Miracle-dz/UniFAR-FTUs huggingface dataset:
From the Cyclooxygenase-2 Inhibitor Celecoxib to a Novel Class of 3-Phosphoinositide-Dependent Protein Kinase-1 Inhibitors

The blockade of Akt activation through the inhibition of 3-phosphoinositide-dependent kinase-1 (PDK-1) represents a major signaling mechanism whereby celecoxib mediates apoptosis. Celecoxib, however, is a weak PDK-1 inhibitor (IC50, 48 μm), requiring at least 30 μm to exhibit discernable effects on the growth of tumor cells in vitro. Here, we report the structure-based optimization of celecoxib to develop PDK-1 inhibitors with greater potency in enzyme inhibition and growth inhibition. Kinetics of PDK-1 inhibition by celecoxib with respect to ATP suggest that celecoxib derivatives inhibit PDK-1 by competing with ATP for binding, a mechanism reminiscent to that of many kinase inhibitors. Structure-activity analysis together with molecular modeling was used to generate compounds that were tested for their potency in inhibiting PDK-1 kinase activity and in inducing apoptosis in PC-3 prostate cancer cells. Docking of potent compounds into the ATP-binding site of PDK-1 was performed for lead optimization, leading to two compounds, OSU-03012 and OSU-03013, with IC50 values in PDK-1 inhibition and apoptosis induction in the low μm range. Exposure of PC-3 cells to these agents led to Akt dephosphorylation and inhibition of p70 S6 kinase activity. Moreover, overexpression of constitutively active forms of PDK-1 and Akt partially protected OSU-03012-induced apoptosis. Screening in a panel of 60 cell lines and more extensive testing in PC-3 cells indicated that the mean concentration for total growth inhibition was ∼3 μm for both agents. Considering the conserved role of PDK-1/Akt signaling in promoting tumorigenesis, these celecoxib analogs are of translational relevance for cancer prevention and therapy.
A High-Throughput UHPLC-QqQ-MS Method for Polyphenol Profiling in Rosé Wines

A rapid, sensitive and selective analysis method using Ultra High Performance Liquid Chromatography coupled to triple-quadrupole Mass Spectrometry (UHPLC-QqQ-MS) has been developed for the quantification of polyphenols in rosé wines. The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, the present method allows the selective quantification of up to 152 phenolic and two additional non-phenolic wine compounds in 30 min without sample purification or pre-concentration, even at low concentration levels. This method was repeatably applied to a set of 12 rosé wines and thus proved to be suitable for high-throughput and large-scale metabolomics studies.
Examining Medication Adherence in Older Women with Coronary Heart Disease

The purposes of this study were to examine medication adherence in older women with coronary heart disease and to identify barriers and facilitators of medication adherence. Methods: The study used a semistructured interview guide and established measures to examine medication taking 3 months after hospital discharge. Results: Thirty-two women completed the study: 65.6% were adherent to medications, but others were less adherent and self-modified their therapy. Over half (52.1%) suffered side effects, 71.9% had experienced psychological barriers, and all had economic barriers. Facilitators included a pillbox system (85%) and discharge medication counseling (90%). Conclusion: Tailored interventions to improve adherence in older women are needed.
Financing Risk and Innovation

We provide a model of investment into new ventures that demonstrates why some places, times and industries should be associated with a greater degree of experimentation by investors. Investors respond to financing risk ? a forecast of limited future funding ? by modifying their focus to finance less innovative firms. Potential shocks to the supply of capital create the need for increased upfront financing, but this protection lowers the real option value of the new venture. In equilibrium, financing risk disproportionately impacts innovative ventures with the greatest real option value. We propose that extremely novel technologies may need `hot' financial markets to get through the initial period of discovery or diffusion.
Reproduction Does Not Adversely Affect Liver Mitochondrial Respiratory Function but Results in Lipid Peroxidation and Increased Antioxidants in House Mice

Reproduction is thought to come at a cost to longevity. Based on the assumption that increased energy expenditure during reproduction is associated with increased free-radical production by mitochondria, oxidative damage has been suggested to drive this trade-off. We examined the impact of reproduction on liver mitochondrial function by utilizing post-reproductive and non-reproductive house mice (Mus musculus) living under semi-natural conditions. The age-matched post-reproductive and non-reproductive groups were compared after the reproductive females returned to a non-reproductive state, so that both groups were in the same physiological state at the time the liver was collected. Despite increased oxidative damage (p = 0.05) and elevated CuZnSOD (p = 0.002) and catalase (p = 0.04) protein levels, reproduction had no negative impacts on the respiratory function of liver mitochondria. Specifically, in a post-reproductive, maintenance state the mitochondrial coupling (i.e., respiratory control ratio) of mouse livers show no negative impacts of reproduction. In fact, there was a trend (p = 0.059) to suggest increased maximal oxygen consumption by liver mitochondria during the ADP stimulated state (i.e., state 3) in post-reproduction. These findings suggest that oxidative damage may not impair mitochondrial respiratory function and question the role of mitochondria in the trade-off between reproduction and longevity. In addition, the findings highlight the importance of quantifying the respiratory function of mitochondria in addition to measuring oxidative damage.
Quorum regulatory small RNAs repress type VI secretion in Vibrio cholerae

Type VI secretion is critical for Vibrio cholerae to successfully combat phagocytic eukaryotes and to survive in the presence of competing bacterial species. V. cholerae type VI secretion system genes are encoded in one large and two small clusters. In V. cholerae, type VI secretion is controlled by quorum sensing, the cell–cell communication process that enables bacteria to orchestrate group behaviours. The quorum‐sensing response regulator LuxO represses type VI secretion genes at low cell density and the quorum‐sensing regulator HapR activates type VI secretion genes at high cell density. We demonstrate that the quorum regulatory small RNAs (Qrr sRNAs) that function between LuxO and HapR in the quorum‐sensing cascade are required for these regulatory effects. The Qrr sRNAs control type VI secretion via two mechanisms: they repress expression of the large type VI secretion system cluster through base pairing and they repress HapR, the activator of the two small type VI secretion clusters. This regulatory arrangement ensures that the large cluster encoding many components of the secretory machine is expressed prior to the two small clusters that encode the secreted effectors. Qrr sRNA‐dependent regulation of the type VI secretion system is conserved in pandemic and non‐pandemic V. cholerae strains.
A run-time modulo scheduling by using a binary translation mechanism

It is well known that innermost loop optimizations have a big effect on the total execution time. Although CGRAs is widely used for this type of optimizations, their usage at run-time has been limited due to the overheads introduced by application analysis, code transformation, and reconfiguration. These steps are normally performed during compile time. In this work, we present the first dynamic translation technique for the modulo scheduling approach that can convert binary code on-the-fly to run on a CGRA. The proposed mechanism ensures software compatibility as it supports different source ISAs. As proof of concept of scaling, a change in the memory bandwidth has been evaluated (from one memory access per cycle to two memory accesses per cycle). Moreover, a comparison to the state-of-the-art static compiler-based approaches for inner loop accelerators has been done by using CGRA and VLIW as target architectures. Additionally, to measure area and performance, the proposed CGRA was prototyped on a FPGA. The area comparisons show that crossbar CGRA (with 16 processing elements) is 1.9x larger than the VLIW 4-issue and 1.3x smaller than a VLIW 8-issue softcore processor, respectively. In addition, it reaches an overall speedup factor of 2.17x and 2.0x in comparison to the 4 and 8-issue, respectively. Our results also demonstrate that the run-time algorithm can reach a near-optimal ILP rate, better than an off-line compiler approach for an n-issue VLIW processor.
Mixed genotype transmission bodies and virions contribute to the maintenance of diversity in an insect virus

An insect nucleopolyhedrovirus naturally survives as a mixture of at least nine genotypes. Infection by multiple genotypes results in the production of virus occlusion bodies (OBs) with greater pathogenicity than those of any genotype alone. We tested the hypothesis that each OB contains a genotypically diverse population of virions. Few insects died following inoculation with an experimental two-genotype mixture at a dose of one OB per insect, but a high proportion of multiple infections were observed (50%), which differed significantly from the frequencies predicted by a non-associated transmission model in which genotypes are segregated into distinct OBs. By contrast, insects that consumed multiple OBs experienced higher mortality and infection frequencies did not differ significantly from those of the non-associated model. Inoculation with genotypically complex wild-type OBs indicated that genotypes tend to be transmitted in association, rather than as independent entities, irrespective of dose. To examine the hypothesis that virions may themselves be genotypically heterogeneous, cell culture plaques derived from individual virions were analysed to reveal that one-third of virions was of mixed genotype, irrespective of the genotypic composition of the OBs. We conclude that co-occlusion of genotypically distinct virions in each OB is an adaptive mechanism that favours the maintenance of virus diversity during insect-to-insect transmission.
Constraining Minimum-Norm Inverse by Phase Synchronization and Signal Power of the Scalp EEG Channels

In this paper, the goal is to further improve the output of the scalp EEG source localization by the Euclidean minimum-norm (MN) inverse during single trials. Trials have been selected based on signal power at specific time intervals in specific locations. Then the source localization has been performed by MN. It has been observed that close to a dominant cortical source of EEG, as determined by the MN, both pairwise phase synchronization of a channel with its nearest neighbors and the cumulative signal power of the channels within that neighborhood become high (normalized values remain above certain thresholds). This has also been verified through simulations on the subject's real head model. The conclusion of our study is that only those sources are to be chosen for which MN inverse, and signal power and phase synchronization profile converge. A novel fast Fourier transform (FFT) based phase synchronization measuring algorithm between a pair of signals has been developed whose time complexity is no more than that of the FFT.
Next generation wired intra-vehicle networks, a review

Automotive electronics is a rapidly expanding area with an increasing number of driver assistance and infotainment devices becoming standard in new vehicles. A review of current networking standards within vehicles reveals a fragmented and proprietary situation with several standards such as MOST, CAN and LVDS dominating, all of which are currently being used by various vehicle manufacturers. Due to the cost of employing a range of networking standards, there is a general desire within the automotive industry to converge on the use of the 802.3 Ethernet for all in-vehicle communication between devices. The introduction of in-vehicle cameras to provide driver assistance applications and the associated high bandwidth requirements of multi camera systems has accelerated the demand for a unifying automotive network architecture. This paper presents an overview of current research present in the literature and identifies trends in the field for the future.
Urban heat islands (UHI) mitigation in densely urban city of Tirana, Albania: Materials, energy, comfort

Urban Heat Island (UHI) is considered as one of the major problems in the 21st century as a result of urbanization and industrialization of human civilization. The urban structures generate a large amount of heat from solar radiations and other sources (i.e. anthropogenic heat). This situation is even worse in cities with high density and large population and extensive economic activities, Tirana, a densely urbanized city, is seriously facing this problem. In this context, the present paper is a review article aiming to present the actual state of the art on the development and the assessment of potential benefits (i.e. materials with high solar reflectance, urban vegetation) as UHI mitigation strategies for buildings and urban structures in Tirana, Albania. The analysis shows that the limited urban vegetation and inner-city neighborhoods structures are those ones in which the hazard potential of the UHI effect is shown to be the greatest. These neighborhoods have limited open space for tree planting and green area and therefore a lower maximum potential benefit. During the warming of the climate these neighborhoods face the greater consequences due to interactions between the UHI effect and global climate change. The results show that implementations of different strategies of urban heat island (UHI) mitigation can reduce negative impacts of hazards in cities, including overheating due to elevated temperatures, air pollution and associated public health effects. Such strategies also can lower the demand for air-conditioning-related energy production, reduce the effects of urban heat island and ultimately living in a better environment
Decoding Motor Unit Activity From Forearm Muscles: Perspectives for Myoelectric Control

We prove the feasibility of decomposing high density surface EMG signals from forearm muscles in non-isometric wrist motor tasks of normally limbed and limb-deficient individuals with the perspective of using the decoded neural information for prosthesis control. For this purpose, we recorded surface EMG signals during motions of three degrees of freedom of the wrist in seven normally limbed subjects and two patients with limb deficiency. The signals were decomposed into individual motor unit activity with a convolutive blind source separation algorithm. On average, for each subject, 16 ± 7 motor units were identified per motor task. The discharge timings of these motor units were estimated with an accuracy > 85%. Moreover, the activity of 6 ± 5 motor units per motor task was consistently detected in all repetitions of the same task. The joint angle at which motor units were first identified was 62.5 ± 26.4% of the range of motion, indicating a prevalence in the identification of high threshold motor units. These findings prove the feasibility of accurate identification of the neural drive to muscles in contractions relevant for myoelectric control, allowing the development of a new generation of myocontrol methods based on motor unit spike trains.
Neuroprotection of photoreceptors by minocycline in light-induced retinal degeneration.

PURPOSE Microglial cells have been found to play pivotal roles in various neuronal degenerative diseases such as Parkinson's and Alzheimer's diseases. Minocycline, a microglial inhibitor, has recently been shown to be neuroprotective in various models of cerebral ischemia and degenerative diseases of the brain. This study was conducted to evaluate the neuroprotective effect of minocycline and the role of microglia in light-induced retinal degeneration. METHODS BALB/cJ mice were exposed to intense green light for 3 hours and observed during 1, 3, or 7 days of dark recovery. The animals received intraperitoneal injections of minocycline or vehicle 1 day before exposure to light for 2, 4, or 8 days, depending on the periods of survival. Morphologic, morphometric, immunohistochemical, and electrophysiological studies were performed to evaluate the efficacy of minocycline in the amelioration of light-induced retinal degeneration and the possible involvement of microglial cells. RESULTS Minocycline treatment provided marked amelioration in the loss of photoreceptors in light-induced retinal degeneration, as evidenced by morphologic, morphometric, and electrophysiologic criteria. Morphologically, the minocycline-treated group showed markedly better preservation of the outer retina after exposure to light. Morphometrically, at 7 days after exposure to light, in the minocycline-treated animals, 89.1% of the normal-appearing photoreceptor nuclei remained, but in the retinas of the vehicle-control group only 38.0% of these nuclei remained. This difference was statistically significant (P < 0.001). At 7 days after exposure to light electroretinography (ERG) showed that minocycline significantly preserved the amplitudes of dark-adapted a- and b-wave and light-adapted b-wave, which were all significantly reduced after exposure to light. Concomitant with this protective effect, at 3 days after exposure to light, the CD11b(+) microglial cells in the outer nuclear layer (ONL) and subretinal space in the minocycline-treated group were significantly decreased (by 63.5%) when compared with those in the light-exposed, vehicle-treated control group (P < 0.01). CONCLUSIONS Minocycline is neuroprotective against light-induced loss of photoreceptors, possibly through the inhibition of retinal microglial activation.
Does an upper limit to river water temperature apply in all places?

There remains continued use of non‐linear, logistic regression models for predicting water temperature from air temperature. A dominant feature of these non‐linear models is an upper bound on river water temperature. This upper bound is often attributed to a large increase in evaporative cooling at high air temperatures, but the exact conditions under which such an increase may occur have not been thoroughly explored. To better understand the appropriateness of the non‐linear model for predicting river water temperatures, it is essential to understand the physical basis for the upper bound and when it should and should not be included in the statistical model. This paper applies and validates an energy balance model against 8 river systems spread across different climate regions of the United States. The energy balance model is then used to develop a diagram relating vapour pressure deficit and air temperature to water temperature. With knowledge of present or future vapour pressure deficit (difference between saturation and actual vapour content in the atmosphere) conditions in a given climate, the diagram can be used to predict the likelihood of an upper bound in the air–water temperature relationship. This investigation offers a fundamental physical explanation of the most appropriate form of statistical models that should be used for predicting future water temperature from air temperature in different geographic regions with different climate conditions. In general, climatic regions that have only a slight increase in vapour pressure deficit with increasing air temperature (typically humid regions) would not be expected to have an upper bound. Conversely, climatic regions in which vapour pressure deficit sharply increases with increasing air temperature (typically arid regions) would be expected to have an upper bound.
Time-Intensity Curve Parameters in Rectal Cancer Measured Using Endorectal Ultrasonography with Sterile Coupling Gels Filling the Rectum: Correlations with Tumor Angiogenesis and Clinicopathological Features

The primary aim of this study was to investigate the relationship between contrast-enhanced ultrasonography (CEUS) imaging parameters and clinicopathological features of rectal carcinoma and assess their potential as new radiological prognostic predictors. A total of 66 rectal carcinoma patients were analyzed with the time-intensity curve of CEUS. The parameter arrival time (AT), time to peak enhancement (TTP), wash-in time (WIT), enhanced intensity (EI), and ascending slope (AS) were measured. Microvessel density (MVD) was evaluated by immunohistochemical staining of surgical specimens. All findings were analysed prospectively and correlated with tumor staging, histological grading, and MVD. The mean values of AT, TTP, WIT, EI, and AS value of the rectal carcinoma were 10.84 ± 3.28 s, 20.61 ± 5.52 s, 9.78 ± 2.83 s, 28.68 ± 4.67 dB, and 3.20 ± 1.10, respectively. A positive linear correlation was found between the EI and MVD in rectal carcinoma (r = 0.295, P = 0.016), and there was a significant difference for EI among histological grading (r = −0.264, P = 0.007). EI decreased as T stage increased with a trend of association noted (P = 0.096). EI of contrast enhanced endorectal ultrasonography provides noninvasive biomarker of tumor angiogenesis in rectal cancer. CEUS data have the potential to predict patient prognosis.
Genetic variability in common wheat germplasm based on coefficients of parentage

The characterization of genetic variability and an estimate of the genetic relationship among varieties are essential to any breeding program, because artificial crosses among less similar parents allow a larger segregation and the combination of different favorable alleles. Genetic variability can be evaluated in different ways, including the Coefficient of Parentage (COP), which estimates the probability of two alleles in two different individuals being identical by descent. In this study, we evaluated the degree of genetic relationship among 53 wheat genotypes, and identified the ancestor genotypes which contributed the most to the current wheat germplasm, as a prediction of the width of the genetic base of this cereal. The results revealed a mean COP of 0.07 and the formation of 22 similarity groups. The ancestor genotypes Ciano 67 and Mentana were those which contributed the most to the current wheat germplasm. According to the COP analyses, the genetic base of wheat rests on a small number of ancestral genotypes.
Bayesian evidence synthesis for a transmission dynamic model for HIV among men who have sex with men

Understanding infectious disease dynamics and the effect on prevalence and incidence is crucial for public health policies. Disease incidence and prevalence are typically not observed directly and increasingly are estimated through the synthesis of indirect information from multiple data sources. We demonstrate how an evidence synthesis approach to the estimation of human immunodeficiency virus (HIV) prevalence in England and Wales can be extended to infer the underlying HIV incidence. Diverse time series of data can be used to obtain yearly “snapshots” (with associated uncertainty) of the proportion of the population in 4 compartments: not at risk, susceptible, HIV positive but undiagnosed, and diagnosed HIV positive. A multistate model for the infection and diagnosis processes is then formulated by expressing the changes in these proportions by a system of differential equations. By parameterizing incidence in terms of prevalence and contact rates, HIV transmission is further modeled. Use of additional data or prior information on demographics, risk behavior change and contact parameters allows simultaneous estimation of the transition rates, compartment prevalences, contact rates, and transmission probabilities.