Miracle-dz/UniFAR-FTUs huggingface dataset:
Truncated abrin A chain expressed in Escherichia coli: A promising vaccine candidate

Abrin toxin (AT) is a highly potent toxin, and is classified as one of the most important biological warfare and bioterrorism agents. There is currently no approved vaccine for AT. Therefore, the development of an effective vaccine is important in the prevention of intoxication by abrin. In this study, five vectors containing different gene of truncated abrin toxin A chain (tATA) fragments were constructed, and two of them (tATA11-126, tATA41-188) were successfully expressed as a soluble form in E.coli strain. Both of the two tATA retained most of their immunogenicity with either low or no toxic effects as determined by both in vitro and in vivo assays. They were used to immunize BALB/c mice three times at an interval of three weeks apart. As a result, the tATA1 can elicite 80% protective efficacy against i.p. challenge of 5 × LD50 of abrin, and the tATA4 provides a better protection, which can elicite 100% protective efficacy against intraperitoneal challenge of 40 × LD50 of abrin. The superior fragment (tATA41-188) should be considered as a promising vaccine candidate for further investigations.
Social Culture and Economic Performance

The connection between obtaining higher paying jobs and undertaking some seemingly irrelevant activity is interpreted as "social culture. " In the context of a society trying to adopt a new technology, I show that by allowing the firms to give preferential treatment to workers based on some "cultural activity," the society can partially overcome an informational free-riding problem. Therefore, social culture may affect the economic performance by altering the effective production technology of the economy.
HDAC inhibitor valproic acid enhances tumor cell kill in adenovirus‐HSVtk mediated suicide gene therapy in HNSCC xenograft mouse model

Safety, efficacy and enhanced transgene expression are the primary concerns while using any vector for gene therapy. One of the widely used vectors in clinical trials is adenovirus which provides a safe way to deliver the therapeutic gene. However, adenovirus has poor transduction efficiency in vivo since most tumor cells express low coxsackie and adenovirus receptors. Similarly transgene expression remains low, possibly because of the chromatization of adenoviral genome upon infection in eukaryotic cells, an effect mediated by histone deacetylases (HDACs). Using a recombinant adenovirus (Ad‐HSVtk) carrying the herpes simplex thymidine kinase (HSVtk) and GFP genes we demonstrate that HDAC inhibitor valproic acid can bring about an increase in CAR expression on host cells and thereby enhanced Ad‐HSVtk infectivity. It also resulted in an increase in transgene (HSVtk and GFP) expression. This, in turn, resulted in increased cell kill of HNSCC cells, following ganciclovir treatment in vitro as well as in vivo in a xenograft nude mouse model.
Impact of 3-tier formularies on drug treatment of attention-deficit/hyperactivity disorder in children.

BACKGROUND Expenditures for medications used to treat attention-deficit/hyperactivity disorder (ADHD) in children have increased rapidly. Many employers and health plans have adopted 3-tier formularies in an attempt to control costs for these and other drugs. OBJECTIVE To assess the effect of copayment increases associated with 3-tier formulary adoption on use and spending patterns for ADHD medications for children. DESIGN AND SETTING Observational study using quasi-experimental design to compare effects on ADHD medication use and spending for children enrolled as dependents in an employer-sponsored plan that made major changes to its pharmacy benefit design and a comparison group of children covered by the same insurer. The plan simultaneously moved from a 1-tier (same copayment required for all drugs) to a 3-tier formulary and implemented an across-the-board copayment increase. The plan later moved 3 drugs from tier 3 to tier 2. PARTICIPANTS An intervention group of 20 326 and a comparison group of 15 776 children aged 18 years and younger. MAIN OUTCOME MEASURES Monthly probability of using an ADHD medication; plan, enrollee, and total ADHD medication spending; and medication continuation. RESULTS A 3-tier formulary implementation resulted in a 17% decrease in the monthly probability of using medication (P<.001), a 20% decrease in expected total medication expenditures, and a substantial shifting of costs from the plan to families (P<.001). Intervention group children using medications in the pre-period were more likely to change to a medication in a different tier after 3-tier adoption, relative to the comparison group (P = .08). The subsequent tier changes resulted in increased plan spending (P<.001) and decreased patient spending (P = .003) for users but no differences in continuation. CONCLUSIONS The copayment increases associated with 3-tier formulary implementation by 1 employer resulted in lower total ADHD medication spending, sizeable increases in out-of-pocket expenditures for families of children with ADHD, and a significant decrease in the probability of using these medications.
Printing patterns of biospecifically-adsorbed protein

The advancement of elastomeric patterning techniques in recent years has significantly enhanced our ability to spatially control biomaterial surface chemistry at the micrometre level. The application of this technology to the patterning of biomolecules onto solid surfaces has created many potential applications including the development of advanced biosensors, combinatorial library screening and the formation of tissue engineering templates. In this paper, we describe the direct patterning of protein by microcontact printing. An important consideration for the fabrication of protein micropatterns intended for these applications is the nature of the protein immobilization to a substrate. To date, the patterning of proteins by direct microcontact printing (μCP) has relied on the non-covalent adsorption to a substrate. Ideally, the proteins need to be firmly anchored onto a surface without adversely effecting their activity. Here, the high affinity avidin-biotin receptor-ligand interaction has been exploited to form arrays of avidin molecules onto a polymeric substrate expressing biotin moieties. This has created a generic technique by which any biotinylated species can be subsequently immobilized into defined patterns. Utilizing atomic force microscopy (AFM), the patterned surfaces have been characterized to molecular resolution. The micropatterned sample supported cell adhesion when biotin-(G)11-GRGDS was bound to the avidin bearing arrays.
Light regulation of carotenoid biosynthesis in the prasinophycean alga Mantoniella squamata

We have studied carotenoid biosynthesis in the prasinophycean alga Mantoniella squamata , which contains a great variety of carotenoids belonging to both the a- and the ß-carotene (Car) biosyntheses pathways. This unusual carotenoid composition allowed us to address the problem of how biosynthesis on the a- and the ß-Car pathway is regulated in response to different light regimes. We found that illumination with 4 h of actinic high light (HL, 250 µmol m^>-2> s^>-1>), and culture growth in permanent light (PL, 60 µmol m^>-2> s^>-1>), induced the de novo synthesis of violaxanthin (Vx) cycle pigments belonging to the ß-Car pathway. Carotenoid synthesis on the a-Car biosynthesis pathway led to a strong accumulation of lutein (L) and dihydrolutein (DhL). Both the newly synthesised Vx cycle pigments and L/DhL can be regarded as intermediate pools of carotenoids that were converted to light-harvesting pigments in low light (LL) periods following the phases of HL illumination. This transition to the light-harvesting pigments included the conversion of Vx to neoxanthin (Nx) on the ß-Car pathway, and the transformation of L/DhL to prasinoxanthin (Px), the main light-harvesting pigment of M. squamata belonging to the a-carotenoids. Isolation of light-harvesting complexes from L-enriched M. squamata cells showed that both L and the Vx cycle pigments were loosely bound to the LHC apoprotein. This peripheral binding is in agreement with their proposed role as intermediate pigments in the biosynthesis of light-harvesting pigments, and should allow a smooth detachment from the protein in periods of LL when the synthesis of Nx and Px is stimulated. We conclude that carotenoid synthesis proceeds in general in an economical way: in both, the a- and the ß-Car pathway HL induces the formation of photoprotective pigments, which in LL periods following the HL illumination are not degraded, but on the contrary are converted to light-harvesting pigments.
Biological activities of endotoxins detoxified by alkylation

It has been previously observed that lipopolysaccharides can be detoxified by alkylation and yet retain their adjuvant activity. Our present findings confirm these results and show, moreover, that these derivatives did not lose their capacity to protect mice against lethal irradiation and lost only partially their ability to interrupt pregnancy or to induce blast transformation of murine B-lymphocytes. However, in contrast with lipopolysaccharides, these alkylated preparations did not enhance the nonspecific resistance of mice to a bacterial infection. The various bilogical functions of endotoxins can therefore be separated and are not uniformly related to their toxicity.
Recovery of cytopathogenic and noncytopathogenic bovine viral diarrhea viruses from cDNA constructs

After cDNA cloning of the genome of bovine viral diarrhea virus (BVDV) isolate CP7, a full-length cDNA clone was constructed. RNA transcribed in vitro from this construct was shown to direct the generation of infectious BVDV upon transfection into bovine cells. To confirm the de novo generation of infectious BVDV from cloned cDNA a genetically tagged virus was constructed. In comparison with parental BVDV, the recombinant virus was slightly retarded in growth. The NS2 coding region of the CP7 genome contains a duplication of 27 nucleotides which is not present in the genome of its noncytopathogenic counterpart, NCP7. Exchange of a small fragment harboring this insertion against the corresponding part of the NCP7 sequence led to recovery of noncytopathogenic BVDV. Alteration of the construct by introduction of a fragment derived from a cytopathogenic BVDV defective interfering particle resulted in a chimeric defective interfering particle which exhibits a cytopathogenic phenotype. These findings confirm the hypothesis that the recombination-induced alterations in the genomes of cytopathogenic BVDV are responsible for the induction of cell lysis.
The Multiple Sclerosis Performance Test (MSPT): An iPad-Based Disability Assessment Tool

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report a new test, the Multiple Sclerosis Performance Test (MSPT), which represents a new approach to quantifying MS related disability. The MSPT takes advantage of advances in computer technology, information technology, biomechanics, and clinical measurement science. The resulting MSPT represents a computer-based platform for precise, valid measurement of MS severity. Based on, but extending the Multiple Sclerosis Functional Composite (MSFC), the MSPT provides precise, quantitative data on walking speed, balance, manual dexterity, visual function, and cognitive processing speed. The MSPT was tested by 51 MS patients and 49 healthy controls (HC). MSPT scores were highly reproducible, correlated strongly with technician-administered test scores, discriminated MS from HC and severe from mild MS, and correlated with patient reported outcomes. Measures of reliability, sensitivity, and clinical meaning for MSPT scores were favorable compared with technician-based testing. The MSPT is a potentially transformative approach for collecting MS disability outcome data for patient care and research. Because the testing is computer-based, test performance can be analyzed in traditional or novel ways and data can be directly entered into research or clinical databases. The MSPT could be widely disseminated to clinicians in practice settings who are not connected to clinical trial performance sites or who are practicing in rural settings, drastically improving access to clinical trials for clinicians and patients. The MSPT could be adapted to out of clinic settings, like the patient’s home, thereby providing more meaningful real world data. The MSPT represents a new paradigm for neuroperformance testing. This method could have the same transformative effect on clinical care and research in MS as standardized computer-adapted testing has had in the education field, with clear potential to accelerate progress in clinical care and research.
Theophylline and Cardiac Stress in Patients with Dyspnea: An Observational Study

Background/Aims: Appreciation of the anti-inflammatory actions of theophylline at low serum concentrations has revived the interest in this drug, but its cardiac side effects remain a concern. The serum level of N-terminal probrain natriuretic peptide (NT-proBNP) is a marker for cardiac stress. This study examined the association between theophylline intake and NT-proBNP. Methods: The effect of theophylline on NT-proBNP was prospectively evaluated by multiple regression analysis in 753 outpatients referred for pulmonary evaluation of dyspnea. Results: Of 548 patients with asthma, chronic obstructive pulmonary disease or respiratory muscle weakness, 107 were taking theophylline (median serum concentration 8.1 µg/ml). The theophylline users were older (mean 64.5 ± 11.6 vs. 56.5 ± 16.8 years, p < 0.01), had severer airway obstruction (p < 0.01) and had a higher prevalence of heart disease (33.6 vs. 23.1%, p = 0.02) than the patients not taking theophylline. Among the patients with heart disease (n = 138), the adjusted levels of NT-proBNP were lower (p < 0.01) in the theophylline-treated patients (n = 36) than in the patients not using theophylline (median 144.5 vs. 236.4 pg/ml). Theophylline had no effect on NT-proBNP in patients without heart disease. Conclusion: The results of this observational study call into question the traditional view that even low-dose theophylline therapy may be detrimental in patients with coexisting heart disease.
Optimizing Sparse Matrix Vector Multiplication on SMP

We describe optimizations of sparse matrix-vector multiplication on uniprocessors and SMPs. The optimization techniques include register blocking, cache blocking, and matrix reordering. We focus on optimizations that improve performance on SMPs, in particular, matrix reordering implemented using two diierent graph algorithms. We present a performance study of this algorithmic kernel, showing how the optimization techniques aaect absolute performance and scalability, how they interact with one another, and how the performance beneets depend on matrix structure.
Back to the Debate: Sternalis Muscle

El musculo esternal (ME) es una variante anatomica en la pared toracica anterior. Mientras que los sitios de fijacion del ME estan acordados, la inervacion y la funcion de este musculo no estan bien establecida. Exploraciones cadavericas y quirurgicas han informado que el ME esta inervado por los nervios pectorales o ramos anteriores de los nervios intercostales, o una combinacion de ambos. El conocimiento del SE es relevante para los proveedores de atencion de salud especializada de imagenes y / o cirugia de la pared toracica anterior. Este documento tiene como objetivo crear conciencia en la comunidad medica de la relevancia clinica de ME a traves de dos reportes de caso y una breve revision bibliografica.
Classical Call-by-need and duality , extended version ?

We study call-by-need from the point of view of the duality between call-by-name and call-by-value. We develop sequent-calculus style versions of call-by-need both in the minimal and classical case. As a result, we obtain a natural extension of call-by-need with control operators. This leads us to introduce a call-by-need λμ-calculus. Finally, by using the dualities principles of λμμ̃-calculus, we show the existence of a new call-by-need calculus, which is distinct from call-by-name, call-byvalue and usual call-by-need theories.
Structural Gray Matter Differences between First-Episode Schizophrenics and Normal Controls Using Voxel-Based Morphometry

The aim of this study was to compare the gray matter segments from T1 structural MR images of the brain in first-episode schizophrenic subjects (n = 34) and normal control subjects (n = 36) using automated voxel-based morphometry (VBM). This study is novel in that few studies have examined subjects in their first episode of schizophrenia. The subjects were recruited for the Edinburgh High Risk project and regional brain volumes were previously measured using a semi-automated volumetric region of interest (ROI) method of analysis. The primary interest was to compare the results from the compatible parts of the ROI study and the primary VBM approach. Our secondary interest was to compare the results of a study-specific template that was constructed from the control group to those using the generic T1 template (152 Montreal Neurological Institute brains) supplied with SPM99 (statistical parametric mapping). The images were processed and statistically analyzed using the SPM99 program. VBM analysis identified significant decreases in gray matter in the schizophrenics relative to the normal control group at the corrected voxel level (P < 0.05) in the right anterior cingulate, right medial frontal lobe, left middle temporal gyrus, left postcentral gyrus, and the left limbic lobe. There were no increases in gray matter in the schizophrenics relative to the control group. The construction of a customized template appeared to improve the detection of structural abnormalities. The analyses were subsequently restricted to voxels within the amygdala-hippocampal complex using the SPM small-volume correction. This identified gray matter decreases in the schizophrenics, at the corrected voxel level (P < 0.05), in the left and right uncus and parahippocampal gyri and the right amygdala. These results are compatible with and extend the relevant findings of the previous volumetric ROI analysis, when allowing for the differences between the methods and interpretation of their results.
Genome Sequence of Ruegeria sp. Strain KLH11, an N-Acylhomoserine Lactone-Producing Bacterium Isolated from the Marine Sponge Mycale laxissima

ABSTRACT Ruegeria sp. strain KLH11, isolated from the marine sponge Mycale laxissima, produces a complex profile of N-acylhomoserine lactone quorum-sensing (QS) molecules. The genome sequence provides insights into the genetic potential of KLH11 to maintain complex QS systems, and this is the first genome report of a cultivated symbiont from a marine sponge.
A new approach to design cascade fault diagnosis observers for flexible spacecraft

This paper proposes a new gyro and star sensor fault diagnosis architecture that designs two groups of cascade H∞ optimal fault observers for a spacecraft with flexible appendages and schemes a Compensation PD controller to achieve fault tolerant control. The basic idea of the approach is to identify the gyro fault to good effect first and then makes a further diagnosis for the star sensor based on the former. The H∞ optimal fault observer in design has the robustness with respect to flexible uncertainties and diagnosis uncertainties. The Compensation PD controller ensures attitude errors maintained to a small set around the equilibrium point for a long time even though gyro and star sensor faults occur simultaneously. Finally, simulation results demonstrate the effectiveness and feasibility of the proposed control algorithm.
Low Expression of NQO 1 Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Patients Treated with TAC Regimen ( breast cancer / neoadjuvant therapy / predictive biomarkers )

The aim of this study was to evaluate preoperative tumour expression of NAD(P)H:quinone oxidoreductase 1 (NQO1) along with other biological markers as potential predictors of pathological complete response (pCR) to neoadjuvant docetaxel, doxorubicin, and cyclophosphamide-containing (TAC) chemotherapy in patients with primary breast cancer. Sixty-one patients who received neoadjuvant chemotherapy (NCT) with TAC regimen were enrolled in this prospective study. The preand postNCT expression of oestrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 1 and 2 (EGFR and HER2), NQO1, Ki-67 proliferation index, multidrug resistance protein 1 (MDR1), p53 and BCL2 were evaluated by immunohistochemistry. The pCR was reached in 14 patients (23 % of the study group). Multivariate analysis Received February 13, 2012. Accepted May 14, 2012. This study was supported by grant from the Ministry of Health of the Czech Republic IGA NS/10373-3/2009. Corresponding authors: Jiří Grim, Department of Oncology and Radiotherapy, University Teaching Hospital in Hradec Králové, Sokolská 581, 500 05 Hradec Králové, Czech Republic. Phone: (+420) 495 834 666; e-mail: grimj@lfhk.cuni. cz Stanislav Mičuda, Department of Pharmacology, Charles Universi ty in Prague, Faculty of Medicine in Hradec Králové, Šimkova 870, 500 38 Hradec Králové, Czech Republic. Phone: (+420) 495 816 313; Fax: (+420) 495 513 022. e-mail: micuda@ lfhk.cuni. cz Abbreviations: BC – breast cancer, ER – oestrogen receptor, HER2 – human epidermal growth factor receptor 2, MDR1 – multidrug resistance protein 1, NCT – neoadjuvant chemothera‐ py, NQO1 – NAD(P)H:quinone oxidoreductase, pCR – patho‐ logical complete response, PPCT – percentage of positive tumour cells, PR – progesterone receptor. demonstrated that patients with ER-, PR-, NQO1negative, and Ki‐67‐positive tumours had a significantly higher chance to achieve pCR. Within the biological subtypes, the highest pCR rate (50 %) was seen in triple-negative (i.e. ER-, PR-, HER2-) tumours. Post-operative evaluation showed that in comparison to pre-operative tissue samples, NQO1 expression was significantly increased, while Ki‐67 and HER2 decreased, in the residual tissue after NCT. In conclusion, the present data suggests that NQO1 expression may be a novel diagnostic biomarker for the prediction of positive response to NCT in patients with breast cancer.
UNC 45 A Confers Resistance to Histone Deacetylase Inhibitors and Retinoic Acid

To identify potential biomarkers of therapy response, we have previously done a large-scale gain-of-function genetic screen to identify genes whose expression confers resistance to histone deacetylase inhibitors (HDACI). This genetic screen identified two genes with a role in retinoic acid signaling, suggesting that HDACIs target retinoic acid signaling as part of their anticancer effect. We study here a third gene identified in this genetic screen, UNC45A, and assess its role in retinoic acid signaling and responses to HDACIs using cell-based proliferation and differentiation assays and transcriptional reporter gene assays. The vertebrate Unc45 genes are known for their roles in muscle development and the assembly and cochaperoning of the muscle motor protein myosin. Here, we report that human UNC45A (GCUNC45) can render transformed cells resistant to treatment with HDACIs. We show that UNC45A also inhibits signaling through the retinoic acid receptor α. Expression of UNC45A inhibits retinoic acid–induced proliferation arrest and differentiation of human neuroblastoma cells and inhibits the induction of endogenous retinoic acid receptor target genes. These data establish an unexpected role for UNC45A in causing resistance to both HDACI drugs and retinoic acid. Moreover, our data lend further support to the notion that HDACIs exert their anticancer effect, at least in part, through an effect on retinoic acid signaling. (Mol Cancer Res 2009;7(11):1861–70)