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Using 9.0 fb−1 of e+e− collision data collected at center-of-mass energies from 4.178 to 4.278 GeV with the BESIII detector at the BEPCII collider, we perform the first search for the radiative transition χc1(3872)→γψ2(3823). No χc1(3872)→γψ2(3823) signal is observed. The upper limit on the ratio of branching fractions B(χc1(3872)→γψ2(3823),ψ2(3823)→γχc1)/B(χc1(3872)→π+π−J/ψ) is set as 0.075 at the 90\% confidence level. Our result contradicts theoretical predictions under the assumption that the χc1(3872) is the pure charmonium state χc1(2P).
We report the first amplitude analysis of the decays D0→π+π−η and D+→π+π0η using a data sample taken with the BESIII detector at the center-of-mass energy of 3.773 GeV, corresponding to an integrated luminosity of 7.9 fb−1. The contribution from the process D0(+)→a0(980)+π−(0) is significantly larger than the D0(+)→a0(980)−(0)π+ contribution. The ratios B(D0→a0(980)+π−)/B(D0→a0(980)−π+) and B(D+→a0(980)+π0)/B(D+→a0(980)0π+) are measured to be 7.5+2.5−0.8stat.±1.7syst. and 2.6±0.6stat.±0.3syst., respectively. The measured D0 ratio disagrees with the theoretical predictions by orders of magnitudes, thus implying a substantial contribution from final-state interactions.
The process e+e−→pp¯π0 is studied at 20 center-of-mass energies ranging from 2.1000 to 3.0800 GeV using 636.8 pb−1 of data collected with the BESIII detector operating at the BEPCII collider. The Born cross sections for e+e−→pp¯π0 are measured with high precision. Since the lowest center-of-mass energy, 2.1000 GeV, is less than 90 MeV above the pp¯π0 energy threshold, we can probe the threshold behavior for this reaction. However, no anomalous threshold enhancement is found in the cross sections for e+e−→pp¯π0.
Based on (2.712±0.014)×109 ψ(3686) events collected by the BESIII collaboration, evidence of the hadronic decay hc→K0SK+π−+c.c. is found with a significance of 4.3σ in the ψ(3686)→π0hc process. The branching fraction of hc→K0SK+π−+c.c. is measured to be (7.3±0.8±1.8)×10−4, where the first and second uncertainties are statistical and systematic, respectively. Combining with the exclusive decay width of ηc→KK¯π, our result indicates inconsistencies with both pQCD and NRQCD predictions.
Six C-even states, denoted as X, with quantum numbers JPC=0−+, 1±+, or 2±+, are searched for via the e+e−→γD±sD∗∓s process using (1667.39±8.84) pb−1 of e+e− collision data collected with the BESIII detector operating at the BEPCII storage ring at center-of-mass energy of s√=(4681.92±0.30) MeV. No statistically significant signal is observed in the mass range from 4.08 to 4.32 GeV/c2. The upper limits of σ[e+e−→γX]⋅B[X→D±sD∗∓s] at a 90% confidence level are determined.
Using data samples collected with the BESIII detector operating at the BEPCII storage ring, the cross section of the inclusive process e+e−→η+X, normalized by the total cross section of e+e−→hadrons, is measured at eight center-of-mass energy points from 2.0000 GeV to 3.6710 GeV. These are the first measurements with momentum dependence in this energy region. Our measurement shows a significant discrepancy from calculations with the existing fragmentation functions. To address this discrepancy, a new QCD analysis is performed at the next-to-next-to-leading order with hadron mass corrections and higher twist effects, which can explain both the established high-energy data and our measurements reasonably well.
Although global- and catchment-scale hydrological models are often shown to accurately simulate long-term runoff time-series, far less is known about their suitability for capturing hydrological extremes, such as droughts. Here we evaluated simulations of hydrological droughts from nine catchment scale hydrological models (CHMs) and eight global scale hydrological models (GHMs) for eight large catchments: Upper Amazon, Lena, Upper Mississippi, Upper Niger, Rhine, Tagus, Upper Yangtze and Upper Yellow. The simulations were conducted within the framework of phase 2a of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP2a). We evaluated the ability of the CHMs, GHMs and their respective ensemble means (Ens-CHM and Ens-GHM) to simulate observed hydrological droughts of at least one month duration, over 31 years (1971–2001). Hydrological drought events were identified from runoff-deficits and the Standardised Runoff Index (SRI). In all catchments, the CHMs performed relatively better than the GHMs, for simulating monthly runoff-deficits. The number of drought events identified under different drought categories (i.e. SRI values of -1 to -1.49, -1.5 to -1.99, and ≤-2) varied significantly between models. All the models, as well as the two ensemble means, have limited abilities to accurately simulate drought events in all eight catchments, in terms of their occurrence and magnitude. Overall, there are opportunities to improve both CHMs and GHMs for better characterisation of hydrological droughts.
Based on 4.5 fb−1 of e+e− collision data accumulated at center-of-mass energies between 4599.53 MeV and 4698.82 MeV with the BESIII detector, the decay Λ+c→nK0Sπ+π0 is observed for the first time with a significance of 9.2σ. The branching fraction is measured to be (0.85±0.13±0.03)%, where the first uncertainty is statistical and the second systematic, which differs from the theoretical prediction based on isospin by 4.4σ. This indicates that there may be resonant contributions or some unknown dynamics in this decay.
Based on 4.5 fb−1 of e+e− collision data accumulated at center-of-mass energies between 4599.53 MeV and 4698.82 MeV with the BESIII detector, the decay Λ+c→nK0Sπ+π0 is observed for the first time with a significance of 9.2σ. The branching fraction is measured to be (0.85±0.13±0.03)%, where the first uncertainty is statistical and the second systematic, which differs from the theoretical prediction based on isospin by 4.4σ. This indicates that there may be resonant contributions or some unknown dynamics in this decay.
The process e+e−→Σ+Σ¯− is studied from threshold up to 3.04 GeV/c2 via the initial-state radiation technique using data with an integrated luminosity of 12.0 fb−1, collected at center-of-mass energies between 3.773 and 4.258 GeV with the BESIII detector at the BEPCII collider. The pair production cross sections and the effective form factors of Σ are measured in eleven Σ+Σ¯− invariant mass intervals from threshold to 3.04 GeV/c2. The results are consistent with the previous results from Belle and BESIII. Furthermore, the branching fractions of the decays J/ψ→Σ+Σ¯− and ψ(3686)→Σ+Σ¯− are determined and the obtained results are consistent with the previous results of BESIII.
The process 𝑒+𝑒−→Σ+¯Σ− is studied from threshold up to 3.04 GeV/𝑐2 via the initial-state radiation technique using data with an integrated luminosity of 12.0 fb−1, collected at center-of-mass energies between 3.773 and 4.258 GeV with the BESIII detector at the BEPCII collider. The pair production cross sections and the effective form factors of Σ are measured in eleven Σ+¯Σ− invariant mass intervals from threshold to 3.04 GeV/𝑐2. The results are consistent with the previous results from Belle and BESIII. Furthermore, the branching fractions of the decays 𝐽/𝜓→Σ+¯Σ− and 𝜓(3686)→Σ+¯Σ− are determined and the obtained results are consistent with the previous results of BESIII.
We search for the di-photon decay of a light pseudoscalar axion-like particle, a, in radiative decays of the J/ψ, using 10 billion J/ψ events collected with the BESIII detector. We find no evidence of a narrow resonance and set upper limits at the 95% confidence level on the product branching fraction B(J/ψ→γa)×B(a→γγ) and the axion-like particle photon coupling constant gaγγ in the ranges of (3.6−49.8)×10−8 and (2.2−103.8)×10−4 GeV−1, respectively, for 0.18≤ma≤2.85 GeV/c2. These are the most stringent limits to date in this mass region.
The absolute branching fraction of the decay Λc(2625)+→Λ+cπ+π− is measured for the first time to be (50.7±5.0stat.±4.9syst.)% with 368.48 pb−1 of e+e− collision data collected by the BESIII detector at the center-of-mass energies of s√=4.918 and 4.950 GeV. This result is lower than the naive prediction of 67\%, obtained from isospin symmetry, by more than 2σ, thereby indicating that the novel mechanism referred to as the \textit{threshold effect}, proposed for the strong decays of Λc(2595)+, also applies to Λc(2625)+. This measurement is necessary to obtain the coupling constants for the transitions between s-wave and p-wave charmed baryons in heavy hadron chiral perturbation theory. In addition, we search for the decay Λc(2595)+→Λ+cπ+π−. No significant signal is observed, and the upper limit on its branching fraction is determined to be 80.8\% at the 90\% confidence level.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
The Cabbibo-favored decay Λ+c→Ξ0K+π0 is studied for the first time using 6.1 fb−1 of e+e− collision data at center-of-mass energies between 4.600 and 4.840 GeV, collected with the BESIII detector at the BEPCII collider. With a double-tag method, the branching fraction of the three-body decay Λ+c→Ξ0K+π0 is measured to be (7.79±1.46±0.71)×10−3, where the first and second uncertainties are statistical and systematic, respectively. The branching fraction of the two-body decay Λ+c→Ξ(1530)0K+ is (5.99±1.04±0.29)×10−3, which is consistent with the previous result of (5.02±0.99±0.31)×10−3. In addition, the upper limit on the branching fraction of the doubly Cabbibo-suppressed decay Λ+c→nK+π0 is 7.1×10−4 at the 90% confidence level. The upper limits on the branching fractions of Λ+c→Σ0K+π0 and ΛK+π0 are also determined to be 1.8×10−3 and 2.0×10−3, respectively.
The Cabbibo-favored decay Λ+c→Ξ0K+π0 is studied for the first time using 6.1 fb−1 of e+e− collision data at center-of-mass energies between 4.600 and 4.840 GeV, collected with the BESIII detector at the BEPCII collider. With a double-tag method, the branching fraction of the three-body decay Λ+c→Ξ0K+π0 is measured to be (7.79±1.46±0.71)×10−3, where the first and second uncertainties are statistical and systematic, respectively. The branching fraction of the two-body decay Λ+c→Ξ(1530)0K+ is (5.99±1.04±0.29)×10−3, which is consistent with the previous result of (5.02±0.99±0.31)×10−3. In addition, the upper limit on the branching fraction of the doubly Cabbibo-suppressed decay Λ+c→nK+π0 is 7.1×10−4 at the 90% confidence level. The upper limits on the branching fractions of Λ+c→Σ0K+π0 and ΛK+π0 are also determined to be 1.8×10−3 and 2.0×10−3, respectively.
The Cabbibo-favored decay Λ+c→Ξ0K+π0 is studied for the first time using 6.1 fb−1 of e+e− collision data at center-of-mass energies between 4.600 and 4.840 GeV, collected with the BESIII detector at the BEPCII collider. With a double-tag method, the branching fraction of the three-body decay Λ+c→Ξ0K+π0 is measured to be (7.79±1.46±0.71)×10−3, where the first and second uncertainties are statistical and systematic, respectively. The branching fraction of the two-body decay Λ+c→Ξ(1530)0K+ is (5.99±1.04±0.29)×10−3, which is consistent with the previous result of (5.02±0.99±0.31)×10−3. In addition, the upper limit on the branching fraction of the doubly Cabbibo-suppressed decay Λ+c→nK+π0 is 7.1×10−4 at the 90% confidence level. The upper limits on the branching fractions of Λ+c→Σ0K+π0 and ΛK+π0 are also determined to be 1.8×10−3 and 2.0×10−3, respectively.
We present the first measurements of charge-dependent correlations on angular difference variables η1 − η2 (pseudorapidity) and φ1 − φ2 (azimuth) for primary charged hadrons with transverse momentum 0.15 <= pt <= 2 GeV/c and |η| <= 1.3 from Au–Au collisions at √sNN = 130 GeV. We observe correlation structures not predicted by theory but consistent with evolution of hadron emission geometry with increasing centrality from one-dimensional fragmentation of color strings along the beam direction to an at least two-dimensional hadronization geometry along the beam and azimuth directions of a hadron-opaque bulk medium.
The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process β-decay chains. These nuclei are attributed to the p and rp process.
For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections.
The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
Data from the first physics run at the Relativistic Heavy-Ion Collider at Brookhaven National Laboratory, Au+Au collisions at sqrt[sNN]=130 GeV, have been analyzed by the STAR Collaboration using three-pion correlations with charged pions to study whether pions are emitted independently at freeze-out. We have made a high-statistics measurement of the three-pion correlation function and calculated the normalized three-particle correlator to obtain a quantitative measurement of the degree of chaoticity of the pion source. It is found that the degree of chaoticity seems to increase with increasing particle multiplicity.
The balance function is a new observable based on the principle that charge is locally conserved when particles are pair produced. Balance functions have been measured for charged particle pairs and identified charged pion pairs in Au+Au collisions at sqrt[sNN]=130 GeV at the Relativistic Heavy Ion Collider using STAR. Balance functions for peripheral collisions have widths consistent with model predictions based on a superposition of nucleon-nucleon scattering. Widths in central collisions are smaller, consistent with trends predicted by models incorporating late hadronization.
Azimuthal anisotropy (v2) and two-particle angular correlations of high pT charged hadrons have been measured in Au+Au collisions at sqrt[sNN]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high pT partons. The monotonic rise of v2(pT) for pT<2 GeV/c is consistent with collective hydrodynamical flow calculations. At pT>3 GeV/c, a saturation of v2 is observed which persists up to pT=6 GeV/c.
Azimuthal anisotropy (v2) and two-particle angular correlations of high pT charged hadrons have been measured in Au+Au collisions at sqrt[sNN]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high pT partons. The monotonic rise of v2(pT) for pT<2 GeV/c is consistent with collective hydrodynamical flow calculations. At pT>3 GeV/c, a saturation of v2 is observed which persists up to pT=6 GeV/c.
Elliptic flow holds much promise for studying the early-time thermalization attained in ultrarelativistic nuclear collisions. Flow measurements also provide a means of distinguishing between hydrodynamic models and calculations which approach the low density (dilute gas) limit. Among the effects that can complicate the interpretation of elliptic flow measurements are azimuthal correlations that are unrelated to the reaction plane (nonflow correlations). Using data for Au + Au collisions at sqrt[sNN]=130 GeV from the STAR time projection chamber, it is found that four-particle correlation analyses can reliably separate flow and nonflow correlation signals. The latter account for on average about 15% of the observed second-harmonic azimuthal correlation, with the largest relative contribution for the most peripheral and the most central collisions. The results are also corrected for the effect of flow variations within centrality bins. This effect is negligible for all but the most central bin, where the correction to the elliptic flow is about a factor of 2. A simple new method for two-particle flow analysis based on scalar products is described. An analysis based on the distribution of the magnitude of the flow vector is also described.
We report the first observation of K*(892)0--> pi K in relativistic heavy ion collisions. The transverse momentum spectrum of (K*0+K*0)/2 from central Au+Au collisions at sqrt[sNN]=130 GeV is presented. The ratios of the K*0 yield derived from these data to the yields of negative hadrons, charged kaons, and phi mesons have been measured in central and minimum bias collisions and compared with model predictions and comparable e+e-, pp, and p-barp results. The data indicate no dramatic reduction of K*0 production in relativistic heavy ion collisions despite expected losses due to rescattering effects.
The STAR Collaboration reports the first observation of exclusive rho 0 photoproduction, AuAu-->AuAu rho 0, and rho 0 production accompanied by mutual nuclear Coulomb excitation, AuAu-->Au [star] Au [star] rho 0, in ultraperipheral heavy-ion collisions. The rho 0 have low transverse momenta, consistent with coherent coupling to both nuclei. The cross sections at sqrt[sNN]=130 GeV agree with theoretical predictions treating rho 0 production and Coulomb excitation as independent processes.
We report STAR results on the azimuthal anisotropy parameter v2 for strange particles K0S, Lambda , and Lambda -bar at midrapidity in Au+Au collisions at sqrt[sNN]=130 GeV at the Relativistic Heavy Ion Collider. The value of v2 as a function of transverse momentum, pt, of the produced particle and collision centrality is presented for both particles up to pt~3.0 GeV/c. A strong pt dependence in v2 is observed up to 2.0 GeV/c. The v2 measurement is compared with hydrodynamic model calculations. The physics implications of the pt integrated v2 magnitude as a function of particle mass are also discussed.
Inclusive transverse momentum distributions of charged hadrons within 0.2<pT<6.0 GeV/c have been measured over a broad range of centrality for Au+Au collisions at sqrt[sNN]=130 GeV. Hadron yields are suppressed at high pT in central collisions relative to peripheral collisions and to a nucleon-nucleon reference scaled for collision geometry. Peripheral collisions are not suppressed relative to the nucleon-nucleon reference. The suppression varies continuously at intermediate centralities. The results indicate significant nuclear medium effects on high-pT hadron production in heavy-ion collisions at high energy.
We report the first measurement of strange ( Lambda ) and antistrange ( Lambda -bar) baryon production from sqrt[sNN]=130 GeV Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Rapidity density and transverse mass distributions at midrapidity are presented as a function of centrality. The yield of Lambda and Lambda -bar hyperons is found to be approximately proportional to the number of negative hadrons. The production of Lambda -bar hyperons relative to negative hadrons increases very rapidly with transverse momentum. The magnitude of the increase cannot be described by existing hadronic string fragmentation models alone.
Two-pion correlation functions in Au+Au collisions at sqrt[sNN] = 130 GeV have been measured by the STAR (solenoidal tracker at RHIC) detector. The source size extracted by fitting the correlations grows with event multiplicity and decreases with transverse momentum. Anomalously large sizes or emission durations, which have been suggested as signals of quark-gluon plasma formation and rehadronization, are not observed. The Hanbury Brown-Twiss parameters display a weak energy dependence over a broad range in sqrt[sNN].
The first measurements of light antinucleus production in Au+Au collisions at the Relativistic Heavy-Ion Collider are reported. The observed production rates for d-bar and 3He-bar are much larger than in lower energy nucleus-nucleus collisions. A coalescence model analysis of the yields indicates that there is little or no increase in the antinucleon freeze-out volume compared to collisions at CERN SPS energy. These analyses also indicate that the 3He-bar freeze-out volume is smaller than the d-bar freeze-out volume.
We present the first measurement of midrapidity vector meson phi production in Au+Au collisions at RHIC (sqrt[sNN]=130 GeV) from the STAR detector. For the 11% highest multiplicity collisions, the slope parameter from an exponential fit to the transverse mass distribution is T=379±50(stat)±45(syst) MeV, the yield dN/dy=5.73±0.37(stat)±0.69(syst) per event, and the ratio N phi /Nh- is found to be 0.021±0.001(stat)±0.004(syst). The measured ratio N phi /Nh- and T for the phi meson at midrapidity do not change for the selected multiplicity bins.
We report first results on elliptic flow of identified particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR TPC at RHIC. The elliptic flow as a function of transverse momentum and centrality differs significantly for particles of different masses. This dependence can be accounted for in hydrodynamic models, indicating that the system created shows a behavior consistent with collective hydrodynamical flow. The fit to the data with a simple model gives information on the temperature and flow velocities at freeze-out.
The minimum-bias multiplicity distribution and the transverse momentum and pseudorapidity distributions for central collisions have been measured for negative hadrons ( h-) in Au+Au interactions at sqrt[sNN] = 130 GeV. The multiplicity density at midrapidity for the 5% most central interactions is dNh-/d eta | eta = 0 = 280±1(stat)±20(syst), an increase per participant of 38% relative to pp-bar collisions at the same energy. The mean transverse momentum is 0.508±0.012 GeV/c and is larger than in central Pb+Pb collisions at lower energies. The scaling of the h- yield per participant is a strong function of pperp. The pseudorapidity distribution is almost constant within | eta |<1.
We report the first measurement of inclusive antiproton production at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV by the STAR experiment at RHIC. The antiproton transverse mass distributions in the measured transverse momentum range of 0.25<pperp<0.95 GeV/c are found to fall less steeply for more central collisions. The extrapolated antiproton rapidity density is found to scale approximately with the negative hadron multiplicity density.
We report results on the ratio of midrapidity antiproton-to-proton yields in Au+Au collisions at sqrt[sNN] = 130 GeV per nucleon pair as measured by the STAR experiment at RHIC. Within the rapidity and transverse momentum range of | y|<0.5 and 0.4<pt<1.0 GeV/c, the ratio is essentially independent of either transverse momentum or rapidity, with an average of 0.65±0.01(stat)±0.07(syst) for minimum bias collisions. Within errors, no strong centrality dependence is observed. The results indicate that at this RHIC energy, although the p-p-bar pair production becomes important at midrapidity, a significant excess of baryons over antibaryons is still present.
Acute myeloid/lymphoid leukemia is a fatal hematological malignancy characterized by accumulation of nonfunctional, immature blasts, which interferes with the production of normal blood cells. Activating mutations of receptor tyrosine kinases are common genetic lesions in leukemia. FLT3-ITD is a frequent activating mutation found in AML patients, leading to uncontrolled proliferation of leukemic blasts. FLT3-ITD directly activates STAT5, leading to the induction of STAT5 target gene expression like PIM kinases and SOCS genes. STAT5 and PIM kinases have been shown to play a crucial role in the FLT3-ITD mediated transformation. On the other hand, the role of SOCS proteins in FLT3-ITD mediated transformation has not been studied to date. SOCS proteins are part of a negative feedback mechanism that controls Jak kinases downstream of cytokine receptors. One of the SOCS family members, SOCS1 has been reported to suppress oncogenecity of several activating kinases implicated in hematologic malignancies. In this thesis the role of these SOCS proteins in FLT3-ITD mediated transformation (in vitro) and leukemogenesis (in vivo) is systematically explored. Expression of FLT3-ITD in cell lines of myeloid (32D) and lymphoid (Ba/F3) origin, led to CIS, SOCS1 and SOCS2 expression. FLT3-ITD expression in primary murine bone marrow stem/progenitor cells led to a 59 fold induction of SOCS1 expression. Furthermore, FLT3-ITD positive AML cell lines (MV4-11, MOLM-13) show kinase dependent CIS, SOCS1, and SOCS3 expression. Importantly SOCS1 is highly expressed in AML patients with FLT3-ITD compared to healthy individuals. SOCS1 protein was expressed in FLT3-ITD transduced murine bone marrow stem cells and SOCS1 expression was abolished with kinase inhibition in MOLM-13 cell line. In conclusion, SOCS1 was highly regulated by FLT3-ITD in myeloid, lymphoid cell lines, in bone marrow stem/progenitors and in AML patient samples. SOCS1 co-expression did not affect FLT3-ITD mediated signaling and proliferation, but abolished IL-3 mediated proliferation and protected 32D cells from interferon-α and interferon-γ mediated growth inhibition. FLT3-ITD expressing 32D cells showed diminished STAT1 activation in response to interferons (α and γ). Alone, SOCS1 strongly inhibited cytokine induced colony formation of bone marrow stem and progenitors, but not FLT3-ITD induced colony formation. Most importantly, in the presence of growth inhibitory interferon-γ, SOCS1 co-expression with FLT3-ITD led to increased colony formation compared to FLT3-ITD alone. Taken together, FLT3-ITD induced and exogenously expressed SOCS1, shielded cells from external cytokines, signals, while not affecting FLT3-ITD induced proliferation/signaling. In further experiments the in vivo effects of SOCS1 were studied in a bone marrow transplantation model. SOCS1 bone marrow transplants were unable to engraft/proliferate in mice. FLT3-ITD was shown to induce a myeloproliferative disease. Both control (empty vector), SOCS1 transplanted mice were normal and did not show any disease phenotype. FLT3-ITD alone and SOCS1 co-expressing FLT3-ITD developed either myeloproliferative disease or acute lymphoblastic leukemia with equal distribution. SOCS1 co-expression with FLT3-ITD led to a decreased latency. Mice transplanted with FLT3-ITD alone and SOCS1 co-expressing FLT3-ITD displayed enlarged spleens, liver and hypercellular bone marrow indicating infiltration of leukemic cells. Mice were also anemic and showed decreased platelet counts. Importantly SOCS1 co-expression particularly shortened the latency of myeloproliferative disease but not of acute lymphoblastic leukemia. In summary, in the context of FLT3-ITD, SOCS1 acts as a ‘conditional oncogene’ and cooperates with FLT3-ITD in the development of myeloproliferative disease. With these data we propose the following model: FLT3-ITD induces SOCS gene expression, which shields cells against proliferation and differentiation signals from cytokines, while not affecting FLT3-ITD mediated proliferative signals. This leaves cells under the dictate of FLT3-ITD thereby contributing to leukemogenesis. Similar to FLT3-ITD, BCR/ABL (P190) (an oncogenic fusion kinase often found in acute lymphoblastic leukemia) induces SOCS gene expression in K562 and long-term cultured cells from patients with acute lymphoblastic leukemia. SOCS1 co-expression does not affect BCR/ABL mediated proliferation while abrogating IL-3 mediated proliferation. These findings suggest that SOCS proteins may play a general co-operative role in the context of oncogenes which aberrantly activate STAT3/5 independently of JAK kinases. This study reveals a novel molecular mechanism of FLT3-ITD mediated leukemogenesis and suggests SOCS genes as potential therapeutic targets.
Treatment with tyrosine kinase inhibitors is the standard of care for Philadelphia chromosome positive leukemias. However the eradication of leukemia initiating cells remains a challenge. Circumstantial evidence suggests that the cytokine microenvironment may play a role in BCR-ABL mediated leukemogenesis and in imatinib resistance. Gene expression analyses of BCR-ABL positive ALL long-term cultured cells revealed strong reduction of SOCS mRNA expression after imatinib treatment, thereby demonstrating a strong inhibition of cytokine signaling. In this study we employed SOCS1—a strong inhibitor of cytokine signaling—as a tool to terminate external cytokine signals in BCR-ABL transformed cells in vitro and in vivo. In colony formation assays with primary bone marrow cells, expression of SOCS1 decreased colony numbers under pro-proliferative cytokines, while it conferred growth resistance to anti-proliferative cytokines. Importantly, co-expression of SOCS1 with BCR-ABL led to the development of a MPD phenotype with a prolonged disease latency compared to BCR-ABL alone in a murine bone marrow transplantation model. Interestingly, SOCS1 co-expression protected 20% of mice from MPD development. In summary, we conclude that under pro-proliferative cytokine stimulation at the onset of myeloproliferative diseases SOCS1 acts as a tumor suppressor, while under anti-proliferative conditions it exerts oncogenic function. Therefore SOCS1 can promote opposing functions depending on the cytokine environment.
Background: Candida spp. are a frequent cause of nosocomial bloodstream infections worldwide.
Objective: To evaluate the use patterns and outcomes associated with intravenous (IV) fluconazole therapy in intensive care units in Spain and Germany.
Patients and methods: The research reported here was a prospective multicenter longitudinal observational study in adult intensive care unit patients receiving IV fluconazole. Demographic, microbiologic, therapy success, length of hospital stay, adverse event, and all-cause mortality data were collected at 14 sites in Spain and five in Germany, from February 2004 to November 2005.
Results: Patients (n = 303) received prophylaxis (n = 29), empiric therapy (n = 140), preemptive therapy (n = 85), or definitive therapy (n = 49). A total of 298 patients (98.4%) were treated with IV fluconazole as first-line therapy. The treating physicians judged therapy successful in 66% of prophylactic, 55% of empiric, 45% of preemptive, and 43% of definitive group patients. In the subgroup of 152 patients with proven and specified Candida infection only, 32% suffered from Candida specified as potentially resistant to IV fluconazole. The overall mortality rate was 42%.
Conclusion: Our study informs treatment decision makers that approximately 32% of the patients with microbiological results available suffered from Candida specified as potentially resistant to IV fluconazole, highlighting the importance of appropriate therapy.
The taxonomic status of the nominal taxon Dryophis prasinus flavescens Wall, 1910 is reevaluated herein. Based on molecular data generated from fresh collections of Ahaetulla prasina (H. Boie in F. Boie, 1827) auctorum from Northeast India and, additionally, morphological data from museum specimens originating from the same areas, we resurrect this taxon as Ahaetulla flavescens (Wall, 1910) comb. nov. We clarify the status, identity and locations of its type specimens, rediscover, redescribe and illustrate those specimens and also designate a lectotype in order to effect a proper taxonomic redefinition of this nominal taxon. We provide further details on the morphology and diagnosis of this species and elucidate its phylogenetic position. We also provide a summary of the natural history and distribution of this species. Adding to the known cryptic diversity and genetic divergence within Southeast Asian populations, this work also hints at the need for a taxonomic revision of the A. prasina complex. This work complements a previous study on the A. prasina complex focusing on populations in Indonesia. Taken together, these two studies represent phylogenetic reconstructions from different populations of the A. prasina complex across its distribution range, on the Asian mainland and the surrounding islands.
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the Xchromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10-9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10-9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
The Indian species of the genera Orionis Shaw and Stenothremma Shaw (Braconidae, Euphorinae) are reviewed. Both genera are reported for the first time from India. Three new species, Orionis shillongensis Gupta, van Achterberg & Pattar sp. nov. from north-eastern India (Meghalaya), O. femorator Gupta, van Achterberg & Pattar sp. nov. from southern India (Karnataka and Tamil Nadu) and Stenothremma flavator Gupta & van Achterberg sp. nov. from southern India (Karnataka) are illustrated and described. A key to the Old World species of Orionis Shaw is provided.