Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular Pharmacokinetics and Intracellular Activity of the Novel Peptide Deformylase Inhibitor GSK1322322 against Staphylococcus aureus Laboratory and Clinical Strains with Various Resistance Phenotypes: Studies with Human THP-1 Monocytes and J774 Murine Macrophages

ABSTRACT GSK1322322 is a peptide deformylase inhibitor active against Staphylococcus aureus strains resistant to currently marketed antibiotics. Our aim was to assess the activity of GSK1322322 against intracellular S. aureus using an in vitro pharmacodynamic model and, in parallel, to examine its cellular pharmacokinetics and intracellular disposition. For intracellular activity analysis, we used an established model of human THP-1 monocytes and tested one fully susceptible S. aureus strain (ATCC 25923) and 8 clinical strains with resistance to oxacillin, vancomycin, daptomycin, macrolides, clindamycin, linezolid, or moxifloxacin. Uptake, accumulation, release, and subcellular distribution (cell fractionation) of [14C]GSK1322322 were examined in uninfected murine J774 macrophages and uninfected and infected THP-1 monocytes. GSK1322322 demonstrated a uniform activity against the intracellular forms of all S. aureus strains tested, disregarding their resistance phenotypes, with a maximal relative efficacy (Emax) of a 0.5 to 1 log10 CFU decrease compared to the original inoculum within 24 h and a static concentration (Cs) close to its MIC in broth. Influx and efflux were very fast (<5 min to equilibrium), and accumulation was about 4-fold, with no or a minimal effect of the broad-spectrum eukaryotic efflux transporter inhibitors gemfibrozil and verapamil. GSK1322322 was recovered in the cell-soluble fraction and was dissociated from the main subcellular organelles and from bacteria (in infected cells). The results of this study show that GSK1322322, as a typical novel deformylase inhibitor, may act against intracellular forms of S. aureus. They also suggest that GSK1322322 has the ability to freely diffuse into and out of eukaryotic cells as well as within subcellular compartments.
Instruction in Clinical Pharmacology: Changes in the Wind

We have presented some views on past, present and potential trends for teaching clinical pharmacology in the medical curriculum. Clinical pharmacology as subject matter in the medical curriculum has been operationally defined for our purposes as: (1) the application of fundamental principles of basic pharmacology to rational drug therapy in humans; and (2) the application of appropriate nuances of the human pharmacology of individual drugs to their use in particular disease states. In terms of improving the results of drug therapy, arguments were advanced for the importance of teaching clinical pharmacology at all levels in the medical curriculum and in postgraduate medical education. The introduction of so many new and potent pharmaceuticals over the past 25 years requires well educated and skilled medical practitioners adept and well versed in the fundamental principles of basic and applied pharmacology, so as to achieve the most prudent, effective and economically sound use of these drugs as possible. This creates a challenge to medical educators, particularly those involved in teaching clinical pharmacology, to devise innovative teaching techniques and curricular changes that foster these goals. In an attempt to address these challenges, we have reviewed some innovative teaching approaches and curricular reforms, both published and unpublished, that have already met with success, and we have also discussed some future trends in teaching both undergraduate and graduate physicians the fundamental principles of rational drug therapy. The challenges and issues involved in these future trends have been identified and will be addressed in subsequent articles in this journal. These will be concerned with teaching clinical pharmacology: (1) in basic medical pharmacology courses; (2) to upperclass medical students; and (3) in continuing medical education programs. Subsequent articles will also deal with new and innovative teaching modalities for clinical pharmacology and with the role of the drug industry in these modalities.
Applying the design structure matrix to system decomposition and integration problems: a review and new directions

Systems engineering of products, processes, and organizations requires tools and techniques for system decomposition and integration. A design structure matrix (DSM) provides a simple, compact, and visual representation of a complex system that supports innovative solutions to decomposition and integration problems. The advantages of DSMs vis-a-vis alternative system representation and analysis techniques have led to their increasing use in a variety of contexts, including product development; project planning, project management, systems engineering, and organization design. This paper reviews two types of DSMs, static and time-based DSMs, and four DSM applications: (1) component-based or architecture DSM, useful for modeling system component relationships and facilitating appropriate architectural decomposition strategies; (2) team-based or organization DSM, beneficial for designing integrated organization structures that account for team interactions; (3) activity-based or schedule DSM, advantageous for modeling the information flow among process activities; and (4) parameter-based (or low-level schedule) DSM, effective for integrating low-level design processes based on physical design parameter relationships. A discussion of each application is accompanied by an industrial example. The review leads to conclusions regarding the benefits of DSMs in practice and barriers to their use. The paper also discusses research directions and new DSM applications, both of which may be approached with a perspective on the four types of DSMs and their relationships.
A Self-Sacrificing N-Methyltransferase Is the Precursor of the Fungal Natural Product Omphalotin.

Research on ribosomally synthesized and posttranslationally modified peptides (RiPPs) has led to an increasing understanding of biosynthetic mechanisms, mostly drawn from bacterial examples. In contrast, reports on RiPPs from fungal producers, apart from the amanitins and phalloidins, are still scarce. The fungal cyclopeptide omphalotin A carries multiple N-methylations on the peptide backbone, a modification previously known only from nonribosomal peptides. Mining the genome of the omphalotin-producing fungus for a precursor peptide led to the identification of two biosynthesis genes, one encoding a methyltransferase OphMA that catalyzes the automethylation of its C-terminus, which is then released and cyclized by the protease OphP. Our findings suggest a novel biosynthesis mechanism for a RiPP in which a modifying enzyme bears its own precursor peptide.
D-SeDGAM: A Dynamic Service Differentiation Based GTS Allocation Mechanism for IEEE 802.15.4 WSN

The plethora of applications for Wireless Sensor Networks (WSN) has experienced significant growth in recent years. Every application has a different set of requirements and it is highly desirable for all of them to share the available resources in an optimized way. The IEEE 802.15. 4 standard for WSN includes guaranteed time slots (GTS) to schedule QoS demanding applications. However, the standard does not provide any type of QoS GTS scheduling mechanism and the authors are unaware of any other work that provides for service differentiation based GTS scheduling. We propose D-SeDGAM, a novel dynamic service based differentiation GTS allocation mechanism to provide QoS and service based differentiation for WSN applications. Our solution takes into account static and transient aspects of QoS provisioning in WSN to construct a dynamic scheduling method. This work demonstrates that D-SeDGAM provides significantly better performance in terms of QoS than the standard allocation method by simultaneously satisfying QoS and service differentiation demands.
Characteristic pattern discovery in videos

In this paper, we present an approach to discover characteristic patterns in videos. We characterize the videos based on frequently occurring patterns like scenes, characters, sequence of frames in an unsupervised setting. With our approach, we are able to detect the representative scenes and characters of movies. We also present a method for detecting video stop-words in broadcast news videos based on the frequency of occurrence of sequence of frames. These are analogous to stop-words in text classification and search. We employ two different video mining schemes; both aimed at detecting frequent and representative patterns. For one of our mining approaches, we use an efficient frequent pattern mining algorithm over a quantized feature space. Our second approach uses a Random Forest to first represent video data as sequences, and then mine the frequent patterns. We validate the proposed approaches on broadcast news videos and our database of 81 Oscar winning movies.
Balance and Mobility Dysfunction and Falls Risk in Older People with Mild to Moderate Alzheimer Disease

ObjectiveThis study aimed to identify the magnitude and type of balance and mobility impairments in people with Alzheimer disease by comparing their performance with that of older people without cognitive impairment. DesignTwenty-five community-dwelling people with mild to moderate Alzheimer disease and a comparison group of 25 cognitively intact age- and sex-matched people completed a comprehensive balance and mobility assessment. This included computerized posturography measures of static and dynamic balance under various conditions, clinical balance, and mobility measures, and measures of falls and falls risk. ResultsThe level of falls risk was higher in people with Alzheimer disease. Standing balance in people with Alzheimer disease was significantly impaired across a range of static and dynamic balance conditions. Activity level, gait, and mobility measures were also impaired, particularly turning and dual tasks. ConclusionsThe findings of the study highlight the value of including balance screening as a routine component of early dementia assessment. This would allow for the early detection of balance dysfunction and the introduction of balance retraining before impairments progress to more advanced levels.
Retrieval of the Extreme Values under Deadline Constraints in Wireless Sensor Networks

We consider a problem of retrieving the extreme value among sensed data under deadline constraints in wireless sensor networks with potential applications to alarm systems. The sensed data is mapped to a score which we adopt as a unified measure of the relative urgency of the data. The objective is to retrieve the data with the maximum score. We propose fully distributed schemes for contention based medium access and data combining. The proposed medium access scheme uses a randomized back-off which is controlled based on the score of the data to be transmitted. Data combining techniques are proposed to further suppress unnecessary traffic and reduce contention. The key observation is that one should aggressively prioritize packets with high score, up to an extent that does not incur excessive contention in channel access. Designed to capture such aspect, the proposed scheme is shown to substantially decrease the latency of the retrieval.
Survey Paper on Clustering Data Streams Based on Shared Density between Micro-Clusters Dure

ME(Student), ICOER ,Wagholi , Pune ,Maharastra,India Assit.Professor, ICOER ,Wagholi , Pune ,Maharastra,India ---------------------------------------------------------------------***--------------------------------------------------------------------Abstract—As more and more applications produce streaming data, clustering data streams has become an important technique for data and knowledge engineering. A typical approach is to summarize the data stream in real-time with an online process into a large number of so called micro-clusters. Micro-clusters represent local density estimates by aggregating the information of many data points in a defined area. On demand, a (modified) conventional clustering algorithm is used in a second offline step to recluster the micro-clusters into larger final clusters. For reclustering, the centers of the micro-clusters are used as pseudo points with the density estimates used as their weights. However, information about density in the area between micro-clusters is not preserved in the online process and reclustering is based on possibly inaccurate assumptions about the distribution of data within and between microclusters (e.g., uniform or Gaussian). This paper describes DBSTREAM, the first micro-clusterbased online clustering component that explicitly captures the density between micro-clusters via a shared density graph. The density information in this graph is then exploited for reclustering based on actual density between adjacent micro-clusters.
Endogenous Flows of Foreign Direct Investment and International Real Business Cycles

This paper models flows of foreign direct investment (FDI) in a two country, two sector DSGE framework. The allocation of capital to production capacity abroad is subject to a search-and-matching friction with endogenous capital reallocation. The model is calibrated on observed inflows and outflows of FDI and leads to dynamics of foreign direct investment consistent with the empirical evidence documented in this paper: relative to domestic investment, FDI is more volatile, and inward and outward flows of FDI are positively correlated. This contrasts with a standard International Real Business Cycle model which predicts a negative correlation and low volatility. Moreover, the model generates cross-country aggregate investment correlations consistent with the data. JEL classification: F41 E32 E22
The high-level similarity of some disparate gene expression measures

Probe-level data from Affymetrix GeneChips can be summarized in many ways to produce probe-set level gene expression measures (GEMs). Disturbingly, the different approaches not only generate quite different measures but they could also yield very different analysis results. Here, we explore the question of how much the analysis results really do differ, first at the gene level, then at the biological process level. We demonstrate that, even though the gene level results may not necessarily match each other particularly well, as long as there is reasonably strong differentiation between the groups in the data, the various GEMs do in fact produce results that are similar to one another at the biological process level. Not only that the results are biologically relevant. As the extent of differentiation drops, the degree of concurrence weakens, although the biological relevance of findings at the biological process level may yet remain.
Physical Activity and the Risk of Prostate Cancer in The Netherlands Cohort Study, Results after 9.3 Years of Follow-up

Background: The aim of the current study was to evaluate the relation between physical activity and prostate cancer risk with specific emphasis on interaction with body mass index (BMI) and baseline energy intake. Methods: The association between prostate cancer and physical activity was evaluated in the Netherlands Cohort Study, conducted among 58,279 men ages 55 to 69 years at entry. Information regarding baseline nonoccupational physical activity, history of sports participation, and occupational physical activity was collected with a questionnaire in 1986. After 9.3 years, 1,386 incident prostate cancer cases were available for case-cohort analyses. Multivariate incidence rate ratios (RR) and corresponding 95% confidence intervals (95% CI) were calculated using Cox regression analyses. Results: Neither baseline nonoccupational physical activity (RR, 1.01; 95% CI, 0.81-1.25 for >90 versus <30 minutes per day), history of sports participation (RR, 1.04; 95% CI, 0.90-1.22 for ever versus never participated), nor occupational physical activity (RR, 0.91; 95% CI, 0.70-1.18 for >12 versus <8 KJ/min energy expenditure in the longest held job) showed an inverse relation with prostate cancer risk. We found an increased risk of prostate cancer for men who were physically active for >1 hour per day in obese men (BMI > 30) and men with a high baseline energy intake. Discussion: The results of this current study do not support the hypothesis that physical activity protects against prostate cancer in men.
Material and Methods

SELECTION O F MATERIAL The material consisted of a random selection of 50 year old male residents of Goteborg “the men born in 1913”. The sample was collected in the following way. Of all men born in 1913 and living in Goteborg in November 1963, those born on any day of the month that was a multiple of 3 were selected. Of these persons, those 464 born on odd days of the month were invited to take part in the present investigation, and 412 accepted the invitation. Judging from the occupational distribution of these men, the sample was socio-economically representative of the coeval male population of Goteborg of that year. In recent years Goteborg has received a fairly large number of immigrants. The present sample included 22. Though many of them were well adapted and had a very good command of Swedish, some had only a poor knowledge of the language and could therefore not be accepted as suitable candidates for such a psychiatric investigation. Since one might also imagine that those who spoke Swedish better were also better adapted than others, exclusion of the latter might mean a selection giving a bias to the material and to the results of the psychiatric examination and limiting the value of any conclusions made. It was therefore decided t o exclude all the 22 men born abroad. This left 390 men for the present investigation, or 84 yo of the original random sample. The sample studied included a few severely disabled men, one confined to bed by rheumatoid arthritis, one with severe oligophrenia, and were unable to participate in the entire investigation. The totals in the tables are therefore not always 390. It might be mentioned that this sample is part of a larger one being studied from various medical and socio-medical angles, C.J Tibblin 1967.
Robust Face Recognition by Constrained Part-based Alignment

Developing a reliable and practical face recognition system is a long-standing goal in computer vision research. Existing literature suggests that pixel-wise face alignment is the key to achieve high-accuracy face recognition. By assuming a human face as piece-wise planar surfaces, where each surface corresponds to a facial part, we develop in this paper a Constrained Part-based Alignment (CPA) algorithm for face recognition across pose and/or expression. Our proposed algorithm is based on a trainable CPA model, which learns appearance evidence of individual parts and a tree-structured shape configuration among different parts. Given a probe face, CPA simultaneously aligns all its parts by fitting them to the appearance evidence with consideration of the constraint from the tree-structured shape configuration. This objective is formulated as a norm minimization problem regularized by graph likelihoods. CPA can be easily integrated with many existing classifiers to perform part-based face recognition. Extensive experiments on benchmark face datasets show that CPA outperforms or is on par with existing methods for robust face recognition across pose, expression, and/or illumination changes.
Environment of ore deposition in the Creede mining district, San Juan Mountains, Colorado; I, Geologic, hydrologic, and geophysical setting

The Creede mining district in the central San Juan Mountains of southwestern Colorado is located along a zone of recurrent faulting just north of the Creede caldera. The character, distribution, and age relations of late faulting and mineralization in this zone suggest that a local stock was emplaced beneath the Creede district in earliest Miocene time, about 24.6 m.y. ago. This postulated stock may be reflected in an observed local gravity low and in what appears to be a group of irregular, low-amplitude magnetic highs and lows that are isolated with considerable difficulty from other anomalies of greater amplitude adjoining them.Mineralization took place in a near-surface environment along concurrently active distentional faults, and both the faulting and mineralization apparently were related to emplacement of the underlying intrusion. Ore was deposited largely along open fractures near the zone where ascending and descending solutions mixed. Most known ore is in the zone just outside the topographic wall of the Creede caldera near where faults cutting the rigid, brittle, and impervious volcanic units intersected the water-filled, marginal, coarse-clastic facies of the sedimentary Creede Formation in the moat of the caldera.
Bronze Age Arrows from Norwegian Alpine Snow Patches

The number of archaeological finds recovered from alpine snow patches in central Norway has increased dramatically during the last decade. In this article, eight Bronze Age (1800–500 B.C.) arrows are presented in detail. The arrows are of great interest to our understanding of Bronze Age archery in general. The finds include two arrows with projectiles made from the freshwater mussel Margaritifera margaritifera, as well as two reindeer antler arrows. These finds are further evidence of the fact that artifacts emerging from melting snow patches in central Norway are getting steadily older. Some contextual observations specific to snow patch sites in a reduced state due to extreme melting are also highlighted.
QoS Routing in Wireless Mesh Networks with Cognitive Radios

In this paper, we study QoS routing in wireless mesh networks with cognitive radios, which involves route selection, channel allocation and scheduling. It turns out to be a hard problem because of the impact of interference and channel heterogeneity. We formally model it as an optimization problem and present an integer linear programming (ILP) formulation to provide optimal solutions. We then present a distributed routing protocol which can select a route and allocate resources for a connection request to satisfy its end-to-end bandwidth requirement. NS2 based simulation results show the performance given by our protocol is close to that of the optimal solution.
Mouse Pancreatic-Cells Exhibit Preserved Glucose Competence After Disruption of the Glucagon-Like Peptide-1 Receptor G e n e

Previous work suggested that glucagon-like peptide 1 (GLP-1) can acutely regulate insulin secretion in two ways, 1) by acting as an incretin, causing amplification of glucose-induced insulin release when glucose is given orally as opposed to intravenous glucose injection; and 2) by keeping the -cell population in a glucosecompetent state. The observation that mice with homozygous disruption of the GLP-1 receptor gene are diabetic with a diminished incretin response to glucose underlines the first function in vivo. Isolated islets of Langerhans from GLP-1 receptor –/– mice were studied to assess the second function in vitro. Absence of pancreatic GLP-1 receptor function was observed in G L P 1 receptor –/– mice, as exemplified by loss of [ 2 I ] G L P 1 binding to pancreatic islets in situ and by the lack of GLP-1 potentiation of glucose-induced insulin secretion from perifused islets. Acute glucose competence of the -cells, assessed by perifusing islets with stepwise increases of the medium glucose concentration, was well preserved in GLP-1 receptor –/– islets in terms of insulin secretion. Furthermore, neither islet nor total pancreatic insulin content was significantly changed in the GLP-1 receptor –/– mice when compared with ageand sex-matched controls. In conclusion, mouse islets exhibit preserved insulin storage capacity and glucosedependent insulin secretion despite the loss of functional GLP-1 receptors. The results demonstrate that the glucose responsiveness of islet -cells is well preserved in the absence of GLP-1 receptor signaling. D i a b e t e s 47:646–652, 1998