Miracle-dz/UniFAR-FTUs huggingface dataset:
Endocannabinoid Signaling at Hypothalamic Steroidogenic Factor-1/Proopiomelanocortin Synapses Is Sex- and Diet-Sensitive

We tested the hypotheses that steroidogenic factor (SF)-1 neurons in the hypothalamic ventromedial nucleus (VMN) provide sexually disparate, endocannabinoid (EC)- and diet-sensitive glutamatergic input onto proopiomelanocortin (POMC) neurons. Electrophysiological recordings were performed in hypothalamic slices from intact and castrated guinea pigs, along with in vitro optogenetic experiments in intact male as well as cycling and ovariectomized female NR5A1-Cre mice. In slices from castrated male and female guinea pigs, depolarized-induced suppression of excitation (DSE) time-dependently reduced the amplitude of evoked excitatory postsynaptic currents (eEPSCs) in POMC neurons generated by electrically stimulating the dorsomedial VMN. Androgen stimulation rapidly enhanced this DSE, which was also found in insulin-resistant, high-fat diet (HFD)-fed males. By contrast, retrograde signaling at VMN/ARC POMC synapses was markedly attenuated in periovulatory females. HFD potentiated central cannabinoid-induced hyperphagia in both males and females, but exerted differential influences on cannabinoid-induced increases in energy expenditure. In NR5A1-Cre mice, the reduction in light-evoked EPSC amplitude caused by postsynaptic depolarization in cycling females was modest in comparison to that seen in intact males. Estradiol attenuated the DSE in light-evoked EPSC amplitude in slices from ovariectomized females. Moreover, the retrograde inhibition of transmission was further accentuated in HFD-fed males. Chemogenetic activation of SF-1 neurons suppressed appetite and increased energy expenditure in males, effects which were attenuated by HFD. Conversely, energy expenditure was increased in estradiol- but not vehicle-treated ovariectomized females. Together with our previous studies indicating that DSE in POMC neurons is EC-mediated, these findings indicate that VMN SF-1/ARC POMC synapses represent a sexually differentiated, EC- and diet-sensitive anorexigenic component within the hypothalamic energy balance circuitry.
Stochastic Feedback Based Continuous-Discrete Cubature Kalman Filtering for Bearings-Only Tracking

Bearings-only tracking only adopts measurements from angle sensors to realize target tracking, thus, the accuracy of the state prediction has a significant influence on the final results of filtering. There exist unpredictable approximation errors in the process of filtering due to state propagation, discretization, linearization or other adverse effects. The idea of online covariance adaption is proposed in this work, where the post covariance information is proved to be effective for the covariance adaption. With theoretical deduction, the relationship between the posterior covariance and the priori covariance is investigated; the priori covariance is modified online based on the feedback rule of covariance updating. The general framework integrates the continuous-discrete cubature Kalman filtering and the feedback rule of covariance updating. Numerical results illustrated that the proposed method has advantages over decreasing unpredictable errors and improving the computational accuracy and efficiency.
Nuclear Receptor Regulation of Aquaglyceroporins in Metabolic Organs

Nuclear receptors, such as the farnesoid X receptor (FXR) and the peroxisome proliferator-activated receptors gamma and alpha (PPAR-γ, -α), are major metabolic regulators in adipose tissue and the liver, where they govern lipid, glucose, and bile acid homeostasis, as well as inflammatory cascades. Glycerol and free fatty acids are the end products of lipid droplet catabolism driven by PPARs. Aquaporins (AQPs), a family of 13 small transmembrane proteins, facilitate the shuttling of water, urea, and/or glycerol. The peculiar role of AQPs in glycerol transport makes them pivotal targets in lipid metabolism, especially considering their tissue-specific regulation by the nuclear receptors PPARγ and PPARα. Here, we review the role of nuclear receptors in the regulation of glycerol shuttling in liver and adipose tissue through the function and expression of AQPs.
Investigation of amino acid specificity in the CydX small protein shows sequence plasticity at the functional level

Small proteins are a new and expanding area of research. Many characterized small proteins are composed of a single hydrophobic α-helix, and the functional requirements of their limited amino acid sequence are not well understood. One hydrophobic small protein, CydX, has been shown to be a component of the cytochrome bd oxidase complex in Escherichia coli, and is required for enzyme function. To investigate small protein sequence specificity, an alanine scanning mutagenesis on the small protein CydX was conducted using mutant alleles expressed from the E. coli chromosome at the wild-type locus. The resulting mutant strains were assayed for CydX function. No single amino acid was required to maintain wild-type resistance to β-mercaptoethanol. However, substitutions of 10-amino acid blocks indicated that the N-terminus of the protein was required for wild-type CydX activity. A series of double mutants showed that multiple mutations at the N-terminus led to β-mercaptoethanol sensitivity in vivo. Triple mutants showed both in vivo and in vitro phenotypes. Together, these data provide evidence suggesting a high level of functional plasticity in CydX, in which multiple amino acids may work cooperatively to facilitate CydX function.
Gibberellins negatively modulate ovule number in plants

ABSTRACT Ovule formation is a complex developmental process in plants, with a strong impact on the production of seeds. Ovule primordia initiation is controlled by a gene network, including components of the signaling pathways of auxin, brassinosteroids and cytokinins. By contrast, gibberellins (GAs) and DELLA proteins, the negative regulators of GA signaling, have never been shown to be involved in ovule initiation. Here, we provide molecular and genetic evidence that points to DELLA proteins as novel players in the determination of ovule number in Arabidopsis and in species of agronomic interest, such as tomato and rapeseed, adding a new layer of complexity to this important developmental process. DELLA activity correlates positively with ovule number, acting as a positive factor for ovule initiation. In addition, ectopic expression of a dominant DELLA in the placenta is sufficient to increase ovule number. The role of DELLA proteins in ovule number does not appear to be related to auxin transport or signaling in the ovule primordia. Possible crosstalk between DELLA proteins and the molecular and hormonal network controlling ovule initiation is also discussed. Summary: The first demonstration that gibberellins are involved in the determination of ovule number in plants, via the activity of DELLA proteins – negative regulators of gibberellin signaling.
Group Recommendation Systems Based on External Social-Trust Networks

With the development of social networks and online mobile communities, group recommendation systems support users’ interaction with similar interests or purposes with others. We often provide some advices to the close friends, such as listening to favorite music and sharing favorite dishes. However, users’ personalities have been ignored by the traditional group recommendation systems while the majority is satisfied. In this paper, a method of group recommendation based on external social-trust networks is proposed, which builds a group profile by analyzing not only users’ preferences, but also the social relationships between members inside and outside of the group. We employ the users’ degree of disagreement to adjust group preference rating by external information of social-trust network. Moreover, having a discussion about different social network utilization ratio, we proposed a method to work for smaller group size. The experimental results show that the proposed method has consistently higher precision and leads to satisfactory recommendations for groups.
RAIN: A Tool for Reliability Assessment of Interconnect Networks—Physics to Software

In this paper, we study the main interconnect aging processes: electromigration, thermomigration and stress migration and propose comprehensive yet compact models for transient and steady states based on hydrostatic stress evolution. Our model can be expressed in terms of voltages only which abstracts away the hydrostatic stress. The model also explains some experimental observations, introduces temperature-dependent Blech’s length criterion and a new time-to-failure formula replacing Black’s empirical model. A tool is developed based on the proposed model which assesses reliability of multi-segment complex interconnect networks. Experimental results obtained on IBM benchmarks validate the model.
SMApproxLib: Library of FPGA-based Approximate Multipliers

The main focus of the existing approximate arithmetic circuits has been on ASIC-based designs. However, due to the architectural differences between ASICs and FPGAs, comparable performance gains cannot be achieved for FPGA-based systems by using the approximations defined, particularly for ASIC-based systems. This paper exploits the structure of the 6-input lookup tables and associated carry chains of modern FPGAs to define a methodology for designing approximate multipliers optimized for FPGA-based systems. Using our presented methodology, we present SMApproxLib, an open source library of approximate multipliers with different bit-widths, output accuracies and performance gains. Being the first open source library of FPGA-based approximate multipliers, SMApproxLib can serve as a benchmark for designing and comparing future FPGA-based approximate arithmetic circuits.
Min-Max-MSE Transceiver Design for MU-MIMO VLC System

This paper considers a multiuser (MU) multiple-input multiple-output (MIMO) visible light communication (VLC) system with broadcast channels. Due to the simultaneous transmission of the different source data to the receivers covered with the light rays, the interuser interference (IUI) may degrade the system performance. We strive to suppress the IUI by minimizing the maximum mean square errors (MSE) under the assumption of the perfect knowledge of channel state information (CSI). However, since the CSI may not be perfectly known in practice, a robust design is required against the channel uncertainties. Additionally, the nonnegativity and the limited linear range of the optical signals have been taken into account in the VLC transceiver designs. Simulation results validate that the proposed min-max-MSE approach can provide fair transmission, compared with the minimization of sum-MSE approach. Furthermore, it is demonstrated that the robust scheme is capable of providing robustness and gaining a considerable bit error rate (BER) performance.
A two-phase Hessian approach improves the DFT relaxation of slabs

A two-phase Hessian approach to DFT slab relaxation of slabs has been implemented and tested. It addresses weaknesses in the modified Broyden and Pfrommer BFGS algorithms specific to relaxing slabs. Complete Hessian and then inverse Hessian matrices with no strain/stress components are first constructed at high force signal-to-noise ratios with no accompanying relaxation. In a second phase the static inverse Hessian is used to relax the slab down to a low force tolerance.
Constitutive and Synaptic Activation of GIRK Channels Differentiates Mature and Newborn Dentate Granule Cells

Sparse neural activity in the dentate gyrus is enforced by powerful networks of inhibitory GABAergic interneurons in combination with low intrinsic excitability of the principal neurons, the dentate granule cells (GCs). Although the cellular and circuit properties that dictate synaptic inhibition are well studied, less is known about mechanisms that confer low GC intrinsic excitability. Here we demonstrate that intact G protein-mediated signaling contributes to the characteristic low resting membrane potential that differentiates mature dentate GCs from CA1 pyramidal cells and developing adult-born GCs. In mature GCs from male and female mice, intact G protein signaling robustly reduces intrinsic excitability, whereas deletion of G protein-activated inwardly rectifying potassium channel 2 (GIRK2) increases excitability and blocks the effects of G protein signaling on intrinsic properties. Similarly, pharmacological manipulation of GABAB receptors (GABABRs) or GIRK channels alters intrinsic excitability and GC spiking behavior. However, adult-born new GCs lack functional GIRK activity, with phasic and constitutive GABABR-mediated GIRK signaling appearing after several weeks of maturation. Phasic activation is interneuron specific, arising primarily from nNOS-expressing interneurons rather than parvalbumin- or somatostatin-expressing interneurons. Together, these results demonstrate that G protein signaling contributes to the intrinsic excitability that differentiates mature and developing dentate GCs and further suggest that late maturation of GIRK channel activity is poised to convert early developmental functions of GABAB receptor signaling into GABABR-mediated inhibition. SIGNIFICANCE STATEMENT The dentate gyrus exhibits sparse neural activity that is essential for the computational function of pattern separation. Sparse activity is ascribed to strong local inhibitory circuits in combination with low intrinsic excitability of the principal neurons, the granule cells. Here we show that constitutive activity of G protein-coupled inwardly rectifying potassium channels (GIRKs) underlies to the hallmark low resting membrane potential and input resistance of mature dentate neurons. Adult-born neurons initially lack functional GIRK channels, with constitutive and phasic GABAB receptor-mediated GIRK inhibition developing in tandem after several weeks of maturation. Our results reveal that GABAB/GIRK activity is an important determinant of low excitability of mature dentate granule cells that may contribute to sparse DG activity in vivo.
Swipe and Tell

When content consumers explicitly judge content positively, we consider them to be engaged. Unfortunately, explicit user evaluations are difficult to collect, as they require user effort. Therefore, we propose to use device interactions as implicit feedback to detect engagement. We assess the usefulness of swipe interactions on tablets for predicting engagement and make the comparison with using traditional features based on time spent. We gathered two unique datasets of more than 250,000 swipes, 100,000 unique article visits, and over 35,000 explicitly judged news articles by modifying two commonly used tablet apps of two newspapers. We tracked all device interactions of 407 experiment participants during one month of habitual news reading. We employed a behavioral metric as a proxy for engagement, because our analysis needed to be scalable to many users, and scanning behavior required us to allow users to indicate engagement quickly. We point out the importance of taking into account content ordering, report the most predictive features, zoom in on briefly read content and on the most frequently read articles. Our findings demonstrate that fine-grained tablet interactions are useful indicators of engagement for newsreaders on tablets. The best features successfully combine both time-based aspects and swipe interactions.
Poster: Are Information Retrieval-Based Bug Localization Techniques Trustworthy?

Information retrieval-based bug localization techniques are evaluated using datasets with an oracle. However, datasets can contain non-buggy files, which affect the reliability of these techniques. To investigate the impact of non-buggy files, we show that a test file can be regarded as a buggy file. Then, we determined if this file caused inaccuracies that would eventually affect the trustworthiness of previous techniques. We further analyzed the impact of test files on IR-based bug localization through three research questions. Our results show that the test files significantly impact the performance of the techniques. Furthermore, MAP increased by a maximum of 21%, and MRR decreased by a maximum of 13%.
1,2,3‐Triazolium‐Based Cationic Amphipathic Peptoid Oligomers Mimicking Antimicrobial Helical Peptides

Amphipathic cationic peptoids (N‐substituted glycine oligomers) represent a promising class of antimicrobial peptide mimics. The aim of this study is to explore the potential of the triazolium group as a cationic moiety and helix inducer to develop potent antimicrobial helical peptoids. Herein we report the first solid‐phase synthesis of peptoid oligomers incorporating 1,2,3‐triazolium‐type side chains and their evaluation against Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus. Several triazolium‐based oligomers, even of short length, selectively kill bacteria over mammalian cells. SEM visualization of S. aureus cells treated with a dodecamer and a hexamer reveals severe cell membrane damage and suggests that the longer oligomer acts by pore formation.
ER-phagy requires Lnp1, a protein that stabilizes rearrangements of the ER network

Significance The endoplasmic reticulum (ER) undergoes autophagy in response to starvation in a process utilizing Atg40, a cortical ER receptor that serves to recruit the machinery needed to assemble an autophagosome. Little is known about the components that work in conjunction with ER cargo receptors. Here we show that autophagy of the ER requires Lnp1, a protein that helps to maintain the structure of the ER by stabilizing rearrangements of the ER network. In the absence of Lnp1 or upon depolymerization of actin, Atg40 puncta fail to distribute to the cell interior, where the autophagy machinery resides, thus blocking incorporation of ER into autophagosomes. These studies show that the localization of Atg40 is critical for its function as a cargo receptor. The endoplasmic reticulum (ER) forms a contiguous network of tubules and sheets that is predominantly associated with the cell cortex in yeast. Upon treatment with rapamycin, the ER undergoes degradation by selective autophagy. This process, termed ER-phagy, requires Atg40, a selective autophagy receptor that localizes to the cortical ER. Here we report that ER-phagy also requires Lnp1, an ER membrane protein that normally resides at the three-way junctions of the ER network, where it serves to stabilize the network as it is continually remodeled. Rapamycin treatment increases the expression of Atg40, driving ER domains marked by Atg40 puncta to associate with Atg11, a scaffold protein needed to form autophagosomes. Although Atg40 largely localizes to the cortical ER, the autophagy machinery resides in the cell interior. The localization of Atg40 to sites of autophagosome formation is blocked in an lnp1Δ mutant or upon treatment of wild-type cells with the actin-depolymerizing drug Latrunculin A. This prevents the association of Atg40 with Atg11 and the packaging of the ER into autophagosomes. We propose that Lnp1 is needed to stabilize the actin-dependent remodeling of the ER that is essential for ER-phagy.
Elevated Levels of Era GTPase Improve Growth, 16S rRNA Processing, and 70S Ribosome Assembly of Escherichia coli Lacking Highly Conserved Multifunctional YbeY Endoribonuclease

This work provides insight into the critical, but still incompletely understood, mechanism of processing of the E. coli 16S rRNA 3′ terminus. The highly conserved GTPase Era is known to bind to the precursor of the 16S rRNA near its 3′ end. Both the endoribonuclease YbeY, which binds to Era, and four exoribonucleases have been implicated in this 3′-end processing. The results reported here offer additional insights into the role of Era in 16S rRNA 3′-end maturation and into the relationship between the action of the endoribonuclease YbeY and that of the four exoribonucleases. This study also hints at why YbeY is essential only in some bacteria and suggests that YbeY could be a target for a new class of antibiotics in these bacteria. ABSTRACT YbeY is a highly conserved, multifunctional endoribonuclease that plays a significant role in ribosome biogenesis and has several additional roles. Here we show that overexpression of the conserved GTPase Era in Escherichia coli partially suppresses the growth defect of a ΔybeY strain while improving 16S rRNA processing and 70S ribosome assembly. This suppression requires both the ability of Era to hydrolyze GTP and the function of three exoribonucleases, RNase II, RNase R, and RNase PH, suggesting a model for the action of Era. Overexpression of Vibrio cholerae Era similarly partially suppresses the defects of an E. coli ΔybeY strain, indicating that this property of Era is conserved in bacteria other than E. coli. IMPORTANCE This work provides insight into the critical, but still incompletely understood, mechanism of processing of the E. coli 16S rRNA 3′ terminus. The highly conserved GTPase Era is known to bind to the precursor of the 16S rRNA near its 3′ end. Both the endoribonuclease YbeY, which binds to Era, and four exoribonucleases have been implicated in this 3′-end processing. The results reported here offer additional insights into the role of Era in 16S rRNA 3′-end maturation and into the relationship between the action of the endoribonuclease YbeY and that of the four exoribonucleases. This study also hints at why YbeY is essential only in some bacteria and suggests that YbeY could be a target for a new class of antibiotics in these bacteria.
Detection of Respiratory Viruses in Deceased Persons, Spain, 2017

During the 2016–17 influenza season in Spain, we tested specimens from 57 elderly deceased persons for respiratory viruses. Influenza viruses were detected in 18% of the specimens and any respiratory virus in 47%. Only 7% of participants had received a diagnosis of infection with the detected virus before death.