Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Drug Loading on the Antitumor Activity of a Monoclonal Antibody Drug Conjugate

Purpose: An antibody-drug conjugate consisting of monomethyl auristatin E (MMAE) conjugated to the anti-CD30 monoclonal antibody (mAb) cAC10, with eight drug moieties per mAb, was previously shown to have potent cytotoxic activity against CD30+ malignant cells. To determine the effect of drug loading on antibody-drug conjugate therapeutic potential, we assessed cAC10 antibody-drug conjugates containing different drug-mAb ratios in vitro and in vivo. Experimental Design: Coupling MMAE to the cysteines that comprise the interchain disulfides of cAC10 created an antibody-drug conjugate population, which was purified using hydrophobic interaction chromatography to yield antibody-drug conjugates with two, four, and eight drugs per antibody (E2, E4, and E8, respectively). Antibody-drug conjugate potency was tested in vitro against CD30+ lines followed by in vivo xenograft models. The maximum-tolerated dose and pharmacokinetic profiles of the antibody-drug conjugates were investigated in mice. Results: Although antibody-drug conjugate potency in vitro was directly dependent on drug loading (IC50 values E8<E4<E2), the in vivo antitumor activity of E4 was comparable with E8 at equal mAb doses, although the E4 contained half the amount of MMAE per mAb. E2 was also an active antitumor agent but required higher doses. The maximum-tolerated dose of E2 in mice was at least double that of E4, which in turn was twice that of E8. MMAE loading affected plasma clearance, as E8 cleared 3-fold faster than E4 and 5-fold faster than E2. Conclusions: By decreasing drug loading per antibody, the therapeutic index was increased demonstrating that drug loading is a key design parameter for antibody-drug conjugates.
Hotspots of diversity in a clonal world — the Mediterranean moss Pleurochaete squarrosa in Central Europe

Diversity patterns of the dioecious haploid Mediterranean moss Pleurochaete squarrosa were analysed from Central and Northwest Europe using nuclear and chloroplast DNA sequencing and enzyme electrophoresis. Across 69 populations, 38 distinct haploid multilocus genotypes (MLGs) were detected, but nearly all populations were clonal. Only five MLGs occurred in more than two regions, and two diversity hotspots were detected. The Kaiserstuhl mountains in Southwest Germany harboured 34 MLGs, 25 being endemic within Central Europe. Levels of linkage disequilibrium and population structure in Kaiserstuhl populations were similar to levels and structure in sexually reproducing populations in the Mediterranean Basin. In the Moselle‐Nahe area, some 250 km north, a comparably high allelic diversity, but no evidence of recombination, was detected. Genetic diversity measures were significantly lower than estimates obtained in the Mediterranean Basin and a GST of 0.89 signified extreme population differentiation. Mantel tests identified a positive correlation on genetic and geographical distance for distances up to 50 km. Seven nrITS and three cpDNA haplotypes were detected, their geographical structure mirroring enzyme data set results. Comparative analysis with Mediterranean data demonstrated multiple recolonization of Central Europe from both the Iberian Peninsula and the Balkans. A suture zone of genotypes was detected along the border of Belgium/France and Germany. Despite P. squarrosa having haploid spore and/or vegetative propagules dispersal, we found patterns of postglacial recolonization of Central Europe comparable with those reported in flowering plants and animals. This study demonstrates the importance of comparative research on population genetics and phylogeography of a diverse range of organisms.
Static and Dynamic Behavior of Liquid Nano-Meniscus Bridge

Static and dynamic behavior of liquid meniscus bridges has been investigated by a newly developed nanorheometer. The liquid nanomeniscus bridges are established between two borosilicale glass spheres of 20 μm in diameter and two kinds of experiment are performed: 1) The pull-off and attracting forces between two glass spheres wetted by OMCTS (Octamethylcyclotetrasiloxane) have been measured as a function of receding and approaching velocity respectively and the pull-off force has been compared with the theoretical value; 2) Normal oscillatory experiment between two glass spheres with meniscus bridge of PFPE (Perfluoropolyether) Zdol has been conducted. Results of the experiments are as follows: 1) The measured pull-off or attracting forces show almost constant values at very low receding and approaching velocities. Whereas, the measured forces deviate from the constant value at a higher velocity than 2.70 μm/s because the viscous force may begin to operate. 2) With such small substrates of 20 μm in diameter, new dynamic behavior originated from the elastic and damping effects of the liquid meniscus bridge emerges: The elastic components of the system are independent of the modulation frequency representing the characteristic of viscoelastic solid; The system is dominated by the viscous component at high frequency and the elastic component at low frequency. At high frequencies and small separations, the liquid behaves as a Newtonian fluid with a constant viscosity. On the other hand, at low frequencies and large separations, the dynamic viscosity of the system is enhanced. Presented as a Society of Tribologists and Lubrication Engineers Paper at the ASME/STLE Tribology Conference in Seattle, Washington, October 1–4, 2000
Correction: Wood Chemical Composition in Species of Cactaceae: The Relationship between Lignification and Stem Morphology

In Cactaceae, wood anatomy is related to stem morphology in terms of the conferred support. In species of cacti with dimorphic wood, a unique process occurs in which the cambium stops producing wide-band tracheids (WBTs) and produces fibers; this is associated with the aging of individuals and increases in size. Stem support and lignification have only been studied in fibrous tree-like species, and studies in species with WBTs or dimorphic wood are lacking. In this study, we approach this process with a chemical focus, emphasizing the role of wood lignification. We hypothesized that the degree of wood lignification in Cactaceae increases with height of the species and that its chemical composition varies with wood anatomy. To test this, we studied the chemical composition (cellulose, hemicellulose, and lignin content) in 13 species (2 WBTs wood, 3 dimorphic, and 8 fibrous) with contrasting growth forms. We also analyzed lignification in dimorphic and fibrous species to determine the chemical features of WBTs and fibers and their relationship with stem support. The lignin contents were characterized by Fourier transform infrared spectroscopy and high performance liquid chromatography. We found that 11 species have a higher percentage (>35%) of lignin in their wood than other angiosperms or gymnosperms. The lignin chemical composition in fibrous species is similar to that of other dicots, but it is markedly heterogeneous in non-fibrous species where WBTs are abundant. The lignification in WBTs is associated with the resistance to high water pressure within cells rather than the contribution to mechanical support. Dimorphic wood species are usually richer in syringyl lignin, and tree-like species with lignified rays have more guaiacyl lignin. The results suggest that wood anatomy and lignin distribution play an important role in the chemical composition of wood, and further research is needed at the cellular level. PLOS ONE | DOI:10.1371/journal.pone. 0123919 April 16, 2015 1 / 17 a11111
Brain dynamics associated with recollective experiences of emotional events

In this study, we used high-density event-related potentials to investigate the brain dynamics underlying the recollective experience for emotional and neutral pictures. Using the remember/know procedure, 12 male participants introspectively indicated whether their recognition was based on conscious recollection (remembered) or familiarity (known). The results show a higher rate of remember responses for emotional relative to neutral pictures, despite an equivalent memory accuracy. In the event-related potentials, the subjective recollective experience for emotional pictures relative to neutral pictures was accompanied by an enhanced old/new effect (500–800 ms) over parietal scalp locations. The results provide electrocortical evidence for a contribution of the parietal old/new effect to the enhanced vividness of individuals' emotional memories and indicate that emotions enhance the subjective belief of recognizing memories.
Man’s Underground Best Friend: Domestic Ferrets, Unlike the Wild Forms, Show Evidence of Dog-Like Social-Cognitive Skills

Recent research has shown that dogs’ possess surprisingly sophisticated human-like social communication skills compared to wolves or chimpanzees. The effects of domestication on the emergence of socio-cognitive skills, however, are still highly debated. One way to investigate this is to compare socialized individuals from closely related domestic and wild species. In the present study we tested domestic ferrets (Mustela furo) and compared their performance to a group of wild Mustela hybrids and to domestic dogs (Canis familiaris). We found that, in contrast to wild Mustela hybrids, both domestic ferrets and dogs tolerated eye-contact for a longer time when facing their owners versus the experimenter and they showed a preference in a two-way choice task towards their owners. Furthermore, domestic ferrets, unlike the wild hybrids, were able to follow human directional gestures (sustained touching; momentary pointing) and could reach the success rate of dogs. Our study provides the first evidence that domestic ferrets, in a certain sense, are more dog-like than their wild counterparts. These findings support the hypothesis that domestic species may share basic socio-cognitive skills that enable them to engage in effectively orchestrated social interactions with humans.
Evidence for an involvement of actin in the positioning and motility of centrosomes

Cultured human polymorphonuclear leukocytes exposed to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) spread on the substratum and undergo centrosome splitting. The two centrioles may separate by a distance of several micrometers, each being surrounded by an aster of microtubules. Here we show that the centriole/aster complexes are in constant, rapid motion through the cytoplasm, carrying with them some of the cytoplasmic granules while pushing aside others, or deforming and displacing the nucleus. An analysis of this unique motility phenomenon was undertaken. We show that intact microtubules are required for TPA-induced centrosome splitting and aster motility, but not for cell spreading. More importantly, disruption of the actin network inhibits both centrosome splitting and cell spreading, and even reverses splitting (induces convergence and fusion of asters) in polymorphonuclear leukocytes pretreated with TPA alone. These observations indicate the existence of a dynamic relationship between microtubules and actin networks and provide evidence for a role of actin in determining the position of the centrosome by way of interaction with the microtubules radiating from it.
Pharmacology of a Novel Central Nervous System–Penetrant P2X7 Antagonist JNJ-42253432

In the central nervous system, the ATP-gated Purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is expressed in glial cells and modulates neurophysiology via release of gliotransmitters, including the proinflammatory cytokine interleukin (IL)-1β. In this study, we characterized JNJ-42253432 [2-methyl-N-([1-(4-phenylpiperazin-1-yl)cyclohexyl]methyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide] as a centrally permeable (brain-to-plasma ratio of 1), high-affinity P2X7 antagonist with desirable pharmacokinetic and pharmacodynamic properties for in vivo testing in rodents. JNJ-42253432 is a high-affinity antagonist for the rat (pKi 9.1 ± 0.07) and human (pKi 7.9 ± 0.08) P2X7 channel. The compound blocked the ATP-induced current and Bz-ATP [2′(3′)-O-(4-benzoylbenzoyl)adenosine-5′-triphosphate tri(triethylammonium)]–induced release of IL-1β in a concentration-dependent manner. When dosed in rats, JNJ-42253432 occupied the brain P2X7 channel with an ED50 of 0.3 mg/kg, corresponding to a mean plasma concentration of 42 ng/ml. The compound blocked the release of IL-1β induced by Bz-ATP in freely moving rat brain. At higher doses/exposure, JNJ-42253432 also increased serotonin levels in the rat brain, which is due to antagonism of the serotonin transporter (SERT) resulting in an ED50 of 10 mg/kg for SERT occupancy. JNJ-42253432 reduced electroencephalography spectral power in the α-1 band in a dose-dependent manner; the compound also attenuated amphetamine-induced hyperactivity. JNJ-42253432 significantly increased both overall social interaction and social preference, an effect that was independent of stress induced by foot-shock. Surprisingly, there was no effect of the compound on either neuropathic pain or inflammatory pain behaviors. In summary, in this study, we characterize JNJ-42253432 as a novel brain-penetrant P2X7 antagonist with high affinity and selectivity for the P2X7 channel.
DifFocus: An approach for image segmentation

A new multi-focus analysis method for image segmentation, based on human visual system focal attention and focusing phenomena, is presented. The main goal is to develop a fast and accurate segmentation algorithm, suitable for real-time applications, such as robotics and autonomous vehicles. The difFocus shows to be fast enough and it achieved the 8th place in the Berkeley Segmentation Benchmark global ranking for both color and grayscale image segmentation. It also shows to be robust to parameter selection, achieving promising results.
Regulatory Phenotype, PD-1 and TLR3 Expression in T Cells and Monocytes from HCV Patients Undergoing Antiviral Therapy: A Randomized Clinical Trial

Background & Aims The cellular immunity has a profound impact on the status of hepatitis C virus (HCV) infection. However, the response of cellular immunity on the virological response in patients with antiviral treatment remains largely unclear. We aimed to clarify the response of peripheral T cells and monocytes in chronic hepatitis C patients with antiviral treatment. Methods Patients with chronic hepatitis C were treated either with interferon alpha-2b plus ribavirin (n = 37) or with pegylated interferon alpha-2a plus ribavirin (n = 33) for up to 24 weeks. Frequencies of peripheral regulatory T-cells (Tregs), programmed death-1 (PD-1) expressing CD4+ T-cells or CD8+ T-cells and toll-like receptor (TLR) 3 expressing CD14+ monocytes were evaluated by flow cytometry in patients at baseline, 12 and 24 weeks following treatment and in 20 healthy controls. Results Frequencies of Tregs, PD-1 and TLR3 expressing cells were higher in patients than those in control subjects (P<0.05). Patients with complete early virological response (cEVR) showed lower Tregs, PD-1 expressing CD4+ or CD8+ T-cells than those without cEVR at 12 weeks (P<0.05). Patients with low TLR3 expressing CD14+ monocytes at baseline had a high rate of cEVR (P<0.05). Conclusions Low peripheral TLR3 expressing CD14+ monocytes at baseline could serve as a predictor for cEVR of antiviral therapy in chronic HCV-infected patients. The cEVR rates were significantly increased in the patients with reduced circulating Tregs, PD-1 expressing CD4+ or CD8+ T-cells. Trial Registration Chinese Clinical Trial Registry ChiCTR10001090.
Visual guidance during competition performance and run‐through training in long jumping

To ensure precise foot placement on the take-off board, long jumpers visually regulate their stride pattern during their run-up. A relationship between how much visual guidance they use and the horizontal distance they jump has not, however, been quantified. Run-up precision is often practiced using run-throughs, which exclude the take-off and, therefore, the high physical stress of the complete long jump. The validity with which this common training method simulates the long jump approach remains, however, to be verified. Four state-standard long jumpers and two heptathletes completed two sessions, each comprising six runthroughs and six competition long jumps. A 50 Hz video camera was manually panned from an elevated platform to film each trial, to enable subsequent gait characteristic evaluations. Linear regression analyses identified that a longer visual regulation phase, measured in time, distance or number of strides, was a key predictor of long jump distance. The number of strides that were visually regulated during the long jump approach was, accordingly, positively correlated with long jump distance (r = 0.67, p = 0.001). The amount of visual regulation used during run-throughs was, however, less than half (p = 0.001) of that observed during long jump approaches. Our results should compel long jump coaches to supplement run-through training with additional visual guidance exercises, to encourage their athletes to visually regulate more of their long jump approach.
Political commitment and loss-aversion

At least since the work of Kydland and Prescott (1977), it is acknowledged that the ability for policy makers to commit to future policies often is of key importance for outomces and welfare. An example is capital income taxation, where the commitment solution typically involve zero capital income taxes after some initial periods, while no commitment may imply empirically much too high taxes. A more realistic intermediate outcome can be supported by trigger strategies where a deviation from a "good" equilibrium is punished by a possibly in…nite revertion to a "bad" Nash-equilibrium. In a political economy setting, < :
Specificity of SAF‐A and lamin B binding in vitro correlates with the satellite DNA bending state

There is evidence that Matrix Attachment Region (MAR)‐binding proteins also bind satellite DNA (satDNA). The aim of the current work was to determine whether the major nuclear matrix (NM) MAR‐binding proteins are able to recognize satDNAs of different locations and what DNA structural features are important for the recognition. In nuclei and NM, a number of the same polypeptides were recognized on a southwestern blot when MAR of immunoglobulin κ gene (Ig κ MAR) and pericentromeric (periCEN) satDNA fragments were used. However, the binding decreased dramatically when human and mouse CEN satDNA were used for the probes. After an NM extract was subjected to ion exchange chromatography, the main DNA‐binding proteins were identified as SAF‐A (scaffold attachment factor A) and lamin B. It was not possible to test the binding of lamin B by gel mobility shift assay (GMSA), but SAF‐A showed an ability to distinguish CEN and periCEN satDNA fragments in GMSA. While periCEN fragments have an abnormally slow mobility on electrophoresis, which is a hallmark of bent DNA, CEN satDNA fragments have a normal mobility. A computer analysis was done using the wedge model (Ulanovsky and Trifonov [ 1987 ] Nature 326:720–722), which describes how the curved state depends on particular nucleotide sequences. The curved states of the fragments predicted by the model are in good agreement with their ability to be recognized by NM proteins. Thus SAF‐A and lamin B are able to recognize conserved structural features of satDNA in the same way that MAR‐binding proteins recognize MARs in spite of a lack of a consensus sequence. CEN and periCEN satDNAs are distinguished by proteins in correlation with the helical curvature of these fragments. J. Cell. Biochem. 83: 218–229, 2001. © 2001 Wiley‐Liss, Inc.
Development of Arabic version of Berlin questionnaire to identify obstructive sleep apnea at risk patients

BACKGROUND: Obstructive sleep apnea (OSA) is a common, under-recognized, under diagnosed, under treated, and serious medical condition in adults. Polysomnography (PSG) is the gold standard for diagnosis of OSA; however, prohibitive cost of the test and rarity of sleep laboratory in the Arabic nations limit its access. So, searching for another simple, economical, reliable, and valid tool for identification of OSA at risk patients is of special public concern. OBJECTIVE: This study was conducted to evaluate the reliability and validity of Arabic version of Berlin questionnaire (ABQ) in detection of OSA at risk patients. METHODS: After hospital ethics approval and formal patients consent, 100 patients were subjected to full night PSG study after their response to the developed ABQ. The patients were classified into both low (30) and high risk (70) for OSA using ABQ and validated against apnea hypopnea index (AHI). Reliability was assessed by internal consistency using Cronbach's alpha test and consistency over time using test retest correlation. RESULTS: The study demonstrated a high degree of internal consistency and stability over time for the developed ABQ. The Cronbach's alpha coefficient for the 10-item tool was 0.92. Validation of ABQ against AHI at cutoff >5 revealed a sensitivity of 97%, specificity of 90%, positive and negative predictive values of 96% and 93%, respectively. CONCLUSION: The ABQ is reliable and valid scale in screening patients for the risk of OSA among Arabic-speaking nations, especially in resource-limited settings.
Modeling and Analysis of Wireless Sensor Networks With/Without Energy Harvesting Using Ginibre Point Processes

In this paper, we analyze the performance of wireless sensor networks using stochastic geometry. In practical networks, since nodes in the networks are not independently placed, there exists a correlation among the locations of the nodes. In order to capture the effect of the correlation, we model the spatial distribution of the nodes as $\alpha $ -Ginibre point processes (GPPs), which reflect the repulsion. It is assumed that each sensor node is associated with the closest gateway and employs a fractional channel inversion power control, which adjusts transmit power based on the contact distance. We first identify the characteristics of the contact distance and transmit power, and then investigate the outage performance of the networks using the derived characteristics. We also examine energy harvesting networks where each sensor harvests energy from radio frequency signals radiated by energy sources and transmits data to its serving gateway when the harvested energy is enough to conduct the fractional channel inversion power control. Since the $\alpha $ -GPP contains the Poisson point process (PPP) as a particular case, our analysis can be interpreted as a generalization of previous works on the networks modeled by PPPs. The accuracy of our analysis is validated through simulation results.