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Extraction residue from Geting bituminous coal (ER GBC ) via ultrasonic extraction with isometric carbon disulfide/acetone binary solvent was subjected to thermal dissolution (TD), thermal dissolution under pressurized nitrogen (TDN), non-catalytic hydroconversion (NCHC), and catalytic hydroconversion (CHC) in cyclohexane at 300 °C for 3 h. The catalyst was prepared by thermally decomposing Fe(CO) 5 and Ni(CO) 4 onto γ-Al 2 O 3 . The reaction mixtures from TD, TDN, NCHC, and CHC were sequentially extracted with petroleum ether, carbon disulfide, methanol, acetone, and isometric acetone/carbon disulfide binary solvent to afford extracts 1–5 (E 1 –E 5 ). Detailed characterizations of the extracts were performed with a gas chromatography/mass spectrometer (GC/MS) and Fourier transform infrared spectrometer. The results show that the yields of E 1 and E 3 from CHC are appreciably higher than those from others, suggesting the great influence of CHC on the breakage of -CH 2 - and -O- linkages connected to condensed aromatic rings. According to analysis with GC/MS, alkanes and arenes are the most abundant species in each E 1 , in which most of the arenes are methylarenes. Arenols and phthalates are the predominant oxygen-containing organic compounds. Arenes with 1 or 2 ring(s) markedly increase by using H 2 , especially in the presence of the catalyst. The H . catalytically generated over FeNi–S/γ-Al 2 O 3 and the stabilizing effect of H 2 on the generated radicals could play crucial roles in cleaving bridged linkages connected to condensed aromatic rings and thereby enhance the yields of alkylarenes through NCHC and CHC. Related mechanisms for the formation of some species derived from NCHC and CHC of ER GBC are discussed.

Shaerhu subbituminous coal (SSBC) and Mengdong lignite (ML) were extracted with petroleum ether under ultrasonication at room temperature to obtain ESSBC and EML, respectively. The extracts were analyzed with a gas chromatograph/mass spectrometer and a positive-ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometer to characterize biomarkers and oxygen-containing species. The biomarkers consist of a homologous series of alkanes and sterenes. The biomarker distributions provide important information on the main origins and microorganism degradation of organic matter in SSBC and ML. Oxygen-containing species, including O2–O4, O2N2, and O1N2 class species, are predominant in the extracts with double bond equivalent (DBE) values of 2–28 and carbon numbers (CNs) of 15–50. The oxygen atoms exist in furan rings, R–O–R′, RCOOR′, and RCOR′ (R and R′ denote an alkyl or aryl group). The species in EML have more varied DBE values and CNs compared with those in ESSBC. Most of the OxN2 (x = 1–2) class species have larger DBE values and CNs than the Ox class species, which might be an evidence for more abundant intermolecular associations, such as hydrogen bonds, among the OxN2 class species than among the Ox class species.

FeNi/γ-Al 2 O 3 was prepared by thermally decomposing iron pentacarbonyl and nickel tetracarbonyl onto γ-Al 2 O 3 . Geting bituminous coal (GBC) was subjected to noncatalytic hydroconversion (NCHC) and catalytic hydroconversion (CHC) in the presence of FeNi/γ-Al 2 O 3 and sulfur at 300 °C for 3 h. The reaction mixtures from both NCHC and CHC were fractionated to extracts 1–5 (E 1 –E 5 ) by sequential extraction. The molecular compositions of E 1 –E 5 were characterized with a Fourier transform infrared spectrometer, gas chromatography/mass spectrometer (GC/MS), and atmospheric solid analysis probe/time of flight-mass spectrometer (ASAP/TOF-MS). The results show that the yields of E 1 –E 5 from CHC of GBC are obviously higher than those from NCHC. According to GC/MS analysis, the group components in E 1 from the CHC are dominated by alkanes, arenes, and arenols in remarkable higher yields than those from NCHC, and most of the arenes and arenols are alkyl-substituted ones. The addition of active hydrogen atoms catalytically generated over FeNi–S/γ-Al 2 O 3 to the ipso -position of condensed aromatic rings (CARs) in GBC could play a crucial role in cleaving–CH 2 − and–O − linkages connected to the CARs and thereby enhanced the yields of alkylarenes and alkylarenols through CHC. Meanwhile, the partial hydrogenation of some CARs during CHC could promote the radical hydrogen transfer along with thermal rupture of some relatively strong bonds to produce soluble molecules. According to ASAP/TOF-MS analysis, the soluble species from both NCHC and CHC have molecular mass distributions ranging from 100 to 500 u . A series of polar and/or involatile organic species.

Two Chinese coals, Shengli lignite and Shenmu–Fugu subbituminous coal, were subjected to non-catalytic hydroconversion (NCHC) and catalytic hydroconversion (CHC) in cyclohexane at 300 °C for 3 h under pressurized hydrogen using a solid acid as the catalyst, which was prepared by impregnating isometric pentachloroantimony and trimethylsilyl trifluoromethanesulfonate into an activated carbon. The reaction mixtures from both NCHC and CHC were sequentially extracted with petroleum ether, carbon disulfide, methanol, acetone, and isometric acetone/carbon disulfide mixed solvent to afford extracts 1–5 (E 1 –E 5 ). The results show that both E 1 and total extract yields from CHC are appreciably higher than those from NCHC of each coal. E 1 from either NCHC or CHC of each coal was analyzed with a gas chromatograph/mass spectrometer (GC/MS) and an atmospheric solids analysis probe/time of flight mass spectrometer (ASAP/TOF-MS). GC/MS analysis shows that each E 1 consists of alkanes, arenes, and oxygen-containing organic compounds (OCOCs), and most of the arenes are methyl-substituted ones, whereas alkenyl groups only appear on benzene ring; most of the OCOCs are arenols, especially alkylarenols. According to ASAP/TOF-MS analysis, organic compounds with molecular masses ranging from 500 to 950 u appear in E 1 from CHC of both coals.

Summary Central to cellular proliferative, survival, and metabolic responses is the serine/threonine kinase mTOR, which is activated in many human cancers. mTOR is present in distinct complexes that are either modulated by AKT (mTORC1) or are upstream and regulatory of it (mTORC2). Governance of mTORC2 activity is poorly understood. Here, we report a transmembrane molecule in hematopoietic progenitor cells that physically interacts with and inhibits RICTOR, an essential component of mTORC2. Upstream of mTORC2 (UT2) negatively regulates mTORC2 enzymatic activity, reducing AKTS473, PKCα, and NDRG1 phosphorylation and increasing FOXO transcriptional activity in an mTORC2-dependent manner. Modulating UT2 levels altered animal survival in a T cell acute lymphoid leukemia (T-ALL) model that is known to be mTORC2 sensitive. These studies identify an inhibitory component upstream of mTORC2 in hematopoietic cells that can reduce mortality from NOTCH-induced T-ALL. A transmembrane inhibitor of mTORC2 may provide an attractive target to affect this critical cell regulatory pathway., Graphical Abstract, Highlights • UT2 is a transmembrane inhibitor of mTORC2 in hematopoietic progenitors • UT2 directly binds RICTOR, limiting the kinase activity of mTORC2 on pAKTS473 • UT2 modulates the outcome of an mTORC2-dependent hematopoietic cancer, In this article, Scadden and colleagues show that an undefined transmembrane molecule upstream of mTORC2 (UT2) negatively regulates AKT signaling via modulation of mTORC2. Their work points to the value of models that can be used to examine niche contributions to oncogenesis and reveals a previously unrecognized transmembrane modulator of a critical pathway with therapeutic implications for cancers such as T-ALL.

A highly dispersive Fe/ZSM-5 as the precursor of Fe–S/ZSM-5 was prepared by decomposing Fe(CO)5 onto ZSM-5 zeolite at 250 °C. Shengli lignite (SL) was isolated to extractable portion (EP) and extraction residue (ER) by exhaustive extraction with isometric carbon disulfide/acetone mixed solvent (IMCDSAMS) under ultrasonic irradiation. The EP and ER were analyzed with a direct analysis in real time ionization source coupled to ion trap mass spectrometer. Both of them and SL were analyzed with a Fourier transform infrared spectrometer. The ER was subjected to non-catalytic hydroconversion (NCHC) and catalytic hydroconversion (CHC) over Fe–S/ZSM-5, which was formed by in situ reaction of Fe/ZSM-5 with sulfur added, in cyclohexane under pressurized hydrogen at 300 °C. The reaction mixtures were sequentially extracted with petroleum ether, carbon disulfide, methanol, acetone, and IMCDSAMS to afford extracts 1–5 (E1–E5), which were analyzed with a gas chromatography/mass spectrometer (GC/MS). As model reactions, the CHCs of di(1-naphthyl)methane (DNM) and diphenylmethane (DPM) over Fe–S/ZSM-5 were also conducted in cyclohexane at 300 °C. The results show that more than 50% of organic matter in the ER was converted to a soluble portion by the CHC, whereas the yield of soluble portion from the NCHC is only 10.52%. GC/MS-detectable species only appear in the E1, which mainly consists of alkanes, arenes, and arenols either from the NCHC or from the CHC. DNM was selectively hydrocracked to naphthalene and 1-methylnaphthalene over Fe–S/ZSM-5, while DPM hydrocracking did not proceed, indicating that Fe–S/ZSM-5 catalyzed the formation of radical hydrogen from molecular hydrogen and subsequent radical hydrogen transfer (RHT) to the ipso-position of naphthalene ring in DNM. Some CH2 and O in the ER could be connected to condensed aromatic rings (CARs). Analogously, RHT to the ipso-position of CARs in the ER resulted in the release of arenes and phenols from the ER.

The balance between oxidative and non-oxidative glucose metabolism is essential for a number of pathophysiological processes. By deleting enzymes that affect aerobic glycolysis with different potencies, we examine how modulating glucose metabolism specifically affects hematopoietic and leukemic cell populations. We find that deficiency in the M2 pyruvate kinase isoform (PKM2) reduces levels of metabolic intermediates important for biosynthesis and impairs progenitor function without perturbing hematopoietic stem cells (HSC), whereas lactate dehydrogenase-A (LDHA) deletion significantly inhibits the function of both HSC and progenitors during hematopoiesis. In contrast, leukemia initiation by transforming alleles putatively affecting either HSC or progenitors is inhibited in the absence of either PKM2 or LDHA, indicating that the cell state-specific responses to metabolic manipulation in hematopoiesis do not apply to the setting of leukemia. This finding suggests that fine-tuning the level of glycolysis may be therapeutically explored for treating leukemia while preserving HSC function., National Institutes of Health (U.S.) (Grants P30CA147882 and R01CA168653), Smith Family Foundation, Burroughs Wellcome Fund, Virginia and D.K. Ludwig Fund for Cancer Research, Damon Runyon Cancer Research Foundation

Ruthenium ion-catalyzed oxidation (RICO) of Huolinguole lignite (HL) was performed to understand the structural features of macromolecular aromatic species in HL by analyzing the resulting soluble species (SSs) with a gas chromatography/mass spectrometer and atmospheric-pressure solids-analysis probe/time of flight-mass spectrometer. The results show that in the SSs, alkanedioic acids are predominantly abundant and most of them are succinic acid and glutaric acid, indicating that HL is rich in bridged linkages (BLs) and CH2CH2 and CH2CH2CH2 are the main BLs connecting aromatic rings. The total yield of benzenecarboxylic acids with less carboxylic groups (CGs) (the number of CGs

Three catalysts were prepared by impregnating the same volume of pentachloroantimony (PCA), trimethylsilyl trifluoromethanesulfonate (TMSTFMS), or isometric PCA and TMSTFMA into an activated carbon (AC). Di(1-naphthyl)methane (DNM) was used as a coal-related model compound to evaluate their catalytic activity. The results show that C ar C alk bond in DNM can be specifically cleaved over each catalyst to afford naphthalene and 1-methylnaphthalene under pressurized hydrogen at temperatures up to 300 °C, but as a new solid acid (NSA), PCA–TMSTFMS/AC is significantly more active for DNM hydrocracking than the other two catalysts. FTIR and SEM analyses reveal the strong interactions among PCA, TMSTFMS, and the AC in the NSA. NH 3 -TPD analysis suggests that the NSA should exhibit appreciably stronger acidity than the other two catalysts. The strong interactions may result in the appreciably stronger acidity of the NSA than that of the other two catalysts and thereby facilitate DNM hydrocracking. It is presumed that H 2 was heterolytically cleaved to immobile H − and mobile H + . The addition of mobile H + to ipso -position of DNM should be crucial step for DNM hydrocracking.

The generation of a B cell repertoire involves producing and subsequently purging autoreactive B cells. Receptor editing, clonal deletion and anergy are key mechanisms of central B cell tolerance. Somatic mutation of antigen-activated B cells within the germinal center produces a second wave of autoreactivity; but the regulatory mechanisms that operate at this phase of B cell activation are poorly understood. We recently identified a post germinal center tolerance checkpoint, where receptor editing is re-induced to extinguish autoreactivity that is generated by somatic hypermutation. Re-induction of the recombinase genes RAG1 and RAG2 in antigen-activated B cells requires antigen to engage the B cell receptor and IL-7 to signal through the IL-7 receptor. We demonstrate that this process requires IL-6 to upregulate IL-7 receptor expression on post germinal center B cells. Diminishing IL-6 by blocking antibody or haplo-insufficiency leads to reduced expression of the IL-7 receptor and RAG and increased titers of anti-DNA antibodies following immunization with a peptide mimetope of DNA. The dependence on IL-6 to initiate receptor editing is B cell intrinsic. Interestingly, estradiol decreases IL-6 expression thereby increasing the anti-DNA response. Our data reveal a novel regulatory cascade to control post germinal center B cell autoreactivity.

How self tolerance is maintained during B cell development in the bone marrow has been a focal area of study in immunology. Receptor editing, anergy and clonal deletion all play important roles in the regulation of autoimmunity in the immature population. The mechanisms of tolerance induction in the periphery, however, are less well characterized. Overexpression of the apoptosis inhibitor Bcl-2 rescues autoreactive B cells from deletion and can contribute to the development of autoimmune disease in certain genetic backgrounds. Using a peptide induced autoimmunity model, we recently identified a peripheral tolerance checkpoint in antigen-activated B cells that have undergone class switching and somatic hypermutation. At this checkpoint, receptor editing, induced by antigen engagement, dampened the autoantibody response. In this study, we show that receptor editing fails to be induced in antigen activated DNA-reactive B cells that overexpress Bcl-2 (Bcl-2 Tg). The failure to induce RAG and receptor editing is likely due, at least partially, to the lack of self antigen. First, the levels of circulating DNA and of apoptotic bodies in the spleen of Bcl-2 Tg mice are significantly lower than in control mice. Second, in Bcl-2 Tg mice, RAG can be induced in a population of antigen-activated B cells by providing exogenous soluble antigen. These data suggest that, in addition to its anti-apoptotic activity, Bcl-2 may indirectly inhibit tolerance induction in B cells acquiring anti-nuclear antigen reactivity after peripheral activation by limiting the availability of self antigen.

We present an unsupervised segmentation algorithm for fully polarimetric synthetic aperture radar (PolSAR) data by using the mean shift clustering. The previous work using the span values of the PolSAR data as the features in the mean shift clustering, however, does not sufficiently exploit the full information contained in the polarimetric covariance matrix. When considering the polarimetric covariance matrices as the feature vectors, the traditional mean shift clustering in the Euclidean space is not applicable anymore, since these matrices do not form a Euclidean space. We first show that by regarding each Hermitian positive definite polarimetric covariance matrix at per pixel as a tensor, the tensor space can be represented as a Riemannian manifold. Then, the mean shift clustering is extended to the Riemannian manifold to explain the theoretical meanings of the tensor clustering and a practical segmentation algorithm based on the metric lying on the manifold is proposed. Experimental results using the real fully PolSAR data and simulated data verify the effectiveness of the proposed method.

Autoantibodies clearly contribute to tissue inflammation in systemic lupus erythematosus. In order to therapeutically target B cells making pathogenic autoantibodies, it is necessary to identify their phenotype. It is also important to understand the defects in B cell repertoire selection that permit pathogenic autoreactive B cells to enter the immunocompetent B cell repertoire. We present the data that both marginal zone and follicular B cells can produce pathogenic autoantibodies. Moreover, we discuss how B cell survival and maturation are regulated centrally prior to antigen activation and in the periphery after antigen activation to form the repertoire that generates the spectrum of circulating antibodies.

Transient left ventricular dysfunction can occur after hypothermic, hyperkalemic cardioplegic arrest and is associated with decreased beta-adrenergic receptor responsiveness. Occupancy of the beta-adrenergic receptor activates adenylate cyclase, which phosphorylates the L-type Ca2+ channel-enhancing myocyte contractility. The goal of this study was to identify potential mechanisms that contribute to the defects in the beta-adrenergic receptor signaling cascade after cardioplegic arrest.Isolated left ventricular porcine myocytes were assigned to one of two treatment groups: (1) cardioplegic arrest (24 mEq/L K+, 4 degrees C x 2 hours, then 5 minutes in 37 degrees C cell media; n = 130) or (2) normothermic control (cell media, 37 degrees C x 2 hours; n = 222). Myocyte contractility was assessed at baseline and after either beta-adrenergic receptor occupancy (25 nmol/L isoproterenol [INN: isoprenaline]), activation of adenylate cyclase (0.5 mumol forskolin), or direct activation of the L-type Ca(2+)-channel (10 nmol/L or 100 nmol/L (-)BayK 8644).Myocyte velocity of shortening (micron/sec) was increased with beta-adrenergic receptor occupancy or direct adenylate cyclase stimulation compared with baseline in the normothermic group (187.3 +/- 6.9, 181.7 +/- 10.2, and 73.9 +/- 2.9, respectively; p0.0001) and after cardioplegic arrest (128.6 +/- 8.9, 124.3 +/- 9.4, and 46.1 +/- 2.6, respectively; p0.0001). However, the response after cardioplegic arrest was significantly reduced compared with normothermic values under all conditions (p = 0.012). Direct activation of the L-type Ca(2+)-channel, which eliminates beta-adrenergic receptor-dependent events, increased myocyte contractility in the normothermic group (161.90 +/- 12.0, p0.0001) and after cardioplegic arrest (92.78 +/- 6.8, p0.0001), but the positive inotropic response appeared reduced compared with normothermic control values (p = 0.003).These findings suggest that contributory mechanisms for the reduced beta-adrenergic receptor-mediated response after hypothermic, hyperkalemic cardioplegic arrest lie downstream from these specific components of the transduction pathway and likely include defects in Ca2+ homeostasis, myofilament Ca2+ sensitivity, or both.