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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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Abstract Peptidoglycan (PG) is the main constituent of the bacterial cell wall. The enzyme UDP‑ N ‑acetylglucosamine enolpyruvyl transferase (MurA) catalyzes the transfer of enolpyruvate from phosphoenolpyruvate to uridinediphospho‑ N ‑acetylglucosamine, which is the first committed step of PG biosynthesis. In this study, we have systematically examined the urea-induced unfolding of Acinetobacter baumannii MurA (AbMurA) using various optical spectroscopic techniques and molecular dynamics (MD) simulations. The urea-induced unfolding of AbMurA was a three-state process, where a metastable intermediate conformation state is populated between 3.0 and 4.0 M. Above 6.0 M urea, AbMurA gets completely unfolded. The transition from the native structure to the partially unfolded metastable state involves ~30% loss of native contacts but little change in the radius of gyration or core hydration properties. The intermediate-to-unfolded state transition was characterized by a large increase in the radius of gyration. MD trajectories simulated in different unfolding conditions suggest that urea destabilizes AbMurA structure weakening hydrophobic interactions and the hydrogen bond network. We observed a clear correlation between both in vitro and in silico studies. To our knowledge, this is also the first report on unfolding/stability analysis of any MurA enzyme. Highlights • Urea-induced unfolding of AbMurA were examined using spectroscopic techniques and MD simulations. • Unfolding of AbMurA was a three-state process, with the presence of a metastable intermediate conformation state. • Transition from the native-to-metastable state involves ~30% loss of native contacts but little change in the radius of gyration. • Intermediate-to-unfolded state transition was characterized by a large increase in the radius of gyration. • Urea destabilizes AbMurA structure by weakening hydrophobic interactions and the hydrogen bond network. [ABSTRACT FROM AUTHOR]

Abstract CaS crystallizes in cubic NaCl (B1) type structure with symmetry Fm 3 ¯ m. In this work, the structural and electronic properties of CaS were investigated by considering the Density Functional calculations within the framework of Generalized Gradient Approximation (GGA) under high pressure. The structural change was found at the B1 type structure of CaS. B1 type structure transformed into another cubic CsCl (B2) type structure with symmetry Pm 3 ¯ m at 36.6 GPa. An intermediate state with symmetry R 3 ¯ m was predicted during this transition. Besides, the effects of the pressure on the electronic properties of CaS were also studied. Both the B1 and B2 type structures exhibited semiconducting behaviors with direct band gaps at the Γ -point and R -point, respectively. Intermediate state was searched during this phase change first time in detail. The obtained results were compared with experimental and theoretical ones in the literature. Graphical abstract Image 1 Highlights • Pressure-induced change in CaS under hydrostatic conditions are presented. • The cubic NaCl-type (B1) structure of CaS transformed to the another cubic CsCl-type (B2) structure at 36.6 GPa. • An intermediate state for B 1 → B 2 transition is firstly predicted in this study. • The electronic properties for the B1 and B2-type structures of CaS are calculated. [ABSTRACT FROM AUTHOR]

Highly sensitive and selective Fe-based gas sensors have been developed by intermediate state nanocomposites where Quasi-Amorphous Intermediate Phase (QUAIPH) and α-Fe 2 O 3 co-exist converting from fusiform β-FeOOH. TGA, SEM, TEM, XRD, FTIR, BET and XPS have been used to characterize the intermediate state nanocomposites. Experiment results reveal that the highest gas sensing performance towards n-butanol can be found when the fusiform β-FeOOH was calcined at 250 °C for one-hour, in which crystalline α-Fe 2 O 3 and QUAIPH co-exist. The highest response towards 100 ppm n-butanol is 145 which is the highest one for alcohols detection comparing with the reported α-Fe 2 O 3 based gas sensors. Besides, the intermediate state nanocomposites also exhibit high selectivity to n-butanol among common VOCs. At last, the sensing mechanism has been speculated, in which the structural hydroxyls may enrich the alcohols on the surface of the nanocomposites and prominently increase the response and selectivity. [ABSTRACT FROM AUTHOR]

Studying the effect of cysteine bridges on different energy levels of multistage folding proteins will enable a better understanding of the process of folding and functioning of globular proteins. In particular, it will create prospects for directed change in the stability and rate of protein folding. In this work, using the method of differential scanning microcalorimetry, we have studied the effect of three cysteine bridges introduced in different structural elements of the green fluorescent protein on the denaturation enthalpies, activation energies, and heat-capacity increments when this protein passes from native to intermediate and transition states. The studies have allowed us to confirm that, with this protein denaturation, the process hardly damages the structure initially, but then changes occur in the protein structure in the region of 4-6 beta sheets. The cysteine bridge introduced in this region decreases the hydration of the second transition state and increases the hydration of the second intermediate state during the thermal denaturation of the green fluorescent protein. [ABSTRACT FROM AUTHOR]

This article deals with the issue which handled the Christian eschatological debate in the twentieth century: the intermediate state. Belief in the existence of the intermediate state, while postmortal situation which exists between death and resurrection, is part of the Catholic theological heritage, Lutheran and Eastern churches. However, some protestant theologians and Catholics of the twentieth century criticized the intermediate eschatology (intermediate state, purgatory, the existence of a separate soul from the body etc.) because understood it as the result of a hellenization of the Christian faith. Thus, with the aim of purifying the Christian faith hellenization and restore its biblical roots ended up defending the reduction of eschatological events at the time of death (resurrection, parousia, judgment, etc.). This thesis raised for lack of biblical foundation and the theological tradition, the critical reaction of some theologians and documents of the Catholic Church. In the basement of this eschatological debate is an indispensable element for theology: the existence of a spiritual principle, which ensures continuity and identity between the subject of historical existence and the final, which subsists between death and resurrection. [ABSTRACT FROM AUTHOR]

Several research teams have reported detection and characterization of various apomyoglobin intermediate states different in their accumulation mode, thus putting a natural question as to proportions of these intermediates. The current report presents spectral properties of sperm whale apomyoglobin studied over a wide range of conditions with the use of circular dichroism and fluorescence techniques. Based on the experimental data, a diagram of apomyoglobin conformational states has been constructed. It shows that though induced by various denaturants, all the observed intermediates belong to one and the same area in the diagram. [ABSTRACT FROM AUTHOR]

This paper investigated the intermediate states and the structure evolution of the dislocation in graphene when it falls freely from the saddle point of the energy landscape. TheO-type dislocation, an unstable equilibrium structure located at the saddle point, is obtained from the lattice theory of the dislocation structure and improved by theabinitiocalculation to take the buckling into account. Intermediate states along the kinetics path in the falling process are obtained from theabinitiosimulation. Once the dislocation falls from the saddle point to the energy valley, thisO-type dislocation transforms into the stable structure that is referred to as theB-type dislocation, and in the meantime, it moves a distance that equals half a Burgers vector. The structure evolution and the energy variation in the free-falling process are revealed explicitly. It is observed that rather than smooth change, a platform manifests itself in the energy curve. The unusual behaviour in the energy curve is mainly originated from symmetry breaking and bond formation in the dislocation core. The results can provide deep insight in the mechanism of the brittle feature of covalent materials. [ABSTRACT FROM PUBLISHER]

Typically, Christian theology includes an understanding of human afterlife consisting of two stages. The first is a disembodied existence as an immaterial being in the time between death and resurrection. Normally, it's affirmed that some disembodied humans go to Heaven/Paradise between one's death and resurrection; this is a state I call The Intermediate State. The second stage is the bodily resurrection. In this paper, I focus on The Intermediate State. Though the majority of the Christian tradition affirms it, I think it's mistaken. To show two reasons why, I argue that a traditional metaphysics of human persons deployed to explicate The Intermediate State brings with it one or the other of at least two untoward consequences for Christian theology. [ABSTRACT FROM AUTHOR]

Advances in the study of Paul's anthropology during the past century have been limited, particularly because of dominant theological approaches that leave many unresolved issues regarding the apostle's understanding of humans. This article introduces a new approach, which grounds Paul's anthropological discourse in eschatology, and underscores the importance of transformation. Through the application of this new approach, the esō anthrōpos, instantiated in believers through the Holy Spirit, is shown to be the locus of renewal, and to encompass the entire human. A clear understanding of this concept provides support for the postulation of an intermediate state in Paul's symbolic universe, a claim that is contested by many scholars. [ABSTRACT FROM AUTHOR]

The translocation of tRNAs coupled with mRNA in the ribosome is a critical process in the elongation cycle of protein synthesis. The translocation entails large-scale conformational changes of the ribosome and involves several intermediate states with tRNAs in different positions with respect to 30S and 50S ribosomal subunits. However, the detailed role of the intermediate states is unknown and the detailed mechanism and pathway of translocation is unclear. Here based on previous structural, biochemical and single-molecule data we present a translocation pathway by incorporating several intermediate states. With the pathway, we study theoretically (i) the kinetics of 30S head rotation associated with translocation catalyzed by wild-type EF-G, (ii) the dynamics of fluctuations between different tRNA states during translocation interfered with EF-G mutants and translocation-specific antibiotics, (iii) the kinetics of tRNA movement in 50S subunit and mRNA movement in 30S subunit in the presence of wild-type EF-G, EF-G mutants and translocation-specific antibiotics, (iv) the dynamics of EF-G sampling to the ribosome during translocation, etc., providing consistent and quantitative explanations of various available biochemical and single-molecule experimental data published in the literature. Moreover, we study the kinetics of 30S head rotation in the presence of EF-G mutants, providing predicted results. These have significant implications for the molecular mechanism and pathway of ribosomal translocation. [ABSTRACT FROM AUTHOR]

Plant aldo-keto reductases of the AKR4C subfamily play key roles during stress and are attractive targets for developing stress-tolerant crops. However, these AKR4Cs show little to no activity with previously-envisioned sugar substrates. We hypothesized a structural basis for the distinctive cofactor binding and substrate specificity of these plant enzymes. To test this, we solved the crystal structure of a novel AKR4C subfamily member, the AKR4C7 from maize, in the apo form and in complex with NADP + . The binary complex revealed an intermediate state of cofactor binding that preceded closure of Loop B, and also indicated that conformational changes upon substrate binding are required to induce a catalytically-favorable conformation of the active-site pocket. Comparative structural analyses of homologues (AKR1B1, AKR4C8 and AKR4C9) showed that evolutionary redesign of plant AKR4Cs weakened interactions that stabilize the closed conformation of Loop B. This in turn decreased cofactor affinity and altered configuration of the substrate-binding site. We propose that these structural modifications contribute to impairment of sugar reductase activity in favor of other substrates in the plant AKR4C subgroup, and that catalysis involves a three-step process relevant to other AKRs. [ABSTRACT FROM AUTHOR]

In this paper, we analyzed the process of decay within QCD factorization (QCDF) and final state interaction (FSI) effects. At first, the decay is calculated via QCDF approach. The result that is found by using the QCDF method is less than the experimental result. Then we considered FSI effect as a sizable correction where there are the intermediate state mesons via the exchange of . The experi mental branching ratio of decay is , and our results by QCDF and FSI are and , respectively. [ABSTRACT FROM AUTHOR]

The intermediate state (IS) of a type-I superconductor is characterized by coexistence of Meissner phase and normal conducting phase. Experiments on the topology of the IS show a variety of universal domain patterns which are also seen in various other physical, chemical or even biological systems on various length and time scales. The possibility to easily tune the domain structure of the IS by a variation of magnetic field or temperature ideally qualifies type-I superconductors as general model systems for the investigation of domain nucleation and distribution. However, the experimental observation of the IS domain structure was up to now restricted to either thin films or surfaces. We demonstrate how neutron grating interferometry (nGI) probes the IS domain distribution in the interior of a bulk single-crystalline lead sample. By means of nGI, we are able to visualize the field penetration process into the superconductor as well as the hysteretic behavior of the intermediate state morphology. Finally, the impact of nGI for investigations on bulk domain nucleation is discussed, as this technique is applicable on many other systems that reveal a phase separation on a micrometer length scale. [ABSTRACT FROM AUTHOR]

Tobacco etch virus protease (TEVp) is widely used to remove fusion tags from recombinant proteins because of its high and unique specificity. This work describes the conformational and the thermodynamic properties in the unfolding/refolding process of TEVp 3M (three-point mutant: L56V/S135G/S219V) induced by temperature. With temperature increasing from 20 to 100 °C, the CD spectra showed a transition trend from α-helix to β-sheet, and the fluorescence emission, synchronous fluorescence, ANS and RLS spectroscopy consistently revealed that the temperature-induced unfolding process behaved in a three-state manner, for there was a relatively stable intermediate state observed around 50 °C. The reversibility of thermal unfolding of TEVp 3M further showed that the transition from the native to the intermediate state was reversible (below 50 °C), however the transition from the intermediate to the unfolded state was irreversible (above 60 °C). Moreover, aggregates were observed above 60 °C as revealed by SDS–PAGE, Thioflavin-T fluorescence and Congo red absorbance. [ABSTRACT FROM AUTHOR]

Prions are responsible for a heterogeneous group of fatal neurodegenerative diseases, involving post-translational modifications of the cellular prion protein. Epidemiological studies on Creutzfeldt-Jakob disease, a prototype prion disorder, show a majority of cases being sporadic, while the remaining occurrences are either genetic or iatrogenic. The molecular mechanisms by which PrP C is converted into its pathological isoform have not yet been established. While point mutations and seeds trigger the protein to cross the energy barriers, thus causing genetic and infectious transmissible spongiform encephalopathies, respectively, the mechanism responsible for sporadic forms remains unclear. Since prion diseases are protein-misfolding disorders, we investigated prion protein folding and stability as functions of different milieus. Using spectroscopic techniques and atomistic simulations, we dissected the contribution of major structural determinants, also defining the energy landscape of prion protein. In particular, we elucidated (i) the essential role of the octapeptide region in prion protein folding and stability, (ii) the presence of a very enthalpically stable intermediate in prion-susceptible species, and (iii) the role of the disulfide bridge in prion protein folding. [ABSTRACT FROM AUTHOR]

The intermediate state in a type-1 superconducting Pb film is studied by using the scanning Hall probe microscopy, which shows quantized flux tubes with distinct flux density. The vorticity of flux tubes are quantified using the monopole model. It is found that the vorticity of the flux tubes can be tuned by using flux expulsion process under different magnetic field and temperatures. The stability of stipe patterns at high fields is studied with new stripe patterns formed after shaking with ah ac field. No flux tube is observed even after shaking with intense ac fields. All the results suggests the stripe patterns have very close energy, which is much favorable than the flux tube state. [ABSTRACT FROM AUTHOR]

[Display omitted] • Anthrax protective antigen (PA) assembles into oligomeric prepores. • PA prepores mature to conformationally distinct pores upon acidification. • D425A PA mutation stalls pH-induced pore maturation at an intermediate state. • D425A intermediate complex shares features of wild type prepore and pore. • pH-induced changes of PA pore maturation are asymmetric. The tripartite protein complex produced by anthrax bacteria (Bacillus anthracis) is a member of the AB family of β-barrel pore-forming toxins. The protective antigen (PA) component forms an oligomeric prepore that assembles on the host cell surface and serves as a scaffold for binding of lethal and edema factors. Following endocytosis, the acidic environment of the late endosome triggers a pH-induced conformational rearrangement to promote maturation of the PA prepore to a functional, membrane spanning pore that facilitates delivery of lethal and edema factors to the cytosol of the infected host. Here, we show that the dominant-negative D425A mutant of PA stalls anthrax pore maturation in an intermediate state at acidic pH. Our 2.7 Å cryo-EM structure of the intermediate state reveals structural rearrangements that involve constriction of the oligomeric pore combined with an intramolecular dissociation of the pore-forming module. In addition to defining the early stages of anthrax pore maturation, the structure identifies asymmetric conformational changes in the oligomeric pore that are influenced by the precise configuration of adjacent protomers. [ABSTRACT FROM AUTHOR]

• Urea-induced conformational changes in F. gigantica MDH were studied using spectroscopic methods and MD simulations. • Non-superimposable Trp fluorescence and far-UV CD curves indicate a partially folded intermediate state. • Unfolding of tertiary structure preceded the secondary structure, linked to loss of enzyme activity. • Intermediate state destabilized due to disrupted hydrogen-bond networks and hydrophobic interactions. • Strong correlation was observed between the data obtained from in-vitro and in-silico approaches. Malate dehydrogenase enzyme plays an essential role in energy metabolism in all eukaryotes. It catalyzes the interconversion of malate to oxaloacetate, producing NAD+/NADH. In the current study, we monitored the urea-induced conformational changes in Fasciola gigantica malate dehydrogenase (FgMDH) structure using multiple spectroscopic techniques combined with all-atom molecular dynamics (MD) simulations. FgMDH showed a two-state cooperative unfolding revealed by intrinsic tryptophan (Trp) fluorescence and CD spectroscopy; however, their non-superimposable curves indicate a partially folded intermediate state formation. The study showed that the unfolding of tertiary structures preceded the secondary structure unfolding. The binding of the fluorescence probe 1-anilino-8-naphthalene sulfonate (ANS) at 1.5 M urea confirmed stabilization of the intermediate state. The free energy of stabilization determined from Trp fluorescence and CD spectroscopy were 11.4 and 13.2 kcal.mol−1, respectively. The loss of enzymatic activity was observed before any significant loss in structural components. This suggested that low urea concentrations induce minor structural changes in the substrate or cofactor binding site leading to activity loss. Quenching of fluorescence intensity also provides information on unfolding and activity loss. MD simulations confirmed that FgMDH formed an intermediate state at 1.5 M urea at 300 K, which destabilized at higher urea concentration and temperature due to disrupted hydrogen-bond networks and hydrophobic interactions. We conclude that a partially folded metastable state is stabilized during the unfolding of cytosolic FgMDH. A strong correlation was observed between the data obtained from in-vitro and in-silico approaches. [ABSTRACT FROM AUTHOR]

Carl Schmitt emphatically rejected intermediate formations between peace and war. Analysing Schmitt's oscillation between the domestic and the international, the article suggests that the notion of ‘intermediate state’ provides a vital route to the core of Schmitt's political theory. The concept emerges in Schmitt's analysis of the Rhineland crisis, recurs in his vehement critique of Weimar pluralism, and, finally, reappears in his theory of modern war from the Third Reich to the Cold War. ‘Intermediate state’ has both qualitative and temporal aspects; it connotes not only categorical confusion and impurity but also instability and limited duration. Despite his criticism, Schmitt himself utilised the ambiguity, polysemy, and normative ambivalence of the intermediate state in his argumentation, finally giving it an open theological reinterpretation in his later work. Schmitt's theory of political conflict, consequently, is problematically bound to the vague intermediate state of perpetual conflict that he sought to avoid, and to the metaphorical aspects of the notion of battle that he explicitly rejected. [ABSTRACT FROM PUBLISHER]

Abstract: γ-glutamyltranspeptidases (γ-GTs) are ubiquitous enzymes that catalyze the hydrolysis of γ-glutamyl bonds in glutathione and glutamine and the transfer of the released γ-glutamyl group to amino acids or short peptides. These enzymes are generally synthesized as precursor proteins, which undergo an intra-molecular autocatalytic cleavage yielding a large and a small subunit. In this study, circular dichroism and intrinsic fluorescence measurements have been used to investigate the structural features and the temperature- and guanidinium hydrochloride (GdnHCl)-induced unfolding of the mature form of the γ-GT from Geobacillus thermodenitrificans (GthGT) and that of its T353A mutant, which represents a mimic of the precursor protein. Data indicate that a) the mutant and the mature GthGT have a different secondary structure content and a slightly different exposure of hydrophobic regions, b) the thermal unfolding processes of both GthGT forms occur through a three-state model, characterized by a stable intermediate species, whereas chemical denaturations proceed through a single transition, c) both GthGT forms exhibit remarkable stability against temperature, but they do not display a strong resistance to the denaturing action of GdnHCl. These findings suggest that electrostatic interactions significantly contribute to the protein stability and that both the precursor and the mature form of GthGT assume compact and stable conformations to resist to the extreme temperatures where G. thermodenidrificans lives. Owing to its thermostability and unique catalytic properties, GthGT is an excellent candidate to be used as a glutaminase in food industry. [Copyright &y& Elsevier]

We previously reported that the thermal unfolding of mouse lipocalin-type prostaglandin D synthase (L-PGDS) is a completely reversible process under acidic conditions and follows a three-state pathway, including an intermediate state (I) between native state (N) and unfolded state. In the present study, we investigated the intermediate state of mouse C65A L-PGDS and clarified the local conformational changes in the upper and bottom regions by using NMR and CD spectroscopy. The 1H-15N HSQC measurements revealed that the backbone conformation was disrupted in the upper region of the β-barrel at 45°C, which is around the Tm value for the N ↔ I transition, but that the signals of the residues located at the bottom region of L-PGDS remained at 54°C, where the maximum accumulation of the intermediate state was found. 1H-NMR and CD measurements showed that the Tm values obtained by monitoring Trp54 at the upper region and Trp43 at the bottom region of the β-barrel were 41.4 and 47.5°C, respectively, suggesting that the conformational change in the upper region occurred at a lower temperature than that in the bottom region. These findings demonstrate that the backbone conformation of the bottom region is still maintained in the intermediate state. [ABSTRACT FROM PUBLISHER]

To investigate the effect of C-terminal helix on the stability of the FF domain, we studied the native domain FF3-71 from human HYPA/FBP11 and the truncated version FF3-60 with C-terminal helix being deleted by molecular dynamics simulations with GROMACS package and GROMOS 43A1 force field. The results indicated that the structures of truncated version FF3-60 were evident different from those of native partner FF3-71. Compared with FF3-71, the FF3-60 lost some native contacts and exhibited some similar structural characters to those of intermediate state. The C-terminal helix played a major role in stabilizing the FF3-71 domain. To a certain degree, the FF domain had a tendency to form an intermediate state without the C-terminal helix. In our knowledge, this was the first study to examine the role of C-terminal helix of FF domain in detail by molecular dynamics simulations, which was useful to understand the three-state folding mechanism of the small FF domain. [ABSTRACT FROM AUTHOR]

Abstract: Thin films of type I superconductors of a thickness comparable or less than a flux penetration length behave like type II superconductors in a mixed state. With decreasing film thickness normal domains carrying a magnetic flux get smaller with smaller number of flux quanta per domain and finally transform into single quantum flux lines, i.e. quantum vortices similar to those found in type II superconductors. We give an evidence of this behavior from the measurements of the nonlinear response of a total magnetic moment to an applied AC magnetic field, directly from the temperature dependence of an AC susceptibility. [Copyright &y& Elsevier]

Abstract: Yeast enolase is stabilized by its natural cofactor Mg2+. This stabilization is ascribed to the reduced subunit dissociation of the holoprotein. Nevertheless, how Mg2+ alters the unfolding mechanism has yet to be fully characterized. Here, we investigate the role of Mg2+ in the denaturation mechanism and unfolding kinetics of yeast enolase. Apo-enolase unfolds through a three-state process (N2 ↔2I→2D). The intermediate species is described as a monomeric molten globule-like conformation that becomes noticeable in the presence of phosphate and is able to recover its native secondary structure when cooled down. Kinetic studies confirmed the presence of the intermediate species, even though it was not noticeable in the thermal scans. The cofactor increases the cooperativity of the unfolding transitions, while the intermediate species becomes less noticeable or nonexistent. Thus, holo-enolase follows a simple two-state mechanism (N2 →2D). Our results indicate smaller unfolding rate-constants in the presence of Mg2+, thus favoring the native state. The temperature dependence of the unfolding rates allowed us to calculate the activation enthalpies of denaturation. Interestingly, despite the different unfolding mechanisms of the apo and holo forms of enolase, they both have similar activation barriers of denaturation (185–190kJmol−1). [Copyright &y& Elsevier]

The multiphoton association reaction He + H → HeH in the electronic ground state is investigated using the time-dependent quantum wave packet method. It is shown that the collision pairs He + H in continuum state transfer into ν = 0 state and then produce stable molecules HeH through emission of two or three photons. The multiphoton transition takes place via intermediate states, and the transfer probability is determined by the collision energy and the intermediate states. The populations of the intermediate states and ν = 0 state can be controlled by the laser duration. The three-photon transition is more efficient than the two-photon transition for producing the molecule HeH in ν = 0 state. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011 [ABSTRACT FROM AUTHOR]

Many Christians who argue against Christian materialism direct their arguments against what I call 'Type-I materialism', the thesis that I cannot exist without my organic body. I distinguish Type-I materialism from Type-II materialism, which entails only that I cannot exist without some body that supports certain mental functions. I set out a version of Type-II materialism, and argue for its superiority to Type-I materialism in an age of science. Moreover, I show that Type-II materialism can accommodate Christian doctrines like the Resurrection of the Body, the Incarnation, and the 'intermediate state' (if there is one). [ABSTRACT FROM AUTHOR]

Abstract: Tissue deposition of fibrillar protein aggregates called amyloid is the root cause of several degenerative diseases. Thus identification of compounds which can prevent or reduce protein aggregation can serve as a potential therapeutic target. In the present study we have shown inhibitory effect of sodium tetrathionate toward Hen egg white lysozyme (HEWL) amyloidogenesis at pH 2.0. Our study reveals that without sulfonation, sodium tetrathionate prevents amyloid fibril progression. Moreover, it shows that formation of disulfide bonds rather than exposure of hydrophobic surface in protein plays a critical role in initiating fibrillation process. Inhibitory effect of reducing agent β-mercaptoethanol toward fibrillation process also confirms the involvement of disulfide bond in initiating HEWL amyloidogenesis. These results provide important information toward understanding key interactions that guide amyloidogenesis, which may facilitate development of potential therapeutics. [Copyright &y& Elsevier]

Abstract: Fibrillar protein aggregates called amyloids are the hallmark of several degenerative diseases. Identification of common drugs which are capable of blocking or inhibiting protein aggregation may be considered as one of the therapeutic approaches directed against amyloid diseases. The present study describes the effect of a few small molecule compounds like clotrimazole, sulconazole and rottlerin towards amyloidogenesis of two model proteins unrelated in terms of structure and sequence such as hen egg white lysozyme and cytochrome c to test promiscuity of amyloid inhibition. Amyloid progression was monitored through Thioflavin T assay and atomic force microscope imaging. Also, the thermodynamic basis of inhibition of fibrillogenesis was analyzed through equilibrium unfolding and unfolding kinetic studies of the proteins in presence of the compounds. Structural alterations in the aggregation-prone intermediate state conformation of the protein in presence of the compounds were monitored through 1-anilino-8-naphthalene sulfonate (ANS) binding studies. Our findings shed some light on the key interactions that guide the path towards protein aggregation and the probable structural and thermodynamic mechanism of inhibition which may provide useful guidelines in development of therapeutics against amyloid diseases. [Copyright &y& Elsevier]

Abstract: Superconducting Pb(x)/Au(25nm) bilayers (x =50, 100nm) patterned with antidot lattices exhibit various matching field anomalies depending on experimental conditions. Magnetization peaks at applied fields H = n[20Oe] (n =integer) resemble superconducting wire network data; cusps are also observed, consistent with predictions of “giant” vortices in low-kappa films. Sharp “staircase” anomalies spaced by 1–3Oe are observed in AC magnetization, possibly a result of depinning of intermediate state domains, or macroscopic quantum tunneling between reproducible states of different quantized flux. [ABSTRACT FROM AUTHOR]

The aim of this study was to understand the mechanisms that allow mSSC lines to be established from SSCs. Small, multilayer clumps of SSCs formed during two to four weeks of in vitro culture and were then transferred to MEF feeders. Small, round, monolayer colonies containing cells destined to convert to mSSCs, designated as intermediate state SSCs (iSSCs), first appeared after two to three passages. During an additional nine passages (47-54 days) under the same culture conditions, iSSCs slowly proliferated and maintained their morphology. Ultimately, a cell type with an ES-like morphology (mSSC) appeared from the iSSC colonies, and two mSSC cell lines were established. The mSSCs had a high proliferative potential in serum-free ES culture medium and have been successfully maintained since their first establishment (> 12 months). We also compared the specific characteristics of iSSCs with those of SSCs and mSSCs using immunocytochemistry, FACS, RT-PCR, DNA methylation, and miRNA analyses. The results suggest that iSSCs represent a morphologically distinct intermediate state with characteristic expression patterns of pluripotency-related genes and miRNAs that arise during the conversion of SSCs into mSSCs. Our results suggest that iSSCs could be a useful model for evaluating and understanding the initiation mechanisms of cell reprogramming. [ABSTRACT FROM AUTHOR]

Abstract: β-Glucosidase enzymes (EC 3.2.1–3.2.3) hydrolyze sugars and are implicated in a wide spectrum of biological processes. Recently, we reported that β-glucosidase has varied kinetic parameters for the natural and synthetic substrates [K.H Nam, S.J. Kim, M.Y. Kim, J.H. Kim, T.S. Yeo, C.M. Lee, H.K Jun, K.Y. Hwang. Crystal structure of engineered beta-glucosidase from a soil metagenome, Proteins 73 (2008) 788-793]. However, an understanding of the kinetic values of β-glucosidase has not yet enabled the elucidation of its molecular function. Here, we report the X-ray crystal structure of β-glucosidase with a glucose and cellobiose fragment from uncultured soil metagenome. From the various crystals, we obtained the pre-reaction (native), intermediate (disaccharide cleavage) and post-reaction (glucose binding) states of the active site pocket. These structures provide snapshots of the catalytic processing of β-glucosidase. In addition, the intermediate state of the crystal structure provides insight into the substrate specificity of β-glucosidase. These structural studies will facilitate elucidation of the architectural mechanism responsible for the substrate recognition of β-glucosidase. [Copyright &y& Elsevier]

Abstract: Heat transfer characteristics in He II have been investigated in relation to superheating. When a good thermal conductor in a narrow two-dimensional channel is heated above the critical heat flux of the λ-transition, superheated He I nucleates in the hottest area of the conductor covered with superheated He II. The spread of superheated He I, which has a low thermal conductivity, forms an intermediate state in which superheated He I coexists with superheated He II. Superheated He I together with superheated He II is apparently stabilized since part of the heat cut off by superheated He I tends to flow in the conductor. Higher heat input turns the intermediate state into a mixed state where superheating and boiling alternate irregularly. [Copyright &y& Elsevier]