Miracle-dz/UniFAR-FTUs huggingface dataset:
The Voltage-dependent Anion Channel 1 Mediates Amyloid β Toxicity and Represents a Potential Target for Alzheimer Disease Therapy*

The voltage-dependent anion channel 1 (VDAC1), found in the mitochondrial outer membrane, forms the main interface between mitochondrial and cellular metabolisms, mediates the passage of a variety of molecules across the mitochondrial outer membrane, and is central to mitochondria-mediated apoptosis. VDAC1 is overexpressed in post-mortem brains of Alzheimer disease (AD) patients. The development and progress of AD are associated with mitochondrial dysfunction resulting from the cytotoxic effects of accumulated amyloid β (Aβ). In this study we demonstrate the involvement of VDAC1 and a VDAC1 N-terminal peptide (VDAC1-N-Ter) in Aβ cell penetration and cell death induction. Aβ directly interacted with VDAC1 and VDAC1-N-Ter, as monitored by VDAC1 channel conductance, surface plasmon resonance, and microscale thermophoresis. Preincubated Aβ interacted with bilayer-reconstituted VDAC1 and increased its conductance ∼2-fold. Incubation of cells with Aβ resulted in mitochondria-mediated apoptotic cell death. However, the presence of non-cell-penetrating VDAC1-N-Ter peptide prevented Aβ cellular entry and Aβ-induced mitochondria-mediated apoptosis. Likewise, silencing VDAC1 expression by specific siRNA prevented Aβ entry into the cytosol as well as Aβ-induced toxicity. Finally, the mode of Aβ-mediated action involves detachment of mitochondria-bound hexokinase, induction of VDAC1 oligomerization, and cytochrome c release, a sequence of events leading to apoptosis. As such, we suggest that Aβ-mediated toxicity involves mitochondrial and plasma membrane VDAC1, leading to mitochondrial dysfunction and apoptosis induction. The VDAC1-N-Ter peptide targeting Aβ cytotoxicity is thus a potential new therapeutic strategy for AD treatment.
Venture capital, innovation, and growth: evidence from Chinese metropolitan data

ABSTRACT Using panel data from 282 Chinese cities from 2003 to 2015, we estimate the impact of venture capital (VC) on innovation, employment, and payroll in metropolitan areas. Controlling for endogeneity, VC investments are significantly positively related to metropolitan innovation, employment, and payroll in a fixed effects panel regression and dynamic GMM estimation. Using the number of IPOs (Initial public offerings) in the city as an instrumental variable to again control for endogeneity, VC remains significant. Our results show that VC is significantly contributing to the metropolitan economy as a whole by supporting innovation, creating jobs, and generating wealth in the local cities.
The use and importance of liposomes in Positron Emission Tomography

Among different imaging modalities, Positron Emission Tomography (PET) gained importance in routine hospital practice depending on ability to diagnose diseases in early stages and tracing of therapy by obtaining metabolic information. The combination of PET with Computed Tomography (CT) forms hybrid imaging modality that gives chance to obtain better images having higher resolution by fusing both functional and anatomical images in the same imaging modality at the same time. Therefore, better contrast agents are essentially needed. The advance in research about developing drug delivery systems as specific nanosized targeted systems gained an additional importance for obtaining better diagnosis and therapy of different diseases. Liposomes appear to be more attractive drug delivery systems in delivering either drugs or imaging ligands to target tissue or organ of diseases with higher accumulation by producing in nano-scale, long circulating by stealth effect and specific targeting by modifying with specific ligands or markers. The combination of positron emitting radionuclides with liposomes are commonly in research level nowadays and there is no commercially available liposome formulation for PET imaging. However by conjugating positron emitter radionuclide with liposomes can form promising diagnostic agents for improved diagnosis and following up treatments by increasing image signal/contrast in the target tissue in lower concentrations by specific targeting as the most important advantage of liposomes. More accurate and earlier diagnosis of several diseases can be obtained even in molecular level with the use of stable and effectively radiolabeled molecular target specific nano sized liposomes with longer half-lived positron emitting radionuclides.
T-cell-derived Interleukin-17 Regulates the Level and Stability of Cyclooxygenase-2 (COX-2) mRNA through Restricted Activation of the p38 Mitogen-activated Protein Kinase Cascade

Although interleukin-17 (IL-17) is the pre-eminent T-cell-derived pro-inflammatory cytokine, its cellular mechanism of action remains poorly understood. We explored novel signaling pathways mediating IL-17 induction of the cyclooxygenase-2 (COX-2) gene in human chondrocytes, synovial fibroblasts, and macrophages. In preliminary work, recombinant human (rh) IL-17 stimulated a rapid (5–15 min), substantial (>8-fold), and sustained (>24 h) increase in COX-2 mRNA, protein, and prostaglandin E2 release. Screening experiments with cell-permeable kinase inhibitors (e.g. SB202190 and p38 inhibitor), Western analysis using specific anti-phospho-antibodies to a variety of mitogen-activated protein kinase cascade intermediates, co-transfection studies using chimeric cytomegalovirus-driven constructs of GAL4 DNA-binding domains fused to the transactivation domains of transcription factors together with Gal-4 binding element-luciferase reporters, ectopic overexpression of activated protein kinase expression plasmids (e.g. MKK3/6), or transfection experiments with wild-type and mutant COX-2 promoter constructs revealed that rhIL-17 induction of the COX-2 gene was mediated exclusively by the stress-activated protein kinase 2/p38 cascade. A rhIL-17-dependent transcriptional pulse (1.76 ± 0.11-fold induction) was initiated by ATF-2/CREB-1 transactivation through the ATF/CRE enhancer site in the proximal promoter. However, steady-state levels of rhIL-17-induced COX-2 mRNA declined rapidly (<2 h) to control levels under wash-out conditions. Adding rhIL-17 to transcriptionally arrested cells stabilized COX-2 mRNA for up to 6 h, a process compromised by SB202190. Deletion analysis using transfected chimeric luciferase-COX-2 mRNA 3′-untranslated region reporter constructs revealed that rhIL-17 increased reporter gene mRNA stability and protein synthesis via distal regions (–545 to –1414 bases) of the 3′-untranslated region. This response was mediated entirely by the stress-activated protein kinase 2/p38 cascade. As such, IL-17 can exert direct transcriptional and post-transcriptional control over target proinflammatory cytokines and oncogenes.
Seasonal Quasi-Vector Autoregressive Models with an Application to Crude Oil Production and Economic Activity in the United States and Canada

We introduce the Seasonal-QVAR (quasi-vector autoregressive) model that we apply to study the relationship between oil production and economic activity. Seasonal-QVAR is a score-driven nonlinear model for the multivariate t distribution. It is an alternative to the basic structural model that disentangles local level and stochastic seasonality. Seasonal-QVAR is robust to extreme observations and it is an extension of Seasonal-VARMA (VAR moving average). We use monthly data from world crude oil production growth, global real economic activity growth and the industrial production growths of the United States and Canada. We address an important economic question about the influence of world crude oil production on the industrial productions of the United States and Canada. We find that the effects of industrial production growth of the United States on world crude oil production growth are about six times higher for the basic structural model and Seasonal-VARMA than for Seasonal-QVAR. We also find that the effects of world crude oil production growth on the industrial production growth of Canada are positive for Seasonal-QVAR, but those effects are negative for Seasonal-VARMA. Likelihood-based performance metrics and transitivity arguments support the estimates of Seasonal- QVAR, as opposed to the basic structural model and Seasonal-VARMA.
Low-frequency sonophoresis: pathologic and thermal effects in dogs.

OBJECTIVE Low-frequency sonophoresis has recently been shown to significantly facilitate transdermal permeability of various substances (e.g., insulin) in animal models, thus eliminating the need to inject such agents. Prior to human trials, the authors studied the safety profile of low-frequency sonophoresis in dogs by evaluating microscopic and temperature changes in the skin after sonophoresis. METHODS An evaluator-blinded canine study of sonophoresis using different energy intensities and probe diameters was performed. Low-frequency ultrasound was applied for 60 seconds to the clipped abdominal skin of 3 anesthetized adult mongrel dogs using a sonicator operating at a frequency of 20 KHz with a maximal energy output of 400 W. The sonicator was immersed in normal saline, and intensities of 4%, 10%, 20%, 30%, and 50% were applied during 600 msec of every second (pulsed mode). Three probes, 1-cm cylindrical, 5-cm cylindrical, and 10-cm disc-shaped, were evaluated. Each experimental condition was performed twice. Subcutaneous temperatures were measured by temperature probe before and after sonophoresis. At 30 minutes post-sonophoresis, full-thickness skin biopsies were taken for blinded histopathologic evaluation. RESULTS Minimal urticarial reactions were noted with the 1-cm probe at intensities of < or = 20% and with the 5-cm probe at 4% intensity. With higher intensity, thermal injuries were observed grossly with erythema and vesicles. The microscopic correlates were papillary and dermal edema with neutrophils and telangiectasia. The conditions producing vesicles grossly had foci of epidermal necrosis, subepidermal vesicles, and degeneration of papillary dermal collagen. With still higher intensities, confluent epidermal necrosis became apparent. Use of the 10-cm probe did not result in any injury. CONCLUSIONS Low-frequency ultrasound at low intensities appears safe for use to enhance the topical delivery of medications, producing only minimal urticarial reactions. Higher-intensity conditions resulted in second-degree burns, most likely attributable to localized heating.
Cooperative games among consumers in the smart grid

Existing studies are to a great extent focus on energy saving mechanisms of individual customers, independently, from other energy consumers. This paper considers an agent-based cooperative model among consumers in the smart grid. The agents in our model act on behalf of residential consumers through techniques such as domestic energy controllers or the smart meters, which are available for end-users in the smart grid. solution concept is proposed based on cooperative games. In this paper, we discuss the performance of the agents' payoff under the concept of coalition formation. Our proposed approach is intended as a decentralized method where coalition formation is achieved through self-organization.
Clinical evaluation of a new tracheal impedance cardiography method

Non‐invasive cardiac output measurement by means of impedance cardiography has been evaluated before, and agreement with other methods has been variable. We decided to study a newly developed tracheal impedance device, that is claimed to be more accurate and reliable. This incorporates new software and mathematical formulae, that are designed to reduce signal noise from diathermy, leading to improved accuracy. In 25 cardiothoracic surgery patients, simultaneous measurements were performed using both pulmonary artery thermodilution and the tracheal impedance device, at five peri‐operative time points: before skin incision; after weaning from cardiopulmonary bypass; after sternal closure; and 30 min and 2 h after arrival in the intensive care unit. Mean cardiac output, bias and 95% limits of agreement were 5.3, 0.03 and −2.8 to 2.8 l.min−1, respectively. Tracheal impedance showed good correlation with measurement trends using thermodilution in 88% of measurements, with a mean (95% limit of agreement) angular bias of −9.0° (−83.3 to 65.3°). However, the wide limits of agreement and high percentage error of 53% that were apparent in this study mean that, in its present guise, tracheal impedance is not an acceptable alternative to thermodilution in cardiac surgical patients.
[Effect of additional chromosome abnormalities on the outcome of newly diagnosed acute promyelocytic leukemia treated with red arsenic sulfide and all trans-retinoic acid plus anthracyclin based protocol].

OBJECTIVE To analyze the effect of additional chromosome abnormalities on the prognosis and the clinical manifestations of acute promyelocytic leukemia (APL) and the reaction of the patients with additional chromosomes to the treatment of combination of red arsenic sulfide, all trans-retinoic acid (ATRA) and anthracyclin. METHODS The clinical data of 158 patients with newly diagnosed APL who were treated with combination of red arsenic sulfide, ATRA, and anthracyclin were analyzed retrospectively. RESULTS The frequency of additional chromosome abnormalities in the APL patients was 18.4%, and trisomy 8 and i17q- were the most to be seen. The disseminated intravascular coagulation rate of the patients with additional chromosome abnormality was 62.1%, significantly higher than that of the patients without additional chromosome abnormality (35.6%, P < 0.05). The complete remission rate of the patients with additional chromosome abnormality was 75.9%, not significantly lower than that of those without additional chromosome abnormality (90.7%), and the relapse rate and incidence rate of central nervous system leukemia were 13.8% and 17.2%, both higher, but not significantly, than those of the patients without additional chromosome abnormality (6.2% and 6.2% respectively) (all P > 0.05). There was no significant difference in survival rate between these 2 groups (P = 0.160). CONCLUSION Additional chromosome abnormality does not significantly influence the prognosis of APL treated with combination of red arsenic sulfide, ATRA, and anthracyclin.
A Novel HOS Approach for Blind Channel Equalization

We present in this paper a new equalization method with over 8 dB advantage in the residual ISI compared to the classical results presented by Godard and Shalvi/Weinstein (kurtosis criteria). A systematic derivation is presented for obtaining the conditional expectation for f(x/z) that does not rely on the knowledge of the convolutional noise power nor imposes any restrictions on the probability distribution of the (unobserved) input sequence. We use Edgeworth series which is directly related to quasi moments thus to cumulants, and the Laplace integral method. Although the Edgeworth expansion and the Laplace integral method are well known in non-linear optimal filtering theory, they have not yet been used in the field of blind equalization
Virtual Instrumentation use in static excitation systems

In the paper is presented a Virtual Instrumentations System developed for the control and dynamic behavior study of a hydro aggregate with synchronous generator with salient poles, having static excitation. The purpose of the work was the achievement of an experimental model of hydro-plant on LabVIEW environment based, that allow to implement various excitation control strategies. The model was designed and built in laboratory, at reduced power of 12 kVA, using a real-time routine.
Does the negative effect of caregiving on work persist over time

Informal caregivers provide valuable services to elderly persons with long-term care needs. However, the time commitment of caregiving often competes against time spent in the labour force. In addition to the momentary trade-off, long-term consequences are possible since especially older workers might find it difficult to re-enter the labour market after a caregiving spell. While several studies document a negative relationship between caregiving and work, little is known about whether this effect is persistent over time. Analysing a large panel data set of 15 European countries and Israel, we show that care provision to an elderly parent has lasting negative effects on employment for both men and women but only women reduce their working hours.
Populism and political development in hybrid regimes: Russia and the development of official populism

Hybrid regimes like electoral authoritarianism blend elements of democratic and non-democratic political practices. Hybrid regimes can develop from populism or can themselves develop populism to explain and justify their democratic shortcomings. Where the latter occurs, populism is a tool of regime stabilisation rather than a form of ‘populism in power’. Moving from using some populist themes to assist regime stabilisation to official populism requires the development of populist discourse to a point where it becomes definitional of what constitutes the relationship between state and society. The paper uses the example of Russia to discuss the uses of populism in a hybrid regime. Populist rhetoric has been used by the Putin regime since the mid-2000s, but was initially balanced by other discourses. This changed during the 2011–2012 electoral cycle as a conservative-traditional populist discourse was deployed that redefined political agency and the relationship of the state to Russian society.
Glutaminase and MMP-9 Downregulation in Cortex and Hippocampus of LPA1 Receptor Null Mice Correlate with Altered Dendritic Spine Plasticity

Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates nervous system development and functions acting through G protein-coupled receptors (GPCRs). Here we explore the crosstalk between LPA1 receptor and glutamatergic transmission by examining expression of glutaminase (GA) isoforms in different brain areas isolated from wild-type (WT) and KOLPA1 mice. Silencing of LPA1 receptor induced a severe down-regulation of Gls-encoded long glutaminase protein variant (KGA) (glutaminase gene encoding the kidney-type isoforms, GLS) protein expression in several brain regions, particularly in brain cortex and hippocampus. Immunohistochemical assessment of protein levels for the second type of glutaminase (GA) isoform, glutaminase gene encoding the liver-type isoforms (GLS2), did not detect substantial differences with regard to WT animals. The regional mRNA levels of GLS were determined by real time RT-PCR and did not show significant variations, except for prefrontal and motor cortex values which clearly diminished in KO mice. Total GA activity was also significantly reduced in prefrontal and motor cortex, but remained essentially unchanged in the hippocampus and rest of brain regions examined, suggesting activation of genetic compensatory mechanisms and/or post-translational modifications to compensate for KGA protein deficit. Remarkably, Golgi staining of hippocampal regions showed an altered morphology of glutamatergic pyramidal cells dendritic spines towards a less mature filopodia-like phenotype, as compared with WT littermates. This structural change correlated with a strong decrease of active matrix-metalloproteinase (MMP) 9 in cerebral cortex and hippocampus of KOLPA1 mice. Taken together, these results demonstrate that LPA signaling through LPA1 influence expression of the main isoenzyme of glutamate biosynthesis with strong repercussions on dendritic spines maturation, which may partially explain the cognitive and learning defects previously reported for this colony of KOLPA1 mice.
Wi-Fi Indoor Localisation: a Deeper Insight Into Patterns in the Fingerprint Map Data

Localisation via Wi‑Fi networks is one of the possible techniques which can be used for positioning inside buildings or in other places without the GPS signal. The accurate indoor positioning system can help users with localisation or navigation within unfamiliar places. Almost all buildings are covered with the Wi‑Fi signal. Using the currently existing infrastructure will minimise cost for construction other types of indoor positioning systems. Among other reasons, usage of Wi‑Fi for positioning is also convenient because almost every mobile device has a Wi‑Fi capability and therefore the system can be easily used by everyone. However, an important factor is the precision of such a solution. The article is focused on the evaluation of Wi‑Fi localisation precision within the university grounds.
Scalable and Flexible Massive MIMO Precoding for 5G H-CRAN

Scalability and flexibility are widely considered as two major design goals for 5G networks. Aiming at these goals, this article first identifies a promising architecture based on the heterogeneous cloud radio access network (H-CRAN), reviews the challenges in MIMO precoding for H-CRAN, and then proposes a scalable and flexible massive MIMO precoding scheme by exploiting the null-space of user signals. Specifically, the system can accomplish effective radio resource management and flexible spatial coordination by distinguishing the intended and victim users' CSI, and avoid the interference by precoding within the null-space for the CSI of victim users. Simulation results indicate that the proposed scheme is capable to effectively alleviate the interference to victim users and support high QoS as well as spectral efficiency.
Transcriptional Regulation of the Human α2(I) Collagen Gene

This study identifies three regions of the human α2(I) collagen promoter involved in the binding of nuclear factors. These regions include sequences from −173 to −155 (footprint I), −133 to −119 (footprint II), and −101 to −72 (footprint III). A novel positive cis-element containing a TCCTCC motif was identified within footprint II. In addition, we demonstrated that a pyrimidine-rich region within footprint I is a binding site for a transcriptional repressor, and a CCAAT motif within footprint III is a binding site for a transcriptional activator. Comparative functional analysis of the cis-acting elements within the proximal 350 base pairs of this promoter, including previously characterized Sp1 binding sites at −300, indicates that constitutive activity of this promoter is regulated equivalently by the three positive cis-acting elements at −300, −125, and −80. Mutations in the repressor site at −160 increase constitutive activity by 4-6-fold. However, simultaneous mutations of the repressor site and the cis-regulatory element at either the −300 or −125 sites result in no increase in constitutive transcription activity suggesting interaction between the activators and repressor elements. In contrast, simultaneous mutation of the CCAAT motif and the repressor site results in about a 4-fold increase, suggesting that activation via the CCAAT motif may be independent of this repressor.