Miracle-dz/UniFAR-FTUs huggingface dataset:
Pliocene and Eocene provide best analogs for near-future climates

Significance The expected departure of future climates from those experienced in human history challenges efforts to adapt. Possible analogs to climates from deep in Earth’s geological past have been suggested but not formally assessed. We compare climates of the coming decades with climates drawn from six geological and historical periods spanning the past 50 My. Our study suggests that climates like those of the Pliocene will prevail as soon as 2030 CE and persist under climate stabilization scenarios. Unmitigated scenarios of greenhouse gas emissions produce climates like those of the Eocene, which suggests that we are effectively rewinding the climate clock by approximately 50 My, reversing a multimillion year cooling trend in less than two centuries. As the world warms due to rising greenhouse gas concentrations, the Earth system moves toward climate states without societal precedent, challenging adaptation. Past Earth system states offer possible model systems for the warming world of the coming decades. These include the climate states of the Early Eocene (ca. 50 Ma), the Mid-Pliocene (3.3–3.0 Ma), the Last Interglacial (129–116 ka), the Mid-Holocene (6 ka), preindustrial (ca. 1850 CE), and the 20th century. Here, we quantitatively assess the similarity of future projected climate states to these six geohistorical benchmarks using simulations from the Hadley Centre Coupled Model Version 3 (HadCM3), the Goddard Institute for Space Studies Model E2-R (GISS), and the Community Climate System Model, Versions 3 and 4 (CCSM) Earth system models. Under the Representative Concentration Pathway 8.5 (RCP8.5) emission scenario, by 2030 CE, future climates most closely resemble Mid-Pliocene climates, and by 2150 CE, they most closely resemble Eocene climates. Under RCP4.5, climate stabilizes at Pliocene-like conditions by 2040 CE. Pliocene-like and Eocene-like climates emerge first in continental interiors and then expand outward. Geologically novel climates are uncommon in RCP4.5 (<1%) but reach 8.7% of the globe under RCP8.5, characterized by high temperatures and precipitation. Hence, RCP4.5 is roughly equivalent to stabilizing at Pliocene-like climates, while unmitigated emission trajectories, such as RCP8.5, are similar to reversing millions of years of long-term cooling on the scale of a few human generations. Both the emergence of geologically novel climates and the rapid reversion to Eocene-like climates may be outside the range of evolutionary adaptive capacity.
Sensing with photoluminescent semiconductor quantum dots

Fluorescent sensors benefit from high signal-to-noise and multiple measurement modalities, enabling a multitude of applications and flexibility of design. Semiconductor nanocrystal quantum dots (QDs) are excellent fluorophores for sensors because of their extraordinary optical properties. They have high thermal and photochemical stability compared to organic dyes or fluorescent proteins and are extremely bright due to their large molar cross-sections. In contrast to organic dyes, QD emission profiles are symmetric, with relatively narrow bandwidths. In addition, the size tunability of their emission color, which is a result of quantum confinement, make QDs exceptional emitters with high color purity from the ultra-violet to near infrared wavelength range. The role of QDs in sensors ranges from simple fluorescent tags, as used in immunoassays, to intrinsic sensors that utilize the inherent photophysical response of QDs to fluctuations in temperature, electric field, or ion concentration. In more complex configurations, QDs and biomolecular recognition moieties like antibodies are combined with a third component to modulate the optical signal via energy transfer. QDs can act as donors, acceptors, or both in energy transfer-based sensors using Förster resonance energy transfer (FRET), nanometal surface energy transfer (NSET), or charge or electron transfer. The changes in both spectral response and photoluminescent lifetimes have been successfully harnessed to produce sensitive sensors and multiplexed devices. While technical challenges related to biofunctionalization and the high cost of laboratory-grade fluorimeters have thus far prevented broad implementation of QD-based sensing in clinical or commercial settings, improvements in bioconjugation methods and detection schemes, including using simple consumer devices like cell phone cameras, are lowering the barrier to broad use of more sensitive QD-based devices.
Triple Stimulation Technique in Amyotrophic Lateral Sclerosis

Purpose: To identify upper motor neuron (UMN) dysfunction using the triple stimulation technique (TST) in amyotrophic lateral sclerosis (ALS). Methods: Fifty ALS and 42 non-ALS patients were examined clinically, using conventional transcranial magnetic stimulation and TST. Results: For ALS patients presenting with UMN in tested limb, the TST amplitude ratio was abnormal in 25 of 28 patients (89.3%). For ALS patients without UMN signs, 6 of 22 patients (27.3%) had an abnormal TST ratio. When clinical signs were not present, both abnormal resting motor threshold and TST indicated a UMN involvement. In non-ALS patients with central motor conduction disorders, the percentage of patients with an abnormal TST was higher for those presenting with clinical UMN signs (9/12, 75.0%) than for those without these signs (1/8, 12.5%). Conclusions: Triple stimulation technique appears to be an accurate, early measure for detecting clinical and subclinical UMN abnormalities in ALS. Triple stimulation technique could also be useful to investigate central motor conduction abnormalities in other disorders.
A quantum machine learning algorithm based on generative models

We propose a quantum learning algorithm for a quantum generative model and prove its advantages compared with classical models. Quantum computing and artificial intelligence, combined together, may revolutionize future technologies. A significant school of thought regarding artificial intelligence is based on generative models. Here, we propose a general quantum algorithm for machine learning based on a quantum generative model. We prove that our proposed model is more capable of representing probability distributions compared with classical generative models and has exponential speedup in learning and inference at least for some instances if a quantum computer cannot be efficiently simulated classically. Our result opens a new direction for quantum machine learning and offers a remarkable example where a quantum algorithm shows exponential improvement over classical algorithms in an important application field.
Measuring the Dispositional Tendency to Spread Oneself Too Thin

This paper describes the development and validation of a scale to measure the dispositional tendency to spread oneself too thin (SOTT) – a tendency that is likely an important antecedent of work-nonwork conflicts. In two studies, we develop and validate a scale for measuring this tendency and examine how it relates to other dispositional causes of role conflicts. In Study 1 we tested our initial item pool using a heterogeneous sample of full-time workers (N = 193) and used exploratory factor analysis to reduce our item pool to a set of five items. In Study 2, using another heterogeneous sample of full-time workers (N = 212), we conducted confirmatory factor analyses to demonstrate that the items fit a unidimensional construct. We also demonstrated that the scale has moderately high test-retest reliability, is distinct from other potentially related constructs, and predicts work-nonwork conflicts above and beyond previously studied dispositional antecedents. We discuss the importance of studying the dispositional tendency to SOTT as a potentially malleable antecedent of work-nonwork conflict and note other employee outcomes that it may also impact.
Inotropic interventions do not change the resting state of myosin motors during cardiac diastole

&NA; When striated (skeletal and cardiac) muscle is in its relaxed state, myosin motors are packed in helical tracks on the surface of the thick filament, folded toward the center of the sarcomere, and unable to bind actin or hydrolyze ATP (OFF state). This raises the question of whatthe mechanism is that integrates the Ca2+‐dependent thin filament activation, making myosin heads available for interaction with actin. Here we test the interdependency of the thin and thick filament regulatory mechanisms in intact trabeculae from the rat heart. We record the x‐ray diffraction signals that mark the state of the thick filament during inotropic interventions (increase in sarcomere length from 1.95 to 2.25 μm and addition of 10−7 M isoprenaline), which potentiate the twitch force developed by an electrically paced trabecula by up to twofold. During diastole, none of the signals related to the OFF state of the thick filament are significantly affected by these interventions, except the intensity of both myosin‐binding protein C‐ and troponin‐related meridional reflections, which reduce by 20% in the presence of isoprenaline. These results indicate that recruitment of myosin motors from their OFF state occurs independently and downstream from thin filament activation. This is in agreement with the recently discovered mechanism based on thick filament mechanosensing in which the number of motors available for interaction with actin rapidly adapts to the stress on the thick filament and thus to the loading conditions of the contraction. The gain of this positive feedback may be modulated by both sarcomere length and the degree of phosphorylation of myosin‐binding protein C. &NA; Thick filament mechanosensing has been proposed as the mechanism by which myosin motors in cardiac muscle become available to bind actin. Accordingly, Caremani et al., using x‐ray diffraction from intact rat trabeculae, show that myosin motors fully return to their OFF state during diastole independently of inotropic interventions.
Long-Term Feature Banks for Detailed Video Understanding

To understand the world, we humans constantly need to relate the present to the past, and put events in context. In this paper, we enable existing video models to do the same. We propose a long-term feature bank—supportive information extracted over the entire span of a video—to augment state-of-the-art video models that otherwise would only view short clips of 2-5 seconds. Our experiments demonstrate that augmenting 3D convolutional networks with a long-term feature bank yields state-of-the-art results on three challenging video datasets: AVA, EPIC-Kitchens, and Charades. Code is available online.
Ethynylpyrene Linked Benzocrown Ethers as Fluorescent Sensors for Metal Ions

Substances containing ethynylpyrenes linked to either one or four benzocrown ethers were synthesized, and their absorption and fluorescence spectroscopic responses to metal ions were assessed. Addition of metal perchlorates to solutions of these substances promotes short wavelength shifts in their absorption and fluorescence maxima and increases in their fluorescence intensities. The magnitudes of the fluorescence intensity increases are dependent on the ring size and number of the crown ether and the nature of the metal cation. Association constants for complex formation were calculated using fluorescence intensity versus concentration data. Analysis using Job's plots showed that the substances containing one benzocrown ether moiety form 1:1 complexes with metal ions. Results of experiments employing repeated addition and removal of Mg(ClO4)2 demonstrate that the ON‐OFF fluorescence response can be repeated at least three times. Results of molecular orbital calculations show that complexation with metal ions lowers the energies of both the π and π* levels of the ethynylpyrene moiety and that in some cases the vacant orbital on the metal becomes the LUMO of the complex. An explanation of the spectroscopic changes promoted by metal ions is proposed in terms of electrostatic repulsion and structural regulation.
Variability of amino acid digestibility of lupin and pea grains in caecectomised laying hens

ABSTRACT 1. The objective of this study was to investigate the variations in amino acid (AA) digestibility of lupin and pea grains in caecectomised laying hens. The relationship between AA digestibility and chemical constituents of the grains was determined. 2. Twelve variants of lupins and peas were each added to a basal diet at a concentration of 300 g/kg, at the expense of maize starch. The lupin and pea variants were separately investigated in two subsequent trials. Each trial consisted of two 7 × 7 Latin squares, each comprising the basal diet and six diets with lupins or peas. 3. Fourteen caecectomised laying hens (LSL-classic) were individually housed in metabolism cages and 120 g/d of experimental diets were provided for eight days. During the last four days, excreta were collected quantitatively and feed intake was recorded. A regression approach was used to determine the AA digestibility of the lupin and pea variants. 4. Amino acid digestibility of the lupins and peas was high, although significant differences in AA digestibility among the lupins and peas were detected. The digestibility of lysine was in the range of 0.87–0.91 and 0.87–0.93 for lupins and peas, respectively. The digestibility of methionine in lupins and peas varied between 0.80–0.88 and 0.72–0.90. Variations in AA digestibility in peas were more pronounced than in lupins. 5. Significant correlations between chemical constituents of lupins, such as alkaloids, and AA digestibility were detected in some cases, without a consistent pattern. In peas, tannin concentration and the insoluble protein fraction were negatively correlated with digestibility of some AAs, but only when one colour flower variant was considered. Trypsin inhibitor activity in peas was negatively correlated with AA digestibility, particularly for the white flower variants.
Anagrelide for Gastrointestinal Stromal Tumor

Purpose: Gastrointestinal stromal tumor (GIST) is a common type of soft-tissue sarcoma. Imatinib, an inhibitor of KIT, platelet-derived growth factor receptor alpha (PDGFRA), and a few other tyrosine kinases, is highly effective for GIST, but advanced GISTs frequently progress on imatinib and other approved tyrosine kinase inhibitors. We investigated phosphodiesterase 3 (PDE3) as a potential therapeutic target in GIST cell lines and xenograft models. Experimental Design: The GIST gene expression profile was interrogated in the MediSapiens IST Online transcriptome database comprising human tissue and cancer samples, and PDE3A and PDE3B expression was studied using IHC on tissue microarrays (TMA) consisting of 630 formalin-fixed human tissue samples. GIST cell lines were screened for sensitivity to 217 anticancer compounds, and the efficacy of PDE inhibitors on GIST was further studied in GIST cell lines and patient-derived mouse xenograft models. Results: GISTs expressed PDE3A and PDE3B frequently compared with other human normal or cancerous tissues both in the in silico database and the TMAs. Anagrelide was identified as the most potent of the PDE3 modulators evaluated. It reduced cell viability, promoted cell death, and influenced cell signaling in GIST cell lines. Anagrelide inhibited tumor growth in GIST xenograft mouse models. Anagrelide was also effective in a GIST xenograft mouse model with KIT exon 9 mutation that may pose a therapeutic challenge, as these GISTs require a high daily dose of imatinib. Conclusions: PDE3A and PDE3B are frequently expressed in GIST. Anagrelide had anticancer efficacy in GIST xenograft models and warrants further testing in clinical trials.
An Educational Intervention to Improve HPV Vaccination: A Cluster Randomized Trial

We examine the effect of a digital educational intervention linked to previous vaccine history on HPV vaccination decisions in urban pediatric settings. BrightcoveDefaultPlayer10.1542/6138649650001PEDS-VA_2018-1457 Video Abstract BACKGROUND: Human papillomavirus (HPV) infection can lead to serious health issues and remains the most common sexually transmitted infection. Despite availability of effective vaccines, HPV vaccination rates are suboptimal. METHODS: In a cluster randomized trial, an intervention used to target parents of adolescents (11–17 years) eligible for a dose of HPV vaccine, was tested in pediatric clinics part of an urban health system. Parents watched a digital video outlining the risks and benefits of vaccine using a tablet in the examination room. The primary outcome was change in HPV vaccine status 2 weeks after the clinic visit. An intention-to-treat analysis for the primary outcome used generalized estimating equations to accommodate the potential cluster effect of clinics. RESULTS: A total of 1596 eligible adolescents were observed during the 7-month trial. One-third of adolescents visited an intervention clinic. Adolescents who attended an intervention clinic were more likely to be younger (11–12 years) than those who attended a control clinic (72.4% vs 49.8%; P < .001). No differences in race or sex were observed. The proportion of adolescents with an observed change in vaccine status was higher for those attending an intervention clinic (64.8%) versus control clinic (50.1%; odds ratio, 1.82; 95% confidence interval, 1.47–2.25; P < .001). Adolescents whose parents watched the video had a 3-times greater odds of receiving a dose of the HPV vaccine (78.0%; odds ratio, 3.07; 95% confidence interval, 1.47–6.42; P = .003). CONCLUSIONS: Educational interventions delivered within a clinical setting hold promise to improve vaccination behaviors.
Neuroplastic Changes in Older Adults Performing Cooperative Hand Movements

The aim of this study was to examine whether older adults use the same task-specific brain activation patterns during two different bimanual hand movement tasks as younger adults. Functional magnetic resonance brain imaging was performed in 18 younger (mean age: 30.3 ± 3.6 years) and 11 older adults (62.6 ± 6.8 years) during the execution of cooperative (mimicking opening a bottle) or non-cooperative (bimanual pro-/supination) hand movements. We expected to see a stronger task-specific involvement of the secondary somatosensory cortex (S2) during cooperative hand movements in older compared to younger adults. However, S2 activation was present in both groups during the cooperative task and was only significantly stronger compared to the non-cooperative task in younger adults. In a whole brain-analysis, the contrast between older and younger adults revealed a hyperactivation of the bilateral dorsal premotor cortex (precentral gyrus), right thalamus, right frontal operculum, anterior cingulate cortex, and supplementary motor areas in older adults (p < 0.001), with some of them being visible after correcting for age. Age was positively associated with fMRI signal changes in these regions across the whole sample. Older adults showed reduced gray matter volume but not in regions showing task-related fMRI group differences. We also found an increase in functional connectivity between SMA, M1, thalamus, and precentral gyri in older adults. In contrast, younger adults showed hyperconnectivity between S2 and S1. We conclude that older compared to younger adults show age-related functional neuroplastic changes in brain regions involved in motor control and performance.
Effects of neuromuscular electrical stimulation on gait performance in chronic stroke with inadequate ankle control - A randomized controlled trial

Neuromuscular electrical stimulation (NMES) has been used to improve muscle strength and decrease spasticity of the ankle joint in stroke patients. However, it is unclear how NMES could influence dynamic spasticity of ankle plantarflexors and gait asymmetry during walking. The study aimed to evaluate the effects of applying NMES over ankle dorsiflexors or plantarflexors on ankle control during walking and gait performance in chronic stroke patients. Twenty-five stroke participants with inadequate ankle control were recruited and randomly assigned to an experimental or a control group. The experimental group received 20 minutes of NMES on either the tibialis anterior muscle (NMES-TA) or the medial gastrocnemius muscle (NMES-MG). The control group received 20 minutes of range of motion and stretching exercises. After the 20 minutes of NMES or exercises, all participants received ambulation training for 15 minutes. Training sessions occurred 3 times per week for 7 weeks. The pre- and post-training assessments included spatio-temporal parameters, ankle range of motion, and dynamic spasticity of ankle plantarflexors during walking. Muscle strength of ankle dorsiflexors and plantarflexors as well as static spasticity of ankle plantarflexors were also examined. The results showed that the static and dynamic spasticity of ankle plantarflexors of the NMES-TA group were significantly decreased after training. Reduction in dynamic spasticity of ankle plantarflexors of the NMES-TA group was significantly greater than that of the NMES-MG group. When compared to the control group, the NMES-TA group had greater improvements in spatial asymmetry, ankle plantarflexion during push off, and muscle strength of ankle dorsiflexors, and the NMES-MG group showed a significant decrease in temporal asymmetry. In summary, NMES on ankle dorsiflexors could be an effective management to enhance gait performance and ankle control during walking in chronic stroke patients. NMES on ankle plantarflexors may improve gait symmetry.
Achieving Automated Organelle Biopsy on Small Single Cells Using a Cell Surgery Robotic System

Single cell surgery such as manipulation or removal of subcellular components or/and organelles from single cells is increasingly used for the study of diseases and their causes in precision medicine. This paper presents a robotic surgery system to achieve automated organelle biopsy of single cells with dimensions of less than 20 μm in diameter. The complexity of spatial detection of the organelle position is reduced by patterning the cells using a microfluidic chip device. A sliding mode nonlinear controller is developed to enable extraction of organelles, such as the mitochondria and the nucleus, from single cells with high precision. An image processing algorithm is also developed to automatically detect the position of the desired organelle. The effectiveness of the proposed robotic surgery system is demonstrated experimentally with automated extraction of mitochondria and nucleus from human acute promyelocytic leukemia cells and human fibroblast cells. Extraction is followed by biological tests to indicate the functionality of biopsied mitochondria as well as the cell viability after removal of mitochondria. The results presented here have revealed that the proposed approach of automated organelle biopsy on single small cells is feasible.
The Antiapoptosis Effect of Geum japonicum Thunb. var. chinense Extracts on Cerebral Ischemia Reperfusion Injury via PI3K/Akt Pathway

Geum japonicum Thunb. var. chinense (GJ) is a type of wild vegetable found in China and other Asian countries; it has been reported that its extracts possess a neuroprotective effect against cerebral ischemia reperfusion (CIR) injury. The aim of this study is to explore the effect GJ extracts on transient focal CIR injury and neurons apoptosis and to clarify its possible underlying mechanisms in vivo. Our results indicated that pretreatment with GJ extracts significantly ameliorated the infarct volume, decreased neurological deficits, lessened neural cells apoptosis, downregulated GFAP activity level, and increased surviving neurons. Moreover, GJ extracts preadministration increased Bcl-2 levels and attenuated the increase in the expressions of Bax and it also lowered the cleaved caspase-3 activity in ischemic cortex tissues which was caused by CIR and increased the expression of PI3K and p-Akt. The above effects of high dose of GJ (GJ-H) group were much better than those of low dose of GJ (GJ-L), which indicated that GJ extracts may be helpful in the suppression of CIR injury with a dose-dependent manner.