Miracle-dz/UniFAR-FTUs huggingface dataset:
Aggregation-Dependent Changes in Susceptibility of Dictyostelium discoideum to Amphotericin B

In this study, the polyene antibiotic amphotericin B was used to induce changes in permeability and viability of the eucaryotic microorganism Dictyostelium discoideum. The results show that as the cells progress from the growth phase through stationary phase to eventual aggregation, they become increasingly resistant to both permeability changes and lysis. Plasma membranes were prepared from cells harvested at exponential growth, stationary phase, and the aggregation-competent stage, and both the neutral lipid and phospholipid content were determined. An increase in the neutral lipid and a decrease in the phospholipid were observed as the cells progressed from growth into aggregation, with the overall result that the phospholipid-sterol ratio decreased during this period. The extent of amphotericin B binding by cells from the different stages was also determined. Aggregation cells exhibited a small but significant increase in binding compared to cells from either of the other two stages. The permeability changes produced by the drug were measured as a function of temperature. Exponentially growing cells showed a marked temperature dependence for the drug effect, whereas aggregating cells did not. Rates of inactivation by the drug were also determined over a range of temperatures. With exponentially growing cells, the rate of inactivation was temperature dependent, whereas with aggregating cells it was not. Finally, drug binding for both growing and aggregating cells was temperature dependent. Thus, no binding was observed for cells of either type at 4°C. This finding suggests that the differences in the temperature dependence of the permeability changes and inactivation between the cells involve parameters other than drug binding.
‘GROWTH OPTIONS AND THE VALUE-SIZE PUZZLE’*

This study presents an intuitive explanation, based on insights of real options theory, for the value size puzzle. Growth firms are not overvalued, but priced for their upward potential. Small growth firms are especially characterized by an asymmetric risk-return relation. Therefore, the value-size premium comprises two parts: a distress premium and a growth discount. Beta underestimates the risk of distressed firms and overestimates the risk of growth firms caused by asymmetries in stock returns. We examine the impact of growth options on equity returns within a panel of 7,167 listed U.S. firms (1981– 2000).
An Asynchronous Linear Predictive Analyzer

Linear predictive analysis is a standard technique in modern digital speech processing. This makes it an interesting implementation area for asynchronous design. We present an asynchronous speed-independent circuit implementation of a linear predictive analysis system. The implementation is built around a program ROM into which the algorithm is encoded. The design process is carried out using the action systems formalism as the development tool. As the result we get an efficient and logically highly reliable system with a potential for low power consumption. We present various block diagrams of the resulting composition and show the details of a set of selected controllers.
Concerns About Meta-analysis of Glucose Control and Cardiovascular Disease in Type 2 Diabetes

TO THE EDITOR: The proposition that glucose lowering affects cardiovascular risk in patients with type 2 diabetes is very important. Although we recognize the value of the article by Kelly and colleagues (1), we would like to draw attention to errors in their metaanalysis that we believe affect the conclusions reached. First, Kelly and colleagues combined data from 3 recent studies (2–4) with 2 substudies of the UKPDS (United Kingdom Prospective Diabetes Study) (5, 6) to suggest that many outcomes differed between the “early” and “late” studies. In so doing, they did not notice that the 411 participants and their associated events in the conventional treatment (diet) group of the metformin substudy, UKPDS 34 (6), were also included in the conventional treatment group in the main study, UKPDS 33 (5). By using the same studies and methodology as Kelly and colleagues, but without doublecounting, we analyzed UKPDS 33 and 34 as 1 study, including the additional data from the intensive treatment group of the patients treated with metformin in UKPDS 34. Thus, the relative risk for cardiovascular death is 1.05 (95% CI, 0.82 to 1.33) instead of 0.97 (CI, 0.76 to 1.24), the relative risk for all-cause mortality is 1.03 (CI, 0.89 to 1.19) instead of 0.98 (CI, 0.84 to 1.15), and the reduction in risk for cardiovascular events is 8 percentage points (CI, 1 to 14 percentage points) instead of 10 percentage points (CI, 2 to 17 percentage points). The recalculation reduces the difference between the early and late trials, with the only end points now showing substantial heterogeneity in overall pooled effect estimates being cardiovascular death (I 75%), all-cause mortality (I 67%), and severe hypoglycemia (I 79%). Second, one might debate whether it was appropriate to include UKPDS 34 in the meta-analysis; trialists involved in the original studies performed a similar meta-analysis without including it (7). Finally, use of different definitions of end points (such as including or not including sudden death as a cardiovascular disease) is a problem that can be solved only with metaanalysis of individual patient data. Therefore, we conclude that little evidence exists of differences in outcomes between early and late trials of glucose control for type 2 diabetes. We think that current epidemiologic and trial evidence suggests that intensive glycemic control will reduce coronary heart disease by about two thirds and will not statistically significantly affect stroke, cardiovascular mortality, or total mortality. Moreover, we believe that data suggest that treating 100 persons with intensive glycemic control for 10 years would prevent about 3 cardiovascular events at the expense of inducing 8 serious hypoglycemic events.
Avoiding the Ionospheric Scintillation Interference on Geosynchronous SAR by Orbit Optimization

L-band geosynchronous synthetic aperture radar (GEO SAR) images will most likely deteriorate in the presence of ionosphere scintillation interference due to the low carrier frequency of GEO SAR. Meanwhile, because of the high orbit and the long working time above the region with the active ionosphere, GEO SAR will experience ionospheric scintillation with a higher probability. To make the GEO SAR avoid being interfered by ionospheric scintillation, we propose an orbit-optimization strategy by utilizing the diurnal and geographical pattern of the ionospheric scintillation occurrence in this letter. As the equatorial region is likely to experience ionospheric scintillation during the specified time window from the early evening after sunset to midnight, the orbit can be optimized by tuning the GEO SAR orbit parameters (e.g., a proper time past perigee) to avoid imaging over the equatorial region during the specified time window. Finally, simulation is conducted to verify the effectiveness of the method under the proposed three types of GEO SAR orbits, and the corresponding effective sets of time past perigee are obtained.
The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo

Abstract Adenosine triphosphate-dependent chromatin remodeling machines play a central role in gene regulation by manipulating chromatin structure. Most genes have a nucleosome-depleted region at the promoter and an array of regularly spaced nucleosomes phased relative to the transcription start site. In vitro, the three known yeast nucleosome spacing enzymes (CHD1, ISW1 and ISW2) form arrays with different spacing. We used genome-wide nucleosome sequencing to determine whether these enzymes space nucleosomes differently in vivo. We find that CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing. In contrast, ISW2 plays a minor role, limited to transcriptionally inactive genes. Heavily transcribed genes show weak phasing and extreme spacing, either very short or very long, and are depleted of linker histone (H1). Genes with longer spacing are enriched in H1, which directs chromatin folding. We propose that CHD1 directs short spacing, resulting in eviction of H1 and chromatin unfolding, whereas ISW1 directs longer spacing, allowing H1 to bind and condense the chromatin. Thus, competition between the two remodelers to set the spacing on each gene may result in a highly dynamic chromatin structure.
Microultrasound imaging of tissue dysplasia

The second most common cause of cancer deaths in the developed world is bowel cancer. Improving the ability to detect and classify lesions as early as possible, allows treatment earlier. The work presented in this thesis is structured around the following detailed aims: Development of high frequency, broadband μUS (micro-ultrasound) imaging transducers through optimization of ultra-thinning processes for lithium niobate (LNO) and fabrication of novel ‘mass-spring’ matching layers using carefully controlled vacuum deposition is demonstrated. The effectiveness of this technique was quantified by applying multiple matching layers to 3 mm diameter 45 MHz LNO μUS transducers using carefully controlled vacuum deposition. The bandwidth of single mass-spring layer μUS transducer was measured to be 46% with an insertion loss of 21 dB. The bandwidth and insertion loss of a multiple matching layer μUS transducer was measured to be 59% and 18 dB respectively. The values were compared with an unmatched transducer which had a bandwidth and insertion loss of 28% and 34 dB respectively. All the experimentally measured values were in agreement with unidimensional acoustic model predictions. μUS tools that can detect and measure microscopic changes in precancerous tissue using a mouse small bowel model with an oncogenic mutation was developed. μUS transducer was used to test the hypothesis that the intestinal tissue morphology of WT (wild type) and Apc Min/+ (adenomatous polyposis coli) diverges with progressing age intervals (60, 90 and 120 days) of mice. A high frequency ultrasound scanning system was designed and the experiments were performed ex vivo using a focused 45 MHz, f-# = 2.85, μUS transducer. The data collected by scanning was used to compute the backscatter coefficients (BSC) and acoustic impedance (Z) of WT and Apc Min/+ mice. The 2D and 3D ultrasound images showed that μUS detects polyps < 500 μm in the scan plane. The measured values of BSC and Z showed differences between normal and precancerous tissue. The differences detected in precancerous murine intestine and human tissue using μUS were correlated with high resolution 3D optical imaging. This novel approach may provide a powerful adjunct to screening endoscopy for improved identification and monitoring, allowing earlier treatment of otherwise undetectable lesions.
Decision Feedback Chip-Level Maximum Likelihood Detection for DS-CDMA in a Frequency-Selective Fading Channel

In direct sequence code division multiple access (DS-CDMA), variable rate transmission can be realized by simply changing the spreading factor SF for the given chip rate. In a frequency-selective fading channel, the transmission performance can be improved by using rake combining. However, when a very low SF is used for achieving a high transmission rate, error floor is produced due to insufficient suppression of inter-chip interference (ICI). In this paper, decision feedback chip-level maximum likelihood detection (DF-CMLD) is proposed that can suppress the ICI. An upper-bound for the conditional bit error rate (BER) is theoretically derived for the given spreading sequence and path gains. The theoretical average BER performance is numerically evaluated by Monte-Carlo numerical computation using the derived conditional BER. The numerical computation results are confirmed by computer simulation of DS-CDMA signal transmission with DF-CMLD.
Ecological Factors Driving Avian Influenza Virus Dynamics in Spanish Wetland Ecosystems

Studies exploring the ecological interactions between avian influenza viruses (AIV), natural hosts and the environment are scarce. Most work has focused on viral survival and transmission under laboratory conditions and through mathematical modelling. However, more integrated studies performed under field conditions are required to validate these results. In this study, we combined information on bird community, environmental factors and viral epidemiology to assess the contribution of biotic and abiotic factors in the occurrence of low pathogenic AIV in Spanish wetlands. For that purpose, seven locations in five different wetlands were studied during two years (2007–2009), including seven sampling visits by location. In each survey, fresh faeces (n = 4578) of wild birds and water samples were collected for viral detection. Also, the vegetation structure, water physical properties of wetlands, climatic conditions and wild bird community composition were determined. An overall AIV prevalence of 1.7%±0.4 was detected in faecal samples with important fluctuations among seasons and locations. Twenty-six AIV were isolated from the 78 RRT-PCR positive samples and eight different haemagglutinines and five neuraminidases were identified, being the combination H3N8 the most frequent. Variation partitioning procedures identified the combination of space and time variables as the most important pure factor – independently to other factors – explaining the variation in AIV prevalence (36.8%), followed by meteorological factor (21.5%) and wild bird community composition/vegetation structure (21.1%). These results contribute to the understanding of AIV ecological drivers in Spanish ecosystems and provide useful guidelines for AIV risk assessment identifying potential hotspots of AIV activity.
A Hybrid Brain-Computer Interface-Based Mail Client

Brain-computer interface-based communication plays an important role in brain-computer interface (BCI) applications; electronic mail is one of the most common communication tools. In this study, we propose a hybrid BCI-based mail client that implements electronic mail communication by means of real-time classification of multimodal features extracted from scalp electroencephalography (EEG). With this BCI mail client, users can receive, read, write, and attach files to their mail. Using a BCI mouse that utilizes hybrid brain signals, that is, motor imagery and P300 potential, the user can select and activate the function keys and links on the mail client graphical user interface (GUI). An adaptive P300 speller is employed for text input. The system has been tested with 6 subjects, and the experimental results validate the efficacy of the proposed method.
Two distinct populations of ARF bound to Golgi membranes

ADP-ribosylation factor (ARF) is a small molecular weight GTP-binding protein (20 kD) and has been implicated in vesicular protein transport. The guanine nucleotide, bound to ARF protein is believed to modulate the activity of ARF but the mechanism of action remains elusive. We have previously reported that ARF binds to Golgi membranes after Brefeldin A-sensitive nucleotide exchange of ARF-bound GDP for GTP gamma S. Here we report that treatment with phosphatidylcholine liposomes effectively removed 40-60% of ARF bound to Golgi membranes with nonhydrolyzable GTP, presumably by competing for binding of activated ARF to lipid bilayers. This revealed the presence of two different pools of ARF on Golgi membranes. Whereas total ARF binding did not appear to be saturable, the liposome-resistant pool is saturable suggesting that this pool of ARF is stabilized by interaction with a Golgi membrane-component. We propose that activation of ARF by a guanine nucleotide-exchange protein results in association of myristoylated ARF GTP with the lipid bilayer of the Golgi apparatus. Once associated with the membrane, activated ARF can diffuse freely to associate stably with a target protein or possibly can be inactivated by a GTPase activating protein (GAP) activity.
Topographic Independent Component Analysis

In ordinary independent component analysis, the components are assumed to be completely independent, and they do not necessarily have any meaningful order relationships. In practice, however, the estimated independent components are often not at all independent. We propose that this residual dependence structure could be used to define a topo-graphic order for the components. In particular, a distance between two components could be defined using their higher-order correlations, and this distance could be used to create a topographic representation. Thus, we obtain a linear decomposition into approximately independent components, where the dependence of two components is approximated by the proximity of the components in the topographic representation.
Involvement of TLR2 and TLR4 in inflammatory immune responses induced by fine and coarse ambient air particulate matter

Induction of proinflammatory mediators by alveolar macrophages exposed to ambient air particulate matter has been suggested to be a key factor in the pathogenesis of inflammatory and allergic diseases in the lungs. However, receptors and mechanisms underlying these responses have not been fully elucidated. In this study, we examined whether TLR2, TLR4, and the key adaptor protein, MyD88, mediate the expression of proinflammatory cytokines and chemokines by mouse peritoneal macrophages exposed to fine and coarse PM. TLR2 deficiency blunted macrophage TNF‐α and IL‐6 expression in response to fine (PM2.5), while not affecting cytokine‐inducing ability of coarse NIST Standard Reference Material (SRM 1648) particles. In contrast, TLR4−/− macrophages showed inhibited cytokine expression upon stimulation with NIST SRM 1648 but exhibited normal responses to PM2.5. Preincubation with polymyxin B markedly suppressed the capacity of NIST SRM 1648 to elicit TNF‐α and IL‐6, indicating endotoxin as a principal inducer of cytokine responses. Overexpression of TLR2 in TLR2/4‐deficient human embryonic kidney 293 cells imparted PM2.5 sensitivity, as judged by IL‐8 gene expression, whereas NIST SRM 1648, but not PM2.5 elicited IL‐8 expression in 293/TLR4/MD‐2 transfectants. Engagement of TLR4 by NIST SRM 1648 induced MyD88‐independent expression of the chemokine RANTES, while TLR2‐reactive NIST IRM PM2.5 failed to up‐regulate this response. Consistent with the shared use of MyD88 by TLR2 and TLR4, cytokine responses of MyD88−/− macrophages to both types of air PM were significantly reduced. These data indicate differential utilization of TLR2 and TLR4 but shared use of MyD88 by fine and coarse air pollution particles.
Roles of Kruppel-associated Box (KRAB)-associated Co-repressor KAP1 Ser-473 Phosphorylation in DNA Damage Response*

Background: KAP1 is important for epigenetic modifications and the DNA damage response. Results: Distinct DNA damage signaling pathways regulate KAP1 Ser-473 phosphorylation (S473p). DNA damage-induced KAP1 S473p regulates KAP1-HP1 and KAP1-E2F1 interactions, gene transcription, DNA repair, and apoptosis. Conclusion: KAP1 S473p is required for efficient DNA repair and cell survival under stress. Significance: Our studies reveal functions for KAP1 S473p under stress. The Kruppel-associated box (KRAB)-associated co-repressor KAP1 is an essential nuclear co-repressor for the KRAB zinc finger protein superfamily of transcriptional factors. Ataxia telangiectasia mutated (ATM)-Chk2 and ATM- and Rad3-related (ATR)-Chk1 are two primary kinase signaling cascades activated in response to DNA damage. A growing body of evidence suggests that ATM and ATR phosphorylate KAP1 at Ser-824 in response to DNA damage and regulate KAP1-dependent chromatin condensation, DNA repair, and gene expression. Here, we show that, depending on the type of DNA damage that occurs, KAP1 Ser-473 can be phosphorylated by ATM-Chk2 or ATR-Chk1 kinases. Phosphorylation of KAP1 at Ser-473 attenuated its binding to the heterochromatin protein 1 family proteins and inhibited its transcriptional repression of KRAB-zinc finger protein (KRAB-ZFP) target genes. Moreover, KAP1 Ser-473 phosphorylation induced by DNA damage stimulated KAP1-E2F1 binding. Overexpression of heterochromatin protein 1 significantly inhibited E2F1-KAP1 binding. Elimination of KAP1 Ser-473 phosphorylation increased E2F1-targeted proapoptotic gene expression and E2F1-induced apoptosis in response to DNA damage. Furthermore, loss of phosphorylation of KAP1 Ser-473 led to less BRCA1 focus formation and slower kinetics of loss of γH2AX foci after DNA damage. KAP1 Ser-473 phosphorylation was required for efficient DNA repair and cell survival in response to DNA damage. Our studies reveal novel functions of KAP1 Ser-473 phosphorylation under stress.
Proving that systems code eventually does something good

In recent years we have seen great progress made in the area of automatic source-level static analysis tools. However, all of today’s program verification tools are limited to properties that guarantee the absence of bad events (called safety properties). Until now no formal software analysis tool has provided support for automatically proving properties that ensure that good events eventually happen (called liveness properties), i.e. no tool has supported proving the absence of liveness bugs. In this paper we present such an automatic tool, called VIVO, which handles both safety and liveness properties of large systems written in C. The tool attempts to prove properties of programs; failed proofs result in counterexamples which are presented back to the user. We have used the tool to automatically prove critical liveness properties of Windows device drivers. Furthermore, we have found several previously unknown liveness bugs.
Fast, On-line Collision Avoidance for Dynamic Vehicles Using Buffered Voronoi Cells

This letter presents a distributed collision avoidance algorithm for multiple dynamic vehicles moving in arbitrary dimensions. In our algorithm, each robot continually computes its buffered Voronoi cell (BVC) and plans its path within the BVC in a receding horizon fashion. We prove that our algorithm guarantees collision avoidance for robots with single integrator dynamics. We show that our algorithm has computational complexity of $O(k)$, which is the same as that of the optimal reciprocal collision avoidance (ORCA) algorithm, and is considerably faster than model predictive control (MPC) and sequential convex programming (SCP) based approaches. Moreover, ORCA and MPC-SCP require relative position, velocity, and even other information, to be exchanged over a communication network among the robots. Our algorithm only requires the sensed relative position, and therefore is well suited for on-line implementation as it does not require a communication network, and it works well with noisy relative position sensors. Furthermore, we provide an extension of our algorithm to robots with higher-order dynamics like quadrotors. We demonstrate the capabilities of our algorithm by comparing it to ORCA in multiple benchmark simulation scenarios, and we present results of over 70 experimental trials using five quadrotors in a motion capture environment.
Quantitative proteome analysis of plasma microparticles for the characterization of HCV‐induced hepatic cirrhosis and hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer‐related deaths worldwide. Cirrhosis induced by hepatitis‐C virus (HCV) infection is the most critical risk factor for HCC. However, the mechanism of HCV‐induced carcinogenesis is not fully understood. Plasma microparticles (PMP) contribute to numerous physiological and pathological processes and contain proteins whose composition correlates to the respective pathophysiological conditions.