Miracle-dz/UniFAR-FTUs huggingface dataset:
Altered drug influx/efflux and enhanced metabolic activity in triclabendazole-resistant liver flukes

Triclabendazole (TCBZ) is a halogenated benzimidazole compound that possesses high activity against immature and adult stages of the liver fluke, Fasciola hepatica. The intensive use of TCBZ in endemic areas of fascioliasis has resulted in the development of liver flukes resistant to this compound. TCBZ sulphoxide (TCBZSO) and TCBZ sulphone (TCBZSO2) are the main molecules recovered in the bloodstream of TCBZ-treated animals. In order to gain some insight into the possible mechanisms of resistance to TCBZ, the goals of the work described here were: to compare the ex vivo transtegumental diffusion of TCBZ parent drug and its sulpho-metabolites (TCBZSO and TCBZSO2) into TCBZ-susceptible and -resistant liver flukes; and to assess the comparative pattern of TCBZ biotransformation by TCBZ-susceptible and -resistant F. hepatica. For the tegumental diffusion studies, TCBZ-susceptible (Cullompton) and -resistant (Sligo) adult flukes collected from untreated infected sheep were incubated (15–180 min) in KRT buffer containing either TCBZ, TCBZSO or TCBZSO2 (5 nmol.ml−1). For the metabolism studies, microsomal fractions obtained from TCBZ-susceptible and -resistant flukes were incubated for 60 min with TCBZ (40 μM), and the amount of the formed metabolic product (TCBZSO) was measured. Drug/metabolite concentrations were quantified by HPLC. All the assayed TCBZ-related molecules penetrated through the tegument of both TCBZ-susceptible and -resistant flukes. However, significantly lower (approximately 50%) concentrations of TCBZ and TCBZSO were recovered within the TCBZ-resistant flukes compared to the TCBZ-susceptible ones over the 180 min incubation period. The rate of TCBZ sulphoxidative metabolism into TCBZSO was significantly higher (39%) in TCBZ-resistant flukes. The flavin-monooxigenase (FMO) enzyme system appears to be the main metabolic pathway involved in the formation of TCBZSO in both TCBZ-susceptible and -resistant flukes. The altered drug influx/efflux and enhanced metabolic capacity identified in TCBZ-resistant liver flukes may account for the development of resistance to TCBZ.
Sending a Laplacian Source Using Hybrid Digital–Analog Codes

In this paper, we study transmission of a memoryless Laplacian source over three types of channels: additive white Laplacian noise (AWLN), additive white Gaussian noise (AWGN), and slow flat-fading Rayleigh channels under both bandwidth compression and bandwidth expansion. For this purpose, we analyze two well-known hybrid digital-analog (HDA) joint source-channel coding schemes for bandwidth compression and one for bandwidth expansion. Then we obtain achievable (absolute-error) distortion regions of the HDA schemes for the matched signal-to-noise ratio (SNR) case as well as the mismatched SNR scenario. Using numerical examples, it is shown that these schemes can achieve a distortion very close to the provided lower bound (for the AWLN channel) and to the optimum performance theoretically attainable bound (for AWGN and Rayleigh fading channels) on mean-absolute error distortion under matched SNR conditions. In addition, a non-linear analog coding scheme is analyzed, and its performance is compared to the HDA schemes for bandwidth compression under both matched and mismatched SNR scenarios. The results show that the HDA schemes outperform the non-linear analog coding over the whole CSNR region.
[Psychometric Properties of the Self- and Observer-Ratings ADHD-SR and Wender-Reimherr-Interview in the Assessment of ADHD Symptoms in Old Age].

Objective and Methods The aim of the study was to explore the psychometric properties of the ADHD self-rating ADHD-SR and the observer-rating Wender-Reimherr-Interview WRI for the assessment of ADHD symptoms in old age by using a sample of 324 subjects between 60 and 99 years. Results In the sample of older people the psychometric properties of the ADHD-SR and the WRI were adequate. Evidence for construct validity is provided through the WRI. Results of logistic analysis's showed a good discrimination of ADHD for both, the ADHD-SR (89.5 % correct classification; OR = 25.91) and the WRI (86.1 % correct classification; OR = 4.7); specificity ranged between 81 % and 94 %. Conclusion The study shows that both, the ADHD-SR and the WRI, are reliable and valid as tools for the assessment of ADHD in older adults.
Transform-Invariance in Local Averaging Classifier for Handwritten Digit Pattern Recognition

In this paper, a classification method designed by combining a local averaging classifier and a tangent distance is proposed for handwritten digit pattern recognition. In practice, first the k-nearest neighbors of an input sample are selected in each class by using a two-sided tangent distance. Next, the mean vectors of the selected transformed-neighbor samples are computed in individual classes. Finally, the input sample is classified to the class that minimizes the one sided tangent distance between the input sample and the mean one. The superior performance of the proposed method is verified with the experiments on benchmark datasets MNIST and USPS.
Evaluation of selective media for Campylobacter isolation when cycloheximide is replaced with amphotericin B

Aims: Laboratory media for the isolation of Campylobacter usually contain various selective agents, designed to allow these bacteria to grow whilst suppressing that of other organisms. For example, cycloheximide has often been incorporated into Campylobacter media to inhibit the growth of fungi. The production and availability of cycloheximide, however, has recently decreased due to concerns relating to its potential toxicity for mammalian cells and the compound has also become more expensive as a result. An alternative antifungal agent is necessary, and to address this, the effect of using amphotericin B in place of cycloheximide in Campylobacter selective broths and agars was examined.
Changes in Hypothalamic Estrogen Receptor-Containing Cell Numbers in Response to Feed Restriction in the Female Lamb

The mechanism whereby undernutrition enhances the ability of estradiol (E) to inhibit reproductive activity is unknown. This study aimed to determine the effect of feed restriction on E receptor (ER)-containing cell numbers in the female sheep hypothalamus. Ovariectomized lambs at 7 months of age received either ad libitum (AL; n = 5) or restricted (FR; n = 10) levels of feed intake. Lambs were weighted weekly and FR lambs fed to lose approximately 15% of their initial body weights over 7 weeks, at the end of which jugular blood samples were collected at 10-min intervals for 5 h to assess the patterns of LH release. After blood collection, lambs were euthanized and hypothalami collected for immunocytochemical detection of ER. Based on LH secretory profiles, FR lambs were subdivided into two groups. The first group (FR + LH; n = 5) exhibited patterns of LH release similar to AL controls. LH secretion in the second group (FR-LH; n = 5) was obviously suppressed. Numbers of ER-containing cells did not differ significantly (p > 0.10) among treatment groups in the bed nucleus stria terminalis, anterior hypothalamic area and arcuate nucleus. ER-containing cell numbers were greater (p < 0.05) in the preoptic area (POA) but less (p < 0.05) in the ventromedial/ventrolateral hypothalamus (VMH/VLH) for FR-LH lambs compared to AL animals. Notably, for both the POA and VMH/VLH, ER-containing cell numbers in the FR + LH animals were intermediate and did not differ (p > 0.10) from either FR-LH or AL lambs. These results suggest that feed restriction differentially alters ER-containing cell numbers in specific regions of the ovine hypothalamus (numbers increased in the POA but decreased in the VMH/VLH). These changes may, at least in part, represent a mechanism whereby undernutrition enhances the ability of E to inhibit reproduction.
Mechanistic Insights in Ethylene Perception and Signal Transduction1

New insights into the ethylene signaling pathway, including dynamic regulatory mechanisms, provide a more comprehensive view of ethylene perception and signal transduction. The gaseous hormone ethylene profoundly affects plant growth, development, and stress responses. Ethylene perception occurs at the endoplasmic reticulum membrane, and signal transduction leads to a transcriptional cascade that initiates diverse responses, often in conjunction with other signals. Recent findings provide a more complete picture of the components and mechanisms in ethylene signaling, now rendering a more dynamic view of this conserved pathway. This includes newly identified protein-protein interactions at the endoplasmic reticulum membrane, as well as the major discoveries that the central regulator ETHYLENE INSENSITIVE2 (EIN2) is the long-sought phosphorylation substrate for the CONSTITUTIVE RESPONSE1 protein kinase, and that cleavage of EIN2 transmits the signal to the nucleus. In the nucleus, hundreds of potential gene targets of the EIN3 master transcription factor have been identified and found to be induced in transcriptional waves, and transcriptional coregulation has been shown to be a mechanism of ethylene cross talk.
Trauma and Hallucinatory Experience in Psychosis

Recent research indicates that there may be phenomenological, symptom, and diagnostic associations between trauma and hallucinations. However, the nature of the relationship is poorly understood from a psychological perspective. We report a theoretically informed phenomenological study. From descriptions of reported traumas and hallucinations, we assessed the rates of four types of hypothesized association between traumas and hallucinations (direct, indirect, stress, and none) in 75 participants with nonaffective psychosis. In a subgroup who had experienced trauma (N = 40), 12.5% had hallucinations with similar themes and content to their traumas, 45% had hallucinations in which the themes were the same but not the content, and 42.5% had no identifiable associations between their hallucinations and previously experienced trauma. Traumas rated as intrusive were significantly associated with hallucinations rated as intrusive, although intrusive hallucinations were not associated with traumas in general. The traumas most likely to be associated with hallucinations were sexual abuse and bullying.
Transcriptional regulation of the Enterococcus faecium BM4147 vancomycin resistance gene cluster by the VanS-VanR two-component regulatory system in Escherichia coli K-12

An Escherichia coli K-12 model system was developed for studying the VanS-VanR two-component regulatory system required for high-level inducible vancomycin resistance in Enterococcus faecium BM4147. Our model system is based on the use of reporter strains with lacZ transcriptional and translational fusions to the PvanR or PvanH promoter of the vanRSHAX gene cluster. These strains also express vanR and vanS behind the native PvanR promoter, the arabinose-inducible ParaB promoter, or the rhamnose-inducible PrhaB promoter. Our reporter strains have the respective fusions stably recombined onto the chromosome in single copy, thereby avoiding aberrant regulatory effects that may occur with plasmid-bearing strains. They were constructed by using allele replacement methods or a conditionally replicative attP plasmid. Using these reporter strains, we demonstrated that (i) the response regulator VanR activates PvanH, but not PvanR, expression upon activation (phosphorylation) by the partner kinase VanS, the noncognate kinase PhoR, or acetyl phosphate, indicating that phospho-VanR (P-VanR) is a transcriptional activator; (ii) VanS interferes with activation of VanR by PhoR or acetyl phosphate, indicating that VanS also acts as a P-VanR phosphatase; and (iii) the conserved, phosphate-accepting histidine (H164) of VanS is required for activation (phosphorylation) of VanR but not for deactivation (dephosphorylation) of P-VanR. Similar reporter strains may be useful in new studies on these and other interactions of the VanS-VanR system (and other systems), screening for inhibitors of these interactions, and deciphering the molecular logic of the signal(s) responsible for activation of the VanS-VanR system in vivo. Advantages of using an E. coli model system for in vivo studies on VanS and VanR are also discussed.
Memetic algorithm for sorting unsigned permutations by reversals

Sorting by reversals unsigned permutations is a problem exhaustively studied in the fields of combinatorics of permutations and bioinformatics with crucial applications in the analysis of evolutionary distance between organisms. This problem was shown to be NP-hard, which gave rise to the development of a series of approximation and heuristic algorithms. Among these approaches, evolutionary algorithms were also proposed, from which to the best of our knowledge a parallel version of the first proposed genetic algorithm computes the highest quality results. These solutions were not optimized for the case when the population reaches a degenerate state, that is when individuals of the population remain very similar, and the procedure still continues consuming computational resources, but without improving the individuals. In this paper, a memetic algorithm is proposed for sorting unsigned permutations by reversals, using the local search as a way to improve the fitness function image of the individuals. Also, the entropy of the population is controlled, such that, when a degenerate state is reached the population is restarted. Several experiments were performed using permutations generated from biological data as well as hundreds of randomly generated permutations of different size, from which some ones were chosen and used as benchmark permutations. Experiments have shown that the proposed memetic algorithm uses more adequately the computational resources and gives competitive results in comparison with the parallel genetic algorithm and outperforms the results of the standard genetic algorithm.
Group Versus Individual Performance Pay in Relational Employment Contracts When Workers are Envious

I compare group to individual performance pay when workers are envious and performance is nonverifiable. Avoiding payoff inequity, the group reward scheme is optimal as long as the firm faces no credibility problem. The individual reward scheme may, however, become superior albeit introducing the prospect of unequal pay. This is due to two reasons: Group incentives are relatively low‐powered compared to individual incentives, requiring higher incentive pay and impeding credibility of the firm. Moreover, with individual rewards, the firm benefits from the incentive‐strengthening effect of envy, allowing for yet smaller overall incentive pay and further softening the credibility constraint. I also show that contracts combining both individual and group rewards are often optimal, depending on the firm's credibility problem. These contracts include joint and relative performance pay schemes.
Increased c‐Fos protein in the brains of scrapie‐infected SAMP8, SAMR1, AKR and C57BL mice

Scrapie is a neurodegenerative disease that occurs naturally in sheep and goats. The histopathological changes include vacuolation, neuronal apoptosis and astrocytosis. The mechanisms involved in neuronal apoptosis are still unknown. Recently, we observed that activated p38 immunohistostaining was increased in scrapie‐infected mice. In many neurodegenerative diseases, activation of the p38 pathway and of the immediate‐early gene termed c‐Fos appears to be required for the initiation of apoptosis. There are similarities in histopathological changes seen in scrapie‐infected mice and in an uninfected senescence‐accelerated mouse strain (SAMP8). This led us to investigate c‐Fos protein levels in the brains of both uninfected and scrapie‐infected SAMP8, SAMR1, AKR and C57BL mice using immunohistochemical methods. The SAMR1 strain served as a control in that it is a mouse strain that does not show accelerated ageing, but has a background that is similar to the SAMP8 strain. AKR was used because it is one of the progenitor strains of both SAM strains and, finally, C57BL is a completely unrelated strain. The results showed a low basal c‐Fos expression in controls and a marked increase in c‐Fos staining in scrapie‐infected mice. In scrapie‐positive mice, c‐Fos immunoreactivity was observed in neurones in the cortex, hippocampus, thalamus, hypothalamus, medulla, midbrain, brainstem, paraterminal body, internal capsule and cerebellar Purkinje cells. Immunoreactivity of c‐Fos was also observed in astrocytes in many brain areas of scrapie‐infected mice, particularly in the hippocampus and cortex. Our results show that normal mouse brain (NMB)‐injected AKR and SAMP8 mice had more c‐Fos production than NMB‐injected SAMR1 or C57BL mice; scrapie‐infection induces significant increases in c‐Fos immunoreactivity in all four mouse strains. Our study suggests that the increase in c‐Fos levels may play a role in the neuronal apoptosis observed in scrapie‐infected mice.
CD95/Fas, Non-Apoptotic Signaling Pathways, and Kinases

Endothelial cells lining new blood vessels that develop during inflammatory disorders or cancers act as doors that either allow or block access to the tumor or inflamed organ. Recent data show that these endothelial cells in cancer tissues and inflamed tissues of lupus patients overexpress CD95L, the biological role of which is a subject of debate. The receptor CD95 (also named Fas or apoptosis antigen 1) belongs to the tumor necrosis factor (TNF) receptor superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance. Because mutations of this receptor or its ligand lead to autoimmune disorders such as systemic lupus erythematosus (SLE) and cancers, CD95 and CD95L were initially thought to play a role in immune homeostasis and tumor elimination via apoptotic signaling pathways. However, recent data reveal that CD95 also evokes non-apoptotic signals, promotes inflammation, and contributes to carcinogenesis; therefore, it is difficult to dissect its apoptotic effects from its non-apoptotic effects during pathogenesis of disease. CD95L is cleaved by metalloproteases and so exists in two different forms: a transmembrane form and a soluble ligand (s-CD95L). We recently observed that the soluble ligand is overexpressed in serum from patients with triple-negative breast cancer or SLE, in whom it contributes to disease severity by activating non-apoptotic signaling pathways and promoting either metastatic dissemination or accumulation of certain T cell subsets in damaged organs. Here, we discuss the roles of CD95 in modulating immune functions via induction of mainly non-apoptotic signaling pathways.
The association between midlife blood pressure levels and late-life cognitive function. The Honolulu-Asia Aging Study.

OBJECTIVE To assess the long-term relationship of midlife blood pressure levels to late-life cognitive function. DESIGN The 4678 surviving cohort members of the prospective Honolulu Heart Program (baseline, 1965-1968) were examined a fourth time in 1991 through 1993 and given a cognitive test. PARTICIPANTS The subjects were 3735 Japanese-American men living in Hawaii in the community or in institutions, with an average age of 78 years at the fourth examination. MAIN OUTCOME MEASURES Cognitive function, measured by the 100-point Cognitive Abilities Screening Instrument (CASI), was categorized into good (reference: a CASI score of 92 to 100), intermediate (< 92 to 82), and poor (< 82). Midlife systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were measured in 1965, 1968, and 1971. A respondent was classified into the following categories if two of three measurements fell into the following groups: for SBP, < 110, 110 to 139, 140 to 159, and > or = 160 mm Hg; and for DBP, < 80, 80 to 89, 90 to 94, and > or = 95 mm Hg. RESULTS When we controlled for age and education, the risk for intermediate and poor cognitive function increased progressively with increasing level of midlife SBP category (P for trend < .03 and < .001, respectively). For every 10-mm Hg increase in SBP there was an increase in risk for intermediate cognitive function of 7% (95% confidence interval [CI], 3% to 11%) and for poor cognitive function of 9% (95% CI, 3% to 16%). Adjustment for prevalent stroke, coronary heart disease, and subclinical atherosclerosis reduced the strength of the relationship between midlife SBP and poor cognitive function to 5% (95% CI, 0% to 12%). The level of cognitive function was not associated with midlife DBP. CONCLUSIONS Midlife SBP is a significant predictor of reduced cognitive function in later life. Early control of SBP levels may reduce the risk for cognitive impairment in old age.
Adaptive filter for a miniature MEMS based attitude and heading reference system

A strapdown Inertial Navigation System (INS) can provide attitude and heading estimates after initialization and alignment. Many factors affect the accuracy and the performance of the system. They mainly are: sensor noise, bias, scale factor error, and alignment error. The Inertial Measurement Unit (IMU) based on the newly developed MEMS technology has wide applications due to its low-cost, small size, and low power consumption. However, the inertial MEMS sensors have large noise, bias and scale factor errors due to drift. The traditional strapdown algorithm using a low-cost MEMS sensor ONLY is difficultly satisfying the attitude and heading performance requirements. An extended Kalman filter with adaptive gain was used to build a miniature attitude and heading reference system based on a stochastic model. The adaptive filter has six states with a time variable transition matrix. The six states are three tilt angles of attitude and three bias errors for the gyroscopes. The filter uses the measurements of three accelerometers and a magnetic compass to drive the state update. When the system is in the non-acceleration mode, the accelerometer measurements of the gravity and the compass measurements of the heading have observability and yield good estimates of the states. When the system is in the high dynamic mode and the bias has converged to an accurate estimate, the attitude calculation will be maintained for a long interval of time. The adaptive filter tunes its gain automatically based on the system dynamics sensed by the accelerometers to yield optimal performance. The paper presents the methodology of the technique, performs the analysis, and gives the testing results of the system based on the adaptive filter. The whole system can be fitted within the size of 5cm /spl times/ 5cm /spl times/ 5cm with analog to digital conversion and digital signal processing boards.