A New Global Unconventional Natural Gas Resource Assessment

In 1997, Rogner published a paper containing an estimate of the natural gas in place in unconventional reservoirs for 11 world regions. Rogner's work was assessing the unconventional gas resource base, and is now considered to be very conservative. Very little is known publicly about technically recoverable unconventional gas resource potential on a global scale. Driven by a new understanding of the size of gas shale resources in the United States, we estimated original gas in place (OGIP) and technically recoverable resource (TRR) in highly uncertain unconventional gas reservoirs, worldwide. We evaluated global unconventional OGIP by (1) developing theoretical statistic relationships between conventional hydrocarbon and unconventional gas; (2) fitting these relationships to North America publically available data; and (3) applying North American theoretical statistical relationships to evaluate the volume of unconventional gas resource of the world. Estimated global unconventional OGIP ranges from 83,300 (P10) to 184,200 (P90) Tcf. To assess global TRR from unconventional gas reservoirs, we developed a computer program that we call Unconventional Gas Resource Assessment System (UGRAS). In the program, we integrated a Monte Carlo technique with an analytical reservoir simulator to estimate the original volume of gas in place and to predict production performance. We used UGRAS to evaluate the probabilistic distribution of OGIP, TRR and recovery factor (RF) for the most productive unconventional gas formations in the North America. The P50 of recovery factor for shale gas, tight sands gas and coalbed methane is 25%, 79% and 41%, respectively. Finally, we applied our global OGIP assessment and these distributions of recovery factor gained from our analyses of plays/formations in the United States to estimate global technically recoverable unconventional gas resource. Global technically recoverable unconventional gas resource is estimated from 43,000 (P10) to 112,000 (P90) Tcf

Shoshonitic enclaves in the high Sr/Y Nyemo pluton, southern Tibet: Implications for Oligocene magma mixing and the onset of extension of the southern Lhasa terrane

Post-collisional potassic and high Sr/Y magmatism in the Lhasa terrane provides critical constraints on the timing and mechanism of subduction of Indian lithosphere and its role in the uplift of the Tibetan Plateau. Here, we report whole-rock geochemistry, mineral geochemistry, zircon U Pb ages, and in situ zircon Hf isotope ratios for the Nyemo pluton, a representative example of such magmatism. The Nyemo pluton is composed of high Sr/Y host rocks and coeval shoshonitic mafic microgranular enclaves (MMEs). Whole-rock compositions of the host rocks and MMEs form linear trends in Harker diagrams, consistent with modification of both end-members by magma mixing. Although the main high Sr/Y phase of the pluton formed by partial melting of the lower crust of the thickened Lhasa terrane, the MMEs display abnormally enriched light rare earth elements, low whole-rock ε_(Nd)(t) and low zircon ε_(Hf)(t) that suggest derivation from low degree melting of hydrous and enriched mantle. Based on the occurrence of shoshonitic magma and high La/Yb and high Sr/Y with adakitic affinity host rocks around 30 Ma, the Nyemo pluton is best explained as a record of onset of extension that resulted from convective removal of the mantle lithosphere beneath Tibet in the Oligocene

Superfolded configuration induced low thermal conductivity in two-dimensional carbon allotropes revealed via machine learning force constant potential

Understanding the fundamental link between structure and functionalization is crucial for the design and optimization of functional materials, since different structural configurations could trigger materials to demonstrate diverse physical, chemical, and electronic properties. However, the correlation between crystal structure and thermal conductivity (\k{appa}) remains enigmatic. In this study, taking two-dimensional (2D) carbon allotropes as study cases, we utilize phonon Boltzmann transport equation (BTE) along with machine learning force constant potential to thoroughly explore the complex folding structure of pure sp2 hybridized carbon materials from the perspective of crystal structure, mode-level phonon resolved thermal transport, and atomic interactions, with the goal of identifying the underlying relationship between 2D geometry and \k{appa}. We propose two potential structure evolution mechanisms for targeted thermal transport properties: in-plane and out-of-plane folding evolutions, which are generally applicable to 2D carbon allotropes. It is revealed that the folded structure produces strong symmetry breaking, and simultaneously produces exceptionally strongly suppressed phonon group velocities, strong phonon-phonon scattering, and weak phonon hydrodynamics, which ultimately lead to low \k{appa}. The insight into the folded effect of atomic structures on thermal transport deepens our understanding of the relationship between structure and functionalization, which offers straightforward guidance for designing novel nanomaterials with targeted \k{appa}, as well as propel developments in materials science and engineering

Blocking interaction between SHP2 and PD‐1 denotes a novel opportunity for developing PD‐1 inhibitors

Small molecular PD‐1 inhibitors are lacking in current immuno‐oncology clinic. PD‐1/PD‐L1 antibody inhibitors currently approved for clinical usage block interaction between PD‐L1 and PD‐1 to enhance cytotoxicity of CD8+ cytotoxic T lymphocyte (CTL). Whether other steps along the PD‐1 signaling pathway can be targeted remains to be determined. Here, we report that methylene blue (MB), an FDA‐approved chemical for treating methemoglobinemia, potently inhibits PD‐1 signaling. MB enhances the cytotoxicity, activation, cell proliferation, and cytokine‐secreting activity of CTL inhibited by PD‐1. Mechanistically, MB blocks interaction between Y248‐phosphorylated immunoreceptor tyrosine‐based switch motif (ITSM) of human PD‐1 and SHP2. MB enables activated CTL to shrink PD‐L1 expressing tumor allografts and autochthonous lung cancers in a transgenic mouse model. MB also effectively counteracts the PD‐1 signaling on human T cells isolated from peripheral blood of healthy donors. Thus, we identify an FDA‐approved chemical capable of potently inhibiting the function of PD‐1. Equally important, our work sheds light on a novel strategy to develop inhibitors targeting PD‐1 signaling axis

Uncovering neuroinflammation-related modules and potential repurposing drugs for Alzheimer's disease through multi-omics data integrative analysis

BackgroundNeuroinflammation is one of the key factors leading to neuron death and synapse dysfunction in Alzheimer's disease (AD). Amyloid-β (Aβ) is thought to have an association with microglia activation and trigger neuroinflammation in AD. However, inflammation response in brain disorders is heterogenous, and thus, it is necessary to unveil the specific gene module of neuroinflammation caused by Aβ in AD, which might provide novel biomarkers for AD diagnosis and help understand the mechanism of the disease.MethodsTranscriptomic datasets of brain region tissues from AD patients and the corresponding normal tissues were first used to identify gene modules through the weighted gene co-expression network analysis (WGCNA) method. Then, key modules highly associated with Aβ accumulation and neuroinflammatory response were pinpointed by combining module expression score and functional information. Meanwhile, the relationship of the Aβ-associated module to the neuron and microglia was explored based on snRNA-seq data. Afterward, transcription factor (TF) enrichment and the SCENIC analysis were performed on the Aβ-associated module to discover the related upstream regulators, and then a PPI network proximity method was employed to repurpose the potential approved drugs for AD.ResultsA total of 16 co-expression modules were primarily obtained by the WGCNA method. Among them, the green module was significantly correlated with Aβ accumulation, and its function was mainly involved in neuroinflammation response and neuron death. Thus, the module was termed the amyloid-β induced neuroinflammation module (AIM). Moreover, the module was negatively correlated with neuron percentage and showed a close association with inflammatory microglia. Finally, based on the module, several important TFs were recognized as potential diagnostic biomarkers for AD, and then 20 possible drugs including ibrutinib and ponatinib were picked out for the disease.ConclusionIn this study, a specific gene module, termed AIM, was identified as a key sub-network of Aβ accumulation and neuroinflammation in AD. Moreover, the module was verified as having an association with neuron degeneration and inflammatory microglia transformation. Moreover, some promising TFs and potential repurposing drugs were presented for AD based on the module. The findings of the study shed new light on the mechanistic investigation of AD and might make benefits the treatment of the disease

STAT1 modification improves therapeutic effects of interferons on lung cancer cells

BACKGROUND: Interferons (IFNs) have potent anti-proliferative, pro-apoptotic, and immunomodulatory activities against cancer. However, the clinical utility of IFNs is limited by toxicity and pharmacokinetics making it difficult to achieve sustained therapeutic levels especially in solid tumors. METHODS: Signal Transducer and Activator of Transcription 1 (STAT1) or a modified STAT1 (designated STAT1-CC) that is hyper-responsive to IFN were overexpressed in lung cancer SPC-A-1 and H1299 cells using lentiviral vectors. Transduction efficiency was monitored using enhanced green fluorescent protein (EGFP) expression. After transduction, cells were treated with interferon-gamma (IFN-γ) or interferon-beta (IFN-β) and monitored for cell proliferation, migration, and invasiveness using Cell Counting Kit-8 and transwell chamber assays and for apoptosis using Annexin V detection by flow cytometry. In addition, levels of STAT1, STAT1 Tyr-701 phosphorylation (pSTAT1), fibronectin, and β-catenin were determined using western blotting. In the case of IFN-γ stimulation, levels of S100A4, proliferating cell nuclear antigen (PCNA), and c-fos expression were also determined. RESULTS: We found that expression of STAT1 or STAT1-CC enhanced the effect of IFN-γ and, IFN-β on inhibition of human lung cancer cell proliferation, migration and invasiveness. Moreover, STAT1 and STAT1-CC expression caused increases in pSTAT1 and decreases in fibronectin and β-catenin levels. STAT1-CC showed increased effects compared to STAT1 on IFN-γ induced pSTAT1 and down-regulation of S100A4, PCNA, and c-fos levels. CONCLUSION: The results show that STAT1-CC exhibited more strength in improving the antitumor response of IFNs in lung cancer cells. Results from this study suggest that combined treatment of IFNs and STAT1-CC might be a feasible approach for the clinical management of lung cancer in the future

Harpin-induced expression and transgenic overexpression of the phloem protein gene AtPP2-A1 in Arabidopsis repress phloem feeding of the green peach aphid Myzus persicae

<p>Abstract</p> <p>Background</p> <p>Treatment of plants with HrpN_Ea, a protein of harpin group produced by Gram-negative plant pathogenic bacteria, induces plant resistance to insect herbivores, including the green peach aphid <it>Myzus persicae</it>, a generalist phloem-feeding insect. Under attacks by phloem-feeding insects, plants defend themselves using the phloem-based defense mechanism, which is supposed to involve the phloem protein 2 (PP2), one of the most abundant proteins in the phloem sap. The purpose of this study was to obtain genetic evidence for the function of the <it>Arabidopsis thaliana </it>(Arabidopsis) PP2-encoding gene <it>AtPP2-A1 </it>in resistance to <it>M. persicae </it>when the plant was treated with HrpN_Eaand after the plant was transformed with <it>AtPP2-A1</it>.</p> <p>Results</p> <p>The electrical penetration graph technique was used to visualize the phloem-feeding activities of apterous agamic <it>M. persicae </it>females on leaves of Arabidopsis plants treated with HrpN_Eaand an inactive protein control, respectively. A repression of phloem feeding was induced by HrpN_Eain wild-type (WT) Arabidopsis but not in <it>atpp2-a1</it>/E/142, the plant mutant that had a defect in the <it>AtPP2-A1 </it>gene, the most HrpN_Ea-responsive of 30 <it>AtPP2 </it>genes. In WT rather than <it>atpp2-a1</it>/E/142, the deterrent effect of HrpN_Eatreatment on the phloem-feeding activity accompanied an enhancement of <it>AtPP2-A1 </it>expression. In PP2OETAt (<it>AtPP2-A1</it>-overexpression transgenic <it>Arabidopsis thaliana</it>) plants, abundant amounts of the <it>AtPP2-A1 </it>gene transcript were detected in different organs, including leaves, stems, calyces, and petals. All these organs had a deterrent effect on the phloem-feeding activity compared with the same organs of the transgenic control plant. When a large-scale aphid population was monitored for 24 hours, there was a significant decrease in the number of aphids that colonized leaves of HrpN_Ea-treated WT and PP2OETAt plants, respectively, compared with control plants.</p> <p>Conclusions</p> <p>The repression in phloem-feeding activities of <it>M. persicae </it>as a result of <it>AtPP2-A1 </it>overexpression, and as a deterrent effect of HrpN_Eatreatment in WT Arabidopsis rather than the <it>atpp2-a1</it>/E/142 mutant suggest that <it>AtPP2-A1 </it>plays a role in plant resistance to the insect, particularly at the phloem-feeding stage. The accompanied change of aphid population in leaf colonies suggests that the function of <it>AtPP2-A1 </it>is related to colonization of the plant.</p

Automatic Search of Meet-in-the-Middle Preimage Attacks on AES-like Hashing

The Meet-in-the-Middle (MITM) preimage attack is highly effective in breaking the preimage resistance of many hash functions, including but not limited to the full MD5, HAVAL, and Tiger, and reduced SHA-0/1/2. It was also shown to be a threat to hash functions built on block ciphers like AES by Sasaki in 2011. Recently, such attacks on AES hashing modes evolved from merely using the freedom of choosing the internal state to also exploiting the freedom of choosing the message state. However, detecting such attacks especially those evolved variants is difficult. In previous works, the search space of the configurations of such attacks is limited, such that manual analysis is practical, which results in sub-optimal solutions. In this paper, we remove artificial limitations in previous works, formulate the essential ideas of the construction of the attack in well-defined ways, and translate the problem of searching for the best attacks into optimization problems under constraints in Mixed-Integer-Linear-Programming (MILP) models. The MILP models capture a large solution space of valid attacks; and the objectives of the MILP models are attack configurations with the minimized computational complexity. With such MILP models and using the off-the-shelf solver, it is efficient to search for the best attacks exhaustively. As a result, we obtain the first attacks against the full (5-round) and an extended (5.5-round) version of Haraka-512 v2, and 8-round AES-128 hashing modes, as well as improved attacks covering more rounds of Haraka-256 v2 and other members of AES and Rijndael hashing modes