Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimization of Single-Base-Pair Mismatch Discrimination in Oligonucleotide Microarrays

ABSTRACT The discrimination between perfect-match and single-base-pair-mismatched nucleic acid duplexes was investigated by using oligonucleotide DNA microarrays and nonequilibrium dissociation rates (melting profiles). DNA and RNA versions of two synthetic targets corresponding to the 16S rRNA sequences of Staphylococcus epidermidis (38 nucleotides) and Nitrosomonas eutropha (39 nucleotides) were hybridized to perfect-match probes (18-mer and 19-mer) and to a set of probes having all possible single-base-pair mismatches. The melting profiles of all probe-target duplexes were determined in parallel by using an imposed temperature step gradient. We derived an optimum wash temperature for each probe and target by using a simple formula to calculate a discrimination index for each temperature of the step gradient. This optimum corresponded to the output of an independent analysis using a customized neural network program. These results together provide an experimental and analytical framework for optimizing mismatch discrimination among all probes on a DNA microarray.
Comparison of the Immunomodulatory Properties of Three Probiotic Strains of Lactobacilli Using Complex Culture Systems: Prediction for In Vivo Efficacy

Background While the use of probiotics to treat or prevent inflammatory bowel disease (IBD) has been proposed, to this point the clinical benefits have been limited. In this report we analyzed the immunological activity of three strains of Lactobacillus to predict their in vivo efficacy in protecting against experimental colitis. Methodology/Principal Findings We compared the immunological properties of Lactobacillus plantarum NCIMB8826, L. rhamnosus GG (LGG), L. paracasei B21060 and pathogenic Salmonella typhimurium (SL1344). We studied the stimulatory effects of these different strains upon dendritic cells (DCs) either directly by co-culture or indirectly via conditioning of an epithelial intermediary. Furthermore, we characterized the effects of these strains in vivo using a Dextran sulphate sodium (DSS) model of colitis. We found that the three strains exhibited different abilities to induce inflammatory cytokine production by DCs with L. plantarum being the most effective followed by LGG and L. paracasei. L. paracasei minimally induced the release of cytokines, while it also inhibited the potential of DCs to both produce inflammatory cytokines (IL-12 and TNF-α) and to drive Th1 T cells in response to Salmonella. This effect on DCs was found under both direct and indirect stimulatory conditions – i.e. mediated by epithelial cells - and was dependent upon an as yet unidentified soluble mediator. When tested in vivo, L. plantarum and LGG exacerbated the development of DSS-induced colitis and caused the death of treated mice, while, conversely L. paracasei was protective. Conclusions We describe a new property of probiotics to either directly or indirectly inhibit DC activation by inflammatory bacteria. Moreover, some immunostimulatory probiotics not only failed to protect against colitis, they actually amplified the disease progression. In conclusion, caution must be exercised when choosing a probiotic strain to treat IBD.
Abscisic Acid Regulates Auxin Homeostasis in Rice Root Tips to Promote Root Hair Elongation

Abscisic acid (ABA) plays an essential role in root hair elongation in plants, but the regulatory mechanism remains to be elucidated. In this study, we found that exogenous ABA can promote rice root hair elongation. Transgenic rice overexpressing SAPK10 (Stress/ABA-activated protein kinase 10) had longer root hairs; rice plants overexpressing OsABIL2 (OsABI-Like 2) had attenuated ABA signaling and shorter root hairs, suggesting that the effect of ABA on root hair elongation depends on the conserved PYR/PP2C/SnRK2 ABA signaling module. Treatment of the DR5-GUS and OsPIN-GUS lines with ABA and an auxin efflux inhibitor showed that ABA-induced root hair elongation depends on polar auxin transport. To examine the transcriptional response to ABA, we divided rice root tips into three regions: short root hair, long root hair and root tip zones; and conducted RNA-seq analysis with or without ABA treatment. Examination of genes involved in auxin transport, biosynthesis and metabolism indicated that ABA promotes auxin biosynthesis and polar auxin transport in the root tip, which may lead to auxin accumulation in the long root hair zone. Our findings shed light on how ABA regulates root hair elongation through crosstalk with auxin biosynthesis and transport to orchestrate plant development.
Capitalizing on Cancer Specific Replication: Oncolytic Viruses as a Versatile Platform for the Enhancement of Cancer Immunotherapy Strategies

The past decade has seen considerable excitement in the use of biological therapies in treating neoplastic disease. In particular, cancer immunotherapy and oncolytic virotherapy have emerged as two frontrunners in this regard with the first FDA approvals for agents in both categories being obtained in the last 5 years. It is becoming increasingly apparent that these two approaches are not mutually exclusive and that much of the therapeutic benefit obtained from the use of oncolytic viruses (OVs) is in fact the result of their immunotherapeutic function. Indeed, OVs have been shown to recruit and activate an antitumor immune response and much of the current work in this field centers around increasing this activity through strategies such as engineering genes for immunomodulators into OV backbones. Because of their broad immunostimulatory functions, OVs can also be rationally combined with a variety of other immunotherapeutic approaches including cancer vaccination strategies, adoptive cell transfer and checkpoint blockade. Therefore, while they are important therapeutics in their own right, the true power of OVs may lie in their ability to enhance the effectiveness of a wide range of immunotherapies.
Role of Hsp17.4-CII as Coregulator and Cytoplasmic Retention Factor of Tomato Heat Stress Transcription Factor HsfA21

HsfA2 is a heat stress (hs)-induced Hsf in peruvian tomato (Lycopersicon peruvianum) and the cultivated form Lycopersicon esculentum. Due to the high activator potential and the continued accumulation during repeated cycles of heat stress and recovery, HsfA2 becomes a dominant Hsf in thermotolerant cells. The formation of heterooligomeric complexes with HsfA1 leads to nuclear retention and enhanced transcriptional activity of HsfA2. This effect seems to represent one part of potential molecular mechanisms involved in its activity control. As shown in this paper, the activity of HsfA2 is also controlled by a network of nucleocytoplasmic small Hsps influencing its solubility, intracellular localization and activator function. By yeast two-hybrid interaction and transient coexpression studies in tobacco (Nicotiana plumbaginifolia) mesophyll protoplasts, we found that tomato (Lycopersicon esculentum) Hsp17.4-CII acts as corepressor of HsfA2. Given appropriate conditions, both proteins together formed large cytosolic aggregates which could be solubilized in presence of class CI sHsps. However, independent of the formation of aggregates or of the nucleocytoplasmic distribution of HsfA2, its transcriptional activity was specifically repressed by interaction of Hsp17.4-CII with the C-terminal activator domain. Although not identical in all aspects, the situation with the highly expressed, heat stress-inducible Arabidopsis HsfA2 was found to be principally similar. In corresponding reporter assays its activity was repressed in presence of AtHsp17.7-CII but not of AtHsp17.6-CII or LpHsp17.4-CII.
The Role of Group Cognition in Enterprise Architecting

Enterprise architecture (EA) models the desired relationships between business processes and technology. Enterprise "architecting" is the process of developing and maintaining the EA. The goal of EA is to align business process and IT for the effective execution of business strategy and the efficient implementation of the associated systems. Thus, the architecting process involves many stakeholders (e.g., architects, IT staff, and business staff) with very diverse perspectives, making coordination of architecting work daunting. Despite their critical importance to EA success, coordination and governance in EA have received very little attention in the literature. In this paper we report on a study based on semi-structured interviews of CIO's, chief architects, technical architects, IT staff, business stakeholders and EA consultants. The focus of the study was to better understand the coordination challenges and best practices leading to EA success. Our results show that various forms of group cognition play a critical role in the effective coordination of architecting.
SPOT: An R Package For Automatic and Interactive Tuning of Optimization Algorithms by Sequential Parameter Optimization

The sequential parameter optimization (spot) package for R (R Development Core Team, 2008) is a toolbox for tuning and understanding simulation and optimization algorithms. Model-based investigations are common approaches in simulation and optimization. Sequential parameter optimization has been developed, because there is a strong need for sound statistical analysis of simulation and optimization algorithms. spot includes methods for tuning based on classical regression and analysis of variance techniques; tree-based models such as CART and random forest; Gaussian process models (Kriging), and combinations of dierent metamodeling approaches. This article exemplies how spot can be used for automatic and interactive tuning.
ATG‐Induced Accelerated Immune Senescence: Clinical Implications in Renal Transplant Recipients

Persistent ATG‐induced CD4+ T cell lymphopenia is associated with serious clinical complications. We tested the hypothesis that ATG induces accelerated immune senescence in renal transplant recipients (RTR). Immune senescence biomarkers were analyzed at transplant and one‐year later in 97 incident RTR −62 patients receiving ATG and 35 receiving anti‐CD25 mAb (α‐CD25). This consisted in: (i) thymic output; (ii) bone marrow renewal of CD34+ hematopoietic progenitor cells (CD34+HPC) and lymphoid (l‐HPC) and myeloid (m‐HPC) progenitor ratio; (iii) T cell phenotype; and (iv) measurement of T cell relative telomere length (RTL) and telomerase activity (RTA). Clinical correlates were analyzed with a 3 year follow‐up. Thymic output significantly decreased one‐year posttransplant in ATG‐treated patients. ATG was associated with a significant decrease in l‐HPC/m‐HPC ratio. Late stage differentiated CD57+/CD28− T cells increased in ATG‐treated patients. One‐year posttransplant T cell RTL and RTA were consequently lower in ATG‐treated patients. ATG is associated with accelerated immune senescence. Increased frequency of late differentiated CD4+ T cell frequency at transplantation tended to be predictive of a higher risk of subsequent opportunistic infections and of acute rejection only in ATG‐treated patients but this needs confirmation. Considering pretransplant immune profile may help to select those patients who may benefit from ATG to prevent severe infections and acute rejection.
Beyond Muscles

Thus far the study of men's body image has been largely restricted to the dimensions of adiposity and muscularity. The aim of this study was to investigate in a systematic way multiple aspects of men's body images, in particular, head hair, body hair, height and penis size, in addition to body weight and muscularity. Questionnaires were completed online by 200 heterosexual men. It was found that men were dissatisfied with all six aspects of their bodies, and worried primarily about body weight, penis size and height. In addition, aspects of weight, muscularity, height and penis size, but not head or body hair, were related to overall appearance self-esteem. It was concluded that men's body image is both multi-faceted and complex.
An Improved Optical Spectrum and New Model Fits of the Likely Brown Dwarf GD 165B

Long thought by some researchers to be an oddity, GD 165B has instead proved to be the first example of a class of very cool objects (the L dwarfs) that, because of dust formation in their photospheres, lack the dominant bands of TiO seen in warmer M dwarfs. Here we present an improved optical (6200-10300 Å) spectrum of GD 165B and identify its prominent spectral features. Among these are newly identified bands of FeH and the first identification of CrH bands in a dwarf. We use the latest generation of model atmospheres, which include the effects of condensation and dust opacities, to derive values of Teff = 1900 ± 100 K and log g = 5.0 ± 0.5 for GD 165B. We also derive a crude age of 1.2-5.5 Gyr for the GD 165 system. A comparison of the temperature and age of GD 165B with evolutionary models predicts GD 165B to be an object in the transition zone between stars and brown dwarfs. Further observational evidence—the discovery of lithium in other dwarfs spectroscopically similar to GD 165B and the scarcity of GD 165B-like companions found by imaging surveys—favors a substellar interpretation for this object. We argue that the weight of this observational evidence, together with the known shortcomings of the evolutionary models (which do not yet include opacity by grains), indicate that GD 165B is probably a brown dwarf.
Altered Connexin Expression after Peripheral Nerve Injury

The identification of connexin32 (Cx32) in myelinating Schwann cells and the association of Cx32 mutations with peripheral neuropathies suggest a functional role for gap junction proteins in the nerve. However, after nerve crush injury, Cx32 expression dramatically decreases in Schwann cells in the degenerating region, returning to control levels at newly formed nodes of Ranvier and Schmidt-Lantermann incisures by 30 days. The present study examined increases in expression of other connexins that occur after peripheral nerve injury. A 56/58-kDa connexin46 (Cx46) protein species was detected in adult rat sciatic nerve, along with very low levels of Cx46 mRNA. However, by 3 days after crush injury, coincident with changes in Schwann cell phenotype, Cx46 mRNA rapidly increased in the degenerating regions. Additionally, the 56/58-kDa Cx46 protein species present in adult nerve decreased and a 53-kDa Cx46 species, which was also present in cultured Schwann cells, became apparent. Connexin43 (Cx43) mRNA and protein, which was localized to perineurial cells in adult nerve, dramatically increased in endoneurial fibroblasts in the crush and distal regions by 3 days, coincident with macrophage infiltration. By 12 days after injury, Cx43 decreased and was comparable to normal nerve. These results suggest that enhanced expression of Cx46 and Cx43, by nonneuronal cells, may be important for the injury and regenerative responses of peripheral nerves.
Laboratory Evaluation of Waste Cooking Oil-Based Bioasphalt as an Alternative Binder for Hot Mix Asphalt

Increased environmental regulations and the rising costs of asphalt binder have encouraged researchers to investigate alternative binders that can be used for hot mix asphalt (HMA). This study focused on using bioasphalt as a possible alternative binder to petroleum-based asphalt. To evaluate bioasphalt as a HMA binder, both binder and mixture tests were performed. Bioasphalt was blended with traditional binders at different percentages (0, 10, 30, and 60%) by weight of the base binder. Binder test results, based on constant shear loading tests and multiple stress creep and recovery tests, showed that the addition of bioasphalt decreased the resistance to fatigue and rutting. The HMA mixture performance tests indicated that the addition of bioasphalt to the mix reduced the stiffness of the mix (dynamic modulus) and its resistance to rutting and fatigue cracking, but increased the resistance to thermal cracking. The moisture susceptibility test shows that bioasphalt mixes passed the minimum tensile strength ratio requirement.
Effect of antiepileptic drugs on bone density in ambulatory patients

BackgroundLong-term antiepileptic drug (AED) use causes multiple abnormalities in calcium and bone metabolism that have been most extensively described in institutionalized patients. The objective is to determine the effect of AED on vitamin D levels and bone density in ambulatory patients and to compare the effects of enzyme-inducing and -noninducing AED and of single vs multiple therapy on bone density. MethodsA cross-sectional evaluation was conducted of 71 patients (42 adults and 29 children/adolescents) on anticonvulsant therapy for at least 6 months who presented to neurologists at a tertiary referral center. Bone mineral density (BMD) as well as serum 25 hydroxy–vitamin D (25-OHD) levels were measured. A detailed questionnaire assessing calcium intake as well as previous and current intake of antiepileptic medications was administered to all patients. Results Over 50% of adults and children/adolescents had low 25-OHD levels, but this finding did not correlate with BMD. Antiepileptic therapy decreased BMD in adults. Generalized seizures, duration of epilepsy, and polypharmacy were significant determinants of BMD, more so at skeletal sites enriched in cortical bone. Subjects on enzyme-inducing drugs such as phenytoin, phenobarbital, carbamazepine, and primidone tended to have lower BMD than those on noninducers such as valproic acid, lamotrigine, clonazepam, gabapentin, topamirate, and ethosuximide. ConclusionEpilepsy and its therapy, including the newer drugs, are risk factors for low bone density, irrespective of vitamin D levels. Skeletal monitoring with the institution of appropriate therapy is indicated in patients on chronic antiepileptic therapy.
A Multilayer MEMS Platform for Single-Cell Electric Impedance Spectroscopy and Electrochemical Analysis

The fabrication and characterization of a micro- chamber electrode array for electrical and electrochemical studies of individual biological cells are presented. The geometry was tailored specifically for measurements from sensory hair cells isolated from the cochlea of the mammalian inner ear. Conventional micro- electromechanical system (MEMS) fabrication techniques were combined with a heat-sealing technique and polydimethylsiloxane micromolding to achieve a multilayered microfluidic system that facilitates cell manipulation and selection. The system allowed for electrical stimulation of individual living cells and interrogation of excitable cell membrane dielectric properties as a function of space and time. A three-electrode impedimetric system was incorporated to provide the additional ability to record the time-dependent concentrations of specific biochemicals in microdomain volumes near identified regions of the cell membrane. The design and fabrication of a robust fluidic and electrical interface are also described. The interface provided the flexibility and simplicity of a "cartridge- based" approach in connecting to the MEMS devices. Cytometric measurement capabilities were characterized by using electric impedance spectroscopy (1 kHz-10 MHz) of isolated outer hair cells. Chemical sensing capability within the microchannel recording chamber was characterized by using cyclic voltammetry with varying concentrations of potassium ferricyanide (K3Fe(CN)6). Chronoamperometric recordings of electrically stimulated PC12 cells highlight the ability of the platform to resolve exocytosis events from individual cells.
Diffusion capacity of the lung for carbon monoxide – A potential marker of impaired gas exchange or of systemic deconditioning in chronic obstructive lung disease?

Gas exchange impairment is primarily caused by ventilation–perfusion mismatch in chronic obstructive pulmonary disease (COPD), where diffusing capacity of the lungs for carbon monoxide (DLCO) remains the clinical measure. This study investigates whether DLCO: (1) can predict respiratory impairment in COPD, that is, changes in oxygen and carbon dioxide (CO2); (2) is associated with combined risk assessment score for COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) score); and (3) is associated with blood glucose and body mass index (BMI). Fifty patients were included retrospectively. DLCO; arterial blood gas at inspired oxygen (FiO2) = 0.21; oxygen saturation (SpO2) at FiO2 = 0.21 (SpO2 21) and FiO2 = 0.15 (SpO2 15) were registered. Difference between arterial and end-tidal CO2 (ΔCO2) was calculated. COPD severity was stratified according to GOLD score. The association between DLCO, SpO2, ΔCO2, GOLD score, blood glucose, and BMI was investigated. Multiple regression showed association between DLCO and GOLD score, BMI, and glucose level (R 2 = 0.6, p < 0.0001). Linear and multiple regression showed an association between DLCO and SpO2 21 (R 2 = 0.3, p = 0.001 and p = 0.03, respectively) without contribution from SpO2 15 or ΔCO2. A stronger association between DLCO and GOLD score than between DLCO and SpO2 could indicate that DLCO is more descriptive of systemic deconditioning than gas exchange in COPD patients. However, further larger studies are needed. A weaker association is seen between DLCO and SpO2 21 without contribution from SpO2 15 and ΔCO2. This could indicate that DLCO is more descriptive of systemic deconditioning than gas exchange in COPD patients. However, further larger studies are needed.
Prefrontal Neurons Represent Motion Signals from Across the Visual Field But for Memory-Guided Comparisons Depend on Neurons Providing These Signals

Visual decisions often involve comparisons of sequential stimuli that can appear at any location in the visual field. The lateral prefrontal cortex (LPFC) in nonhuman primates, shown to play an important role in such comparisons, receives information about contralateral stimuli directly from sensory neurons in the same hemisphere, and about ipsilateral stimuli indirectly from neurons in the opposite hemisphere. This asymmetry of sensory inputs into the LPFC poses the question of whether and how its neurons incorporate sensory information arriving from the two hemispheres during memory-guided comparisons of visual motion. We found that, although responses of individual LPFC neurons to contralateral stimuli were stronger and emerged 40 ms earlier, they carried remarkably similar signals about motion direction in the two hemifields, with comparable direction selectivity and similar direction preferences. This similarity was also apparent around the time of the comparison between the current and remembered stimulus because both ipsilateral and contralateral responses showed similar signals reflecting the remembered direction. However, despite availability in the LPFC of motion information from across the visual field, these “comparison effects” required for the comparison stimuli to appear at the same retinal location. This strict dependence on spatial overlap of the comparison stimuli suggests participation of neurons with localized receptive fields in the comparison process. These results suggest that while LPFC incorporates many key aspects of the information arriving from sensory neurons residing in opposite hemispheres, it continues relying on the interactions with these neurons at the time of generating signals leading to successful perceptual decisions. SIGNIFICANCE STATEMENT Visual decisions often involve comparisons of sequential visual motion that can appear at any location in the visual field. We show that during such comparisons, the lateral prefrontal cortex (LPFC) contains accurate representation of visual motion from across the visual field, supplied by motion processing neurons. However, at the time of comparison, LPFC neurons can only use this information to compute the differences between the stimuli, if stimuli appear at the same retinal location, implicating neurons with localized receptive fields in the comparison process. These findings show that sensory comparisons rely on the interactions between LPFC and sensory neurons that not only supply sensory signals but also actively participate in the comparison of these signals at the time of the decision.