The activity of nine peptide deformylase (PDF) inhibitors undergoing clinical evaluation were compared with co-amoxiclav, levofloxacin, moxifloxacin, erythromycin and telithromycin against a range of respiratory and skin pathogens (n=166). The PDF inhibitor showed good activity against Streptococcus pneumoniae, Moxarella catarrhalis, Group A streptococci and Staphylococcus aureus irrespective of beta-lactam or fluoroquinolone susceptibility. Against Haemophilus influenzae, MIC(90) values were generally higher. BB-88488 was the most active compound. Overall these data suggest that PDF inhibitors are an interesting new class of antimicrobial worthy of further investigation in the treatment of respiratory tract and skin infections.

The instantaneous structure of the cyanide-bridged negative thermal expansion (NTE) material Zn(CN)(2) has been probed using atomic pair distribution function (PDF) analysis of high energy X-ray scattering data (100-400 K). The temperature dependence of the atomic separations extracted from the PDFs indicates an increase of the average transverse displacement of the cyanide bridge from the line connecting the Zn(II) centers with increasing temperature. This allows the contraction of non-nearest-neighbor Zn...Zn' and Zn...C/N distances despite the observed expansion of the individual direct Zn-C/N and C-N bonds. Thus, this analysis provides definitive structural confirmation that an increase in the average displacement of bridging atoms is the origin of the NTE behavior. The lattice parameters reveal a slight reduction in the NTE behavior at high temperature from a minimum coefficient of thermal expansion (alpha = dl/ldT) of -19.8 x 10(-6) K(-1) below 180 K, which is attributed to interaction between the doubly interpenetrated frameworks that comprise the structure.

In the Visible Korean project, serially sectioned images of the pelvis were made from a female cadaver. Outlines of significant structures in the sectioned images were drawn and stacked to build surface models. To improve the accessibility and informational content of these data, a five-step process was designed and implemented. First, 154 pelvic structures were outlined with additional surface reconstruction to prepare the image data. Second, the sectioned and outlined images (in a browsing software) as well as the surface models (in a PDF file) were placed on the Visible Korean homepage in a readily-accessible format. Third, all image data were visualized with interactive elements to stimulate creative learning. Fourth, two-dimensional (2D) images and three-dimensional (3D) models were superimposed on one another to provide context and spatial information for students viewing these data. Fifth, images were designed such that structure names would be shown when the mouse pointer hovered over the 2D images or the 3D models. The state-of-the-art sectioned images, outlined images, and surface models, arranged and systematized as described in this study, will aid students in understanding the anatomy of female pelvis. The graphic data accompanied by corresponding magnetic resonance images and computed tomographs are expected to promote the production of 3D simulators for clinical practice.

Polymerase chain reaction (PCR) is an important diagnostic tool for the amplification of DNA. The PCR process can be treated as a problem in biochemical engineering. This study focuses on the development of a mathematical model of the polymerase chain reaction. The PCR process consists of three steps: denaturation of target DNA, annealing of sequence-specific oligonucleotide primers and the enzyme-catalyzed elongation of the annealed complex (primer:DNA:polymerase). The denaturation step separates the double strands of DNA; this model assumes denaturation is complete. The annealing step describes the formation of a primer-fragment complex followed by the attachment of the polymerase to form a ternary complex. This step is complicated by competitive annealing between primers and incomplete fragments including primer-primer reactions. The elongation step is modeled by a stochastic method. Species that compete during the elongation step are deoxynucleotide triphosphates dCTP, dATP, dTTP, dGTP, dUTP, and pyrophosphate. Thermal deamination of dCTP to form dUTP is included in the model. The probability for a species to arrive at the active site is based on its molar fraction. The number of random insertion events depends on the average processing speed of the polymerase and the elongation time of the simulation. The numerical stochastic experiment is repeated a sufficient number of times to construct a probability density distribution (PDF). The moment of the PDF and the annealing step products provide the product distribution at the end of the elongation step. The overall yield is compared to six experimental values of the yield. In all cases the comparisons are very good.

The time course of the concentration of radiocalcium was studied in the serum, skeleton, pelt, muscles, and pooled internal organs of 10-day-old rats. Within 10 hours of injection, the specific activity of the tissue groups exceeded the specific activity of the serum and remained above it during the period studied (120 hours). Chemical and autoradiographic analyses showed how rapidly most of the injected Ca(45) found its way into the skeleton. A model was constructed with the assumption that the skeleton constitutes an essentially irreversible reservoir for the tracer in a multicompartment system in which the blood is the central or feeding compartment. The rate of transfer of the tracer from the soft tissue compartments to the serum was calculated from the equation See PDF for Equation in which C = concentration in serum (expressed as a series of exponential terms) C' = concentration in a given soft tissue Substitution in the integrated form of this equation yielded equations which had the major properties of the empirical equations fitted to the experimental points. The relative order of transfer constants (k'(-1)) was: organs>>/= pelt>> muscle.

The neuropeptide pigment-dispersing factor (PDF) plays an essential role in the circadian clock of the fruit fly Drosophila melanogaster, but many details of PDF signaling in the clock network are still unknown. We tried to interfere with PDF signaling by blocking the GTPase Shibire in PDF neurons. Shibire is an ortholog of the mammalian Dynamins and is essential for endocytosis of clathrin-coated vesicles at the plasma membrane. Such endocytosis is used for neurotransmitter reuptake by presynaptic neurons, which is a prerequisite of synaptic vesicle recycling, and receptor-mediated endocytosis in the postsynaptic neuron, which leads to signal termination. By blocking Shibire function via overexpression of a dominant negative mutant form of Shibire in PDF neurons, we slowed down the behavioral rhythm by 3 h. This effect was absent in PDF receptor null mutants, indicating that we interfered with PDF receptor-mediated endocytosis. Because we obtained similar behavioral phenotypes by increasing the PDF level in regions close to PDF neurons, we conclude that blocking Shibire did prolong PDF signaling in the neurons that respond to PDF. Obviously, terminating the PDF signaling via receptor-mediated endocytosis is a crucial step in determining the period of behavioral rhythms.

One of the main design challenges in wireless sensor networks (WSNs) is achieving a high-data-rate transmission for individual sensor devices. The high altitude platform (HAP) is an important communication relay platform for WSNs and next-generation wireless networks. Multiple-input multiple-output (MIMO) techniques provide the diversity and multiplexing gain, which can improve the network performance effectively. In this paper, a virtual MIMO (V-MIMO) model is proposed by networking multiple HAPs with the concept of multiple assets in view (MAV). In a shadowed Rician fading channel, the diversity performance is investigated. The probability density function (PDF) and cumulative distribution function (CDF) of the received signal-to-noise ratio (SNR) are derived. In addition, the average symbol error rate (ASER) with BPSK and QPSK is given for the V-MIMO model. The system capacity is studied for both perfect channel state information (CSI) and unknown CSI individually. The ergodic capacity with various SNR and Rician factors for different network configurations is also analyzed. The simulation results validate the effectiveness of the performance analysis. It is shown that the performance of the HAPs network in WSNs can be significantly improved by utilizing the MAV to achieve overlapping coverage, with the help of the V-MIMO techniques.

Pregnancy complicated with leukemia is rare. Validated data, out of which conclusions may be drawn regarding the management of pregnancy with leukemia are sparse. We report 5 cases of leukemia diagnosed during pregnancy with an overview of published literature (Ref. 19). Full Text (Free, PDF) www.bmj.sk.

We consider the task of independent component analysis when the independent sources are known to be nonnegative and well-grounded, so that they have a nonzero probability density function (pdf) in the region of zero. We propose the use of a "nonnegative principal component analysis (nonnegative PCA)" algorithm, which is a special case of the nonlinear PCA algorithm, but with a rectification nonlinearity, and we conjecture that this algorithm will find such nonnegative well-grounded independent sources, under reasonable initial conditions. While the algorithm has proved difficult to analyze in the general case, we give some analytical results that are consistent with this conjecture and some numerical simulations that illustrate its operation.

This study presents a new automatic spike sorting method based on feature extraction by Laplacian eigenmaps combined with k-means clustering. The performance of the proposed method was compared against previously reported algorithms such as principal component analysis (PCA) and amplitude-based feature extraction. Two types of classifier (namely k-means and classification expectation-maximization) were incorporated within the spike sorting algorithms, in order to find a suitable classifier for the feature sets. Simulated data sets and in-vivo tetrode multichannel recordings were employed to assess the performance of the spike sorting algorithms. The results show that the proposed algorithm yields significantly improved performance with mean sorting accuracy of 73% and sorting error of 10% compared to PCA which combined with k-means had a sorting accuracy of 58% and sorting error of 10%.A correction was made to this article on 22 February 2011. The spacing of the title was amended on the abstract page. No changes were made to the article PDF and the print version was unaffected.

We study non-Gaussian probability density functions (PDF's) of multiplicative log-normal models in which the multiplication of Gaussian and log-normally distributed random variables is considered. To describe the PDF of the velocity difference between two points in fully developed turbulent flows, the non-Gaussian PDF model was originally introduced by Castaing [Physica D 46, 177 (1990)]. In practical applications, an experimental PDF is approximated with Castaing's model by tuning a single non-Gaussian parameter, which corresponds to the logarithmic variance of the log-normally distributed variable in the model. In this paper, we propose an estimator of the non-Gaussian parameter based on the q th order absolute moments. To test the estimator, we introduce two types of stochastic processes within the framework of the multiplicative log-normal model. One is a sequence of independent and identically distributed random variables. The other is a log-normal cascade-type multiplicative process. By analyzing the numerically generated time series, we demonstrate that the estimator can reliably determine the theoretical value of the non-Gaussian parameter. Scale dependence of the non-Gaussian parameter in multiplicative log-normal models is also studied, both analytically and numerically. As an application of the estimator, we demonstrate that non-Gaussian PDF's observed in the S&P500 index fluctuations are well described by the multiplicative log-normal model.

Pigment-dispersing factor (PDF) was recently reported to be a principal circadian neuromodulator involved in transmitting circadian rhythms of daily locomotion in insects. In Drosophila, PDF functions in some of the neurons expressing the clock genes period, timeless, Clock, and cycle, and those clock genes in turn regulate pdf gene expression. In the present study, we cloned a cDNA encoding PDF in the brain of a nocturnal insect, the cricket Gryllus bimaculatus, and found that an isolated clone (310 bp) codes for an extraordinarily short precursor protein with no definite signal sequence, but a nuclear localization signal (NLS)-like sequence instead. The cricket PDF exhibits high sequence identity (78-94%) and similarity (89-100%) to insect PDFs and also to crustacean beta-PDH peptides. In the optic lobes of G. bimaculatus there are PDF-immunoreactive neurons in both the medulla and lamina neuropiles. Among the strongly immunoreactive lamina PDF neurons, on electron microscopy we identified cells exhibiting distinct staining that is not only cytoplasmic but also nuclear. When GFP-fused PDF precursor proteins were expressed in COS-7 cells, distinct translocation of the fusion protein into the nucleus was observed. This is the first finding of PDF peptide in the nucleus, which suggests a fundamental role of PDF peptide per se in the circadian clock system.

BACKGROUND

Infra-red photocoagulation is used as an instrumental treatment for bleeding hemorrhoids. During this procedure the tissue is coagulated by infrared radiation. For treatment, mechanical pressure and radiation energy are applied simultaneously to ablate the blood supply to the hemorrhoidal mass.

METHODS

This study describes the results of infrared photocoagulation of Grade I and II bleeding hemorrhoids with 5-year follow-up.

RESULTS

300 patients treated by infrared coagulation were followed up for a period of 60 months. 39 patients had persistence or recurrence of bleeding. Other post procedure complaints included post defecation discomfort, pruritus and discharge per anus. No patient had any septic or infective complication.

CONCLUSIONS

This retrospective study shows that infra red coagulation for hemorrhoids in early stages could be an easy and effective alternative to conventional methods as it is quick, painless and safe. The procedure can be repeated in case of recurrence and should be considered as an alternative to conventional treatment in hemorrhoids (Ref. 30). Full Text (Free, PDF) www.bmj.sk.

We present three examples of interactive, 3D volume rendering models embedded in a PDF publication. The examples are drawn from three different morphological methods - confocal microscopy, serial sectioning and microcomputed tomography - performed on members of the phylum Mollusca. A description of the entire technical procedure from specimen preparation to embedding of the visual model including 3D labels in the document is provided. For comparison, volume rendering with standard visualization software, and surface rendering incorporated in the 3D PDF figures, are provided. The principal advantages and disadvantages of the techniques and models are discussed. Volume rendering for serial sections is relatively work-intensive, while confocal data have limitations in terms of 3D presentation. Volume renderings are normally downsampled in resolution to achieve a reasonable PDF file size, however intentional information is largely retained. We conclude that volume rendering of 3D data sets is a valuable technique and should become standard in PDF versions of biomedical publications.

I consider the effect on MSTW partons distribution functions (PDFs) due to changes in the choices of theoretical procedure used in the fit. I first consider using the 3-flavour fixed flavour number scheme instead of the standard general mass variable flavour number scheme used in the MSTW analysis. This results in the light quarks increasing at all relatively small [Formula: see text] values, the gluon distribution becoming smaller at high values of [Formula: see text] and larger at small [Formula: see text], the preferred value of the coupling constant [Formula: see text] falling, particularly at NNLO, and the fit quality deteriorates. I also consider lowering the kinematic cut on [Formula: see text] for DIS data and simultaneously introducing higher twist terms which are fit to data. This results in much smaller effects on both PDFs and [Formula: see text] than the scheme change, except for quarks at very high [Formula: see text]. I show that the structure function one obtains from a fixed input set of PDFs using the fixed flavour scheme and variable flavour scheme differ significantly for [Formula: see text] at high [Formula: see text], and that this is due to the fact that in the fixed flavour scheme there is a slow convergence of large logarithmic terms of the form [Formula: see text] relevant for this regime. I conclude that some of the most significant differences in PDF sets are largely due to the choice of flavour scheme used.

OBJECTIVE

It is often assumed that aging is accompanied by diverse and constant functional and cognitive decline, and it is therefore surprising that the well-being of older persons does not appear to decline in the same way. This study investigates longitudinally whether well-being in older persons changes due to Persistent Deterioration of Functioning (PDF).

METHODS

Data were collected in the context of the Longitudinal Aging Study Amsterdam (LASA). Conditions of PDF are persistent decline in cognitive functioning, physical functioning and increase in chronic diseases. Measurements of well-being included life satisfaction, positive affect, and valuation of life. T-tests were used to analyse mean difference scores for well-being, and univariate and multivariate regression analyses were performed to examine changes in three well-being outcomes in relation to PDF.

RESULTS

Cross-sectional analyses showed significant differences and associations between the two PDF subgroups and non- PDF for well-being at T3. In longitudinal analyses, we found significant decreases in and associations with wellbeing over time in respondents fulfilling one PDF condition (mild PDF). For respondents fulfilling two or more PDF conditions (severe PDF), longitudinally no significant associations were found.

CONCLUSIONS

Cognitive aspects of well-being (life satisfaction and valuation of life) and the affective element (positive affect) of well-being appear to be influenced negatively by mild PDF, whereas well-being does not seem to be diminished in persons with more severe PDF. This may be due to the ability to accept finally the inevitable situation of severe PDF.

OBJECTIVE

To determine the effect of glutathione S-transferases M1 and T1 polymorphisms on the risk of senile cataract among Egyptians.

BACKGROUND

The glutathione S-transferases (GSTs) are polymorphic enzymes that are important in the protection against oxidative damage.

METHODS

Using a multiplex polymerase chain reaction (PCR), GSTM1 and GSTT1 gene polymorphisms were evaluated in 53 Egyptians with senile cataract and in 73 healthy individuals of the control group.

RESULTS

The frequency of GSTM1-positive individuals among the senile cataract group was significantly higher than in controls. The risk among the GSTM1-positive individuals of developing senile cataract was even higher in females. It is also increased with combination of "GSTM1-positive and GSTT1-positive" genotypes. However the combination of "GSTM1-null, GSTT1-positive" was found to be protective (OR = 0.47; 95 % CI: 0.22-0.99; p = 0.045).

CONCLUSIONS

The GSTMI-positive genotype and the combined "GSTM1-positive/GSTT1-positive" genotype may be associated with an increased risk of development of senile cataract among Egyptians. However, the "GSTM1-null/GSTT1-positive" genotype was found to be protective. Therefore, when evaluating the role of a particular GST gene in disease susceptibility, the whole pattern of different biotransformation enzymes should be taken into account (Tab. 4, Fig. 1, Ref. 36). Full Text (Free, PDF) www.bmj.sk.

As a tension-free repair technique, Lichtenstein operation has gained great popularity worldwide during the last decade. Expert centres do this technique using local anaesthesia in nearly 95 % of cases. However, general anaesthesia is used in many hospitals, while regional anaesthesia is preferred in some centres. To date, no study has compared different types of anesthesia in respect of inflammatory response and oxidative stress specifically. The objective of this prospective study was to compare local, spinal and general types of anesthesia regarding their effects on inflammatory response and oxidative stress in Lichtenstein hernia repair. Lichtenstein hernia repair causes only a mild oxidative stress. While total WBC and neutrophil count responses fade away after 24 hours in patients who are operated under local anaesthesia, these changes in spinal and general types of anaesthesia cases stay valid at 24th hour. Spinal anaesthesia is seen to be more advantageous than local and general types of anaesthesia when C-reactive protein as an acute phase marker is considered. Total antioxidant status shows minor alterations in three types of anaesthesia, however, general anaesthesia seems to be the least reliable among them. Overall, local and spinal anaesthesia methods can be accepted as better alternatives in comparison with general anaesthesia in regard to oxidative stress (Tab. 2, Ref. 25). Full Text (Free, PDF) www.bmj.sk.

In the original version of Table 1 published online, upward arrows to indicate increased translocation of PAMPs were missing from the row entitled 'Translocation' for both the column on alcoholic liver disease and nonalcoholic fatty liver disease. This error has now been updated in the PDF and HTML version of the article.

Great efforts have been directed to the dissection of the cell-autonomous circadian oscillator in Drosophila. However, less information is available regarding how this oscillator controls rhythmic rest-activity cycles. We have identified a viable allele of roundabout, robo(hy), where the period of locomotor activity is shortened. From its role in axon-pathfinding, we anticipated developmental defects in clock-relevant structures. However, robo(hy) produced minor defects in the architecture of the circuits essential for rhythmic behaviour. ROBO's presence within the circadian circuit strengthened the possibility of a novel role for ROBO at this postdevelopmental stage. Genetic interactions between pdf (01) and robo(hy) suggest that ROBO could alter the communication within different clusters of the circadian network, thus impinging on two basic properties, periodicity and/or rhythmicity. Early translocation of PERIOD to the nucleus in robo(hy) pacemaker cells indicated that shortened activity rhythms were derived from alterations in the molecular oscillator. Herein we present a mutation affecting clock function associated with a molecule involved in circuit assembly and maintenance.

None of the procedures described serves by itself to differentiate streptococci of human and bovine origin with certainty, though each of them serves as a strong presumptive test. Most strains fall easily into the human or bovine group by all the tests. Eliminating these from consideration we have left certain irregular strains listed in Table VII. See PDF for Structure Taking all characters into consideration we are inclined to regard Strains J-E7, Cheese 1, and Cheese 2 as undoubtedly of bovine origin. Strain J-MJ also is representative of a group of streptococci which Jones has found in milk and which is being further studied by him. There remains Strain J-C65 which for the present must be regarded as of doubtful origin.

Cytokine-induced killer (CIK) cell therapy has recently been used as an adjuvant setting following resection of hepatocellular carcinoma (HCC), while its benefit remains unclear. This study aimed to evaluate the efficacy of adjuvant CIK application in solitary HCC patients undergoing curative resection with stratification of microvascular invasion (MVI).In total, specimens and data from 307 solitary HCC patients undergoing curative resection between January 2007 and December 2010 were included. Of these, 102 patients received CIK treatment after surgery (CIK group), whereas 205 patients did not (control group). Pathological evaluation was used to retrospectively determine MVI status. The CIK group had 60 MVI-negative and 42 MVI-positive patients, while the numbers in control group were 124 and 81. Kaplan-Meier and Cox regression analyses were used to validate possible effects of CIK treatment on disease free survival (DFS) and overall survival (OS) as appropriate.For all patients, the CIK group exhibited significantly higher OS than the control group (log-rank test; PDFS = 0.055, POS = 0.020). Further analysis based on MVI stratification showed that for patients with MVI, DFS and OS did not differ between the 2 groups (PDFS = 0.439, POS = 0.374). For patients without MVI, the CIK group exhibited better DFS and OS than the control group (PDFS = 0.042, POS = 0.007), and multivariate analyses demonstrated that CIK treatment was an independent prognostic factor both for DFS and OS.For solitary HCC, CIK cell therapy after curative resection improves DFS and OS for patients without MVI, but has no statistically significant survival benefit for patients with MVI.

A few types of peptidergic clock neurons have been identified in the fruitfly Drosophila, whereas in blowflies, only pigment-dispersing factor (PDF)-immunoreactive lateral ventral clock neurons (LN(v)s) have been described. In blowflies, but not Drosophila, a subset of these PDF-expressing neurons supplies axon branches to a region outside the synaptic layer of the lamina, the most peripheral optic lobe neuropil. In Drosophila, similar lamina processes are instead supplied by non-clock neurons (LMIo) that express myoinhibitory peptide (MIP). We have investigated the distribution of MIP-immunoreactive neurons in the visual system of the blowfly Calliphora vomitoria and found neurons resembling the three LMIos, but without processes to the lamina. In Calliphora, PDF-immunoreactive processes of LN(v)s in the lamina closely impinge on branching serotonin-immunoreactive axon terminations in the same region. We have also identified, in the blowfly, two types of putative clock neurons that label with an antiserum to ion-transport peptide (ITP). The presence of serotonin-immunoreactive neurons supplying processes to the lamina seems to be a conserved feature in dipteran flies. The morphology of the two types of ITP-immunoreactive clock neurons might also be conserved. However, peptidergic neurons with branches converging on the serotonin-immunoreactive neurons in the lamina are of different morphological types and express PDF in blowflies and MIP in Drosophila. The central circuitry of these PDF- and MIP-expressing neurons probably differs; consequently, whether their convergence on serotonergic neurons subserves similar functions in the two species is unclear.

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca²⁺ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca²⁺ baseline concentration and frequency of oscillating Ca²⁺ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca²⁺ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1-4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca²⁺ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K⁺ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K⁺ and Na⁺ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance.