Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacodynamic monitoring of BAY 43‐9006 (Sorafenib) in phase I clinical trials involving solid tumor and AML/MDS patients, using flow cytometry to monitor activation of the ERK pathway in peripheral blood cells

We previously reported a flow cytometry technique to monitor pharmacodynamic effects of the raf kinase inhibitor BAY 43‐9006 based on the ability of phorbol ester (PMA) to phosphorylate extracellular‐regulated kinase (ERK) in peripheral blood (Chow et al., Cytometry 2001;46:72–78). In this article, we describe its application to phase I trials of BAY 43‐9006 in solid tumor and AML/MDS patients.
γδ T Cells and dendritic cells in refractory Lyme arthritis

Lyme disease is a multisystem infection transmitted by tick vectors with an incidence of up to 300,000 individuals/yr in the United States. The primary treatments are oral or i.v. antibiotics. Despite treatment, some individuals do not recover and have prolonged symptoms affecting multiple organs, including the nervous system and connective tissues. Inflammatory arthritis is a common symptom associated with Lyme pathology. In the past decades, γδ T cells have emerged as candidates that contribute to the transition from innate to adaptive responses. These cells are also differentially regulated within the synovia of patients affected by RLA. Here, we review and discuss potential cellular mechanisms involving γδ T cells and DCs in RLA. TLR signaling and antigen processing and presentation will be the key concepts that we review in aid of understanding the impact of γδ T cells in RLA.
Factors affecting blind localization of a glass micropipette using a high-density microelectrode array

High-density microelectrode arrays (HDMEAs) provide the capability to measure extracellular electric potential from brain slices and dissociated cell cultures at high spatiotemporal resolution, which is attractive for neuroscience. Since the HDMEA enables to record the activity of single neurons at sub-cellular resolution, a combination with intracellular recording techniques, such as patch clamp, will allow for new in vitro experiments. Such combination technique requires precise localization of both the cell of interest and the glass micropipette (GM) with respect to the HDMEA. Here, we present a methodology to locate the three-dimensional (3D) position of a GM on the HDMEA without the use of an optical microscope. For the (x, y) position, the achieved accuracy is (±2μm, ±5μm), which is less than the electrode pitch of 18μm. For the z-position, the obtained accuracy is ±2μm for distances of 5-50μm between the GM tip and the HDMEA surface. We also observed that variations in size of GM tips and HDMEA electrodes have minimal effects on the blind localization performance. This approach shows the feasibility of automated navigation of a GM atop the HDMEA to patch a single cell in vitro.
Phrasal compounds in Turkish: Distinguishing citations from quotations

Abstract To date, studies of phrasal compounds, most of which are on Germanic languages, have been inconclusive with respect to whether the non-heads are phrases or quotations. In this paper, I present syntactic, semantic, and prosodic evidence from a typologically different language, Turkish, to distinguish between the two types. I will show that what look like equally complex constructions turn out to differ radically in complexity and in terms of their internal structure; phrases that are sensitive to syntax versus quotations which are not, and head-complement relations versus type-token relations. I further discuss the structural implications of having phrasal units within morphological units, arguing that this is a natural phenomenon within frameworks where the relation between morphology and syntax is bidirectional.
Geostatistics as a tool to study mite dispersion in physic nut plantations

Abstract Spatial distribution studies in pest management identify the locations where pest attacks on crops are most severe, enabling us to understand and predict the movement of such pests. Studies on the spatial distribution of two mite species, however, are rather scarce. The mites Polyphagotarsonemus latus and Tetranychus bastosi are the major pests affecting physic nut plantations (Jatropha curcas). Therefore, the objective of this study was to measure the spatial distributions of P. latus and T. bastosi in the physic nut plantations. Mite densities were monitored over 2 years in two different plantations. Sample locations were georeferenced. The experimental data were analyzed using geostatistical analyses. The total mite density was found to be higher when only one species was present (T. bastosi). When both the mite species were found in the same plantation, their peak densities occurred at different times. These mites, however, exhibited uniform spatial distribution when found at extreme densities (low or high). However, the mites showed an aggregated distribution in intermediate densities. Mite spatial distribution models were isotropic. Mite colonization commenced at the periphery of the areas under study, whereas the high-density patches extended until they reached 30 m in diameter. This has not been reported for J. curcas plants before.
Single dose intravenous dexmedetomidine prolongs spinal anesthesia with hyperbaric bupivacaine

Background and Introduction: Spinal block, a known technique to obtain anaesthesia for infraumblical surgeries. Now physician have advantage of using adjuvant to prolong the effect of intrathecal block, which can be given either intravenously or intrathecally, dexmedetomidine is one of them. We studied effect of intravenous dexmedetomidine for prolongation of duration of intrathecal block of 0.5% bupivacaine block. Objective: To evaluate the effect of intravenous dexmedetomidine on sensory regression, hemodynamic profile, level of sedation and postoperative analgesia. Methodology: 60 patients of ASA grade I and II posted for elective infraumblical surgeries were included in the study and randomly allocated into two groups. Group D recieved intrathecal 0.5% bupivacaine heavy, followed by infusion of intravenous dexmedetomidine 0.5mic/kg over 10 min, patients in group C received intrathecal 0.5% bupivacaine heavy 3ml followed by infusion of same volume of normal saline as placebo. Results: Two segment regression of sensory block was achieved at 139.0 ± 13.797 in group D whereas in group C it was only 96.67 ± 7.649min, the total duration of analgesia achieved in both study groups was 234.67 ± 7.649min and 164.17 ± 6.170min respectively in group D and group C. The time at which first analgesic was given to the patients when VAS >3 achieved that is in group D at 234.67 ± 7.649min and in group C at 164.17 ± 6.170min. Inj diclofenac sodium 75mg intramuscular was used as rescue analgesic.
Comparison of the bronchodilating effects of albuterol delivered by valved vs. non‐valved spacers in pediatric asthma

Inhaled therapy using a metered‐dose inhaler (MDI) with attached valved holding chamber has been increasingly recognized as the optimal method for delivering bronchodilators for asthma treatment. However, mainly due to the high cost of these valved holding chambers in many developing countries, the use of non‐valved spacers is frequent, despite the scarce evidence that supports their efficacy. The aim of this study was to compare the bronchodilator response to albuterol administered by MDI with and without a valved spacer.
A Parametric Investigation of Pattern Separation Processes in the Medial Temporal Lobe

The hippocampus is thought to be involved in memory formation and consolidation, with computational models proposing the process of pattern separation as a means for encoding overlapping memories. Previous research has used semantically related targets and lures to investigate hippocampal responses to mnemonic interference. Here, we attempted to define the response function of the human hippocampus and its inputs during pattern separation by parametrically varying target-lure similarity in a continuous recognition task. We also investigated the effect of task demands (intentional vs incidental encoding) on pattern separation processes. We collected functional magnetic resonance imaging data while participants were shown a series of objects. In the intentional paradigm, participants identified objects as “new” (novel stimuli), “old” (exact repetitions), or “rotated” (previously seen objects that were subsequently rotated by varied degrees). In the incidental paradigm, participants were shown the same stimuli but identified objects as “toy” or “not toy. ” Activation in the hippocampus was best fit with a power function, consistent with predictions made by computational models of pattern separation processes in the hippocampus. The degree of pattern separation was driven by the information most relevant to the task: pattern separation was seen in the left hippocampus when semantic information was more important to the task and seen in the right hippocampus when spatial information was more important. We also present data illustrating that top-down processes modulate activity in the ventral visual processing stream.
An Integrated Model of Pop Culture Fans’ Travel Decision-Making Processes

This study integrated the Model of Goal-directed Behavior (MGB) and the Attention, Interest, Desire, and Actions (AIDA) model into a conceptual framework to examine how pop culture influences decisions to visit a pop culture–featured destination. Findings revealed that visit intentions were significantly influenced by variables in the two models (MGB and AIDA), highlighting that attention to pop culture and positive anticipated emotions played important roles in unifying them. Results suggest that the integrated framework offers a comprehensive and coherent perspective on the complicated decision-making process of pop culture fans, which enhances the explanatory power for predicting future intentions. Thus, this paper offers an innovative approach to integrating models from the disciplines of psychology and advertising.
Imipenem concentrations in colorectal surgery and impact on the colonic microflora

Twenty patients undergoing colorectal surgery were given, as prophylaxis, imipenem-cilastatin intravenously. Ten of them received a dose of 0.5/0.5 g of imipenem-cilastatin at induction of anesthesia, followed by subsequent doses of 0.5/0.5 g every 6 h for 48 h. The other 10 patients were given 1.0/1.0 g imipenem-cilastatin in the same way for 48 h. Samples from serum, intestinal mucosa, and feces were taken for analysis of imipenem concentrations during the day of surgery. The mean concentrations in serum at 1 h after the first imipenem dose were 15.9 +/- 1.7 micrograms/ml for the 0.5-g dose and 68.2 +/- 8.2 micrograms/ml for the 1.0-g dose. The mean half-lives were 1.5 and 1.4 h, respectively, and the mean areas under the serum concentration-time curve were 41.2 +/- 6.0 and 128.3 +/- 13.5 mg.h/liter, respectively. The imipenem concentrations in the intestinal mucosa varied between less than 0.1 and 3.6 mg/kg for the 0.5-g dose and 3.2 and 13.4 mg/kg for the 1.0-g dose. The concentrations in the fecal samples varied between less than 0.1 and 5.0 mg/kg for the 0.5-g dose and 0.7 and 11.3 mg/kg for the 1.0-g dose. Fecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. The aerobic bacteria--staphylococci, streptococci, enterococci, and enteroaerobic enterococci, and enterobacteria--were and anaerobic bacteria. The aerobic bacteria--staphylococci, streptococci, enterococci, and enterobacteria--were suppressed significantly during the imipenem prophylaxis period. Among the anaerobic bacteria, cocci, bifidobacteria, eubacteria, lactobacilli, clostridia, fusobacteria, and bacteroides decreased markedly during the same period. The microfloras were normalized after 2 weeks. There were no differences between the patients receiving 0.5-g doses of imipenem and those receiving 1.0-g of imipenem. No postoperative infections occurred.
Food microbe tracker: a web-based tool for storage and comparison of food-associated microbes.

Large amounts of molecular subtyping information are generated by the private sector, academia, and government agencies. However, use of subtype data is limited by a lack of effective data storage and sharing mechanisms that allow comparison of subtype data from multiple sources. Currently available subtype databases are generally limited in scope to a few data types (e.g., MLST. net) or are not publicly available (e.g., PulseNet). We describe the development and initial implementation of Food Microbe Tracker, a public Web-based database that allows archiving and exchange of a variety of molecular subtype data that can be cross-referenced with isolate source data, genetic data, and phenotypic characteristics. Data can be queried with a variety of search criteria, including DNA sequences and banding pattern data (e.g., ribotype or pulsed-field gel electrophoresis type). Food Microbe Tracker allows the deposition of data on any bacterial genus and species, bacteriophages, and other viruses. The bacterial genera and species that currently have the most entries in this database are Listeria monocytogenes, Salmonella, Streptococcus spp. , Pseudomonas spp. , Bacillus spp. , and Paenibacillus spp. , with over 40,000 isolates. The combination of pathogen and spoilage microorganism data in the database will facilitate source tracking and outbreak detection, improve discovery of emerging subtypes, and increase our understanding of transmission and ecology of these microbes. Continued addition of subtyping, genetic or phenotypic data for a variety of microbial species will broaden the database and facilitate large-scale studies on the diversity of food-associated microbes.
Cognitive Cost of Using Augmented Reality Displays

This paper presents the results of two cognitive load studies comparing three augmented reality display technologies: spatial augmented reality, the optical see-through Microsoft HoloLens, and the video see-through Samsung Gear VR. In particular, the two experiments focused on isolating the cognitive load cost of receiving instructions for a button-pressing procedural task. The studies employed a self-assessment cognitive load methodology, as well as an additional dual-task cognitive load methodology. The results showed that spatial augmented reality led to increased performance and reduced cognitive load. Additionally, it was discovered that a limited field of view can introduce increased cognitive load requirements. The findings suggest that some of the inherent restrictions of head-mounted displays materialize as increased user cognitive load.
Optimal background matching camouflage

Background matching is the most familiar and widespread camouflage strategy: avoiding detection by having a similar colour and pattern to the background. Optimizing background matching is straightforward in a homogeneous environment, or when the habitat has very distinct sub-types and there is divergent selection leading to polymorphism. However, most backgrounds have continuous variation in colour and texture, so what is the best solution? Not all samples of the background are likely to be equally inconspicuous, and laboratory experiments on birds and humans support this view. Theory suggests that the most probable background sample (in the statistical sense), at the size of the prey, would, on average, be the most cryptic. We present an analysis, based on realistic assumptions about low-level vision, that estimates the distribution of background colours and visual textures, and predicts the best camouflage. We present data from a field experiment that tests and supports our predictions, using artificial moth-like targets under bird predation. Additionally, we present analogous data for humans, under tightly controlled viewing conditions, searching for targets on a computer screen. These data show that, in the absence of predator learning, the best single camouflage pattern for heterogeneous backgrounds is the most probable sample.
Sunitinib in the treatment of metastatic renal cell carcinoma

Sunitinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that targets various receptors, including vascular endothelial growth factor receptors (VEGFRs). Sunitinib received approval in 2006 and became a standard treatment option in the first-line treatment of metastatic renal cell cancer (mRCC) after a phase III trial showed superiority compared with interferon alpha (IFN-α). Sunitinib has also shown activity in second-line treatment in several trials. Most of the combination trials with sunitinib with various agents have led to considerable toxicity without improving efficacy. Sunitinib alone causes significant side effects and has a distinct profile with diarrhoea, hypertension, skin effects hypothyroidism, fatigue and nausea of special interest. The recommended dose of sunitinib in mRCC is 50 mg orally daily for 4 weeks, followed by 2 weeks off treatment (4/2 schedule). An alternative 2 weeks on, 1 week off schedule (2/1 schedule) seems to be of similar efficacy and better tolerability and could be more widely used in the future. An intermittent treatment strategy with a stop in remission and re-induction after progression showed efficacy in smaller trials and is currently being evaluated in a phase III trial. Direct comparison of sunitinib with pazopanib in first-line treatment showed a similar efficacy for both TKIs with a distinct toxicity profile. Data from two phase II trials showed that sunitinib has also activity in non-clear cell cancer and is an option due to a lack of better alternatives. Currently, after immune checkpoint inhibitors have shown very promising results in the second-line treatment of RCC, they are being tested in a number of phase III trials in the first-line setting. The future will show the position of sunitinib in the first-line treatment of RCC in the era of the immune checkpoint inhibitors.
Sex differences in cyclosporine pharmacokinetics and ABCB1 gene expression in mononuclear blood cells in African American and Caucasian renal transplant recipients

Cyclosporine exhibits pharmacokinetic and pharmacodynamic variability in renal transplant recipients (RTR) attributed to P‐glycoprotein (P‐gp), an ABCB1 efflux transporter that influences bioavailability and intracellular distribution. Data on race and sex influences on P‐gp in RTR are lacking. We investigated sex and race influences on cyclosporine pharmacokinetics and ABCB1 gene expression in peripheral blood mononuclear cells (PBMC). Fifty‐four female and male African American and Caucasian stable RTR receiving cyclosporine and mycophenolic acid completed a 12‐hour study. ABCB1 gene expression was assessed in PBMCs pre‐dose and 4 hours after cyclosporine. Statistical analysis used mixed effects models on transformed, normalized ABCB1 expression and cyclosporine pharmacokinetics. Sex and race differences were observed for the dose‐normalized area under the concentration curve (AUC0–12/Dose) [P = . 0004], apparent clearance [P = . 0004] and clearance/body mass index (CL/BMI) [P = . 027] with slowest clearance and greatest drug exposure in females. Sex and race differences were found pre‐dose and 4 hours for ABCB1 [P < . 0001] with females having less expression than males. ABCB1 differences were observed between pre‐dose and 4 hours [P = . 0009]. Female RTR had slower cyclosporine clearance and lower ABCB1 gene expression in PBMC suggesting reduced efflux activity and greater intracellular drug exposure.
Potential trajectories of the upcoming forest trading mechanism in Pará State, Brazilian Amazon

In 2012, the Brazilian government revised the federal Forest Code that governs the use of forest resources on rural properties. The revisions included a forest trading mechanism whereby landowners who deforested more than what is legally allowed before 2008 could absolve their deforestation “debts” by purchasing Environmental Reserve Quotas (CRA) from landowners who conserved more forest than legally required. CRA holds promise as a tool to complement command-and-control initiatives to reduce deforestation and incentivize restoration. However, the success of this instrument depends on how its implementation is governed. This study builds on a few recent assessments of the potential of the CRA in Brazil–but that are focused on biophysical potential–by assessing how a few key implementation decisions may influence the CRA market development. Specifically, this study estimates how decisions on who can participate will likely influence the potential forest surplus and forest debt for the CRA market, and takes into account governance characteristics relevant to the State of Pará, eastern Amazonia. In particular, the study evaluates the effects in the CRA market eligibility after simulating a validation of properties in the environmental rural registry (CAR) and assessing different scenarios surrounding land tenure status of properties. Results show how regulatory decisions on CRA market eligibility will determine the extent to which CRA will serve as a tool to support forest conservation or as a low-cost path to help illegal deforesters to comply with legislation, but with limited additional environmental benefits. The study reviews regulatory options that would reduce the risk of forest oversupply, and thereby increase the additionality of the areas eligible for CRA. Overall, the study demonstrates the importance of including governance as well as biophysical characteristics in assessing the potential of forest trading tools to deliver additional environmental conservation and restoration benefits.
The gnyRDBHAL Cluster Is Involved in Acyclic Isoprenoid Degradation in Pseudomonas aeruginosa

ABSTRACT Pseudomonas aeruginosa PAO1 mutants affected in the ability to degrade acyclic isoprenoids were isolated with transposon mutagenesis. The gny cluster (for geranoyl), which encodes the enzymes involved in the lower pathway of acyclic isoprenoid degradation, was identified. The gny cluster is constituted by five probable structural genes, gnyDBHAL, and a possible regulatory gene, gnyR. Mutations in the gnyD, gnyB, gnyA, or gnyL gene caused inability to assimilate acyclic isoprenoids of the citronellol family of compounds. Transcriptional analysis showed that expression of the gnyB gene was induced by citronellol and repressed by glucose, whereas expression of the gnyR gene had the opposite behavior. Western blot analysis of citronellol-grown cultures showed induction of biotinylated proteins of 70 and 73 kDa, which probably correspond to 3-methylcrotonoyl-coenzyme A (CoA) carboxylase and geranoyl-CoA carboxylase (GCCase) alpha subunits, respectively. The 73-kDa biotinylated protein, identified as the α-GCCase subunit, is encoded by gnyA. Intermediary metabolites of the isoprenoid pathway, citronellic and geranic acids, were shown to accumulate in gnyB and gnyA mutants. Our data suggest that the protein products encoded in the gny cluster are the β and α subunits of geranoyl-CoA carboxylase (GnyB and GnyA), the citronelloyl-CoA dehydrogenase (GnyD), the γ-carboxygeranoyl-CoA hydratase (GnyH), and the 3-hydroxy-γ-carboxygeranoyl-CoA lyase (GnyL). We conclude that the gnyRDBHAL cluster is involved in isoprenoid catabolism.