Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of CSF-1R Supports T-Cell Mediated Melanoma Therapy

Tumor associated macrophages (TAM) can promote angiogenesis, invasiveness and immunosuppression. The cytokine CSF-1 (or M-CSF) is an important factor of TAM recruitment and differentiation and several pharmacological agents targeting the CSF-1 receptor (CSF-1R) have been developed to regulate TAM in solid cancers. We show that the kinase inhibitor PLX3397 strongly dampened the systemic and local accumulation of macrophages driven by B16F10 melanomas, without affecting Gr-1+ myeloid derived suppressor cells. Removal of intratumoral macrophages was remarkably efficient and a modest, but statistically significant, delay in melanoma outgrowth was observed. Importantly, CSF-1R inhibition strongly enhanced tumor control by immunotherapy using tumor-specific CD8 T cells. Elevated IFNγ production by T cells was observed in mice treated with the combination of PLX3397 and immunotherapy. These results support the combined use of CSF-1R inhibition with CD8 T cell immunotherapy, especially for macrophage-stimulating tumors.
ANALYSIS OF SPDES ARISING IN PATH SAMPLING PART II: THE NONLINEAR CASE

In many applications, it is important to be able to sample paths of SDEs conditional on observations of various kinds. This paper studies SPDEs which solve such sampling problems. The SPDE may be viewed as an infinite-dimensional analogue of the Langevin equation used in finite-dimensional sampling. In this paper, conditioned nonlinear SDEs, leading to nonlinear SPDEs for the sampling, are studied. In addition, a class of preconditioned SPDEs is studied, found by applying a Green’s operator to the SPDE in such a way that the invariant measure remains unchanged; such infinite dimensional evolution equations are important for the development of practical algorithms for sampling infinite dimensional problems. The resulting SPDEs provide several significant challenges in the theory of SPDEs. The two primary ones are the presence of nonlinear boundary conditions, involving first order derivatives, and a loss of the smoothing property in the case of the pre-conditioned SPDEs. These challenges are overcome and a theory of existence, uniqueness and ergodicity is developed in sufficient generality to subsume the sampling problems of interest to us. The Gaussian theory developed in Part I of this paper considers Gaussian SDEs, leading to linear Gaussian SPDEs for sampling. This Gaussian theory is used as the basis for deriving nonlinear SPDEs which affect the desired sampling in the nonlinear case, via a change of measure.
Recruitment of apical dendritic T‐type Ca2+ channels by backpropagating spikes underlies de novo intrinsic bursting in hippocampal epileptogenesis

A single episode of status epilepticus (SE) induced in rodents by the convulsant pilocarpine, produces, after a latent period of ≥ 2 weeks, a chronic epileptic condition. During the latent period of epileptogenesis, most CA1 pyramidal cells that normally fire in a regular pattern, acquire low‐threshold bursting behaviour, generating high‐frequency clusters of 3–5 spikes as their minimal response to depolarizing stimuli. Recruitment of a Ni2+‐ and amiloride‐sensitive T‐type Ca2+ current (ICaT), shown to be up‐regulated after SE, plays a critical role in burst generation in most cases. Several lines of evidence suggest that ICaT driving bursting is located in the apical dendrites. Thus, bursting was suppressed by focally applying Ni2+ to the apical dendrites, but not to the soma. It was also suppressed by applying either tetrodotoxin or the KV7/M‐type K+ channel agonist retigabine to the apical dendrites. Severing the distal apical dendrites ∼150 μm from the pyramidal layer also abolished this activity. Intradendritic recordings indicated that evoked bursts are associated with local Ni2+‐sensitive slow spikes. Blocking persistent Na+ current did not modify bursting in most cases. We conclude that SE‐induced increase in ICaT density in the apical dendrites facilitates their depolarization by the backpropagating somatic spike. The ICaT‐driven dendritic depolarization, in turn, spreads towards the soma, initiating another backpropagating spike, and so forth, thereby creating a spike burst. The early appearance and predominance of ICaT‐driven low‐threshold bursting in CA1 pyramidal cells that experienced SE most probably contribute to the emergence of abnormal network discharges and may also play a role in the circuitry reorganization associated with epileptogenesis.
An Aspect-Oriented Programming Model for Bag-of-Tasks Grid Applications

This paper presents a novel programming model for explicitly separating parallelization and middleware-specific concerns in bag-of-tasks (BoT) grid applications. The model uses Java threads for application decomposition, and aspect-oriented programming to dynamically (and transparently) convert the application's thread objects into independent grid tasks, using the services of a specific grid middleware API. This paper also describes early experimental results showing the model's modularity gains and performance overhead, when applied to implement BoT grid applications using OurGrid.
Planar Bulk MOSFETs Versus FinFETs: An Analog/RF Perspective

Comparison of digital and analog figures-of-merit of FinFETs and planar bulk MOSFETs reveals an interesting tradeoff in the analog/RF design space. It is found that FinFETs possess the following key advantages over bulk MOSFETs: reduced leakage, excellent subthreshold slope, and better voltage gain without degradation of noise or linearity. This makes them attractive for digital and low-frequency RF applications around 5 GHz, where the performance-power tradeoff is important. On the other hand, in high-frequency applications, planar bulk MOSFETs are seen to hold the advantage over FinFETs due to their higher peak transconductance. However, this comes at a cost of a reduced voltage gain of bulk MOSFETs
High-Intensity Training and Salivary Immunoglobulin A Responses in Professional Top-Level Soccer Players: Effect of Training Intensity

Abstract Owen, AL, Wong, DP, Dunlop, G, Groussard, C, Kebsi, W, Dellal, A, Morgans, R, and Zouhal, H. High-intensity training and salivary immunoglobulin A responses in professional top-level soccer players: Effect of training intensity. J Strength Cond Res 30(9): 2460–2469, 2016—This study aimed (a) to test the hypothesis that salivary immunoglobulin A (s-IgA) would vary with training intensity sessions (low-intensity [LI] vs. high-intensity sessions [HI]) during a traditional training program divided into 4 training periods and (b) to identify key variables (e.g., GPS data, rating of perceived exertion [RPE], and training duration), which could affect s-IgA. Saliva samples of 10 elite professional soccer players were collected (a) before the investigation started to establish the baseline level and (b) before and after each 4 training sessions (LI vs. HI). Training intensity was monitored as internal (through heart rate responses and RPE) and external (through GPS) loads. High-intensity sessions were associated with higher external load (GPS) and with higher RPE. Baseline and pretraining s-IgA did not differ between the 4 training sessions both for HI and LI. Post-training s-IgA were not different (in absolute value and in percentage of change) between HI and LI sessions at the first 3 periods. However, at the fourth period, s-IgA concentration for HI session was significantly lower (p ⩽ 0.05) than the LI session. The percentage change between s-IgA post-training and s-IgA baseline concentrations differ significantly (p ⩽ 0.05) between HI and LI training sessions. Significant correlations between s-IgA and training intensity were also noted. High-intensity soccer training sessions might cause a significant decrease in s-IgA values during the postexercise window as compared with LI sessions. This study encourages coaches to monitor s-IgA in routine, particularly during HI training periods, to take precautions to avoid upper respiratory tract infection in highly trained soccer players.
Distinctive sequence patterns in metazoan and yeast nucleosomes: Implications for linker histone binding to AT-rich and methylated DNA

Linker histones (LHs) bind to the DNA entry/exit points of nucleosomes and demonstrate preference for AT-rich DNA, although the recognized sequence patterns remain unknown. These patterns are expected to be more pronounced in metazoan nucleosomes with abundant LHs, compared to yeast nucleosomes with few LHs. To test this hypothesis, we compared the nucleosome core particle (NCP) sequences from chicken, Drosophila and yeast, extending them by the flanking sequences extracted from the genomes. We found that the known ∼10-bp periodic oscillation of AT-rich elements goes beyond the ends of yeast nucleosomes, but is distorted in metazoan sequences where the ‘out-of-phase’ AT-peaks appear at the NCP ends. The observed difference is likely to be associated with sequence-specific LH binding. We therefore propose a new structural model for LH binding to metazoan nucleosomes, postulating that the highly conserved nonpolar ‘wing’ region of the LH globular domain (tetrapeptide GVGA) recognizes AT-rich fragments through hydrophobic interactions with the thymine methyl groups. These interactions lead to DNA bending at the NCP ends and formation of a ‘stem-like’ structure. The same mechanism accounts for the high affinity of LH to methylated DNA—a feature critical for stabilization of the higher-order structure of chromatin and for repression of transcription.
Intersubjectivity before language Three windows on preverbal sharing

There has been a revolution in our understanding of intersubjectivity. This revolution has many roots. Three findings of special interest are represented in the present volume: (a) the landmark work on preverbal intersubjectivity by Trevarthen (b) the findings of neonatal imitation, which demonstrates a social connected-ness that is literally present at birth (e. three suggest a close coupling between self and other with profound implications for shared emotions (e. The revolution did not occur at the dead of night, but was well discussed. For example, there has been (a) a discussion of the relevance of the new findings for clinical psychology in a special issue of the Psychoanalytic Dialogues (Beebe, Sorter, Rustin, & Knoblauch 2003), (b) a special issue of the Philosophical Transactions of the Royal Society: Biological Sciences concerning social neuroscience (Frith & Wolpert 2003), and (c) several edited books in the past 5 years examining the implications of infant intersubjectivity for topics ranging from artificial intelli-The intellectual ferment derives in large measure from the fact that, within our lifetimes, we have witnessed the overturning of one of the most pervasive myths in social science – the myth of the asocial infant. On classical views of human development , the newborn is cut off from others. Freud and his followers proposed a distinction between a physical and psychological birth. When the baby is born there is a physical birth but not yet an interpersonal birth (Freud 1911; Mahler, Pine, & Bergman 1975). The baby is like an unhatched chick, incapable of interacting as a social being because a 'barrier' leaves the newborn cut off from external reality. Freud struggles to find a metaphor for the newborn-parent relationship and ended up likening the child's situation to the isolation found inside a shell: " A neat example of a psychical system shut off from the stimuli of the external world. is afforded by a bird's egg with its food supply enclosed in its shell; for it, the care provided by its mother is limited to the provision of warmth " (Freud 1911: 220). Piaget's (1952, 1954) newborn is similar, but he uses a philosophical rather than biological metaphor. He believed that the baby is 'radically egocentric' or even 'solipsistic. ' The neonate has only a few reflexes at her disposal (e.g., sucking, grasping), and people are registered only to the extent that they can be assimilated to these action schemes. The child …
Non-causal error control for video streaming over wireless packet networks

Video streaming systems usually employ a reasonably large receiver buffer to deal with jitter. The existence of such a buffer allows us to implement non-causal algorithms for video processing at the receiver. In this paper we describe an error control scheme that takes advantage of this fact, and employs a non-causal error concealment algorithm. We use the knowledge of the packet loss realization for the previously transmitted data to adjust the transmission strategy for the future data, knowing that this future data will be used to conceal the data in the previously lost packets. We demonstrate that such a strategy can be several times more energy efficient than AR.
Classifying news stories using memory based reasoning

We describe a method for classifying news stories using Memory Based Reasoning (MBR) a k-nearest neighbor method), that does not require manual topic definitions. Using an already coded training database of about 50,000 stories from the Dow Jones Press Release News Wire, and SEEKER [Stanfill] (a text retrieval system that supports relevance feedback) as the underlying match engine, codes are assigned to new, unseen stories with a recall of about 80% and precision of about 70%. There are about 350 different codes to be assigned. Using a massively parallel supercomputer, we leverage the information already contained in the thousands of coded stories and are able to code a story in about 2 seconds. Given SEEKER, the text retrieval system, we achieved these results in about two person-months. We believe this approach is effective in reducing the development time to implement classification systems involving large number of topics for the purpose of classification, message routing etc.
Global-scale modeling of groundwater recharge

Abstract. Long-term average groundwater recharge, which is equivalent to renewable groundwater resources, is the major limiting factor for the sustainable use of groundwater. Compared to surface water resources, groundwater resources are more protected from pollution, and their use is less restricted by seasonal and inter-annual flow variations. To support water management in a globalized world, it is necessary to estimate groundwater recharge at the global scale. Here, we present a best estimate of global-scale long-term average diffuse groundwater recharge (i.e. renewable groundwater resources) that has been calculated by the most recent version of the WaterGAP Global Hydrology Model WGHM (spatial resolution of 0.5° by 0.5°, daily time steps). The estimate was obtained using two state-of-the-art global data sets of gridded observed precipitation that we corrected for measurement errors, which also allowed to quantify the uncertainty due to these equally uncertain data sets. The standard WGHM groundwater recharge algorithm was modified for semi-arid and arid regions, based on independent estimates of diffuse groundwater recharge, which lead to an unbiased estimation of groundwater recharge in these regions. WGHM was tuned against observed long-term average river discharge at 1235 gauging stations by adjusting, individually for each basin, the partitioning of precipitation into evapotranspiration and total runoff. We estimate that global groundwater recharge was 12 666 km3/yr for the climate normal 1961–1990, i.e. 32% of total renewable water resources. In semi-arid and arid regions, mountainous regions, permafrost regions and in the Asian Monsoon region, groundwater recharge accounts for a lower fraction of total runoff, which makes these regions particularly vulnerable to seasonal and inter-annual precipitation variability and water pollution. Average per-capita renewable groundwater resources of countries vary between 8 m3/(capita yr) for Egypt to more than 1 million m3/(capita yr) for the Falkland Islands, the global average in the year 2000 being 2091 m3/(capita yr). Regarding the uncertainty of estimated groundwater resources due to the two precipitation data sets, deviation from the mean is 1.1% for the global value, and less than 1% for 50 out of the 165 countries considered, between 1 and 5% for 62, between 5 and 20% for 43 and between 20 and 80% for 10 countries. Deviations at the grid scale can be much larger, ranging between 0 and 186 mm/yr.
Analysis of Time-Dependent Flow-Sensitive PC-MRI Data

Many flow visualization techniques, especially integration-based methods, are problematic when the measured data exhibit noise and discretization issues. Particularly, this is the case for flow-sensitive phase-contrast magnetic resonance imaging (PC-MRI) data sets which not only record anatomic information, but also time-varying flow information. We propose a novel approach for the visualization of such data sets using integration-based methods. Our ideas are based upon finite-time Lyapunov exponents (FTLE) and enable identification of vessel boundaries in the data as high regions of separation. This allows us to correctly restrict integration-based visualization to blood vessels. We validate our technique by comparing our approach to existing anatomy-based methods as well as addressing the benefits and limitations of using FTLE to restrict flow. We also discuss the importance of parameters, i.e., advection length and data resolution, in establishing a well-defined vessel boundary. We extract appropriate flow lines and surfaces that enable the visualization of blood flow within the vessels. We further enhance the visualization by analyzing flow behavior in the seeded region and generating simplified depictions.
Some unique biologic characteristics of the Masai of East Africa.

Abstract The Masai of East Africa exhibit some unique biologic characteristics. Despite their customary diet composed of 66 per cent calories as fat, they have persistent low serum cholesterol and beta-lipoprotein levels. Post-mortem examinations provided direct proof of a paucity of atherosclerosis. Metabolic studies revealed that the Masai absorbed large amounts of dietary cholesterol, but also possessed a highly efficient negative feedback control of endogenous cholesterol biosynthesis to compensate for the influx of dietary cholesterol. Two unusual serum-protein patterns were observed: the presence of a double alpha2 band; and a high level of serum IgA that is apparent at an early age (four years). The high ratios of phospholipid to cholesterol and bile acid to cholesterol in their gallbladder bile explain the extreme rarity of cholesterol gallstones. All these characteristics may reflect a long-term biologic adaptation of the tribe.
Caffeinated energy drinks: risks assumed with consumption when competing, working, and drinking.

Recently, we had a 21-year-old patient admitted for severe anxiety, resting tremor, and chest pain. An assessment revealed that the young man had consumed multiple caffeinated energy drinks and shots with alcohol. Caffeine toxicity was the discharge diagnosis and intoxication. All other drug screens were negative. I was surprised how significant the symptoms were. Based on reports from the patient and his friends, the symptoms of tremor, nausea, and tachycardia occurred very soon after ingestion of multiple energy drinks in a short period. How common is caffeine toxicity? Why are there not more health warnings regarding use of these products? They certainly don’t appear dangerous.
Plyometric Training Performance in Elite-Oriented Prepubertal Female Gymnasts

Abstract Marina, M and Jemni, M. Plyometric training performance in elite-oriented prepubertal female gymnasts. J Strength Cond Res 28(4): 1015–1025, 2014—We studied the effectiveness of a combined strength and plyometric training program (experimental period) on jumping performance when compared with a training routine on apparatus (control period) over 2 successive gymnastics training seasons. Nine female elite-orientated gymnasts (around 30-hour training per week) were participated in the study. The study was based on a 20-month longitudinal design covering 2 training seasons separated by a competitive period and transition periods. Each season included 1 control and 1 experimental period (Ctrl&Dgr;1 + Ex&Dgr;1 and Ctrl&Dgr;2 + Ex&Dgr;2, respectively). Before and after each control and experimental period, we assessed plyometric performance by means of drop jumps (DJs) from 20, 40, 60, 80, and 100 cm. The jump performance variables considered were flight time (FT), contact time (CT), flight-contact ratio (FC), and estimated mechanical power (also called Bosco expression [BE]), all of which were expressed as raw data and normalized (expressed as a percentage) with respect to the recordings at the beginning of each period of analysis. Flight time was the only variable to increase not only during both experimental periods but also during both controls. Our results confirmed larger relative increments of all the variables (FT, CT, BE, and FC), except for CT at DJs of 80 and 100 cm, during the experimental periods than during their respective previous control periods. Despite the additive effect of growth, development, and maturation, the gymnasts were not able to maintain the DJ performance accomplished during Ex&Dgr;1, thereby confirming detraining during the competitive and transition periods. We conclude that a combination of heavy resistance training with high impact plyometric jumps is effective in prepubertal gymnasts, despite their initial high level of physical conditioning.
β-Galactoside α2,6-Sialyltranferase 1 Promotes Transforming Growth Factor-β-mediated Epithelial-Mesenchymal Transition*

Background: Molecular mechanisms underlying the effect of sialylation on tumor progression remain unclear. Results: ST6GAL1 promoted the TGF-β-induced EMT through down-regulation of E-cadherin-mediated cell adhesion and up-regulation of integrin-mediated cell migration. Conclusion: Expression of ST6GAL1 is critical for sufficient induction of EMT. Significance: α2,6-Sialylation of N-glycans may play a role in EMT. β-Galactoside α2,6-sialyltranferase 1 (ST6GAL1) catalyzes the addition of terminal α2,6-sialylation to N-glycans. Increased expression of ST6GAL1 has been reported in diverse carcinomas and highly correlates with tumor progression. Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. Conversely, overexpression of ST6GAL1 increased the turnover of cell surface E-cadherin and promoted TGF-β-induced EMT. Overexpressing β-galactoside α2,3-sialyltranferase 4 had little influence on EMT, indicating specificity for α2,6-sialylation. The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells was partially reversed by ST6GAL1 silencing. Moreover, ST6GAL1 knockdown inhibited the phosphorylation of Akt, but not Smad2, suggesting that ST6GAL1 contributes to EMT through a non-Smad signaling pathway. Taken together, our data indicate that ST6GAL1 promotes TGF-β-dependent EMT as well as maintenance of the mesenchymal state by growth signaling, providing a plausible mechanism whereby up-regulated ST6GAL1 may promote malignant progression.