Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards Zero-Shot Autonomous Inter-Task Mapping through Object-Oriented Task Description

The successful use of Reinforcement Learning in complex tasks depends on techniques to scale-up classical learning algorithms because they suffer from the curse of dimensionality. Transfer Learning approaches have been used to accelerate learning by reusing knowledge gathered from the solution of previous tasks. However, discovering how different tasks are related is a very complex undertaking if a human is not available (or is unable) to manually establish a mapping between tasks. We here propose an algorithm to autonomously estimate a Probabilistic Inter-TAsk Mapping (PITAM) across tasks described in an object-oriented manner, which requires less domain knowledge than a handcrafted Inter-Task Mapping. We also propose two strategies for Temporal-Difference algorithms to transfer knowledge using learned PITAMs. Our experiments evaluate varied scenarios in which the source and target tasks differ in several aspects, and our proposal presents benefits over both regular learning and Q-value Reuse using a detailed InterTask Mapping.
Interleukin-1β Signaling in Dendritic Cells Induces Antiviral Interferon Responses

ABSTRACT Induction of interferon beta (IFN-β), IFN-stimulated genes (ISGs), and inflammatory responses is critical for control of viral infection. We recently identified an essential linkage of stimulation of the inflammatory cytokine interleukin-1β (IL-1β) and induction of ISGs that function as host restriction pathways against the emerging flavivirus West Nile virus (WNV) in vivo. Here we utilized ex vivo global transcriptome analysis of primary dendritic cells, known targets of WNV replication, to define gene signatures required for this IL-1β-driven antiviral response. Dendritic cells that were deficient in IL-1 receptor signaling showed dysregulation of cell-intrinsic defense genes and loss of viral control during WNV infection. Surprisingly, we found that in wild-type cells, IL-1β treatment, in the absence of infection, drove the transcription of IFN-β and ISGs at late times following treatment. Expression of these antiviral innate immune genes was dependent on the transcription factor IFN regulatory factor 3 (IRF3) and appears to reflect a general shift in IL-1β signaling from an early inflammatory response to a late IFN-mediated response. These data demonstrate that inflammatory and antiviral signals integrate to control viral infection in myeloid cells through a process of IL-1β-to-IRF3 signaling crosstalk. Strategies to exploit these cytokines in the activation of host defense programs should be investigated as novel therapeutic approaches against individual pathogens. IMPORTANCE West Nile virus is an emerging mosquito-borne flavivirus that can result in serious illness, neuropathology, and death in infected individuals. Currently, there are no vaccines or therapies for human use against West Nile virus. Immune control of West Nile virus infection requires inflammatory and antiviral responses, though the effect that each arm of this response has on the other is unclear. The significance of our research is in defining how virus-induced inflammatory responses regulate critical antiviral immune programs for effective control of West Nile virus infection. These data identify essential mechanisms of immune control that can inform therapeutic efforts against West Nile virus, with potential efficacy against other neuroinvasive viruses. West Nile virus is an emerging mosquito-borne flavivirus that can result in serious illness, neuropathology, and death in infected individuals. Currently, there are no vaccines or therapies for human use against West Nile virus. Immune control of West Nile virus infection requires inflammatory and antiviral responses, though the effect that each arm of this response has on the other is unclear. The significance of our research is in defining how virus-induced inflammatory responses regulate critical antiviral immune programs for effective control of West Nile virus infection. These data identify essential mechanisms of immune control that can inform therapeutic efforts against West Nile virus, with potential efficacy against other neuroinvasive viruses.
Assessing the Feasibility of a Social Media to Promote Weight Management Engagement in Adolescents with Severe Obesity: Pilot Study

Background Severe obesity in adolescents has deleterious physical and psychological complications necessitating frequent multi-disciplinary clinic visits. Greater treatment engagement has been equated with weight-loss. However, traditional medical weight-loss programs for adolescents have high attrition rates. Social media is widely used by adolescents and may enhance medical weight management engagement and success. Objective The first objective was to examine the acceptability and feasibility of using a private social media group as an adjunct to medical weight management in youth ages 14 to 20 years with severe obesity [body mass index (BMI) ≥ 35 kg/m2]. The second objective was to pilot test the use of social media to improve treatment engagement and decrease attrition rates. Methods In this single arm, 12 week pre-post study, participants attended individual clinic visits and participated in a moderated private social media group that received nutrition, exercise, and behavior change social media communications or “posts” 3 to 4 times/week. Youth commented and/or liked posts from the moderator and each other. Social media engagement was measured with the number of likes and comments on social media. Clinic attrition was compared, measuring clinic visit attendance 12 weeks prior, during, and after the intervention with mixed linear regression models. Correlations of social media engagement with changes from baseline for BMI, BMI-z score, and psychosocial measures were fit. Results All 13 enrolled youth completed the study and reported that the group was enjoyable, helpful, reinforced their weight management program, and would recommend using social media to support other youth. The pilot trial was acceptable and feasible. Youth mean weekly engagement (likes + comments) in social media was greater than once a day (8.6 ±3.6). Compared to 12 weeks prior to the intervention, there was no significant decrease in clinic visit attendance at the end of the intervention (M=.231, P=.69) or 12 weeks at the conclusion of the intervention (M=.589, P=.28). Increased social media comments correlated with weight change (r=–.633, P=.04). Conclusions This pilot trial demonstrated that the use of social media as an adjunct to medical weight management was feasible and acceptable to adolescents with severe obesity. Based upon these preliminary findings, social media may be an effective way to mitigate attrition from obesity treatment programs, and improve health outcomes in this high-risk population.
Korean Red Ginseng Pretreatment Protects Against Long-Term Sensorimotor Deficits After Ischemic Stroke Likely Through Nrf2

Endogenous neuroprotective mechanisms by which the brain protects itself against noxious stimuli and recovers from ischemic damage are key targets of stroke research, ultimately facilitating functional recovery. Transcriptional factor Nrf2, enriched in astrocytes, is a master regulator of endogenous defense systems against oxidative stress and inflammation. Korean Red Ginseng (Ginseng), one most widely used herbal medicine, has exhibited promising potentials in neuroprotection. Our study aimed to determine whether the standardized Ginseng extract pretreatment could attenuate acute sensorimotor deficits and improve long-term functional recovery after ischemic stroke though Nrf2 pathway and whether reactive astrogliosis is associated with such effect. Adult Nrf2−/− and matched wildtype control (WT) mice were pretreated with Ginseng orally for 7 days prior to permanent distal middle cerebral artery occlusion (pdMCAO). Using an optimized method that can accurately assess either severe or mild pdMCAO-induced sensorimotor deficits, neurobehavioral tests were performed over 28 days. The progression of lesion volume and the evolution of astrocytic and microglial activation were determined in the acute stage of ischemic stroke after pdMCAO (0–3 days). Nrf2-downstream target antioxidant genes expression levels was assessed by Western blot. We found that Ginseng pretreatment ameliorated acute sensorimotor deficits and promoted long-term functional recovery, prevented the acute enlargement of lesion volume (36.37 ± 7.45% on day 3), attenuated reactive astroglial progression but not microglia activation, and enhanced the induction of Nrf2-downstream target proteins after ischemic insult in WT mice, an effect which was lost in Nrf2 knockouts. The spatiotemporal pattern of reactive astrogliosis evaluation correlated well with acute ischemic damage progression in an Nrf2-dependent fashion during the acute phase of ischemia. In contrast, Nrf2 deficiency mice exhibited exacerbated ischemic condition compared to WT controls. Together, Ginseng pretreatment protects against acute sensorimotor deficits and promotes its long-term recovery after pdMCAO, at least partly, through Nrf2 activation, highlighting the potential efficacy of oral consumption of Ginseng for stroke preventative intervention in patients who are at great risk of recurrent stroke or transient ischemic attack. The attenuated reactive astrogliosis contributes to the Nrf2 pathway related neuroprotection against acute ischemic outcome and substantially long-term sensorimotor deficits in the context of ischemic stroke under pdMCAO.
Short and Long Term Outcome of Bilateral Pallidal Stimulation in Chorea-Acanthocytosis

Background Chorea-acanthocytosis (ChAc) is a neuroacanthocytosis syndrome presenting with severe movement disorders poorly responsive to drug therapy. Case reports suggest that bilateral deep brain stimulation (DBS) of the ventro-postero-lateral internal globus pallidus (GPi) may benefit these patients. To explore this issue, the present multicentre (n=12) retrospective study collected the short and long term outcome of 15 patients who underwent DBS. Methods Data were collected in a standardized way 2-6 months preoperatively, 1-5 months (early) and 6 months or more (late) after surgery at the last follow-up visit (mean follow-up: 29.5 months). Results Motor severity, assessed by the Unified Huntington’s Disease Rating Scale-Motor Score, UHDRS-MS), was significantly reduced at both early and late post-surgery time points (mean improvement 54.3% and 44.1%, respectively). Functional capacity (UHDRS-Functional Capacity Score) was also significantly improved at both post-surgery time points (mean 75.5% and 73.3%, respectively), whereas incapacity (UHDRS-Independence Score) improvement reached significance at early post-surgery only (mean 37.3%). Long term significant improvement of motor symptom severity (≥20 % from baseline) was observed in 61.5 % of the patients. Chorea and dystonia improved, whereas effects on dysarthria and swallowing were variable. Parkinsonism did not improve. Linear regression analysis showed that preoperative motor severity predicted motor improvement at both post-surgery time points. The most serious adverse event was device infection and cerebral abscess, and one patient died suddenly of unclear cause, 4 years after surgery. Conclusion This study shows that bilateral DBS of the GPi effectively reduces the severity of drug-resistant hyperkinetic movement disorders such as present in ChAc.
Natural selection beyond genes: Identification and analyses of evolutionarily conserved elements in the genome of the collared flycatcher (Ficedula albicollis)

It is becoming increasingly clear that a significant proportion of the functional sequence within eukaryotic genomes is noncoding. However, since the identification of conserved elements (CEs) has been restricted to a limited number of model organisms, the dynamics and evolutionary character of the genomic landscape of conserved, and hence likely functional, sequence is poorly understood in most species. Moreover, identification and analysis of the full suite of functional sequence are particularly important for the understanding of the genetic basis of trait loci identified in genome scans or quantitative trait locus mapping efforts. We report that ~6.6% of the collared flycatcher genome (74.0 Mb) is spanned by ~1.28 million CEs, a higher proportion of the genome but a lower total amount of conserved sequence than has been reported in mammals. We identified >200,000 CEs specific to either the archosaur, avian, neoavian or passeridan lineages, constituting candidates for lineage‐specific adaptations. Importantly, no less than ~71% of CE sites were nonexonic (52.6 Mb), and conserved nonexonic sequence density was negatively correlated with functional exonic density at local genomic scales. Additionally, nucleotide diversity was strongly reduced at nonexonic conserved sites (0.00153) relative to intergenic nonconserved sites (0.00427). By integrating deep transcriptome sequencing and additional genome annotation, we identified novel protein‐coding genes, long noncoding RNA genes and transposon‐derived (exapted) CEs. The approach taken here based on the use of a progressive cactus whole‐genome alignment to identify CEs should be readily applicable to nonmodel organisms in general and help to reveal the rich repertoire of putatively functional noncoding sequence as targets for selection.
Talc-filled water-based barrier coatings

Water-based barrier dispersion coatings are often filled in order to improve barrier properties, runnability and economics. Talc is the most common pigment used. However, optimizing the coating composition requires compromises between the various functional properties, such as heat-sealability, blocking, barrier, and flexibility. The aim of this study was to compare talc grades and dispersing agents in water-based coatings as far as barrier properties, surface and optical properties, and particle orientation were concerned. In this case, an optimal talc grade for barrier coatings has an average particle size of approximately 30% of coating thickness for the best particle alignment and lowest water vapor transmission rate. Grease or water barrier indicated no correlation with the particle orientation. Removal of large particles and a narrow particle size distribution are favorable. The average size of the particles should not exceed 50% of coating thickness.
A Novel Pulse-Chase SILAC Strategy Measures Changes in Protein Decay and Synthesis Rates Induced by Perturbation of Proteostasis with an Hsp90 Inhibitor

Standard proteomics methods allow the relative quantitation of levels of thousands of proteins in two or more samples. While such methods are invaluable for defining the variations in protein concentrations which follow the perturbation of a biological system, they do not offer information on the mechanisms underlying such changes. Expanding on previous work [1], we developed a pulse-chase (pc) variant of SILAC (stable isotope labeling by amino acids in cell culture). pcSILAC can quantitate in one experiment and for two conditions the relative levels of proteins newly synthesized in a given time as well as the relative levels of remaining preexisting proteins. We validated the method studying the drug-mediated inhibition of the Hsp90 molecular chaperone, which is known to lead to increased synthesis of stress response proteins as well as the increased decay of Hsp90 “clients”. We showed that pcSILAC can give information on changes in global cellular proteostasis induced by treatment with the inhibitor, which are normally not captured by standard relative quantitation techniques. Furthermore, we have developed a mathematical model and computational framework that uses pcSILAC data to determine degradation constants kd and synthesis rates Vs for proteins in both control and drug-treated cells. The results show that Hsp90 inhibition induced a generalized slowdown of protein synthesis and an increase in protein decay. Treatment with the inhibitor also resulted in widespread protein-specific changes in relative synthesis rates, together with variations in protein decay rates. The latter were more restricted to individual proteins or protein families than the variations in synthesis. Our results establish pcSILAC as a viable workflow for the mechanistic dissection of changes in the proteome which follow perturbations. Data are available via ProteomeXchange with identifier PXD000538.
Functional near-infrared spectroscopy study on tonic pain activation by cold pressor test

Abstract. Functional near-infrared spectroscopy (fNIRS) has recently been suggested for monitoring cortical hemodynamic response to experimental and clinical acute pain. However, the hemodynamic response to a tonic, noxious cold stimulus, and its relation with subjective pain sensation is not fully characterized. We investigated the relationship between pain threshold and tolerance and the evoked hemodynamic response to cold pressor tests (CPTs) at varying intensities and explored the gender effect. Twenty-one healthy individuals (10 males and 11 females) performed four CPTs at 1°C, 5°C, 10°C, and 15°C. Deoxyhemoglobin (HHb) and oxyhemoglobin (HbO2) were measured continuously on the forehead by two “far” and two “near” channels in addition to pain scores, threshold, and tolerance. We found a significant within-subject correlation between pain threshold and the immediate HbO2 response at the right frontal region. Gender difference and asymmetrical activation were observed in the “far” channels but not the “near” channels, suggesting a hemispheric preference in response to noxious cold stimuli. No gender difference was found in pain threshold, tolerance, or scores. This research adds to the body of literature suggesting the use of fNIRS for bedside assessment of pain in addition to behavioral and subjective measures for comprehensive, multimodal pain management.
(Invited) Tip Cleaning and Sample Design for High Resolution MOSCAP x-KPFM

Kelvin probe force microscopy (KPFM) is a unique technique that can provide two-dimensional potential profiles inside a working device. A procedure is described to obtain high-resolution KPFM results on ultra-high vacuum (UHV) cleaved III-V MOSCAPs. Two tip preparation methods: field emission and Cr coating show reproducible high spatial and energy resolution KPFM images. A unique sample design has been developed which is compatible with UHV cross-sectional KPFM (x-KPFM). Key design features are high density of devices on the cleave face, a buried device interface, and a cleavable gate contact. Using x-KPFM, the first UHV cleaved MOSCAP surface potential mapping is demonstrated.
Clinical Efficacy of Jump Training Augmented With Body Weight Support After ACL Reconstruction: A Randomized Controlled Trial

Background: Limited knee flexion and increased muscle co-contraction during jump landing are believed to diminish outcomes after anterior cruciate ligament (ACL) reconstruction. The efficacy of jump training to improve patients’ mechanical and neuromuscular deficits is understudied. Hypothesis: Jump training will improve functional, mechanical, and neuromuscular outcomes and higher repetition training augmented by body weight support will result in better retention of gains. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Thirty athletes (18 months after surgery) were screened, and 19 with mechanical deficits and limited clinical outcomes were enrolled in the trial. Testing included the International Knee Documentation Committee (IKDC) questionnaire, leg landing mechanics via motion analysis, knee joint effusion using a stroke test, and a surface electromyography–generated co-contraction index during a single-legged landing. Participants were randomly assigned to 1 of 2 groups: jump training with normal body weight (JTBW) and high-repetition jump training with body weight support (JTBWS). Knee effusion grading throughout training was used to assess joint tolerance. Changes in outcomes over time were analyzed with mixed-effects modeling. Immediate outcomes were compared with retention testing at 8 weeks after training by use of 2-way analyses of variance with effects of time and group. Results: Significant effects of time were found during the training phase for all outcome measures, but no effects of group or sex were found. IKDC score (pooled; mean ± SD) increased from 76 ± 12 to 87 ± 8 (P < .001). Knee flexion during single-legged landing increased from 57° ± 11° to 73° ± 9° (P < .001). Average co-contraction index decreased from 37 ± 15 to 19 ± 6 (P < .001). All measures were retained over the retention period in both groups. The relative risk of knee effusion of the JTBW group versus the JTBWS group was 4.2 (95% CI, 2.25-7.71; P < .001). Conclusion: Jump training mitigated some risk factors for second injury and osteoarthritis in patients after ACL reconstruction. Training made lasting improvements in physical function measures as well as mechanical and neuromuscular coordination deficits. Higher repetitions used with body weight support did not improve retention but substantially reduced risk for effusion. Clinical Relevance: Jump training is an efficacious intervention for athletes with poor outcomes after ACL reconstruction, and training with body weight support lessens the risk for excessive joint stress during practice. Registration: NCT02148172 (ClinicalTrials.gov identifier)
Cognitive Reserve Profiles in Chronic Schizophrenia: Effects on Theory of Mind Performance and Improvement after Training

Abstract Objectives: Cognitive reserve (CR), defined as individual differences in the ability to cope with brain damage, seem to be associated to the several psychopathological features in psychiatric patients, such as the functional outcome. This study aims to identify different profiles of CR by combining intelligence quotient (IQ) and premorbid functioning, two measures independently associated to CR in previous works, as well as to explore CR effect on both Theory of Mind (ToM) baseline performance and improvement after socio-cognitive trainings. Methods: Sixty patients with chronic schizophrenia underwent a socio-cognitive rehabilitation. All patients were assessed for psychopathology, neurocognition, and ToM at baseline and post-treatment. CR profiles were explored with K-means cluster analysis, while differences between clusters in both baseline assessments and post-treatment ToM improvement, were analyzed by means of analysis of variance and repeated measures analysis of covariance. Results: The analysis revealed three CR profiles, respectively, characterized by low early premorbid functioning and mild intellectual impairment, average/high early premorbid functioning trend with moderate intellectual impairment and good early premorbid functioning associated to IQ within normal limits. Analyses showed a significant effect of CR on both baseline ToM performance and treatment outcome: patients with higher CR reached significantly better ToM scores. Conclusions: These results underline the clinical relevance of defining CR profiles of patients to customize trainings: subjects with a lower CR may benefit from more intensive programs. A deeper knowledge about CR may considerably increase our understanding of individual differences and thus potentiate treatment outcome. (JINS, 2018, 24, 563–571)