Miracle-dz/UniFAR-FTUs huggingface dataset:
EFFECT OF HERBAL BIOENHANCERS ON SAQUINAVIR IN HUMA N Caco-2 CELL MONOLAYERS AND PHARMACOKINETICS IN RATS

Purpose: Membrane-bound efflux transporters, such as P-glycoprotein (P-gp), may limit the entry and distribution of HIV-1 protease inhibitors saquinavir (SQN) and may be the reason for low and variable oral bioavailability. The purpose is to investigate in vitro mechanisms of gastrointestinal absorption of saquinavir mesylate, in presence and absence of herbal bioenhancers using human Caco-2 cells. To investigate the correlation of Caco-2 out come with animal pharmacokinetic studies for bioavailability enhancement. Method: Confluent epithelial layers of human Caco-2 cells mimicking the intestinal barrier. Pharmacokinetic studies using Male Sprague-Dawley (SD) rats. Results: Saquinavir showed polarized transport through Caco-2 cell monolayers in the basolateral to apical direction (secretory pathway). Saquinavir has shown an efflux ratio (B-A / A-B) of > 25 and reduced to ~ 2 when saquinavir co-administered with herbal bioenhancers. Active efflux was temperature dependent, saturable and inhibited by verapamil. In presence of herbal bioenhancers the permeability of saquinavir was increased. Oral bioavailability was also increased in rat by ~ 10 folds. Conclusions: Saquinavir is a substrate for an efflux mechanism in the gut, most likely P-glycoprotein, which acts as a counter-transporter for the drug. This may partially account for the low and variable oral bioavailability of saquinavir. After co-administration with herbal enhancers the permeability of saquinavir was increased. These herbal bioenhancers may be acting as an inhibitor of P-gp and may help by improving the oral bioavailability of saquinavir.
Illumination Estimation from Dichromatic Planes

Adopting the dichromatic reflection model under the assumption of neutral interface reflection, the color of the illuminating light can be estimated by intersecting the planes that the color response of two or more different materials describe. From the color response of any given region, most approaches estimate a single plane on the assumption that only a single material is imaged. This assumption, however, is often violated in cluttered scenes. In this paper, rather than a single planar model, several coexisting planes are used to explain the observed color response. In estimating the illuminant, a set of candidate lights is assessed for goodness of fit given the assumed number of coexisting planes. The candidate light giving the minimum error fit is then chosen as representative of the scene illuminant. The performance of the proposed approach is explored on real images.
Free Fatty Acids in the Rat Brain in Moderate and Severe Hypoxia

Abstract: The effects of mild, moderate, and severe hypoxia on cerebral cortical concentrations of free fatty acids (FFAs) were investigated in artificially ventilated rats under nitrous oxide anaesthesia. No change occurred during either mild (arterial Po2 35–40 mm Hg) or moderate (Po2 25–30 mm Hg) hypoxia. The effects of severe hypoxia (Po2 about 20 mm Hg) combined with hypotension (mean arterial blood pressure 80–85 mm Hg) varied with the EEG pattern and the tissue energy state. Thus, a major increase in total as well as in individual FFAs occurred first when EEG was severely depressed (almost isoelectric) and energy homeostasis disrupted. On a relative basis the greatest change occurred in free arachidonic acid. It is concluded that hypoxia is associated with an increase in the concentrations of FFAs in brain tissue, provided that tissue oxygen deficiency is severe enough to cause tissue energy failure. However, an increase in FFAs does not invariably accompany minor reductions in the adenylate energy charge (EC) of the tissue.
Identification of protein coding regions in the human genome by quadratic discriminant analysis.

A new method for predicting internal coding exons in genomic DNA sequences has been developed. This method is based on a prediction algorithm that uses the quadratic discriminant function for multivariate statistical pattern recognition. Substantial improvements have been made (with only 9 discriminant variables) when compared with existing methods: HEXON [Solovyev, V. V. , Salamov, A. A. & Lawrence, C. B. (1994) Nucleic Acids Res. 22, 5156-5163] (based on linear discriminant analysis) and GRAIL2 [Uberbacher, E. C. & Mural, R. J. (1991) Proc. Natl. Acad. Sci. USA 88, 11261-11265] (based on neural networks). A computer program called MZEF is freely available to the genome community and allows users to adjust prior probability and to output alternative overlapping exons.
Short- and Long-Term Mortality in Severe Sepsis/Septic Shock in a Setting with Low Antibiotic Resistance: A Prospective Observational Study in a Swedish University Hospital

Background: There is little epidemiologic data on sepsis, particularly in areas of low antibiotic resistance. Here we report a prospective observational study of severe sepsis and septic shock in patients admitted to the Intensive Care Unit (ICU) at Karolinska University Hospital, Sweden. We aimed to evaluate short- and long-term mortality, and risk factors for sepsis-related death. A second aim was to investigate patient care in relation to gender. Methods: One hundred and one patients with severe sepsis and septic shock, admitted to the ICU between 2005 and 2009, were prospectively enrolled in the study. Defined primary endpoints were day 28, hospital, and 1-year mortality. Risk factors for sepsis-related death was evaluated with a multivariate analysis in a pooled analysis with two previous sepsis cohorts. In the subset of patient admitted to the ICU through the emergency department (ED), time to clinician evaluation and time to antibiotics were assessed in relation to gender. Results: In the septic cohort, the day 28, hospital, and 1-year mortality rates were 19, 29, and 34%, respectively. Ninety-three percent of the patients received adequate antibiotics from the beginning. Multi-resistant bacteria were only found in three cases. Among the 43 patients admitted to the ICU through the ED, the median time to antibiotics was 86 min (interquartile range 52–165), and overall 77% received appropriate antibiotics within 2 h. Female patients received antibiotics significantly later compared to male patients (p = 0.047). Conclusion: The results demonstrate relatively low mortality rates among ICU patients with severe sepsis/septic shock, as compared to reports from outside Scandinavia. Early adequate antibiotic treatment and the low incidence of resistant isolates may partly explain these findings. Importantly, a gender difference in time to antibiotic therapy was seen.
The Hidden Cost of Economic Development: The Biological Standard of Living in Antebellum Pennsylvania

Preface The 'antebellum puzzle' in Pennsylvania Historical anthropometrics: theory, method, and the state of the field Trade, economic restructuring, and physical stature variation Antebellum Pennsylvania: a test environment for the biological effects of market integration Variation and trends in the stature of antebellum Pennsylvania Conclusion Appendix Bibliography Index.
Systematic review of postural control and lateral ankle instability, part II: is balance training clinically effective?

OBJECTIVE To answer the following clinical questions: (1) Can prophylactic balance and coordination training reduce the risk of sustaining a lateral ankle sprain? (2) Can balance and coordination training improve treatment outcomes associated with acute ankle sprains? (3) Can balance and coordination training improve treatment outcomes in patients with chronic ankle instability? DATA SOURCES PubMed and CINAHL entries from 1966 through October 2006 were searched using the terms ankle sprain, ankle instability, balance, chronic ankle instability, functional ankle instability, postural control, and postural sway. STUDY SELECTION Only studies assessing the influence of balance training on the primary outcomes of risk of ankle sprain or instrumented postural control measures derived from testing on a stable force plate using the modified Romberg test were included. Studies had to provide results for calculation of relative risk reduction and numbers needed to treat for the injury prevention outcomes or effect sizes for the postural control measures. DATA EXTRACTION We calculated the relative risk reduction and numbers needed to treat to assess the effect of balance training on the risk of incurring an ankle sprain. Effect sizes were estimated with the Cohen d for comparisons of postural control performance between trained and untrained groups. DATA SYNTHESIS Prophylactic balance training substantially reduced the risk of sustaining ankle sprains, with a greater effect seen in those with a history of a previous sprain. Completing at least 6 weeks of balance training after an acute ankle sprain substantially reduced the risk of recurrent ankle sprains; however, consistent improvements in instrumented measures of postural control were not associated with training. Evidence is lacking to assess the reduction in the risk of recurrent sprains and inconclusive to demonstrate improved instrumented postural control measures in those with chronic ankle instability who complete balance training. CONCLUSIONS Balance training can be used prophylactically or after an acute ankle sprain in an effort to reduce future ankle sprains, but current evidence is insufficient to assess this effect in patients with chronic ankle instability.
A distributed MPC scheme with low communication requirements

In this work, we consider the problem of controlling two linear systems coupled through the inputs. We propose a novel distributed model predictive control method based on game theory in which two different agents communicate in order to find a cooperative solution to the centralized control problem. We assume that each agent only has partial information of the model and the state of the system. The class of systems considered arises naturally in multi-input multi-output processes in which a transfer function model is obtained using standard identification techniques. The performance and the robustness of the proposed control scheme with respect to data losses in the communications are illustrated by extensive simulations.
Influence of diet pellet hardness and particle size on food utilization by mice, rats and hamsters

Increasing hardness of diet pellets reduced food wastage by each species. Also, less wastage occurred when pellets made from finely ground materials were given, an effect that was not related to hardness. The hardest diet reduced growth of the mice by reducing true food consumption and a poorer food conversion efficiency (true food consumption/growth) was obtained. Apparent food consumption increased with the softness of the diet and food utilization (apparent food consumption/growth) of the softest diets was less efficient than those of the others. Grinding of the raw materials prior to pelleting had no effect on food conversion, but food utilization was less efficient because of the greater wastage of pellets from coarsely ground materials and consequent apparent food consumption.
Identification and characterization of genes encoding sex pheromone cAM373 activity in Enterococcus faecalis and Staphylococcus aureus

The sex pheromone cAM373 of Enterococcus faecalis and the related staph‐cAM373 of Staphylococcus aureus were found to correspond to heptapeptides located within the C‐termini of the signal sequences of putative prelipoproteins. The deduced mature forms of the lipoproteins share no detectable homology and presumably serve unrelated functions in the cells. The chromosomally encoded genetic determinants for production of the pheromones have been identified and designated camE (encoding cAM373) and camS (encoding staph‐cAM373). Truncated and full‐length clones of camE were generated in Escherichia coli, in which cAM373 activity was expressed. In E. faecalis, insertional inactivation in the middle of camE had no detectable phenotypic effects on the pheromone system. Establishment of an in frame translation stop codon within the signal sequence resulted in reduction of cAM373 activity to 3% of normal levels. The camS determinant has homologues in Staphylococcus epidermidis, Bacillus subtilis and Listeria monocytogenes; however, corresponding heptapeptides present within those sequences do not resemble staph‐cAM373 closely. The particular significance of staph‐cAM373 as a potential intergeneric inducer of transfer‐proficient genetic elements is discussed.
Non-fused Phospholes as Fluorescent Probes for Imaging of Lipid Droplets in Living Cells

Molecular tools for fluorescent imaging of specific compartments in cells are essential for understanding the function and activity of cells. Here, we report the synthesis of a series of pyridyl- and thienyl-substituted phospholes and the evaluation of these dyes for fluorescent imaging of cells. The thienyl-substituted phospholes proved to be successful for staining of cultured normal and malignant cells due to their fluorescent properties and low toxicity. Co-staining experiments demonstrated that these probes target lipid droplets, which are, lipid-storage organelles found in the cytosol of nearly all cell types. Our findings confirm that thienyl-substituted phospholes can be utilized as fluorescent tools for vital staining of cells, and we foresee that these fluorescent dyes might be used in studies to unravel the roles that lipid droplets play in cellular physiology and in diseases.
Genomic Survey and Biochemical Analysis of Recombinant Candidate Cyanobacteriochromes Reveals Enrichment for Near UV/Violet Sensors in the Halotolerant and Alkaliphilic Cyanobacterium Microcoleus IPPAS B353*

Background: Cyanobacteriochromes (CBCRs), photoreceptors that sense red to near-UV light, were not previously reported in the cyanobacterium Microcoleus. Results: The Microcoleus genome encodes seven CBCR proteins covalently attached to phycocyanobilin or phycoviolobilin. Conclusion: Near-UV and violet CBCRs are enriched in Microcoleus, whereas red- and green-sensitive CBCRs are absent. Significance: This is the first report of CBCRs in the Microcoleus genome. Cyanobacteriochromes (CBCRs), which are exclusive to and widespread among cyanobacteria, are photoproteins that sense the entire range of near-UV and visible light. CBCRs are related to the red/far-red phytochromes that utilize linear tetrapyrrole (bilin) chromophores. Best characterized from the unicellular cyanobacterium Synechocystis sp. PCC 6803 and the multicellular heterocyst forming filamentous cyanobacteria Nostoc punctiforme ATCC 29133 and Anabaena sp. PCC 7120, CBCRs have been poorly investigated in mat-forming, nonheterocystous cyanobacteria. In this study, we sequenced the genome of one of such species, Microcoleus IPPAS B353 (Microcoleus B353), and identified two phytochromes and seven CBCRs with one or more bilin-binding cGMP-specific phosphodiesterase, adenylyl cyclase and FhlA (GAF) domains. Biochemical and spectroscopic measurements of 23 purified GAF proteins from phycocyanobilin (PCB) producing recombinant Escherichia coli indicated that 13 of these proteins formed near-UV and visible light-absorbing covalent adducts: 10 GAFs contained PCB chromophores, whereas three contained the PCB isomer, phycoviolobilin (PVB). Furthermore, the complement of Microcoleus B353 CBCRs is enriched in near-UV and violet sensors, but lacks red/green and green/red CBCRs that are widely distributed in other cyanobacteria. We hypothesize that enrichment in short wavelength-absorbing CBCRs is critical for acclimation to high-light environments where this organism is found.
Mannose‐binding lectin engagement with late apoptotic and necrotic cells

The serum opsonin mannose‐binding lectin (MBL) has been shown to be involved in the handling of apoptotic cells. However, at what stage in the process this happens and whether this mediates activation of complement is unknown. Cells rendered apoptotic or necrotic were incubated with purified MBL/MBL‐associated serine protease (MASP) complexes and assessed by flow cytometry and fluorescence microscopy. MBL bound specifically to late apoptotic cells, as well as to apoptotic blebs and to necrotic cells, but not to early apoptotic cells. Binding of MBL could be inhibited by EDTA as well as with an antibody against the CRD region. Addition of C1q, another serum opsonin involved in the handling of apoptotic cells, prior to MBL partly inhibited MBL binding to apoptotic cells and vice versa. MBL/MASP could initiate deposition of purified complement C4 on the target cells. However, addition of MBL/MASP to whole serum deficient for both C1q and MBL did not enhance deposition of C4, but MBL enhanced phagocytosis of apoptotic cells by macrophages. These results demonstrate that MBL interacts with structures exposed on cells rendered late apoptotic or necrotic and facilitates uptake by macrophages. Thus, MBL may promote non‐inflammatory sequestration of dying host cells.
Experimental model of invasion and metastasis by orthotopic transplantation of oral squamous and adenoid cystic carcinomas into the tongue of nude mice.

Three squamous cell carcinoma (SCC) cell lines established from oral cancer, seven specimens of SCC and three of adenoid cystic carcinomas taken from the oral cavity during operations were transplanted into the tongues of nude mice. Metastases to the regional lymph nodes and the lungs were examined histologically. We were able to transplant every cell line or specimen of tissue into the tongue of nude mice, and found that cancer transplanted in the tongue invaded diffusely to the surrounding tissues without forming a capsule, and that the mode of invasion of the transplanted SCC was similar to that of the biopsy specimen of the patient from whom the material had been obtained. We also found that all three of the SCC cell lines, 3 of the 7 SCC specimens and 2 of the 3 adenoid cystic carcinoma tissues metastasized to the regional lymph node. SCC did not metastasize to the lung, but in two of the three adenoid cystic carcinomas we did see micrometastases to the lung. The study indicates that this method can be used as a model of metastasis in oral squamous cell carcinoma and adenoid cystic carcinoma to show the stages of metastasis in cancer.
Multi-objective ACO algorithms to minimise the makespan and the total rejection cost on BPMs with arbitrary job weights

ABSTRACT In this paper, we investigate the batch-scheduling problem with rejection on parallel machines with non-identical job sizes and arbitrary job-rejected weights. If a job is rejected, the corresponding penalty has to be paid. Our objective is to minimise the makespan of the processed jobs and the total rejection cost of the rejected jobs. Based on the selected multi-objective optimisation approaches, two problems, P1 and P2, are considered. In P1, the two objectives are linearly combined into one single objective. In P2, the two objectives are simultaneously minimised and the Pareto non-dominated solution set is to be found. Based on the ant colony optimisation (ACO), two algorithms, called LACO and PACO, are proposed to address the two problems, respectively. Two different objective-oriented pheromone matrices and heuristic information are designed. Additionally, a local optimisation algorithm is adopted to improve the solution quality. Finally, simulated experiments are conducted, and the comparative results verify the effectiveness and efficiency of the proposed algorithms, especially on large-scale instances.
A CMOS linear tunable transconductor for continuous-time tunable Gm-C filters

A novel CMOS linear transconductor is presented. It is basically an improvement of the classical telescopic cascode OTA with source degeneration in which the resistor has been implemented using quasi-floating-gates transistors. It also allows compact implementation of common mode voltage control circuitry in order to save area and power consumption. This transconductor has been designed in a 0.5 mum CMOS technology and the results obtained show a THD of -61 dB at 10 Mhz for a 1 Vpp output voltage. In order to show the feasibility for the implementation of tunable Gm-C filters using the proposed transconductor, a 1 MHz tunable third order Chebyshev low-pass filter suitable for Bluetooth applications has been experimentally validated.
Depressive personality styles and bipolar spectrum disorders: prospective tests of the event congruency hypothesis.

OBJECTIVES Research on unipolar depression has found that life events that are congruent with an individual's personality style increase vulnerability to depression (event congruency hypothesis). We tested whether the interaction of personality style and congruent life events predicted prospective increases in depressive and hypomanic symptoms among bipolar spectrum individuals over a 4-month follow-up. METHODS We followed 106 bipolar II or cyclothymic individuals prospectively for 4 months. Participants completed three measures of personality style at time 1 and a life event scale and semi-structured life events and diagnostic interviews at follow-up. Life events were coded as congruent or non-congruent with the personality styles. RESULTS A personality style characterized by self-criticism and performance evaluation interacted with congruent negative and positive events, respectively, to predict increases in depressive and hypomanic symptoms, respectively, over the 4 months. In contrast, an attachment-oriented personality style buffered against depression following congruent negative events. CONCLUSION Consistent with the event congruency hypothesis, a personality style focused on performance, high self-standards, and self-criticism may increase vulnerability to both depressive and hypomanic symptoms when bipolar individuals confront life events congruent with this style. In contrast, a personality style concerned with attachment to others may buffer against depression when bipolar individuals face congruent negative events.
The statistical analysis of individual defects constituting NBTI and its implications for modeling DC- and AC-stress

The physical origin of the Negative Bias Temperature Instability (NBTI) is still under debate. In this work we analyze the single defects constituting NBTI. We introduce a new measurement technique stimulating a charging of these defects. By employing a statistical analysis of many stochastic stimulation processes of the same defect we are able to determine the electric field and the temperature dependence of these defects with great precision. Based on our experiments we present and verify a new, physics-based, quantitative model allowing a precise prediction of NBTI degradation and recovery. This model takes the stress history into account and also provides a prediction for degradation due to AC-NBTI and an understanding of the special features seen in conjunction with AC-NBTI.
A LEGO experiment for embedded control system design

This article describes a simple, portable, yet effective experimental setup for use in courses that do not have dedicated laboratory facilities. Since the setup is based on LEGO parts and equipment, the experiment can be developed easily and relatively inexpensively. When combined with NQC freeware, students are exposed to programming embedded processors. Students also gain experience with the implementation of dynamic controllers and with non-ideal and nonlinear features present in real-world mechatronic systems. The experiment is especially effective when used for projects in introductory signals, systems, and controls courses.