Miracle-dz/UniFAR-FTUs huggingface dataset:
The Nitrogen Cascade

Abstract Human production of food and energy is the dominant continental process that breaks the triple bond in molecular nitrogen (N2) and creates reactive nitrogen (Nr) species. Circulation of anthropogenic Nr in Earth’s atmosphere, hydrosphere, and biosphere has a wide variety of consequences, which are magnified with time as Nr moves along its biogeochemical pathway. The same atom of Nr can cause multiple effects in the atmosphere, in terrestrial ecosystems, in freshwater and marine systems, and on human health. We call this sequence of effects the nitrogen cascade. As the cascade progresses, the origin of Nr becomes unimportant. Reactive nitrogen does not cascade at the same rate through all environmental systems; some systems have the ability to accumulate Nr, which leads to lag times in the continuation of the cascade. These lags slow the cascade and result in Nr accumulation in certain reservoirs, which in turn can enhance the effects of Nr on that environment. The only way to eliminate Nr accumulation and stop the cascade is to convert Nr back to nonreactive N2.
Pharmaceutical powder technology — from art to science: the challenge of the FDA's Process Analytical Technology initiative

Abstract —This paper describes with typical examples the state of art. The list of examples includes the problems of non-robust formulations and critical processes. The paper demonstrates the necessity and the challenge of the FDA's Process Analytical Technology initiative, which is an important stimulus to develop a rigorous scientific framework in the area of pharmaceutical powder technology. The paper suggests a kind of ‘road map’ to achieve as fast as possible the top of the ‘knowledge pyramid’. The road map includes the extensive use of a multivariate design of experiments, the use of artificial neural networks (ANN), the use of the laws of physical pharmacy and percolation theory, and, last but not least, tries to ‘translate’ the existing laws of physical chemistry into the area of pharmaceutical powder technology, where we have the problem that the number of particles involved is much lower than the Avogadro number NA. For this reason it will be of interest to monitor closely the progress in nanoscience, especially in the area of mathematical modeling of the fascinating special physical properties of nanoparticles, which again consist of a finite number N of atoms, respectively molecules, with N ≪ N A .
The effect of positive and negative message framing on short term continuous positive airway pressure compliance in patients with obstructive sleep apnea.

Background Continuous positive airway pressure (CPAP), the best available treatment for obstructive sleep apnea (OSA), requires long-term compliance to be effective. Behavioral interventions may be used to improve adherence to CPAP. We aimed to investigate whether positive or negative message framing impacts on CPAP compliance in patients with OSA, when compared to standard care. Methods Consenting patients with confirmed OSA were randomly allocated to receive along with their CPAP either positively or negatively framed messages (Pos; Neg), or standard care (Con). Standardized motivational messages were read out to patients during an initial teaching session and through weekly telephone calls. Patients' compliance data were reviewed 2 and 6 weeks following CPAP initiation. Results We randomized 112 patients to groups that were matched for age, BMI, and OSA severity. The positively framed group (Pos) showed greater CPAP usage after 2 weeks (total use 53.7±31.4 hours) as compared to the negatively framed and the control group (35.6±27.4 and 40.8±33.5 hours, P<0.05); however, no differences were seen at 6 weeks. There were more dropouts in the control group than in either framed groups (Pos n=5; Neg n=8; Con n=11; P<0.05). Conclusions Positively framed messages can improve CPAP adherence in patients with OSA in the short-term; however, strategies for implementing its long-term use need to be developed.
When Does Repository KMS Use Lift Performance? The Role of Alternative Knowledge Sources and Task Environments

Despite a general consensus that use of information technology (IT) is an important link between IT investments and performance, the extant literature provides only a limited explanation as to when the use of IT lifts performance. We posit that the impact of knowledge management systems (KMS) usage is contingent on users' alternative sources of knowledge as well as their specific task environments. We investigate under what conditions repository KMS use leads to higher performance outcomes in a retail grocery context. We use a unique longitudinal dataset composed of objective measures of KMS use and sales performance of 273 managers over 146 weeks collected from a retail grocery chain. We obtain two main results. First, we find a diminishing impact of KMS use for managers who also use other sources of codified knowledge, namely physical or computerized alternative knowledge sources, whereas a complementary relationship seems to exist between KMS use and social sources of knowledge. Second, KMS use produces higher benefits for managers whose task environments require a greater volume of information and knowledge, but smaller benefits for those managers whose task environments demand rapidly changing information and knowledge. Our work contributes to both the IT business value and the KM literature by studying the contingent impact of IT usage while broadening the theoretical scope of the situated knowledge performance framework with a critical empirical test based on fine-grained objective and longitudinal data.
Cell Block Alone as an Ideal Preparatory Method for Hemorrhagic Thyroid Nodule Aspirates Procured Without Onsite Cytologists

OBJECTIVE To study diagnostic efficacy of direct smears (DS) vs. cell block (CB) alone in hemorrhagic thyroid fine needle aspirations (FNAs) performed without a cytotechnologist or cytopathologist. STUDY DESIGN Ultrasound-guided thyroid FNAs from an offsite location were retrospectively searched during a 53-month period. Aspirates in the initial 13 months were submitted as air-dried DSs. Subsequent specimens were submitted as CBs. Each case was classified into 1 of 4 categories: (1) nondiagnostic, (2) nonneoplastic, (3) follicular lesions and (4) papillary thyroid carcinoma (PTC). RESULTS There were 77 aspirates: DS = 20 (26%) and CB = 57 (74%). Two cases had both DSs and CBs. Diagnoses of DS: nondiagnostic = 12 (60%); nonneoplastic = 7 (35%); follicular lesion = 1 (5%). Diagnoses of CB cases: nondiagnostic = 4 (7.0%); nonneoplastic = 43 (75.4%); follicular lesion, including 1 Hürthle cell neoplasm = 7 (12.3%), PTC = 3 (5.3%). Repeat FNAs on 4 nondiagnostic cases (3 DSs, 1 CB) utilizing the CB-only technique were diagnostic and included nodular goiter, follicular neoplasm, PTC, and reactive lymph node. CONCLUSION Without onsite assessment, CB alone is superior to DSs for hemorrhagic thyroid FNAs. It shows increased diagnostic efficacy and slide reduction and obviates repeat FNAs.
G-protein–coupled receptor GPR161 is overexpressed in breast cancer and is a promoter of cell proliferation and invasion

Significance Recent advances in DNA sequencing and bioinformatics tools have allowed the large-scale characterization of genetic alterations in human tumors. We exploited genomics data to identify commonly occurring alterations in G-protein–coupled receptors (GPCRs) in triple-negative breast cancer (TNBC), a subset of breast cancer with poor prognosis and lacking effective targeted therapy. We have discovered that the orphan GPCR, G-protein–coupled receptor 161 (GPR161), is overexpressed specifically in TNBC and correlates with poor prognosis. We identify GPR161 as a regulator of mammary epithelial cell proliferation and invasion in a mammalian target of rapamycin signaling-pathway–dependent manner. Down-regulation of GPR161 in a TNBC-derived cell line impairs cell growth, suggesting that GPR161 is a drug target for breast cancer. Triple-negative breast cancer (TNBC) accounts for 20% of breast cancer in women and lacks an effective targeted therapy. Therefore, finding common vulnerabilities in these tumors represents an opportunity for more effective treatment. Despite the growing appreciation of G-protein–coupled receptor (GPCR)-mediated signaling in cancer pathogenesis, very little is known about the role GPCRs play in TNBC. Using genomic information of human breast cancer, we have discovered that the orphan GPCR, G-protein–coupled receptor 161 (GPR161) is overexpressed specifically in TNBC and correlates with poor prognosis. Knockdown of GPR161 impairs proliferation of human basal breast cancer cell lines. Overexpression of GPR161 in human mammary epithelial cells increases cell proliferation, migration, intracellular accumulation of E-cadherin, and formation of multiacinar structures in 3D culture. GPR161 forms a signaling complex with the scaffold proteins β-arrestin 2 and Ile Gln motif containing GTPase Activating Protein 1, a regulator of mammalian target of rapamycin complex 1 and E-cadherin. Consistently, GPR161 amplified breast tumors and cells overexpressing GPR161 activate mammalian target of rapamycin signaling and decrease Ile Gln motif containing GTPase Activating Protein 1 phosphorylation. Thus, we identify the orphan GPCR, GPR161, as an important regulator and a potential drug target for TNBC.
Towards robust hexapedal running with serial elastic actuation: A 3D simulation study

The legs of a future generation of hexapedal robots should enable highly articulated walking as well as robust running within the same platform. Following a hypothesis from biology [2], robustness and stability of walking mainly result from feedback control while being anchored in selfstabilizing properties of the feedforward driven mechanical structure in case of running. The advantage of this shift from feedback to feedforward control with increasing velocity is, that it allows careful and highly adaptive locomotion at low speeds while the complexity of control is reduced at high speeds. In order to embed a fast locomotion mode within the structure of an articulated leg its individual functional behavior during running needs to be understood, first.
Acoustic Oddball during NREM Sleep: A Combined EEG/fMRI Study

Background A condition vital for the consolidation and maintenance of sleep is generally reduced responsiveness to external stimuli. Despite this, the sleeper maintains a level of stimulus processing that allows to respond to potentially dangerous environmental signals. The mechanisms that subserve these contradictory functions are only incompletely understood. Methodology/Principal Findings Using combined EEG/fMRI we investigated the neural substrate of sleep protection by applying an acoustic oddball paradigm during light NREM sleep. Further, we studied the role of evoked K-complexes (KCs), an electroencephalographic hallmark of NREM sleep with a still unknown role for sleep protection. Our main results were: (1) Other than in wakefulness, rare tones did not induce a blood oxygenation level dependent (BOLD) signal increase in the auditory pathway but a strong negative BOLD response in motor areas and the amygdala. (2) Stratification of rare tones by the presence of evoked KCs detected activation of the auditory cortex, hippocampus, superior and middle frontal gyri and posterior cingulate only for rare tones followed by a KC. (3) The typical high frontocentral EEG deflections of KCs were not paralleled by a BOLD equivalent. Conclusions/Significance We observed that rare tones lead to transient disengagement of motor and amygdala responses during light NREM sleep. We interpret this as a sleep protective mechanism to delimit motor responses and to reduce the sensitivity of the amygdala towards further incoming stimuli. Evoked KCs are suggested to originate from a brain state with relatively increased stimulus processing, revealing an activity pattern resembling novelty processing as previously reported during wakefulness. The KC itself is not reflected by increased metabolic demand in BOLD based imaging, arguing that evoked KCs result from increased neural synchronicity without altered metabolic demand.
Discourse, Syntax, and Prosody: The Brain Reveals an Immediate Interaction

Speech is structured into parts by syntactic and prosodic breaks. In locally syntactic ambiguous sentences, the detection of a syntactic break necessarily follows detection of a corresponding prosodic break, making an investigation of the immediate interplay of syntactic and prosodic information impossible when studying sentences in isolation. This problem can be solved, however, by embedding sentences in a discourse context that induces the expectation of either the presence or the absence of a syntactic break right at a prosodic break. Event-related potentials (ERPs) were compared to acoustically identical sentences in these different contexts. We found in two experiments that the closure positive shift, an ERP component known to be elicited by prosodic breaks, was reduced in size when a prosodic break was aligned with a syntactic break. These results establish that the brain matches prosodic information against syntactic information immediately.
Crystal Structure of Plant Legumain Reveals a Unique Two-Chain State with pH-Dependent Activity Regulation[CC-BY]

A novel activation state of a plant legumain reconciles previous data on its protease and ligase stabilities and activities, which allow it to cyclize or fuse peptides with unique functions. The vacuolar cysteine protease legumain can cleave and selectively rebuild peptide bonds, thereby vastly expanding the sequential repertoire of biomolecules. In this context, plant legumains have recently attracted particular interest. Furthermore, legumains have important roles in many physiological processes, including programmed cell death. Their efficient peptide bond ligase activity has gained tremendous interest in the design of cyclic peptides for drug design. However, the mechanistic understanding of these dual activities is incomplete and partly conflicting. Here, we present the crystal structure of a plant legumain, Arabidopsis thaliana isoform-γ (AtLEGγ). Employing a conserved legumain fold, the plant legumain AtLEGγ revealed unique mechanisms of autoactivation, including a plant-specific two-chain activation state, which remains conformationally stable at neutral pH, which is a prerequisite for full ligase activity and survival in different cell compartments. The charge distribution around the α6-helix mediates the pH-dependent dimerization and serves as a gatekeeper for the active site, thus regulating its protease and ligase activity.
Triphenylphosphonium Moiety Modulates Proteolytic Stability and Potentiates Neuroprotective Activity of Antioxidant Tetrapeptides in Vitro

Although delocalized lipophilic cations have been identified as effective cellular and mitochondrial carriers for a range of natural and synthetic drug molecules, little is known about their effects on pharmacological properties of peptides. The effect of triphenylphosphonium (TPP) cation on bioactivity of antioxidant tetrapeptides based on the model opioid YRFK motif was studied. Two tetrapeptide variants with L-arginine (YRFK) and D-arginine (YrFK) were synthesized and coupled with carboxyethyl-TPP (TPP-3) and carboxypentyl-TPP (TPP-6) units. The TPP moiety noticeably promoted YRFK cleavage by trypsin, but effectively prevented digestion of more resistant YrFK attributed, respectively, to structure-organizing and shielding effects of the TPP cation on conformational variants of the tetrapeptide motif. The TPP moiety enhanced radical scavenging activity of the modified YRFK in a model Fenton-like reaction, whereas decreased reactivity was revealed for both YrFK and its TPP derivative. The starting motifs and modified oligopeptides, especially the TPP-6 derivatives, suppressed acute oxidative stress in neuronal PC-12 cells during a brief exposure similarly with glutathione. The effect of oligopeptides was compared upon culturing of PC-12 cells with CoCl2, L-glutamic acid, or menadione to mimic physiologically relevant oxidative states. The cytoprotective activity of oligopeptides significantly depended on the type of oxidative factor, order of treatment and peptide structure. Pronounced cell-protective effect was established for the TPP-modified oligopeptides, which surpassed that of the unmodified motifs. The protease-resistant TPP-modified YrFK showed the highest activity when administered 24 h prior to the cell damage. Our results suggest that the TPP cation can be used as a modifier for small therapeutic peptides to improve their pharmacokinetic and pharmacological properties.
Miscibility, Morphology, and Thermal Properties of Poly(Trimethylene Terephthalate)/Polycarbonate

Abstract Poly(trimethylene terephthalate)/polycarbonate (PTT/PC) blends were prepared by melt blending and rapid quenching in ice water. The miscibility and thermal properties were investigated using differential scanning calorimeter (DSC) and dynamic mechanical analysis (DMA). The blend's morphologies were investigated using scanning and transmission electron microscopies. Both DSC and DMA results suggested that PTT and PC were very limited, partially miscible pairs. The melting point, melt crystallization, and cold crystallization exotherms in the blends of PTT were depressed by the presence and amount of PC. When the PC content was <50 wt%, PC spherical particles were found to distribute evenly in the PTT matrix; at 50–60 wt%, the two‐phase structures were close to being bicontinuous. At higher PC content, PTT formed a string‐like texture in the PC matrix. The PTT spherulitic morphologies in PTT/PC blends were found to be very sensitive to PC and PC content. When the PC content was ≥60 wt%, the blends crystallized as an agglomeration of tiny PTT crystals.
Direction Tracking of Multiple Moving Targets Using Quantum Particle Swarm Optimization

Based on weighted signal covariance (WSC) matrix and maximum likelihood (ML) estimation, a directionof-arrival (DOA) estimation method of multiple moving targets is designed and named as WSC-ML in the presence of impulse noise. In order to overcome the shortcoming of the multidimensional search cost of maximum likelihood estimation, a novel continuous quantum particle swarm optimization (QPSO) is proposed for this continuous optimization problem. And a tracking method of multiple moving targets in impulsive noise environment is proposed and named as QPSO-WSC-ML. Later, we make use of rank-one updating to update the weighted signal covariance matrix of WSC-ML. Simulation results illustrate the proposed QPSO-WSC-ML method is efficient and robust for the direction tracking of multiple moving targets in the presence of impulse noise.
The mental time travel continuum: on the architecture, capacity, versatility and extension of the mental bridge into the past and future

Abstract Mental time travel (MTT) is the ability to remember past events and to anticipate or imagine events in the future. MTT globally serves to optimize decision-making processes, improve problem-solving capabilities and prepare for future needs. MTT is also essential in providing our concept of self, which includes knowledge of our personality, our strengths and weaknesses, as well as our preferences and aversions. We will give an overview in which ways the capacity of animals to perform MTT is different from humans. Based on the existing literature, we conclude that MTT might represent a quantitative rather than qualitative entity with a continuum of MTT capacities in both humans and nonhuman animals. Given its high complexity, MTT requires a large processing capacity in order to integrate multimodal stimuli during the reconstruction of past and/or future events. We suggest that these operations depend on a highly specialized working memory subsystem, ‘the MTT platform’, which might represent a necessary additional component in the multi-component working memory model by Alan Baddeley.
Multi-objective optimization and analysis of electrical discharge machining process during micro-hole machining of D3 die steel employing salt mixed de-ionized water dielectric

Article info: Abstract Correct selection of manufacturing condition is one of the most important aspects which should be considered in the majority of manufacturing processes, particularly in the process related to advanced machining process like electrical discharge machining. In electrical discharge machining (EDM), dielectric fluid plays an important role since machining characteristics are greatly influenced by the nature or characteristics of employed dielectric. Moreover, adding various types of abrasives or salt in the fluid at different concentrations also affect the machining performance because of changing dielectric strength property. The present paper addressed the influence of NaNO3 mixed de-ionized water as a dielectric fluid on micro-hole machining performance criteria such as material removal rate (MRR), tool wear rate (TWR), overcut (OC) and taper during machining of D3 die steel plate. Received: 23/08/2012 Accepted: 10/03/2013 Online: 11/09/2013
Impact of pneumococcal conjugate vaccines for children in high- and non–high-income countries

ABSTRACT Introduction: The high level of effectiveness of pneumococcal conjugate vaccines (PCVs) was demonstrated initially in high-income countries (HICs). However, because the burden of pneumococcal diseases (PDs) is greater in non–high-income countries (NHICs) than HICs, the assessment of these vaccines in this latter setting is crucial. Areas covered: PubMed was used to search for literature related to the effectiveness of PCVs. Several studies described the effectiveness of PCVs in NHICs, and we compare the impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and pneumonia in HICs and NHICs. Expert commentary: Implementation of PCVs has been effective in both HICs and NHICs. The decline in overall incidence of PD is due to the disappearance of most vaccine serotypes, which is straightforward and comparable across the different settings. As expected, the decrease in overall incidence of PD was eroded in part by the increasing incidence of IPD due to non-vaccine serotypes. We need to continue a multi-faceted surveillance of IPD and carriage.
PVDF membrane formation by diffusion‐induced phase separation‐morphology prediction based on phase behavior and mass transfer modeling

The equilibrium phase behavior of water (nonsolvent)-DMF (solvent)-PVDF system at 25°C was investigated via both theoretical and experimental approaches. Using binary interaction parameters, χij, obtained previously, the theoretical phase boundaries were computed and were found to match closely the measured binodal and crystallization-induced gelation data. Membranes were prepared using the isothermal immersion-precipitation processes in various dope and bath conditions. The formed membranes demonstrated a broad spectrum of morphologies: At one extreme, asymmetric structure was obtained featuring a continuous tight skin and a sublayer composed of parallel macrovoids and cellular pores; at the other limit, skinless microporous membrane was produced with spherical particles packed into a bi-continuous structure. The crystalline characters of PVDF gels and membranes were examined by small angle light scattering, scanning electron microscopy, and differential scanning calorimetry techniques. In addition, diffusion trajectories and concentration profiles in the membrane solution before precipitation were calculated for the immersion process. These results predicted reasonably the various morphologies observed in the membranes. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 2079–2092, 1999