Miracle-dz/UniFAR-FTUs huggingface dataset:
Bringing cell therapy to tumors: considerations for optimal CAR binder design

Abstract Chimeric antigen receptor (CAR)-T cells have revolutionized the immunotherapy of B-cell malignancies and are poised to expand the range of their impact across a broad range of oncology and non-oncology indications. Critical to the success of a given CAR is the choice of binding domain, as this is the key driver for specificity and plays an important role (along with the rest of the CAR structure) in determining efficacy, potency and durability of the cell therapy. While antibodies have proven to be effective sources of CAR binding domains, it has become apparent that the desired attributes for a CAR binding domain do differ from those of a recombinant antibody. This review will address key factors that need to be considered in choosing the optimal binding domain for a given CAR and how binder properties influence and are influenced by the rest of the CAR.
FLOWS AND FLOW CHARACTERISTICS OF SPOOL VALVE

Both experimental and numerical investigations were undertaken on a spool valve to clarify the flow characteristics. Numerical analysis has been carried out by the finite-volume method (FVM) in a wide range of Reynolds numbers and valve openings on the assumption that the flow in the spool valve is unsteady, laminar, incompressible and axial symmetric. The measurement tests have been conducted to investigate the flow force, flow coefficient and velocity coefficient. To understand the flow configuration in the spool valve, flow visualization tests have also been done. Numerical results are in good agreement with experimental ones. Thus, the numerical predictions can be used for spool valve design.
Shape perception from binocular disparity and structure-from-motion

ABSTRACT When two sources of depth information are combined, the result might be dominance of one source, cooperative interaction between the sources, or an additive combination of the sources. For transparent stereo-motion displays we found a cooperative interaction: structure-from-motion facilitates disparity processing, probably by helping to resolve the stereo correspondence problem. For opaque stimuli the combination of structure-from-motion and stereopsis appears to be additive. 1. INTRODUCTION Binocular disparity1 and structure-from-motion (SFM)2 are two of the principal sources of information available for recovering 3-D relationships from 2-D images. However, neither binocular disparity nor SFM alone completely specifiesboth an object's shape and orientation relative to an observer. Binocular disparity unambiguously specifies near/far relations,but the shape of the object is only determined up to a scale factor (jerceived fixation distance). 1 Structure-from-motion, onthe other hand, may provide information about object shape, but near/far relations between the object and the observer are notspecified.3 Because these two sources of information provide human observers with related but non-redundant informationabout shape and depth, the combination of binocular disparity and SFM could possibly provide a more robust representation
The impact of stroke on spousal and family income: a difference-in-difference study from Swedish national registries.

AIM To investigates the financial consequences in the overall population spouses of persons with stroke in Sweden as well as for subgroups based on spouses age, sex and modified Rankin Scale (mRS) of the person with stroke. METHODS The study population consists of spouses aged ≤ 60 during the year of their partner's stroke event. Each spouse was matched to four reference individuals. This longitudinal registry data covers spouses and a reference population between 2005 and 2016. We use difference-in-differences to estimate the impact on individual income from paid work, disposable individual income, and disposable family income. RESULTS The primary analysis shows a small and statistically insignificant decrease on spouses' individual income from paid work and disposable individual income. In the subgroup analysis based on mRS, the largest effect is seen in mRS 4-5, where spouses' individual income from paid work and disposable individual income increases after their partner's stroke. Further, younger female spouses' individual income from paid work decreases by 1 614 EUR (p = 0.008) on average. CONCLUSION The financial consequences are small in the overall population of spouses. However, for some subgroups, younger women, and spouses of persons with stroke and mRS 4-5, the financial consequences are more prominent.
Phage-induced bacterial morphological changes reveal a phage-derived antimicrobial affecting cell wall integrity

ABSTRACT In a looming post-antibiotic era, antibiotic alternatives have become key players in the combat against pathogens. Although recent advances in genomic research allow scientists to fully explore an organism’s genome in the search for novel antibacterial molecules, laborious work is still needed in order to dissect each individual gene product for its antibacterial activity. Here, we exploited phage-induced bacterial morphological changes as anchors to explore and discover a potential phage-derived antimicrobial embedded in the phage genome. We found that, upon vibriophage KVP40 infection, Vibrio parahaemolyticus exhibited morphological changes similar to those observed when treated with mecillinam, a cell wall synthesis inhibitor, suggesting the mechanism of pre-killing that KVP40 exerts inside the bacterial cell upon sieging the host. Genome analysis revealed that, of all the annotated gene products in the KVP40 genome that are involved in cell wall degradation, lytic transglycosylase (LT) is of particular interest for subsequent functional studies. A single-cell morphological analysis revealed that heterologous expression of wild-type KVP40-LT induced similar bacterial morphological changes to those treated with the whole phage or mecillinam, prior to cell burst. On the contrary, neither the morphology nor the viability of the bacteria expressing signal-peptide truncated- or catalytic mutant E80A- KVP40-LT was affected, suggesting the necessity of these domains for the antibacterial activities. Altogether, this research paves the way for the future development of the discovery of phage-derived antimicrobials that is guided through phage-induced morphological changes.
Parametric study of scavenging of atmospheric aerosols of various chemical species during thunderstorm and nonthunderstorm rain events

[1] The overall collision efficiencies between falling raindrops and particles of selected chemical composition are computed theoretically by considering the contributions of collection mechanisms due to Brownian diffusion, directional interception, inertial impaction and phoretic effects caused by thermal and concentration gradients for the rainfall associated with thunderstorm and nonthunderstorm events. Computations of collision efficiency are performed for the particles in the diameter range of 0.02–0.2 μm (in 0.02 μm steps), 0.2–2 μm (in 0.2 μm steps) and 2–10 μm (in 1 μm steps) and for raindrops in size range of 200–5800 μm (in 200 μm steps). The results show order of magnitude difference in collision efficiencies for the case of thunderstorm and nonthunderstorm rain, and it reduces with increase in particle size from 0.02 to 0.8 μm for the particles of KNO3 because of decrease in magnitude of electrical forces. The effect of rain associated with thunderstorms and nonthunderstorms on scavenging rates for the particles of CaCO3, KNO3, (NH4)2SO4 and aerodynamic size is evaluated in terms of mean mass scavenging coefficients for polydispersed aerosols lying in size regimes of 0.02–0.2 μm, 0.2–2 μm and 2–10 μm. Mean mass scavenging coefficients are found to exhibit maximum potential for the particles of CaCO3 as compared to those of KNO3, (NH4)2SO4 and aerodynamic size particles. Present results may be useful to evaluate the Pollutant Standard Index (PSI) or Air Quality Index (AQI), when the atmosphere undergoes rain during thunderstorm and nonthunderstorm conditions.
Auditory Test of Processing Speed: Preliminary validation of a smartphone-based test of mental speed

Background: The Symbol Digit Modalities Test (SDMT) is a gold-standard measure of cognitive efficiency and processing speed for people with multiple sclerosis (PwMS) but relies on vision and oculomotor function. Objectives: To develop and validate a new processing speed test with minimal memory involvement and no eye function requirements. Methods: We created an Auditory Test of Processing Speed (ATOPS). A total of 122 PwMS, of whom 33 were severely disabled (median Expanded Disability Status Scale 8.0) and 37 healthy volunteers (HVs), were enrolled. We assessed sensitivity to discriminate MS participants from HVs, convergent validity between ATOPS and SDMT, sensitivity to discriminate between cognitively impaired (CI) and cognitively preserved (CP) MS participants, and correlations with MS pathology (overall brain lesion burden). Acceptability was examined with completion rates and participant ratings of ATOPS. Results: ATOPS discriminated PwMS from HVs (d = 0.739–0.856), correlated with SDMT (|r| = 0.528–0.587), discriminated between CI and CP PwMS (d = 0.623–0.776), and correlated with lesion burden (r = 0.332–0.436). All groups indicated high favorability of ATOPS and severely disabled MS patients could be assessed by ATOPS more frequently than by SDMT (100% vs. 72.4% completion). Conclusions: ATOPS is a novel, accessible, and acceptable cognitive processing speed test that may be useful in clinical and/or research settings.
Bhlhe40 limits early IL-10 production from CD4+ T cells during Plasmodium yoelii 17X infection

ABSTRACT The cytokine IL-10 suppresses T-cell-mediated immunity, which is required to control infection with Plasmodium yoelii. Consequently, IL-10 can delay the time needed to resolve this infection, leading to a higher parasite burden. While the pathways that lead to IL-10 production by CD4+ T cells are well defined, much less is known about the mediators that suppress the expression of this potent anti-inflammatory cytokine. Here, we show that the transcription factor basic helix-loop-helix family member e40 (Bhlhe40) contributes to controlling parasite burden in response to P. yoelii infection in mice. Loss of Bhlhe40 expression in mice results in higher Il10 expression, higher peak parasitemia, and a delay in parasite clearance. The observed phenotype was not due to defects in T-cell activation and proliferation or the humoral response. Nor was it due to changes in regulatory T-cell numbers. However, blocking IL-10 signaling reversed the outcome in Bhlhe40−/ − mice, suggesting that excess IL-10 production limits their ability to control the infection properly. In addition to suppressing Il10 expression in CD4+ T cells, Bhlhe40 can promote Ifng expression. Indeed, IFN-γ production by CD4+ T cells isolated from the liver was significantly affected by the loss of Bhlhe40. Lastly, Bhlhe40 deletion in T cells resulted in a phenotype similar to that observed in the Bhlhe40−/ − mice, indicating that Bhlhe40 expression in T cells contributes to the ability of mice to control infection with P. yoelii.
The advantage of intergenic regions as genomic features for machine-learning-based host attribution of Salmonella Typhimurium from the USA

Salmonella enterica is a taxonomically diverse pathogen with over 2600 serovars associated with a wide variety of animal hosts including humans, other mammals, birds and reptiles. Some serovars are host-specific or host-restricted and cause disease in distinct host species, while others, such as serovar S. Typhimurium (STm), are generalists and have the potential to colonize a wide variety of species. However, even within generalist serovars such as STm it is becoming clear that pathovariants exist that differ in tropism and virulence. Identifying the genetic factors underlying host specificity is complex, but the availability of thousands of genome sequences and advances in machine learning have made it possible to build specific host prediction models to aid outbreak control and predict the human pathogenic potential of isolates from animals and other reservoirs. We have advanced this area by building host-association prediction models trained on a wide range of genomic features and compared them with predictions based on nearest-neighbour phylogeny. SNPs, protein variants (PVs), antimicrobial resistance (AMR) profiles and intergenic regions (IGRs) were extracted from 3883 high-quality STm assemblies collected from humans, swine, bovine and poultry in the USA, and used to construct Random Forest (RF) machine learning models. An additional 244 recent STm assemblies from farm animals were used as a test set for further validation. The models based on PVs and IGRs had the best performance in terms of predicting the host of origin of isolates and outperformed nearest-neighbour phylogenetic host prediction as well as models based on SNPs or AMR data. However, the models did not yield reliable predictions when tested with isolates that were phylogenetically distinct from the training set. The IGR and PV models were often able to differentiate human isolates in clusters where the majority of isolates were from a single animal source. Notably, IGRs were the feature with the best performance across multiple models which may be due to IGRs acting as both a representation of their flanking genes, equivalent to PVs, while also capturing genomic regulatory variation, such as altered promoter regions. The IGR and PV models predict that ~45 % of the human infections with STm in the USA originate from bovine, ~40 % from poultry and ~14.5 % from swine, although sequences of isolates from other sources were not used for training. In summary, the research demonstrates a significant gain in accuracy for models with IGRs and PVs as features compared to SNP-based and core genome phylogeny predictions when applied within the existing population structure. This article contains data hosted by Microreact.
Influence of visual perception on movement decisions by an ungulate prey species

ABSTRACT Visual perception is dynamic and depends on physiological properties of a species’ visual system and physical characteristics of the environment. White-tailed deer (Odocoileus virginianus) are most sensitive to short- and mid-wavelength light (e.g. blue and green). Wavelength enrichment varies spatially and temporally across the landscape. We assessed how the visual perception of deer influences their movement decisions. From August to September 2019, we recorded 10-min locations from 15 GPS-collared adult male deer in Central Florida. We used Hidden-Markov models to identify periods of movement by deer and subset these data into three time periods based on temporal changes in light environments. We modeled resource selection during movement using path-selection functions and simulated 10 available paths for every path used. We developed five a priori models and used 10-fold cross validation to assess our top model's performance for each time period. During the day, deer selected to move through woodland shade, avoided forest shade, and neither selected nor avoided small gaps. At twilight, deer avoided wetlands as cloud cover increased but neither selected nor avoided other cover types. Visual cues and signals are likely more conspicuous to deer in short-wavelength-enriched woodland shade during the day, while at twilight in long-wavelength-enriched wetlands during cloud cover, visual cues are likely less conspicuous. The nocturnal light environment did not influence resource selection and likely has little effect on deer movements because it's relatively homogenous. Our findings suggest visual perception relative to light environments is likely an underappreciated driver of behaviors and decision-making by an ungulate prey species.
Assessing Anxiety-Related Impairment in Children and Adolescents

Anxiety disorders (ADs) frequently lead to significant impairment across important domains of youth functioning. Yet until recently, clinical research and assessment have largely neglected the measurement of anxiety-related impairment. In this article, we review the evidence for five extant rating scales of youth anxiety-related impairment, guided by widely used evaluative criteria. Emerging psychometric data show the potential utility of these rating scales for achieving different assessment functions. Of the five scales, the Child Anxiety Impact Scale, particularly the parent-report version, has been the most researched one. Promising psychometric data support its use for assessing anxiety-related impairment in school, social, and family/home domains of functioning. We conclude with recommendations for growing this research base and for incorporating these rating scales into the youth AD clinical and research assessment process.
Effects of the Earth's rotation and bottom slope on a density current descending a sloping bottom

[1] The dynamic and transport processes associated with the descent of dense water along a sloping bottom are investigated by numerical experiments. The focus is on effects of the Earth's rotation (the Coriolis parameter f) and bottom slope (inclination S). Before baroclinic instability grows to finite amplitude (development stage), downslope volume transport agrees roughly with an estimate based on the Ekman layer theory. The volume transport decreases with increasing f, and it is larger in steep slope cases. The offshore extension scale of the dense water region is mainly determined by internal radius of deformation, which decreases with increasing f and increases with increasing S. The growth rate of the baroclinic instability increases with increasing f and S. The baroclinic instability is also affected by energy transfer due to Reynolds stress, especially in the low- and mid-latitude regions. After the instability grows to finite amplitude (mature stage), the dense water is effectively transported offshore by the eddy flows. The eddy transport decreases with increasing f, and it is lower in steep slope cases than in gentle slope cases. That is, although the flow instability becomes stronger with increasing f and S in the development stage, the offshore eddy transport of dense water becomes less efficient with increasing f and S in the mature stage. The mechanisms of these effects are also examined in detail.
A rice variation map derived from 10 548 rice accessions reveals the importance of rare variants

Abstract Detailed knowledge of the genetic variations in diverse crop populations forms the basis for genetic crop improvement and gene functional studies. In the present study, we analyzed a large rice population with a total of 10 548 accessions to construct a rice super-population variation map (RSPVM), consisting of 54 378 986 single nucleotide polymorphisms, 11 119 947 insertion/deletion mutations and 184 736 presence/absence variations. Assessment of variation detection efficiency for different population sizes revealed a sharp increase of all types of variation as the population size increased and a gradual saturation of that after the population size reached 10 000. Variant frequency analysis indicated that ∼90% of the obtained variants were rare, and would therefore likely be difficult to detect in a relatively small population. Among the rare variants, only 2.7% were predicted to be deleterious. Population structure, genetic diversity and gene functional polymorphism of this large population were evaluated based on different subsets of RSPVM, demonstrating the great potential of RSPVM for use in downstream applications. Our study provides both a rich genetic basis for understanding natural rice variations and a powerful tool for exploiting great potential of rare variants in future rice research, including population genetics and functional genomics.
Ubiquitin signaling and the proteasome drive human DNA–protein crosslink repair

Abstract DNA–protein crosslinks (DPCs) are large cytotoxic DNA lesions that form following exposure to chemotherapeutic drugs and environmental chemicals. Nucleotide excision repair (NER) and homologous recombination (HR) promote survival following exposure to DPC-inducing agents. However, it is not known how cells recognize DPC lesions, or what mechanisms selectively target DPC lesions to these respective repair pathways. To address these questions, we examined DPC recognition and repair by transfecting a synthetic DPC lesion comprised of the human oxoguanine glycosylase (OGG1) protein crosslinked to double-stranded M13MP18 into human cells. In wild-type cells, this lesion is efficiently repaired, whereas cells deficient in NER can only repair this lesion if an un-damaged homologous donor is co-transfected. Transfected DPC is subject to rapid K63 polyubiquitination. In NER proficient cells, the DPC is subject to K48 polyubiquitination, and is removed via a proteasome-dependent mechanism. In NER-deficient cells, the DNA–conjugated protein is not subject to K48 polyubiquitination. Instead, the K63 tag remains attached, and is only lost when a homologous donor molecule is present. Taken together, these results support a model in which selective addition of polyubiquitin chains to DNA-crosslinked protein leads to selective recruitment of the proteasome and the cellular NER and recombinational DNA repair machinery.
First in human measurements of abscess cavity optical properties and methylene blue uptake prior to photodynamic therapy by in vivo diffuse reflectance spectroscopy

Significance: Efficacious photodynamic therapy (PDT) of abscess cavities requires personalized treatment planning. This relies on knowledge of abscess wall optical properties, which we report for the first time in human subjects. Aim: The objective was to extract optical properties and photosensitizer concentration from spatially-resolved diffuse reflectance measurements of abscess cavities prior to methylene blue (MB) PDT, as part of a Phase 1 clinical trial. Approach: Diffuse reflectance spectra were collected at the abscess wall of 13 human subjects using a custom fiber-optic probe and optical spectroscopy system, before and after MB administration. A Monte Carlo lookup table was used to extract optical properties. Results: Pre-MB abscess wall absorption coefficients at 665 nm were 0.15+/-0.1 cm-1 (0.03-0.36 cm-1) and 10.74+/-15.81 cm-1 (0.08-49.3 cm-1) post-MB. Reduced scattering coefficients at 665 nm were 8.45+/-2.37 cm-1 (4.8-13.2 cm-1) and 5.6+/-2.26 cm-1 (1.6-9.9 cm-1) for pre-MB and post-MB, respectively. Oxygen saturations were found to be 58.83+/-35.78% (5.6-100%) pre-MB and 36.29+/-25.1% (0.0001-76.4%) post-MB. Determined MB concentrations were 71.83+/-108.22 uM (0-311 uM). Conclusions: We observed substantial inter-subject variation in both native wall optical properties and methylene blue uptake. This underscores the importance of making these measurements for patient-specific treatment planning.