The increased frequency of combined El Niño and positive IOD events since 1965s and its impacts on maritime continent hydroclimates.

The Indian and Pacific Oceans surround the Maritime Continent (MC). Major modes of sea surface temperature variability in both oceans, including the Indian Ocean Dipole (IOD) and El Niño-Southern Oscillation (ENSO), can strongly affect precipitation on the MC. The prevalence of fires in the MC is closely associated with precipitation amount and terrestrial water storage in September and October.

Comprehensive identification of mRNA isoforms reveals the diversity of neural cell-surface molecules with roles in retinal development and disease.

Genes encoding cell-surface proteins control nervous system development and are implicated in neurological disorders. These genes produce alternative mRNA isoforms which remain poorly characterized, impeding understanding of how disease-associated mutations cause pathology. Here we introduce a strategy to define complete portfolios of full-length isoforms encoded by individual genes.

ERRγ Promotes Angiogenesis, Mitochondrial Biogenesis, and Oxidative Remodeling in PGC1α/β-Deficient Muscle.

PGC1α is a pleiotropic co-factor that affects angiogenesis, mitochondrial biogenesis, and oxidative muscle remodeling via its association with multiple transcription factors, including the master oxidative nuclear receptor ERRγ. To decipher their epistatic relationship, we explored ERRγ gain of function in muscle-specific PGC1α/β double-knockout (PKO) mice. ERRγ-driven transcriptional reprogramming largely rescues muscle damage and improves muscle function in PKO mice, inducing mitochondrial biogenesis, antioxidant defense, angiogenesis, and a glycolytic-to-oxidative fiber-type transformation independent of PGC1α/β.

A Novel Ultrasensitive In Situ Hybridization Approach to Detect Short Sequences and Splice Variants with Cellular Resolution.

Investigating the expression of RNAs that differ by short or single nucleotide sequences at a single-cell level in tissue has been limited by the sensitivity and specificity of in situ hybridization (ISH) techniques. Detection of short isoform-specific sequences requires RNA isolation for PCR analysis-an approach that loses the regional and cell-type-specific distribution of isoforms. Having the capability to distinguish the differential expression of RNA variants in tissue is critical because alterations in mRNA splicing and editing, as well as coding single nucleotide polymorphisms, have been associated with numerous cancers, neurological and psychiatric disorders.

PPARδ Promotes Running Endurance by Preserving Glucose.

Management of energy stores is critical during endurance exercise; a shift in substrate utilization from glucose toward fat is a hallmark of trained muscle. Here we show that this key metabolic adaptation is both dependent on muscle PPARδ and stimulated by PPARδ ligand. Furthermore, we find that muscle PPARδ expression positively correlates with endurance performance in BXD mouse reference populations.

Diagnosis of HPV driven oropharyngeal cancers: Comparing p16 based algorithms with the RNAscope HPV-test.

Background: Accurate identification of HPV-driven oropharyngeal cancer (OPC) is a major issue and none of the current diagnostic approaches is ideal. An in situ hybridization (ISH) assay that detects high-risk HPV E6/E7 mRNA, called the RNAscope HPV-test, has been recently developed. Studies have suggested that this assay may become a standard to define HPV-status.

Ribonucleic Acid In Situ Hybridization Is a More Sensitive Method Than Immunohistochemistry in Detection of Thyroid Transcription Factor 1 and Napsin A Expression in Lung Adenocarcinomas.

Context: TTF-1 and napsin A immunomarkers have a crucial role in differentiating lung adenocarcinoma from lung squamous cell carcinoma and in identifying a primary lung adenocarcinoma when working on a tumor of unknown origin.

Objectives: To investigate the diagnostic sensitivity of ribonucleic acid in situ hybridization (RNAscope) in the detection of expression of these biomarkers in lung adenocarcinomas and to compare RNAscope to immunohistochemical techniques.

Design: Both RNAscope and the immunohistochemical assays for TTF-1 and napsin A were performed on tissue microarray sections containing 80 lung adenocarcinomas and 80 lung squamous cell carcinomas.

Autophagy regulates T lymphocyte proliferation through selective degradation of the cell-cycle inhibitor CDKN1B/p27Kip1.

The highly conserved cellular degradation pathway, macroautophagy, regulates the homeostasis of organelles and promotes the survival of T lymphocytes. Previous results indicate that Atg3-, Atg5-, or Pik3c3/Vps34-deficient T cells cannot proliferate efficiently. Here we demonstrate that the proliferation of Atg7-deficient T cells is defective.

c-FLIP protects T lymphocytes from apoptosis in the intrinsic pathway.

Apoptosis can be induced by either death receptors on the plasma membrane (extrinsic pathway) or the damage of the genome and/or cellular organelles (intrinsic pathway). Previous studies suggest that cellular caspase 8 (FLICE)-like inhibitory protein (c-FLIP) promotes cell survival in death receptor-induced apoptosis pathway in T lymphocytes. Independent of death receptor signaling, mitochondria sense apoptotic stimuli and mediate the activation of effector caspases.

Autophagy, a novel pathway to regulate calcium mobilization in T lymphocytes.

The T lymphocyte response initiates with the recognition of MHC/peptides on antigen presenting cells by the T cell receptor (TCR). After the TCR engagement, the proximal signaling pathways are activated for downstream cellular events. Among these pathways, the calcium-signaling flux is activated through the depletion of endoplasmic reticulum (ER) calcium stores and plays pivotal roles in T cell proliferation, cell survival, and apoptosis.

CFLAR/c-FLIPL: a star in the autophagy, apoptosis and necroptosis alliance.

Necroptosis, a caspase-independent, receptor (TNFRSF)-interacting serine-threonine kinase 1 (RIPK1)/RIPK3-dependent necrotic cell death, occurs in cells when apoptosis is blocked. A high level of macroautophagy (herein referred to as autophagy) is usually detected in necroptotic cells, although it is still controversial as to whether excessive autophagy leads to cell death or is cytoprotective. In a recently published paper, we show that the anti-apoptotic protein CFLAR (CASP8 and FADD-like apoptosis regulator) long isoform (CFLARL) plays a critical role in all three fundamental intracellular processes: autophagy, necroptosis, and apoptosis in T lymphocytes.

Molecular dynamics study on the correlation between structure and sensitivity for defective RDX crystals and their PBXs.

Molecular dynamics simulation was applied to investigate the sensitivities of perfect and defective RDX (cyclotrimethylene trinitramine) crystals, as well as their PBXs (polymer-bonded explosives) with the polymeric binder F(2311), in the NPT (constant number of particles, constant pressure, constant temperature) ensemble using the COMPASS force field. Five kinds of defects-two dislocations, one vacancy, and two types of doping-were considered separately. The bond length distribution and the maximum (L (max)) and average (L (ave)) bond lengths of the N-NO(2) trigger bonds in RDX were obtained and their relationships to the sensitivities of RDX and PBXs are discussed.

Cyclo-hexa-peptides at the water/cyclohexane interface: a molecular dynamics simulation.

Molecular dynamic (MD) simulations have been performed to study the behaviors of ten kinds of cyclo-hexa-peptides (CHPs) composed of amino acids with the diverse hydrophilic/hydrophobic side chains at the water/cyclohexane interface. All the CHPs take the "horse-saddle" conformations at the interface and the hydrophilicity/hydrophobicity of the side chains influences the backbones' structural deformations. The orientations and distributions of the CHPs at the interface and the differences of interaction energies (ΔΔE) between the CHPs and the two liquid phases have been determined.

Macroautophagy in T lymphocyte development and function.

Macroautophagy (referred to as autophagy) is a fundamental intracellular process characterized by the sequestration of cytoplasmic compartments through double-membrane vesicles, termed autophagosomes. Recent studies have established important roles of autophagy in regulating T lymphocyte development and function. Resting T lymphocytes have basal levels of autophagy that is upregulated by T cell receptor stimulation.

Theoretical prediction of properties of aliphatic polynitrates.

Aliphatic polynitrates are studied using the density functional theory B3LYP method with basis set 6-31G*. The assigned infrared spectrum is obtained and is used to compute the thermodynamic properties based on the frequencies scaled by 0.96 and the principle of statistic thermodynamics.

Looking for high energy density compounds applicable for propellant among the derivatives of DPO with -N3, -ONO2, and -NNO2 groups.

The derivatives of DPO (2,5-dipicryl-1,3,4-oxadiazole) are optimized to obtain their molecular geometries and electronic structures at the DFT-B3LYP/6-31G* level. The bond length is focused to primarily predict thermal stability and the pyrolysis mechanism of the title compounds. Detonation properties are evaluated using the modified Kamlet-Jacobs equations based on the calculated densities and heats of formation.

A theoretical study on the vibrational spectra and thermodynamic properties for the nitro derivatives of phenols.

The nitro derivatives of phenols are optimized to obtain their molecular geometries and electronic structures at the DFT-B3LYP/6-31 G* level. Their IR spectra are obtained and assigned by vibrational analysis and are reliable compared with the experimental results. Based on the frequencies scaled by 0.

Packing structures and periodic band calculations on DPO (2,5-dipicryl-1,3,4-oxadiazole).

Molecular mechanics (MM) method with Compass and Dreiding force fields is used to predict molecular packing for DPO among the 7 most possible space groups (P2(1)/c, P-1, P2(1)2(1)2(1), P2(1), Pbca, C2/c, and Pna2(1)), respectively. Then, periodic band calculations are performed on the predicted crystals using the DFT-GGA-RPBE method. Obtained density of state (DOS) shows that C-O, CN-O(2) and N-N bonds are possibly the trigger bond during thermolysis.

Theoretical investigation on structures, densities, detonation properties, and the pyrolysis mechanism of the derivatives of HNS.

The derivatives of 2,2',4,4',6,6'-hexanitrostilbene (HNS) are optimized to obtain their molecular geometries and electronic structures at the DFT-B3LYP/6-31G* level. Detonation properties are evaluated using the modified Kamlet-Jacobs equations based on the calculated densities and heats of formation. It is found that there are good linear relationships between the density, detonation velocity, detonation pressure, and number of nitro, amino, and hydroxy groups.

Theoretical studies of solid bicyclo-HMX: effects of hydrostatic pressure and temperature.

On the basis of density functional theory (DFT) and molecular dynamics (MD), the structural, electronic, and mechanical properties of the energetic material bicyclo-HMX have been studied. The crystal structure optimized by the LDA/CA-PZ method compares well with the experimental data. Band structure and density of states calculations indicate that bicyclo-HMX is an insulator with the band gap of ca.

Density functional theory study of piperidine and diazocine compounds.

Density functional theory calculations at the B3LYP/6-311G** level were performed to predict the heats of formation (HOFs) for three eight-membered ring compounds and four six-membered ring compounds via designed isodesmic reactions. In the isodesmic reactions designed for the computation of HOFs (CH(3)CH(2))(2)NNO(2) and piperidine were chosen as reference compounds. The HOFs for -NO(2) substituted derivations are larger than those of -NF(2) substituent groups.

Nonisothermal decomposition kinetics and computational studies on the properties of 2,4,6,8-tetranitro-2,4,6,8-tetraazabicyclo[3,3,1]onan-3,7-dione (TNPDU).

The thermal decomposition and the nonisothermal kinetics of the thermal decomposition reaction of 2,4,6,8-tetranitro-2,4,6,8-tetraazabicyclo[3,3,1]onan-3,7-dione (TNPDU) were studied under the nonisothermal condition by differential scanning calorimetry (DSC) and thermogravimetry-derivative thermogravimetry (TG-DTG) methods. The kinetic model function in differential form and the value of Ea and A of the decomposition reaction of TNPDU are f(alpha) = 3(1 - alpha)[-ln(1 - alpha)](2/3), 141.72 kJ mol(-1), and 10(11.

Strain energies of cubane derivatives with different substituent groups.

Homodesmotic reaction and isodesmotic reaction were designed for the computation of strain energies (SE) for a series of cubane derivatives. Total energies of the optimized geometric structures at the DFT-B3LYP/6-31G* level were used to derive the SE. The SE value of cubane is 169.

DFT studies on the four polymorphs of crystalline CL-20 and the influences of hydrostatic pressure on epsilon-CL-20 crystal.

Based on density functional theory (DFT), four different methods with the generalized gradient approximation (GGA) have been employed to investigate the structural and electronic properties of the four polymorphs (alpha.H2O, beta, gamma, and epsilon phases) of CL-20, which is a well-known high energy density compound (HEDC). The relaxed crystal structures compare well with experimental data.