Miracle-dz/UniFAR-FTUs huggingface dataset:
A Population-Genetic Lens into the Process of Gene Loss Following Whole-Genome Duplication

Abstract Whole-genome duplications (WGDs) have occurred in many eukaryotic lineages. However, the underlying evolutionary forces and molecular mechanisms responsible for the long-term retention of gene duplicates created by WGDs are not well understood. We employ a population-genomic approach to understand the selective forces acting on paralogs and investigate ongoing duplicate-gene loss in multiple species of Paramecium that share an ancient WGD. We show that mutations that abolish protein function are more likely to be segregating in retained WGD paralogs than in single-copy genes, most likely because of ongoing nonfunctionalization post-WGD. This relaxation of purifying selection occurs in only one WGD paralog, accompanied by the gradual fixation of nonsynonymous mutations and reduction in levels of expression, and occurs over a long period of evolutionary time, “marking” one locus for future loss. Concordantly, the fitness effects of new nonsynonymous mutations and frameshift-causing indels are significantly more deleterious in the highly expressed copy compared with their paralogs with lower expression. Our results provide a novel mechanistic model of gene duplicate loss following WGDs, wherein selection acts on the sum of functional activity of both duplicate genes, allowing the two to wander in expression and functional space, until one duplicate locus eventually degenerates enough in functional efficiency or expression that its contribution to total activity is too insignificant to be retained by purifying selection. Retention of duplicates by such mechanisms predicts long times to duplicate-gene loss, which should not be falsely attributed to retention due to gain/change in function.
Friend or foe: Hybrid proline-rich proteins determine how plants respond to beneficial and pathogenic microbes

Abstract Plant plastids generate signals, including some derived from lipids, that need to be mobilized to effect signaling. We used informatics to discover potential plastid membrane proteins involved in microbial responses in Arabidopsis (Arabidopsis thaliana). Among these are proteins co-regulated with the systemic immunity component AZELAIC ACID INDUCED 1, a hybrid proline-rich protein (HyPRP), and HyPRP superfamily members. HyPRPs have a transmembrane domain, a proline-rich region (PRR), and a lipid transfer protein domain. The precise subcellular location(s) and function(s) are unknown for most HyPRP family members. As predicted by informatics, a subset of HyPRPs has a pool of proteins that target plastid outer envelope membranes via a mechanism that requires the PRR. Additionally, two HyPRPs may be associated with thylakoid membranes. Most of the plastid- and nonplastid-localized family members also have pools that localize to the endoplasmic reticulum, plasma membrane, or plasmodesmata. HyPRPs with plastid pools regulate, positively or negatively, systemic immunity against the pathogen Pseudomonas syringae. HyPRPs also regulate the interaction with the plant growth-promoting rhizobacteria Pseudomonas simiae WCS417 in the roots to influence colonization, root system architecture, and/or biomass. Thus, HyPRPs have broad and distinct roles in immunity, development, and growth responses to microbes and reside at sites that may facilitate signal molecule transport.
Forecasting daily maximum temperature of Umeå

The aim of this study is to get some approach which can help in improving the predictions of daily temperature of Umea. Weather forecasts are available through various sources nowadays. There are various software and methods available for time series forecasting. Our aim is to investigate the daily maximum temperatures of Umea, and compare the performance of some methods in forecasting these temperatures. Here we analyse the data of daily maximum temperatures and find the predictions for some local period using methods of autoregressive integrated moving average (ARIMA), exponential smoothing (ETS), and cubic splines. The forecast package in R is used for this purpose and automatic forecasting methods available in the package are applied for modelling with ARIMA, ETS, and cubic splines. The thesis begins with some initial modelling on univariate time series of daily maximum temperatures. The data of daily maximum temperatures of Umea from 2008 to 2013 are used to compare the methods using various lengths of training period. On the basis of accuracy measures we try to choose the best method. Keeping in mind the fact that there are various factors which can cause the variability in daily temperature, we try to improve the forecasts in the next part of thesis by using multivariate time series forecasting method on the time series of maximum temperatures together with some other variables. Vector auto regressive (VAR) model from the vars package in R is used to analyse the multivariate time series.Results: ARIMA is selected as the best method in comparison with ETS and cubic smoothing splines to forecast one-step-ahead daily maximum temperature of Umea, with the training period of one year. It is observed that ARIMA also provides better forecasts of daily temperatures for the next two or three days. On the basis of this study, VAR (for multivariate time series) does not help to improve the forecasts significantly. The proposed ARIMA with one year training period is compatible with the forecasts of daily maximum temperature of Umea obtained from Swedish Meteorological and Hydrological Institute (SMHI).
Intolerance of Transgressive Protest Actions: The Differential Roles of Deontological and Utilitarian Morality

The current research examines intolerance of protest actions by focusing on two major questions: (a) How intolerant are people of transgressive protest actions of their least-liked versus most-liked groups? and (b) how do individual differences in deontological and utilitarian moral predisposition relate to intolerance of transgressive protest actions by these two groups? In two survey-embedded experiments using nationally representative samples from two West European countries (Germany, Netherlands), we found that people were overwhelmingly intolerant of morally transgressive protest actions by both their most-liked and least-liked groups, although slightly less so for the former. In addition, deontological moral predisposition was related to increased intolerance of protest actions regardless of whether it was committed by a most-liked or least-liked group. Individual difference in utilitarian moral predisposition was related to increased acceptance of protest actions regardless of group, but especially when the actions were perceived as serving the greater good.
Quantification of quetiapine fumarate based on electrochemical analysis by reduced graphene oxide modified nano‐silica functionalized with polydopamine and gold nanostars: A novel pharmaceutical analysis strategy

Quetiapine fumarate (QF) is an antipsychotic drug that has been most widely prescribed as an antipsychotic. In this regard, sensitive recognition of QF in bodily fluids must be done accurately. In this work, an electrochemical sensor for QF detection was fabricated, using GNSs‐PDA@SiO2 modified rGO stabilized on glassy carbon electrode. According to the electrical nature of gold nanoparticles (GNPs), polydopamine (PDA), and its composition with nano‐silica, the proposed hybrid material is able to enhance the electro‐oxidation signals of QF toward its sensitive detection in complex biological media. The morphology of synthesized polymeric nanocomposites and various surfaces of electrodes were investigated using Field Emission Scanning Electron Microscopy and Energy‐Dispersive X‐Ray Spectroscopy methods. Using the square wave voltammetry technique, the fabricated electrochemical sensor could detect QF in the linear range of 500 μM to 3 mM, which low limit of quantification was obtained as 500 μM, indicating the sensor's appropriate sensitivity. For the first time, the application of novel hybrid material (GNSs‐PDA@SiO2) for pharmaceutical analysis in human plasma was studied using electrochemical sensor technology. Based on the obtained analytical results, engineered nano‐surface led to entrapment and oxidation of QF in real samples. So, a novel and efficient method for the analysis of QF was designed and validated, which opens a new horizon for pharmaceutical analysis and therapeutic drug monitoring.
Molecular and metabolic characteristics of wastewater associated Escherichia coli strains

Summary We previously characterized the genetic diversity of Escherichia coli strains isolated from septic tanks in the Canberra region, Australia. In this study, we used repetitive element palindromic (REP) PCR fingerprinting to identify dominant REP‐types belonging to phylogroups A and B1 strains across septic tanks. Subsequently, 76 E. coli strains were selected for whole‐genome sequencing and phenotype microarrays. Comparative genome analysis was performed to compare septic tank E. coli genomes with a collection of 433 E. coli isolates from different hosts and freshwater. Clonal complexes (CCs) 10 (n = 15) and 399 (n = 10) along with sequence type (ST) 401 (n = 9) were the common lineages in septic tanks. CC10 strains have been detected from animal hosts and freshwater, whereas CC399 and ST401 strains appeared to be associated with septic tanks as they were uncommon in isolates from other sources. Comparative genome analysis revealed that CC399 and ST401 were genetically distinct from other isolates and carried an abundance of niche‐specific traits involved in environmental adaptation. These strains also showed distinct metabolic characteristics, such as the ability to utilize pectin, which may provide a fitness advantage under nutrient‐limited conditions. The results of this study characterized the adaptive mechanisms allowing E. coli to persist in wastewater.
Exploring the role of recently-qualified English teachers in developing technology use in language classrooms through communities of practice

It is widely recognised that many experienced and well-qualified teachers struggle with using technology effectively in the English language classroom and even those with strong motivation to develop their technology skills can feel a lack of support in their efforts to incorporate it into their teaching. This study explores the use of technology in English language teaching in six secondary schools across Malaysia, in particular focusing on how communities of practice might be useful in developing technology use in English classes within the schools and the potential role recently-qualified teachers might play in this. Data for the study was collected from questionnaires, online reflection tasks, interviews, focus groups and field notes. Findings suggest that given the right conditions, such as opportunities for professional development and sharing this with a community of practice, and a group of teachers with a collaborative mindset, then such a community, focused on developing technology use, can flourish. This in turn will generate greater use of technology in the classroom. In addition, the study indicates that recently-qualified teachers are capable of taking on a guiding role within such a community. However, for their potential in this role to be maximised, some level of formal recognition of the role seems beneficial in terms of empowering them to take a lead, even among more senior colleagues.
Pathogenic Mutation of TDP-43 Impairs RNA Processing in a Cell Type-Specific Manner: Implications for the Pathogenesis of ALS/FTLD

Abstract Transactivating response element DNA-binding protein of 43 kDa (TDP-43), which is encoded by the TARDBP gene, is an RNA-binding protein with fundamental RNA processing activities, and its loss-of-function (LOF) has a central role in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TARDBP mutations are postulated to inactivate TDP-43 functions, leading to impaired RNA processing. However, it has not been fully examined how mutant TDP-43 affects global RNA regulation, especially in human cell models. Here, we examined global RNA processing in forebrain cortical neurons derived from human induced pluripotent stem cells (iPSCs) with a pathogenic TARDBP mutation encoding the TDP-43K263E protein. In neurons expressing mutant TDP-43, we detected disrupted RNA regulation, including global changes in gene expression, missplicing, and aberrant polyadenylation, all of which were highly similar to those induced by TDP-43 knock-down. This mutation-induced TDP-43 LOF was not because of the cytoplasmic mislocalization of TDP-43. Intriguingly, in nonneuronal cells, including iPSCs and neural progenitor cells (NPCs), we did not observe impairments in RNA processing, thus indicating that the K263E mutation results in neuron-specific LOF of TDP-43. This study characterizes global RNA processing impairments induced by mutant TDP-43 and reveals the unprecedented cell type specificity of TDP-43 LOF in ALS/FTLD pathogenesis.
Pentosan polysulfate for the treatment of hemorrhagic cystitis after allogeneic hematopoietic cell transplant

Introduction Hemorrhagic cystitis can commonly occur following an allogeneic hematopoietic cell transplant and treatment options are currently limited. Pentosan polysulfate, a heparin-like, sulfated polysaccharide, is used to relieve bladder pain and discomfort associated with interstitial cystitis. Initial reports in patients with hemorrhagic cystitis demonstrate that pentosan polysulfate may hasten hemorrhagic cystitis resolution and control symptoms. Methods and results This report includes a retrospective case series of six patients who received pentosan polysulfate for the treatment of hemorrhagic cystitis following an allogeneic hematopoietic cell transplant. Pentosan polysulfate was initiated at a median of 4.5 days (range: 3–18) following hemorrhagic cystitis onset and continued for a median duration of 17.5 days (range: 7–64). Four patients were tested for BK virus and all were found to have BK viremia and viruria around the time of pentosan polysulfate initiation. The median number of red blood cell transfusions seemed to decrease in the patients initiated on pentosan polysulfate. All patients received a multi-agent treatment regimen, which included pentosan polysulfate, and half the patients had symptom resolution. The median time to symptom resolution from pentosan polysulfate initiation was 9 days (range: 7–10). Conclusion Pentosan polysulfate was well-tolerated and seemed to assist with symptom resolution. Future studies are needed to confirm the impact of pentosan polysulfate on the treatment of hemorrhagic cystitis.
An Eight-Element Compact Low-Profile Planar MIMO Antenna Using LC Resonance with High Isolation

An eight-element compact low-profile multi-input multi-output (MIMO) antenna is proposed for wireless local area network (WLAN) mobile applications. The proposed antenna consists of eight inverted-F antennas with an isolation-enhanced structure. By inserting the isolation-enhanced structure between the antenna elements, the slot and capacitor pair generates additional resonant frequency and decreases mutual coupling between the antenna elements. The overall size of the proposed antenna is only 33 mm× 33 mm, which is integrated into an area of just 0.5 λ× 0.5 λ. The proposed antenna meets 5-GHz WLAN standards with an operation bandwidth of 4.86 - 5.27 GHz and achieves an isolation of approximately 30 dB at 5 GHz. The simulated and measured results for the proposed antenna are presented and compared.
Structure-activity relationship data and ligand-receptor interactions identify novel agonists consistent with sulfakinin tissue-specific signaling in Drosophila melanogaster heart.

BACKGROUND The structures and activities of invertebrate sulfakinins that influence gut motility and heart rate are like the vertebrate cholecystokinin (CCK) peptides. Typical of sulfakinin precursors Drosophila melanogaster encodes non-sulfated drosulfakinin I (nsDSK I; FDDYGHMRF-NH2) and nsDSK II (GGDDQFDDYGHMRF-NH2) that bind DSK-R1 and DSK-R2. To explore the role of the nsDSK II N-terminal extension (GGDDQ) in gut we delineated its structure-activity relationship (SAR) and identified novel agonists. We then predicted the nsDSK II extension SAR is tissue specific consistent with cardiac CCK structure activity and signaling being different from gut. METHODS To evaluate our hypothesis, we tested single-substituted alanine and asparagine analogs in heart. RESULTS We found alanyl-substituted analogs were less active in heart than nsDSK II; in gut they include a super agonist and a protean agonist. Additionally, we discovered ns[N4]DSK II was more active than nsDSK II in pupal heart, while ns[N3]DSK II was inactive. In contrast, ns[N3]DSK II and ns[N4]DSK II were super agonists in adult heart, yet inactive in larva. Although we reported nsDSK II acts through DSK-R2 in gut, its identity in heart was unknown. CONCLUSIONS Here we reviewed ligand-receptor interactions in conjunction with SAR data to suggest nsDSK II acts through DSK-R1 in heart consistent with sulfakinin tissue-specific signaling.
“It Looks Like You’re Making Very Healthy Choices”: Attending to the Lifeworld and Medicine in Photo-Based Talk in Primary Care

ABSTRACT Addressing patient-clinician communication barriers to improve multiple chronic disease care is a public health priority. While significant research exists about the patient-clinician encounter, less is known about how to support patient-clinician communication about lifestyle changes that includes the context of people’s lives. Data come from a larger photo-based primary care study collected from 13 participants who were adults 60 or older with at least two chronic conditions, in English, Chinese (Cantonese or Mandarin), or Spanish. We use discourse analysis of three examples as anchor points demonstrating different interactional pathways for the photo-based communication. Patients and clinicians can move smoothly through a pathway in which photos are shared, clinicians acknowledge and align with the patient’s explanation, and clinicians frame their medical evaluations of food choices, nutrition suggestions, and shared goal-setting by invoking the voice of lifeworld (VOL). On the other hand, when clinicians solely press the voice of medicine (VOM) in their evaluations of patients’ pictures with little attention to patients’ presentations, it can lead to patient resistance and difficulty moving to the next activity. Because photo-sharing is still relatively novel, it offers unique interactional spaces for both clinicians and patients. Photo-sharing offers a sanctioned moment for a primary care visit to operate in the VOL and promote goal-setting that both parties can agree upon, even if clinicians and patients framed the activity as one in which patients’ lifeworld choices should be assessed as medically healthy or unhealthy based on the ultimate judgment of clinicians operating from the VOM.
An intelligent MOS transistor featuring gate-level weighted sum and threshold operations

A novel functional MOS transistor which behaves much more intelligently than a mere switching device has been developed. The device has a floating gate whose potential is controlled by a plural number of input gates via capacitive coupling. The transistor is called a 'neuron MOSFET' due to its similarity to biological neurons in that the transistor turns on when the weighted sum of all input signals exceeds a certain threshold value. Test devices were fabricated using a double-polysilicon NMOS process. The analysis of the basic device operation and its experimental verification are presented. A number of interesting applications of the neuron MOSFET are described which include a variable threshold transistor, a neuron circuit, a single-gate D/A (digital-to-analog) converter, and a soft hardware logic circuit. <<ETX>>
An examination of the effects of distress intolerance and rating of perceived exertion on changes in mood and anxiety following aerobic exercise among treatment-seeking smokers

ABSTRACT Aerobic exercise is frequently used as an intervention for depression and smoking cessation because of its antidepressant and anxiolytic effects. Distress intolerance (DI) is a proposed individual difference factor that, coupled with a higher rating of perceived exertion during exercise, may significantly impact the acute mood and anxiolytic effects of exercise. The current study examined the interactive effect of maximum rating of perceived exertion (RPE) and DI on change in mood and anxiety. Treatment-seeking smokers (M age = 45.32; 72% female) with elevated depressive symptoms completed a 1-mile treadmill walk at their preferred intensity and self-reported their RPE during the test. Analyses were conducted to examine whether there was an interactive effect of maximum RPE and DI on change in self-reported mood and anxiety from before to after the walk test. Findings indicate a significant moderating effect of RPE at lower ratings. Individuals reporting a low maximum RPE and higher DI exhibit a greater change in mood over the course of an exercise session, whereas individuals reporting a low maximum RPE and a lower DI exhibit smaller changes in mood. These results indicate that the subjective effects of exercise within a population of cigarette smokers could be improved by tailoring exercise intensity to individual characteristics. Mild to moderate-intensity exercise, as compared to high-intensity exercise, may result in greater changes in mood for individuals endorsing difficulty tolerating affective and physical distress.
Function of ceramide transfer protein for biogenesis and sphingolipid composition of extracellular vesicles

Abstract The formation of extracellular vesicles (EVs) is induced by the sphingolipid ceramide. How this pathway is regulated is not entirely understood. Here, we report that the ceramide transport protein (CERT) mediates a non‐vesicular transport of ceramide between the endoplasmic reticulum (ER) and the multivesicular endosome at contact sites. The process depends on the interaction of CERT's PH domain with PI4P generated by PI4KIIα at endosomes. Furthermore, a complex is formed between the START domain of CERT, which carries ceramide, and the Tsg101 protein, which is part of the endosomal sorting complex required for transport (ESCRT‐I). Inhibition of ceramide biosynthesis reduces CERT‐Tsg101 complex formation. Overexpression of CERT increases EV secretion while its inhibition reduces EV formation and the concentration of ceramides and sphingomyelins in EVs. In conclusion, we discovered a function of CERT in regulating the sphingolipid composition and biogenesis of EVs, which links ceramide to the ESCRT‐dependent pathway.