Miracle-dz/UniFAR-FTUs huggingface dataset:
Partially Observable Risk-Sensitive Markov Decision Processes

We consider the problem of minimizing a certainty equivalent of the total or discounted cost over a finite and an infinite time horizon that is generated by a partially observable Markov decision process (POMDP). In contrast to a risk-neutral decision maker, this optimization criterion takes the variability of the cost into account. It contains as a special case the classical risk-sensitive optimization criterion with an exponential utility. We show that this optimization problem can be solved by embedding the problem into a completely observable Markov decision process with extended state space and give conditions under which an optimal policy exists. The state space has to be extended by the joint conditional distribution of current unobserved state and accumulated cost. In case of an exponential utility, the problem simplifies considerably and we rediscover what in previous literature has been named information state. However, since we do not use any change of measure techniques here, our approach is s.
Discrete Modules and Mesoscale Functional Circuits for Thermal Nociception within Primate S1 Cortex

This study addresses one long-standing question of whether functional separations are preserved for somatosensory modalities of touch, heat, and cold nociception within primate primary somatosensory (S1) cortex. This information is critical for understanding how the nature of pain is represented in the primate brain. Using a combination of submillimeter-resolution fMRI and microelectrode local field potential (LFP) and spike recordings, we identified spatially segregated cortical zones for processing touch and nociceptive heat and cold stimuli in somatotopically appropriate areas 3a, 3b, 1, and 2 of S1 in male monkeys. The distances between zones were comparable (∼3.4 mm) across stimulus modalities (heat, cold, and tactile), indicating the existence of uniform, modality-specific modules. Stimulus-evoked LFP maps validated the fMRI maps in areas 3b and 1. Isolation of heat and cold nociceptive neurons from the fMRI zones confirmed the validity of using fMRI to probe nociceptive regions and circuits. Resting-state fMRI analysis revealed distinct intrinsic functional circuits among functionally related zones. We discovered distinct modular structures and networks for thermal nociception within S1 cortex, a finding that has significant implications for studying chronic pain syndromes and guiding the selection of neuromodulation targets for chronic pain management. SIGNIFICANCE STATEMENT Primate S1 subregions contain discrete heat and cold nociceptive modules. Modules with the same properties exhibit strong functional connection. Nociceptive fMRI response coincides with LFP and spike activities of nociceptive neurons. Functional separation of heat and cold pain is retained within primate S1 cortex.
Efficient Community-Based Data Distribution Over Multicast Trees

Communities are important attributes of today’s networking, since people who join networks tend to join communities. Thus, community detection is an important issue in designing algorithms for delay-tolerant networks (DTNs). Multicasting is an appropriate method to share information within a community or between communities, because it delivers messages from a source to a group of targets using limited resources. This paper addresses the problem of detecting communities in weighted networks with irregular topologies. Based on communities, we propose an efficient data distribution algorithm for DTNs. The distribution strategy is based on the construction of a number of multicast trees, where each tree can be used to select the best relay node for each target to improve multicast efficiency. The proposed strategy provides better delivery ratio compared with other strategies and it reduces latencies when multiple nodes from a community need to multicast to other community members.
Automated high throughput microscale antibody purification workflows for accelerating antibody discovery

ABSTRACT To rapidly find “best-in-class” antibody therapeutics, it has become essential to develop high throughput (HTP) processes that allow rapid assessment of antibodies for functional and molecular properties. Consequently, it is critical to have access to sufficient amounts of high quality antibody, to carry out accurate and quantitative characterization. We have developed automated workflows using liquid handling systems to conduct affinity-based purification either in batch or tip column mode. Here, we demonstrate the capability to purify >2000 antibodies per day from microscale (1 mL) cultures. Our optimized, automated process for human IgG1 purification using MabSelect SuRe resin achieves ∼70% recovery over a wide range of antibody loads, up to 500 µg. This HTP process works well for hybridoma-derived antibodies that can be purified by MabSelect SuRe resin. For rat IgG2a, which is often encountered in hybridoma cultures and is challenging to purify via an HTP process, we established automated purification with GammaBind Plus resin. Using these HTP purification processes, we can efficiently recover sufficient amounts of antibodies from mammalian transient or hybridoma cultures with quality comparable to conventional column purification.
Sample size required for various methods of assessing bone status in commercial leghorn hens.

A study was conducted to determine the appropriate sample size required for various methods used to assess tibial bone status in commercial Leghorn hens. The methods used were in vivo bone mineral content (BMC), in vivo bone density (BD), in vitro BMC, in vitro BD, tibia bone breaking strength (TBS), and percentage bone ash (BA). Dietary total P levels of . 4, . 45, . 5, . 55, and . 7% were used as treatment source of variation. Twenty hens were sampled randomly to represent each dietary treatment. The CV for each bone status comparison method was estimated and was used in a procedure to estimate the sample size requirement for detecting a difference of delta between treatments. The sample size required to detect the difference between treatment means varied depending on 1) the method used to compare bone status 2) the difference between the treatment means to be detected as significant (delta); and 3) the level of significance (alpha) assumed. The sample size required for various methods are tabulated at . 01, . 05, and . 1 level of significance and for 2.5, 5,7.5, 10, 15, and 20% delta. To detect an actual difference of 5% from the mean to be significant, at the . 05 level of significance, a sample size of 44, 22, 31, 23, 47, and 85 hens per treatment would be necessary for in vivo BMC, in vivo BD, in vitro BMC, in vitro BD, TBS, and BA methods, respectively. The estimated sample size values would help researchers in designing experiments that involve bone status comparison of commercial Leghorn hens.
ZNF281 enhances cardiac reprogramming by modulating cardiac and inflammatory gene expression

Zhou et al. discovered that the zinc finger transcription factor ZNF281 potently stimulates cardiac reprogramming by genome-wide association with GATA4 on cardiac enhancers. Concomitantly, ZNF281 suppresses expression of genes associated with inflammatory signaling, suggesting the antagonistic convergence of cardiac and inflammatory transcriptional programs.
Isolaurenidificin and Bromlaurenidificin, Two New C15-Acetogenins from the Red Alga Laurencia obtusa

Chromatographic fractionation of the CH2Cl2/MeOH extract of the Red Sea red alga Laurencia obtusa gave two new hexahydrofuro[3,2-b]furan-based C15-acetogenins, namely, isolaurenidificin (1) and bromlaurenidificin (2). The chemical structures were elucidated based on extensive analyses of their spectral data. Compounds 1 and 2 showed no toxicity (LC50 > 12 mM) using Artemia salina as test organism. Both compounds showed weak cytotoxicity against A549, HepG-2, HCT116, MCF-7, and PC-3 cells, however, they exhibited a relatively potent cytotoxic activity against peripheral blood neutrophils. This can be attributed partly to induction of apoptosis.
Different aberrant mentalizing networks in males and females with autism spectrum disorders: Evidence from resting-state functional magnetic resonance imaging

Previous studies have found that individuals with autism spectrum disorders show impairments in mentalizing processes and aberrant brain activity compared with typically developing participants. However, the findings are mainly from male participants and the aberrant effects in autism spectrum disorder females and sex differences are still unclear. To address these issues, this study analyzed intrinsic functional connectivity of mentalizing regions using resting-state functional magnetic resonance imaging data of 48 autism spectrum disorder males and females and 48 typically developing participants in autism brain imaging data exchange. Whole-brain analyses showed that autism spectrum disorder males had hyperconnectivity in functional connectivity of the bilateral temporal-parietal junction, whereas autism spectrum disorder females showed hypoconnectivity in functional connectivity of the medial prefrontal cortex, precuneus, and right temporal-parietal junction. Interaction between sex and autism was found in both short- and long-distance functional connectivity effects, confirming that autism spectrum disorder males showed overconnectivity, while autism spectrum disorder females showed underconnectivity. Furthermore, a regression analysis revealed that in autism spectrum disorder, males and females demonstrated different relations between the functional connectivity effects of the mentalizing regions and the core autism spectrum disorder deficits. These results suggest sex differences in the mentalizing network in autism spectrum disorder individuals. Future work is needed to examine how sex interacts with other factors such as age and the sex differences during mentalizing task performance.
Novel long‐acting antagonists of muscarinic ACh receptors

The aim of this study was to develop potent and long‐acting antagonists of muscarinic ACh receptors. The 4‐hexyloxy and 4‐butyloxy derivatives of 1‐[2‐(4‐oxidobenzoyloxy)ethyl]‐1,2,3,6‐tetrahydropyridin‐1‐ium were synthesized and tested for biological activity. Antagonists with long‐residence time at receptors are therapeutic targets for the treatment of several neurological and psychiatric human diseases. Their long‐acting effects allow for reduced daily doses and adverse effects.
Late life leisure activities and risk of cognitive decline.

BACKGROUND Studies concerning the effect of different types of leisure activities on various cognitive domains are limited. This study tests the hypothesis that mental, physical, and social activities have a domain-specific protection against cognitive decline. METHODS A cohort of a geographically defined population in China was examined in 2003-2005 and followed for an average of 2.4 years. Leisure activities were assessed in 1,463 adults aged 65 years and older without cognitive or physical impairment at baseline, and their cognitive performances were tested at baseline and follow-up examinations. RESULTS High level of mental activity was related to less decline in global cognition (β = -.23, p < .01), language (β = -.11, p < .05), and executive function (β = -.13, p < .05) in ANCOVA models adjusting for age, gender, education, history of stroke, body mass index, Apolipoprotein E genotype, and baseline cognition. High level of physical activity was related to less decline in episodic memory (β = -.08, p < .05) and language (β = -.15, p < .01). High level of social activity was associated with less decline in global cognition (β = -.11, p < .05). Further, a dose-response pattern was observed: although participants who did not engage in any of the three activities experienced a significant global cognitive decline, those who engaged in any one of the activities maintained their cognition, and those who engaged in two or three activities improved their cognition. The same pattern was observed in men and in women. CONCLUSIONS Leisure activities in old age may protect against cognitive decline for both women and men, and different types of activities seem to benefit different cognitive domains.
Anatomical characterization of subcortical descending projections to the inferior colliculus in mouse

Descending projections from the thalamus and related structures to the midbrain are evolutionarily highly conserved. However, the basic organization of this auditory thalamotectal pathway has not yet been characterized. The purpose of this study was to obtain a better understanding of the anatomical and neurochemical features of this pathway. Analysis of the distributions of retrogradely labeled cells after focal injections of retrograde tracer into the inferior colliculus (IC) of the mouse revealed that most of the subcortical descending projections originated in the brachium of the IC and the paralaminar portions of the auditory thalamus. In addition, the vast majority of thalamotectal cells were found to be negative for the calcium‐binding proteins calbindin, parvalbumin, or calretinin. Using two different strains of GAD‐GFP mice, as well as immunostaining for GABA, we found that a subset of neurons in the brachium of the IC is GABAergic, suggesting that part of this descending pathway is inhibitory. Finally, dual retrograde injections into the IC and amygdala plus corpus striatum as well into the IC and auditory cortex did not reveal any double labeling. These data suggest that the thalamocollicular pathway comprises a unique population of thalamic neurons that do not contain typical calcium‐binding proteins and do not project to other paralaminar thalamic forebrain targets, and that a previously undescribed descending GABAergic pathway emanates from the brachium of the IC. J. Comp. Neurol. 525:885–900, 2017. © 2016 Wiley Periodicals, Inc.
Aberrant MicroRNA Expression in Patients With Endometrial Cancer

Objective Current evidence suggests that no single serum biomarker displays satisfactory diagnostic performance in patients with endometrial carcinoma (EC), the most frequent gynecological cancer in developed countries. However, aberrant tissue microRNA (miRNA) expression has been recently described in EC. Therefore, this study aimed to investigate the differential expression of 4 serum miRNAs and their association with CA125 (cancer antigen 125) and HE4 (human epididymis protein 4) in EC patients and in a control population. Methods Forty-six consecutive women with EC and 28 matched control subjects without a history of cancer or other diseases were enrolled. Total serum RNA was extracted using mirVana PARIS Kit. TaqMan MicroRNA Assay was used for quantitative real-time reverse transcriptase–polymerase chain reaction on ABI 7500 Sequence Detection System to assess differential miRNAs expression. The relative expression levels of 4 miRNAs (miR-222, miR-223, miR-186, and miR-204) were normalized to miR-16 and calculated using the 2-△Ct approach. Results Serum levels of miR-186, miR-222, and miR-223 appeared to be significantly higher in patients compared with control subjects (P = 0.004, P = 0.002, and P < 0.0001). Contrarily, serum miR-204 was found to be significantly lower in EC patients (P < 0.0001). The diagnostic performance of miRNAs was found to be significantly better than that of CA125. Among the various biomarker tested, serum miR-204 and HE4 exhibited the best diagnostic performance for discriminating EC patients from control subjects. Conclusions These results underpin that the 4 miRNAs that we have investigated are implicated in development and progression of EC, thus opening new avenues in EC diagnostics.
The influence of social determinants of health among young adults after they have left foster care in the US

AIMS AND OBJECTIVES To describe the influence of the social determinants of health on health care seeking among young adults after they left foster care. BACKGROUND Extensive research suggests that stakeholders in foster care systems throughout the world struggle to consistently and effectively manage the health and well-being of youth. These struggles extend beyond time in foster care as indicated by poor health and social outcomes throughout the life course. Evidence that describes how young adults address health and related social needs after leaving foster care is missing. DESIGN A phenomenological design, Phenomenology of Practice, was used to collect data. Content analysis was used to analyse the data, using constructs from the Healthy People 2020 SDOH Model to organise the data. METHODS Thirteen young adults who left foster care in the southwestern US were recruited using convenience sampling. Data were collected via individual interviews. RESULTS Young adults formerly in foster care reported using and lacking social support networks to navigate SDOH. The interrelatedness of SDOH on health outcomes after foster care is evident. CONCLUSIONS Social support networks can help explain how young adults are both able and unable to navigate systems to address health issues. Evaluating social networks used to access care is an important aspect of assessment and intervention for these vulnerable young adults. RELEVANCE TO CLINICAL PRACTICE Healthcare providers facilitate healthcare access for young adults who have been in foster care through evaluation of social determinants. Assessment and care planning based on social determinants for those who have been in foster care are critical to ensure the efficacy of interventions designed to address health outcomes. Social support systems are key factors for young adults formerly in foster care to access resources, substantiating the need for ongoing assessment and development of these support systems.
Concurrent chemoradiotherapy versus radiotherapy alone for “biopsy‐only” glioblastoma multiforme

Combined temozolomide and radiotherapy (RT) is the standard postoperative therapy for glioblastoma multiforme (GBM). However, the clearest benefit of concurrent chemoradiotherapy (CRT) observed in clinical trials has been among patients who undergo surgical resection. Whether the improved survival with CRT extends to patients who undergo “biopsy only” is less certain. The authors compared overall survival (OS) in a national cohort of patients with GBM who underwent biopsy and received either RT alone or CRT during the temozolomide era.
An evaluation of recent GOCE geopotential models in Brazil

An evaluation of recent GOCE geopotential models in Brazil Several global geopotential models based on Gravity field and steady-state Ocean Circulation Explorer (GOCE) data have been published in the last two years. Some of these models use combinations of different satellite missions, while others use only GOCE data. This paper presents the evaluation and analysis of each approach using GOCE data in the Southeast of Brazil. Two assessments have been made. We compared the geoid heights derived from GOCE-based models with the geoidal heights from 176 GPS stations on leveling benchmarks. The findings show an improvement in GOCE-based models TIM_R3 (0.40 m) and DIR_R3 (0.39 m) for degree and order 210 in relation to EGM2008 (0.44 m) in terms of RMS. For the other models the results did not exceed 0.44 m. The second evaluation reports the comparison in terms of gravity disturbances between terrestrial gravity data and the models. The results, in terms of RMS and up to degree and order 210, indicate slightly low GOCO 02S values (10.34 mGal), TIM_R2 (10.37 mGal) and TIM_R3 (10.47 mGal) compared to EGM2008 (10.66 mGal). We also applied the residual terrain model and, as a result, the RMS errors were reduced by ~35% (~6.0 mGal) in the entire area and by ~45% in the mountain region.
Wearable Microsensor Array for Multiplexed Heavy Metal Monitoring of Body Fluids

A flexible and wearable microsensor array is described for simultaneous multiplexed monitoring of heavy metals in human body fluids. Zn, Cd, Pb, Cu, and Hg ions are chosen as target analytes for detection via electrochemical square wave anodic stripping voltammetry (SWASV) on Au and Bi microelectrodes. The oxidation peaks of these metals are calibrated and compensated by incorporating a skin temperature sensor. High selectivity, repeatability, and flexibility of the sensor arrays are presented. Human sweat and urine samples are collected for heavy metal analysis, and measured results from the microsensors are validated through inductively coupled plasma mass spectrometry (ICP-MS). Real-time on-body evaluation of heavy metal (e.g., zinc and copper) levels in sweat of human subjects by cycling is performed to examine the change in concentrations with time. This platform is anticipated to provide insightful information about an individual’s health state such as heavy metal exposure and aid the related clinic.
Effects of Between- and Within-Subject Variability on Autonomic Cardiorespiratory Activity during Sleep and Their Limitations on Sleep Staging: A Multilevel Analysis

Autonomic cardiorespiratory activity changes across sleep stages. However, it is unknown to what extent it is affected by between- and within-subject variability during sleep. As it is hypothesized that the variability is caused by differences in subject demographics (age, gender, and body mass index), time, and physiology, we quantified these effects and investigated how they limit reliable cardiorespiratory-based sleep staging. Six representative parameters obtained from 165 overnight heartbeat and respiration recordings were analyzed. Multilevel models were used to evaluate the effects evoked by differences in sleep stages, demographics, time, and physiology between and within subjects. Results show that the between- and within-subject effects were found to be significant for each parameter. When adjusted by sleep stages, the effects in physiology between and within subjects explained more than 80% of total variance but the time and demographic effects explained less. If these effects are corrected, profound improvements in sleep staging can be observed. These results indicate that the differences in subject demographics, time, and physiology present significant effects on cardiorespiratory activity during sleep. The primary effects come from the physiological variability between and within subjects, markedly limiting the sleep staging performance. Efforts to diminish these effects will be the main challenge.