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We present first-principles solubility calculations of H–/[OH]−mixing in binary alkali metal hydrides MH and their corresponding hydroxides MOH, for M ={Li, Na, K, Rb, Cs}. Solid solubility in the MH–MOH system may play an important role in solid-phase reactions involving the MH system, including for example many aluminum-based complex hydrides of the alkali metals, such as NaAlH4and LiAlH4. Our results indicate that the available cell volume for H–and OH–groups correlates strongly with mixing, and MOH is soluble in MH for M ={Na, K, and Rb} where available volumes for H–and OH–anions differ by less than about 15%, very similar to a Hume–Rothery type rule for intermetallics. The predicted mixing temperatures for the K and Rb systems are lower than for the Na system, in part because of the similarity in MH and MOH primitive cell volumes. Critical temperature diagrams for the formation of solid solution MH–MOH mixtures as a function of MOH concentration are calculated using a free energy minimization in the grand canonical ensemble. Differential scanning calorimetry and in situ X-ray diffraction measurements of the NaH1–x(OH)xsystem are presented for a range of compositions (0.3 ≤ x≤ 1.0). As the temperature is raised, the polymorphic phase transitions present in NaOH occur concomitantly with H–/OH–mixing, eventually forming a single-phase cubic structure; the behavior is fully reversible on cooling. Finally, the formation of solid solution MH/MOH reduces the decomposition temperature of NaH1–x(OH)xto lower temperatures than pure NaH while increasing the stability in the KH and RbH systems.

1H and 27Al NMR is used to reveal the motions of AlH4anions in KAlH4. Line-narrowing from rotations and from translational diffusion is observed in the NMR of both nuclei. Unlike the anions in NaAlH4and LiAlH4that are not rotating on the NMR time scale at room temperature, the KAlH4anions are already rotating rapidly at 23 °C. Based on the onset of rotation-induced line narrowing, the 1H T1minimum, and the low- temperature hydrogen T1ρ minimum associated with reorientations, the rotational activation energy Erot,act= 0.28 eV is determined. Similarly, we use the onset temperature of translational motion-induced line narrowing and the high-temperature T1ρminimum to determine the diffusion activation energy Ediff,act= 0.70 eV. Lack of sharp structure in the first-order quadrupole pattern and the absence of second-order quadrupole structure in the 27Al NMR data suggest asymmetry (η ≠ 0) and/or variations in the anion electric field gradients from structural disorder.

AbstractVisual cortical areas in the two sides of the brain are interconnected by interhemispheric fibers passing through the splenium of the corpus callosum. In this review, we summarize data concerning the anatomical features of visual callosal connections, their roles in basic visual processing, and how their alterations contribute to visual deficits in different human neuropathologies. Splenial fibers represent a population of excitatory axons with varying diameters, which interconnect cortical columns with similar functional properties (i.e., same orientation selectivity) in the two hemispheres. Their branches activate simultaneously distinct iso-oriented columns in the contralateral hemisphere, thus mediating forms of stimulus-dependent interhemispheric synchronization. Callosal branches also make synapses onto GABAergic cells, resulting in an inhibitory modulation of visual processing that involves both iso-oriented and cross-oriented cortical networks. Interhemispheric inhibition appears to predominate at short latencies following callosal activation, whereas excitation becomes more robust with increasing delays. These callosal effects are dynamically adapted to the incoming visual activity, so that stimuli providing only weak afferent input are facilitated by callosal pathways, whereas strong visual input via the retinogeniculate pathway tends to be offset by transcallosal inhibition. We also review data highlighting the contribution of callosal input activity to maturation of visual function during early ‘critical periods’ in brain development and describe how interhemispheric transfer of visual information is rerouted in cases of callosal agenesis or following splenial damage. Finally, we provide an overview of alterations in splenium anatomy or function that may be at the basis of visual defects in several pathologic conditions.

The presence of approximately 10 mol % NaOH mixed with NaH powder is shown to result in much more rapid hydrogen motion in the NaH above 150 °C, as indicated by the onset of hydrogen NMR line narrowing at this temperature. A similar result appears for air-exposed NaH due to the formation of hydroxide from atmospheric H2O. The NMR line narrowing is too rapid, as a function of temperature, to be described by thermal activation; rather, it is suggestive of a phase transition. Indeed, differential scanning calorimetry finds, after an initial thermal cycle, a reversible thermal anomaly indicating a phase transition near 150 °C. Powder X-ray diffraction with an excess of NaOH displays a remarkable lattice expansion of the NaH in the temperature range of 100–240 °C where the (200), (220), and (311) reflections indicate a volume lattice expansion of up to 11%; the expansion is reversible upon cycling. The data thus point to a reversible phase transition in which NaOH enters the NaH structure above 150 °C and exits the NaH below that temperature. First-principles calculations using OH-substituted NaH supercells indicate significant solubility in the NaH lattice and find a transition temperature and enthalpy change that are in approximate agreement with differential scanning calorimetry (DSC) measurements, confirming the presence of a phase transition.

The genetic alterations are responsible for the altered protein expression in tumors. The knowledge of the link between the altered protein expression and genetic alterations may provide potentially important biological and clinical information. In this study, the expression of some protein markers (Gal-3, p21Kip1, CK19) known to be associated to the papillary thyroid carcinoma (PTC) was assessed in a series of surgical samples by immunohistochemistry, and the association between expression of these markers and the BRAFV600Emutation was investigated. Gal-3 positive staining was evident in 26 % of benign nodules. The BRAFV600Emutation and Gal-3 expression, were found in 55.5 and 87 % of PTC respectively, and were unlinked. The expression of CK19 in benign nodules was weak and limited to scattered follicular cells. Diffuse cytoplasmatic expression of CK19 was present in malignant tumors in a variable percentage of cells. A higher percentage of CK19 expressing cells was associated with BRAFV600E(P≤ 0.001). All benign nodules displayed nuclear p27kip1 in more than 15 % of the cells. Twenty-nine PTC showed a cytoplasmatic staining with negative nuclei. PTC with cytoplasmatic or 0–5 % of cells with nuclear staining, 6–15 % or >15 % of cells with nuclear staining were 72 (66.7 %), 24 (22.2 %), and 12 (11.1 %) respectively. In BRAFV600Epositive tumors, the cytoplasmatic localization of p27kip1 was significantly more frequent (P= 0.024). In conclusion, we provide evidences that BRAFV600Eis non-associated with Gal-3 expression, whereas it is associated with cytoplasmatic localization of p27kip1 and higher CK19 expression in PTC.

The degeneration of pre-synaptic boutons in the stratum radiatum of the dorsal hippocampus is one of earliest components of neurodegeneration in several models of murine prion disease. We recently showed that blockade of synaptic transmission by infusion of botulinum neurotoxin A (BoNT/A) into the hippocampus several weeks prior to the onset of degeneration, had no detectable impact on the extent of the synaptic degeneration.1We elaborate here on the rationale for these experiments and highlight why we believe that this negative result is interesting and important. We also discuss new observations that might provide insights into the molecular events that underlie synapse degeneration.

Follicular lymphoma (FL) is one of the most common forms of the low-grade non-Hodgkin's lymphoma in adults, with a characteristic translocation, t(14;18)(q32;q21) that deregulates the expression of the BCL2gene. The clinical course of FL patients is variable, whereby a subset of patients survive for long periods even without relapses, whereas the majority have frequent relapses with shorter survival. We have analyzed a series of 186 FLs, studying the correlation between clinical outcome and the tumor cell expression of a set of immunohistochemical markers, using an automated procedure for tissue microarrays to reduce the subjectivity of scoring. The results identified several markers associated with differences in overall survival (OS) in univariate analyses, such as Cyclin E, Mdm2, CD10, p21, IgD, Bcl-xL, CD30, and E2F6. Cases with a higher level of expression of Cyclin E, Mdm2, p21, IgD, Bcl-xL, CD30, and E2F6 were associated with a significantly shorter OS. On the other hand, strong CD10 expression was linked to a significantly better outcome. A Cox model was then constructed, integrating the Follicular Lymphoma International Prognostic Index (FLIPI) score and a restricted selection of three immunohistochemical markers: Cyclin E, Mdm2, and CD10 expression. A potentially useful finding is that the integrated FLIPI plus immunohistochemical model can be used to identify a subset of 26 patients (almost 20% of the total series), with a survival probability of 100% at 5 years. This not only confirms that a group of FL cases may have a very good clinical course, but also indicates that this group can be identified using this integrated clinical and immunohistochemical approach.

Clinical and experimental studies clearly demonstrate that prolonged seizures and status epilepticus induce neuronal cell death in the brain. Recent evidence suggests that induction of apoptosis contributes greatly to seizure-induced brain damage. We recently demonstrated that intrahippocampal delivery of botulinum neurotoxin E (BoNTE) in the rat hippocampus is able to prevent neuronal loss, which occurs after kainic-acid-induced seizures. Here, we investigated the molecular mechanisms of BoNTE-mediated neuroprotection. We found that intrahippocampal administration of BoNTE prevents the upregulation of apoptotic proteins (phosphorylated c-Jun and cleaved caspase 3), which occurs in hippocampal neurones following kainic acid seizures. These results demonstrate that the neuroprotective action of BoNTE on seizure-injured hippocampal neurons involves the blockade of well-characterized apoptotic pathways.

Introduction

Aurora/Ipl1-related kinases are a conserved family of proteins that have multiple functions during mitotic progression. High levels of Aurora kinases are characteristic of rapidly dividing cells and tumours. Aurora B encodes a protein that associates with condensing chromatin, concentrates at centromeres, and then relocates onto the central spindle at anaphase. In this study the expression and the localisation of Aurora B throughout germinal epithelial progression in normal testis and its neoplastic counterpart were analysed. Immunocytochemistry and RT-PCR analysis of mouse germinal epithelium cells showed the presence of Aurora B in spermatogonia and occasionally in spermatocytes. Western blot analysis revealed the typical Aurora B isoform ( approximately 41 kDa) in the same cellular types. A similar distribution was observed in human testis by immunohistochemistry. Moreover, the distribution and the expression of Aurora B were investigated in neoplasms derived from germ cells. Surgical samples of seminomas were analysed, and a high percentage of Aurora B positive cells (51%) was detected; the expression of Aurora B was significantly related to the MIB-1 proliferation marker (R=0.816). The data presented here demonstrate that Aurora B expression occurs in spermatogonial division. Furthermore, our results indicate that the expression of Aurora B is a consistent feature of human seminomas.

This study explores whether the presence of somatic mutations or a biased use of IgVHgenes were associated with the clinical features in a series of 96 patients with mantle cell lymphoma (MCL). The cases were studied by seminested polymerase chain reaction using primers from the FR1 and JHregions. There was an unexpectedly high frequency of somatic mutations, with 29 of 103 sequences showing more than 2% of mutations. Biased usage of specific VHsegments was also found; the most widely used genes in this series wereVH3-21(10 cases),VH3-23(9 cases),VH4-34(11 cases), andVH4-59(9 cases).VHmutation frequency, taking into account different thresholds, did not distinguish different overall survival probabilities. Nevertheless, a more frequent use ofVH3-21or VH4-59(8 of 18) was observed in the group of long-term survivors (18 cases > 5 years; P< .01). None of these long-term survivors presented the VH3-23gene rearrangement. As in other lymphoproliferative disorders, the expression of CD38 or p53 or both was associated with a poorer survival probability. This nonrandom usage of IgVHsegments suggests that specific antigens may play a pathogenically relevant role in the genesis or progression of subsets of MCL cases and may help in distinguishing a significant group of MCL long-term survivors.

This study explores whether the presence of somatic mutations or a biased use of IgVH genes were associated with the clinical features in a series of 96 patients with mantle cell lymphoma (MCL). The cases were studied by seminested polymerase chain reaction using primers from the FR1 and JHregions. There was an unexpectedly high frequency of somatic mutations, with 29 of 103 sequences showing more than 2% of mutations. Biased usage of specific VH segments was also found; the most widely used genes in this series wereVH3-21 (10 cases),VH3-23 (9 cases),VH4-34 (11 cases), andVH4-59 (9 cases).VH mutation frequency, taking into account different thresholds, did not distinguish different overall survival probabilities. Nevertheless, a more frequent use ofVH3-21 or VH4-59 (8 of 18) was observed in the group of long-term survivors (18 cases > 5 years; P < .01). None of these long-term survivors presented the VH3-23 gene rearrangement. As in other lymphoproliferative disorders, the expression of CD38 or p53 or both was associated with a poorer survival probability. This nonrandom usage of IgVH segments suggests that specific antigens may play a pathogenically relevant role in the genesis or progression of subsets of MCL cases and may help in distinguishing a significant group of MCL long-term survivors.

A comparative study was made on one Mysticete (the fin whale, Balaenoptera physalus) and one Odontocete species (the striped dolphin, Stenella coeruleoalba) by measuring several morphological characteristics seen in cross sections of the optic nerve. We found that the two cetacean nerves share a number of specializations that distinguish them from the optic nerve of terrestrial mammals. Fiber density is approximately two-fold lower than in land mammals. A corresponding increase in the cross-sectional area occupied by astrocytes is observed. A population of “giant” (up to 15 μm in diameter) optic axons is present in both the B. physalus and the S. coeruleoalba nerve. It is argued that these features probably reflect common adaptations to the constraints imposed by the aquatic environment. “Giant” optic axons might ensure short-latency detection of preys and other targets during navigation while the increased astroglial content might be related to the maintenance of neuronal function during periods of anaerobic metabolism under water.

This study compares the costs and outcomes of domiciliary and hospital-based chemotherapy, using a prospective randomized cross-over design. Eighty-seven eligible patients were recruited from oncology services at two metropolitan hospitals in Sydney, Australia. Forty patients completed study evaluation requirements, having two months of chemotherapy in each location (home and hospital). The domiciliary service was staffed by hospital-based oncology nurses. Marginal costs of domiciliary treatment over hospital treatment were estimated from the health service perspective. Home-based care was more expensive, largely due to extra nurse time. About half of the eligible patients (n = 87) and 73 percent of the evaluated patients (n = 40) preferred domiciliary care. Most evaluated patients and their informal carers were satisfied with the medical care provided, regardless of location. Patient needs were well met in either location, and no differences were found in quality of life. At current throughput rates, providing chemotherapy in the home was more expensive than providing it in hospital. However, if the demand for chemotherapy were to exceed ward capacity by up to 50 percent, moving chemotherapy into the home could provide a less costly strategy for the expansion of a chemotherapy service without compromising patient outcomes.

The formalism of a transmission line is applied to the study of the optical response of a nonlinear multilayer filter filled with a quadratic material. A second-harmonic generation process is taken into account under mismatching conditions, i.e., an undepleted-pump beam. The pump beam’s evolution as a function of its intensity through the multilayer is studied. Examples of multilayer structures are discussed.

Features General Motors' transition from an automobile manufacturer to an aircraft manufacturer during the World War II in the United States. Japanese's development of the fighter plane Zero; Partnership with Grumman Aircraft Engineering Corp. to develop the Wildcats and Avengers planes; Plants' undergoing procedural and work-force transformation; GM's success in aircraft production.

Among the primary mesenchymal tumors of the hypopharynx and larynx, lipomas are rare. Macroscopically, they often resemble a retention cyst or laryngeal nodule. Spindle cell lipomas (SCLs) are an uncommon variant of lipoma. SCLs are extremely rare in the larynx; as far as we know, only 4 cases have been previously described in the literature. We present a new case of laryngeal SCL in a 65-year-old man who presented with a 1-year history of hoarseness, choking spells, stridor, and dyspnea. Examination revealed the presence of a large polyp on the left true vocal fold that had caused stenosis of the posterior glottis. The polyp was removed endoscopically, and the patient's stridor and dyspnea resolved. Histologically, the tumor was composed of bland, CD34-positive spindle cells with an abundant fibrous and myxoid stroma interspersed with mature fatty tissue. The patient was free of local recurrence at 2 years of follow-up.

Introduction:Obesity and psychosocial stress (PS), two stigmata of Western society increasingly coexisting in the same individual, are risk factors for cardiovascular disease and cognitive deficits. However, the effects of PS on cardiac and hippocampal phenotype of obese subjects are still unknown. Furthermore, Brain-Derived Neurotrophic Factor (BDNF) can regulate the hippocampal and cardiac homeostasis; thus, its depletion may explain PS/obesity-induced dysfunction at both levels.Hypothesis:Obese mice exposed to PS display cardiac and hippocampal impairment associated to local BDNF depletion.Methods:Forty adult male C57BL6/J mice were subjected to: 1) normocaloric diet (ND) for 18 weeks (Control); 2) high-fat diet (HFD) for 18 weeks (Ob); 3) ND and resident-intruder paradigm (RIP) to trigger PS (PS); 4) HFD and RIP (Ob+PS). Left ventricular (LV) function was evaluated by pressure-volume loops. Spatial memory was assessed by Y-maze. LV ROS levels were measured by EPR. Myocardial apoptosis, fibrosis and vascular density were histologically evaluated. Hippocampus was assayed to evaluate volume, neurogenesis and synaptic plasticity. Tissue BDNF levels were measured by ELISA.Results:Preload recruitable stroke work and LV elastance, load-independent indexes of LV contractility, were impaired only in Ob+PS group (-44% and -41%, respectively, both p<0.01 vs. Control). Moreover, combined regimen jeopardized also myocardial relaxation (tau), (p<0.05 vs. Control), without affecting arterial elastance. Obesity/PS significantly increased LV oxidative stress, apoptosis and fibrosis, without changing vascular density, while halving cardiac BDNF (-48%, p<0.01 vs. all groups). Spatial memory was compromised only in Ob+PS group (p<0.05 vs. Control) consistent with reduced hippocampal volume (-27%, p<0.05 vs. all groups), neurogenesis (-33%, p<0.001 vs. Control), synaptic plasticity (-29%, p<0.05 vs. Control) and local BDNF levels (-52%, p<0.01 vs. Control; p<0.05 vs. PS and Ob).Conclusions:PS triggers prominent myocardial and hippocampal dysfunction in obese mice. PS-challenged obese mice exhibit BDNF depletion in both remodeled tissues. Therefore, PS may jam heart-brain communication of obese mice though local BDNF exhaustion.

Rehabilitation is considered the most effective treatment for promoting the recovery of motor deficits after stroke. One of the most challenging experimental goals is to unambiguously link brain rewiring to motor improvement prompted by rehabilitative therapy. Previous work showed that robotic training combined with transient inactivation of the contralesional cortex promotes a generalized recovery in a mouse model of stroke. Here, we use advanced optical imaging and manipulation tools to study cortical remodeling induced by this rehabilitation paradigm. We show that the stabilization of peri-infarct synaptic contacts accompanies increased vascular density induced by angiogenesis. Furthermore, temporal and spatial features of cortical activation recover toward pre-stroke conditions through the progressive formation of a new motor representation in the peri-infarct area. In the same animals, we observe reinforcement of inter-hemispheric connectivity. Our results provide evidence that combined rehabilitation promotes the restoration of structural and functional features distinctive of healthy neuronal networks.

We describe clinicopathologic features, laboratory data, and imaging and therapeutic management of a rare case of Hashimoto thyroiditis arising in struma ovarii. The patient was a 38-year-old woman with clinical symptoms of hyperthyroidism. Laboratory data showed elevated levels of total and free thyroxine, low thyrotropin level, and positive specific antithyroid antibodies without ultrasound evidence of morphologic abnormalities of the thyroid gland. Pelvic ultrasonography and magnetic resonance imaging of the abdomen showed bilateral solid ovarian masses containing cystic and fat areas diagnostic of teratoma. The performance of a 131I whole-body scan demonstrated a focus of intense uptake in the pelvis with minimal residual thyroid gland. The patient had a bilateral oophorectomy, and histologic examination revealed thyroid tissue in both masses with all the features of Hashimoto thyroiditis in the right ovary. Symptoms of hyperthyroidism diminished after the surgery, and the thyroid hormone levels and antithyroid antibodies were in the normal range in 1 month. The present case further confirms the rare occurrence of Hashimoto thyroiditis in struma ovarii. This diagnosis should be suggested in the differential diagnosis of patients with symptoms of thyroid disease and a normal thyroid gland.

The article talks about the innovative move of Australia and China towards sustainable fisheries. It mentions the commitments of Australian government to sustainable seafood certification by paying the full assessment process for fisheries to become Marine Stewardship Council (MSC) certified. Also noted is the MSC-certified fishery in China.

Follicular lymphoma (FL) is the most common type of low-grade non-Hodgkin’s lymphoma. A subset of FL patients shows a favorable treatment response, and remains in complete remission with long-term follow-up, while another subset of patients has a clinical course characterized by frequent relapses and a shorter survival. Survival predictors for FL are mainly based on clinical data, and they seem to lack accuracy enough predicting survival among patients with advanced stage disease. The aim of this study is to build a survival predictor based on a set of biological markers using Tissue Micro Arrays (TMA). To this purpose, we have retrospectively analysed the expression of a group of 40 selected genes - related with apoptosis control, cell cycle, B-cell differentiation and signaling- in a series of 192 FLs using TMA. The association of these molecules with survival, and their usefulness to discriminate among FLIPI groups was evaluated. Results were quantified using different tools; singularly nuclear markers were scanned using the Bliss system and the quantitative expression was measured using the TMAscore v.1.0 image analysis software (Bacus Laboratories, Inc.). The mean overall survival (OS) was 74 months, and 38 months for progression-free survival (PFS). Statistically significant differences in OS were found with the Follicular Lymphoma International Prognostic Index (FLIPI) score (p < 0.01). No significant OS or PFS differences were observed between FL grades 1–3, between grades 3a and 3b, or using Ki67 expression. Univariate analysis revealed several TMA markers with capacity to predict OS and PFS. After multivariate analysis, a set of 4 apoptosis and cell-cycle markers was integrated into a FLIPI-independent clinical predictor, with the capacity to recognize two groups of FL patients with statistically significant differences in OS (83% versus 43% of OS at 120 months; p< 0.001). Then, patients were classified into low-risk (FLIPI: 0–2) and high-risk groups (FLIPI: 3–5), and the protein-based predictor model was used in both groups. High-risk FLIPI patients were stratified by the protein-based predictor into two groups with OS probability of 79,3% versus 14,2% at 120 months, p < 0.001, and low-risk FLIPI patients were also separated into two groups with OS probability of 100% versus 60,4% at 120 months, p < 0.01. The model is now being validated in a blind set. These results suggest that an integrated use of the FLIPI and the protein-based model could reach a higher accuracy predicting survival in FL.