Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterisation of artemisinin–chloroquinoline hybrids for potential metabolic liabilities

Abstract 1. Chemotherapy remains the effective way of controlling malaria infections. Many of the treatments have been rendered ineffective as a result of drug resistance by plasmodia species as well as toxicity. Molecular hybridisation is one of the techniques used in the synthesis of new-generation antimalarial techniques. In this paper, we explore some potential metabolic challenges associated with this technique. 2. In vitro metabolic clearance and metabolite identification were performed in cryopreserved hepatocytes. Reaction phenotyping and inhibition studies were conducted in human liver microsomes and recombinant cytochrome P450s (CYPs) 3. Metabolism in hepatocytes was not extensive with less than 25% of the hybrids being metabolised by contributing CYP enzymes. The hybrids were, however, potent inhibitors of CYPs 2C9 2C19 and 3A4. 4. Our data indicated that artemisinin–chloroquinoline hybrid both gained and lost favourable properties from the individual pharmacophoric units from which they were built. This highlights the challenges associated with the molecular hybridisation technique and a need to optimise the chemistry in an effort to maintain good properties while addressing new liabilities that arise.
Using iterative simulation to incorporate load-dependent lead times in master planning heuristics

In this paper, we consider heuristics for master planning in semiconductor manufacturing. While lead times are typically assumed as fixed in production planning, we use iterative simulation to take load-dependent lead times into account. An AutoSched AP simulation model of a semiconductor supply chain is used for implementing the scheme. Simulation results show that the iterative scheme converges fast and leads to less variable, more profitable production plans compared to planes obtained by the fixed lead time approach.
A Comparison between Fixed Priority and EDF Scheduling accounting for Cache Related Pre-emption Delays

In multitasking real-time systems, the choice of scheduling algorithm is an important factor to ensure that response time requirements are met while maximising limited system resources. Two popular scheduling algorithms include fixed priority (FP) and earliest deadline first (EDF). While they have been studied in great detail before, they have not been compared when taking into account cache related pre-emption delays (CRPD). Memory and cache are split into a number of blocks containing instructions and data. During a pre-emption, cache blocks from the pre-empting task can evict those of the pre-empted task. When the pre-empted task is resumed, if it then has to re-load the evicted blocks, CRPD are introduced which then affect the schedulability of the task. In this paper we compare FP and EDF scheduling algorithms in the presence of CRPD using the state-of-the-art CRPD analysis. We find that when CRPD is accounted for, the performance gains offered by EDF over FP, while still notable, are diminished. Furthermore, we find that under scenarios that cause relatively high CRPD, task layout optimisation techniques can be applied to allow FP to schedule tasksets at a similar processor utilisation to EDF. Thus making the choice of the task layout in memory as important as the choice of scheduling algorithm. This is very relevant for industry, as it is much cheaper and simpler to adjust the task layout through the linker than it is to switch the scheduling algorithm.
Liposome‐mediated transfer of vascular endothelial growth factor cDNA augments survival of random‐pattern skin flaps in the rat

Tissue engineering is an application for gene therapy that is in its infancy. We show that simple liposomal‐mediated gene transfer could result in a potentially useful biological effect in the field of wound healing. cDNA encoding the 165 amino acid form of vascular endothelial growth factor complexed to commercially available liposomes was injected into rat skin 1 week before raising a random pattern 3 × 10 cm flap. The flap survival was enhanced by 14 percent, and was accomplished without accessing the arterial inflow of the territory. These results were statistically significant (p < 0.002) and reproducible. No adverse effects were seen. Histological analysis of the angiogenesis localized much of the new vessel formation to the area around the hair follicles. Polymerase chain reaction amplification of extracted flap tissue confirmed the presence of the transgene.
Exact Structure Discovery in Bayesian Networks with Less Space

The fastest known exact algorithms for score-based structure discovery in Bayesian networks on n nodes run in time and space 2nnO(1). The usage of these algorithms is limited to networks on at most around 25 nodes mainly due to the space requirement. Here, we study space--time tradeoffs for finding an optimal network structure. When little space is available, we apply the Gurevich--Shelah recurrence---originally proposed for the Hamiltonian path problem---and obtain time 22n-snO(1) in space 2snO(1) for any s = n/2, n/4, n/8, . ; we assume the indegree of each node is bounded by a constant. For the more practical setting with moderate amounts of space, we present a novel scheme. It yields running time 2n(3/2)pnO(1) in space 2n(3/4)pnO(1) for any p = 0, 1, . , n/2; these bounds hold as long as the indegrees are at most 0.238n. Furthermore, the latter scheme allows easy and efficient parallelization beyond previous algorithms. We also explore empirically the potential of the presented techniques.
Synchronization and packet separation in wireless ad hoc networks by known modulus algorithms

In mobile asynchronous ad hoc networks, multiple users may transmit packets at the same time. If a collision occurs, then in current systems both packets are lost and need to be retransmitted, reducing the overall throughput. To mitigate this, we consider to extend the receiver with a small antenna array, so that it can suppress interfering signals. To characterize the signal of interest, we propose to modulate it at the symbol rate by a known amplitude variation. This allows the corresponding multichannel receiver to estimate the beamformer weights that will suppress the interfering sources. We introduce "known modulus algorithms" to achieve this. We also derive synchronization algorithms to estimate the offset of the desired packet in an observation window, among interfering data packets. The algorithms are illustrated via simulations.
Scanning Patterns of Faces do not Explain Impaired Emotion Recognition in Huntington Disease: Evidence for a High Level Mechanism

In the current study, we aimed to investigate the emotion recognition impairment in Huntington’s disease (HD) patients and define whether this deficit is caused by impaired scanning patterns of the face. To achieve this goal, we recorded eye movements during a two-alternative forced-choice emotion recognition task. HD patients in pre-symptomatic (n = 16) and symptomatic (n = 9) disease stages were tested and their performance was compared to a control group (n = 22). In our emotion recognition task, participants had to indicate whether a face reflected one of six basic emotions. In addition, and in order to define whether emotion recognition was altered when the participants were forced to look at a specific component of the face, we used a second task where only limited facial information was provided (eyes/mouth in partially masked faces). Behavioral results showed no differences in the ability to recognize emotions between pre-symptomatic gene carriers and controls. However, an emotion recognition deficit was found for all six basic emotion categories in early stage HD. Analysis of eye movement patterns showed that patient and controls used similar scanning strategies. Patterns of deficits were similar regardless of whether parts of the faces were masked or not, thereby confirming that selective attention to particular face parts is not underlying the deficits. These results suggest that the emotion recognition deficits in symptomatic HD patients cannot be explained by impaired scanning patterns of faces. Furthermore, no selective deficit for recognition of disgust was found in pre-symptomatic HD patients.
Variance and Autocorrelation of the Spontaneous Slow Brain Activity

Slow (<0.1 Hz) oscillatory activity in the human brain, as measured by functional magnetic imaging, has been used to identify neural networks and their dysfunction in specific brain diseases. Its intrinsic properties may also be useful to investigate brain functions. We investigated the two functional maps: variance and first order autocorrelation coefficient (r 1). These two maps had distinct spatial distributions and the values were significantly different among the subdivisions of the precuneus and posterior cingulate cortex that were identified in functional connectivity (FC) studies. The results reinforce the functional segregation of these subdivisions and indicate that the intrinsic properties of the slow brain activity have physiological relevance. Further, we propose a sample size (degree of freedom) correction when assessing the statistical significance of FC strength with r 1 values, which enables a better understanding of the network changes related to various brain diseases.
Characterization and 2D NMR study of the stable [9–21, 15–27] 2 disulfide intermediate in the folding of the 3 disulfide trypsin inhibitor EETI II

The three disulfide Ecballium elaterium trypsin inhibitor II (EETI II) reduction with dithiothreitol (DTT) and re‐oxidation of the fully reduced derivative have been examined. A common stable intermediate has been observed for both processes. Isolation and sequencing of carboxymethylated material showed that the intermediate lacks the [2–19] bridge. The NMR study showed a very strong structural conservation as compared to the native EETI II, suggesting that the bridges are the [9–21] and [15–27] native ones. The differences occurred in sections 2–7 (containing the free cysteine 2 and the Arg 4‐Ile 5 active site) and 19–21 (containing the second free cysteine). Distance geometry calculations and restrained molecular dynamics refinements were also in favor of a [9–21, 15–27] arrangement and resulted in a well‐conserved (7–28) segment.
Is there a threshold of hepatic iron concentration that leads to cirrhosis in C282Y hemochromatosis?

OBJECTIVE:The relationship between the degree of iron overload and the presence of cirrhosis has not been clearly established in hemochromatosis. Severe iron overload occurs without cirrhosis and moderate iron overload can occur with cirrhosis. Previous estimates may have overestimated the problem because of the overdiagnosis of hemochromatosis in patients with alcoholic liver disease and chronic viral hepatitis. The objective of this study was to determine if a threshold for hepatic iron concentration leads to the development of cirrhosis in C282Y hemochromatosis.METHODS:This study included only hemochromatosis patients who were homozygotes for the C282Y mutation of the HFE gene and had undergone liver biopsy with hepatic iron concentration. Analysis of the thresholds for cirrhosis were determined using receiver operating characteristic (ROC) curve analysis.RESULTS:Data were available on 100 C282Y homozygotes (62 men, 38 women; mean age 51, range 18–74 yr). ROC curve analysis showed an area under the curve for hepatic iron concentration versus cirrhosis of 0.85 (95% CI = 0.75–0.96). The threshold for the prediction of cirrhosis was 283 μmol/g. At that threshold, the sensitivity was 85% and specificity 84%. CONCLUSIONS:From this analysis, it appears that a hepatic iron concentration >283 μmol/g is associated with cirrhosis. However, the low sensitivity of this threshold suggests that other cofactors contribute to the development of cirrhosis in hemochromatosis. Early diagnosis is encouraged to initiate iron depletion before the development of cirrhosis.
Involvement of p38α Mitogen-activated Protein Kinase in Lung Metastasis of Tumor Cells*

To study the role of p38 mitogen-activated protein kinase (p38) activity during the process of metastasis, p38α+/- mice were subjected to an in vivo metastasis assay. The number of lung colonies of tumor cells intravenously injected in p38α+/- mice was markedly decreased compared with that in wild-type (WT) mice. On the other hand, the time-dependent increase in tumor volume after subcutaneous tumor cells transplantation was comparable between WT and p38α+/- mice. Platelets of p38α+/- mice were poorly bound to tumor cells in vitro and in vivo compared with those of WT mice. E- and P-selectin mRNAs were markedly induced in the lung after intravenous injection of tumor cells. However, the induction of these selectin mRNAs in p38α+/- mice was weaker than that in WT mice. Furthermore, the resting expression levels of E-selectin in lung endothelial cells and P-selectin in platelets of p38α+/- mice were suppressed compared with those of WT mice. The number of tumor cells attached on lung endothelial cells of p38α+/- mice was significantly reduced compared with that of WT mice. The transmigrating activity of tumor cells through lung endothelial cells of p38α+/- mice was similar to that of WT mice. These results suggest that p38α plays an important role in extravasation of tumor cells, possibly through regulating the formation of tumor-platelet aggregates and their interaction with the endothelium involved in a step of hematogenous metastasis.
Clipless and Sutureless Laparoscopic Adrenalectomy Carried Out With the LigaSure Device in 32 Patients

Background Laparoscopic adrenalectomy has become the standard procedure for treating patents with adrenal masses. The purpose of this study was to evaluate the use of the LigaSure vessel closure system during laparoscopic adrenalectomy. Methods The LigaSure device was used in 32 patients undergoing laparoscopic adrenalectomy for adrenal masses. Adrenalectomy was carried out without the use of clips or sutures for vessel closure. In 1 patient the adrenal tumor had invaded the ipsilateral kidney, so laparoscopic nephrectomy was also carried out during the same operation. In another patient, a renal cell carcinoma in the left kidney had metastasized to the right adrenal gland. Both the kidney and the contralateral adrenal gland were removed laparoscopically during the same operation. Results Adrenal masses had a mean greatest diameter of 3.48 cm (range 2 to 11 cm). Mean operative time was 83.2 minutes (range 30 to 190 min). Mean blood loss was 36.2 mL (range 10 to 140 mL). No conversions to open surgery were necessary. No patients experienced major bleeding intraoperatively or postoperatively. Adrenal tumor types included adrenocortical adenoma (16 patients), pheochromocytoma (13 patients), malignant pheochromocytoma (1 patient), chromophobic carcinoma (1 patient), and metastasis from a renal cell carcinoma (1 patient). Conclusions For vessel closure during laparoscopic adrenalectomy, the LigaSure device seems to be safe and effective. For patients with conditions such as renal cell carcinoma combined with metastasis to the contralateral adrenal gland, nephrectomy, and contralateral adrenalectomy can be carried out during the same laparoscopic operation.
Dynamic Resolution in the Co-Evolution of Morphology and Control

Evolutionary robotics is a promising approach to overcoming the limitations and biases of human designers in producing control strategies for autonomous robots. However, most work in evolutionary robotics remains solely concerned with optimizing control strategies for existing morphologies. By contrast, natural evolution, the only process that has produced intelligent agents to date, may modify both the control (brain) and morphology (body) of organisms. Therefore, co-evolving morphology along with control may provide a better path towards realizing intelligent robots. This paper presents a novel method for co-evolving morphology and control using CPPN-NEAT. This method is capable of dynamically adjusting the resolution at which components of the robot are created: a large number of small sized components may be present in some body locations while a smaller number of larger sized components is present in other locations. Advantages of this capability are demonstrated on a simple task, and implications for using this methodology to create more complex robots are discussed.
parkin-induced defects in neurophysiology and locomotion are generated by metabolic dysfunction and not oxidative stress

Parkinson's disease (PD) is characterized by movement disorders, including bradykinesia. Analysis of inherited, juvenile PD, identified several genes linked via a common pathway to mitochondrial dysfunction. In this study, we demonstrate that the larva of the Drosophila parkin mutant faithfully models the locomotory and metabolic defects of PD and is an excellent system for investigating their inter-relationship. parkin larvae displayed a marked bradykinesia that was caused by a reduction in both the frequency of peristalsis and speed of muscle contractions. Rescue experiments confirmed that this phenotype was due to a defect in the nervous system and not in the muscle. Furthermore, recordings of motoneuron activity in parkin larvae revealed reduced bursting and a striking reduction in evoked and miniature excitatory junction potentials, suggesting a neuronal deficit. This was supported by our observations in parkin larvae that the resting potential was depolarized, oxygen consumption and ATP concentration were drastically reduced while lactate was increased. These findings suggest that neuronal mitochondrial respiration is severely compromised and there is a compensatory switch to glycolysis for energy production. parkin mutants also possessed overgrown neuromuscular synapses, indicative of oxidative stress, which could be rescued by overexpression of parkin or scavengers of reactive oxygen species (ROS). Surprisingly, scavengers of ROS did not rescue the resting membrane potential and locomotory phenotypes. We therefore propose that mitochondrial dysfunction in parkin mutants induces Parkinsonian bradykinesia via a neuronal energy deficit and resulting synaptic failure, rather than as a consequence of downstream oxidative stress.
Investigating the influence of depth and degree of genotypic change on fitness in genetic programming

In this paper we investigate the influence of (a) the amount of variation generated in the genotype and (b) the depth of application of variation operators on the offspring fitness in genetic programming. Simulation results on three common test problems indicate that for certain features of the fitness distribution the location of the variation may play as important a role as the choice of the applied operators.
A validation of measures associated with the risk factors in technology outsourcing

In recent years, many firms have adopted outsourcing as a means to govern their information technology (IT) operations. While outsourcing is associated with several important benefits, it also entails risk. The main purpose of this study was to validate measures of the risk factors associated with outsourcing IT operations. Insights from transaction costs theory suggest that risk factors are inherent in the transaction itself, the supplier and the client. A survey of 132 senior IT executives was conducted to assess the measures, and reliability and validity assessment was performed using PLS.
A Proposed Theoretical Model for M-Learning Adoption in Developing Countries

This paper investigates the use of wireless technologies in education with particular reference to the potential for m-learning in developing countries. The reports of a number of current m-learning projects are explored, from which the perceived benefits of using wireless technologies in education, and potential barriers to their use are derived. The use of wireless technologies in education impacts learner motivation, collaboration and mobility, which results in benefits for learners, parents and teachers. Benefits are perceived to outweigh the difficulties encountered when integrating wireless technologies in education. Considerations to be examined include limitations of the devices, pedagogical issues, safety and security concerns, training and support issues, as well as cost considerations. By examining the recommendations from developed countries, wireless technologies can be adopted by the educational sector in developing countries. These recommendations include the establishment of guidelines and principles to ensure the appropriate use of wireless technologies, designing the devices with the end user in mind, and involving all stakeholders concerned. The proposed theoretical model for m-learning adoption in a developing country emphasises the importance of taking a systems view of all the elements that need to be in place in an m-learning environment, including the necessary stakeholders and key elements (communication infrastructure, mobile devices, learners and teachers), in order to ensure the effective adoption of wireless technologies in education. This model embraces the key issues with regard to m-learning as well as the critical success factors that are essential in ensuring successful adoption.
Labial and lingual/palatal bone thickness of maxillary and mandibular anteriors in human cadavers in Koreans

Purpose The aim of this study is to evaluate the buccal and lingual bone thickness in the anterior teeth and the relationship between bone thickness and the tissue biotype. Methods Three male and two female human cadaver heads (mean age, 55.4 years) were used in this study. First, the biotype of periodontium was evaluated and categorized into a thick or a thin group. Next, full thickness reflections of the mandible and the maxilla to expose the underlying bone for accurate measurements in the anterior regions were performed. After the removal of the half of the alveolar bone, the probe with a stopper was used to measure the thickness of bone plate at the alveolar crest (AC), 3 mm apical to the alveolar crest (AC-3), 6 mm apical to the alveolar crest (AC-6), and 9 mm apical to the alveolar crest (AC-9). Results Four of them had a thick biotype. There was no penetration or dehiscence. The thickness of the buccal plates at the alveolar crest were 0.97±0.18 mm, 0.78±0.21 mm, and 0.95±0.35 mm in the maxillary central incisors, lateral incisors, and canines, respectively. The thickness of the labial plates at the alveolar crest were 0.86±0.59 mm, 0.88±0.70 mm, and 1.17±0.70 mm in the mandibular central incisors, lateral incisors and canines, respectively. Conclusions The thickness of the labial plate in the maxillary anteriors is very thin that great caution is needed for placing an implant. The present study showed the bone thickness of maxillary and mandibular anteriors at different positions. Therefore, these data can be useful for the understanding of the bone thickness of the anteriors and a successful implant placement.