted into Greek according to international guidelines. To validate the Greek SarQoL®, we assessed its validity (discriminative power, construct validity), reliability (internal consistency, test–retest reliability) and floor/ceiling effects. Participants were divided into sarcopenic and non-sarcopenic. Sarcopenic subjects apart from the Greek SarQoL (SarQoLGR) filled out the Greek versions of two generic questionnaires; Short Form-36 and EuroQoL 5-dimension. Results: The Greek SarQoL questionnaire was translated without major difficulties. SarQoLGR mean scores were 52.12 ± 11.04 (range: 24.74–71.81) for sarcopenic subjects and 68.23 ± 14.1 (range: 24.83–94.81) for non-sarcopenic ones. Results indicated good discriminative power across sarcopenic and non-sarcopenic subjects (p = 0.01), high internal consistency (Cronbach’s alpha of 0.96) and excellent test–retest reliability (ICC = 0.96, 95% CI = 0.95–0.97). Neither a floor nor a ceiling effect was observed. Conclusions: The Greek SarQoL was found to be a reliable and valid measure of quality of life for sarcopenic patients. It is therefore, available for use in future clinical research and practice. Implications for rehabilitation The Greek version of the SarQoL® questionnaire is a valid and reliable outcome measure for assessing patients with sarcopenia. The Greek SarQoL is recommended to be use in clinical settings and research. The Greek SarQoL® questionnaire is available online www.sarqol. org.