Miracle-dz/UniFAR-FTUs huggingface dataset:
Decoupled Address Translation for Heterogeneous Memory Systems

The support for the heterogeneous memory in the conventional virtual memory has an inherent problem. For the efficient translation in the critical translation lookaside buffers (TLBs), the page size has been growing. However, the heterogeneous memory management requires a nimble fine-grained migration mechanism to quickly move necessary memory portions to the precious fast memory.To address the challenges posed by the conflicting goals in the heterogeneous memory support, this paper proposes to decouple the address translation into a two-step process. The decoupling resolves the conflict as the critical core-side TLBs perform the translation to an intermediate address space, and the memory-side translation provides the actual physical location of the memory devices.
Studies on dietary fiber and its mechanisms in counteracting amaranth toxicity

食物繊維(DF)は,元来食物中の非消化成分を表現するのに使われていた用語である。 DF の定義として『ヒトの消化酵素によって消化されない食品成分の総体』が現在のところ受け入れ られている。 したがって,DFの生理的効果発現の場は主に消化管腔内であり,消化管との物理 的・化学的相互作用を介しての消化管機能の調節,消化管腔内の内部環境(pH,腸内の細菌の 量・質など)の調節,他の食物成分との相互作用などに影響を与えることにより効果を示すと考 えられる。 DFの生理的効果は,DFの有する物理・化学的特性ならびに消化管各部位の機能と 密接に関連している。 このDFの生理作用のなかに,様々な有害物質に対する毒性軽減効果が ある。 この効果の発現機構を解明することは,DFの新しい未知の栄養的な役割を明らかにする うえで重要な課題であると思われる。 そこで,本研究はラットにおけるアマランス(食用赤色2 号,AM)過剰毒性をモデルとしてこの毒性に対するDFの防止効果の発現機構を解明すること を目的とし,多角度から実験を行なった。 その概要を示すと,以下の通りである。
Fetal Heart Rate Variability Is Affected by Fetal Movements: A Systematic Review

Introduction: Fetal heart rate variability (FHRV) evaluates the fetal neurological state, which is poorly assessed by conventional prenatal surveillance including cardiotocography (CTG). Accurate FHRV on a beat-to-beat basis, assessed by time domain and spectral domain analyses, has shown promising results in the scope of fetal surveillance. However, accepted standards for these techniques are lacking, and the influence of fetal breathing movements and gross movements may be especially challenging. Thus, current standards for equivalent assessments in adults prescribe rest and controlled respiration. The aim of this review is to clarify the importance of fetal movements on FHRV. Methods: A systematic review in accordance with the PRISMA guidelines based on publications in the EMBASE, the MEDLINE, and the Cochrane Library databases was performed. Studies describing the impact of fetal movements on time domain, spectral domain and entropy analyses in healthy human fetuses were reviewed. Only studies based on fetal electrocardiography or fetal magnetocardiography were included. PROSPERO registration number: CRD42018068806. Results: In total, 14 observational studies were included. Fetal movement detection, signal processing, length, and selection of appropriate time series varied across studies. Despite these divergences, all studies showed an increase in overall FHRV in the moving fetus compared to the resting fetus. Especially short-term, vagal mediated indexes showed an increase during fetal breathing movements including an increase in Root Mean Square of the Successive Differences (RMSSD) and High Frequency power (HF) and a decrease in Low Frequency power/High Frequency power (LF/HF). These findings were present even in analyses restricted to one specific fetal behavioral state defined by Nijhuis. On the other hand, fetal body movements seemed to increase parameters supposed to represent the sympathetic response [LF and Standard Deviation of RR-intervals from normal sinus beats (SDNN)] proportionally more than parameters representing the parasympathetic response (RMSSD, HF). Results regarding entropy analyses were inconclusive. Conclusion: Time domain analyses as well as spectral domain analyses are affected by fetal movements. Fetal movements and especially breathing movements should be considered in these analyses of FHRV.
Permian insects from the Beaufort Group of Natal, South Africa

An account is given of the fossil insects of the Beaufort Group (Late Permian) investigated since the last publication by Riek (1976). The Odonata and Trichoptera are reported for the first time; specimens are assigned to three known genera not previously recorded in South Africa; eight new species are descriptionbed, two in new genera. The new taxa are as follows. Megasecoptera: Karoohymen minutus sp. n. ; Homoptera: Permocicada thompsoni sp. n. , Stenotegmocicada triclades gen. n. et sp. n. , Afrostenivicia rediae gen. n. et sp. n. ; Mecoptera: Callietheira granthami sp. n. , Prochoristella balgowanensis and P. bulwerensis spp. n. , Neochoristella goodalli sp. n. Several previously descriptionbed taxa are recorded from additional sites.
Frontal Brain Activity and Subjective Arousal During Emotional Picture Viewing in Nightmare Sufferers

Nightmares are intensely negative dreams that awaken the dreamer. Frequent nightmares are thought to reflect an executive deficit in regulating arousal. Within a diathesis-stress framework, this arousal is specific to negative contexts, though a differential susceptibility framework predicts elevated arousal in response to both negative and positive contexts. The current study tested these predictions by assessing subjective arousal and changes in frontal oxyhemoglobin (oxyHB) concentrations during negative and positive picture-viewing in nightmare sufferers (NM) and control subjects (CTL). 27 NM and 27 CTL subjects aged 18–35 rated subjective arousal on a 1–9 scale following sequences of negative, neutral and positive images; changes in oxyHB were measured by Near-Infrared Spectroscopy (NIRS) using a 2 × 4 template on the frontal pole. Participants also completed the Highly Sensitive Person Scale, a trait marker for differential susceptibility; and completed a dream diary reporting negative and positive dream emotionality. The NM group had higher trait sensitivity, yet higher ratings of negative but not positive emotion in diary dreams. NM compared to CTL subjects reported higher subjective arousal in response to picture-viewing regardless of valence. Dysphoric dream distress, measured prospectively, was negatively associated with frontal activation when viewing negative pictures. Results suggest NM sufferers are highly sensitive to images regardless of valence according to subjective measures, and that there is a neural basis to level of trait and prospective nightmare distress. Future longitudinal or intervention studies should further explore positive emotion sensitivity and imagery in NM sufferers.
The Effect of COVID-19 on Loneliness in the Elderly. An Empirical Comparison of Pre-and Peri-Pandemic Loneliness in Community-Dwelling Elderly

Old-age loneliness is a global problem with many members of the scientific community suspecting increased loneliness in the elderly population during COVID-19 and the associated safety measures. Although hypothesized, a direct comparison of loneliness before and during the pandemic is hard to achieve without a survey of loneliness prior to the pandemic. This study provides a direct comparison of reported loneliness before and during the pandemic using 1:1 propensity score matching (PSM) on a pre- and a peri-pandemic sample of elderly (60+ years) individuals from Lower Austria, a county of Austria (Europe). Differences on a loneliness index computed from the short De Jong Gierveld scale were found to be significant, evidencing that loneliness in the elderly population had in fact risen slightly during the COVID-19 pandemic and its associated safety measures. Although the reported loneliness remained rather low, this result illustrated the effect of the “new normal” under COVID-19. As loneliness is a risk factor for physical and mental illness, this result is important in planning the future handling of the pandemic, as safety measures seem to have a negative impact on loneliness. This work confirms the anticipated increase in loneliness in the elderly population during COVID-19.
Survival Outcomes and Prognostic Analysis Following Greater Cytoreductive Radiotherapy in Patients With Metastatic Prostate Cancer

Purpose: To assess the survival outcomes of patients with metastatic prostate cancer (mPCa) who undergo greater cytoreductive radiotherapy in a real-world clinical practice and determine their prognostic factors. Methods: We performed a retrospective study of 160 patients with mPCa who underwent cytoreductive radiotherapy between 2009 and 2018 at a single institution. The degree of the cytoreductive burden was calculated for each patient. Overall survival (OS) was calculated from the date of detection of metastases. Variables associated with prostate-specific antigen (PSA) response and OS were evaluated via univariate and multivariate analyses. Results: The median follow-up period was 47.2 months. The median OS was 42.3 months with a 5-year OS rate of 37.9%. The PSA levels of 90 patients (56.7%) decline by > 50% after radiotherapy. The 5-year OS rates of patients who underwent total, major, and minor cytoreductive radiotherapy were 53.4, 38.2, 17.6%, respectively; the corresponding median OS intervals were 62.5, 41.0, and 24.4 months, respectively (P < 0.001). A greater extent of cytoreduction (P < 0.05), lower PSA at radiotherapy initiation [hazard ratio 0.51, 95% confidence interval [CI] 0.33–0.78; P = 0.002] and better PSA response [hazard ratio 0.47, 95% CI 0.30–0.72; P < 0.001] were independent factors associated with superior OS. A high metastatic burden (as defined in the CHAARTED trial) was the only independent predictor of a poorer PSA response (odds ratio 0.36, 95% CI 0.19–0.69; P = 0.002). Grade 2 late gastrointestinal and genitourinary toxicities were observed in 3 and 2 patients, respectively, and only 1 patient had grade 3 late gastrointestinal toxicity. Conclusion: Cytoreductive radiotherapy is effective and safe in select patients with mPCa. Greater cytoreduction, together with lower PSA at radiotherapy initiation and improved PSA response are favorable prognostic factors. Further studies are needed to confirm our findings.
Design and Preparation of Molecularly Imprinted Membranes for Selective Separation of Acteoside

Acteoside (ACT) belongs to a type of phenylethanoid glycosides (PhGs), and it is worthy of obtaining high-purity due to its significant medicinal functions. In this study, a novel class of MIMs was designed and synthesized with PVDF membranes as the base membrane for high selective separation and enrichment of ACT. The effects of the different functional monomers, the amounts of functional monomers, crosslinking agents, and initiators on the separation properties of MIMs were investigated. Furthermore, adsorption ability, permeation capacity, and reusability of MIMs were discussed for ACT. It indicated that MIM7 was the optimal performance of MIMs. The adsorption ability of MIM7 for ACT was 62.83 mg/g, and the selectivity factor (α) of MIM7 was up to 2.74 and its permeability factor (β) was greater than 2.66. Moreover, the adsorption amount of MIM7 was still more than 88.57% of the initial value after five cycles. As an ACT imprinted layer of MIMs only had recognition sites for ACT molecules, which recombined with the recognition sites in the membrane permeation experiment, ACT molecules penetration was hindered. However, the analogs of ECH successfully passed MIMs. It indicated that the selective MIMs for ACT followed the mechanism of delayed permeation. This work provides an important reference for the high permselective separation of natural products.
Moderation-Mediation Effects in Bilingualism and Cognitive Reserve

We first provide a critical review of the existing findings on bilingualism as a contributor to cognitive reserve from moderator-mediator warranting cause-effect research conclusions. We next address the question of direct or indirect effects between bilingualism and neurocognitive protective factors influencing the associated age-related mental deficits. The existing findings support bilingualism as a predictor and as a moderator. Third, we propose cognitive reserve models of bilingualism describing analytical approaches that allow testing of these models and hypotheses related to path strength and causal relationships between predictors, moderators, and mediators. Lastly and most importantly, we suggest using large datasets available via open repositories. This can aid in the testing of theoretical models, clarifying the roles of moderators and mediators, and assessing the research viability of multi-causal paths that can influence cognitive reserve. Creating collaborative datasets to test these models would greatly advance our field and identify critical variables in the study of the bilingual aging brain.
Investigation of the Autoregulator-Receptor System in the Pristinamycin Producer Streptomyces pristinaespiralis

Pristinamycin biosynthesis in Streptomyces pristinaespiralis is governed by a complex hierarchical signaling cascade involving seven different transcriptional regulators (SpbR, PapR1, PapR2, PapR3, PapR4, PapR5, and PapR6). The signaling cascade is triggered by γ-butyrolactone (GBL)-like effector molecules, whereby the chemical structure of the effector, as well as its biosynthetic origin is unknown so far. Three of the pristinamycin transcriptional regulators (SpbR, PapR3, and PapR5) belong to the type of γ-butyrolactone receptor (GBLR). GBLRs are known to either act as “real” GBLRs, which bind GBLs as ligands or as “pseudo” GBLRs binding antibiotics or intermediates thereof as effector molecules. In this study, we performed electromobility shift assays (EMSAs) with SpbR, PapR3, and PapR5, respectively, in the presence of potential ligand samples. Thereby we could show that all three GBLRs bind synthetic 1,4-butyrolactone but not pristinamycin as ligand, suggesting that SpbR, PapR3, and PapR5 act as “real” GBLRs in S. pristinaespiralis. Furthermore, we identified a cytochrome P450 monooxygenase encoding gene snbU as potential biosynthesis gene for the GBLR-interacting ligand. Inactivation of snbU resulted in an increased pristinamycin production, which indicated that SnbU has a regulatory influence on pristinamycin production. EMSAs with culture extract samples from the snbU mutant did not influence the target binding ability of SpbR, PapR3, and PapR5 anymore, in contrast to culture supernatant samples from the S. pristinaespiralis wild-type or the pristinamycin deficient mutant papR2::apra, which demonstrates that SnbU is involved in the synthesis of the GBLR-interacting ligand.
Natural Pigments of Microbial Origin

The world demands new solutions and products to be used as dyes for industrial applications. Microbial pigments represent an eco-friendly alternative as they can be produced in large amounts through biotechnological processes and do not present environmental risks, as they are easily decomposable. Moreover, some of these metabolites are recognized for their biological activities, which qualify them for potential uses as food colorants and nutraceuticals, protecting against degenerative diseases related with oxidative stress. Because of their genetic simplicity as compared with plants, microorganisms may be a better source to understand biosynthetic mechanisms and to be engineered for producing high pigment yields. Despite the origin of the pigmented microorganism, it seems very important to develop protocols using organic industrial residues and agricultural byproducts as substrates for pigment production and find novel green strategies for rapid pigment extraction. This review looks for the most recent studies that describe microbial pigments from microalgae, fungi, and bacteria. In particular, the underexploited tools of omics science such as proteomics and metabolomics are addressed. The use of techniques involving mass spectrometry, allows to identify different protein and metabolite profiles that may be associated with a variety of biotechnologically-relevant pathways of pigment synthesis.
Potent and Quick Responses to Conspecific Faces and Snakes in the Anterior Cingulate Cortex of Monkeys

Appropriate processing of others’ facial emotions is a fundamental ability of primates in social situations. Several moods and anxiety disorders such as depression cause a negative bias in the perception of facial emotions. Depressive patients show abnormalities of activity and gray matter volume in the perigenual portion of the anterior cingulate cortex (ACC) and an increase of activation in the amygdala. However, it is not known whether neurons in the ACC have a function in the processing of facial emotions. Furthermore, detecting predators quickly and taking avoidance behavior are important functions in a matter of life and death for wild monkeys. the existence of predators in their vicinity is life-and-death information for monkeys. In the present study, we recorded the activity of single neurons from the monkey ACC and examined the responsiveness of the ACC neurons to various visual stimuli including monkey faces, snakes, foods, and artificial objects. About one-fourth of the recorded neurons showed a significant change in activity in response to the stimuli. The ACC neurons exhibited high selectivity to certain stimuli, and more neurons exhibited the maximal response to monkey faces and snakes than to foods and objects. The responses to monkey faces and snakes were faster and stronger compared to those to foods and objects. Almost all of the neurons that responded to video stimuli responded strongly to negative facial stimuli, threats, and scream. Most of the responsive neurons were located in the cingulate gyrus or the ventral bank of the cingulate sulcus just above or anterior to the genu of the corpus callosum, that is, the perigenual portion of the ACC, which has a strong mutual connection with the amygdala. These results suggest that the perigenual portion of the ACC in addition to the amygdala processes emotional information, especially negative life-and-death information such as conspecifics’ faces and snakes.
Identification of Novel Genes Involved in Escherichia coli Persistence to Tosufloxacin

Persisters are metabolically quiescent phenotypic variants of the wild type that are tolerant to cidal antibiotics, and the mechanisms of persister formation and survival are complex and not completely understood. To identify genes involved in persistence to tosufloxacin, which has higher activity against persisters than most other quinolones, we screened the E. coli KEIO mutant library using a different condition from most persister mutant screens (6 h) with a longer exposure of 18 h with tosufloxacin. We identified 18 mutants (acrA, acrB, ddlB, dnaG, gltI, hlpA, lpcA, recG, recN, rfaH, ruvC, surA, tatC, tolQ, uvrD, xseA, and ydfI) that failed to form tosufloxacin tolerant persisters. Among them, gltI, hlpA, ruvC, ddlB, ydfI, and tatC are unique genes involved in E. coli persistence to tosufloxacin which have not been reported before. Furthermore, deletion mutants in genes coding periplasmic proteins (surA, lpcA, hlpA, and gltI) had more defect in persistence to tosufloxacin than the other identified mutants, with surA and lpcA mutants being the most prominent. The “deep” persister phenotype of surA and lpcA mutants was further confirmed both in vitro and in vivo. Compared with the wild type strain E. coli BW25113 in vitro, the persister phenotype of the surA and lpcA mutants was decreased more than 100–1,000-fold in persistence to various antibiotics, acidic, hyperosmotic and heat conditions. In addition, in both stationary phase bacteria and biofilm bacteria infection mouse models, the surA and lpcA mutants had lower survival and persistence than the parent uropathogenic strain UTI89, suggesting that the in vitro identified persister mechanisms (surA and lpcA) are operative and valid for in vivo persistence. Our findings provide new insight into the mechanisms of persister formation and maintenance under tosufloxacin and will likely provide novel therapeutic and vaccine targets for developing more effective treatment and prevention of persistent E. coli infections.
Premorbid Social Functioning and Affective Symptoms Predict Subjective Outcome Among Outpatients With Schizophrenia

Improving the subjective outcome of patients is an important target in the treatment of schizophrenia. Accordingly, the aim of the present study was to examine the association of factors deemed relevant in this context, i.e., premorbid functioning, residual symptoms, and side effects of antipsychotic medication, with subjective outcome. To this end, 70 clinically stable outpatients with schizophrenia were included into a cross-sectional study. Premorbid functioning, psychopathology, and side effects were assessed by using the Premorbid Adjustment Scale, the Positive and Negative Syndrome Scale, and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale, respectively. Subjective outcome was measured in terms of life satisfaction (Life Satisfaction Questionnaire), self-esteem (Index of Self-Esteem), and needs for care (Berliner Bedürfnisinventar). Both premorbid social functioning and affective symptoms predicted life satisfaction, self-esteem, and patients’ basic needs, whereas positive and negative symptoms predicted needs in the health, social, and functional domains. Concerning side effects, parkinsonism and akathisia showed a significant negative correlation with self-esteem. These findings highlight the complex nature of subjective outcome in patients suffering from schizophrenia. Evidently, premorbid social functioning plays a prominent role in the experienced subjective outcome during the course of the illness. Furthermore, these preliminary findings underscore that constant efforts are essential to treat residual symptoms of the disorder and to avoid extrapyramidal motor side effects of antipsychotic medication. Longitudinal studies are needed to investigate this latter point in more detail.
New Insights on the Effects of Methylphenidate in Attention Deficit Hyperactivity Disorder

This narrative review describes an overview of the multiple effects of methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD) and its potential neurobiological targets. It addressed the following aspects: 1) MPH effects on attention and executive functions in ADHD; 2) the relation between MPH efficacy and dopamine transporter gene (DAT) polymorphism; and 3) the role of MPH as an epigenetic modulator in ADHD. Literature analysis showed that MPH, the most commonly used psychostimulant in the therapy of ADHD, acts on multiple components of the disorder. Marked improvements in attentional and executive dysfunction have been observed in children with ADHD during treatment with MPH, as well as reductions in neurological soft signs. MPH efficacy may be influenced by polymorphisms in the DAT, and better responses to treatment were associated with the 10/10 genotype. Innovative lines of research have suggested that ADHD etiopathogenesis and its neuropsychological phenotypes also depend on the expression levels of human endogenous retrovirus (HERV). In particular, several studies have revealed that ADHD is associated with HERV-H over-expression and that MPH administration results in decreased expression levels of this retroviral family and a reduction in the main symptoms of the disorder. In conclusion, there is a confirmed role for MPH as an elective drug in the therapy of ADHD alone or in association with behavioral therapy. Its effectiveness can vary based on DAT polymorphisms and can act as a modulator of HERV-H gene expression, pointing to targets for a precision medicine approach.