Miracle-dz/UniFAR-FTUs huggingface dataset:
A B Cell Receptor with Two Igα Cytoplasmic Domains Supports Development of Mature But Anergic B Cells

B cell receptor (BCR) signaling is mediated through immunoglobulin (Ig)α and Igβ a membrane-bound heterodimer. Igα and Igβ are redundant in their ability to support early B cell development, but their roles in mature B cells have not been defined. To examine the function of Igα–Igβ in mature B cells in vivo we exchanged the cytoplasmic domain of Igα for the cytoplasmic domain of Igβ by gene targeting (Igβc→αc mice). Igβc→αc B cells had lower levels of surface IgM and higher levels of BCR internalization than wild-type B cells. The mutant B cells were able to complete all stages of development and were long lived, but failed to differentiate into B1a cells. In addition, Igβc→αc B cells showed decreased proliferative and Ca2+ responses to BCR stimulation in vitro, and were anergic to T-independent and -dependent antigens in vivo.
Laser-Based Adaptive Cruise Control for Intelligent Vehicles

Vehicle and highway automation is believed to reduce the risk of accident, improve safety, increase capacity, reduce fuel consumption and enchance overall comfort and performance for drivers. One of the most important research topics in the field of Intelligent Transportation Systems (ITS) is Adaptive Cruise Control (ACC), aiming at adapting the vehicle speed to a predefined value while keeping a safe gap with regard to potential obstacles. For this purpose, a laserscanner system provides the distance between the ego vehicle and the preceding vehicle on the road. The complete system can be understood as a Laser-based ACC controller, based on Fuzzy Logic, which assists the vehicle velocity control offering driving strategies and actuation over the throttle of a car. This controller is embedded in an automatic driving system installed in two testbed mass-produced cars operating in a real environment. The results obtained in these experiments show a good performance of the Laser-based gap controller, which is adaptable to all speeds and safe gap selections.
Sleep findings in Brazilian children with congenital Zika syndrome

Study Objectives Zika virus infection during pregnancy may result in congenital Zika syndrome (CZS), whose characteristics are being described. Methods The present study aimed to investigate the sleep characteristics of 136 infants/toddlers (88 with CZS and 48 with typical development (TD), age and gender matched, 60% girls and 40% boys in both groups) using the Brief Infant Sleep Questionnaire. The ages of children in both groups ranged from 5 to 24 months (CZS 15.9 ± 0.4 vs. TD 15.8 ± 1.0 months, P= 0.90). Results The results show that 34.1% of CZS and 2% of TD children were defined as poor sleepers, 15% of CZS and 2% of TD children remained awake at night for a period longer than 1 hour, and 24% of CZS and 2% of TD children slept less than 9 hours. The CZS group showed shorter total sleep time (CZS 11.24 ± 2.6 vs. TD 12.02 ± 1.9 hours, P= 0.03) and shorter nocturnal sleep duration than the TD group (CZS 8.2 ± 0.2 vs. TD 9.4 ± 0.2 hours, P= 0.0002). In contrast to the control group (P= 0.02, r= -0.34), in the CZS group, no correlation was found between age and nocturnal wakefulness. Future studies should explore these data in relation to the development and maturation of the central nervous system of these children. Conclusions Considering the well-known consequences of poor sleep quality on health in several populations, the presence of sleep disorders should be considered in CZS using multidisciplinary treatments.
Ultrahigh-throughput–directed enzyme evolution by absorbance-activated droplet sorting (AADS)

Significance Directed enzyme evolution is a powerful approach for discovering new catalysts with applications in green chemistry and elsewhere. However, “hits” in sequence space are rare: If too few members of a library are examined, the chances of success of a campaign are limited. Ultrahigh-throughput screening in emulsion droplets has dramatically increased the odds but requires a fluorescent reaction product that triggers selection of hits. We now introduce an absorbance-based microfluidic droplet sorter that broadens the scope of assays to those producing UV/Vis-active chromophores and demonstrate its usefulness by evolving a dehydrogenase based on the screening of half a million library members. Making ultrahigh-throughput screening possible for previously inaccessible reactions enables much wider use of microfluidic droplet sorters for laboratory evolution. Ultrahigh-throughput screening, in which members of enzyme libraries compartmentalized in water-in-oil emulsion droplets are assayed, has emerged as a powerful format for directed evolution and functional metagenomics but is currently limited to fluorescence readouts. Here we describe a highly efficient microfluidic absorbance-activated droplet sorter (AADS) that extends the range of assays amenable to this approach. Using this module, microdroplets can be sorted based on absorbance readout at rates of up to 300 droplets per second (i.e., >1 million droplets per hour). To validate this device, we implemented a miniaturized coupled assay for NAD+-dependent amino acid dehydrogenases. The detection limit (10 μM in a coupled assay producing a formazan dye) enables accurate kinetic readouts sensitive enough to detect a minimum of 1,300 turnovers per enzyme molecule, expressed in a single cell, and released by lysis within a droplet. Sorting experiments showed that the AADS successfully enriched active variants up to 2,800-fold from an overwhelming majority of inactive ones at ∼100 Hz. To demonstrate the utility of this module for protein engineering, two rounds of directed evolution were performed to improve the activity of phenylalanine dehydrogenase toward its native substrate. Fourteen hits showed increased activity (improved >4.5-fold in lysate; kcat increased >2.7-fold), soluble protein expression levels (up 60%), and thermostability (Tm, 12 °C higher). The AADS module makes the most widely used optical detection format amenable to screens of unprecedented size, paving the way for the implementation of chromogenic assays in droplet microfluidics workflows.
p62- and ubiquitin-dependent stress-induced autophagy of the mammalian 26S proteasome

Significance Whereas the role of the ubiquitin system in protein degradation is well established, little is known regarding the regulation of its own components, including its catalytic arm, the 26S proteasome. Here we show that in stressed mammalian cells, the proteasome is targeted by autophagy, which requires site-specific ubiquitination of its ubiquitin receptors. The process is mediated by the p62/SQSTM1 adapter and requires its ubiquitin-associated domain. Independently, p62 serves also as a shuttling protein for ubiquitinated substrates, using its PB1 domain. This places p62 in a pivotal position where under certain conditions it binds to the proteasome as a protease, whereas in other conditions it recognizes the proteasome as a prey. The regulation of this intricate “decision making” process remains elusive. The ubiquitin-proteasome system and autophagy are the two main proteolytic systems involved in, among other functions, the maintenance of cell integrity by eliminating misfolded and damaged proteins and organelles. Both systems remove their targets after their conjugation with ubiquitin. An interesting, yet incompletely understood problem relates to the fate of the components of the two systems. Here we provide evidence that amino acid starvation enhances polyubiquitination on specific sites of the proteasome, a modification essential for its targeting to the autophagic machinery. The uptake of the ubiquitinated proteasome is mediated by its interaction with the ubiquitin-associated domain of p62/SQSTM1, a process that also requires interaction with LC3. Importantly, deletion of the PB1 domain of p62, which is important for the targeting of ubiquitinated substrates to the proteasome, has no effect on stress-induced autophagy of this proteolytic machinery, suggesting that the domain of p62 that binds to the proteasome determines the function of p62 in either targeting substrates to the proteasome or targeting the proteasome to autophagy.
Phantom-based comparison of the accuracy of point clouds extracted from stereo cameras and laser range scanner

Using computational models, images acquired pre-operatively can be updated to account for intraoperative brain shift in image-guided surgical (IGS) systems. An optically tracked textured laser range scanner (tLRS) furnishes the 3D coordinates of cortical surface points (3D point clouds) over the surgical field of view and provides a correspondence between these and the pre-operative MR image. However, integration of the acquired tLRS data into a clinically acceptable system compatible throughout the clinical workflow of tumor resection has been challenging. This is because acquiring the tLRS data requires moving the scanner in and out of the surgical field, thus limiting the number of acquisitions. Large differences between acquisitions caused by tumor resection and tissue manipulation make it difficult to establish correspondence and estimate brain motion. An alternative to the tLRS is to use temporally dense feature-rich stereo surgical video data provided by the operating microscope. This allows for quick digitization of the cortical surface in 3D and can help continuously update the IGS system. In order to understand the tradeoffs between these approaches as input to an IGS system, we compare the accuracy of the 3D point clouds extracted from the stereo video system of the surgical microscope and the tLRS for phantom objects in this paper. We show that the stereovision system of the surgical microscope achieves accuracy in the 0.46-1.5mm range on our phantom objects and is a viable alternative to the tLRS for neurosurgical applications.
Genetic Basis for Developmental Homeostasis of Germline Stem Cell Niche Number: A Network of Tramtrack-Group Nuclear BTB Factors

The potential to produce new cells during adult life depends on the number of stem cell niches and the capacity of stem cells to divide, and is therefore under the control of programs ensuring developmental homeostasis. However, it remains generally unknown how the number of stem cell niches is controlled. In the insect ovary, each germline stem cell (GSC) niche is embedded in a functional unit called an ovariole. The number of ovarioles, and thus the number of GSC niches, varies widely among species. In Drosophila, morphogenesis of ovarioles starts in larvae with the formation of terminal filaments (TFs), each made of 8–10 cells that pile up and sort in stacks. TFs constitute organizers of individual germline stem cell niches during larval and early pupal development. In the Drosophila melanogaster subgroup, the number of ovarioles varies interspecifically from 8 to 20. Here we show that pipsqueak, Trithorax-like, batman and the bric-à-brac (bab) locus, all encoding nuclear BTB/POZ factors of the Tramtrack Group, are involved in limiting the number of ovarioles in D. melanogaster. At least two different processes are differentially perturbed by reducing the function of these genes. We found that when the bab dose is reduced, sorting of TF cells into TFs was affected such that each TF contains fewer cells and more TFs are formed. In contrast, psq mutants exhibited a greater number of TF cells per ovary, with a normal number of cells per TF, thereby leading to formation of more TFs per ovary than in the wild type. Our results indicate that two parallel genetic pathways under the control of a network of nuclear BTB factors are combined in order to negatively control the number of germline stem cell niches.
Ras and TGF-β signaling enhance cancer progression by promoting the ΔNp63 transcriptional program

In tumors with mutant p53, both Ras and TGF-β promote metastatic disease by stimulating ΔNp63 activity. Metastatic convergence at ΔNp63 The p53 family of transcription factors, which includes p53, p63, and p73, is implicated in both tumor-suppressive and tumorigenic functions. Activation of the Ras and transforming growth factor–β (TGF-β) signaling pathways are similarly enigmatic with both tumor-suppressing and tumor-promoting activity. Deciphering their roles in various stages of tumor development is critical to developing targeted therapeutics. Vasilaki et al. found that these factors are all connected in the development of some cancers. Activation of Ras or TGF-β signaling stimulated the transcriptional activity of the isoform ΔNp63 in breast or squamous cancer cells by suppressing the abundance of the mutant form of p53, an inhibitor of ΔNp63 and also a feature implicated in early tumorigenesis. Increased abundance of ΔNp63 in breast cancer cells stimulated metastatic behaviors in culture and in mice and correlated with poor prognosis in patients with mutant p53–positive tumors. These findings provide some insight into dichotic, stage-specific signals in tumorigenesis. Identification of this downstream common effector could also offer new therapeutic opportunities for some advanced Ras- or TGF-β–driven tumors. The p53 family of transcription factors includes p63, which is a master regulator of gene expression in epithelial cells. Determining whether p63 is tumor-suppressive or tumorigenic is complicated by isoform-specific and cellular context–dependent protein associations, as well as antagonism from mutant p53. ΔNp63 is an amino-terminal–truncated isoform, that is, the predominant isoform expressed in cancer cells of epithelial origin. In HaCaT keratinocytes, which have mutant p53 and ΔNp63, we found that mutant p53 antagonized ΔNp63 transcriptional activity but that activation of Ras or transforming growth factor–β (TGF-β) signaling pathways reduced the abundance of mutant p53 and strengthened target gene binding and activity of ΔNp63. Among the products of ΔNp63-induced genes was dual-specificity phosphatase 6 (DUSP6), which promoted the degradation of mutant p53, likely by dephosphorylating p53. Knocking down all forms of p63 or DUSP6 and DUSP7 (DUSP6/7) inhibited the basal or TGF-β–induced or epidermal growth factor (which activates Ras)–induced migration and invasion in cultures of p53-mutant breast cancer and squamous skin cancer cells. Alternatively, overexpressing ΔNp63 in the breast cancer cells increased their capacity to colonize various tissues upon intracardiac injection in mice, and this was inhibited by knocking down DUSP6/7 in these ΔNp63-overexpressing cells. High abundance of ΔNp63 in various tumors correlated with poor prognosis in patients, and this correlation was stronger in patients whose tumors also had a mutation in the gene encoding p53. Thus, oncogenic Ras and TGF-β signaling stimulate cancer progression through activation of the ΔNp63 transcriptional program.
UCD-S1: A hybrid model for detecting semantic relations between noun pairs in text

We describe a supervised learning approach to categorizing inter-noun relations, based on Support Vector Machines, that builds a different classifier for each of seven semantic relations. Each model uses the same learning strategy, while a simple voting procedure based on five trained discriminators with various blends of features determines the final categorization. The features that characterize each of the noun pairs are a blend of lexical-semantic categories extracted from WordNet and several flavors of syntactic patterns extracted from various corpora, including Wikipedia and the WMTS corpus.
Metabolic correlates of cognitive function in children with unilateral Sturge–Weber syndrome: Evidence for regional functional reorganization and crowding

To evaluate metabolic changes in the ipsi‐ and contralateral hemisphere in children showing a cognitive profile consistent with early reorganization of cognitive function, we evaluated the regional glucose uptake, interhemispheric metabolic connectivity, and cognitive function in children with unilateral SWS. Interictal 2‐deoxy‐2[18F]fluoro‐D‐glucose (FDG)‐PET scans of 27 children with unilateral SWS and mild epilepsy and 27 age‐matched control (non‐SWS children with epilepsy and normal FDG‐PET) were compared using statistical parametric mapping (SPM). Regional FDG‐PET abnormalities calculated as SPM(t) scores in the SWS group were correlated with cognitive function (IQ) in left‐ and right‐hemispheric subgroups. Interhemispheric metabolic connectivity between homotopic cortical regions was also calculated. Verbal IQ was substantially (≥10 points difference) higher than non‐verbal IQ in 61% of the right‐ and 71% of the left‐hemispheric SWS group. FDG SPM(t) scores in the affected hemisphere showed strong positive correlations with IQ in the left‐hemispheric, but not in right‐hemispheric SWS group in several frontal, parietal, and temporal cortical regions. Significant positive interhemispheric metabolic connectivity, present in controls, was diminished in the SWS group. In addition, the left‐hemispheric SWS group showed inverse metabolic interhemispheric correlations in specific parietal, temporal, and occipital regions. FDG SPM(t) scores in the same regions of the right (unaffected) hemisphere showed inverse correlations with IQ. These findings suggest that left‐hemispheric lesions in SWS often result in early reorganization of verbal functions while interfering with (“crowding”) their non‐verbal cognitive abilities. These cognitive changes are associated with specific metabolic abnormalities in the contralateral hemisphere not directly affected by SWS.
Human Immunodeficiency Virus Infection Impairs Th1 and Th17 Mycobacterium tuberculosis–Specific T-Cell Responses

Background Human immunodeficiency virus (HIV)-infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cell responses contributed to this increased risk. Methods Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa, were evaluated. Using a whole-blood flow cytometry assay, we measured expression of interferon gamma, tumor necrosis factor alpha, interleukin 2, and interleukin 17 in CD4+ and CD8+ T cells in response to Mtb antigens (PPD, ESAT-6/CFP-10 [EC], and DosR regulon-encoded α-crystallin [Rv2031c]). Results Fewer HIV-infected individuals had detectable CD4+ and CD8+ T-cell responses to PPD and Rv2031c than HIV-uninfected subjects. Mtb-specific T cells showed distinct patterns of cytokine expression comprising both Th1 (CD4 and CD8) and Th17 (CD4) cytokines, the latter at highest frequency for Rv2031c. Th17 antigen-specific responses to all antigens tested were specifically impaired in HIV-infected individuals. Conclusions HIV-associated impairment of CD4+ and CD8+Mtb-specific T-cell responses is antigen specific, particularly impacting responses to PPD and Rv2031c. Preferential depletion of Th17 cytokine-expressing CD4+ T cells suggests this T-cell subset may be key to TB susceptibility in HIV-infected individuals.
Biodegradable stents made of pure Mg and AZ91 alloythrough SPS sintering

The implantation of stents is an effective procedure to unblock the arteries of patients with serious heart problems. Traditionally, stents are made of inert materials such as stainless steel and titanium alloys. It has been shown that the traditional stents can cause restenosis or thrombosis. In recent years the proposal of biodegradable stents is attracting the interest of the industry and the research, since the stent is mechanically needed only in the first year, eliminating the problems caused by the long duration of the implant. Magnesium (Mg) alloys are of increasing interest because of their engineering properties, including the high strength to density ratio. Recently, they have been also proposed as biomaterials for the production of bioabsorbable stents and for other medical devices due to its harmless effect to human body when compared with other structural materials. In this work, the possibility to produce biodegradable stents made of magnesium starting from the powder is investigated. Pure Mg and the AZ91 Mg powders were used in the present study. Pure Mg powder was sintered by Spark Plasma Sintering at 400 and 470 °C, and the AZ91 powder was sintered at 400 °C without homogenization and at 470 °C after homogenization. The preforms produced by sintering were then submitted to hot compression, rod extrusion and tube extrusion at 330 and 380 °C with different strain rates. During all the process was not possible to obtain recrystallization or grain refinement on pure Mg, and after the tube extrusion it has shown a high brittleness and sever defects, which led to the decision of proceed only with AZ91 alloy. The AZ91 presented good recrystallization in al process, always following the Zener-Hollomon relation. The grain size obtained was as small as 1.5 μm. The AZ91 tube was then submitted to manual machining and laser cutting and it was possible to obtain the stent precursors. The results of the present investigation have demonstrated the suitability of the proposed route for producing Mg-based stents. It is clear, however, that the process has to be further optimized, investigating also the possibility of using different types of powder with a tailored composition.
Chase: Taming Concurrent Broadcast for Flooding in Asynchronous Duty Cycle Networks

Asynchronous duty cycle is widely used for energy constraint wireless nodes to save energy. The basic flooding service in asynchronous duty cycle networks, however, is still far from efficient due to severe packet collisions and contentions. We present Chase, an efficient and fully distributed concurrent broadcast layer for flooding in asynchronous duty cycle networks. The main idea of Chase is to meet the strict signal time and strength requirements (e.g., Capture Effect) for concurrent broadcast while reducing contentions and collisions. We propose a distributed random inter-preamble packet interval adjustment approach to constructively satisfy the requirements. Even when requirements cannot be satisfied due to physical constraints (e.g., the difference of signal strength is less than a 3 dB), we propose a lightweight signal pattern recognition-based approach to identify such a circumstance and extend radio-on time for packet delivery. We implement Chase in TinyOS with TelosB nodes and extensively evaluate its performance. The implementation does not have any specific requirement on the hardware and can be easily extended to other platforms. The evaluation results also show that Chase can significantly improve flooding efficiency in asynchronous duty cycle networks.
The Small GTPase Rheb Affects Central Brain Neuronal Morphology and Memory Formation in Drosophila

Mutations in either of two tumor suppressor genes, TSC1 or TSC2, cause tuberous sclerosis complex (TSC), a syndrome resulting in benign hamartomatous tumors and neurological disorders. Cellular growth defects and neuronal disorganization associated with TSC are believed to be due to upregulated TOR signaling. We overexpressed Rheb, an upstream regulator of TOR, in two different subsets of D. melanogaster central brain neurons in order to upregulate the Tsc-Rheb-TOR pathway. Overexpression of Rheb in either the mushroom bodies or the insulin producing cells resulted in enlarged axon projections and cell bodies, which continued to increase in size with prolonged Rheb expression as the animals aged. Additionally, Rheb overexpression in the mushroom bodies resulted in deficiencies in 3 hr but not immediate appetitive memory. Thus, Rheb overexpression in the central brain neurons of flies causes not only morphological phenotypes, but behavioral and aging phenotypes that may mirror symptoms of TSC.