1,663 research outputs found
Ab initio study of the CE magnetic phase in half-doped manganites: Purely magnetic versus double exchange description
The leading electronic interactions governing the local physics of the CE
phase of half-doped manganites are extracted from correlated ab initio
calculations performed on an embedded cluster. The electronic structure of the
low-energy states is dominated by double exchange configurations and
O-2 to Mn-3d charge transfer configurations. The model spectra of
both a purely magnetic non-symmetric Heisenberg Hamiltonian involving a
magnetic oxygen and two non-symmetric double exchange models are compared to
the \textit{ab initio} one. While a satisfactory agreement between the
Heisenberg spectrum and the calculated one is obtained, the best description is
provided by a double exchange model involving excited non-Hund atomic states.
This refined model not only perfectly reproduces the spectrum of the embedded
cluster in the crystal geometry, but also gives a full description of the local
double-well potential energy curve of the ground state (resulting from the
interaction of the charge localized electronic configurations) and the local
potential energy curves of all excited states ruled by the double exchange
mechanism
Immune and virologic responses to Truvada or Combivir as a first-line therapy of HIV-infected, treatment-naïve patients
Methods 107 HIV-infected, ARV-naive patients were prospectively enrolled and treated with TVD (300 mg TDF + 200 mg FTC QD) or CBV (300 mg AZT + 150 mg 3TC BID) in combination with EFV (600 mg QD) or a PI (LPV/r, ATV/ r, fAPV/r and SQV/r). Twenty-seven patients received TVD-EFV, 33 received TVD-PI, 24 received CBV-EFV, and 23 received CBV-PI. Fifty-one of these patients have, so far, reached 12 months of therapy. Clinical, immunological and virologic parameters at baseline and after 12 months of therapy are presented
Collagen release by human hepatic stellate cells requires vitamin C and is efficiently blocked by hydroxylase inhibition
Liver fibrosis is characterized by the accumulation of extracellular matrix proteins, mainly composed of collagen. Hepatic stellate cells (HSCs) mediate liver fibrosis by secreting collagen. Vitamin C (ascorbic acid) is a cofactor of prolyl-hydroxylases that modify newly synthesized collagen on the route for secretion. Unlike most animals, humans cannot synthesize ascorbic acid and its role in liver fibrosis remains unclear. Here, we determined the effect of ascorbic acid and prolyl-hydroxylase inhibition on collagen production and secretion by human HSCs. Primary human HSCs (p-hHSCs) and the human HSCscell line LX-2 were treated with ascorbic acid, transforming growth factor-beta (TGFβ) and/or the pan-hydroxylase inhibitor dimethyloxalylglycine (DMOG). Expression of collagen-I was analyzed by RT-qPCR (COL1A1), Western blotting, and immunofluorescence microscopy. Collagen secretion was determined in the medium by Western blotting for collagen-I and by HPLC for hydroxyproline concentrations. Expression of solute carrier family 23 members 1 and 2 (SLC23A1/SLC23A2), encoding sodium-dependent vitamin C transporters 1 and 2 (SVCT1/SVCT2) was quantified in healthy and cirrhotic human tissue. In the absence of ascorbic acid, collagen-I accumulated intracellularly in p-hHSCs and LX-2 cells, which was potentiated by TGFβ. Ascorbic acid co-treatment strongly promoted collagen-I excretion and enhanced extracellular hydroxyproline concentrations, without affecting collagen-I (COL1A1) mRNA levels. DMOG inhibited collagen-I release even in the presence of ascorbic acid and suppressed COL1A1 and alpha-smooth muscle actin (αSMA/ACTA2) mRNA levels, also under hypoxic conditions. Hepatocytes express both ascorbic acid transporters, while p-hHSCs and LX-2 express the only SVCT2, which is selectively enhanced in cirrhotic livers. Human HSCs rely on ascorbic acid for the efficient secretion of collagen-I, which can be effectively blocked by hydroxylase antagonists, revealing new therapeutic targets to treat liver fibrosis
Domain Walls in Two-Component Dynamical Lattices
We introduce domain-wall (DW) states in the bimodal discrete nonlinear
Schr{\"{o}}dinger equation, in which the modes are coupled by cross phase
modulation (XPM). By means of continuation from various initial patterns taken
in the anti-continuum (AC) limit, we find a number of different solutions of
the DW type, for which different stability scenarios are identified. In the
case of strong XPM coupling, DW configurations contain a single mode at each
end of the chain. The most fundamental solution of this type is found to be
always stable. Another solution, which is generated by a different AC pattern,
demonstrates behavior which is unusual for nonlinear dynamical lattices: it is
unstable for small values of the coupling constant (which measures the
ratio of the nonlinearity and coupling lengths), and becomes stable at larger
. Stable bound states of DWs are also found. DW configurations generated by
more sophisticated AC patterns are identified as well, but they are either
completely unstable, or are stable only at small values of . In the case of
weak XPM, a natural DW solution is the one which contains a combination of both
polarizations, with the phase difference between them 0 and at the
opposite ends of the lattice. This solution is unstable at all values of ,
but the instability is very weak for large , indicating stabilization as the
continuum limit is approached. The stability of DWs is also verified by direct
simulations, and the evolution of unstable DWs is simulated too; in particular,
it is found that, in the weak-XPM system, the instability may give rise to a
moving DW.Comment: 14 pages, 14 figures, Phys. Rev. E (in press
Relative Aerobic Load of Daily Activities After Stroke
Objective: Individuals after stroke are less active, experience more fatigue, and perform activities at a slower pace than peers with no impairments. These problems might be caused by an increased aerobic energy expenditure during daily tasks and a decreased aerobic capacity after stroke. The aim of this study was to quantify relative aerobic load (ie, the ratio between aerobic energy expenditure and aerobic capacity) during daily-life activities after stroke. Methods: Seventy-nine individuals after stroke (14 in Functional Ambulation Category [FAC] 3, 25 in FAC 4, and 40 in FAC 5) and 22 peers matched for age, sex, and body mass index performed a maximal exercise test and 5 daily-life activities at a preferred pace for 5 minutes. Aerobic energy expenditure (mL O2/kg/min) and economy (mL O2/kg/unit of distance) were derived from oxygen uptake (V˙O2). Relative aerobic load was defined as aerobic energy expenditure divided by peak aerobic capacity (%V˙O2peak) and by V˙O2 at the ventilatory threshold (%V˙O2-VT) and compared in individuals after stroke and individuals with no impairments. Results: Individuals after stroke performed activities at a significantly higher relative aerobic load (39%-82% V˙O2peak) than peers with no impairments (38%-66% V˙O2peak), despite moving at a significantly slower pace. Aerobic capacity in individuals after stroke was significantly lower than that in peers with no impairments. Movement was less economical in individuals after stroke than in peers with no impairments. Conclusion: Individuals after stroke experience a high relative aerobic load during cyclic daily-life activities, despite adopting a slower movement pace than peers with no impairments. Perhaps individuals after stroke limit their movement pace to operate at sustainable relative aerobic load levels at the expense of pace and economy. Impact: Improving aerobic capacity through structured aerobic training in a rehabilitation program should be further investigated as a potential intervention to improve mobility and functioning after stroke.</p
99mTc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy
PURPOSE: The purpose of this study was to determine the value of (99m)Tc Hynic-rh-Annexin-V-Scintigraphy (TAVS), a non-invasive in vivo technique to demonstrate apoptosis in patients with head and neck squamous cell carcinoma. METHODS: TAVS were performed before and within 48 h after the first course of cisplatin-based chemoradiation. Radiation dose given to the tumour at the time of post-treatment TAVS was 6-8 Gy. Single-photon emission tomography data were co-registered to planning CT scan. Complete sets of these data were available for 13 patients. The radiation dose at post-treatment TAVS was calculated for several regions of interest (ROI): primary tumour, involved lymph nodes and salivary glands. Annexin uptake was determined in each ROI, and the difference between post-treatment and baseline TAVS represented the absolute Annexin uptake: Delta uptake (DeltaU). RESULTS: In 24 of 26 parotid glands, treatment-induced Annexin uptake was observed. Mean DeltaU was significantly correlated with the mean radiation dose given to the parotid glands (r = 0.59, p = 0.002): Glands that received higher doses showed more Annexin uptake. DeltaU in primary tumour and pathological lymph nodes showed large inter-patient differences. A high correlation was observed on an inter-patient level (r = 0.71, p = 0.006) between the maximum DeltaU in primary tumour and in the lymph nodes. CONCLUSIONS: Within the dose range of 0-8 Gy, Annexin-V-scintigraphy showed a radiation-dose-dependent uptake in parotid glands, indicative of early apoptosis during treatment. The inter-individual spread in Annexin uptake in primary tumours could not be related to differences in dose or tumour volume, but the Annexin uptake in tumour and lymph nodes were closely correlated. This effect might represent a tumour-specific apoptotic respons
Pregnancy-associated serum N-glycome changes studied by high-throughput MALDI-TOF-MS
Pregnancy requires partial suppression of the immune system to ensure maternal-foetal tolerance. Protein glycosylation, and especially terminal sialic acid linkages, are of prime importance in regulating the pro- and anti-inflammatory immune responses. However, little is known about pregnancy-associated changes of the serum N-glycome and sialic acid linkages. Using a combination of recently developed methods, i.e. derivatisation that allows the distinction between α2,3- and α2,6-linked sialic acids by high-throughput MALDI-TOF-MS and software-assisted data processing, we analysed the serum N-glycome of a cohort of 29 healthy women at 6 time points during and after pregnancy. A total of 77 N-glycans were followed over time, confirming in part previous findings while also revealing novel associations (e.g. an increase of FA2BG1S1(6), FA2G1S1(6) and A2BG2S2(6) with delivery). From the individual glycans we calculated 42 derived traits. With these, an increase during pregnancy and decrease after delivery was observed for both α2,3- and α2,6-linked sialylation. Additionally, a difference in the recovery speed after delivery was observed for α2,3- and α2,6-linked sialylation of triantennary glycans. In conclusion, our new high-throughput workflow allowed the identification of novel plasma glycosylation changes with pregnancy
Brain functional connectivity alterations associated with neuropsychological performance 6-9 months following SARS-CoV-2 infection.
Neuropsychological deficits and brain damage following SARS-CoV-2 infection are not well understood. Then, 116 patients, with either severe, moderate, or mild disease in the acute phase underwent neuropsychological and olfactory tests, as well as completed psychiatric and respiratory questionnaires at 223 ± 42 days postinfection. Additionally, a subgroup of 50 patients underwent functional magnetic resonance imaging. Patients in the severe group displayed poorer verbal episodic memory performances, and moderate patients had reduced mental flexibility. Neuroimaging revealed patterns of hypofunctional and hyperfunctional connectivities in severe patients, while only hyperconnectivity patterns were observed for moderate. The default mode, somatosensory, dorsal attention, subcortical, and cerebellar networks were implicated. Partial least squares correlations analysis confirmed specific association between memory, executive functions performances and brain functional connectivity. The severity of the infection in the acute phase is a predictor of neuropsychological performance 6-9 months following SARS-CoV-2 infection. SARS-CoV-2 infection causes long-term memory and executive dysfunctions, related to large-scale functional brain connectivity alterations
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