Miracle-dz/UniFAR-FTUs huggingface dataset:
Impaired Neurovascular Coupling by Transhemispheric Diaschisis in Rat Cerebral Cortex

In acute brain disorders, elimination of the excitatory output from an injured brain region reduces activity in connecting brain regions remote from the lesion site (i.e., diaschisis). The authors examined the effect of functional ablation of the left cerebral cortex by cortical spreading depression (CSD) or topical application of tetrodotoxin on single cell spiking activity, baseline CBF, and neurovascular coupling in the right rat sensory cortex. CSD or tetrodotoxin in left cortex reduced the right cortical spontaneous spike rate by 36% and 45%, respectively. Baseline CBF in the right cortex was unaffected by a left-sided CSD, but decreased by 12% for left cortical application of tetrodotoxin. This suggested dissociation between spontaneous spiking activity and basal CBF. Left infraorbital nerve stimulation evoked local field potentials in right cerebral cortex that were reduced in amplitude by 19% for left CSD and by 23% for left tetrodotoxin application. The corresponding declines in the evoked CBF responses were 42% for CSD and 23% for tetrodotoxin. Vascular reactivity to adenosine remained unchanged in right cortex. Thus, transhemispheric diaschisis produced a pronounced decrease in the spontaneous spike rate accompanied by no reduction or a small reduction in basal CBF, and an attenuation in amplitudes of evoked synaptic responses and corresponding rises in CBF. The findings suggest that disturbed neurovascular coupling may contribute to the disturbance in brain function in acute transhemispheric diaschisis.
Does Diffusion-Weighted MR Imaging Change the Follow-Up Strategy in Cases with Residual Cholesteatoma?

OBJECTIVE To analyze the effectiveness of diffusion-weighted magnetic resonance imaging (DW-MRI) in the evaluation of recurrent cholesteatomas. MATERIALS AND METHODS Twenty-three patients undergoing second-look surgery were included in our study. There were 14 men and 9 women with ages ranging from 10 to 50. All patients underwent DW-MRI prior to second-look surgery. All magnetic resonance imaging (MRI) examinations were performed with a 1.5-T MRI unit using a standard 8-channel neurovascular coil. DW-MRI and apparent diffusion coefficient maps were included in the examination. Cholesteatoma was diagnosed on the DW-MRI as a marked hyperintense signal in comparison with brain tissue. All cases were classified as positive or negative. RESULTS The sensitivity and specificity of DW-MRI were 86% and 87%, respectively. The positive predictive value of DW-MRI was 92%, while the negative predictive value was 77%. CONCLUSION The DW-MRI technique is an important and effective technique in the evaluation of residual cholesteatoma. It can be an alternative method to second-look surgery, which can spare patients repeat operations.
The immune system and glaucoma

Purpose of review Compelling evidence obtained from studies over the last decade strongly suggests the involvement of immune system regulation in cell fate decisions in glia and retinal ganglion cells that lead to glaucomatous optic nerve degeneration. Recent findings Recent studies reveal seemingly conflicting roles of the immune system in glaucomatous optic nerve degeneration. T cells directed against specific antigens may have a beneficial effect to protect neurons from the consequences of axonal injury. However, the immune response in glaucoma also has the capacity to cause neuronal injury. The balance between the benefit of protective immunity and the risk of inducing an autoimmune neurodegenerative disease is critical. The immunoregulatory function of glial cells and the presence of tissue stress seem to be important factors that determine the balance between diverse roles of the immune system in glaucomatous optic nerve degeneration. Thus, the net effect of immunoregulation may be either neuroprotective or neurodestructive. Summary Despite the neuroprotective features of the immune system, an autoimmune component, resulting from a failure to properly control aberrant, stress-induced immune response, likely accompanies the progression of neurodegeneration in glaucoma in some patients. A better understanding of the diverse roles of the immune system in all forms of glaucomatous optic nerve degeneration will facilitate the development of effective neuroprotective strategies in glaucoma. The basis of a sustainable neuroprotective strategy is to harness immunoregulation of glial and retinal ganglion cell fate to maximize beneficial effects, while minimizing negative sequelae, for therapeutic gain.
Analysis of mandatory CSR expenditure in India: a survey

In this study of Indian corporations, we investigate the drivers and barriers of corporate social responsibility (CSR) expenditure, determine the attitude of corporates towards CSR activities and the impact of making CSR spending mandatory. We surveyed 223 corporations and found that the attitudes of companies to CSR spending largely vary with age, size and type of ownership. The making of CSR spending mandatory for large corporations did not elicit the forecasted increase in the level of spending because it was avoided by many corporations for whom it became mandatory and a large number for whom it is not mandatory, reduced their level of expenditure. The Indian Government has already had to amend the legislation to more precisely specify the direction of the expenditure and may have to further amend it to encourage increased spending on CSR activities.
Evaluation of breast tumour cell contamination in the bone marrow and leukapheresis collections by RT‐PCR for cytokeratin‐19 mRNA

There is considerable interest in an autologous transplantation (AT) programme for patients with high‐risk breast cancer; however, the issue of the incidence of occult bone marrow (BM) micrometastasis at diagnosis, and the cancer contamination of peripheral blood stem cell (PBSC) collections used for haematological rescue, is still debated. The presence of BM micrometastasis was evaluated in bilateral BM biopsies obtained at diagnosis of 33 patients with stage II/IIIA breast cancer using: (i) a ‘nested’ reverse transcriptase‐polymerase chain reaction (RT‐PCR) assay for cytokeratin 19 (K19) mRNA, (ii) histology, and (iii) immunohistochemistry (IHC) analysis with a panel of three monoclonal antibodies. The RT‐PCR assay only was used to determine contamination of PBSC collections obtained after priming with recombinant human granulocyte‐colony stimulating factor (rhG‐CSF). K19 transcripts in one or both BM samples were detected in 48% of patients at diagnosis, with an overall 85% concordance with the results of IHC analysis. On the other hand, 56% of PCR‐ and IHC‐positive BM samples were diagnosed as ‘normal’ on histological analysis. 57% of patients showed K19 mRNA in at least one PBSC collection; the possibility to have contaminated PBSC collections was significantly higher in patients with K19 positivity in BM at diagnosis. In four patients who had shown K19 positivity in BM and in PBSC collections, immunoselected CD34+ cells used for haematological rescue were K19‐negative. There was a trend towards longer relapse free survival (RFS) in patients transplanted with K19‐negative PBSC collections as compared to the others. In conclusion, a substantial proportion of patients with high‐risk non‐metastatic breast cancer present occult BM micrometastasis at diagnosis and also show cancer contamination of PBSC collections used for AT. These might represent a category of patients with poorer prognosis after AT, and possible candidates for more intensive and/or alternative therapeutic regimens, including AT with purged PBSCs.
CD44 is involved in selective leucocyte extravasation during inflammatory central nervous system disease

Clinical signs of experimental autoimmune encephalomyelitis (EAE) are associated with the selective recruitment of CD4+ memory (CD45RBlow CD44high) T cells into the central nervous system (CNS). However, we have found that many of these recently recruited memory cells are CD44low, suggesting that the CD44 antigen may be involved in, and transiently lost during, the extravasation process. Indeed, administration of a CD44‐specific antibody (IM7.8.1) induced leucocyte CD44 shedding and both prevented the development and ameliorated the severity of established EAE by inhibiting mononuclear cell infiltration into the CNS. Trafficking of cells into lymph nodes, however, a property mainly of naïve cells, was essentially unaffected. In contrast, treatment with antibody to very late activation antigen‐4 (VLA‐4) prevented homing to both the CNS and to lymph nodes. This study contests previous reports that dismissed a role for CD44 in inflammation of the CNS and, coupled with observations in murine dermatitis and arthritis, suggests that CD44 is involved in the homing of primed lymphocytes to sites of inflammation. CD44 should therefore be considered a target for immunotherapy of T‐cell‐mediated inflammatory diseases, such as multiple sclerosis.
Hypnotic administration for anesthesia using sliding-mode control

Nowadays general anesthesia is maintained using as the controller the human intervention, relying only on the quick and certain response of the anesthesiologist to the surrounding conditions, in order to provide the adequate state of anesthesia for the three main components - hypnosis, analgesia and paralysis. One of the most advantageous breakthroughs in anesthesia has been the appearance of depth of anesthesia monitors, assisting anesthesiologists in the hard job of knowing the hypnotic state of a patient. This information allows a way of closing the loop for administration of the hypnotic drug, and a more secure maintenance of hypnosis. The objective of this work was to apply sliding-mode control techniques to the model structure of the hypnotic in the human body (measured by the effect), and evaluate the robustness of this method to expected deviations from the average patient.
Causes of withdrawal of duodenal levodopa infusion in advanced Parkinson disease

Objective: We performed a real-life observation of patients with Parkinson disease (PD) who received duodenal levodopa infusion (DLI) to determine which adverse events caused treatment discontinuation and when such events occurred. Methods: All consecutive patients with PD treated at the Carlo Besta Neurological Institute were included. The patients were evaluated at baseline and after DLI at regular intervals. Their motor condition was assessed and adverse events were recorded. Results: Thirty-five patients with PD (15 men and 20 women) were included. They received DLI implants between October 2007 and September 2013. Four patients died of causes unrelated to the procedure. At the end of the study, 21 patients (60%) were still on treatment. DLI provided efficacious motor control in all patients. Discontinuation was most frequently caused by device- or infusion-related adverse events. Ten patients of the remaining 31 discontinued DLI. There were 2 main causes of withdrawal: stoma infection (4 patients), and worsening of dyskinesias not manageable with infusion reduction (3 patients). In most patients, discontinuations occurred during the first year after implant. Risk of discontinuation was related to age at implant, but no other demographic or clinical variables. Conclusions: We identified 2 main causes leading to DLI withdrawal during the first year postimplant and suggest adopting measures to prevent such occurrences. Elderly patients are at higher risk of treatment discontinuation.
Interventions for Executive Function Deficits in Children and Adolescents

Abstract For children with neurodevelopmental or acquired disorders, deficits in executive function (EF) processes (i.e., attention, working memory, cognitive flexibility, and problem solving), are often evident. Moreover, EF deficits are associated with academic difficulties, behavioral and social difficulties, and long-term psychological maladjustment rendering prevention and intervention of EF deficits an important consideration. Many methods exist to address EF processes; this review will focus on pharmacological, cognitive/metacognitive, computerized, and neurofeedback approaches. Across research reviewed, results tend to vary depending on age, disorder, comorbid conditions, and outcome measures. Notably, there is limited research to suggest long-term maintenance of changes in symptom presentation, improved developmental trajectory, normalization of EF processes, or alteration to the associated neural connections. Implications for practice and future research for evidence-based interventions to address EF are discussed.
Manganese (II) and substrate interaction with unadenylylated glutamine synthetase (Escherichia coli w). II. Electron paramagnetic resonance and nuclear magnetic resonance studies of enzyme-bound manganese(II) with substrates and a potential transition-state analogue, methionine sulfoximine.

The enhancement of the longitudinal proton relaxation rate of solvent water protons which occurs when Mn(II) is bound to the "tight" metal ion site of unadenylylated glutamine synthetase (GS) was used to determine the binding constant of L-methionine (SR)-sulfoximine to GS-Mn(II) complexes. The binary enhancement for GS-Mn(II) is 22 at 24 MHz, 25 degrees C. The enhancement is lowered in the presence of the sulfoximine and the computed dissociation constant is 30 muM with epsilont, the enhancement for the ternary complex, equal to 3.0. Titration curves for the sulfoximine were also obtained in the presence of Mg-ADP, Mg-ADP plus Pi, and Mg-ATP. The dissociation constants were 9, 5, and 0.8 muM, respectively. The progressive tightening of the dissociation constants is symptomatic of conformational changes at the active site as the total subsite occupied by ATP is filled. The number of rapidly exchanging water molecules drops from 2 to approximately 0.1 when saturating concentrations of L-methionine (SR)-sulfoximine and nucleotide are present. The kinetically determined KI value of approximately 4 muM for the sulfoximine is about three orders of magnitude tighter than thee Km' value of approximately 3 mM for L-glutamate. The previously mentioned dissociation constants obtained by enhancement titrations are also orders of magnitude tighter than Km'. These data suggest that L-methionine (SR)-sulfoximine is a "transition-state" analogue for the glutamine synthetase reaction.
Architectural Discourse and the Memory of Nazism in the federal Republic of Germany, 1977-1997

The ten-year anniversary of the Historians' Debate provides an opportu nity not only for revisiting the most famous controversy over the Nazi past in recent years but for examining another important, if less well known, struggle over memory from the same period. Nearly a decade before German historians became embroiled in the Historikerstreit, German architects and architectural critics were engaged in a less publicized but equally heated controversy which can justifiably be termed the "Architects' Debate. " Like the Historians' Debate, the Architects' Debate erupted over the sensitive question of whether the Nazi past should maintain its exceptional status or acquire a normalized place in German consciousness and identity. In the same way that German historians argued about the proper place of the Third Reich in the overall sweep of German history, German architects argued about the Nazi era's lessons for the present and future architectural development of the Federal Republic. Unlike the quarrel among the historians, which ended a decade ago, however, recent architectural controversies in Berlin reveal that the Architects' Debate has persisted into the present. And yet, in light of the similarities between the two controversies, the continuation of the Architects' Debate suggests that the Historians' Debate, at least in some of its core aspects, may not be completely over either. Although it began over a decade ago, the Historikerstreit and its significance for German memory of the Third Reich can be better appreciated by
The Action Observation System when Observing Hand Actions in Autism and Typical Development

Social impairments in individuals with autism spectrum disorders (ASD) may be in part due to difficulty perceiving and recognizing the actions of others. Evidence from imitation studies, which involves both observation and execution of an action, suggests differences, in individuals with ASD, between the ability to imitate goal‐directed actions involving objects (transitive actions) and the ability to imitate actions that do not involve objects (intransitive actions). In the present study, we examined whether there were differences in how ASD adolescents encoded transitive and intransitive actions compared to typically developing (TD) adolescents, by having participants view videos of a hand reaching across a screen toward an object or to where an object would be while functional magnetic resonance images were collected. Analyses focused on areas within the action observation network (AON), which is activated during the observation of actions performed by others. We hypothesized that the AON would differentiate transitive from intransitive actions only in the ASD group. However, results revealed that object presence modulated activity in the right inferior frontal gyrus and supramarginal gyrus of the TD group, a differentiation that was not seen in the ASD group. Furthermore, there were no significant group differences between the TD and ASD groups in any of the conditions. This suggests that there is not a global deficit of the AON in individuals with ASD while observing transitive and intransitive actions. Autism Res 2015, 8: 284–296. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
A Dynamic Analysis of Changes in the Nasolabial Fold Using Magnetic Resonance Imaging: Implications for Facial Rejuvenation and Facial Animation Surgery

&NA; An anatomic study was performed on living subjects using magnetic resonance imaging (MRI) to distinguish the relative contribution of skin, subcutaneous tissue, and muscle to dynamic changes in the nasolabial fold during facial animation and aging. MRI scans with the face in repose and then holding a full smile were performed in both young and old adult subjects. Anatomic landmarks were identified, and measurements characterizing their position were made on the MRI console. MRI resulted in excellent image resolution of facial tissue planes. Comparison between young and old subjects with the face in repose demonstrated that progressive thickening of the dependent portion of the cheek fat pad and overlying skin, with no appreciable change in the muscle plane comprising the levators of the upper lip, resulted in a deeper and more acute nasolabial fold in older subjects. In both age groups there was significant shortening of the mimetic muscles with smiling, with the lateral mimetic muscles drawn closer to the underlying facial bones. This was accompanied by redistribution of the cheek fat pad, thereby maintaining projection of surface landmarks within the cheek mass in young subjects with smiling. These findings indicate that in order to diminish the nasolabial fold, surgery for facial rejuvenation should be directed to the skin and subcutaneous tissue planes superficial to the mimetic muscles to the upper lip. In order to recreate a natural nasolabial fold during surgery for facial reanimation, contraction of the levator muscles to the upper lip should result in redistribution of the cheek fat pad without change in surface projection of the cheek mass or upper lip; this can only be accomplished if the reconstructed levator muscle is positioned deep to the cheek fat pad, with its insertion toward the deep (mucosal) surface of the upper lip.
Characterization of the Molecular Defect in Factor VR506A(*)

A poor anticoagulant response of plasma to activated protein C is correlated with a single mutation in the factor V molecule (Arg506 → Gln). Factor V was purified to homogeneity from plasma of two unrelated patients (patient I, factor VI, and patient II, factor VII), who are homozygous for this mutation. The factor V molecule from both patients has normal procoagulant activity when compared with factor V isolated from normal plasma in both a clotting time-based assay and in an assay measuring α-thrombin formation. The cleavage and subsequent inactivation by activated protein C (APC) of the α-thrombin-activated membrane-bound cofactor (factor Va) from both patients were analyzed and compared with the cleavage and inactivation of normal human factor Va. In normal factor Va, cleavage at Arg506 generates a Mr = 75,000 fragment and a Mr = 28,000/26,000 doublet and is necessary for the optimum exposure of the sites for subsequent cleavage at Arg506 and Arg679. Proteolysis at these sites leads to the appearance of Mr = 45,000 and 30,000 fragments and a Mr = 22,000/20,000 doublet. Cleavage at Arg506 is membrane-dependent and is required for complete inactivation. Following 5 min of incubation with APC (5.4 nM) membrane-bound normal factor Va (280 nM) has virtually no cofactor activity whereas under similar experimental conditions factor VaI and factor VaII retain approximately 50% of their initial activity. After 1 h of incubation with APC, factor VaI retains 20% of its initial cofactor activity whereas factor VaII has 10% remaining cofactor activity. The initial loss in cofactor activity (∼70%) of membrane-bound factor VaI and factor VaII during the first 10 min of the inactivation reaction is correlated with cleavage at Arg506 and appearance of a Mr = 45,000 fragment and a Mr = 62,000/60,000 doublet. Subsequently, the Mr = 62,000/60,000 doublet is cleaved at Arg679 to generate a Mr = 56,000/54,000 doublet resulting in complete loss of cofactor activity. Both procofactors, factor VI and factor VII, were inactivated following cleavage at Arg506 and Arg679, with APC inactivation rates equivalent to those observed for normal factor V. Our data demonstrate that: 1) cleavage at Arg506 is required for optimum exposure of the cleavage sites at Arg506 and Arg679 and rapid inactivation of membrane-bound factor Va; and 2) cleavage at Arg506 by APC on membrane-bound factor V occurs at the same rate in both normal and APC-resistant individuals. Thus cleavage at Arg506 and Arg679 and subsequent inactivation of the membrane-bound procofactor, factor V, does not require prior cleavage at Arg506 for optimum exposure.
Insertion element IS5 contains a third gene.

We have previously shown that IS5 contains two genes encoded on opposite DNA strands within the same stretch of DNA. Here we present evidence that a third gene and its promoter are present on IS5. The newly discovered gene, ins5C, is contained within the longest gene of IS5, ins5A, but encoded by the complementary DNA strand. The three genes comprise a total of 519 codons present on the 1195‐bp element. The arrangement of these genes represents a coding structure of unprecedented compactness.
Relational and median variants of Possibilistic Fuzzy C-Means

In this article we propose a relational and a median possibilistic clustering method. Both methods are modifications of Possibilistic Fuzzy C-Means as introduced by Pal et al. [1]. The proposed algorithms are applicable for abstract non-vectorial data objects where only the dissimilarities of the objects are known. For the relational version we assume a Euclidean data embedding. For data where this assumption is not feasible we introduce a median variant restricting prototypes to be data objects themselves.