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All the cards seem to be stacked against belief in immortality. Nonetheless, the resources of particular religious traditions may avail where generic philosophical solutions fall short. With attention to the boredom and narcissism critiques, intimations of deathlessness in Śāntideva's radical altruism, and recent Christian debates on the soul and the intermediate state, I propose two criteria for a coherent religion-specific belief in immortality: (1) the belief is supported by a fully realized religious tradition, (2) the belief satisfies the demand for self-transcendence as well as for self-preservation. Where self-transcendence and self-preservation are kept in balance, and where the whole idea rests upon the lattice-work of a fully realized religious tradition, immortality is a fitting object of belief. Moreover, such belief is compatible with considerable speculative freedom concerning matter and spirit, body and soul, and personal identity over time. [ABSTRACT FROM AUTHOR]

Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) are derived from pre- and post-implantation embryos, representing the initial "naïve" and final "primed" states of pluripotency, respectively. In this study, novel reprogrammed pluripotent stem cells (rPSCs) were induced from mouse EpiSCs using a chemically defined medium containing mouse LIF, BMP4, CHIR99021, XAV939, and SB203580. The rPSCs exhibited domed clones and expressed key pluripotency genes, with both X chromosomes active in female cells. Furthermore, rPSCs differentiated into cells of all three germ layers in vivo through teratoma formation. Regarding epigenetic modifications, the DNA methylation of Oct4, Sox2, and Nanog promoter regions and the mRNA levels of Dnmt3a, Dnmt3b, and Dnmt1 were reduced in rPSCs compared with EpiSCs. However, the miR-290 family was significantly upregulated in rPSCs. After removing SB203580, an inhibitor of the p38 MAPK pathway, the cell colonies changed from domed to flat, with a significant decrease in the expression of pluripotency genes and the miR-290 family. Conversely, overexpression of pri-miR-290 reversed these changes. In addition, Map2k6 was identified as a direct target gene of miR-291b-3p, indicating that the miR-290 family maintains pluripotency and self-renewal in rPSCs by regulating the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Protein folding is a prominent area of research in the life sciences. Exendin-4, a 39-amino acid peptide hormone, is of particular interest due to its potential therapeutic applications. In this study, we employed a steered molecular dynamics method to investigate the folding of Exendin-4. Our simulations reveal an intermediate state during the folding process, suggesting a more complex three-state mode of folding. Structural analysis indicates that Exendin-4 folds through two distinct pathways: pathway 1 involves gradual growth of a helical structure after the collapse of the hydrophobic core in the Trp-cage, while pathway 2 involves initial formation of local microdomains (helical structure and Trp-cage) which then combine with each other to form a stable native structure. We found that the folding along these pathways follows the hydrophobic collapse mechanism and the diffusion-collision mechanism, respectively. We believe that these two mechanisms together govern the folding of Exendin-4. These results significantly differ from those observed in most small protein folding. Our study on the folding of Exendin-4 will advance our understanding of the protein folding mechanism. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 virus, commonly known as COVID-19, occurred in 2019. It is a highly contagious illness with effects ranging from mild symptoms to severe illness. It is also one of the best-known pathogens since more than 200,000 scientific papers occurred in the last few years. With the publication of the SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in a complex with human ACE2 (hACE2) (PDB (6LZG)), the molecular analysis of one of the most crucial steps on the infection pathway was possible. The aim of this manuscript is to simulate the most widely spread mutants of SARS-CoV-2, namely Alpha, Beta, Gamma, Delta, Omicron, and the first recognized variant (natural wild type). With the wide search of the hypersurface of the potential energy performed using the UNRES force field, the intermediate state of the ACE2–RBD complex was found. R403, K/N/T417, L455, F486, Y489, F495, Y501, and Y505 played a crucial role in the protein recognition mechanism. The intermediate state cannot be very stable since it will prevent the infection cascade. [ABSTRACT FROM AUTHOR]

Abstract The transient and elusive intermediate states are the keys in self‐assembly processes, which are common phenomena shaping the structure, properties, and functionalities of assembled materials across many scientific domains. However, the understanding about the intermediate states of self‐assembly process is always challenging and limited. In this review, we focus on these states by combining theoretical and experimental approaches. By examining a wide variety of self‐assembly systems that span from biological to metal–organic nanostructures, this review uncovers the wealth of intermediate states of self‐assembled materials. In addition to combining the current knowledge, it will identify challenges and provide a new insight into the opportunities for future research.

Multidrug resistance poses a major challenge to antibiotic therapy. A principal cause of antibiotic resistance is through active export by efflux pumps embedded in the bacterial membrane. Major facilitator superfamily (MFS) efflux pumps constitute a major group of transporters, which are often related to quinolone resistance in clinical settings. Although a rocker-switch model is proposed for description of their conformational transitions, detailed changes in this process remain poorly understood. Here we used MdfA from E. coli as a representative MFS efflux pump to investigate factors that can affect its conformational transition in silico. Molecular dynamics (MD) simulations of MdfA's inward and outward conformations revealed an intermediate state between these two conformations. By comparison of the subtle differences between the intermediate state and the average state, we indicated that conformational transition from outward to inward was initiated by protonation of the periplasmic side. Subsequently, hydrophilic interaction of the periplasmic side with water was promoted and the regional structure of helix 1 was altered to favor this process. As the hydrophobic interaction between MdfA and membrane was also increased, energy was concentrated and stored for the opposite transition. In parallel, salt bridges at the cytoplasmic side were altered to lower probabilities to facilitate the entrance of substrate. In summary, we described the total and local changes during MdfA's conformational transition, providing insights for the development of potential inhibitors. [ABSTRACT FROM AUTHOR]

As our catalog of cell states expands, appropriate characterization of these states and the transitions between them is crucial. Here we discuss the roles of intermediate cell states (ICSs) in this growing collection. We begin with definitions and discuss evidence for the existence of ICSs and their relevance in various tissues. We then provide a list of possible functions for ICSs with examples. Finally, we describe means by which ICSs and their functional roles can be identified from single-cell data or predicted from models.

Mitochondrial carnitine/acylcarnitine carrier (CAC) is a member of the mitochondrial carrier (MC) family and imports acylcarnitine into the mitochondrial matrix in exchange for carnitine, playing a pivotal role in carnitine shuttle, crucial for fatty acid oxidation. The crystallized structure of CAC has not been solved yet, however, the availability of several in vitro/in silico studies, also based on the crystallized structures of the ADP/ATP carrier in the cytosolic-conformation and in the matrix-conformation, has made possible to confirm the hypothesis of the single-binding centered-gated pore mechanism for all the members of the MC family. In addition, our recent bioinformatics analyses allowed quantifying in silico the importance of protein residues of MC substrate binding region, of those involved in the formation of the matrix and cytosolic gates, and of those belonging to the Pro/Gly (PG) levels, proposed to be crucial for the tilting/kinking/bending of the six MC transmembrane helices, funneling the substrate translocation pathway. Here we present a combined in silico/in vitro analysis employed for investigating the role played by a group of 6 proline residues and 6 glycine residues, highly conserved in CAC, belonging to MC PG-levels. Residues of the PG-levels surround the similarly located MC common substrate binding region, and were proposed to lead conformational changes and substrate translocation, following substrate binding. For our analysis, we employed 3D molecular modeling approaches, alanine scanning site-directed mutagenesis and in vitro transport assays. Our analysis reveals that P130 (H3), G268 (H6) and G220 (H5), mutated in alanine, affect severely CAC transport activity (mutant catalytic efficiency lower than 5 % compared to the wild type CAC), most likely due to their major role in triggering CAC conformational changes, following carnitine binding. Notably, P30A (H1) and G121A (H3) CAC mutants, increase the carnitine uptake up to 217 % and 112 %, respectively, compared to the wild type CAC. • A 3D comparative model of the carnitine/acylcarnitine carrier (CAC) in m-conformation has been provided for the first time. • The 3D models of CAC in c-conformation or in m-conformation highlight the position of CAC PG level residues with respect to carnitine docked in the CAC catalytic pocket. • In vitro site-directed mutagenesis of Pro/Gly residues of the CAC PG levels determines important changes in CAC kinetic parameters. • PG level residues play a crucial role in tilting/kinking/bending MC transmembrane helices after substrate binding. [ABSTRACT FROM AUTHOR]

The manufacturing process of STT-MRAM requires unique steps to fabricate and integrate magnetic tunnel junction (MTJ) devices which are data-storing elements. Thus, understanding the defects in MTJs and their faulty behaviors are paramount for developing high-quality test solutions. This article applies the advanced device-aware test to intermediate (IM) state defects in MTJ devices based on silicon measurements and circuit simulations. An IM state manifests itself as an abnormal third resistive state, which differs from the two bi-stable states of MTJ. We performed silicon measurements on MTJ devices with diameter ranging from 60nm to 120nm; the results show that the occurrence probability of IM state strongly depends on the switching direction, device size, and bias voltage. We demonstrate that the conventional resistor-based fault modeling and test approach fails to appropriately model and test such a defect. Therefore, device-aware test is applied. We first physically model the defect and incorporate it into a Verilog-A MTJ compact model and calibrate it with silicon data. Thereafter, this model is used for a systematic fault analysis based on circuit simulations to obtain accurate and realistic faults in a pre-defined fault space. Our simulation results show that an IM state defect leads to intermittent write transition faults. Finally, we propose and implement a device-aware test solution to detect the IM state defect. [ABSTRACT FROM AUTHOR]

This work examines with the form of the well-known sum: p + q = 1 – which is the sum of the probabilities of opposite events, in particular: the sum of the probabilities of the operational and non-operational (failure) states of a single element (a creation characterised by one output and any number of inputs). It was found that without significantly compromising the accuracy of the previous analyses, it was possible to introduce an additional component to the sum: iiipq3, a component that embodies the probability of an intermediate state, or a reduced operational state. With a constant value of the sum of the components in question, their variation as a function of probability q was determined, following which in the function of the same variable the variation of the entropy of an element's i state was examined using Chapman-Kolmogorov equations; here the focus was on investigating the intensity of the transition from the operational state to the non-operational state or an intermediate state, and from an intermediate state to the non-operational state. The meaning of intermediate probability was also referenced to the object: its diagnostic program, the entropy of structure, the full set of discriminable states, and the relevant transition intensities. It became indispensable in this respect to describe the object using the language of graph theory, in which the basic concepts are layers and an availability matrix. It should be noted that the subject object is an entity that comprises a set of individual elements, with a number and structure of connections that are consistent with the purpose of this entity.

Objectives: Diagnosis of patients suspected of mild dementia (MD) is a challenge and patient numbers continue to rise. A short test triaging patients in need of a neuropsychological assessment (NPA) is welcome. The Montreal cognitive assessment (MoCA) has high sensitivity at the original cutoff <26 for MD, but results in too many false-positive (FP) referrals in clinical practice (low specificity). A cutoff that finds all patients at high risk of MD without referring to many patients not (yet) in need of an NPA is needed. A difficulty is who is to be considered at risk, as definitions for disease (e.g. MD) do not always define health at the same time and thereby create subthreshold disorders. Design: In this study, we compared different selection strategies to efficiently identify patients in need of an NPA. Using the MoCA with a double threshold tackles the dilemma of increasing the specificity without decreasing the sensitivity and creates the opportunity to distinguish the clinical (MD) and subclinical (MCI) state and hence to get their appropriate policy. Setting/participants: Patients referred to old-age psychiatry suspected of cognitive impairment that could benefit from an NPA (n = 693). Results: The optimal strategy was a two-stage selection process using the MoCA with a double threshold as an add-on after initial assessment. By selecting who is likely to have dementia and should be assessed further (MoCA<21), who should be discharged (≥26), and who's course should be monitored actively as they are at increased risk (21<26). Conclusion: By using two cutoffs, the clinical value of the MoCA improved for triaging. A double-threshold MoCA not only gave the best results; accuracy, PPV, NPV, and reducing FP referrals by 65%, still correctly triaging most MD patients. It also identified most MCIs whose intermediate state justifies active monitoring. [ABSTRACT FROM AUTHOR]

Background and Aim: Acquired Immunodeficiency Syndrome (AIDS) caused by Human Immunodeficiency Virus (HIV), is a chronic and potentially life-threatening disease. Numerous factors affect its development and progression. Therefore, the present study attempted to identify characteristics impacting the prognosis and progression of AIDS using multistate models. Methods & Materials: The present retrospective study consisted of 2185 patients affected with HIV referring to Behavioral Disease Counseling Centers in Tehran City, Iran, from 2004 to 2013. We considered multiple states of AIDS, tuberculosis, and tuberculosis/AIDS in the natural history of the disease (from the onset of HIV disease until death occurred). Then, we applied the multistate models, to examine the effect of contextual demographic and clinical variables on survival time; subsequently, the transition probabilities of HIV. Ethical Considerations: This study was approved by the Research Ethics Committee of Hamadan University of Medical Sciences (Code: IR.UMSHA.REC.1396.117). Results: HIV-Related deaths in individuals with an incarnation history were 2.40 times higher than in those without the prison history. Death risk was also 1.70 and 1.80 times higher in those aged 25-44 and 44 years, respectively, compared to the individuals aged less than 25 years. An inverse relationship was also found between CD4 levels and the risk of death in our participants. Conclusion: Antiretroviral therapy, CD4 count, age, and history of imprisonment were the main factors in the progression of the disease and subsequent death in HIV patients. Thus, preventing the further spread of the disease to the community and controlling the disease in the patients requires targeted educational and therapeutic interventions; accordingly, the community will be familiarized with transmission routes and the preventing principle of disease. Furthermore, we can encourage patients to visit the healthcare centers early.

Although the hexagonal close-packed (HCP) to face centered cubic (FCC) martensitic phase transformation has been frequently observed and discussed in many HCP metals and alloys, the detailed phase transformation path has been disputed. Here, we studied the potential phase transformation path from HCP to FCC phase in high-purity hafnium (Hf) under torsional deformation condition. Results indicated that the HCP to FCC phase transformation was not accomplished directly by the glide of a/3 [ 1 1 ¯ 00 ] Shockley partial dislocations on every other {0001} planes, but progressively transitions to the FCC lattice through multiple intermediate states. The complete phase transformation process can be further refined as: HCP → body-centered tetragonal (BCT)-like structure → 12R long-period stacking-ordered (LPSO) structure → FCC, and each step was accommodated by basal stacking faults. This work is instructive on the phase transformation from HCP to FCC not only in Hf but also in other HCP metals. [Display omitted] [ABSTRACT FROM AUTHOR]

In plants, algae and cyanobacteria, Photosystem II (PSII) catalyzes the light-driven splitting of water at a protein-bound Mn4CaO5-cluster, the water-oxidizing complex (WOC). In the photosynthetic organisms, the light-driven formation of the WOC from dissolved metal ions is a key process because it is essential in both initial activation and continuous repair of PSII. Structural information is required for understanding of this chaperone-free metal-cluster assembly. For the first time, we obtained a structure of PSII from Thermosynechococcus elongatus without the Mn4CaO5-cluster. Surprisingly, cluster-removal leaves the positions of all coordinating amino acid residues and most nearby water molecules largely unaffected, resulting in a pre-organized ligand shell for kinetically competent and error-free photo-assembly of the Mn4CaO5-cluster. First experiments initiating (i) partial disassembly and (ii) partial re-assembly after complete depletion of the Mn4CaO5-cluster agree with a specific bi-manganese cluster, likely a di-µ-oxo bridged pair of Mn(III) ions, as an assembly intermediate.

Tuning and probing electrical states of molybdenum disulfide (MoS2) with single-unit-cell thickness are attractive for next-generation nanoelectronics by virtue of unique electronic and optical attributes. In this work, we first demonstrated a plasmonic-based phase imaging of individual metal nanoparticles to directly visualize the characteristic switching of the electron-doping regime and near-complete suppression of the conductivity regime for an MoS2 monolayer by modulating potential. Intermediate states of electrical switching for the MoS2 monolayer are directly imaged by ultrasensitive phase variation of a single Au nanoparticle, which is attributable to the reversible switching between classical electromag-netic plasmonic coupling and quantum plasmonic coupling. This model can be operated as a logical inverter converting a logical signal 0-1 and as a universal logical NOR gate electronic directly imaged by plasmonic technique, potentially finding applications in novel nanoelectronics and optoelectronics. [ABSTRACT FROM AUTHOR]

Oligopeptidase B (OPB) is the least studied group from the prolyl oligopeptidase family. OPBs are found in bacteria and parasitic protozoa and represent pathogenesis factors of the corresponding infections. OPBs consist of two domains connected by a hinge region and have the characteristics of conformational dynamics, which include two types of movements: the bridging/separation of α/β-hydrolase catalytic and β-propeller-regulatory domains and the movement of a loop carrying catalytic histidine, which regulates an assembly/disassembly of the catalytic triad. In this work, an elucidation of the interdomain dynamics of OPB from Serratia proteamaculans (SpOPB) with and without modification of the hinge region was performed using a combination of X-ray diffraction analysis and small-angle X-ray scattering, which was complemented with an essential dynamics sampling (EDS) simulation. The first crystal structure of catalytically deficient SpOPB (SpOPBS532A) with an intact hinge sequence is reported. Similarly to SpOPB with modified hinges, SpOPBS532A was crystallized in the presence of spermine and adopted an intermediate conformation in the crystal lattice. Despite the similarity of the crystal structures, a difference in the catalytic triad residue arrangement was detected, which explained the inhibitory effect of the hinge modification. The SpOPBS532A structure reconstituted to the wild-type form was used as a starting point to the classical MD followed by EDS simulation, which allowed us to simulate the domain separation and the transition of the enzyme from the intermediate to open conformation. The obtained open state model was in good agreement with the experimental SAXS data. [ABSTRACT FROM AUTHOR]

After Buddhism was transmitted to Tibet, it became localized and absorbed various religious and cultural elements. Subsequently, when Tibetan Buddhism was transmitted to different countries and regions, it again became fused with local customs and beliefs, to form diverse types of Tibetan Buddhism. The object of this research is the Intermediate-state ritual regularly held for the deceased at Nona Hwatsang Center which belongs to the rNying ma lineage, which combines Chinese Buddhist doctrines with Tibetan Buddhist methods, and incorporates the form of religious activity of Han people. Past research on the Chanting-Service Ritual focuses on discussing religious thought and hospice care. This paper discusses how the perception is dynamically constructed and destroyed during the intermediate state by "incurving" the three-time sound and images in the ritual. The distinctive part of the Intermediate-state ritual is the gurus with high authority performing religious functions through playing the dead gurus' videos. The videos are used to imitate and present the sounds and images so that they might be heard and seen during the intermediate state, as instructed by the authoritative scriptures. In addition, the lay group guides the deceased's consciousness to dynamically perceive the sounds and images from the perspective of the Threefold Contemplation for self-liberating. Furthermore, in this research, Gilles Deleuze's theoretical structure of images is adopted to discuss the individual perceptions constructed dynamically through the interaction among various elements and karma during an individual's life. However, the deceased should realize the common perception of Buddha nature, which is constructed in Buddhist doctrines and has the effect of destroying the individual perceptions, and the mind's journey to the Pure Land. [ABSTRACT FROM AUTHOR]

Epithelial-to-mesenchymal transition (EMT) plays a significant role in cancer metastasis. A series of models have focused on EMT regulation by TGF-β network. However, how EMT is regulated under hypoxia is less understood. We developed a model of HIF-1α network to explore the potential link between EMT and the network topology. Our results revealed that three positive feedback loops, composed of HIF-1α and its three targets SNAIL, TWIST, and miR-210, should be sequentially activated to induce EMT under aggravating hypoxia. We suggested that the number of the positive feedback loops is critical for determining the number of stable states in EMT. Our work may advance the understanding of the significance of network topology in the regulation of EMT. [ABSTRACT FROM AUTHOR]

Ternary logic device technologies have been actively researched due to the potential benefits such as lower power consumption, smaller device count, smaller area, and higher data processing density, compared to their binary counterparts. In this work, scaling prospect of ZnO stacked nanosheet channel ternary field effect transistor has been investigated. The benefits of scaling geometric parameters such as gate dielectric thickness, channel length, and source/drain charge injection area are examined. 90 % lower power consumption in the intermediate state is achieved at Vdd = 1 V with a noise margin of 130 mV, compared to other emerging ternary logic devices. The feasibility for stable ternary circuit operation is confirmed as well. [ABSTRACT FROM AUTHOR]

The article analyzes Old Testament terminologies and descriptions concerning the so-called "Intermediate State", the realm where the souls of the dead remain after their bodies are placed in the tomb. Such descriptions and terminologies are limited when compared to certain New Testament passages, like the Parable of the Rich man and Lazarus. However, they show that the souls remain in a state of consciousness, in the Place of the Dead, or Sheol, where they occupy distinct and separate positions, according to the results of their lives, namely, a situation of comfort (the righteous) or punishment (the unrighteous). There are no descriptions in the Old Testament suggesting that the souls of the saved are up in the heavens, in eternal glory. Nevertheless, they find themselves in a state of bliss, waiting for the resurrection, when they finally will experience perfect glory. [ABSTRACT FROM AUTHOR]

This study aimed to explore and describe existential experiences after cancer treatment. An exploratory phenomenological hermeneutical design was used following in-depth interviews with 21 people. The study revealed experiences of multifaceted suffering in the form of limitations in everyday life, inner struggles, and bearing the burden alone. Existential suffering after cancer treatment was revealed as like being in a process of transition, in an intermediate state, as moving between suffering and enduring, and alternating between alienworld and homeworld. A new and broader professional perspective is needed to establish rehabilitation services based on multifaceted experiences of suffering. This means a shift in focus from biomedical symptoms towards understanding of existential meaning for the person. [ABSTRACT FROM AUTHOR]

Nanopore sensing is a label-free single-molecule technique that enables the study of the dynamical structural properties of proteins. Here, we detect the translocation of cytochrome c (Cyt c ) through an asymmetric thin nanopore with photothermal heating to evaluate the influence of temperature on Cyt c conformation during its translocation in an electric field. Before Cyt c translocates through an asymmetric thin SiN x nanopore, ∼1 ms trapping events occur due to electric field-induced denaturation. These trapping events were corroborated by a control analysis with a transmission electron microscopy-drilled pore and denaturant buffer. Cyt c translocation events exhibited markedly greater broad current blockade when the pores were photothermally heated. Collectively, our molecular dynamics simulation predicted that an increased temperature facilitates denaturation of the α-helical structure of Cyt c , resulting in greater blockade current during Cyt c trapping. Our photothermal heating method can be used to study the influence of temperature on protein conformation at the single-molecule level in a label-free manner.

In this study, the physical states of cellulose in 1-allyl-3-methylimidazolium chloride (AmimCl) were analyzed via rheological observations under three different conditions: namely, steady state, small amplitude oscillatory shear, and large amplitude oscillatory shear conditions. The physical state of the solution changed from an isotropic phase to a gel structure via a liquid crystalline (LC) phase as the concentration increased. The rheological analysis showed that the 16 wt% solution was physically gelled in the anisotropic phase. This instantaneous gelation at the LC phase markedly enhanced the mechanical performance of the film obtained from the solution. This study provides a fundamental strategy for significant improvement in the mechanical properties of cellulose fibers or films. [ABSTRACT FROM AUTHOR]

Background and Aim Acquired Immunodeficiency Syndrome (AIDS) caused by Human Immunodeficiency Virus (HIV), is a chronic and potentially life-threatening disease. Numerous factors affect its development and progression. Therefore, the present study attempted to identify characteristics impacting the prognosis and progression of AIDS using multistate models. Methods & Materials The present retrospective study consisted of 2185 patients affected with HIV referring to Behavioral Disease Counseling Centers in Tehran City, Iran, from 2004 to 2013. We considered multiple states of AIDS, tuberculosis, and tuberculosis/AIDS in the natural history of the disease (from the onset of HIV disease until death occurred). Then, we applied the multistate models, to examine the effect of contextual demographic and clinical variables on survival time; subsequently, the transition probabilities of HIV. Ethical Considerations This study was approved by the Research Ethics Committee of Hamadan University of Medical Sciences (Code: IR.UMSHA.REC.1396.117). Results HIV-Related deaths in individuals with an incarnation history were 2.40 times higher than in those without the prison history. Death risk was also 1.70 and 1.80 times higher in those aged 25-44 and 44 years, respectively, compared to the individuals aged less than 25 years. An inverse relationship was also found between CD4 levels and the risk of death in our participants. Conclusion Antiretroviral therapy, CD4 count, age, and history of imprisonment were the main factors in the progression of the disease and subsequent death in HIV patients. Thus, preventing the further spread of the disease to the community and controlling the disease in the patients requires targeted educational and therapeutic interventions; accordingly, the community will be familiarized with transmission routes and the preventing principle of disease. Furthermore, we can encourage patients to visit the healthcare centers early. [ABSTRACT FROM AUTHOR]

Abstract Introduction Accumulation of vascular smooth muscle cells (VSMCs) within the neointimal region is a hallmark of atherosclerosis and vessel injury. Evidence has shown that Sca-1-positive (Sca-1+) progenitor cells residing in the vascular adventitia play a crucial role in VSMC assemblages and intimal lesions. However, the underlying mechanisms, especially in the circumstances of vascular injury, remain unknown. Methods and results The neointimal formation model in rats was established by carotid artery balloon injury using a 2F-Forgaty catheter. Most Sca-1+ cells first appeared at the adventitia of the vascular wall. S100B expressions were highest within the adventitia on the first day after vessel injury. Along with the sequentially increasing trend of S100B expression in the intima, media, and adventitia, respectively, the numbers of Sca-1+ cells were prominently increased at the media or neointima during the time course of neointimal formation. Furthermore, the Sca-1+ cells were markedly increased in the tunica media on the third day of vessel injury, SDF-1α expressions were obviously increased, and SDF-1α levels and Sca-1+ cells were almost synchronously increased within the neointima on the seventh day of vessel injury. These effects could effectually be reversed by knockdown of S100B by shRNA, RAGE inhibitor (SPF-ZM1), or CXCR4 blocker (AMD3100), indicating that migration of Sca-1+ cells from the adventitia into the neointima was associated with S100B/RAGE and SDF-1α/CXCR4. More importantly, the intermediate state of double-positive Sca-1+ and α-SMA cells was first found in the neointima of injured arteries, which could be substantially abrogated by using shRNA for S100B or blockade of CXCR4. S100B dose-dependently regulated SDF-1α expressions in VSMCs by activating PI3K/AKT and NF-κB, which were markedly abolished by PI3K/AKT inhibitor wortmannin and enhanced by p65 blocker PDTC. Furthermore, S100B was involved in human umbilical cord-derived Sca-1+ progenitor cells’ differentiation into VSMCs, especially in maintaining the intermediate state of double-positive Sca-1+ and α-SMA. Conclusions S100B triggered neointimal formation in rat injured arteries by maintaining the intermediate state of double-positive Sca-1+ progenitor and VSMCs, which were associated with direct activation of RAGE by S100B and indirect induction of SDF-1α by activating PI3K/AKT and NF-κB.

In this paper, I propose to imagine, through Non–Cartesian substance dualism (NCSD), how we could resurrect. Even though many objections have been addressed to the classic conception of eschatology since the beginning of the century of eschatology, I propose we have some reasons to think that a more corporeal conception of the eschaton is not only desirable but also metaphysically possible and compatible with biblical data. I shall explore what I call the Christ Body Argument, which invites us to reject, on the one hand, a disembodied existence in heaven, and on the other side to adopt a corporeal existence of Christ in heaven. A kind of Dualism, and more precisely, one possessing NCSD’s virtues, could play a role in exploring this new theological option. I expect to show that NCSD is a metaphysical option allowing us to understand better what we are. If we hope and believe in the resurrection of the dead, NCSD provides an interesting model to think about it.

Purpose This study aimed to explore and describe existential experiences after cancer treatment. Method An exploratory phenomenological hermeneutical design was used following in-depth interviews with 21 people. Results The study revealed experiences of multifaceted suffering in the form of limitations in everyday life, inner struggles, and bearing the burden alone. Conclusions Existential suffering after cancer treatment was revealed as like being in a process of transition, in an intermediate state, as moving between suffering and enduring, and alternating between alienworld and homeworld. A new and broader professional perspective is needed to establish rehabilitation services based on multifaceted experiences of suffering. This means a shift in focus from biomedical symptoms towards understanding of existential meaning for the person.

Oligopeptidase B (OPB) is the least studied group from the prolyl oligopeptidase family. OPBs are found in bacteria and parasitic protozoa and represent pathogenesis factors of the corresponding infections. OPBs consist of two domains connected by a hinge region and have the characteristics of conformational dynamics, which include two types of movements: the bridging/separation of α/β-hydrolase catalytic and β-propeller-regulatory domains and the movement of a loop carrying catalytic histidine, which regulates an assembly/disassembly of the catalytic triad. In this work, an elucidation of the interdomain dynamics of OPB from Serratia proteamaculans (SpOPB) with and without modification of the hinge region was performed using a combination of X-ray diffraction analysis and small-angle X-ray scattering, which was complemented with an essential dynamics sampling (EDS) simulation. The first crystal structure of catalytically deficient SpOPB (SpOPBS532A) with an intact hinge sequence is reported. Similarly to SpOPB with modified hinges, SpOPBS532A was crystallized in the presence of spermine and adopted an intermediate conformation in the crystal lattice. Despite the similarity of the crystal structures, a difference in the catalytic triad residue arrangement was detected, which explained the inhibitory effect of the hinge modification. The SpOPBS532A structure reconstituted to the wild-type form was used as a starting point to the classical MD followed by EDS simulation, which allowed us to simulate the domain separation and the transition of the enzyme from the intermediate to open conformation. The obtained open state model was in good agreement with the experimental SAXS data.

The renewal of Eschatology has been an ecumenical process that began at the end of the 19th century and continues to the present day. It is marked by a more precise expression of what Christian revelation really demonstrates in this regard. Also, it encourages an in-depth knowledge of the history of Theology, in order to be enriched with its values and not to dwell on deficiencies already verified in the past. This article has three aims: (1) to provide an overview of the anthropological elements upon which Aquinas based his Eschatology; (2) to summarize the main features of the Eschatology he wrote in the last decade of his life; (3) in the light of Aquinas' insight, to introduce the analogy of mutilation as a tool for a better understanding of the intermediate state. The conclusion identifies the values and deficiencies of the Eschatology of the mature Thomas Aquinas. [ABSTRACT FROM AUTHOR]

Modern medical technology has transformed the way people live and the way they die. Today, in some instances the process of dying takes longer, due to more advanced medical treatment and therefore requires more sophisticated care than before. This contributes to the fact that terminally ill people are wrestling with the reality of death. This article endeavours to investigate the phenomenon of death from a biblical perspective and specifically attempts to answer questions such as ‘What is death?’, ‘Is there an intermediate state?’, and ‘What is “heaven” like?’ The article is written in such a way that it equips therapists with biblical information which can clearly be communicated to terminally ill Christian believers to assist them in coping with their trauma and uncertainties; it also intends to remove the sting of death and obtain more clarity on an existence beyond death.

The importance of accounting for the inhomogeneity of the magnetic field distribution and roundness of domain walls near the surface of type-I superconductors in the intermediate state for forming the equilibrium flux structure was predicted by Landau eight decades ago. Further studies confirmed this prediction and extended it to all equilibrium properties of this state. Here we report on direct depth-resolved measurements of the field distribution and shape of domains near the surface of high-purity type-I (indium) films in a perpendicular field using Low-Energy Muon Spin Rotation spectroscopy. We find that at low applied fields (in about half of the field range of the intermediate state) the field distribution and domains' shape agrees with that proposed by Tinkham. However, for high fields our data suggest that reality differs from theoretical expectations. In particular, the width of the superconducting laminae can expand near the surface leading to formation of a maximum in the static magnetic field in the current-free space outside the sample. A possible interpretation of these experimental results is discussed. [ABSTRACT FROM AUTHOR]

Food safety and risks are urgent issues in the process of Chinese society’s life transition from “stuffed” (Chi bao) to “satisfying” (Chi hao). There are quite a few Christians in the field of ecological agriculture that produces safe and healthy food. This article mainly discusses the ethical practice based on faith: whether it is possible and how to solve the problem of using fake and shoddy production to mix the real ones in the process of safe and healthy food production; whether there is any possibility and how to break the “Titanic” phenomenon in the distribution of food during the process of food distribution. This article discovers and refines the “intermediate state of ethical practice” in the field work of four farms and one platform, in order to promote and supplement the recognition and understanding of ethical practice itself. Through the observation of the “intermediate state of ethical practice”, we can truly understand the meaning of Max Weber’s discussion of the possible and impossible ethical practice. [ABSTRACT FROM AUTHOR]

Due to increase in load demand the use of distributed generation has been increased in the distribution system. Voltage profile as well as voltage security state of the distribution system can be improved by incorporating Distributed Generator (DG) of particular sizes at specific locations. In this article, modified spider monkey optimization (MSMO) technique has been proposed for finding out the optimal size and location of DGs to improve stability of the network. This method is a modification of recently developed swarm intelligent technique called spider monkey optimization (SMO) technique. Here minimization of voltage deviation is considered as objective function. The performance of MSMO technique has been tested on IEEE 33 bus, IEEE 69 bus, and Indian 85 bus practical radial distribution system. The results obtained by MSMO-based technique are compared with the results of other existing methods, which show that MSMO algorithm outperforms other standard optimization techniques in terms of voltage profile improvement of the system which proves the efficiency of the proposed method. MSMO-based DG insertion also enhances voltage security state of the system. [ABSTRACT FROM AUTHOR]

In this work, density functional theory calculations in the framework of local density approximation (LDA) are performed using the Siesta software package in order to theoretically predict the phase transition mechanism and electronic properties of lead telluride (PbTe) under high hydrostatic pressure. PbTe undergoes a structural phase transformation from the cubic NaCl-type structure (B1) belongs to Fm 3 ¯ m space group to another cubic CsCl-type structure (B2) belongs to Pm 3 ¯ m space group with the influence of external pressure through the simulations. According to simulation results, we suggest a phase transition mechanism having four intermediate states with space groups of P 1 ¯ , C 2 / m , R 3 ¯ m and Cmmm. [ABSTRACT FROM AUTHOR]

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Medium states are common anomalies in spin-transfer torque magnetoresistance random access memory (STT-MRAM). In this work, these medium states are systematically studied using an ultrafast characterization system and compared with the normal parallel (P) and antiparallel (AP) states. The medium states that exist in the switching processes both from the AP state to the P state (AP2P) and from the P state to the AP state (P2AP) are presented. To obtain a deeper understanding of the medium states, the temperature and voltage dependences of the state rates are investigated. It is found that the medium states are more persistent at low temperatures and have a state rate with a symmetric voltage dependence. Consequently, it is confirmed that medium states should be one of the sources of bifurcated switching in STT-MRAMs. [ABSTRACT FROM AUTHOR]

Kinesin dimer walks processively along a microtubule (MT) protofilament in a hand‐over‐hand manner, transiting alternately between one‐head‐bound (1HB) and two‐heads‐bound (2HB) states. In 1HB state, one head bound by adenosine diphosphate (ADP) is detached from MT and the other head is bound to MT. Here, using all‐atom molecular dynamics simulations we determined the position and orientation of the detached ADP‐head relative to the MT‐bound head in 1HB state. We showed that in 1HB state when the MT‐bound head is in ADP or nucleotide‐free state, with its neck linker being undocked, the detached ADP‐head and the MT‐bound head have the high binding energy, and after adenosine triphosphate (ATP) binds to the MT‐bound head, with its neck linker being docked, the binding energy between the two heads is reduced greatly. These results reveal how the kinesin dimer retains 1HB state before ATP binding and how the dimer transits from 1HB to 2HB state after ATP binding. Key residues involved in the head‐head interaction in 1HB state were identified. [ABSTRACT FROM AUTHOR]

Modern medical technology has transformed the way people live and the way they die. Today, in some instances the process of dying takes longer, due to more advanced medical treatment and therefore requires more sophisticated care than before. This contributes to the fact that terminally ill people are wrestling with the reality of death. This article endeavours to investigate the phenomenon of death from a biblical perspective and specifically attempts to answer questions such as 'What is death?', 'Is there an intermediate state?', and 'What is "heaven" like?' The article is written in such a way that it equips therapists with biblical information which can clearly be communicated to terminally ill Christian believers to assist them in coping with their trauma and uncertainties; it also intends to remove the sting of death and obtain more clarity on an existence beyond death. [ABSTRACT FROM AUTHOR]