Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct but overlapping binding sites of agonist and antagonist at the relaxin family peptide 3 (RXFP3) receptor

The relaxin-3 neuropeptide activates the relaxin family peptide 3 (RXFP3) receptor to modulate stress, appetite, and cognition. RXFP3 shows promise as a target for treating neurological disorders, but realization of its clinical potential requires development of smaller RXFP3-specific drugs that can penetrate the blood–brain barrier. Designing such drugs is challenging and requires structural knowledge of agonist- and antagonist-binding modes. Here, we used structure–activity data for relaxin-3 and a peptide RXFP3 antagonist termed R3 B1–22R to guide receptor mutagenesis and develop models of their binding modes. RXFP3 residues were alanine-substituted individually and in combination and tested in cell-based binding and functional assays to refine models of agonist and antagonist binding to active- and inactive-state homology models of RXFP3, respectively. These models suggested that both agonists and antagonists interact with RXFP3 via similar residues in their B-chain central helix. The models further suggested that the B-chain Trp27 inserts into the binding pocket of RXFP3 and interacts with Trp138 and Lys271, the latter through a salt bridge with the C-terminal carboxyl group of Trp27 in relaxin-3. R3 B1–22R, which does not contain Trp27, used a non-native Arg23 residue to form cation–π and salt-bridge interactions with Trp138 and Glu141 in RXFP3, explaining a key contribution of Arg23 to affinity. Overall, relaxin-3 and R3 B1–22R appear to share similar binding residues but may differ in binding modes, leading to active and inactive RXFP3 conformational states, respectively. These mechanistic insights may assist structure-based drug design of smaller relaxin-3 mimetics to manage neurological disorders.
A Framework for Updating Functionalities Based on the MAPE Loop Mechanism

Embedded systems that realize specific functions are usually hardware constrained systems running dedicated software. These embedded systems rarely take into account the possibility to change functions after their release. As a result, it would be difficult to change some function from outside an embedded system in its operational environment. In order to keep up with the need of quickly reacting to changes affecting requirements and environments, it is paramount to find a way to update the functions of these systems. We constructed a programming framework for updating functions based on the MAPE loop mechanism, which is generally used to develop self-adaptive systems. We regard MAPE loop as a set of independent components that make it easy to separate the updating functions from other functions. We apply our framework to a web application and an embedded system. The proposed framework is independent of the target embedded system and makes it possible to easily inject new functions into it.
Photoprotective Non-photochemical Quenching Does Not Prevent Kleptoplasts From Net Photoinactivation

The enigmatic association of photosynthetically active chloroplasts from algae and some sacoglossan sea slugs, called functional kleptoplasty, is a functional unique system of photosymbioses observed in metazoans. Besides the specific adaptations of the slugs necessary to incorporate and maintain the plastids, the organelles need to ensure optimal photosynthesis. Photoprotective mechanisms in the plastids, namely the xanthophyll cycle (XC) and the high-energy dependent quenching (qE) part of the non-photochemical quenching (NPQ), and of the repair of the D1 protein of Photosystem II (PSII) are considered crucial for kleptoplast longevity in the slugs. Here, we studied the sea slugs Elysia viridis fed with the naturally occurring XC and qE-deficient Bryopsis hypnoides, and E. timida fed on Acetabularia acetabulum, an alga that possesses both mechanisms. The aim of the study was to understand (i) whether qE remains active after ingestion of kleptoplasts by E. timida, (ii) how different light intensities affect the photosynthetic activity of kleptoplasts with and without photoprotection mechanisms, and (iii) if the kleptoplasts are able to repair photodamaged D1 protein. With regard to NPQ, freshly incorporated kleptoplasts responded to different light stress in the same manner as the chloroplasts in their native host algae. Even after three weeks of incorporation the qE part of NPQ was present in the kleptoplasts of E. timida. However, the presence of the qE component of NPQ did not prevent the kleptoplasts from significant PSII photoinactivation under high light intensities. This is probably due to the fact that the kleptoplasts have a reduced PSII repair capacity, despite plastid encoded repair mechanisms in every sacoglossan food source. Hence, photoprotective mechanisms are probably not a key factor explaining kleptoplast longevity in Sacoglossa sea slugs.
Universal Proof Theory: Semi-analytic Rules and Uniform Interpolation

In [7] and [8], Iemhoff introduced a connection between the existence of a terminating sequent calculi of a certain kind and the uniform interpolation property of the super-intuitionistic logic that the calculus captures. In this paper, we will generalize this relationship to also cover the substructural setting on the one hand and a much more powerful class of rules on the other. The resulted relationship then provides a uniform method to establish uniform interpolation property for the logics $\mathbf{FL_e}$, $\mathbf{FL_{ew}}$, $\mathbf{CFL_e}$, $\mathbf{CFL_{ew}}$, $\mathbf{IPC}$, $\mathbf{CPC}$ and their $\mathbf{K}$ and $\mathbf{KD}$-type modal extensions. More interestingly though, on the negative side, we will show that no extension of $\mathbf{FL_e}$ can enjoy a certain natural type of terminating sequent calculus unless it has the uniform interpolation property. It excludes almost all super-intutionistic logics and the logics $\mathbf{K4}$ and $\mathbf{S4}$ from having such a reasonable calculus.
Butylbenzene and tert-Butylbenzene—Sorption on Sand Particles and Biodegradation in the Presence of Plant Natural Surfactants

The effects of hydrocarbons sorption on sand and saponins presence in the system on butylbenzene and tert-butylbenzene biological degradation was investigated. Additionally, the impact of saponins-containing plant extracts on environmental microorganisms was studied. Results of cell surface property measurements in samples with saponins only revealed changes in cell surface hydrophobicity, electrokinetic potential and membrane permeability when compared to corresponding values for glucose-grown microbes. Subsequently, in sorption experiments, the hydrocarbon adsorption kinetics in bacteria-free samples were better explained with the pseudo-second order kinetic model as compared to the pseudo-first order and intraparticular diffusion models. Moreover, the equilibrium data fitted better to the Freundlich isotherm for both benzene derivatives. In the samples combining hydrocarbons sorption and biological degradation in the presence of saponins, alkane-substituted hydrocarbons removal was accelerated from 40% to 90% after 14 days and the best surfactant in this aspect was S. officinalis extract.
Understanding the Origins of Weak Cryptographic Algorithms Used for Signing Android Apps

Android applications are digitally signed using developers' signing keys. As each key is associated with a developer, it can be used to establish trust between applications published by the author (that is, apps signed with the same key are allowed to update themselves if package names are identical, or access each other's resources). However, if a digital signature is generated using a weak algorithm such as MD5, then apps signed with the corresponding key are exposed to several risks (such as hijacking apps with fake updates or granting permissions to a malicious app). In this work, we analyze several Android apps to identify the threats caused using weak algorithms. Our study uncovered the following findings: Of the more than one million apps collected from Google Play, 223 and 52,866 were digitally signed using the weak algorithms of 512-bit RSA key and MD5, respectively. We identified the causal mechanisms of generating certificates that employ weak algorithms, and that they can be attributed to app-building frameworks and online app-building services. Based on these findings, we provide guidelines for stakeholders of the Android app distribution ecosystem.
Gastrin-Releasing Peptide Receptor Antagonism Induces Protection from Lethal Sepsis: Involvement of Toll-like Receptor 4 Signaling

In sepsis, toll-like receptor (TLR)-4 modulates the migration of neutrophils to infectious foci, favoring bacteremia and mortality. In experimental sepsis, organ dysfunction and cytokines released by activated macrophages can be reduced by gastrin-releasing peptide (GRP) receptor (GRPR) antagonist RC-3095. Here we report a link between GRPR and TLR-4 in experimental models and in sepsis patients. RAW 264.7 culture cells were exposed to lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α and RC-3095 (10 ng/mL). Male Wistar rats were subjected to cecal ligation and puncture (CLP), and RC-3095 was administered (3 mg/kg, subcutaneously); after 6 h, we removed the blood, bronchoalveolar lavage, peritoneal lavage and lung. Human patients with a clinical diagnosis of sepsis received a continuous infusion with RC-3095 (3 mg/kg, intravenous) over a period of 12 h, and plasma was collected before and after RC-3095 administration and, in a different set of patients with systemic inflammatory response syndrome (SIRS) or sepsis, GRP plasma levels were determined. RC-3095 inhibited TLR-4, extracellular-signal-related kinase (ERK)-1/2, Jun NH2-terminal kinase (JNK) and Akt and decreased activation of activator protein 1 (AP-1), nuclear factor (NF)-κB and interleukin (IL)-6 in macrophages stimulated by LPS. It also decreased IL-6 release from macrophages stimulated by TNF-α. RC-3095 treatment in CLP rats decreased lung TLR-4, reduced the migration of cells to the lung and reduced systemic cytokines and bacterial dissemination. Patients with sepsis and systemic inflammatory response syndrome have elevated plasma levels of GRP, which associates with clinical outcome in the sepsis patients. These findings highlight the role of GRPR signaling in sepsis outcome and the beneficial action of GRPR antagonists in controlling the inflammatory response in sepsis through a mechanism involving at least inhibition of TLR-4 signaling.
Increased number of monocytes and plasma levels of MCP‐1 and YKL‐40 in first‐episode psychosis

Accumulating evidence implicates immune activation in the development of schizophrenia. Here, monocyte numbers, monocyte chemoattractant protein‐1 (MCP‐1) and chitinase‐3‐like protein 1 (YKL‐40) were investigated in plasma and cerebrospinal fluid (CSF) in first‐episode psychosis (FEP) patients.
MPEG-4 constant-quality constant-bit-rate controls

Most video rate-control research emphasizes constant bit-rate (CBR) applications. These aim to produce a CBR bitstream with the highest possible quality, within a bitrate constraint and with no consideration for quality variation. In this paper, two MPEG-4 Constant-Quality (CQ) CBR control algorithms are proposed. These aim to produce a CBR bitstream that meets a target quality level whenever possible. The Frame-level Laplacian CQ (FLCQ) algorithm uses a distortion model based on a Laplacian model for the DCT coefficients. In contrast, the Macroblock-level Viterbi CQ (MVCQ) algorithm uses the Viterbi algorithm to determine the best combination of macroblock QP’s. “CQ” is measured by the deviation of the mean quality from the target quality, and by the quality variance over time. Simulation results suggest that the proposed algorithms perform better than Q2 and TM5 under these measures. In some cases, they produce bitstreams with fewer bits while having a higher average PSNR, and smaller variance. The FLCQ algorithm has more variation in quality than the MVCQ algorithm. With extra computational complexity, the MVCQ algorithm gives the best performance over all algorithms tested. Often, it precisely meets the target PSNR with no variation. This is truly a CQ rate-control algorithm.
Long Short-Term Memory Neural Networks for Artificial Dialogue Generation

This paper investigates both of user and system modeling to extend an existing corpus of human-machine dialogue data with simulated/artificial dialogues. To simulate and generate such artificial dialogues, a long-short term memory (LSTM) neural network system is proposed. The LSTM neural network is an Encoder-Decoder built on a bidirectional multilayer architecture where the input sequence to the encoder is a list of user dialogue acts and the decoder output sequence is a list of system dialogue acts. All dialogue acts are defined at the intent level and are extracted from the TownInfo corpus for tourist information provided by the FP7 CLASSiC Project funded by European Union. The proposed LSTM configuration is compared to a fully connected Hidden Markov Model (HMM) based architecture where the states are the user dialogues acts and the observations are the system dialogue acts. After carrying out different experiments, the results obtained on the TownInfo corpus showed that the LSTM-based system outperforms the HMM-based system.
Interactive 3D Visual Analysis of Atmospheric Fronts

Atmospheric fronts play a central role in meteorology, as the boundaries between different air masses and as fundamental features of extra-tropical cyclones. They appear in numerous conceptual model depictions of extra-tropical weather systems. Conceptually, fronts are three-dimensional surfaces in space possessing an innate structural complexity, yet in meteorology, both manual and objective identification and depiction have historically focused on the structure in two dimensions. In this work, we -a team of visualization scientists and meteorologists-propose a novel visualization approach to analyze the three-dimensional structure of atmospheric fronts and related physical and dynamical processes. We build upon existing approaches to objectively identify fronts as lines in two dimensions and extend these to obtain frontal surfaces in three dimensions, using the magnitude of temperature change along the gradient of a moist potential temperature field as the primary identifying factor. We introduce the use of normal curves in the temperature gradient field to visualize a frontal zone (i.e., the transitional zone between the air masses) and the distribution of atmospheric variables in such zones. To enable for the first time a statistical analysis of frontal zones, we present a new approach to obtain the volume enclosed by a zone, by classifying grid boxes that intersect with normal curves emanating from a selected front. We introduce our method by means of an idealized numerical simulation and demonstrate its use with two real-world cases using numerical weather prediction data.
Conservation of preparatory neural events in monkey motor cortex regardless of how movement is initiated

A time-consuming preparatory stage is hypothesized to precede voluntary movement. A putative neural substrate of motor preparation occurs when a delay separates instruction and execution cues. When readiness is sustained during the delay, sustained neural activity is observed in motor and premotor areas. Yet whether delay-period activity reflects an essential preparatory stage is controversial. In particular, it has remained ambiguous whether delay-period-like activity appears before non-delayed movements. To overcome that ambiguity, we leveraged a recently developed analysis method that parses population responses into putatively preparatory and movement-related components. We examined cortical responses when reaches were initiated after an imposed delay, at a self-chosen time, or reactively with low latency and no delay. Putatively preparatory events were conserved across all contexts. Our findings support the hypothesis that an appropriate preparatory state is consistently achieved before movement onset. However, our results reveal that this process can consume surprisingly little time.
Combining e‐mental health intervention development with human computer interaction (HCI) design to enhance technology‐facilitated recovery for people with depression and/or anxiety conditions: An integrative literature review

Computer scientists contend that understanding human computer interaction (HCI) is an important factor in developing successful computer user experiences. Mental health professionals across a range of disciplines are increasingly developing and implementing Internet-based treatments for people with a variety of mental health conditions. Many therapeutic and economic benefits are associated with technology-enabled treatments for a range of mental health disorders. Despite this, the role of HCI and associated design elements remains poorly understood in regard to the impact on patient safety, effectiveness, and to adherence of treatment for computer users who engage with e-mental health interventions. An integrative literature review was conducted to investigate how adequately HCI and user-centred design is incorporated in the development of e-mental health interventions for depression and anxiety, and subsequently reported in literature to inform evidence-based practice. The PRISMA model was used to locate, select, and include 30 relevant articles. The main finding of this review is that Internet-based e-mental health interventions are routinely implemented without sufficiently describing the relevant HCI design features applied. This is a limitation that in turn jeopardizes the assessment validity of e-mental interventions generally, leaving those who administer the interventions with incomplete evidence to support the safe, reliable, dependable, credible, and trustworthy implementation of the interventions. The recommendation arising from this review is that human computer interaction should be carefully considered when mental health nurses and other practitioners adopt e-mental health interventions for therapeutic purposes to assure the quality and safety of e-mental health interventions on offer to patients.
Near-Infrared-Fluorescent Erythrocyte-Mimicking Particles: Physical and Optical Characteristics

Exogenous fluorescent materials activated by near-infrared (NIR) light can offer deep optical imaging with subcellular resolution, and enhanced image contrast. We have engineered NIR particles by doping hemoglobin-depleted erythrocyte ghosts (EGs) with indocyanine green (ICG). We refer to these optical particles as NIR erythrocyte-mimicking transducers (NETs). A particular feature of NETs is that their diameters can be tuned from micrometer to nanometer scale, thereby, providing a capability for broad NIR biomedical imaging applications. Herein, we investigate the effects of ICG concentration on key material properties of micrometer-sized NETs, and nanometer-sized NETs fabricated by either sonication or mechanical extrusion of EGs. The zeta potentials of NETs do not vary significantly with ICG concentration, suggesting that ICG is encapsulated within NETs regardless of particle size or ICG concentration. Loading efficiency of ICG into the NETs monotonically decreases with increasing values of ICG concentration. Based on quantitative analyses of the fluorescence emission spectra of the NETs, we determine that 20 μM ICG utilized during fabrication of NETs presents an optimal concentration that maximizes the integrated fluorescence emission for micrometer- and nanometer-sized NETs. Encapsulation of the ICG in these constructs also enhances the fluorescence stability and quantum yield of ICG. These results guide the engineering of NETs with maximal NIR emission for imaging applications such as fluorescence-guided tumor resection and real-time angiography.
Cardiolaminopathies from bench to bedside: challenges in clinical decision-making with focus on arrhythmia-related outcomes

ABSTRACT Lamin A/C gene mutations can be associated with cardiac diseases, usually referred to as ‘cardiolaminopathies’ characterized by arrhythmic disorders and/or left ventricular or biventricular dysfunction up to an overt picture of heart failure. The phenotypic cardiac manifestations of laminopathies are frequently mixed in complex clinical patterns and specifically may include bradyarrhythmias (sinus node disease or atrioventricular blocks), atrial arrhythmias (atrial fibrillation, atrial flutter, atrial standstill), ventricular tachyarrhythmias and heart failure of variable degrees of severity. Family history, physical examination, laboratory findings (specifically serum creatine phosphokinase values) and ECG findings are often important ‘red flags’ in diagnosing a ‘cardiolaminopathy’. Sudden arrhythmic death, thromboembolic events or stroke and severe heart failure requiring heart transplantation are the most dramatic complications of the evolution of cardiolaminopathies and appropriate risk stratification is clinically needed combined with clinical follow-up. Treatment with cardiac electrical implantable devices is indicated in case of bradyarrhythmias (implant of a device with pacemaker functions), risk of life-threatening ventricular tachyarrhythmias (implant of an ICD) or in case of heart failure with wide QRS interval (implant of a device for cardiac resynchronization). New technologies introduced in the last 5 years can help physicians to reduce device-related complications, thanks to the extension of device longevity and availability of leadless pacemakers or defibrillators, to be implanted in appropriately selected patients. An improved knowledge of the complex pathophysiological pathways involved in cardiolaminopathies and in the determinants of their progression to more severe forms will help to improve clinical management and to better target pharmacological and non-pharmacological treatments.
Identification of protein complexes associated with myocardial infarction using a bioinformatics approach

Myocardial infarction (MI) is a leading cause of mortality and disability worldwide. Determination of the molecular mechanisms underlying the disease is crucial for identifying possible therapeutic targets and designing effective treatments. On the basis that MI may be caused by dysfunctional protein complexes rather than single genes, the present study aimed to use a bioinformatics approach to identifying complexes that may serve important roles in the development of MI. By investigating the proteins involved in these identified complexes, numerous proteins have been reported that are related to MI, whereas other proteins interacted with MI-related proteins, which implied that these protein complexes may indeed be related to the development of MI. The protein complexes detected in the present study may aid in our understanding of the molecular mechanisms that underlie MI pathogenesis.
Online disclosure neither now nor never: When would a "later" button work?

The combination of personal demographic data, taste preferences, public disclosure of friend networks and now increasing usage of tools for instantly updating status (e.g., Twitter, Facebook) has fundamentally altered users' understanding of the temporality of information and its (semi-)permanence. A recent exploratory study found users were more willing to share items as time passed, and a major finding included a latent willingness (40% of sharing scenarios) to disclose information at a later date, neither “now” nor “never”. This study further explicates these findings by examining in greater detail the nature of the role of temporality in disclosure willingness.