Miracle-dz/UniFAR-FTUs huggingface dataset:
GAMMA KNIFE RADIOSURGERY IN YOUNGER PATIENTS WITH VESTIBULAR SCHWANNOMAS

OBJECTIVEManagement options for patients with vestibular schwannoma include observation, surgical resection, stereotactic radiosurgery (SRS), and stereotactic radiation therapy. In younger patients, resection is often advocated because of concern regarding the long-term effects of radiation. We studied tumor response and clinical outcomes after SRS in such patients. METHODSWe reviewed long-term outcomes in 55 patients with vestibular schwannomas. Patients were 40 years of age or younger, underwent gamma knife (GK) SRS between 1987 and 2003, and were followed up for a minimum of 4 years. The median patient age was 35 years (range, 13–40 years). Forty-one patients had Gardner-Robertson class 1 to 4 hearing. Thirteen patients (24%) had undergone surgical removal. The median tumor volume was 1.7 mm3. The median tumor margin dose was 13.0 Gy (range, 11–20 Gy). RESULTSAt a median of 5.3 years, (range, 4–20 years), 2 of 55 patients underwent GK SRS for a second time; 1 of these patients had had a recurrence after initial resection. The 5-year rate of freedom from additional management was 96%. Hearing preservation rates (i.e., remaining within the same Gardner-Robertson hearing class) were 93%, 87%, and 87% at 3, 5, and 10 years, respectively. In patients with serviceable hearing before SRS, it was maintained in 100%, 93%, and 93% of patients at 3, 5, and 10 years, respectively. Hearing preservation was related to a margin dose lower than 13 Gy (P = 0.017). At the last assessment, facial and trigeminal nerve function was preserved in 98.2% and 96.4% of patients, respectively; the only facial deficit (House-Brackmann grade III) occurred in a patient who received a tumor dose of 20 Gy early in our experience (1988). None of the patients treated with doses lower than 13 Gy experienced facial or trigeminal neuropathy. All patients continued their previous level of activity or employment after GK SRS. No patient developed a secondary radiation-related tumor. CONCLUSIONOur experience indicates that GK SRS is an effective management strategy for younger patients with vestibular schwannoma, most of whom have no additional cranial nerve dysfunction.
Fossils know it best: using a new set of fossil calibrations to improve the temporal phylogenetic framework of murid rodents (Rodentia: Myomorpha: Muroidea: Muridae)

Murid rodents (Rodentia: Myomorpha: Muroidea: Muridae) represent the most diverse and abundant mammalian group. In this study, we reconstruct a dated phylogeny of the family using a multilocus dataset (six nuclear and nine mitochondrial gene fragments) encompassing 160 species representing 82 distinct murid genera from four extant subfamilies (Deomyinae, Gerbillinae, Lophiomyinae, and Murinae). In comparison with previous studies on murid or muroid rodents, our work stands out for the implementation of multiple fossil constraints within the Muridae thanks to a thorough review of the fossil record. Before being assigned to specific nodes of the phylogeny, all potential fossil constraints were carefully assessed; they were also subjected to several cross-validation analyses. The resulting phylogeny is consistent with previous phylogenetic studies on murids, and recovers the monophyly of all sampled murid subfamilies and tribes. Based on nine controlled fossil calibrations, our inferred temporal timeframe indicates that the murid family likely originated in the course of the Early Miocene, 23.0-16.0 million years ago (Ma), and that most major lineages (i.e. tribes) have started diversifying ca. 10 Ma. Historical biogeography analyses support the Paleotropical origin for the family, with an initial internal split (vicariance event) followed by subsequent migrations between Afrotropical and Indomalayan lineages. During the course of their diversification, the biogeographic pattern of murids is marked by several dispersal events toward the Australasian and the Palearctic regions, mostly from the Indomalaya. The Afrotropical region was also secondarily colonized at least three times from the Indomalaya, indicating that the latter region has acted as a major centre of diversification for the family.
CD11b+/Gr-1+ Myeloid Suppressor Cells Cause T Cell Dysfunction after Traumatic Stress1

T cell dysfunction that occurs after surgery or trauma is associated with a poor clinical outcome. We describe that myeloid suppressor cells expressing CD11b+/Gr-1+ markers invade the spleen after traumatic stress and suppress T cell function through the production of arginase 1. We created a consistent model of traumatic stress in C57BL/6 mice to perform this work. A significant number of CD11b+/Gr-1+ cells expressing arginase 1 accumulated in T cell zones around the germinal centers of the white pulp of the spleen within 6 h of trauma and lasted for at least 72 h. Increased arginase activity and arginase 1 expression, along with increased [3H]arginine uptake, l-arginine depletion, and l-ornithine accumulation in the culture medium, were observed exclusively in CD11b+/Gr-1+ cells after traumatic stress. Flow cytometry revealed CD11b+/Gr-1+ as a heterogeneous myeloid suppressor cell also expressing low levels of MHC class I and II, CD80, CD86, CD31, and others. When compared with controls, trauma-induced CD11b+/Gr-1+ cells significantly inhibited CD3/CD28-mediated T cell proliferation, TCR ζ-chain expression, and IL-2 production. The suppressive effects by trauma CD11b+/Gr-1+ cells were overcome with the arginase antagonist N-hydroxy-nor-l-arginine or extrasupplementation of medium with l-arginine. Poor Ag-presenting capacity of control and trauma-induced CD11b+/Gr-1+ cells was detected in allogeneic murine leukocyte reaction. This study demonstrates that CD11b+/Gr-1+ cells invade the spleen following traumatic stress and cause T cell dysfunction by an arginase-mediated mechanism, probably that of arginine depletion. Understanding the mechanism of immune suppression by these cells has important clinical implications in the treatment of immune dysfunction after trauma or surgery.
Universal Limit Laws for Depths in Random Trees

Random binary search trees, b-ary search trees, median-of-(2k+1) trees, quadtrees, simplex trees, tries, and digital search trees are special cases of random split trees. For these trees, we offer a universal law of large numbers and a limit law for the depth of the last inserted point, as well as a law of large numbers for the height.
Model for Assessment and Computational Analysis of the Concentration of Zinc Dissolved during Leaching of Sphalerite in Butanoic Acid Solution

A model for assessment and computational analysis of the concentration of zinc dissolved during leaching of sphalerite in butanoic acid solution has been derived. The model Zn = Antilog [(exp(γ/α))0.6173] is dependent on the initial and final pH of the leaching solution. The validity of the model was found to be rooted in the expression (Log Zn)1.62 = exp(γ/α) where both sides of the expression are approximately equal to 3. The maximum deviation of the model-predicted concentrations of dissolved zinc from that of the corresponding experimental values is less than 14% which is quite within the acceptable deviation limit of experimental results.
Inhibition of the Formation of the Spf1p Phosphoenzyme by Ca2+*

P5-ATPases are important for processes associated with the endosomal-lysosomal system of eukaryotic cells. In humans, the loss of function of P5-ATPases causes neurodegeneration. In the yeast Saccharomyces cerevisiae, deletion of P5-ATPase Spf1p gives rise to endoplasmic reticulum stress. The reaction cycle of P5-ATPases is poorly characterized. Here, we showed that the formation of the Spf1p catalytic phosphoenzyme was fast in a reaction medium containing ATP, Mg2+, and EGTA. Low concentrations of Ca2+ in the phosphorylation medium decreased the rate of phosphorylation and the maximal level of phosphoenzyme. Neither Mn2+ nor Mg2+ had an inhibitory effect on the formation of the phosphoenzyme similar to that of Ca2+. The Km for ATP in the phosphorylation reaction was ∼1 μm and did not significantly change in the presence of Ca2+. Half-maximal phosphorylation was attained at 8 μm Mg2+, but higher concentrations partially protected from Ca2+ inhibition. In conditions similar to those used for phosphorylation, Ca2+ had a small effect accelerating dephosphorylation and minimally affected ATPase activity, suggesting that the formation of the phosphoenzyme was not the limiting step of the ATP hydrolytic cycle.
Number and brightness image analysis reveals ATF‐induced dimerization kinetics of uPAR in the cell membrane

We studied the molecular forms of the GPI‐anchored urokinase plasminogen activator receptor (uPAR‐mEGFP) in the human embryo kidney (HEK293) cell membrane and demonstrated that the binding of the amino‐terminal fragment (ATF) of urokinase plasminogen activator is sufficient to induce the dimerization of the receptor. We followed the association kinetics and determined precisely the dimeric stoichiometry of uPAR‐mEGFP complexes by applying number and brightness (N&B) image analysis. N&B is a novel fluctuation‐based approach for measuring the molecular brightness of fluorophores in an image time sequence in live cells. Because N&B is very sensitive to long‐term temporal fluctuations and photobleaching, we have introduced a filtering protocol that corrects for these important sources of error. Critical experimental parameters in N&B analysis are illustrated and analyzed by simulation studies. Control experiments are based on mEGFP‐GPI, mEGFP‐mEGFP‐GPI, and mCherry‐GPI, expressed in HEK293. This work provides a first direct demonstration of the dimerization of uPAR in live cells. We also provide the first methodological guide on N&B to discern minor changes in molecular composition such as those due to dimerization events, which are involved in fundamental cell signaling mechanisms. —Hellriegel, C. , Caiolfa, V. R. , Corti, V. , Sidenius, N. , Zamai, M. Number and brightness image analysis reveals ATF‐induced dimerization kinetics of uPAR in the cell membrane. FASEB J. 25, 2883–2897 (2011). www.fasebj. org
Frequency modulation entrains slow neural oscillations and optimizes human listening behavior

The human ability to continuously track dynamic environmental stimuli, in particular speech, is proposed to profit from “entrainment” of endogenous neural oscillations, which involves phase reorganization such that “optimal” phase comes into line with temporally expected critical events, resulting in improved processing. The current experiment goes beyond previous work in this domain by addressing two thus far unanswered questions. First, how general is neural entrainment to environmental rhythms: Can neural oscillations be entrained by temporal dynamics of ongoing rhythmic stimuli without abrupt onsets? Second, does neural entrainment optimize performance of the perceptual system: Does human auditory perception benefit from neural phase reorganization? In a human electroencephalography study, listeners detected short gaps distributed uniformly with respect to the phase angle of a 3-Hz frequency-modulated stimulus. Listeners’ ability to detect gaps in the frequency-modulated sound was not uniformly distributed in time, but clustered in certain preferred phases of the modulation. Moreover, the optimal stimulus phase was individually determined by the neural delta oscillation entrained by the stimulus. Finally, delta phase predicted behavior better than stimulus phase or the event-related potential after the gap. This study demonstrates behavioral benefits of phase realignment in response to frequency-modulated auditory stimuli, overall suggesting that frequency fluctuations in natural environmental input provide a pacing signal for endogenous neural oscillations, thereby influencing perceptual processing.
Association and path analysis for seed cotton yield improvement in interspecific crosses of cotton (gossypium spp).

Correlation studies made with parents, F1’s of 15 (lines) x 4 (testers) and one check hybrid (TCHB 213) in interspecific crosses of cotton (Gossypium spp) revealed that plant height, number of sympodial branches per plant, number of bolls per plant along with 2.5 per cent span length, bundle strength and elongation percentage showed significant positive association with seed cotton yield per plant at genotypic level indicating that these characters can be improve simultaneously. The direct and indirect effect of path analysis revealed that the number of bolls per plant, boll weight, number of sympodial branches per plant, plant height, 2.5 per cent span length, bundle strength, elongation percentage, lint index and seed index are the major yield contributing traits in interspecific crosses and should be considered for improving yield under wide hybridization in cotton. The correlation and path co-efficient analysis revealed that simultaneous selection based on plant height, number of bolls per plant, number of sympodial branches per plant, 2.5 per cent span length, bundle strength and elongation percentage may be promising in improving the seed cotton yield per plant.
Proneurotrophin‐3 may induce Sortilin‐dependent death in inner ear neurons

The precursor of the neurotrophin (NT) nerve growth factor (NGF) (proNGF) serves physiological functions distinct from its mature counterpart as it induces neuronal apoptosis through activation of a p75 NT receptor (p75NTR) and Sortilin death‐signalling complex. The NTs brain‐derived nerve growth factor (BDNF) and NT3 provide essential trophic support to auditory neurons. Injury to the NT‐secreting cells in the inner ear is followed by irreversible degeneration of spiral ganglion neurons with consequences such as impaired hearing or deafness. Lack of mature NTs may explain the degeneration of spiral ganglion neurons, but another mechanism is possible as unprocessed proNTs released from the injured cells may contribute to the degeneration by induction of apoptosis. Recent studies demonstrate that proBDNF, like proNGF, is a potent inducer of Sortilin:p75NTR‐mediated apoptosis. In addition, a coincident upregulation of proBDNF and p75NTR has been observed in degenerating spiral ganglion neurons, but the Sortilin expression in the inner ear is unresolved. Here we demonstrate that Sortilin and p75NTR are coexpressed in neurons of the neonatal inner ear. Furthermore, we establish that proNT3 exhibits high‐affinity binding to Sortilin and has the capacity to enhance cell surface Sortilin:p75NTR complex formation as well as to mediate apoptosis in neurons coexpressing p75NTR and Sortilin. Based on the examination of wildtype and Sortilin‐deficient mouse embryos, Sortilin does not significantly influence the developmental selection of spiral ganglion neurons. However, our results suggest that proNT3 and proBDNF may play important roles in the response to noise‐induced injuries or ototoxic damage via the Sortilin:p75NTR death‐signalling complex.
Ghrelin regulates phasic dopamine and nucleus accumbens signaling evoked by food‐predictive stimuli

Environmental stimuli that signal food availability hold powerful sway over motivated behavior and promote feeding, in part, by activating the mesolimbic system. These food‐predictive cues evoke brief (phasic) changes in nucleus accumbens (NAc) dopamine concentration and in the activity of individual NAc neurons. Phasic fluctuations in mesolimbic signaling have been directly linked to goal‐directed behaviors, including behaviors elicited by food‐predictive cues. Food‐seeking behavior is also strongly influenced by physiological state (i.e., hunger vs. satiety). Ghrelin, a stomach hormone that crosses the blood‐brain barrier, is linked to the perception of hunger and drives food intake, including intake potentiated by environmental cues. Notwithstanding, whether ghrelin regulates phasic mesolimbic signaling evoked by food‐predictive stimuli is unknown. Here, rats underwent Pavlovian conditioning in which one cue predicted the delivery of rewarding food (CS+) and a second cue predicted nothing (CS−). After training, we measured the effect of ghrelin infused into the lateral ventricle (LV) on sub‐second fluctuations in NAc dopamine using fast‐scan cyclic voltammetry and individual NAc neuron activity using in vivo electrophysiology in separate groups of rats. LV ghrelin augmented both phasic dopamine and phasic increases in the activity of NAc neurons evoked by the CS+. Importantly, ghrelin did not affect the dopamine nor NAc neuron response to the CS−, suggesting that ghrelin selectively modulated mesolimbic signaling evoked by motivationally significant stimuli. These data demonstrate that ghrelin, a hunger signal linked to physiological state, can regulate cue‐evoked mesolimbic signals that underlie food‐directed behaviors. Cues that predict food availability powerfully regulate food‐seeking behavior. Here we show that cue‐evoked changes in both nucleus accumbens (NAc) dopamine (DA) and NAc cell activity are modulated by intra‐cranial infusions of the stomach hormone ghrelin ‐ a hormone known to act centrally to promote food intake. These data demonstrate that hormones associated with physiological state (i.e., hunger) can affect encoding of food‐predictive cues in brain regions that drive food‐motivated behavior.
Proteomic analysis on the expression of outer membrane proteins of Vibrio alginolyticus at different sodium concentrations

The ability of osmoregulation is crucial to marine pathogens that always face the change of osmotic pressure when they shift between natural marine water‐bodies and hosts. Previous studies indicated that the expressional patterns of outer membrane proteins (OMPs) changed when Gram‐negative bacteria were transferred in different environments. In the present study, proteomic methodologies were used to investigate the expressional pattern of OMPs of Vibrio alginolyticus, a universal marine pathogen, at different Na+ concentrations. OmpW, OmpV, and Omp TolC were determined to be osmotic stress responsive proteins. Of the three proteins, importantly, OmpV and OmpW showed distinctly reverse changes to each other, indicating that the two proteins might be the two components varied with changed NaCl concentrations. In addition, our results suggest that closely related species of bacteria with available whole genomic databases should be applied after item microorganism species was used when proteins from a bacterium with unavailable whole genomic information were identified by PMF. Therefore, our results not only expand our knowledge on osmotic stress responsive proteins, but also provide valuable information for strategies on screening of these proteins.
Neural correlates of trait anxiety in fear extinction

Background Fear conditioning involves the amygdala as the main neural structure for learning fear responses whereas fear extinction mainly activates the inhibitory prefrontal cortex (PFC). In this study we investigated whether individual differences in trait anxiety affect amygdala and dorsal anterior cingulate cortex (dACC) activation during fear conditioning and extinction. Method Thirty-two healthy subjects were investigated by functional magnetic resonance imaging (fMRI) at 3 T while performing a cued fear-conditioning task. All participants completed the trait version of the State-Trait Anxiety Inventory (STAI-T). Activations of the amygdala and the dACC were examined with respect to the effects of trait anxiety. Results Analysis of the fMRI data demonstrated enhanced activation in fear-related brain areas, such as the insula and the ACC, during both fear conditioning and extinction. Activation of the amygdala appeared only during the late acquisition phase whereas deactivation was observed during extinction. Regression analyses revealed that highly trait-anxious subjects exhibited sustained amygdala activation and reduced dACC involvement during the extinction of conditioned responses. Conclusions This study reveals that high levels of trait anxiety are associated with both increased amygdala activation and reduced dACC recruitment during the extinction of conditioned fear. This hyper-responsitivity of the amygdala and the deficient cognitive control during the extinction of conditioned fear in anxious subjects reflect an increased resistance to extinct fear responses and may thereby enhance the vulnerability to developing anxiety disorders.
Robust adaptive model predictive control based on comparison model

This paper proposes an adaptive model predictive control (MPC) algorithm for constrained linear systems, which updates the estimation of system parameters on-line and produces the control input subject to the given input/state constraints. This method is based on a robust MPC algorithm using comparison models, which enable us to estimate the prediction error bounds of uncertain systems, and an adaptive mechanism. First, a new parameter update method based on the moving horizon estimation is proposed, which allows us to predict the worst-case estimation error bound over the prediction horizon. Second, we propose an adaptive MPC algorithm developed by combining the on-line parameter estimation with MPC method based on the modified comparison model which is extended to be applicable to the time varying-case. This method guarantees the feasibility and the stability of the closed-loop systems in the presence of system constraints. Finally, a numerical example is given to demonstrate its effectiveness.
Limited value of testing for intrinsic factor antibodies with negative gastric parietal cell antibodies in pernicious anaemia

Background: The appropriate testing strategy for diagnosing pernicious anaemia using gastric parietal cell (GPC) and/or intrinsic factor antibodies (IFA) is controversial. Intrinsic factor antibodies are found in only about 70% of cases. Indirect immunofluorescence screening for gastric parietal cell antibodies is more sensitive, labour intensive, and less specific. Methods: The frequency of antibody positivity (IFA and/or GPC) was retrospectively examined in patients tested for both autoantibodies over a three-year period. It was investigated whether B12 levels were related to antibody status. These findings were validated in a prospective study of IFA in 91 GPC negative patients with low B12 levels. Results: Of 847 samples identified in the retrospective study, 4 (0.47%) were positive for only intrinsic factor antibodies, 731 (86.3%) positive for GPC alone, and 112 (13.2%) for both. Student t test on log-transformed data showed B12 levels had no bearing on autoantibody status. 91 consecutive patients with low B12 levels were tested for both autoantibodies; all were negative for gastric parietal cell antibodies. Only one sample was positive for intrinsic factor antibody using the porcine intrinsic factor assay, but was negative by a human recombinant intrinsic factor-based ELISA. Conclusions: This study provides evidence that testing for gastric parietal cell antibodies is an appropriate screening test for pernicious anaemia, with intrinsic factor antibodies reserved for confirmatory testing or in patients with other autoantibodies that mask the GPC pattern; B12 levels are not related to autoantibody status.