Miracle-dz/UniFAR-FTUs huggingface dataset:
Decentralized SGD with Asynchronous, Local and Quantized Updates.

The ability to scale distributed optimization to large node counts has been one of the main enablers of recent progress in machine learning. To this end, several techniques have been explored, such as asynchronous, decentralized, or quantized communication--which significantly reduce the cost of synchronization, and the ability for nodes to perform several local model updates before communicating--which reduces the frequency of synchronization. In this paper, we show that these techniques, which have so far been considered independently, can be jointly leveraged to minimize distribution cost for training neural network models via stochastic gradient descent (SGD). We consider a setting with minimal coordination: we have a large number of nodes on a communication graph, each with a local subset of data, performing independent SGD updates onto their local models. After some number of local updates, each node chooses an interaction partner uniformly at random from its neighbors, and averages a possibly quantized version of its local model with the neighbor's model. Our first contribution is in proving that, even under such a relaxed setting, SGD can still be guaranteed to converge under standard assumptions. The proof is based on a new connection with parallel load-balancing processes, and improves existing techniques by jointly handling decentralization, asynchrony, quantization, and local updates, and by bounding their impact. On the practical side, we implement variants of our algorithm and deploy them onto distributed environments, and show that they can successfully converge and scale for large-scale image classification and translation tasks, matching or even slightly improving the accuracy of previous methods.
Social cognition in the blind brain: A coordinate‐based meta‐analysis

Social cognition skills are typically acquired on the basis of visual information (e.g., the observation of gaze, facial expressions, gestures). In light of this, a critical issue is whether and how the lack of visual experience affects neurocognitive mechanisms underlying social skills. This issue has been largely neglected in the literature on blindness, despite difficulties in social interactions may be particular salient in the life of blind individuals (especially children). Here we provide a meta‐analysis of neuroimaging studies reporting brain activations associated to the representation of self and others' in early blind individuals and in sighted controls. Our results indicate that early blindness does not critically impact on the development of the “social brain,” with social tasks performed on the basis of auditory or tactile information driving consistent activations in nodes of the action observation network, typically active during actual observation of others in sighted individuals. Interestingly though, activations along this network appeared more left‐lateralized in the blind than in sighted participants. These results may have important implications for the development of specific training programs to improve social skills in blind children and young adults.
Negative CG dinucleotide bias: An explanation based on feedback loops between Arginine codon assignments and theoretical minimal RNA rings

Theoretical minimal RNA rings are candidate primordial genes evolved for non‐redundant coding of the genetic code's 22 coding signals (one codon per biogenic amino acid, a start and a stop codon) over the shortest possible length: 29520 22‐nucleotide‐long RNA rings solve this min‐max constraint. Numerous RNA ring properties are reminiscent of natural genes. Here we present analyses showing that all RNA rings lack dinucleotide CG (a mutable, chemically instable dinucleotide coding for Arginine), bearing a resemblance to known CG‐depleted genomes. CG in “incomplete” RNA rings (not coding for all coding signals, with only 3–12 nucleotides) gradually decreases towards CG absence in complete, 22‐nucleotide‐long RNA rings. Presumably, feedback loops during RNA ring growth during evolution (when amino acid assignment fixed the genetic code) assigned Arg to codons lacking CG (AGR) to avoid CG. Hence, as a chemical property of base pairs, CG mutability restructured the genetic code, thereby establishing itself as genetically encoded biological information.
Resistance to Intervention: Paclitaxel in Breast Cancer.

Breast cancer stands as the most prevalent cancer in women globally, and contributes to highest percentage in mortality to cancer related deaths in women. Paclitaxel (PTX) is heavily relied on as a frontline chemotherapy in breast cancer treatment, especially in advanced metastatic cancer. Generation of resistance to PTX often derails clinical management and adversely affects patient outcomes. Defining the molecular mechanism underlying PTX resistance is mostly sought for to aid in overcoming resistance, and this oriented research has led to the understanding of a range of PTX resistance related therapeutic targets. PTX resistance pathways that involve major regulatory proteins/RNAs like RNF8/Twist/ROR1, TLR, ErbB3/ErbB2, BRCA1-IRIS, MENA, LIN9, MiRNA, FoxM1 and IRAK1 have expanded the complexity of resistance mechanisms, and brought newer insights for development of drug targets. This resistance related targets can be dealt with synthetic/natural therapeutics in combination with PTX. The present review encompasses recent understanding of PTX resistance mechanisms in breast cancer and possible therapeutic combinations to overcome resistance.
Mobile Health App With Social Media to Support Self-Management for Patients With Chronic Kidney Disease: Prospective Randomized Controlled Study

Background Chronic kidney disease (CKD) is a global health burden. Self-management plays a key role in improving modifiable risk factors. Objective The aim of this study was to evaluate the effectiveness of wearable devices, a health management platform, and social media at improving the self-management of CKD, with the goal of establishing a new self-management intervention model. Methods In a 90-day prospective experimental study, a total of 60 people with CKD at stages 1-4 were enrolled in the intervention group (n=30) and control group (n=30). All participants were provided with wearable devices that collected exercise-related data. All participants maintained dietary diaries using a smartphone app. All dietary and exercise information was then uploaded to a health management platform. Suggestions about diet and exercise were provided to the intervention group only, and a social media group was created to inspire the participants in the intervention group. Participants’ self-efficacy and self-management questionnaire scores, Kidney Disease Quality of Life scores, body composition, and laboratory examinations before and after the intervention were compared between the intervention and control groups. Results A total of 49 participants completed the study (25 in the intervention group and 24 in the control group); 74% of the participants were men and the mean age was 51.22 years. There were no differences in measured baseline characteristics between the groups except for educational background. After the intervention, the intervention group showed significantly higher scores for self-efficacy (mean 171.28, SD 22.92 vs mean 142.21, SD 26.36; P<.001) and self-management (mean 54.16, SD 6.71 vs mean 47.58, SD 6.42; P=.001). Kidney Disease Quality of Life scores were also higher in the intervention group (mean 293.16, SD 34.21 vs mean 276.37, SD 32.21; P=.02). The number of steps per day increased in the intervention group (9768.56 in week 1 and 11,389.12 in week 12). The estimated glomerular filtration rate (eGFR) of the intervention group was higher than that of the control group (mean 72.47, SD 24.28 vs mean 59.69, SD 22.25 mL/min/1.73m2; P=.03) and the decline in eGFR was significantly slower in the intervention group (–0.56 vs –4.58 mL/min/1.73m2). There were no differences in body composition between groups postintervention. Conclusions The use of wearable devices, a health management platform, and social media support not only strengthened self-efficacy and self-management but also improved quality of life and a slower eGFR decline in people with CKD at stages 1-4. These results outline a new self-management model to promote healthy lifestyle behaviors for patients with CKD. Trial Registration ClinicalTrials.gov NCT04617431; https://www.clinicaltrials. gov/ct2/show/NCT04617431
Assessment of body fluid in critically ill patients with acute kidney injury requiring continuous renal replacement therapy

patients with acute kidney injury (AKI) who require continuous renal replacement therapy (CRRT), including elderly age, systemic inflammation, oliguria, fluid imbalance, comorbidities, and need for mechanical ventilation [1-4]. Nevertheless, prognostic factors that accurately predict outcomes have not been determined. Among the prognostic factors under consideration, there is growing interest in the clinical role of negative or positive fluid balance associated with fluid resuscitation [5]. Most importantly, an ideal method of body fluid assessment should be an easy, objective, and reproducible evaluation, and a treatment plan based on the results should confirm whether it affects the outcomes of the patient. The pathogenesis of AKI in critical illness is multi-factorial and complex. Therefore, therapeutic interventions for patients with AKI remain heterogeneous. In particular, it can be said that it is representative issues to determine an appropriate fluid administration dose and fluid removal amount, and the timing of renal replacement therapy. Fluid overload is strongly associated with adverse clinical outcomes and may contribute to development and persistence of AKI in critically ill patients [5]. Assessment of volume status in patients with AKI requiring renal replacement therapy is important not only for maintaining hemodynamic stability, but also for improving the outcomes of AKI. However, the traditional methods for detecting degree and severity of fluid imbalance have several limitations. Furthermore, there is no clinical gold standard that can be used as a guide for fluid administration to prevent fluid overload in patients with AKI. Many studies have consistently highlighted the clinical significance of fluid overload in critically ill patients. Jhee et al [6] also showed a relationship between fluid overload and mortality in elderly patients with AKI requiring CRRT. Their multicenter prospective cohort study clearly showed that critically ill patients with positive fluid balance for 72 hours prior to CRRT initiation were associated with higher mortality compared to those without. However, despite such clear results, attention should be paid to important issues in their research. First, as the researchers noted, it is important to define fluid overload using a decisive rather than arbitrary method. Various methods such as clinical examination, serial weights, cumulative fluid balance (CFB), chest Xray, lung ultrasound, echocardiography, and bioimpedance analysis can be used to evaluate volume status, but they all have limitations. Therefore, because there is no rapid, objective, non-invasive, and relatively affordable method to quantitatively assess volume status, it is difficult to set a treatment policy for critically ill patients with AKI requiring CRRT. Unlike the study by Jhee et al [6], some have defined the criteria for fluid overload as a Assessment of body fluid in critically ill patients with acute kidney injury requiring continuous renal replacement therapy
NanoTracker: force-sensing optical tweezers for quantitative single-molecule nanomanipulation

In the past decade, experiments involving the manipulation and observation of nanostructures with light using optical tweezers methodology have developed from proof-of-principle experiments to an established quantitative technique in fields ranging from (bio)physics to cell biology. With optical tweezers, microscopically small objects can be held and manipulated. At the same time, the forces exerted on the trapped objects can be accurately measured. With the Prism-Award winning NanoTracker a platform for performing experiments using specimen from single molecules to whole cells is available. With two time-continuous traps, it allows the controlled trapping and accurate tracking of nanoparticles, suspended either in a microfluidic multichannel flow chamber or even in a temperaturecontrolled open Petri dish. With its 3D detection system, particle displacements in the trap can be recorded with nanometer precision. Moreover, dynamic forces acting on the particle can be measured with better than picoNewton resolution on a microsecond time-scale. Here, we discuss design features of and measurements done with the NanoTracker platform. In particular, we show how one of the hallmarks of single-molecule biophysics, the overstretching transition of DNA, can be studied in a versatile manner and used for protein-DNA interaction mechanics. Moreover, on the lower side of the force range the other benchmark single-molecule biophysics, kinesin's 8-nm steps and stall forces, are shown to be measurable. With the NanoTracker, optical tweezers finally transcend from the labs of self-building scientists who helped the technique mature, to a turn-key system able to serve a much wider community of researchers in the life sciences.
Directly converted astrocytes retain the ageing features of the donor fibroblasts and elucidate the astrocytic contribution to human CNS health and disease

Astrocytes are highly specialised cells, responsible for CNS homeostasis and neuronal activity. Lack of human in vitro systems able to recapitulate the functional changes affecting astrocytes during ageing represents a major limitation to studying mechanisms and potential therapies aiming to preserve neuronal health. Here, we show that induced astrocytes from fibroblasts donors in their childhood or adulthood display age‐related transcriptional differences and functionally diverge in a spectrum of age‐associated features, such as altered nuclear compartmentalisation, nucleocytoplasmic shuttling properties, oxidative stress response and DNA damage response. Remarkably, we also show an age‐related differential response of induced neural progenitor cells derived astrocytes (iNPC‐As) in their ability to support neurons in co‐culture upon pro‐inflammatory stimuli. These results show that iNPC‐As are a renewable, readily available resource of human glia that retain the age‐related features of the donor fibroblasts, making them a unique and valuable model to interrogate human astrocyte function over time in human CNS health and disease.
Stress-induced phase transitions in diamond

A phase transformation in diamond into an intermediate carbon phase (ICP) was revealed in regions of maximal shear stress of diamond anvils. The transition was stimulated by additional stresses supplied to the compressed anvils with torque by a rotation of the anvil around the anvil's axis; maximal shear stress approached 55 GPa during the rotation. Creation of an ICP is considered as a mechanism of the stress-induced stability loss of the diamond structure. The characteristic Raman bands of ICP near 250, 500, 650–850 and 1050–1390 cm−1 were observed in the failure regions.
Glutathione ethyl ester supplementation prevents airway hyper-responsiveness in mice

Background Oxidative stress plays an important role in the pathogenesis of asthma. Glutathione (GSH) is considered to be one of the most important antioxidants. Our study systematically investigated the effect of the GSH alternative, glutathione ethyl ester (GSH-EE), on airway hyper-responsiveness (AHR) in mice. Methods Sixty-three male specific pathogen-free mice were used. Asthma was induced using a single dose of ovalbumin (OVA). The normal group (n=15) received vehicle only [Al(OH)3 in saline]. Then, 48 mice were divided into two groups, including a control group who received sodium phosphate buffer (pH =7.4), and the GSH-EE group who received 0.1% GSH-EE. AHR was measured 2, 6, and 12 hours after exposure to nebulized OVA (0.01%). The animals were then sacrificed, and lung tissue and the bronchi-alveolar lavage fluid (BALF) were harvested. Factors involved in the antioxidant response to asthma were then measured in these tissues, including thiol content (from GSH and protein), γ-glutamylcysteine synthetase (γ-GCS) activity and expression, and nuclear factor-erythroid-2-related factor (Nrf2) expression. Results The GSH-EE group showed a significant attenuation of AHR (P<0.01) 2 hours after OVA challenge, and significantly enhanced thiol contents by approximately 45% (P<0.05) at 2 and 6 hours after the last OVA challenge, compared to the control group. γ-GCS activity was also higher in the GSH-EE group compared to the control group at different time points (P<0.01). γ-GCSh and Nrf2 protein expression increased in the GSH-EE group and the control group compared with the normal group, but there was no statistically significant difference (P>0.05) between the GSH-EE group and the control group. Conclusions GSH-EE supplementation can prevent AHR in asthmatic mice during the early stages. It may function by serving as a precursor for GSH biosynthesis and by protecting sulfhydryl groups from oxidation.
Measuring improvement and deterioration in myalgic encephalomyelitis/chronic fatigue syndrome: the pitfalls of the Chalder Fatigue Questionnaire

Adamson et al. considered a 2-point decrease in Chalder Fatigue Questionnaire score to indicate improvement in fatigue and a 2-point increase in Chalder Fatigue Questionnaire score to indicate deterioration in fatigue. While intuitively appealing, data exist that suggest a more complex relationship between changes in Chalder Fatigue Questionnaire scores and clinical change. Collin and Crawley studied treatment outcomes at 11 specialist myalgic encephalomyelitis/chronic fatigue syndrome clinics in England. The authors tabulated mean change in Chalder Fatigue Questionnaire score at one year against Clinical Global Impression scores (see additional file 1, table S3). A 2-point decrease in Chalder Fatigue Questionnaire score was reported patients who deemed their health as follows: ‘no change’, ‘a little worse’, ‘much worse’ and ‘very much worse’. The mean changes in Chalder Fatigue Questionnaire score in those categories were similar, with overlapping 95% confidence intervals within the range [ 4.77, 2.29]. This suggests that a 2-point decrease in Chalder Fatigue Questionnaire score indicates deterioration or no change in the health of a person with myalgic encephalomyelitis/chronic fatigue syndrome, not improvement. Adamson et al. report a mean change in Chalder Fatigue Questionnaire score of 6.52, corresponding to the ‘a little better’ category in Collin and Crawley’s data. For comparison, the mean change of those ‘much better’ was an 11-point decrease in Chalder Fatigue Questionnaire score, and ‘very much better’ was a 14.9-point decrease. Studies using the Chalder Fatigue Questionnaire as a primary outcome measure may miss or underestimate deterioration, because the Chalder Fatigue Questionnaire obscures it. Studies may overestimate improvement if a 2-point decrease on the Chalder Fatigue Questionnaire is used, when a 10point decrease may be a more appropriate lower bound. Anchoring one subjective measure to another can hint at cut-offs for clinically important differences, but the use of more objective outcome measures such as actigraphy would be preferable. The unpopularity of such measures among myalgic encephalomyelitis/chronic fatigue syndrome researchers may be linked with the stubborn refusal of more objective outcome measures to budge with current specialist treatment.
Angle-resolved spectroscopy using a radial angular filter array

This paper presents a novel optical filter called the Radial Angular Filter Array (RAFA) for real-time measurement of the angular and spectral distribution of diffuse light exiting a turbid medium. The RAFA consists of a radiallydistributed series of 48 micro-channels micro-machined into a silicon substrate. To test the device, we constructed an angle-resolved spectroscopy system by integrating a wideband light source, the RAFA, and an imaging spectrometer. The collimated broadband light source was configured to trans-illuminate a turbid sample over a wide range of wavelengths in the near infrared spectral region. The RAFA was used to collect the angular distribution of light exiting the turbid sample. The imaging spectrometer decomposed the output of the RAFA into hyperspectral images representative of scatter angle and wavelength. By scanning the RAFA and imaging spectrometer over the sample, the intensity of the scattered light was acquired as a function of location on the sample surface, wavelength, and angle relative to the surface normal. With angle resolved spectroscopy it will be possible to characterize the optical properties of turbid samples in great detail.
The geometry of resource constraint: an empirical study of the golden snub-nosed monkey.

Apposite conceptualization and measurement of resource variation is critical for understanding many issues in ecology, including ecological niches, persistence and distribution of populations, the structure of communities, and population resilience to perturbations. We apply the nutritional geometry framework to conceptualise and quantify the responses of a temperate-living primate, the golden snub-nosed monkey (Rhinopithecus roxellana) to variation in resource quality and quantity and in nutrient requirements associated with seasonal environments. We present a geometric model distinguishing qualitative constraint, quantitative constraint, and "pseudo-constraint" whereby nutrient intakes resemble response to qualitative resource constraint but are in fact driven by variation in nutrient requirements. The model is applied to analyse nutrient intakes recorded in 164 full day observations of monkeys from two populations, one wild and the other captive, across seasons. Additionally, we recorded the diet of a single animal over 32 consecutive days in the wild. Despite considerable differences in available resources, the captive and wild populations showed marked similarities in nutrient intakes, including indistinguishable amounts and ratios of ingested macronutrients during summer and autumn and strong year-round maintenance of protein compared to seasonally variable fat and carbohydrate intakes. These similarities suggest homeostatically regulated nutritional targets and provide reference points to identify factors driving population differences in macronutrient intake in winter and spring. Our framework enabled us to distinguish examples of quantitative, qualitative, and "pseudo-constraint". We suggest that this approach can increase the resolution at which resource constraint is conceptualised and measured in ecological studies.
Primary and promiscuous functions coexist during evolutionary innovation through whole protein domain acquisitions

Molecular examples of evolutionary innovation are scarce and generally involve point mutations. Innovation can occur through larger rearrangements, but here experimental data is extremely limited. Integron integrases innovated from double-strand- toward single-strand-DNA recombination through the acquisition of the I2 α-helix. To investigate how this transition was possible, we have evolved integrase IntI1 to what should correspond to an early innovation state by selecting for its ancestral activity. Using synonymous alleles to enlarge sequence space exploration, we have retrieved 13 mutations affecting both I2 and the multimerization domains of IntI1. We circumvented epistasis constraints among them using a combinatorial library that revealed their individual and collective fitness effects. We obtained up to 104-fold increases in ancestral activity with various asymmetrical trade-offs in single-strand-DNA recombination. We show that high levels of primary and promiscuous functions could have initially coexisted following I2 acquisition, paving the way for a gradual evolution toward innovation.