Miracle-dz/UniFAR-FTUs huggingface dataset:
Non‐fibrillar β‐amyloid abates spike‐timing‐dependent synaptic potentiation at excitatory synapses in layer 2/3 of the neocortex by targeting postsynaptic AMPA receptors

Cognitive decline in Alzheimer's disease (AD) stems from the progressive dysfunction of synaptic connections within cortical neuronal microcircuits. Recently, soluble amyloid β protein oligomers (Aβols) have been identified as critical triggers for early synaptic disorganization. However, it remains unknown whether a deficit of Hebbian‐related synaptic plasticity occurs during the early phase of AD. Therefore, we studied whether age‐dependent Aβ accumulation affects the induction of spike‐timing‐dependent synaptic potentiation at excitatory synapses on neocortical layer 2/3 (L2/3) pyramidal cells in the APPswe/PS1dE9 transgenic mouse model of AD. Synaptic potentiation at excitatory synapses onto L2/3 pyramidal cells was significantly reduced at the onset of Aβ pathology and was virtually absent in mice with advanced Aβ burden. A decreased α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)/N‐methyl‐d‐aspartate (NMDA) receptor‐mediated current ratio implicated postsynaptic mechanisms underlying Aβ synaptotoxicity. The integral role of Aβols in these processes was verified by showing that pretreatment of cortical slices with Aβ(25−35)ols disrupted spike‐timing‐dependent synaptic potentiation at unitary connections between L2/3 pyramidal cells, and reduced the amplitude of miniature excitatory postsynaptic currents therein. A robust decrement of AMPA, but not NMDA, receptor‐mediated currents in nucleated patches from L2/3 pyramidal cells confirmed that Aβols perturb basal glutamatergic synaptic transmission by affecting postsynaptic AMPA receptors. Inhibition of AMPA receptor desensitization by cyclothiazide significantly increased the amplitude of excitatory postsynaptic potentials evoked by afferent stimulation, and rescued synaptic plasticity even in mice with pronounced Aβ pathology. We propose that soluble Aβols trigger the diminution of synaptic plasticity in neocortical pyramidal cell networks during early stages of AD pathogenesis by preferentially targeting postsynaptic AMPA receptors.
Molecular characterization of five new S alleles associated with self-incompatibility in local Spanish almond cultivars

Almond is a highly heterozygous species with a high number of S-alleles controlling its gametophytic self-incompatibility system (GSI). In this work we have analysed Spanish local almond cultivars for S-RNase allele diversity. By cloning and sequencing five new S-RNase alleles were identified: S31 (804 bp) in 'Pou de Felanitx' and 'Totsol', S32 (855 bp) in 'Taiatona', S33 (1165 bp) in 'Pou d'Establiments' and 'Muel', S34 (1663 bp) in 'Pane-Barquets', and S35 (1658 bp) in 'Planeta de les Garrigues'. The high number of new alleles identified reveals the wide diversity of almond germplasm still existing and requiring characterisation, and points to the possibility of new findings by a wider study focusing on other provenances.
Crystal structure of At2g03760, a putative steroid sulfotransferase from Arabidopsis thaliana

David W. Smith, Kenneth A. Johnson, Craig A. Bingman, David J. Aceti, Paul G. Blommel, Russell L. Wrobel, Ronnie O. Frederick, Qin Zhao, Hassan Sreenath, Brian G. Fox, Brian F. Volkman, Won Bae Jeon, Craig S. Newman, Eldon L. Ulrich, Adrian D. Hegeman, Todd Kimball, Sandy Thao, Michael R. Sussman, John L. Markley, and George N. Phillips, Jr.* Center for Eukaryotic Structural Genomics, Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin Center for Eukaryotic Structural Genomics, Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin
Photovoltaic power systems: A review of topologies, converters and controls

Renewable energy resources will likely be an integral part of future electrical systems. Photovoltaics in particular are receiving significant research attention in terms of developing the photovoltaic (PV) system to improve efficiency and to meet grid codes, as well as developing intelligent methods of control. This paper presents a review of the main established PV system topologies as well as the emerging multilevel converter based topologies. The Model Predictive Control (MPC) method for converter control is also presented, with particular emphasis on the key features for PV applications.
“Drug-Induced Liver Injury Clinical Consortia: a global research response for a worldwide health challenge”

The hepatic safety of drugs is a major concern of the pharmaceutical industry throughout the whole process of drug development. Whereas the intrinsic toxicity of a few drugs will become evident during the early stages of this process (i.e. in cellular cultures or animal studies), for the bulk of hazardous medications, which will injure the liver in rare occasions, the hepatotoxicity profile may remain hidden in both preclinical and clinical phases. Actually, clinical trials are able to identify relatively common adverse reactions (i.e. occurring at a rate greater than 1 per 1000 exposed subjects), but are generally underpowered to detect the low incidence of idiosyncratic drug-induced liver injury (DILI). [1] The multifactorial nature of the idiosyncratic chemical damage targeting the liver depends on the interaction of the drug physicochemical properties with the host factors that make the subjects susceptible on rare instances. [2] No reliable methods for accurately predicting the occurrence of toxic liver damage on a given individual are still available. Hence, information on the true hepatic safety profile for the bulk of drugs relies on observational studies and requires the exposure of hundreds of thousands of subjects once the medication reaches the market. If an ‘outbreak’ of reports of liver damage linked to a particular drug use were detected, regulatory measures, including warnings and withdrawals, to limit the number of affected individuals would follow. Nowadays, however, many old drugs with hepatotoxic potential still remain in therapeutic use either because their true risk figures have not been fully recognized or due to a favorable benefit/risk balance (i.e. flucloxacillin, amoxicillin-clavulanate). Until recently, hepatotoxicity had not received enough attention from the academic investigators due to its relative rarity and data on hepatotoxicity of drugs were mostly compiled by the pharmaceutical industry under restrictive access rules or were simply unavailable. Indeed, the absence of valid diagnostic biomarkers means that DILI remains a ‘diagnosis of exclusion’, which limits the ‘scientific’ accuracy of the information retrieved and may discourage investigators from being involved on this topic. All these limitations represent an important barrier for proper case identification and characterization as well as for the availability of consistent epidemiological data.
Centrifuge Coating for Low-Waste Solution Processing of Transparent Nanostructured Electrodes

Centrifuge coating was implemented to fabricate nanostructured conductive layers through solution processing at room temperature. This coating procedure allows fast evaporation, thereby fixing the nanomaterials in their dispersed state onto a substrate by the centrifuge action. Material wastes were minimized by mitigating the effects of particle reaggregation. Using this method, we fabricate single-wall nanotube coatings on different substrates such as polyethylene terephthalate, polydimethylsiloxane, and an acrylic elastomer with no prior surface modification of the substrate. The effects of the choice of solvents on the morphology and subsequent performance of the coating network are studied.
A Transverse Tubule NADPH Oxidase Activity Stimulates Calcium Release from Isolated Triads via Ryanodine Receptor Type 1 S -Glutathionylation*

We report here the presence of an NADPH oxidase (NOX) activity both in intact and in isolated transverse tubules and in triads isolated from mammalian skeletal muscle, as established by immunochemical, enzymatic, and pharmacological criteria. Immunohistochemical determinations with NOX antibodies showed that the gp91phox membrane subunit and the cytoplasmic regulatory p47phox subunit co-localized in transverse tubules of adult mice fibers with the α1s subunit of dihydropyridine receptors. Western blot analysis revealed that isolated triads contained the integral membrane subunits gp91phox and p22phox, which were markedly enriched in isolated transverse tubules but absent from junctional sarcoplasmic reticulum vesicles. Isolated triads and transverse tubules, but not junctional sarcoplasmic reticulum, also contained varying amounts of the cytoplasmic NOX regulatory subunits p47phox and p67phox. NADPH or NADH elicited superoxide anion and hydrogen peroxide generation by isolated triads; both activities were inhibited by NOX inhibitors but not by rotenone. NADH diminished the total thiol content of triads by one-third; catalase or apocynin, a NOX inhibitor, prevented this effect. NADPH enhanced the activity of ryanodine receptor type 1 (RyR1) in triads, measured through [3H]ryanodine binding and calcium release kinetics, and increased significantly RyR1 S-glutathionylation over basal levels. Preincubation with reducing agents or NOX inhibitors abolished the enhancement of RyR1 activity produced by NADPH and prevented NADPH-induced RyR1 S-glutathionylation. We propose that reactive oxygen species generated by the transverse tubule NOX activate via redox modification the neighboring RyR1 Ca2+ release channels. Possible implications of this putative mechanism for skeletal muscle function are discussed.
Perioperative complications associated with operative treatment of acetabular fractures.

BACKGROUND Perioperative complications in a large number of consecutive patients with displaced acetabular fractures treated operatively were evaluated in an effort to elucidate potentially preventable complications. METHODS Perioperative complications were identified and evaluated in 131 consecutive patients with displaced acetabular fractures treated operatively using the Kocher-Langenbeck surgical exposure. The perioperative complications were identified using a registry. RESULTS There were a total of 76 complications related to the acetabular fracture and patient polytrauma. Eighteen complications resulted from technical errors and the patient's postoperative course. Obese patients frequently had unusual perioperative complications. CONCLUSION Perioperative complications occur commonly in patients with displaced acetabular fractures treated operatively using a Kocher-Langenbeck surgical exposure. Some of these complications may be avoidable, and are related to polytrauma. Most technical complications should be avoidable. Unusual complications were identified, especially in obese patients.
Dextrocardia, atrial septal defect, severe developmental delay, facial anomalies, and supernumerary ribs in a child with a complex unbalanced 8;22 translocation including partial 8p duplication

We report on a child with dextrocardia, atrial septal defect (ASD), severe developmental delay, hypotonia, 13 pairs of ribs, left preauricular choristoma, hirsutism, and craniofacial abnormalities. Prenatal cytogenetic evaluation showed karyotype 46,XY,? dup(8p)ish del(8)pter. Postnatal array CGH demonstrated a 6.8 Mb terminal deletion at 8p23.3–p23, an interstitial 31.1 Mb duplication within 8p23.1–p11, and a terminal duplication of 0.24 Mb at 22q13.33, refining the karyotype to 46,XY,der(8)dup(8)(p23.1p11.1)t(8;22)(p23.1;q13.1). ish der(8)dup(8)(p23.1p11.1)t(8;22)(p23.1;q13.1) (D8S504‐,MS607 + ,ARSA + ,D8Z1 + , RP115713 + +). Previous reports of distal 8p deletion, 8p duplication, and distal 22q duplication have shown similar manifestations, including congenital heart disease, intellectual impairment, and multiple minor anomalies. We correlate the patient's clinical findings with these particular areas of copy number. This case study supports the use of aCGH to identify subtle chromosomal rearrangement in infants with cardiac malformation as their most significant or only apparent birth defect. Additionally, it illustrates why aCGH is essential in the description of chromosome rearrangements, even those seemingly visible via routine karyotype. This method shows that there is often greater complexity submicroscopically, essential to an adequate understanding of a patient's genotype and phenotype. © 2012 Wiley Periodicals, Inc.
Assessment of Neuropsychological Function Through Use of the Cambridge Neuropsychological Testing Automated Battery: Performance in 4- to 12-Year-Old Children

In this article, children's performance on subtasks from the Cambridge Neuropsychological Testing Automated Battery (CANTAB) is described. Two samples were recruited, one of which included children who spoke English as a second language. Children in this group also completed subtests from the Wechsler Intelligence Scale for Children-Third Revision (WISC-III). Despite the fact that ESL children scored over 1 SD below the norm on the WISC-III Vocabulary subtest, there were no CANTAB performance distinctions between primary versus secondary English-language speakers. In addition, several aspects of CANTAB performance were significantly correlated with verbal and nonverbal IQ. When developmental trends were examined, findings indicated that several aspects of frontal lobe function (memory span, working memory, and planning skills) are not functionally mature by the age of 12 years. Implications for use of the CANTAB in clinical studies are discussed.
Some chemicals present in industrial and consumer products, food and drinking-water.

Reading is a hobby to open the knowledge windows. Besides, it can provide the inspiration and spirit to face this life. By this way, concomitant with the technology development, many companies serve the e-book or book in soft file. The system of this book of course will be much easier. No worry to forget bringing the some chemicals present in industrial and consumer products food and drinking water iarc monographs on the evaluation of the carcinogenic risks to humans book. You can open the device and get the book by on-line.
Changing Leadership Behaviours: a Journey towards a Data Driven Culture

Student retention is important to all Higher Education Institutions. This has driven considerable research and focus, much of which concluded that each institution must define those factors by which it can identify student retention risk. These factors include student attendance, engagement, participation, academic performance, socio-economic background, etc. Once these factors are identified the institution then works to put some sort of proactive intervention programme in place to prevent the student moving from a retention risk to a retention statistic. Much of the research supports the move towards data driven decision making for each institution: use data to identify the retention risk early, make some sort of intervention with the student with a view to mitigating the risk. Unsurprisingly, the research has predominantly focused on the behaviour of the student and providing data to institutional leaders who then drive interventions aimed at altering the at risk student’s behaviour. However, very little research has considered how this data is impacting on the leaders themselves. This move towards a data driven culture has a significant dependency on leaders making data driven decisions and thus their behaviour is also an important factor. This paper looks at the impact a move towards a data driven culture can have on leadership behaviour.
Simulation of the March 9, 1995, substorm: Auroral brightening and the onset of lobe reconnection

A global MHD simulation of an isolated substorm that occurred on March 9, 1995 is presented. The simulation, driven with solar wind data provided by the Wind satellite, reproduced to a surprising degree the evolution of substorm activity. The onset of the expansion phase was coincident with the penetration of an electric field spike into the near‐Earth region. This impulse launched a tailward propagating signal (rarefaction wave) that enhanced reconnection in the mid tail. Substorm intensification was correlated with the enhancement of the reconnection rate at the preexisting reconnection region located at 30 RE. The importance of the electric field spike in correlating ionospheric and magnetospheric aspects of the substorm is emphasized.
Update on Temporal Dynamics of Stomatal Behavior Temporal Dynamics of Stomatal Behavior : Modeling and Implications for Photosynthesis and Water Use 1 [ OPEN ]

School of Biological Sciences, University of Essex, Colchester CO4 3SQ, United Kingdom (S.R.M.V.-C., J.S.A.M., T.L.); Division of Crop and Plant Science, School of Biosciences, University of Nottingham, Nottingham LE12 5RD, United Kingdom (L.M.); Laboratory of Plant Physiology and Biophysics, University of Glasgow, Glasgow G12 8QQ, United Kingdom (M.R.B.); and Plant Sciences, University of Cambridge, Cambridge CB2 3EA, United Kingdom (H.G.)
Constraining Ribosomal RNA Conformational Space Favaretto

Despite the potential for many possible secondarystructure conformations, the native sequence of ribosomal RNA (rRNA) is able to find the correct and universally conserved core fold. This study reports a computational analysis investigating two mechanisms that appear to constrain rRNA secondarystructure conformational space: ribosomal proteins and rRNA sequence composition. The analysis was carried out by using rRNA–ribosomal protein interaction data for the Escherichia coli 16S rRNA and free energy minimization software for secondarystructure prediction. The results indicate that selection pressures on rRNA sequence composition and ribosomal protein–rRNA interaction play a key role in constraining the rRNA secondary structure to a single stable form.
Pattern co-occurrence matrix to reduce the low frequency problem and effective pattern discovery

Useful information from a text document can be extracted using text mining techniques. Many text mining methods are generally uses term or keyword based approach. They all have advantages, but get stuck into the issue of synonymy: two terms have the same meaning and polysemy: one term has many meanings. So phrase based approaches are suggested, but they are not performing better than term based approaches. Instead of term based methods pattern mining methods are suggested, but there is still an open research issue of utilizing and modifying these discovered patterns. Pattern mining methods suffer from pattern misinterpretation and low frequency problem. This paper presents an effective technique to extract patterns that applies the pattern taxonomy model to get close sequential patterns. Pattern deploying process is used to reduce the pattern misinterpretation problem. Pattern co-occurrence matrix (PCM) is applied get the important relationship between close sequential patterns and removes patterns with zero co-occurrence weight. PCM and Inner Pattern Evolution process gives the benefit of reducing low frequency problem. This increases effectiveness of extracting interesting and accurate to the topic information.
FPGA Implementation of a GLST-MIMO System

This paper presents an FPGA implementation of a GLST-MIMO detector for GLST-MIMO wireless communication systems. The proposed system provides a maximum of 600 Mbps using the 80 MHz baseband bandwidth of the 4times2 MIMO scheme. The GLST-MIMO detector adopts a detection algorithm to low-computational complexity, as low as O(MTx 2) = O(42) (MTx : number of transmit antennas) per symbol interval, by using the orthogonality of the channel matrix. The GLST-MIMO detector architecture meets the timing constraints of real-time processing.
On-target JAK2/STAT3 inhibition slows disease progression in orthotopic xenografts of human glioblastoma brain tumor stem cells.

BACKGROUND Glioblastoma multiforme (GBM) is characterized by an aggressive clinical course, therapeutic resistance, and striking molecular heterogeneity. GBM-derived brain tumor stem cells (BTSCs) closely model this molecular heterogeneity and likely have a key role in tumor recurrence and therapeutic resistance. Emerging evidence indicates that Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 is an important mediator of tumor cell survival, growth, and invasion in a large group of GBM. Here, we used a large set of molecularly heterogeneous BTSCs to evaluate the translational potential of JAK2/STAT3 therapeutics. METHODS BTSCs were cultured from GBM patients and MGMT promoter methylation, and the mutation statuses of EGFR, PTEN, and TP53 were determined. Endogenous JAK2/STAT3 activity was assessed in human GBM tissue, BTSCs, and orthotopic xenografts by immunohistochemistry and Western blotting. STAT3 short hairpin (sh)RNA, cucurbitacin-I, and WP1066 were used to inhibit JAK2/STAT3 activity in vitro and in vivo. RESULTS The JAK2/STAT3 pathway was demonstrated to be highly activated in human GBM, molecularly heterogeneous BTSCs derived from these tumors, and BTSC xenografts. STAT3 shRNA knockdown or cucurbitacin-I and WP1066 administration resulted in on-target JAK2/STAT3 inhibition and dramatically reduced BTSC survival regardless of endogenous MGMT promoter methylation or EGFR, PTEN, and TP53 mutational status. BTSC orthotopic xenografts maintained the high levels of activated JAK2/STAT3 seen in their parent human tumors. Intraperitoneal WP1066 reduced intratumoral JAK2/STAT3 activity and prolonged animal survival. CONCLUSION Our study demonstrates the in vitro and in vivo efficacy of on-target JAK2/STAT3 inhibition in heterogeneous BTSC lines that closely emulate the genomic and tumorigenic characteristics of human GBM.
HIV Mucosal Vaccine: Nasal Immunization with gp160-Encapsulated Hemagglutinating Virus of Japan-Liposome Induces Antigen-Specific CTLs and Neutralizing Antibody Responses1

Nasal immunization of normal mice with HIVgp160-encapsulated hemagglutinating virus of Japan (HVJ)-liposome induced high titers of gp160-specific neutralizing IgG in serum and IgA in nasal wash, saliva, fecal extract, and vaginal wash, along with both Th1- and Th2-type responses. HIVgp160-specific IgG- and IgA-producing cells were also detected in mononuclear cells isolated from spleen, nasal cavity, salivary gland, intestinal lamina propria, and vaginal tissue of nasally immunized mice. In addition, CD8+ CTLs were induced in mice nasally immunized with gp160-HVJ-liposome. These findings suggest that two layers of effective HIV-specific humoral and cellular immunity, in mucosal and systemic sites, were induced by this nasal vaccine. In immunodeficient mice, nasal immunization with gp160-HVJ-liposome induced Ag-specific immune responses for the systemic and mucosal compartments of both Th1 (IFN-γ−/−) and Th2 (IL-4−/−). In vitro Ag-specific serum IgG Ab and vaginal wash samples possessing IgA and IgG Abs that had been induced by nasal immunization with gp160-HVJ-liposome were able to neutralize a clinically isolated strain of HIV-MN strain isolated from Japanese hemophiliac patients. Taken together, these results suggest that, for the prevention and control of AIDS, nasally administered gp160-HVJ-liposome is a powerful immunization tool that induces necessary Ag-specific immune responses at different stages of HIV infection.