Miracle-dz/UniFAR-FTUs huggingface dataset:
The new National Tuberculosis Control Programme in Israel, a country of high immigration.

SETTING Israel has implemented a new tuberculosis (TB) control programme in response to the rise in the incidence of tuberculosis due to immigration in the last decade. It complies with World Health Organization guidelines, and also includes specific measures addressing the needs of immigrants. We describe the new programme and compare the outcome of treatment prior and after its realisation. METHODS Each component of the new strategy was scrutinised, aspects that did not function well were identified and how we contended with these issues is described. Analysis of outcome of treatment was according to WHO/IUATLD definitions. RESULTS Better and clearer organisation of TB treatment in all its aspects, including cultural sensitivity, has been obtained. Compliance improved from less than 27% for successful outcome before the new programme to more than 75% after. In addition to the improvement in completion rates, the universal use of directly observed treatment has ensured enhanced adherence. CONCLUSION Using legislative, administrative and budgetary measures, as well as clinical guidelines published by the Ministry of Health, the TB infrastructure in Israel has been successfully reorganised. The decision to do so was not only clinically and organisationally justifiable, it is also economically viable.
Deconstructing (and reconstructing) cell migration

An overriding objective in cell biology is to be able to relate properties of particular molecular components to cell behavioral functions and even physiology. In the “traditional” mode of molecular cell biology, this objective has been tackled on a molecule‐by‐molecule basis, and in the “future” mode sometimes termed “functional genomics,” it might be attacked in a high‐throughput, parallel manner. Regardless of the manner of approach, the relationship between molecular‐level properties and cell‐level function is exceedingly difficult to elucidate because of the large number of relevant components involved, their high degree of interconnectedness, and the inescapable fact that they operate as physico‐chemical entities—according to the laws of kinetics and mechanics—in space and time within the cell. Cell migration is a prominent representative example of such a cell behavioral function that requires increased understanding for both scientific and technological advance. This article presents a framework, derived from an engineering perspective regarding complex systems, intended to aid in developing improved understanding of how properties of molecular components influence the function of cell migration. That is, cell population migration behavior can be deconstructed as follows: first in terms of a mathematical model comprising cell population parameters (random motility, chemotaxis/haptotaxis, and chemokinesis/haptokinesis coefficients), which in turn depend on characteristics of individual cell paths that can be analyzed in terms of a mathematical model comprising individual cell parameters (translocation speed, directional persistence time, chemotactic/haptotactic index), which in turn depend on cell‐level physical processes underlying motility (membrane extension and retraction, cell/substratum adhesion, cell contractile force, front‐vs.‐rear asymmetry), which in turn depend on molecular‐level properties of the plethora of components involved in governance and regulation of these processes. Hence, the influence of any molecular component on cell population migration can be understood by reconstructing these relationships from the molecular level to the physical process level to the individual cell path level to the cell population distribution level. This approach requires combining experimental, theoretical, and computational methodologies from molecular biology, biochemistry, biophysics, and bioengineering. Micros. Res. Tech. 43:358–368, 1998. © 1998 Wiley‐Liss, Inc.
CmWRKY15 Facilitates Alternaria tenuissima Infection of Chrysanthemum

Abscisic acid (ABA) has an important role in the responses of plants to pathogens due to its ability to induce stomatal closure and interact with salicylic acid (SA) and jasmonic acid (JA). WRKY transcription factors serve as antagonistic or synergistic regulators in the response of plants to a variety of pathogens. Here, we demonstrated that CmWRKY15, a group IIa WRKY family member, was not transcriptionally activated in yeast cells. Subcellular localization experiments in which onion epidermal cells were transiently transfected with CmWRKY15 indicated that CmWRKY15 localized to the nucleus in vivo. The expression of CmWRKY15 could be markedly induced by the presence of Alternaria tenuissima inoculum in chrysanthemum. Furthermore, the disease severity index (DSI) data of CmWRKY15-overexpressing plants indicated that CmWRKY15 overexpression enhanced the susceptibility of chrysanthemum to A. tenuissima infection compared to controls. To illustrate the mechanisms by which CmWRKY15 regulates the response to A. tenuissima inoculation, the expression levels of ABA-responsive and ABA signaling genes, such as ABF4, ABI4, ABI5, MYB2, RAB18, DREB1A, DREB2A, PYL2, PP2C, RCAR1, SnRK2.2, SnRK2.3, NCED3A, NCED3B, GTG1, AKT1, AKT2, KAT1, KAT2, and KC1were compared between transgenic plants and controls. In summary, our data suggest that CmWRKY15 might facilitate A. tenuissima infection by antagonistically regulating the expression of ABA-responsive genes and genes involved in ABA signaling, either directly or indirectly.
Ceramide-platform formation and -induced biophysical changes in a fluid phospholipid membrane

To understand the formation and properties of ceramide-enriched domains in cell membranes, the biophysical properties of the binary system palmitoyloleoylphosphatidylcholine (POPC)/palmitoylceramide were thoroughly characterized. Diverse fluorescent probes and parameters were necessary to unravel the complexity of this apparently simple system. For the first time, a complete phase diagram is reported, characterizing the lamellar phases of these mixtures, and providing a quantitative framework integrating biophysical and biological studies. The diagram suggests that in resting cells no ceramide domains exist, but upon apoptotic stimuli, platforms may form. Moreover, our data show that 2 mol% of Cer strongly affects the POPC fluid matrix, suggesting that a small increase in Cer levels can significantly affect cell membrane properties. In this work, we also show that Cer domains, formed in conditions similar to physiological, are extremely ordered and rigid. The domains composition is estimated from the phase diagram and their large size was concluded from fluorescence resonance energy transfer. Dynamic light scattering and electron microscopy were used to characterize the system morphology, which is highly dependent on ceramide content and includes vesiculation and tubular structure formation.
Purification of a mouse nuclear factor that binds to both the A and B cores of the polyomavirus enhancer

We have previously identified a protein factor, PEBP2 (polyomavirus enhancer-binding protein), in the nuclear extract from mouse NIH 3T3 cells which binds to the sequence motif, PEA2, located within the polyomavirus enhancer A element. Upon cellular transformation with activated oncogene c-Ha-ras, this factor frequently undergoes drastic molecular modifications into an altered form having a considerably reduced molecular size. In this study, the altered form, PEBP3, was purified to near homogeneity. The purified PEBP3 comprised two sets of families of polypeptides, alpha-1 to alpha-4 and beta-1 to beta-2, which were 30 to 35 kilodaltons and 20 to 25 kilodaltons in size, respectively. Both kinds of polypeptides possessed DNA-binding activities with exactly the same sequence specificity. Individual alpha or beta polypeptides complexed with DNA showed faster gel mobilities than did PEBP3. However, the original gel retardation pattern was restored when alpha and beta polypeptides were mixed together in any arbitrary pair. These observation along with the results of UV- and chemical-cross-linking studies led us to conclude that PEBP3 is a heterodimer of alpha and beta subunits, potentially having a divalent DNA-binding activity. Furthermore, PEBP3 was found to bind a second, hitherto-unnoticed site of the polyomavirus enhancer that is located within the B element and coincides with the sequence previously known as the simian virus 40 enhancer core homology. From comparison of this and the original binding sites, the consensus sequence for PEBP3 was defined to be PuACCPuCA. These findings provided new insights into the biological significance of PEBP3 and PEBP2.
Changes in Normal Force During Passive Dynamic Touch: Contact Mechanics and Perception

Using a force-controlled robotic platform, we investigated the contact mechanics and psychophysical responses induced by negative and positive modulations in normal force during passive dynamic touch. In the natural state of the finger, the applied normal force modulation induces a correlated change in the tangential force. In a second condition, we applied talcum powder to the fingerpad, which induced a significant modification in the slope of the correlated tangential change. In both conditions, the same ten participants had to detect the interval that contained a decrease or an increase in the pre-stimulation normal force of 1 N. In the natural state, the 75% just noticeable difference for this task was found to be a ratio of 0.19 and 0.18 for decreases and increases, respectively. With talcum powder on the fingerpad, the normal force thresholds remained stable, following the Weber law of constant just noticeable differences, while the tangential force thresholds changed in the same way as the correlation slopes. This result suggests that participants predominantly relied on the normal force changes to perform the detection task. In addition, participants were asked to report whether the force decreased or increased. Their performance was generally poor at this second task even for above-threshold changes. However, their accuracy slightly improved with the talcum powder, which might be due to the reduced finger-surface friction.
Interleukin-4 and 13 induce the expression and release of monocyte chemoattractant protein 1, interleukin-6 and stem cell factor from human detrusor smooth muscle cells: synergy with interleukin-1beta and tumor necrosis factor-alpha.

PURPOSE Interstitial cystitis is characterized by an increased number of activated MCs in the detrusor muscle. However, to our knowledge the factors that influence the anatomical relationship between MCs and HDSMCs are unknown. MCP-1, IL-6 and SCF have a critical role in the regulation of MC development, signaling and function. We investigated whether HDSMCs are capable of expressing and releasing MCP-1, IL-6 and SCF in response to IL-4, IL-13, IL-1beta and tumor necrosis factor-alpha. MATERIALS AND METHODS HDSMCs were isolated and cultured using an explant technique. Protein expression, and the secretion of MCP-1, IL-6 and SCF were assayed by semiquantitative reverse transcriptase-polymerase chain reaction and specific enzyme-linked immunosorbent assay. RESULTS Unstimulated cells released low amounts of MCP-1, IL-6 and SCF. In cells stimulated by IL-4 MCP-1 mRNA was up-regulated by a mean factor +/- SD of 3.5 +/- 1.3, IL-6 mRNA was up-regulated by 3.8 +/- 1.3, the soluble form of SCF was up-regulated by 3.2 +/- 0.6 and the membrane bound form of SCF was up-regulated by 7.9 +/- 5.6. For IL-13 stimulated cells the values were 2.6 +/- 1.5, 3.6 +/- 2.1, 2.9 +/- 1.6 and 5.7 +/- 3.7, respectively. Soluble SCF mRNA expression was 5 times higher than the expression of mSCF mRNA. IL-4 and IL-13 given separately stimulated MCP-1, IL-6 and SCF secretion in a concentration (0.01 to 100 ng/ml) and time (0 to 24 hours) dependent manner. Furthermore, IL-1beta and tumor necrosis factor-alpha alone induced significant release of MCP-1, IL-6 and SCF but in combination with IL-4 or IL-13 it induced greater secretion of MCP-1, IL-6 and SCF. CONCLUSIONS To our knowledge these findings demonstrate for the first time that HDSMCs express and release MCP-1 and IL-6, and show relatively high expression of soluble SCF. This supports our hypothesis that HDSMCs may have an active role by orchestrating the local inflammatory response in the bladder wall with possible implications for the pathophysiology of detrusor mastocytosis.
Comparative Behavioral Pharmacology of Three Pyrrolidine-Containing Synthetic Cathinone Derivatives

Synthetic cathinones, often sold as “bath salts,” are a popular class of recreational drugs used as quasi-legal alternatives to cocaine, methamphetamine, and methylenedioxymethamphetamine. The increased prevalence and health consequences of synthetic cathinone use has prompted regulatory agencies to control a number of these compounds; however, a broad class of analogous compounds known as the second-generation cathinones has been brought to the market to take the place of the banned synthetic cathinone derivatives. The current study aims to characterize the behavioral pharmacology of three pyrrolidinylated second-generation cathinones: 4-methyl-α-pyrrolidinopropiophenone (4ʹ-MePPP), α-pyrrolidinopropiobutiophenone (α-PBP), and α-pyrrolidinopentiophenone (α-PVP). Locomotor activity was tested in mice over an 8-hour period. The discriminative stimulus effects of these compounds were tested in rats trained to discriminate either cocaine or methamphetamine. The rewarding effects of these drugs were assessed in mice using conditioned place preference. Both α-PBP and α-PVP produced long-lasting increases in locomotor activity across a wide range of doses, whereas 4ʹ-MePPP produced locomotor stimulation only at 30 mg/kg. Both α-PBP and α-PVP fully substituted for the discriminative stimulus effects of both cocaine and methamphetamine, whereas 4ʹ-MePPP substituted fully for the discriminative stimulus effects of methamphetamine only. Both α-PBP and α-PVP produced conditioned place preference in an inverted U-shaped dose effect, whereas 4ʹ-MePPP did not produce conditioned place preference. These findings suggest that α-PBP and α-PVP are likely to be recreationally used and have potential for addiction and abuse, but 4ʹ-MePPP may not.
A Phase I, Dose-Escalation Study of the Multitargeted Receptor Tyrosine Kinase Inhibitor, Golvatinib, in Patients with Advanced Solid Tumors

Purpose: Receptor tyrosine kinases c-Met and Ron transduce signals regulating cell migration and matrix invasion. This phase I dose-escalation trial tested golvatinib, a highly potent, small-molecule, ATP-competitive inhibitor of c-Met and multiple members of the Eph receptor family plus c-Kit and Ron. Experimental Design: Patients with advanced solid tumors received golvatinib orally, once daily, continuously. Using a “3+3” design, dosing started at 100 mg once daily, escalating to the maximum tolerated dose (MTD) defined by dose-limiting toxicities. Pharmacokinetic, pharmacodynamic, and preliminary antitumor activity was assessed during dose escalation and in a MTD expansion cohort. Results: Thirty-four patients were treated at six dose levels. The MTD was determined as 400 mg once daily. Three dose-limiting toxicities were observed: grade 3 increased γ-glutamyltransferase and alkaline phosphatase (200 mg), repeated grade 2 fatigue, and grade 3 fatigue (50.0%). Frequent treatment-related adverse events (with incidence >10%) included diarrhea (58.8%), nausea (50%), vomiting (44.1%), fatigue (41.2%), decreased appetite (32.4%), elevated alanine aminotransferase (32.4%), elevated aspartate aminotransferase (20.6%), dry skin (11.8%), and dysgeusia (11.8%). Best overall response was stable disease (median duration 85 days, range 85–237). Pharmacokinetics demonstrated high variability, although maximum plasma concentration and area under the plasma concentration–time curve increased with dose. Soluble urokinase-type plasminogen activator receptor, VEGFR2, c-Met, and angiopoietin-2 levels increased after dose. Posttreatment decrease in either p-c-Met or p-ERK was observed in 3 of 4 paired biopsies at MTD. Conclusions: Golvatinib at the MTD of 400 mg once daily was well tolerated with pharmacodynamic evidence of c-Met target modulation. Clin Cancer Res; 20(24); 6284–94. ©2014 AACR.
Potential of crops uncommon to alabama for management of root-knot and soybean cyst nematodes.

Vigna unguiculata, Cassia fasiculata, and Sesamum indicum did not support Meloidogyne arenaria, M. incognita, or Heterodera glycines race 4 in greenhouse studies with soils from peanut and soybean fields. Fagopyron eseulentum, Cyamopsis tetragonoloba, and Cucurbita pepo were hosts to the two Meloidogyne spp. but were nonhosts to H. glycines. Meloidogyne arenaria and M. incognita galled but reproduced poorly in the roots of three types of Amaranthus cruentus, and low densities of these two Meloidogyne spp. (< 10 second-stage juveniles/100 cm(3) soil) occurred in soil cultivated with this crop. In a field study no juveniles of M. arenaria determined at peanut harvest were recovered from plots with Ricinus communis, Gossypium hirsutum, Aeschynomene americana, C. fasiculata, or S. indicum. Peanut plots averaged 120 juveniles/100 cm(3) soil. Application of aldicarb (12 kg a.i./ha broadcast) in peanut resulted in an average of 27 juveniles/100 cm(3) soil. Several crops were as effective as aldicarb treatment for reducing soil juvenile population densities of M. arenaria.
Differential patterns of insulin‐like growth factor‐I and ‐II mRNA expression in medulloblastoma

Insulin‐like growth factors (IGFs) play an important role in tumour growth and development. We hypothesized that this is also the case for medulloblastomas, which are highly malignant cerebellar brain tumours usually occurring in children. In these tumours the expression patterns of IGF‐I and ‐II mRNA were studied. Tumour specimens obtained from 12 children and two adults at diagnosis were hybridized in situ with digoxigenin‐labelled cRNA probes for hIGF‐I and hIGF‐II mRNAs. In all cases, tumour cells showed abundant expression of IGF‐I mRNA. Nine of the 14 tumours showed variable but significant IGF‐II expression. In these tumours, the hybridization signal almost exclusively colocalized with a subpopulation of Ki‐M1P positive cells that were identified as ramified microglia (RM) cells. In the five tumours without IGF‐II expression, microglia/brain macrophages with a more rounded amoeboid‐like morphology predominated. RM cells in normal cerebellar tissues, residing abundantly in areas of the white and, to a less extent, in the grey matter, were IGF‐II mRNA‐negative. These RM cells showed a thinner and more extensively branched appearance and were more evenly distributed than those encountered in medulloblastoma. Probably, during the transformation from the resting ramified towards the amoeboid morphology (or vice versa) IGF‐II mRNA expression is only temporarily induced. The physiological meaning of the induction of IGF‐II mRNA expression by these cells in medulloblastoma remains unclear but any IGF‐II peptide synthesized could exert unfavourable mitogenic and antiapoptotic effects on adjacent tumour cells. However, in this relatively small number of cases we could not find any indications for a relationship between clinical characteristics of the various cases and the extent of IGF‐II mRNA expression.
Multiattribute Decisionmaking Using a Fuzzy Heuristic Approach

Multiattribute decisionaking (DM) is treated as a special kind of structured human problem solving. Emphasis is placed on the use of the available knowledge about utilities, which is obtained by combining heuristics and traditional aggregation methods. In this way, the problem of partial utilities and their interdependence may be solved. A fuzzy approach to DM is described, incorporating linguistic variables, relations, and algorithms. It is summarized in a formal model and illustrated by an example.
Accurate segmentation for right ventricles based on Multi-Atlas

A new image registration and fusion method based on Multi-Atlas was proposed in this thesis. It treats all Atlas images as a series of data nodes and clusters them through massage propagation to obtain different exemplars, then uses these exemplars to participate in the normal atlas segmentation, orders them based on the dice similar coefficient, iterate, gets the final accurate segmentation. In term of registration, three-step registration is adopted: first rigid registration, then affine registration and B spline registration. Besides, fusion strategy called Joint Label Fusion is used, which is first used for right ventricle. The method makes split operation by registration and fusion method based on Multi-Atlas image, corrects a Multi-Atlas label fusion error caused by the registration, thereby optimizes segmentation result.
Attenuated Total Reflection Surface-Enhanced Infrared Absorption Spectroscopy of Carboxyl Terminated Self-Assembled Monolayers on Gold

A new recipe for surface-enhanced infrared absorption (SEIRA) active island Au films with improved adhesion in aqueous solution, low resistivity, and enhancement of the infrared (IR) absorption of about 300 was developed. The Au films prepared were utilized in studies of the ionization of self-assembled monolayers of 11-mercaptoundecanoic acid in Na2SO4 aqueous solutions by attenuated total reflection surface-enhanced infrared absorption (ATR-SEIRA) spectroscopy. It was found that the carboxyl end groups of the self-assembled monolayer turn into carboxylate anions on going from anodic to cathodic potentials or from acidic to alkaline pH. The water molecules close to the self-assembled monolayer in acidic solutions or at anodic potentials are preferentially aligned with their dipole moments parallel to the interface. This type of alignment can be ascribed to the dipole–dipole interaction between the carboxyl groups and the water molecules. On the other hand, in alkaline solutions or at cathodic potentials the structure of water close to the self-assembled monolayer is essentially bulk-like, with randomly oriented water molecules. This observation suggests that in alkaline solutions or at cathodic potentials the charge of the carboxylate anions is almost completely compensated for by strongly adsorbed counter cations. As a result, the electric field close to the surface of the ionized self-assembled monolayer is weak and has little influence on the orientation and hydrogen bonding of the water molecules.