Stacking fault energies (SFE) were determined in additively manufactured (AM) stainless steel (SS 316 L) and equiatomic CrCoNi medium-entropy alloys. AM specimens were fabricated via directed energy ...deposition and tensile loaded at room temperature. In situ neutron diffraction was performed to obtain a number of faulting-embedded diffraction peaks simultaneously from a set of (hkl) grains during deformation. The peak profiles diffracted from imperfect crystal structures were analyzed to correlate stacking fault probabilities and mean-square lattice strains to the SFE. The result shows that averaged SFEs are 32.8 mJ/m
for the AM SS 316 L and 15.1 mJ/m
for the AM CrCoNi alloys. Meanwhile, during deformation, the SFE varies from 46 to 21 mJ/m
(AM SS 316 L) and 24 to 11 mJ/m
(AM CrCoNi) from initial to stabilized stages, respectively. The transient SFEs are attributed to the deformation activity changes from dislocation slip to twinning as straining. The twinning deformation substructure and atomic stacking faults were confirmed by electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM). The significant variance of the SFE suggests the critical twinning stress as 830 ± 25 MPa for the AM SS 316 L and 790 ± 40 MPa for AM CrCoNi, respectively.
Aims: Microglia are involved in neurodegeneration, are prime targets for anti‐inflammatory therapy and are potential biomarkers of disease progression. For example, positron emission tomography ...imaging employing radioligands for the mitochondrial translocator protein of 18 kDa (TSPO, formerly known as the peripheral benzodiazepine receptor) is being scrutinized to detect neuroinflammation in various diseases. TSPO is presumably present in activated microglia, but may be present in other neural cells. Methods: We sought to elucidate the protein expression in normal human central nervous system, several neurological diseases (HIV encephalitis, Alzheimer's disease, multiple sclerosis and stroke) and simian immunodeficiency virus encephalitis by performing immunohistochemistry with two anti‐TSPO antibodies. Results: Although the overall parenchymal staining was minimal in normal brain, endothelial and smooth muscle cells, subpial glia, intravascular monocytes and ependymal cells were TSPO‐positive. In disease states, elevated TSPO was present in parenchymal microglia, macrophages and some hypertrophic astrocytes, but the distribution of TSPO varied depending on the disease, disease stage and proximity to the lesion or relation to infection. Staining with the two antibodies correlated well in white matter, but one antibody also stained cortical neurones. Quantitative analysis demonstrated a significant increase in TSPO in the white matter of HIV encephalitis compared with brains without encephalitis. TSPO expression was also increased in simian immunodeficiency virus encephalitis. Conclusions: This report provides the first comprehensive immunohistochemical analysis of the expression of TSPO. The results are useful for informing the usage of positron emission tomography as an imaging modality and have an impact on the potential use of TSPO as an anti‐inflammatory pharmacological target.
Background
Although transarterial chemoembolization is recommended as the standard treatment for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma (BCLC‐B HCC), other treatments ...including liver resection have been used. This study aimed to determine the survival benefit of treatment strategies including resection for BCLC‐B HCC compared with non‐surgical treatments.
Methods
The nationwide multicentre database of the Korean Liver Cancer Association was reviewed. Patients with BCLC‐B HCC who underwent liver resection as a first or second treatment within 2 years of diagnosis and patients who received non‐surgical treatment were selected randomly. Survival outcomes of propensity score‐matched groups were compared.
Results
Among 887 randomly selected patients with BCLC‐B HCC, 83 underwent liver resection as first or second treatment and 597 had non‐surgical treatment. After propensity score matching, the two groups were well balanced (80 patients in each group). Overall median survival in the resection group was better than that for patients receiving non‐surgical treatment (50·9 versus 22·1 months respectively; P < 0·001). The 1‐, 2‐, 3‐ and 5‐year overall survival rates in the resection group were 90, 88, 75 and 63 per cent, compared with 79, 48, 35 and 22 per cent in the no‐surgery group (P < 0·001). In multivariable analysis, non‐surgical treatment only (hazard ratio (HR) 3·35, 95 per cent c.i. 2·16 to 5·19; P < 0·001), albumin level below 3·5 g/dl (HR 1·96, 1·22 to 3·15; P = 0·005) and largest tumour size greater than 5·0 cm (HR 1·81, 1·20 to 2·75; P = 0·005) were independent predictors of worse overall survival.
Conclusion
Treatment strategies that include liver resection offer a survival benefit compared with non‐surgical treatments for potentially resectable BCLC‐B HCC.
Selected patients benefit
AIMS: To identify an actinobacterial strain that can promote growth and alleviate salinity stress in tomato plants. METHODS AND RESULTS: Actinobacteria were isolated from agricultural soil and ...screened for ACC deaminase activity, production of indole acetic acid (IAA), solubilization of tricalcium phosphate and sodium chloride (NaCl) salinity tolerance. Among the several strains tested, one strain designated PGPA39 exhibited higher IAA production, and phosphate solubilization in addition to ACC deaminase activity, and tolerance to 1 mol l⁻¹NaCl. Strain PGPA39 was identified as a Streptomyces strain based on 16S rDNA sequence and designated Streptomyces sp. strain PGPA39. It promoted the growth of Arabidopsis seedlings in vitro as evidenced by a significant increase in plant biomass and number of lateral roots. Salinity stress‐alleviating activity of PGPA39 was evaluated using ‘Micro Tom’ tomato plants with 180 mmol l⁻¹NaCl stress under gnotobiotic condition. A significant increase in plant biomass and chlorophyll content and a reduction in leaf proline content were observed in PGPA39‐inoculated tomato plants under salt stress compared with control and salt‐stressed noninoculated plants. CONCLUSIONS: Streptomyces sp. strain PGPA39 alleviated salt stress and promoted the growth of tomato plants. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows the potential of Streptomyces sp. strain PGPA39 in alleviating salinity stress in tomato plants and could be utilized for stress alleviation in crop plants under field conditions.
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Through-silicon via (TSV) has been used for 3-dimentional integrated circuits. Mechanical stresses in Cu and Si around the TSV were measured using synchrotron X-ray microdiffraction. ...The hydrostatic stress in Cu TSV went from high tensile of 234MPa in the as-fabricated state, to −196MPa (compressive) during thermal annealing (in situ measurement), to 167MPa in the post-annealed state. Due to this stress, the keep-away distance in Si was determined to be about 17μm. Our results suggest that Cu stress may lead to reliability as well as integration issues, while Si stress may lead to device performance concerns.
We aimed to evaluate the long-term clinical outcomes and prognostic factors of symptomatic intracranial unruptured vertebrobasilar artery dissection (siu-VBD).
A total of 191 patients (M:F = 127:64; ...median age, 46 years) with siu-VBD were treated between January 2001 and December 2008. Presentations, treatments, outcomes, and prognostic factors were retrospectively analyzed.
Clinical manifestations were ischemic symptoms with headache (n = 97) or without headache (n = 13) and headache without ischemic symptoms (n = 81). Forty-six patients (24.1%) underwent endovascular treatment. The remaining 145 patients (75.9%) were medically treated with anticoagulants (n = 49), antiplatelets (n = 48), or analgesics alone (n = 48). Clinical follow-up data were available in 178 patients (102 ischemic and 76 nonischemic) at 15 to 102 months (mean, 46 months). None of the siu-VBD hemorrhaged. All 76 patients without ischemic presentation had favorable outcomes (modified Rankin Scale, 0-1). Of the 102 patients with ischemic presentation, outcomes were favorable in 92 and unfavorable in 10 patients. Four patients died; 3 died of causes unrelated to VBD, and one died as a result of basilar artery (BA) dissection. Old age (odds ratio OR 1.099; 95% confidence interval CI 1.103-1.204; p = 0.042) and BA involvement (OR 11.886; 95% CI 1.416-99.794; p = 0.023) were independent predictors of unfavorable outcomes in siu-VBD with ischemic presentation.
Clinical outcomes for siu-VBD were favorable in all patients without ischemic symptoms and in most patients with ischemic presentation. None of the siu-VBD caused subarachnoid hemorrhage. Old age and BA involvement were independent predictors of unfavorable outcome in siu-VBD with ischemic presentation.
There have been inconsistencies on the prognosis and controversies as to the proper management of acute basilar artery dissection. The aim of this study was to evaluate acute basilar artery ...dissection and its outcome after management.
A total of 21 patients (mean age, 53 years; range, 24-78 years) with acute basilar artery dissection were identified between January 2001 and October 2007. Clinical presentation, management, and outcomes were retrospectively evaluated.
The patients presented with subarachnoid hemorrhage (n = 10), brain stem ischemia (n = 10), or stem compression sign (n = 1). Ruptured basilar artery dissections were treated by stent placement with coiling (n = 4), single stent placement (n = 3), or conservatively (n = 3). Of the patients treated with endovascular technique, 6 had favorable outcome (modified Rankin scale mRS, 0-2) and the remaining patient, who was treated by single stent placement, died from rebleeding. All 3 conservatively managed patients experienced rebleeding, of whom 2 died and the other was moderately disabled. Unruptured basilar artery dissections were treated conservatively (n = 7) or by stent placement (n = 4). Of the patients with unruptured basilar artery dissection, 9 had favorable outcome and the remaining 2 patients, both of whom were conservatively managed, had poor outcome because of infarct progression. The group with the ruptured basilar artery dissection revealed a higher mortality rate than the group with the unruptured dissection (30% vs 0%). The group treated with endovascular means revealed more favorable outcome than the group that was treated with conservative measures (90.9% vs 50%).
The ruptured basilar artery dissections were at high risk for rebleeding, resulting in a grave outcome. Stent placement with or without coiling may be considered to prevent rebleeding in ruptured basilar dissections and judiciously considered in unruptured dissections with signs of progressive brain stem ischemia.
Owing to its tumor tropism and prolonged transgene expression, mesenchymal stem cell (MSC) has been considered as an ideal delivery vehicle for cancer gene therapies or therapeutic vaccines. In this ...study, we demonstrated that intratumoral (i.t.) injection of MSCs expressing modified interleukin-12 (MSCs/IL-12M) exhibited stronger tumor-specific T-cell responses and antitumor effects as well as more sustained expressions of IL-12 and interferon (IFN)-γ in both sera and tumor sites than did IL-12M-expressing adenovirus (rAd/IL-12M) in mice bearing both solid and metastatic tumors. Subcutaneous (s.c.) injection of MSCs/IL-12M at contralateral site of tumor exhibited similar levels of serum IL-12 and IFN-γ as i.t. injection, but much weaker antitumor effects in both B16F10 melanoma and TC-1 cervical cancer models than i.t. injection. Although intravenous (i.v.) injection elicited earlier peak serum levels of cytokines, it induced weaker tumor-specific T-cell responses and antitumor effects than i.t. injection, indicating that serum cytokine levels are not surrogate indicators of antitumor effects. Taken together, these results indicated that MSC is more efficient than adenovirus as a cytokine gene delivery vehicle and that i.t. injection of MSCs/IL-12M is the best approach to induce strong tumor-specific T-cell responses that correlate with anti-metastatic effects as well as inhibition of solid tumor growth, although MSCs themselves have an ability to migrate into the tumor site. In addition, MSCs/IL-12M embedded in Matrigel (MSCs/IL-12M/Matrigel) exhibited significant antitumor effects even in immunodeficient mice such as SCID and BNX mice lacking T, B and natural killer (NK) cells, but not in IFN-γ knockout mice. Our findings provide an optimal approach for designing an efficient clinical protocol of MSC-based cytokine gene therapy to induce strong tumor-specific T-cell responses and therapeutic anticancer efficacy.
Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a ...possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1
; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca
/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1
; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.
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