Miracle-dz/UniFAR-FTUs huggingface dataset:
Revealing roles of competing local structural orderings in crystallization of polymorphic systems

We reveal a spatiotemporal fluctuation of local orders inside intermediates during colloidal crystallization. Most systems have more than two stable crystalline states in the phase diagram, which is known as polymorphism. Crystallization in such a system is often under strong influence of competing orderings linked to those crystals. However, how such competition affects crystal nucleation and ordering toward the final crystalline state is largely unknown. This is primarily because the competition takes place locally and thus is masked by large positional fluctuations. We develop a unique method to correctly identify local symmetries by removing their distortions due to positional fluctuations. This allows us to experimentally access the spatiotemporal fluctuations of local symmetries at a single-particle level in crystallization of a charged colloidal system near the body-centered cubic–face-centered cubic border. Thus, we successfully reveal the crucial roles of competing ordering in the initial selection of polymorphs and the final grain boundary motion toward the most stable state from a microscopic perspective.
Context-Dependent IL-1 mRNA-Destabilization by TTP Prevents Dysregulation of Immune Homeostasis Under Steady State Conditions

The bioavailability of the major pro-inflammatory cytokines IL-1α and IL-1β is tightly controlled by transcription and post-translational processing to prevent hyperinflammation. The role of mRNA decay in maintenance of physiological IL-1 amounts remained unknown. Here we show that the down-regulation of Il1a and Il1b mRNA by the mRNA-destabilizing protein TTP (gene Zfp36) is required for immune homeostasis. The TTP deficiency syndrome, a multi organ inflammation in TTP−/− mice, was significantly ameliorated upon deletion of the IL-1 receptor. Il1a and Il1b played non-redundant roles in triggering the pathological IL-1 signaling in TTP−/− mice. Accordingly, tissues from TTP−/− animals contained increased amounts of Il1b mRNA. Unexpectedly, TTP destabilized Il1b mRNA in cell type-specific ways as evident from RNA-Seq and mRNA stability assays. These results demonstrate that TTP-driven mRNA destabilization depends on the cellular context. Moreover, such context-defined mRNA decay is essential for keeping steady state IL-1 levels in the physiological range.
Mechanisms of RNA N6-Methyladenosine in Hepatocellular Carcinoma: From the Perspectives of Etiology

N6-Methyladenosine (m6A) is the most common RNA internal modification in eukaryotic cells. Its regulatory effects at the post-transcriptional level on both messenger RNAs (mRNAs) and noncoding RNAs have been widely studied; these include alternative splicing, stability, translation efficiency, nucleus export, and degradation. m6A modification is implicated in a series of physiological and pathological activities, such as embryonic stem cell differentiation, immunoregulation, adipogenesis, and cancer development. Recently, the significance of m6A methylation has been identified in both viral hepatitis and non-alcohol fatty liver disease (NAFLD), which are major risk factors in the development of hepatocellular carcinoma (HCC). Given the high incidence and mortality rate of HCC worldwide, it is of great importance to elucidate the mechanisms underlying HCC initiation and progression. m6A as an emerging research focus has great potential to facilitate the understanding of HCC, particularly from an etiological perspective. Thus, in this review, we summarize recent progress in understanding m6A modification related to viral hepatitis, NAFLD, and HCC, including their mechanisms and clinical applications.
Understanding soil health and associated farmers' perceptions in Colombian coffee systems

Soil health (SH) is important to the economics and environmental impacts of crop production, including coffee (Coffea spp.) culture. This study was conducted to gain insights into farmers' perceptions related to SH concepts and their realities on Colombian coffee farms. A total of 223 soil samples were collected from 145 coffee farms in Cauca, Colombia, that vary by municipality, their membership status with a coffee co-op (member or non-member), and farmer gender. Samples were analyzed for 13 SH indicators, including wet aggregate stability (WAS), available water capacity (AWC), respiration rate, pH, active carbon (AC), organic matter (OM), protein, phosphorus (P), potassium (K), magnesium (Mg), iron (Fe), manganese (Mn), and zinc (Zn). Farmer co-op membership and municipality, but not farmer gender, were significant factors for SH status on farms. Farmer co-op members were asked to identify on their farms the plot that they perceived to have the highest soil fertility and the plot with the lowest soil fertility, which allowed for the evaluation of (1) the correctness of farmers' SH perception, i.e., whether their perception was aligned with or similar to scientific measurements of SH, and (2) which SH indicators strongly influence farmer perception of SH. Farmers' perceptions were found to be in line with the scientific laboratory measurements of SH, and their perceptions were significantly positively influenced by the soil's organic matter and protein contents but negatively influenced by soil respiration. Finally, SH perception correctness was not correlated with farmer gender, locality, or SH conditions.
How the effects of actions become our own

The feeling that physical events are caused by us is tied to our action planning rather than being a mere post hoc deduction. Every day, we do things that cause effects in the outside world with little doubt about who caused what. To some, this sense of agency derives from a post hoc reconstruction of a likely causal relationship between an event and our preceding movements; others propose that the sense of agency originates from prospective comparisons of motor programs and their effects. Using functional magnetic resonance imaging, we found that the sense of agency is associated with a brain network including the pre–supplementary motor area (SMA) and dorsal parietal cortex. Transcranial magnetic stimulation affected the sense of agency only when delivered over the pre-SMA and specifically when time-locked to action planning, rather than when the physical consequences of the actions appeared. These findings make a prospective theory of the sense of agency more likely.
Basking behaviour in the rock hyrax (Procavia capensis) during winter

ABSTRACT Basking is a behaviour frequently observed in the rock hyrax (Procavia capensis) during winter that supposedly plays a significant role in rewarming from nocturnal hypothermia. This behaviour, together with changes in body temperature and changes in black bulb temperatures (Tbb) were investigated in the natural environment. In this study, rock hyraxes did not reduce their body temperature substantially overnight and thus basking was not used for rewarming but rather to maintain constant body temperatures under low ambient conditions. Frequency of basking changed throughout the day as Tbb increased and decreased. Different basking postures (hunched or flat), orientations to the sun and basking bout lengths were modified depending on Tbb experienced. There was no difference in body temperature between the two basking postures at any Tbb. It appears that rock hyraxes did not use basking behaviour as a way of warming up after night-time but used it during the day as a diurnal energy conserving mechanism.
Cell cycle state proteomics and classification using in-cell protease digests and mass spectrometry

Proteomic analysis of rare cell states is a major challenge. We report an advance to our PRoteomics of Intracellular iMMUnostained cell Subsets (PRIMMUS) workflow whereby fixed cells are directly digested by proteases in cellulo for mass spectrometry-based proteomics. This decreased the cell number requirement by two orders of magnitude to
Clinical and Recent Patents Applications of PD-1/PD-L1 Targeting Immunotherapy in Cancer Treatment—Current Progress, Strategy, and Future Perspective

Targeting PD-L1 and PD-1 interactions is a relatively new therapeutic strategy used to treat cancer. Inhibitors of PD-1/PD-L1 include peptides, small molecule chemical compounds, and antibodies. Several approved antibodies targeting PD-1 or PD-L1 have been patented with good curative effect in various cancer types in clinical practices. While the current antibody therapy is facing development bottleneck, some companies have tried to develop PD-L1 companion tests to select patients with better diagnosis potential. Meanwhile, many companies have recently synthesized small molecule inhibitors of PD-1/PD-L1 interactions and focused on searching for novel biomarker to predict the efficacy of anti-PD-1/PD-L1 drugs. This review summarized clinical studies and patent applications related to PD-1/PD-L1 targeted therapy and also discussed progress in inhibitors of PD-1/PD-L1.
Human Thymic Involution and Aging in Humanized Mice

Thymic involution is an important factor leading to the aging of the immune system. Most of what we know regarding thymic aging comes from mouse models, and the nature of the thymic aging process in humans remains largely unexplored due to the lack of a model system that permits longitudinal studies of human thymic involution. In this study, we sought to explore the potential to examine human thymic involution in humanized mice, constructed by transplantation of fetal human thymus and CD34+ hematopoietic stem/progenitor cells into immunodeficient mice. In these humanized mice, the human thymic graft first underwent acute recoverable involution caused presumably by transplantation stress, followed by an age-related chronic form of involution. Although both the early recoverable and later age-related thymic involution were associated with a decrease in thymic epithelial cells and recent thymic emigrants, only the latter was associated with an increase in adipose tissue mass in the thymus. Furthermore, human thymic grafts showed a dramatic reduction in FOXN1 and AIRE expression by 10 weeks post-transplantation. This study indicates that human thymus retains its intrinsic mechanisms of aging and susceptibility to stress-induced involution when transplanted into immunodeficient mice, offering a potentially useful in vivo model to study human thymic involution and to test therapeutic interventions.
On-Chip Training Spiking Neural Networks Using Approximated Backpropagation With Analog Synaptic Devices

Hardware-based spiking neural networks (SNNs) inspired by a biological nervous system are regarded as an innovative computing system with very low power consumption and massively parallel operation. To train SNNs with supervision, we propose an efficient on-chip training scheme approximating backpropagation algorithm suitable for hardware implementation. We show that the accuracy of the proposed scheme for SNNs is close to that of conventional artificial neural networks (ANNs) by using the stochastic characteristics of neurons. In a hardware configuration, gated Schottky diodes (GSDs) are used as synaptic devices, which have a saturated current with respect to the input voltage. We design the SNN system by using the proposed on-chip training scheme with the GSDs, which can update their conductance in parallel to speed up the overall system. The performance of the on-chip training SNN system is validated through MNIST data set classification based on network size and total time step. The SNN systems achieve accuracy of 97.83% with 1 hidden layer and 98.44% with 4 hidden layers in fully connected neural networks. We then evaluate the effect of non-linearity and asymmetry of conductance response for long-term potentiation (LTP) and long-term depression (LTD) on the performance of the on-chip training SNN system. In addition, the impact of device variations on the performance of the on-chip training SNN system is evaluated.
Supervised Machine Learning Applied to Wearable Sensor Data Can Accurately Classify Functional Fitness Exercises Within a Continuous Workout

Observing, classifying and assessing human movements is important in many applied fields, including human-computer interface, clinical assessment, activity monitoring and sports performance. The redundancy of options in planning and implementing motor programmes, the inter- and intra-individual variability in movement execution, and the time-continuous, high-dimensional nature of motion data make segmenting sequential movements into a smaller set of discrete classes of actions non-trivial. We aimed to develop and validate a method for the automatic classification of four popular functional fitness drills, which are commonly performed in current circuit training routines. Five inertial measurement units were located on the upper and lower limb, and on the trunk of fourteen participants. Positions were chosen by keeping into account the dynamics of the movement and the positions where commercially-available smart technologies are typically secured. Accelerations and angular velocities were acquired continuously from the units and used to train and test different supervised learning models, including k-Nearest Neighbors (kNN) and support-vector machine (SVM) algorithms. The use of different kernel functions, as well as different strategies to segment continuous inertial data were explored. Classification performance was assessed from both the training dataset (k-fold cross-validation), and a test dataset (leave-one-subject-out validation). Classification from different subsets of the measurement units was also evaluated (1-sensor and 2-sensor data). SVM with a cubic kernel and fed with data from 600 ms windows with a 10% overlap gave the best classification performances, yielding to an overall accuracy of 97.8%. This approach did not misclassify any functional fitness movement for another, but confused relatively frequently (2.8–18.9%) a fitness movement phase with the transition between subsequent repetitions of the same task or different drills. Among 1-sensor configurations, the upper arm achieved the best classification performance (96.4% accuracy), whereas combining the upper arm and the thigh sensors obtained the highest level of accuracy (97.6%) from 2-sensors movement tracking. We found that supervised learning can successfully classify complex sequential movements such as those of functional fitness workouts. Our approach, which could exploit technologies currently available in the consumer market, demonstrated exciting potential for future on-field applications including unstructured training.
Commentary: Coronavirus and Obesity: Could Insulin Resistance Mediate the Severity of Covid-19 Infection?

Insulin Resistance (IR) might be a potential key factor behind the COVID-19 severity found in people with obesity. An article published on Frontiers Public Health supported the evidence of possible mechanisms linking IR and COVID-19 severity via the upregulation of ACE 2, the protein involved in virus entry (1). This research area is worthy of being investigated further for its implication in the prevention and treatment of this dramatic pandemic. We need to understand the molecular mechanisms related to the higher risk both of being infected by SARS-CoV-2 and of developing a more severe disease (COVID-19).
Experimental and Numerical Studies on the Focused Waves Generated by Double Wave Groups

From the experiment of Li et al. (2015) it was observed that the generation of freak waves in random wave trains may be attributed to the focusing of double wave groups with different peak frequencies. In order to investigate this generation process, a modified wave focusing experiment is carried out, in which the focused waves are generated by two wave groups with different peak frequency differences, assumed to focus at the same point and time. By analyzing the evolutions of the free surface elevation and wavelet spectra of the experimental data, it can be verified that the focusing of double wave groups can reproduce the generation process of the freak waves in random wave trains well. Phase lags of the double wave groups focusing relative to the linear superposition of the corresponding single wave group and changes in the amplitude spectra during the focusing process are obviously observed. The method for the symmetry-based separation of harmonics illustrates that the phase shifts are mainly caused by the third-order non-linearity due to interactions between the two wave groups, rather than the even-order non-linearity. Third-order non-linearity makes the amplitude of waves small in the high-frequency region, resulting in a shift of the actual focusing location from the target location. Further investigations are conducted with the numerical simulation based on the High Order Spectral (HOS) method. The wavenumber-frequency spectra explain the evolution of the amplitude spectra and changes in the dispersive properties both in time and space, demonstrating that the third-order non-linearity changes the dispersion relationship of the wave components more intuitively. The above phenomena become obvious for the cases with smaller peak frequency differences wave spectra. All these observations will lead to a better understanding of the mechanism of freak wave generation and lay an important foundation for the low-cost and large-scale development and utilization of ocean wave energy resources.
Coordinated Operation of Gas and Electricity Systems for Flexibility Study

The increased interdependencies between electricity and gas systems driven by gas-fired power plants and gas electricity-driven compressors necessitates detailed investigation of such interdependencies, especially in the context of an increased share of renewable energy sources. In this paper, the value of an integrated approach for operating gas and electricity systems is assessed. An outer approximation with equality relaxation (OA/ER) method is used to deal with the optimization class of the mixed-integer non-linear problem of the integrated operation of gas and electricity systems. This method significantly improved the efficiency of the solution algorithm and achieved a nearly 40% reduction in computation time compared to successive linear programming. The value of flexibility technologies, including flexible gas compressors, demand-side response, battery storage, and power-to-gas, is quantified in the operation of integrated gas and electricity systems in GB 2030 energy scenarios for different renewable generation penetration levels. The modeling demonstrates that the flexibility options will enable significant cost savings in the annual operational costs of gas and electricity systems (up to 21%). On the other hand, the analysis carried out indicates that deployment of flexibility technologies appropriately supports the interaction between gas and electricity systems.
Inflammation and Corticospinal Functioning in Multiple Sclerosis: A TMS Perspective

Transcranial magnetic stimulation (TMS) has been employed in multiple sclerosis (MS) to assess the integrity of the corticospinal tract and the corpus callosum and to explore some physiological properties of the motor cortex. Specific alterations of TMS measures have been strongly associated to different pathophysiological mechanisms, particularly to demyelination and neuronal loss. Moreover, TMS has contributed to investigate the neurophysiological basis of MS symptoms, particularly those not completely explained by conventional structural damage, such as fatigue. However, variability existing between studies suggests that alternative mechanisms should be involved. Knowledge of MS pathophysiology has been enriched by experimental studies in animal models (i.e., experimental autoimmune encephalomyelitis) demonstrating that inflammation alters synaptic transmission, promoting hyperexcitability and neuronal damage. Accordingly, TMS studies have demonstrated an imbalance between cortical excitation and inhibition in MS. In particular, cerebrospinal fluid concentrations of different proinflammatory and anti-inflammatory molecules have been associated to corticospinal hyperexcitability, highlighting that inflammatory synaptopathy may represent a key pathophysiological mechanism in MS. In this perspective article, we discuss whether corticospinal excitability alterations assessed with TMS in MS patients could be useful to explain the pathophysiological correlates and their relationships with specific MS clinical characteristics and symptoms. Furthermore, we discuss evidence indicating that, in MS patients, inflammatory synaptopathy could be present since the early phases, could specifically characterize relapses, and could progressively increase during the disease course.
Medium spiny neurons activity reveals the discrete segregation of mouse dorsal striatum

Behavioural studies differentiate the rodent dorsal striatum (DS) into lateral and medial regions; however, anatomical evidence suggests that it is a unified structure. To understand striatal dynamics and basal ganglia functions, it is essential to clarify the circuitry that supports this behavioural-based segregation. Here, we show that the mouse DS is made of two non-overlapping functional circuits divided by a boundary. Combining in vivo optopatch-clamp and extracellular recordings of spontaneous and evoked sensory activity, we demonstrate different coupling of lateral and medial striatum to the cortex together with an independent integration of the spontaneous activity, due to particular corticostriatal connectivity and local attributes of each region. Additionally, we show differences in slow and fast oscillations and in the electrophysiological properties between striatonigral and striatopallidal neurons. In summary, these results demonstrate that the rodent DS is segregated in two neuronal circuits, in homology with the caudate and putamen nuclei of primates.
Heart Rate Behavior in Speed Climbing

Speed climbing is an Olympic discipline within the combined sport climbing event in 2020 for the first time. Speed climbing is a high-speed and anaerobic exercise against gravity over a few seconds with extreme psychological pressure. Although there is some literature on heart rate (HR) when lead climbing, there is no literature on the behavior of the HR when speed climbing. The HR of seven near-elite participants was measured with a Polar HR monitor while climbing a 10- and 15-m wall, respectively, three times each, with pauses of 5 min between the first and last three climbs and a 20-min pause between the third and fourth climb. The average climbing times on the 10- and 15-m walls were 9.16 ± 3.06 s and 14.95 ± 3.14 s, respectively (data pooled between climbing heights). The peak HR on the 10- and 15-m walls were 164.57 ± 7.45 bpm and 176.43 ± 8.09 bpm. The rates of change in HR were as follows: average HR acceleration before peak HR, 2.53 ± 0.80 bpm/s; peak HR acceleration before peak HR, 4.16 ± 1.08 bpm/s; and average HR deceleration after peak HR, −0.98 ± 0.30 bpm/s. The average HR during the pauses ranged from 105.80 to 117.89 bpm. From the results, in comparison to the literature, we conclude that athletes, trained for sustaining high physical exertion and psychological pressure, have a far smaller HR acceleration than untrained people during light and unstressful exercises. Furthermore, the current rule that athletes shall have a minimum resting time of 5 min between climbing attempts during a speed climbing competition seems justified as sufficient time for HR recovery.