Several members of the Actinomycetales, including the medically important mycobacteria, produce 1-D-myo-inosityl-2-(N-acetyl-L-cysteinyl)amino-2-deoxy-alpha-D- glucop yranoside (trivial name ...mycothiol) as their principal low-molecular-mass thiol. The pseudo-disaccharide component of mycothiol, 1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside (alpha-D-GI), was synthesized by ligation of 1-D,L-2,3,4,5, 6-penta-O-acetyl-myo-inositol to 3,4,6-tri-O-acetyl-2-deoxy- 2-(2,4-dinitrophenylamino)-alpha-D-glu- copyranosyl bromide to give, in the first instance, an isomeric mixture of alpha- and beta-linked pseudo-disaccharides. The alpha-coupled D,D and D,L isomers, alpha-D-GI and alpha-L-GI respectively, were purified from the mixture by TLC, followed by removal of the protecting groups. A cell-free extract of Mycobacterium smegmatis catalysed the ligation of cysteine, acetate and alpha-D-GI in the presence of ATP and Mg2+ to form mycothiol, as judged by HPLC. When no acetate was added to the incubation mixture, an additional thiol accumulated. In the presence of 14Cacetate no radiolabel was recovered in this species, but only in mycothiol. The additional thiol was isolated as the bimane derivative, and 1H and 1H-1H COSY NMR spectra confirmed its identity as desacetylmycothiol. A more complete conversion of desacetylmycothiol into mycothiol was achieved in the presence of acetyl-S-CoA. These results indicate that the biosynthesis of mycothiol proceeds by the sequential addition of cysteine and acetate to alpha-D-GI. The inositol moiety appears to be an important determinant of specificity, since alpha-L-GI was poorly utilized.
Abstract
High-statistics
$$\pi ^-\pi ^-$$
π
-
π
-
and
$$\pi ^+\pi ^+$$
π
+
π
+
femtoscopy data are presented for Au + Au collisions at
$$\sqrt{s_\mathrm{NN}} = 2.4~\hbox {GeV}$$
s
NN
=
2.4
GeV
, ...measured with HADES at SIS18/GSI. The experimental correlation functions allow the determination of the space-time extent of the corresponding emission sources via a comparison to models. The emission source, parametrized as three-dimensional Gaussian distribution, is studied in dependence on pair transverse momentum, azimuthal emission angle with respect to the reaction plane, collision centrality and beam energy. For all centralities and transverse momenta, a geometrical distribution of ellipsoidal shape is found in the plane perpendicular to the beam direction with the larger extension perpendicular to the reaction plane. For large transverse momenta, the corresponding eccentricity approaches the initial eccentricity. The eccentricity is smallest for most central collisions, where the shape is almost circular. The magnitude of the tilt angle of the emission ellipsoid in the reaction plane decreases with increasing centrality and increasing transverse momentum. All source radii increase with centrality, largely exhibiting a linear rise with the cube root of the number of participants. A substantial charge-sign difference of the source radii is found, appearing most pronounced at low transverse momentum. The extracted source parameters are consistent with the extrapolation of their energy dependence down from higher energies.
High-statistics π-π- and π+π+ femtoscopy data are presented for Au + Au collisions at sNN=2.4GeV, measured with HADES at SIS18/GSI. The experimental correlation functions allow the determination of ...the space-time extent of the corresponding emission sources via a comparison to models. The emission source, parametrized as three-dimensional Gaussian distribution, is studied in dependence on pair transverse momentum, azimuthal emission angle with respect to the reaction plane, collision centrality and beam energy. For all centralities and transverse momenta, a geometrical distribution of ellipsoidal shape is found in the plane perpendicular to the beam direction with the larger extension perpendicular to the reaction plane. For large transverse momenta, the corresponding eccentricity approaches the initial eccentricity. The eccentricity is smallest for most central collisions, where the shape is almost circular. The magnitude of the tilt angle of the emission ellipsoid in the reaction plane decreases with increasing centrality and increasing transverse momentum. All source radii increase with centrality, largely exhibiting a linear rise with the cube root of the number of participants. A substantial charge-sign difference of the source radii is found, appearing most pronounced at low transverse momentum. The extracted source parameters are consistent with the extrapolation of their energy dependence down from higher energies.
We present high-statistic data on charged-pion emission from Au + Au collisions at
s
NN
=
2.4
GeV
(corresponding to
E
beam
=
1.23
A GeV
) in four centrality classes in the range 0–40% of the most ...central collisions. The data are analyzed as a function of transverse momentum, transverse mass, rapidity, and polar angle. Pion multiplicity per participating nucleon decreases moderately with increasing centrality. The polar angular distributions are found to be non-isotropic even for the most central event class. Our results on pion multiplicity fit well into the general trend of the available world data, but undershoot by
2.5
σ
data from the FOPI experiment measured at slightly lower beam energy. We compare our data to state-of-the-art transport model calculations (PHSD, IQMD, PHQMD, GiBUU and SMASH) and find substantial differences between the measurement and the results of these calculations.
Retrospective analysis of 139 ventilation-perfusion (V/Q) lung scans obtained for suspected pulmonary embolism (PE) was undertaken, using the Biello criteria for interpretation. All scans were ...correlated with chest radiographs obtained within 24 hours and with pulmonary angiograms obtained within 72 hours of the V/Q study. The prevalence of PE in the high-, intermediate-, and low-probability groups was 89.5%, 49.3%, and 3.6%, respectively. Using minor modifications of these criteria, V/Q scans interpreted as high or low probability had a sensitivity of 97.1%, specificity of 94.3%, and accuracy of 95.7%. Perfusion defects corresponding to radiographic abnormalities that were present for at least 10 days were less likely to be associated with PE. Separate analysis of 27 perfusion-only lung scans that met all other criteria for inclusion in the study confirmed the nonspecificity of perfusion-only lung imaging and indicated the need for ventilation imaging with Tc-99m-DTPA aerosol or Kr-81m gas for portable studies.
Using an adaptive trial design to minimize the exposure of patients to inactive agents and to detect more active regimens sooner, investigators found that adding veliparib and carboplatin to standard ...therapy improved outcome in triple-negative breast cancer.
Breast cancer is genetically and clinically heterogeneous, which makes it challenging to identify effective patient-specific therapies. Although mortality due to breast cancer in the United States has decreased, more than 40,000 women in the United States still die from this disease each year.
1
Further decreases in mortality will require therapeutic options that target biologic properties of tumors and can be delivered early enough in the disease course to make a clinical difference.
The neoadjuvant approach facilitates the evaluation of an individual patient's response to treatment and holds promise for the development of experimental therapies for disease while it is still . . .
Abstract
Objective
To examine whether demographic variables can assist in predicting executive dysfunction in individuals with temporal lobe epilepsy (TLE).
Method
Data were collected from ...presurgical evaluations of 13 individuals with TLE (67% females, mean age 34 ± 12) at the University of California, San Francisco Epilepsy Center. Executive functions were assessed using subtests from the D-KEFS (Verbal Fluency and Color/Word Interference Tests) and the Trail Making Test B. Given that depression and anxiety symptoms have been previously shown to be associated with poorer executive performance in individuals with TLE (Paradiso et al., 2001), predictability of the BDI-II and BAI scores were also tested. Linear regression analyses were used to test predictive values of demographic variables (age, age at seizure onset ASO, years of education, gender, and right vs. left temporal epileptogenic source).
Results
ASO (β = .75, p = .021), gender (β = .632, p = .041), and education (β = .555, p = .05) explained 66% of the variance in the Verbal Fluency Switching scaled scores (R²=.66, F(4,8)= 3.876, p = .049). Education (β = .772, p = .009) and ASO (β = .686, p = .023) explained 70% of the variance in Verbal Fluency Switching Accuracy scaled scores (R² = .708, F(4,8) = 4.844, p = .028). Age (β = -.862, p = .003) and seizure onset (β = .457, p = .049) explained 52% of the variance in BAI scores (R² = .525, F(4,16) = 3.319, p = .032).
Conclusions
ASO predicted category switching and anxiety severity, while none of the demographic variables explored in this study predicted visuomotor switching. Further research should explore the efficacy of early interventions to protect against future executive dysfunction in TLE.
Among patients with HER2-positive, hormone-receptor–negative locally advanced breast cancer, the addition of neratinib to standard therapy resulted in higher rates of pathological complete response, ...with some higher rates of toxic effects.
The treatment of aggressive, locally advanced breast cancers increasingly includes neoadjuvant therapy before surgical resection, thus providing a window of opportunity to tailor treatments on the basis of early assessments of the molecular characteristics of the cancer and their response to therapy. The existence of a well-characterized, surrogate end point — pathological complete response as assessed at the time of surgery — that is strongly correlated with both event-free survival and overall survival makes neoadjuvant therapy a particularly useful context for the rapid clinical development of targeted therapies. The I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic . . .
The diagnostic performance of single-photon emission computed tomography (SPECT) and planar imaging of thallium-201 uptake for the detection of coronary artery disease (CAD) was compared in 79 ...patients who underwent both dipyridamole thallium-201 scintigraphy and coronary angiography. Clinical subgroups were assigned by severity of CAD, presence of a prior myocardial infarction and the number of narrowed coronary arteries. The overall detection of CAD was 89% for SPECT and 67% for planar (p less than 0.001). For the anterior vascular territory, sensitivities for SPECT and planar imaging were 69 and 44% (p less than 0.01), respectively; for the posterior vascular territory, sensitivities were 80 and 54% (p less than 0.01). Receiver-operating characteristic analysis, using a 5-point evaluation scale, was performed for the anterior and posterior vascular territories. Receiver-operating characteristic curves generated for SPECT and planar studies demonstrated improved diagnostic performance by SPECT in the anterior vascular territory, but showed similar performance in the posterior territory because of lower SPECT specificity despite higher sensitivity at clinically relevant decision thresholds. In each clinical subgroup of patients, the detection of CAD by SPECT was significantly superior to that by planar imaging, regardless of the severity of stenosis or the number of significantly narrowed coronary arteries, or whether a myocardial infarction was present. Thus, SPECT thallium-201 scintigraphy is an important and necessary clinical tool for detecting CAD after dipyridamole infusion.
The HADES collaboration uses the e
+
e
−
production as a probe of the resonance matter produced in collisions at incident energies of 1-3.5 GeV/nucleon at GSI. Elementary reactions provide useful ...references for these studies and give information on resonance Dalitz decays (R→Ne
+
e
−
). Such processes are sensitive to the structure of time-like electromagnetic baryon transitions in a kinematic range where (off-shell) vector mesons play a crucial role. Results obtained in proton-proton reactions and in a commissioning pion-beam experiment are reported and prospects for future pion beam experiments and for first hyperon Dalitz decay measurements are described. The connection with the investigations of medium effects to be continued with HADES in the next years at SIS18 and SIS100 is also discussed.
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