Miracle-dz/UniFAR-FTUs huggingface dataset:
ABC Transporters during Epilepsy and Mechanisms Underlying Multidrug Resistance in Refractory Epilepsy

Summary: It is estimated 20–25% of the epileptic patients fails to achieve good control with the different antiepileptic drugs (AEDs) treatments, developing refractory epilepsy (RE). Discovered first in cancer, the activity of P‐glycoprotein (P‐gp) and others ABC transporters as multidrug‐resistance‐associated proteins (MRPs) and breast cancer resistant protein (BCRP) are directly related with the refractoriness. We have observed the overexpression of these all transporters in the brain of patients with RE, and according with other authors, all these data suggests an active drug efflux from brain. Both constitutive and seizure induced brain P‐gp overexpression was also suggested. As confirmation of these clinical evidences, different models of experimental epilepsy have demonstrated P‐gp overexpression on blood brain barrier (BBB) and brain parenchyma cells, as astrocytes and neurons. In our model, early P‐pg detection in vessel‐related cells and later additional P‐gp detection in neurons, correlated with the gradual loss of protective effect of phenytoin. The progressive neuronal P‐gp expression, depending on intensity and time‐constancy of seizure‐injury, was in agreement with the development of “P‐gp‐positive seizure‐axis” proposed by Kwan & Brodie, who also showed that the development of RE directly correlated with the number and frequency of seizures before initiation of drug therapy. P‐gp expression in excretory organs suggests that P‐gp have a central role in drug elimination. Persistent low levels of AEDs in plasma and P‐gp brain overexpression in several RE pediatric patients were reported. We also observed in adult RE patients, an increased liver clearance of 99mTc‐hexakis‐2‐methoxyisobutylisonitrile (99mTc‐MIBI) (a P‐gp substrate), and the surgically treated cases showed P‐gp brain overexpression. These results suggest the systemic hyperactivity of P‐gp in RE patients, including brain P‐gp over‐expression should be suspected when persistent subtherapeutic levels of AEDs in plasma are detected. P‐gp neuronal expression described in both clinical and experimental reports indicates that additional mechanisms could be operative from seizure‐affected P‐gp‐positive neurons, due to AEDs targets are expressed at membrane level. An alternative mechanism was demonstrated in P‐gp‐expressed cells that exhibit lower membrane potential (Δψ0=−10 to –20) compared to normal physiological Δψ0 of –60 mV. Under this situation and irrespective to the P‐gp pharmacoresistant property or type of drug treatment selected, P‐gp‐expressed neurons could increase their sensitivity to new seizures perhaps as an epileptogenic mechanism. The understanding of properties of these ABC transporters can offer new tools for better selection of more effective preventive or therapeutic strategies and avoid the invasive surgical treatments for RE.
New composite right/left-handed transmission line using substrate integrated waveguide and metal-patches

A new Composite Right/Left-Handed Transmission Line (CRLH-TL) for millimeter wave frequency is proposed and investigated theoretically and experimentally. It consists of a Substrate Integrated Waveguide (SIW) with slit apertures and a dielectric film with metal patches. A prototype of SIW Metal-patch type CRLH-TL that satisfies the balance condition is designed. Dispersion diagram and S-parameters are derived numerically, and typical field distributions of RH and LH transmission and the zero-order resonance are shown. The experimental results of the proposed SIW Metal-patch type CRLH-TL agree the analytical results well. Because both the layers of the SIW and the metal-patched dielectric film compose simple planar periodic structure, the SIW Metal-patch type CRLH-TL has advantage of simple manufacturing. It is expected to be one of the basic structure of CRLH-TL or components such as leaky wave antenna and LH coupler above 10 GHz or millimeter wave frequency.
The effect of recombinant bovine somatotrophin on ovarian follicular growth and development in heifers.

The effects of recombinant bovine somatotrophin (BST) on the dynamics of ovarian follicular growth and development and peripheral insulin concentrations were investigated. Initially, studies were carried out in a population of Hereford x Friesian heifers to validate the ultrasound technique. In the first experiment, 12 heifers were injected daily with either 25 mg BST or vehicle for two oestrous cycles, and the effects on follicular dynamics and peripheral insulin were determined. In a second experiment, 12 heifers were given a single injection of 10 ml saline or 320 mg BST in a sustained-release formulation to examine the temporal relationships between growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin and the number of follicles. The validation studies demonstrated that small follicles (< 5 mm in diameter) could be clearly detected by real-time ultrasound, and that 75% (9 of 12) of heifers showed three waves of dominant follicle development during the oestrous cycle, whereas the remainder had only two waves. The changes in the numbers of follicles of the three size categories (< 5 mm, small; 5-10 mm, medium-sized and > 10 mm, large) also displayed a wave pattern similar to that of the dominant follicle, with a marked reduction in the number of subordinate follicles as the dominant follicle grew and reached its maximum size. In Expt 1, BST treatment increased the number of small follicles and caused a rise in peripheral insulin concentrations (P < 0.01) throughout the treatment period. (ABSTRACT TRUNCATED AT 250 WORDS)
Mutation Analysis of the 5′ Untranslated Region of the Cold Shock cspA mRNA of Escherichia coli

ABSTRACT The mRNA for CspA, a major cold shock protein in Escherichia coli, contains an unusually long (159 bases) 5′ untranslated region (5′-UTR), and its stability has been shown to play a major role in cold shock induction of CspA. The 5′-UTR of the cspAmRNA has a negative effect on its expression at 37°C but has a positive effect upon cold shock. In this report, a series ofcspA-lacZ fusions having a 26- to 32-base deletion in the 5′-UTR were constructed to examine the roles of specific regions within the 5′-UTR in cspA expression. It was found that none of the deletion mutations had significant effects on the stability of mRNA at both 37 and 15°C. However, two mutations (Δ56-86 and Δ86-117) caused a substantial increase of β-galactosidase activity at 37°C, indicating that the deleted regions contain a negativecis element(s) for translation. A mutation (Δ2-27) deleting the highly conserved cold box sequence had little effect on cold shock induction of β-galactosidase. Interestingly, three mutations (Δ28-55, Δ86-117, and Δ118-143) caused poor cold shock induction of β-galactosidase. In particular, the Δ118-143 mutation reduced the translation efficiency of the cspA mRNA to less than 10% of that of the wild-type construct. The deleted region contains a 13-base sequence named upstream box (bases 123 to 135), which is highly conserved in cspA, cspB,cspG, and cspI, and is located 11 bases upstream of the Shine-Dalgarno (SD) sequence. The upstream box might be another cis element involved in translation efficiency of the cspA mRNA in addition to the SD sequence and the downstream box sequence. The relationship between the mRNA secondary structure and translation efficiency is discussed.
Complexity Theory

Several years ago a prominent Australian politician, responsible for a new program to 'Network the Nation' used this diagram to try to explain what he envisaged. Popularly referred to as 'The Noodle Nation', the diagram was ridiculed for its apparent complexity. It seems that there are better ways to deal with complex issues!
Factor structure of the Alcohol Use Disorders Identification Test (AUDIT) for men and women in different age groups.

OBJECTIVE Our main aim was to investigate the factor structure of the Alcohol Use Disorders Identification Test (AUDIT) in a Finnish population sample. METHOD The AUDIT was completed by 3,125 men (mean age = 26.2 years) and 6,006 women (mean age = 26.1 years). RESULTS At a cutoff score of 8 or more, 49.8% of the men and 23.9% of the women would be identified as potentially engaged in excessive alcohol use. Exploratory factor analyses suggested a two-factor solution for both men and women. However, the factor structure was not invariant between men and women or in the different age groups among men. CONCLUSIONS This is one of the largest known general population studies on alcohol use in recent years in Finland. The findings support a two-factor solution, and it is suggested that the AUDIT cutoff scores should be tailored according to age, gender, and drinking culture.
Adaptive Virtual RSU Scheduling for Scalable Coverage under Bidirectional Vehicle Traffic Flow

Over the past decades, vehicular ad hoc networks (VANETs) have been a core networking technology to provide drivers and passengers with safety and convenience. As a new emerging technology, the vehicular cloud computing (VCC) can provide cloud services for various data-intensive applications in VANETs, such as multimedia streaming. However, the vehicle mobility and intermittent connectivity present challenges to the large-scale data dissemination with underlying computing and networking architecture. In this paper, we will explore the service scheduling of virtual RSUs for diverse request demands in the dynamic traffic flow in vehicular cloud environment. Specifically, we formulate the RSU allocation problem as maximum service capacity with multiple-source and multiple-destination, and propose a bidirectional RSU allocation strategy. In addition, we formulate the content replication in distributed RSUs as the minimum replication set coverage problem in a two-layer mapping model, and analyze the solutions in different scenarios. Numerical results further prove the superiority of our proposed solution, as well as the scalability to various traffic condition variations.
Disseminated tetracycline resistance in oral streptococci: implication of a conjugative transposon

A DNA sequence specifying tetracycline resistance (Tcr) has been previously cloned from a clinical isolate of Streptococcus mutans designated U202 (J. A. Tobian and F. L. Macrina, J. Bacteriol. 152:215-222, 1982). We used this sequence as a molecular probe in studying the dissemination of Tcr among oral streptococcal species isolated from patients treated with tetracycline. Eleven strains (including S. sanguis I, S. sanguis II, S. mitis, and S. salivarius) from seven patients were examined by Southern blot analysis. Seven strains showed strong hybridization to the Tcr probe, two showed weak hybridization, and two did not display detectable hybridization. Based on previous characterization of the cloned sequence, our data suggest the dissemination of the tetM class of resistance determinants among these oral streptococci. One of the clinical S. sanguis I isolates studied was able to transfer its Tcr phenotype to other oral streptococci and to enteric streptococci in the absence of plasmid DNA. This transfer appeared to be conjugation-like on the basis of its insensitivity to DNase and its dependence on intimate cell-to-cell contact. Using the cloned Tcr sequence, we were able to study the progeny of the matings. Our data suggest that this resistance transfer element occupies a chromosomal location in streptococcal cells and that it strongly resembles the conjugative transposon Tn916 in its behavior.
Interspecific Comparisons and the Potential Importance of Nutrient Excretion by Benthic Fishes in a Large Reservoir

Abstract Fishes can provide an important link between benthic and pelagic habitats by removing nutrients from sediments and excreting them into the water column. The relative importance of nutrients excreted by fishes to ecosystem productivity may vary among species and with abiotic conditions. I measured excretion rates of three benthic feeding fishes, gizzard shad Dorosoma cepedianum, smallmouth buffalo Ictiobus bubalus, and river carpsucker Carpiodes carpio, to examine the potential contribution of these species to the nutrient budget of a large southern reservoir. All species showed a significant relationship between log excretion rate and log body mass but no differences among species in the slopes or intercepts. For all species combined, the slope of the relationship was less than 1, suggesting a less than proportional increase in excretion rate with size. Using mean standing crop estimates from published cove rotenone surveys in Oklahoma, the nutrient loading to Lake Texoma by these fishes was esti.
Activity of nitric oxide synthase in mature and immature human spermatozoa

Nitric oxide (NO) is known to be involved in multiple signal transduction pathways of male germ cells, including sperm capacitation. In somatic cells, NO production was found to be part of apoptosis signalling. The aim of our study was to further clarify the role of NO in spermatozoa by investigation of NO synthase activity with regard to sperm maturity and sperm apoptosis signalling. Semen specimens from 19 healthy donors were subjected to density gradient centrifugation to separate the predominantly mature and immature sperm fraction. NO synthase activity was evaluated using diaminofluoresceine‐2‐diacetate by FACS. Apoptosis signalling was monitored by flowcytometric analyses of caspase‐3 (CP3) and integrity of the transmembrane mitochondrial potential (TMP). TUNEL assay was used to detect DNA fragmentations. Maturity of human spermatozoa was associated with increased NO synthase activity and inactivated apoptosis signalling (lower levels of disrupted TMP, active CP3 and DNA fragmentations, P < 0.05). Activation of apoptosis signalling was significantly negatively correlated to NO production, indicating a rather anti‐apoptotic effect of NO. This might underline the recently proposed role of NO in physiological sperm signal transduction, e.g. during capacitation.
Total Synthesis of Hybocarpone, a Cytotoxic Naphthazarin Derivative from the Lichen Lecanora hybocarpa, and Related Compounds

The concise synthesis of the lichen-derived antitumor agent hybocarpone (1) and its analogs is described. A new synthetic approach is based on the direct oxidative dimerization of the available naphthazarin precursors in the formation of the binaphtho[2,3-b; 2,3-d]furantetraone structure. It was shown that the first step to tetrahydrofuran features is the bridging hindered S*,S* and R*,S* carbon-carbon bonds of the molecules, setting the relative configurations of the 5aS*,6aS*,12aS*,12bS* and 5aS*,6aR*,12aR*,12bS* diastereomers.
A computationally light scheme for enhanced privacy in LTE

In the authentication and key agreement protocol adopted in LTE, pseudonyms are employed for identity presentation, so that the real identity of the subscriber remains confidential. However, there are occasions where pseudonyms may fail to serve its purpose. In such a situation, there is a backup provision that allows the network to request the subscriber for its real identity. But, here lies the problem; when the real identity is transmitted by the subscriber, his/her privacy gets compromised, as s/he may get tracked/profiled through the real identity. In this paper, a computationally light scheme to replace the backup provision for identity presentation is proposed, where the need to transmit the real identity is eliminated. Unlike other proposals, in this scheme a divergent strategy is adopted at the network; instead of using the real identity to locate the secret key of the subscriber, it is exactly the other way round.
The Use of Recombinant Activated FVII in Postpartum Hemorrhage

Severe bleeding remains a leading cause of morbidity and mortality in obstetrics. The first-line standard treatment of massive postpartum hemorrhage (PPH) includes medical measures directed at improving uterine tone, replacement of lost intravascular volume, blood and coagulation factors, and surgical or invasive procedures. Recently, a number of case reports or case series have reported the successful “off-label” use of recombinant activated factor VII (rFVIIa) in PPH unresponsive to conventional treatments. In this review, a critical analysis of the published literature on the use of rFVIIa in severe PPH was performed. Overall, a total of 272 PPH women were collected among the largest case series and/or international registries. No randomized controlled trials have been conducted in this area. Currently, the literature data suggest that, at a median dose of 81.5 μg/kg, rFVIIa is effective in stopping or reducing bleeding in 85% of the cases. Finally, on the basis of the evidence from the literature and on own experience, we included some recommendations and an algorithm on the therapeutic role of rFVIIa in the management of PPH.
What would drivers like to know during automated driving? Information needs at different levels of automation.

Automated driving changes the role of the driver from an active operator towards a supervisor during partially automated driving and passenger in the highly automated driving mode. To foster successful interaction between humans and automated systems, feedback on automation stages and behaviors is considered a key factor. The present study used a two-step procedure to investigate drivers’ information needs during partially and highly automated driving in comparison to manual driving for highway scenarios. The first step consisted in an expert focus group on expected information needs. Results showed that independent from specific scenarios, information should provide transparency, comprehensibility, and predictability of system actions. This includes the current system status, the remaining time to a change in the level of automation, the fallback level as well as reasons and a preview for ongoing and subsequent maneuvers. In the second step, results from the expert focus group were used to set up a driving simulator study. A sample of 20 participants performed three highway trips on the same route either in the manual, partially automated (hands-on, permanent monitoring, no secondary task) as well as highly automated condition (cloze test on a laptop as secondary task). Questionnaires and interviews about information needs were applied after each trip and glance behavior was analyzed. Information needs showed great variance between the drivers, which can mainly be explained by trust in automation. Partially automated driving was considered more exhausting than the other conditions due to the continuous supervision task. Information needs for the automated conditions were primarily related to the supervision of the system, whereas requested information during manual driving was centered on performing the current driving task. Glance data supported these patterns: during partially automated driving, drivers showed most and longer control glances at the mirrors and instrument cluster. Secondary task engagement during highly automated driving varied in dependence of trust in automation and the perceived complexity of the situation. However, less salient objects in a situation, such as traffic signs, were not perceived and no control glances were performed. It can be concluded that information needs change for partially and highly automated driving. Requested information is primarily focused on the status, transparency and comprehensibility of system action in contrast to driving-task related information during manual driving. These changes need to be considered in the human-machine-interface (HMI) design for automated driving. Corresponding author: Matthias Beggiato, TU Chemnitz, Cognitive and Engineering Psychology, Wilhelm-Raabe-Straße 43, 09120 Chemnitz, Germany. phone: +49(0)371-531-38654; fax: +49(0)371-531-838654; e-mail: matthias.beggiato@psychologie.tu-chemnitz.de. Acknowledgements: We would like to thank André Dettmann for the technical support of the driving simulator study.
Carcinoma-Associated Mesenchymal Stem Cells Promote Chemoresistance in Ovarian Cancer Stem Cells via PDGF Signaling

Within the ovarian cancer tumor microenvironment, cancer stem-like cells (CSC) interact with carcinoma associated mesenchymal stem/stromal cells (CA-MSC) through multiple secreted cytokines and growth factors. These paracrine interactions have been revealed to cause enrichment of CSC and their chemoprotection; however, it is still not known if platelet-derived growth factor (PDGF) signaling is involved in facilitating these responses. In order to probe this undiscovered bidirectional communication, we created a model of ovarian malignant ascites in the three-dimensional (3D) hanging drop heterospheroid array, with CSC and CA-MSC. We hypothesized that PDGF secretion by CA-MSC increases self-renewal, migration, epithelial to mesenchymal transition (EMT) and chemoresistance in ovarian CSC. Our results indicate that PDGF signaling in the CSC-MSC heterospheroids significantly increased stemness, metastatic potential and chemoresistance of CSC. Knockdown of PDGFB in MSC resulted in abrogation of these phenotypes in the heterospheroids. Our studies also reveal a cross-talk between PDGF and Hedgehog signaling in ovarian cancer. Overall, our data suggest that when the stromal signaling via PDGF to ovarian CSC is blocked in addition to chemotherapy pressure, the tumor cells are significantly more sensitive to chemotherapy. Our results emphasize the importance of disrupting the signals from the microenvironment to the tumor cells, in order to improve response rates. These findings may lead to the development of combination therapies targeting stromal signaling (such as PDGF and Hedgehog) that can abrogate the tumorigenic, metastatic and platinum resistant phenotypes of ovarian CSC through additional investigations.
Protein Tyrosine Phosphorylation in Human Platelets during Shear Stress-Induced Platelet Aggregation (SIPA) Is Regulated by Glycoprotein (GP) Ib/IX as well as GP IIb/IIIa and Requires Intact Cytoskeleton and Endogenous ADP

Summary Shear stress-induced platelet aggregation (SIPA) may be essential in thrombus formation in pathologically stenotic arteries. Intracellular events during SIPA are, however, poorly understood. Washed platelets were exposed to shear stress (108 dyne/cm2) in the presence of von Willebrand factor (vWf, 10 μg/ml) and 1 mM CaCl2 for various time intervals, and then lyzed in SDS. Platelet proteins were separated by 10% SDS-PAGE and tyrosine phosphorylated proteins were detected by immunoblotting with an anti-phosphotyrosine monoclonal antibody. Increased tyrosine phosphorylation of proteins of 130, 100, 85, 74, 70, 64, 58, and 40 kDa was observed within 30 s after the beginning of exposure of platelets to high shear force and the degree of tyrosine phosphorylation continued to increase up to approximately 2 min after the exposure. A monoclonal antibody (MoAb) against vWf-binding domain of glycoprotein (GP) Ibα (GUR83-35), anti-vWf MoAb that inhibits binding of vWf to GPIbα (NMC-4), or a MoAb against GP IIb/IIIa complex (AP-2) inhibited SIPA as well as tyrosine phosphorylation of these proteins. Apyrase (an ADP scavenger, 2 U/ml), EDTA (5 mM), or RGDS peptide (200 μg/ml) also had inhibitory effects on both SIPA and tyrosine phosphorylation. However, Cytochalasin D (2 μM) or staurosporin (1 μM) did not affect SIPA, while they inhibited SIPA-associated tyrosine phosphorylation of those proteins. SIPA-associated tyrosine phosphorylation is a novel post-aggregatory pathway in signal transduction, which is dependent on the binding of vWf to GP Ib/IX and GP IIb/IIIa, endogenous ADP, and intact cytoskeleton.