Miracle-dz/UniFAR-FTUs huggingface dataset:
Limited Mitochondrial Activity Coupled With Strong Expression of CD34, CD90 and EPCR Determines the Functional Fitness of ex vivo Expanded Human Hematopoietic Stem Cells

Ex vivo expansion strategies of human hematopoietic stem cell (HSC) grafts with suboptimal stem cell dose have emerged as promising strategies for improving outcomes of HSC transplantation in patients with hematological malignancies. While exposure of HSCs to ex vivo cultures expands the number of phenotypically identifiable HSCs, it frequently alters the transcriptomic and metabolic profiles, therefore, compromising their long-term (LT) hematopoietic reconstitution capacity. Within the heterogeneous pool of expanded HSCs, the precise phenotypic, transcriptomic and metabolic profile and thus, the identity of HSCs that confer LT repopulation potential remains poorly described. Utilizing valproic acid (VPA) in ex vivo cultures of umbilical cord blood (UCB)-CD34+ cells, we demonstrate that expanded HSCs phenotypically marked by expression of the stem cell markers CD34, CD90 and EPCR (CD201) are highly enriched for LT-HSCs. Furthermore, we report that low mitochondrial membrane potential, and, hence, mitochondrial activity distinguishes LT-HSCs within the expanded pool of phenotypically defined HSCs. Remarkably, such reduced mitochondrial activity is restricted to cells with the highest expression levels of CD34, CD90 and EPCR phenotypic markers. Together, our findings reveal that high expression of CD34, CD90 and EPCR in conjunction with low mitochondrial activity is critical for identification of functional LT-HSCs generated within ex vivo expansion cultures.
Inference of Genetic Networks From Time-Series and Static Gene Expression Data: Combining a Random-Forest-Based Inference Method With Feature Selection Methods

Several researchers have focused on random-forest-based inference methods because of their excellent performance. Some of these inference methods also have a useful ability to analyze both time-series and static gene expression data. However, they are only of use in ranking all of the candidate regulations by assigning them confidence values. None have been capable of detecting the regulations that actually affect a gene of interest. In this study, we propose a method to remove unpromising candidate regulations by combining the random-forest-based inference method with a series of feature selection methods. In addition to detecting unpromising regulations, our proposed method uses outputs from the feature selection methods to adjust the confidence values of all of the candidate regulations that have been computed by the random-forest-based inference method. Numerical experiments showed that the combined application with the feature selection methods improved the performance of the random-forest-based inference method on 99 of the 100 trials performed on the artificial problems. However, the improvement tends to be small, since our combined method succeeded in removing only 19% of the candidate regulations at most. The combined application with the feature selection methods moreover makes the computational cost higher. While a bigger improvement at a lower computational cost would be ideal, we see no impediments to our investigation, given that our aim is to extract as much useful information as possible from a limited amount of gene expression data.
Case Series: Gene Expression Analysis in Canine Vogt-Koyanagi-Harada/Uveodermatologic Syndrome and Vitiligo Reveals Conserved Immunopathogenesis Pathways Between Dog and Human Autoimmune Pigmentary Disorders

Vogt-Koyanagi-Harada syndrome (VKH) and vitiligo are autoimmune diseases that target melanocytes. VKH affects several organs such as the skin, hair follicle, eyes, ears, and meninges, whereas vitiligo is often limited to the skin and mucosa. Many studies have identified immune genes, pathways and cells that drive the pathogeneses of VKH and vitiligo, including interleukins, chemokines, cytotoxic T-cells, and other leukocytes. Here, we present case studies of 2 canines with VKH and 1 with vitiligo, which occurred spontaneously in client-owned companion dogs. We performed comparative transcriptomics and immunohistochemistry studies on lesional skin biopsies from these cases in order to determine if the immunopathogenesis of autoimmune responses against melanocytes are conserved. In dogs, we found enrichment of T cell gene signatures, with upregulation of IFNG, TNF, PRF1, IL15, CTSW, CXCL10, and CCL5 in both VKH and vitiligo in dogs compared to healthy controls. Similar findings were reported in humans, suggesting that these genes play a role in the pathogenesis of spontaneous VKH and vitiligo. T cell-associated genes, including FOXP3 and TBX21, were enriched, while IGFBP5, FOXO1, and PECAM1 were decreased compared to healthy controls. Further, we identified TGFB3, SFRP2, and CXCL7 as additional potential drivers of autoimmune pigmentary disorders. Future studies exploring the immunopathogenesis of spontaneous autoimmunity will expand our understanding of these disorders, and will be useful in developing targeted therapies, repurposing drugs for veterinary and human medicine, and predicting disease prognosis and treatment response.
Microbial Greenhouse Gas Dynamics Associated With Warming Coastal Permafrost, Western Canadian Arctic

Permafrost sediments contain one of the largest reservoirs of organic carbon on Earth that is relatively stable when it remains frozen. As air temperatures increase, the shallow permafrost thaws which allows this organic matter to be converted into potent greenhouse gases such as methane (CH4) and carbon dioxide (CO2) through microbial processes. Along the Beaufort Sea coast in the vicinity of the Tuktoyaktuk Peninsula, Northwest Territories, Canada, warming air temperatures are causing the active layer above permafrost to deepen, and a number of active periglacial processes are causing rapid erosion of previously frozen permafrost. In this paper, we consider the biogeochemical consequences of these processes on the permafrost sediments found at Tuktoyaktuk Island. Our goals were to document the in situ carbon characteristics which can support microbial activity, and then consider rates of such activity if the permafrost material were to warm even further. Samples were collected from a 12 m permafrost core positioned on the top of the island adjacent to an eroding coastal bluff. Downcore CH4, total organic carbon and dissolved organic carbon (DOC) concentrations and stable carbon isotopes revealed variable in situ CH4 concentrations down core with a sub-surface peak just below the current active layer. The highest DOC concentrations were observed in the active layer. Controlled incubations of sediment from various depths were carried out from several depths anaerobically under thawed (5°C and 15°C) and under frozen (−20°C and −5°C) conditions. These incubations resulted in gross production rates of CH4 and CO2 that increased upon thawing, as expected, but also showed appreciable production rates under frozen conditions. This dataset presents the potential for sediments below the active layer to produce potent greenhouse gases, even under frozen conditions, which could be an important atmospheric source in the actively eroding coastal zone even prior to thawing.
Revisiting Inherent Noise Floors for Interconnect Prediction

Today's synthesis, placement and routing (SP&R) tools routinely handle millions of instances. Accurate prediction of outcomes is needed to avoid long wasted runtimes from, e.g., unroutable floor-plans or placements. However, tool outputs have inherent noise that implies a lower bound on prediction error [10] [7]. The goal of interconnect prediction naturally raises a question of “How accurate can interconnect prediction be? " In this work, we revisit the topic of inherent noise and “chaos" in IC implementation flows, to characterize current noise floors on interconnect prediction. We study effects on commercial P&R tool outcomes of such previously-identified noise sources as reordering and renaming in instance cells, nets, and master cells. We also perform studies for macro placement, by slightly shifting the location of macro placement blockages in the center of the layout floorplan. We find that recent commercial tool versions still show significant routed wirelength noise of up to 7% when netlist reordering is applied, and 11.5% when macro placement blockages are shifted. Finally, we also raise the question of “How should predictions be used? ” by showing example scenarios where advance knowledge of physical design outcomes can potentially worsen noise and predictability.
Identifying Psychological Symptoms Based on Facial Movements

Background: Many methods have been proposed to automatically identify the presence of mental illness, but these have mostly focused on one specific mental illness. In some non-professional scenarios, it would be more helpful to understand an individual's mental health status from all perspectives. Methods: We recruited 100 participants. Their multi-dimensional psychological symptoms of mental health were evaluated using the Symptom Checklist 90 (SCL-90) and their facial movements under neutral stimulation were recorded using Microsoft Kinect. We extracted the time-series characteristics of the key points as the input, and the subscale scores of the SCL-90 as the output to build facial prediction models. Finally, the convergent validity, discriminant validity, criterion validity, and the split-half reliability were respectively assessed using a multitrait-multimethod matrix and correlation coefficients. Results: The correlation coefficients between the predicted values and actual scores were 0.26 and 0.42 (P < 0.01), which indicated good criterion validity. All models except depression had high convergent validity but low discriminant validity. Results also indicated good levels of split-half reliability for each model [from 0.516 (hostility) to 0.817 (interpersonal sensitivity)] (P < 0.001). Conclusion: The validity and reliability of facial prediction models were confirmed for the measurement of mental health based on the SCL-90. Our research demonstrated that fine-grained aspects of mental health can be identified from the face, and provided a feasible evaluation method for multi-dimensional prediction models.
Proton Therapy for Intracranial Meningioma for the Treatment of Primary/Recurrent Disease Including Re-Irradiation

Meningeal tumors represent approximately 10–25% of primary brain tumors and occur usually in elderly female patients. Most meningiomas are benign (80–85%) and for symptomatic and/or large tumors, surgery, with or without radiation therapy (RT), has been long established as an effective means of local tumor control. RT can be delivered to inoperable lesions or to those with non-benign histology and for Simpson I–III and IV–V resection. RT can be delivered with photons or particles (protons or carbon ions) in stereotactic or non-stereotactic conditions. Particle therapy delivered for these tumors uses the physical properties of charged carbon ions or protons to spare normal brain tissue (i.e. Bragg peak), with or without or a dose-escalation paradigm for non-benign lesions. PT can substantially decrease the dose delivered to the non-target brain tissues, including but not limited to the hippocampi, optic apparatus or cochlea. Only a limited number of meningioma patients have been treated with PT in the adjuvant or recurrent setting, as well as for inoperable lesions with pencil beam scanning and with protons only. Approximately 500 patients with image-defined or WHO grade I meningioma have been treated with protons. The reported outcome, usually 5-year local tumor control, ranges from 85 to 99% (median, 96%). For WHO grade II or III patients, the outcome of only 97 patients has been published, reporting a median tumor local control rate of 52% (range, 38–71.1). Only 24 recurring patients treated previously with photon radiotherapy and re-treated with PT were reported. The clinical outcome of these challenging patients seems interesting, provided that they presented initially with benign tumors, are not in the elderly category and have been treated previously with conventional radiation dose of photons. Overall, the number of meningioma patients treated or-re-irradiated with this treatment modality is small and the clinical evidence level is somewhat low (i.e. 3b–5). In this review, we detail the results of upfront PT delivered to patients with meningioma in the adjuvant setting and for inoperable tumors. The outcome of meningioma patients treated with this radiation modality for recurrent tumors, with or without previous RT, will also be reviewed.
Art Training in Dementia: A Randomized Controlled Trial

Objectives The present study explores the effect of visual art training on people with dementia, utilizing a randomized control trial design, in order to investigate the effects of an 8-week visual art training program on cognition. In particular, the study examines overall cognition, delayed recall, and working memory, which show deficits in people with dementia. Method Fifty-three individuals with dementia were randomly assigned into either an art training (n = 27) or usual-activity waitlist control group (n = 26). Overall cognition and delayed recall were assessed with the Montreal Cognitive Assessment (MoCA), and working memory was assessed with the Backward Digit Span task. Results There were no group differences in overall cognition, or working memory, while a difference in delayed recall was undetermined, based on post-test—pre-test difference scores. Groups were comparable at baseline on all measures. Conclusion The measures of cognition, delayed recall, and working memory used in this study were not affected by an 8-week visual art training program. Clinical Trial Registration www.ClinicalTrials. gov, identifier NCT03175822.
Adaptive Visually Servoed Tracking Control for Wheeled Mobile Robot with Uncertain Model Parameters in Complex Environment

This paper investigates the stabilization and trajectory tracking problem of wheeled mobile robot with a ceiling-mounted camera in complex environment. First, an adaptive visual servoing controller is proposed based on the uncalibrated kinematic model due to the complex operation environment. Then, an adaptive controller is derived to provide a solution of uncertain dynamic control for a wheeled mobile robot subject to parametric uncertainties. Furthermore, the proposed controllers can be applied to a more general situation where the parallelism requirement between the image plane and operation plane is no more needed. The overparameterization of regressor matrices is avoided by exploring the structure of the camera-robot system, and thus, the computational complexity of the controller can be simplified. The Lyapunov method is employed to testify the stability of a closed-loop system. Finally, simulation results are presented to demonstrate the performance of the suggested control.
Closing a Backdoor to Dual Citizenship: The German Citizenship Law Reform of 2000 and the Abolishment of the “Domestic Clause”

The German citizenship law underwent a paradigmatic amendment in 2000. One often overlooked change of this reform was the abolishment of the domestic clause (“Inlandsklausel”) that implied a substantial restriction to de facto dual citizenship acceptance. Combining data from the German Socio-Economic Panel Study (waves 1993–2006) with original data on origin country policies on dual citizenship and citizenship reacquisition, we analyse the impact of the abolishment of the domestic clause on naturalization rates. We apply a difference-in-difference design to investigate the causal impact of this element of the reform which has remained under-studied. We do not find an impact of the abolishment of the domestic clause on naturalization rates, neither among the general migrant population, nor among Turkish migrants who are alleged to be targeted specifically by this reform. These results suggest that a more restrictive approach to dual citizenship did not dissuade migrants from acquiring German citizenship after 2000.
Does Birth-Related Trauma Last? Prevalence and Risk Factors for Posttraumatic Stress in Mothers and Fathers of VLBW Preterm and Term Born Children 5 Years After Birth

Previous research suggests that the birth of a preterm child with very low birth weight (VLBW; <1,500 g) can be traumatic for both parents and lead to short-term consequences like clinical levels of posttraumatic stress symptoms (PTSS) or even to the development of a Posttraumatic Stress Disorder (PTSD). However, little is known about possible mid- and long-term psychological consequences in affected parents. The purpose of this study were (a) to examine the prevalence of parental birth-related PTSS and PTSD in a group of parents with VLBW preterm infants compared to parents of full-term infants 5 years after birth and (b) to investigate potential associations with risk factors for parental PTSS at 5 years postpartum. Perinatal factors (VLBW preterm or term, perceived stress during birth), psychological factors (perceived social support and PTSS 4–6 weeks postpartum, psychiatric lifetime diagnosis) and sociodemographic characteristics (number of children, singleton or multiple birth, socio-economic status), were included in the analysis. The sample consisted of 144 families (77 VLBW, 67 term birth) who participated in the prospective longitudinal cohort study “Hamburg study of VLBW and full-term infant development” (HaFEn-study) and were initially recruited at three perinatal care centers in Hamburg, Germany. PTSD prevalence and PTSS of mothers and fathers were assessed with the Impact of Event Scale-Revised (IES-R), social support with the Questionnaire of Social Support (SOZU-K-22), and lifetime psychiatric diagnoses with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID-I). Data were analyzed by hierarchic multiple regression analyses. Results showed that 5 years after birth none of the parents fulfilled the criteria for a birth-related PTSD diagnosis. For mothers, postnatal PTSS and a VLBW preterm birth significantly predicted PTSS 5 years postpartum. For fathers, psychiatric lifetime diagnosis and postnatal PTSS significantly predicted PTSS 5 years after birth. Early identification of parents with higher risk of PTSS, especially after VLBW preterm birth, and their clinical needs seems beneficial to reduce the risk of long-term consequences. More research is needed on the paternal perspective and on potential effects of preterm birth on both parents and their children's mental health outcomes.
Modulation of Muscle Pain Is Not Somatotopically Restricted: An Experimental Model Using Concurrent Hypertonic-Normal Saline Infusions in Humans

We have previously shown that during muscle pain induced by infusion of hypertonic saline (HS), concurrent application of vibration and gentle brushing to overlying and adjacent skin regions increases the overall pain. In the current study, we focused on muscle-muscle interactions and tested whether HS-induced muscle pain can be modulated by innocuous/sub-perceptual stimulation of adjacent, contralateral, and remote muscles. Psychophysical observations were made in 23 healthy participants. HS (5%) was infused into a forearm muscle (flexor carpi ulnaris) to produce a stable baseline pain. In separate experiments, in each of the three test locations (n = 10 per site)—ipsilateral hand (abductor digiti minimi), contralateral forearm (flexor carpi ulnaris), and contralateral leg (tibialis anterior)—50 μl of 0.9% normal saline (NS) was infused (in triplicate) before, during, and upon cessation of HS-induced muscle pain in the forearm. In the absence of background pain, the infusion of NS was imperceptible to all participants. In the presence of HS-induced pain in the forearm, the concurrent infusion of NS into the ipsilateral hand, contralateral forearm, and contralateral leg increased the overall pain by 16, 12, and 15%, respectively. These effects were significant, reproducible, and time-locked to NS infusions. Further, the NS-evoked increase in pain was almost always ascribed to the forearm where HS was infused with no discernible percept attributed to the sites of NS infusion. Based on these observations, we conclude that intramuscular infusion of HS results in muscle hyperalgesia to sub-perceptual stimulation of muscle afferents in a somatotopically unrestricted manner, indicating the involvement of a central (likely supra-spinal) mechanism.
Altered White Matter and Layer VIb Neurons in Heterozygous Disc1 Mutant, a Mouse Model of Schizophrenia

Increased white matter neuron density has been associated with neuropsychiatric disorders including schizophrenia. However, the pathogenic features of these neurons are still largely unknown. Subplate neurons, the earliest generated neurons in the developing cortex have also been associated with schizophrenia and autism. The link between these neurons and mental disorders is also not well established. Since cortical layer VIb neurons are believed to be the remnant of subplate neurons in the adult rodent brain, in this study, we aimed to examine the cytoarchitecture of neurons in cortical layer VIb and the underlying white matter in heterozygous Disc1 mutant (Het) mice, a mouse model of schizophrenia. In the white matter, the number of NeuN-positive neurons was quite low in the external capsule; however, the density of these cells was found increased (54%) in Het mice compared with wildtype (WT) littermates. The density of PV-positive neurons was unchanged in the mutants. In the cortical layer VIb, the density of CTGF-positive neurons increased (21.5%) in Het mice, whereas the number of Cplx3-positive cells reduced (16.1%) in these mutants, compared with WT mice. Layer VIb neurons can be classified by their morphological characters. The morphology of Type I pyramidal neurons was comparable between genotypes while the dendritic length and complexity of Type II multipolar neurons were significantly reduced in Het mice. White matter neurons and layer VIb neurons receive synaptic inputs and modulate the process of sensory information and sleep/arousal pattern. Aberrances of these neurons in Disc1 mutants implies altered brain functions in these mice.
Pathfinding for 2.5D Interconnect Technologies

As conventional technology scaling becomes harder, 2.5D integration provides a viable pathway to building larger systems at lower cost. Therefore recently, there has been a proliferation of multiple 2.5D integration technologies that offer different interconnect characteristics such as wiring pitch, bump/pad pitch, inter-die distance, etc. All these factors affect the interconnect metrics of bandwidth, latency and energy-per-bit which ultimately determine system performance. There are other factors such as the choice of ESD circuitry, dicing technology and signaling voltage that also influence these interconnect metrics. In this work, we propose a novel pathfinding methodology for 2.5D interconnect technologies, which seeks to identify the trade-offs among the different factors which affect the performance metrics. We show that incessant scaling of the critical dimensions of the interconnect is not very useful. We emphasize the importance of managing ESD and dicing in improving energy efficiency of these interconnects. We also show that a heterogeneous chiplet ecosystem comes with significant I/O energy penalties. Overall, we demonstrate that a holistic approach considering features of 2.5D integration technology, chiplet technology and various other factors need to be considered and optimized simultaneously to maximize the performance and cost benefits of these integration solutions.