Miracle-dz/UniFAR-FTUs huggingface dataset:
Strategic design and three-dimensional analysis of antiviral drug combinations

The development of new drugs effective against human viral diseases has proven to be both difficult and time-consuming. Indeed, there are but 10 drugs licensed for such applications in the United States today. An attractive solution to this problem may be to optimize the efficacy and selectivity of existing antiviral drugs by combining them with agents that strategically block carefully selected metabolic pathways. This approach was used in the rational design of a three-drug combination to increase the apparent potency of acyclovir against herpes simplex virus. Recent advances in analytical techniques have made the evaluation of this complex drug strategy both possible and practical. A modified version of a previously described analytical method was used to identify optimal drug concentrations and to quantitate statistically significant synergy. Concentrations of 0.25 microM 5-fluorodeoxyuridine, 3.6 microM 2-acetylpyridine thiosemicarbazone, and 0.3 microM acyclovir were determined to be optimal in terms of antiviral activity. The volume of synergy produced was nearly 2,000 microM3% at a 95% level of confidence (corresponding to a 186-fold decrease in the apparent 50% inhibitory concentration of acyclovir with the addition of 0.25 microM 5-fluorodeoxyuridine and 3.6 microM 2-acetylpyridine thiosemicarbazone). We anticipate that this strategic approach and the supporting three-dimensional analytical method will prove valuable in designing and understanding multidrug therapies.
A genome assembly-integrated dog 1 Mb BAC microarray: a cytogenetic resource for canine cancer studies and comparative genomic analysis

Molecular cytogenetic studies have been instrumental in defining the nature of numerical and structural chromosome changes in human cancers, but their significance remains to be fully understood. The emergence of high quality genome assemblies for several model organisms provides exciting opportunities to develop novel genome-integrated molecular cytogenetic resources that now permit a comparative approach to evaluating the relevance of tumor-associated chromosome aberrations, both within and between species. We have used the dog genome sequence assembly to identify a framework panel of 2,097 bacterial artificial chromosome (BAC) clones, selected at intervals of approximately one megabase. Each clone has been evaluated by multicolor fluorescence in situ hybridization (FISH) to confirm its unique cytogenetic location in concordance with its reported position in the genome assembly, providing new information on the organization of the dog genome. This panel of BAC clones also represents a powerful cytogenetic resource with numerous potential applications. We have used the clone set to develop a genome-wide microarray for comparative genomic hybridization (aCGH) analysis, and demonstrate its application in detection of tumor-associated DNA copy number aberrations (CNAs) including single copy deletions and amplifications, regional aneuploidy and whole chromosome aneuploidy. We also show how individual clones selected from the BAC panel can be used as FISH probes in direct evaluation of tumor karyotypes, to verify and explore CNAs detected using aCGH analysis. This cytogenetically validated, genome integrated BAC clone panel has enormous potential for aiding gene discovery through a comparative approach to molecular oncology.
Interstitial Fibrosis, Left Ventricular Remodeling, and Myocardial Mechanical Behavior in a Population-Based Multiethnic Cohort: The Multi-Ethnic Study of Atherosclerosis (MESA) Study

Background—Tagged cardiac magnetic resonance provides detailed information on regional myocardial function and mechanical behavior. T1 mapping by cardiac magnetic resonance allows noninvasive quantification of myocardial extracellular expansion (ECE), which has been related to interstitial fibrosis in previous clinical and subclinical studies. We assessed sex-associated differences in the relation of ECE to left ventricular (LV) remodeling and myocardial systolic and diastolic deformation in a large community-based multiethnic population. Methods and Results—Midventricular midwall peak circumferential shortening and early diastolic strain rate and LV torsion and torsional recoil rate were determined using cardiac magnetic resonance tagging. Midventricular short-axis T1 maps were acquired in the same examination pre- and postcontrast injection using Modified Look-Locker Inversion-Recovery sequence. Multivariable linear regression (estimated regression coefficient, B) was used to adjust for risk factors and subclinical disease measures. Of 1230 participants, 114 had a visible myocardial scar by late gadolinium enhancement. Participants without a visible myocardial scar (n=1116) had no history of previous clinical events. In the latter group, multivariable linear regression demonstrated that lower postcontrast T1 times, reflecting greater ECE, were associated with lower circumferential shortening (B=−0.1; P=0.0001), lower LV end-diastolic volume index (B=0.6; P=0.0001), and lower LV end-diastolic mass index (B=0.4; P=0.0001). In addition, lower postcontrast T1 times were associated with lower early diastolic strain rate (B=0.01; P=0.03) in women only and lower LV torsion (B=0.005; P=0.03) and lower LV ejection fraction (B=0.2, P=0.01) in men only. Conclusions—Greater ECE is associated with reduced LV end-diastolic volume index and LV end-diastolic mass index in a large multiethnic population without history of previous cardiovascular events. In addition, greater ECE is associated with reduced circumferential shortening, lower early diastolic strain rate, and a preserved ejection fraction in women, whereas in men, greater ECE is associated with greater LV dysfunction manifested as reduced circumferential shortening, reduced LV torsion, and reduced ejection fraction.
Journal of Graph Algorithms and Applications Graph Drawing by High-dimensional Embedding

We present a novel approach to the aesthetic drawing of undirected graphs. The method has two phases: first embed the graph in a very high dimension and then project it into the 2-D plane using principal components analysis. Running time is linear in the graph size, and experiments we have carried out show the ability of the method to draw graphs of 10 5 nodes in few seconds. The new method appears to have several advantages over classical methods, including a significantly better running time, a useful inherent capability to exhibit the graph in various dimensions, and an effective means for interactive exploration of large graphs.
Utilizing Model Structure for Efficient Simultaneous Localization and Mapping for a UAV Application

This contribution aims at unifying two recent trends in applied particle filtering (PF). The first trend is the major impact in simultaneous localization and mapping (SLAM) applications, utilizing the FastSLAM algorithm. The second one is the implications of the marginalized particle filter (MPF) or the Rao-Blackwellized particle filter (RBPF) in positioning and tracking applications. Using the standard FastSLAM algorithm, only low-dimensional vehicle models are computationally feasible. In this work, an algorithm is introduced which merges FastSLAM and MPF, and the result is an algorithm for SLAM applications, where state vectors of higher dimensions can be used. Results using experimental data from a UAV (helicopter) are presented. The algorithm fuses measurements from on-board inertial sensors (accelerometer and gyro) and vision in order to solve the SLAM problem, i.e., enable navigation over a long period of time.
Isolation of hCG and its Characterization by Radioimmunoassay, Enzyme‐Immunoassay, and Radio‐Receptor Assay

Abstract The nature of human chorionic gonadotropin (hCG) molecules present during early pregnancy of Indian women is poorly understood. Therefore, a study has been undertaken to isolate hCG and characterize different forms of hCG from urine. The hCG molecules from urine of pregnant women (45–75 days post LMP) were adsorbed onto kaolin, eluted with ammonium hydroxide, and precipitated using acetone and then lyophilized. The lyophilized extract was subjected to Sephadex G‐100 chromatography followed by ion‐exchange fractionation. Three major fractions of protein (i.e., Peaks I, II, and III) associated with carbohydrate activity were obtained. Peaks II and III eventually resolved into a single peak I following repeated ion exchange chromatography, which suggested the presence of aggregates of molecules. Further purification on an affinity column resolved all three peak fractions into one unadsorbed and two adsorbed (A and B) fractions. These adsorbed fractions were characterized by radioreceptor assay (RRA), radioimmunoassay (RIA), and enzyme linked immunosorbent assay (ELISA). The activity was standardized against WHO reference preparation 75/589. Peaks I (A and B) were found to have maximum at about 75% of immunologically potent hCG, followed by peaks II (40%) and III (5%). The molecular sizes of peaks I, II, and III on a Sephadex G‐200 column corresponded to 27,500D, 66,000D, and 84,000D, respectively. Relative mobilities of all adsorbed fractions in sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE) showed the presence of hCG‐α (mol. wt. 19,539D) and hCG‐β (28,870D) subunits. The presence of both subunits of hCG were also revealed by Western blot analysis. For the first time, we report the low molecular weight hCG molecule, of 27,500D by size exclusion chromatography, which has immunological and biological activity as measured by RIA, ELISA, and RRA.
ProBiS-CHARMMing: Web Interface for Prediction and Optimization of Ligands in Protein Binding Sites

Proteins often exist only as apo structures (unligated) in the Protein Data Bank, with their corresponding holo structures (with ligands) unavailable. However, apoproteins may not represent the amino-acid residue arrangement upon ligand binding well, which is especially problematic for molecular docking. We developed the ProBiS-CHARMMing web interface by connecting the ProBiS ( http://probis.cmm.ki.si ) and CHARMMing ( http://www.charmming.org ) web servers into one functional unit that enables prediction of protein-ligand complexes and allows for their geometry optimization and interaction energy calculation. The ProBiS web server predicts ligands (small compounds, proteins, nucleic acids, and single-atom ligands) that may bind to a query protein. This is achieved by comparing its surface structure against a nonredundant database of protein structures and finding those that have binding sites similar to that of the query protein. Existing ligands found in the similar binding sites are then transposed to the query according to predictions from ProBiS. The CHARMMing web server enables, among other things, minimization and potential energy calculation for a wide variety of biomolecular systems, and it is used here to optimize the geometry of the predicted protein-ligand complex structures using the CHARMM force field and to calculate their interaction energies with the corresponding query proteins. We show how ProBiS-CHARMMing can be used to predict ligands and their poses for a particular binding site, and minimize the predicted protein-ligand complexes to obtain representations of holoproteins. The ProBiS-CHARMMing web interface is freely available for academic users at http://probis.nih. gov.
Promises in Air‐Sea Fully Coupled Data Assimilation for Future Hurricane Prediction

The recent article by Li and Toumi (2018, https://doi.org/10.1029/2018GL079677) published in Geophysical Research Letters explored the potential for improving tropical cyclone intensity forecasts by assimilating synthetic coastal surface currents from high‐frequency radar observations. Although it is an idealized study using simulated observations, this may signal the beginning of a new frontier in future hurricane prediction through ingesting in situ and remotely sensed observations of oceanic currents into fully coupled systems. Assimilation of oceanic observations can improve not only the state estimation of both oceanic and atmospheric variables but it also has the potential to better estimate uncertain model physics' parameters such as the air‐sea exchange coefficients.
A Regional Power in the Making: Ethiopian Diplomacy in the Horn of Africa

Ethiopia’s regional engagement and foreign policy is based on its Foreign Affairs and National Security Policy and Strategy (FANSPS), launched in 2002. The country is a key player in the Horn of Africa and, despite recent internal conflict, crucial for maintaining stability in the region. Its government engages robustly at the regional and continental level, mainly through multilateral agencies such as the Intergovernmental Authority on Development (IGAD) and the AU; and it is seen as a trustworthy mediator in East Africa and the Horn. This role is aided by the relative strength of its military and its active participation in regional peace and security operations; its capacity and willingness to combat terrorism; a pan-Africanist legacy; and its effective utilisation of multilateral platforms. Domestic problems include a grave democratic deficit; sectarian politics; corruption; the absence of constitutional accountability, judicial review and parliamentary oversight; the violation of human rights; and extreme poverty, all of which pose a threat to internal peace and security. Its response to these domestic threats remains the main determinant of Ethiopia’s foreign policy. Externally, terrorism and neighbouring states’ expansionist policies, continued enmity with Eritrea and rivalry with Egypt over the Nile River threaten Ethiopia’s pursuit of peace and social development, both domestic and regional. Although the fundamentals of the FANSPS remain pertinent after two decades, it is time that Ethiopia turns from an exceedingly inward-looking foreign policy focused exclusively on domestic vulnerabilities towards a more balanced approach, to forestall external threats and seize legitimate opportunities. Proportionality demands adequate attention to external threats and opportunities; hence it is time to take stock of its current approach and, in doing so, consider economic and trade opportunities, in particular access to the sea and port services. Emerging geopolitical and geo-economic issues may impair Ethiopia’s diplomatic achievements if the FANSPS is not urgently reappraised.
Genetic and Environmental Influences on Body Size in Early Childhood: A Twin Birth-Cohort Study

Abstract Genetic and environmental contributions to body size from birth to 5 years in a population-based twin cohort were studied. Sex differences in gene–environment etiology were also explored. Analyses used data from the Quebec Newborn Twin Study (QNTS), a population-based birth cohort of 672 twin pairs. The final sample consisted of 177 complete twin pairs. Heritability of weight was moderate at birth while common environmental factors accounted for almost half of the variance. Influence of family environment disappeared by 5 months and genetic effects were high (approximately 90%) for both sexes at 5 months and 5 years. Adjustment of weight for height yielded similar results as for weight alone. Slight but significant sex-limitation of genetic effects was observed at 5 months. Overall, genetic factors accounted for 40% of birthweight variance, with intrauterine environment influences explaining almost half. However, genetic factors accounted for most of the variance in weight. These results do not imply a lack of environmental effects on body weight, but rather a lack of: (1) environmental effects that are independent from genetic liability, and/or (2) a lack of significant environmental variation in the population (e.g., uniform nutritional habits) that leaves genetic differences between children to generate most of the variance in weight.
Autonomous Distributed LQR/APF Control Algorithm for Multiple Small Spacecraft during Simultaneous Close Proximity Operations

An autonomous distributed LQR/APF control algorithm for multiple small spacecraft during simultaneous close proximity operations has been developed. This research contributes to the control of multiple small spacecraft for emerging operation, which may include inspection, assembly, or servicing. A control algorithm is proposed which combines the control effort efficiency of the Linear Quadratic Regulator (LQR) and the robust collision avoidance capability of the Artificial Potential Function (APF) methods. The LQR control effort serves as the attractive force toward goal positions, while APF-based repulsive functions provide collision avoidance for both fixed and moving obstacles. Refinement of both the APF and LQR control algorithms to small spacecraft applications offered insight and enhancement of the resulting control algorithm. Comprehensive performance evaluation of the multiple small spacecraft LQR/APF control algorithm is conducted for simultaneous close proximity maneuvers, such as convergence, rally, rendezvous, and docking maneuvers. These simulations show the developed LQR/APF control algorithm to be both robust and efficient based on the primary metrics of maneuver duration and required v ∆ . Promising simulation results are presented for simultaneous multiple small spacecraft gathering, rendezvous, and docking maneuvers.
European Conference on Information Systems ( ECIS ) 2009 Bitching , Bouncing and Brawling-How Backchannels Brought Colour to Conference Calls

This paper addresses the research question: How do digital backchannels, mediated by Real-Time Communications, facilitate the progress of conference calls? It is argued that whilst the fields of Distributed Work and Computer Supported Collaborative Work have been studied in depth, research into Real-Time Communications (RTC) and Instant Messaging (IM) is at an early stage. There is a paucity of research into the use of these technologies in distributed settings within organisations, especially from a perspective of generating social cohesion within teams. Furthermore, there is no known research into the use of instant messaging to mediate “hidden” interactions between individuals, through digital backchannels, within conference calls. Qualitative empirical evidence is obtained from two case studies of teams using an established corporate RTC product. Goffman's Interaction Order (1983) is presented a suitable lens through which to interpret this mediated form of interaction. Empirical evidence points to concurrent working and use of digital backchannels during meetings and conference calls. Dramaturgy (Goffman 1959) is used to identify and analyse three interaction styles of “bitching”, “bouncing” and “brawling”. It is found that interactions over digital backchannels fulfil criteria of Interaction Ritual (Goffman 1967) and may contribute to the creation of social cohesion.
Discovery of Aggregate Usage Profiles for Web Personalization

1 Please direct correspondence to mobasher@cs.depaul. edu Abstract: Web usage mining, possibly used in conjunction with standard approaches to personalization such as collaborative filtering, can help address some of the shortcomings of these techniques, including reliance on subjective user ratings, lack of scalability, and poor performance in the face highdimensional and sparse data. However, the discovery of patterns from usage data by itself is not sufficient for performing the personalization tasks. The critical step is the effective derivation of good quality and useful (i.e., actionable) "aggregate usage profiles" from these patterns. In this paper we present and experimentally evaluate two techniques, based on clustering of user transactions and clustering of pageviews, in order to discover overlapping aggregate profiles that can be effectively used by recommender systems for real-time personalization. We evaluate these techniques both in terms of the quality of the individual profiles generated, as well as in the context of providing recommendations as an integrated part of a personalization engine.
Evidence That Humans Metabolize Benzene via Two Pathways

Background Recent evidence has shown that humans metabolize benzene more efficiently at environmental air concentrations than at concentrations > 1 ppm. This led us to speculate that an unidentified metabolic pathway was mainly responsible for benzene metabolism at ambient levels. Objective We statistically tested whether human metabolism of benzene is better fitted by a kinetic model having two pathways rather than one. Methods We fit Michaelis-Menten-like models to levels of urinary benzene metabolites and the corresponding air concentrations for 263 nonsmoking Chinese females. Estimated benzene concentrations ranged from less than 0.001 ppm to 299 ppm, with 10th and 90th percentile values of 0.002 ppm and 8.97 ppm, respectively. Results Using values of Akaike’s information criterion obtained under the two models, we found strong statistical evidence favoring two metabolic pathways, with respective affinities (benzene air concentrations analogous to Km values) of 301 ppm for the low-affinity pathway (probably dominated by cytochrome P450 enzyme 2E1) and 0.594 ppm for the high-affinity pathway (unknown). The exposure-specific metabolite level predicted by our two-pathway model at nonsaturating concentrations was 184 μM/ppm of benzene, a value close to an independent estimate of 194 μM/ppm for a typical nonsmoking Chinese female. Our results indicate that a nonsmoking woman would metabolize about three times more benzene from the ambient environment under the two-pathway model (184 μM/ppm) than under the one-pathway model (68.6 μM/ppm). In fact, 73% of the ambient benzene dose would be metabolized via the unidentified high-affinity pathway. Conclusion Because regulatory risk assessments have assumed nonsaturating metabolism of benzene in persons exposed to air concentrations well above 10 ppm, our findings suggest that the true leukemia risks could be substantially greater than currently thought at ambient levels of exposure—about 3-fold higher among nonsmoking females in the general population.
Size-dependent pigmentation-pattern formation in embryos of Alligator mississippiensis: time of initiation of pattern generation mechanism

The pigmentation pattern of Alligator mississippiensis was examined. The number of white stripes on the dorsal side of embryos (stages 21–28) and hatchlings from eggs incubated at 30°C (100% females) and 33°C (100% males) was recorded. Total length, nape–rump length and tail length were recorded for each embryo and hatchling. The number of white stripes was affected by incubation temperature but not sex ; hatchlings incubated a t 33°C had two more white stripes than those at 30°C, despite being the same length. Five female hatchlings produced at 33°C by manipulation of the temperature, had the same number of stripes as males that developed under the same incubation temperatures. The appearance of the pigmentation was accelerated in embryos incubated at 33°C, occurring eight days earlier than at 30°C. At the time just before the first signs of pigment deposition, embryos from 33°C were longer than those at 30°C. If the stripe formation is size dependent this explains why hatchlings at 33°C have more stripes than hatchlings from 30°C. The mechanism that produces the stripe patterns is unknown. We describe key elements a pattern formation mechanism must possess to produce such stripes and suggest a possible mechanism, based on cell movement driven by chemotaxis. We apply the mathematical model to dorsal patterning on A. mississippiensis. We show how length at pattern formation is the prime factor in determining stripe number and how the pattern can be formed in the observed anterior–posterior sequence. We present numerical simulations and show that the qualitative behaviour is consistent with the experimental results.