Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vivo Evaluation of P-glycoprotein Function at the Blood-Brain Barrier in Nonhuman Primates Using [11C]Verapamil

P-glycoprotein (P-gp) is a major efflux transporter contributing to the efflux of a range of xenobiotic compounds at the blood-brain barrier (BBB). In the present study, we evaluated the P-gp function at the BBB using positron emission tomography (PET) in nonhuman primates. Serial brain PET scans were obtained in three rhesus monkeys after intravenous administration of [11C]verapamil under control and P-gp inhibition conditions ([PSC833 ([3′-keto-Me-Bmt1]-[Val2]-cyclosporin) 20 mg/kg/2 h]). The parent [11C]verapamil and its metabolites in plasma were determined by HPLC with a positron detector. The initial brain uptake clearance calculated from the integration plot was used for the quantitative analysis. After intravenous administration, [11C]verapamil was taken up rapidly into the brain (time to reach the peak, 0.58 min). The blood level of [11C]verapamil decreased rapidly, and it underwent metabolism with time. The inhibition of P-gp by PSC833 increased the brain uptake of [11C]verapamil 4.61-fold (0.141 versus 0.651 ml/g brain/min, p < 0.05). These results suggest that PET measurement with [11C]verapamil can be used for the evaluation of P-gp function at the BBB in the living brain.
Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain

The α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. Here, a series of novel α-aminoamides containing an indole ring were designed and synthesized. These compounds were evaluated in mice using a formalin test and they exhibited significant anti-allodynia activities. However, the analgesic mechanism of these compounds remains unclear; a subset of the synthesized compounds can only moderately inhibit the sodium ion channel, Nav1.7, in a whole-cell patch clamp assay. Overall, these results suggest that introduction of an indole moiety to α-aminoamide derivatives can significantly improve their bioactivity and further study is warranted.
Accommodating Technological Innovation: Identity, Genetic Testing and the Internet

To evaluate the need for legal change stemming from technological innovation we need to look beyond the accommodations of specific rules and on to the impact of technological innovation on social structures, institutes and values. In this article I study how social tensions created by recent technological innovations produce a need to elevate a legal interest from the shadows of legal discourse into the forefront of legal debate. Specifically, I examine two innovations that are exerting significant influence on our lives - genetic testing and the Internet - and their impact on our normative conception of identity. This socially oriented approach leads to several insights. First, I show that a host of seemingly unrelated social and legal controversies emanating from these technologies can be traced to a common tension. I demonstrate that by altering social structures through which we perceive our identity, genetic testing and the Internet induce novel societal tensions Secondly, I find that despite the role identity tensions play in controversies implicating genetic testing and the Internet, these tensions are not addressed in the legal debate. Furthermore, I show that our legal tools often fail to even indirectly protect identity interests. The study of identity tensions, therefore, uncovers a need for legal adjustment to accommodate the social changes resulting from the diffusion of these new technologies. The failure to address identity interests combined with the frequent failure to provide for their protection calls for the incorporation of identity interests into our legal debate. Identity interests need to be considered in controversies as diverse as the physician's duty to warn relatives of a patient's genetic condition and commercial profiling on the Internet. Specifically, I propose two potential resolutions: (i) direct incorporation of an independent identity interest and; (ii) indirect incorporation through the readjustment of existing doctrinal tools. I suggest that the pressures applied by the new technologies make both options viable by creating the need for inducing long overdue changes in our traditionally conservative legal discourse.
Functional differences between afferent fibers in the hypogastric and pelvic nerves innervating female reproductive organs in the rat.

1. The uterus, cervix, and vaginal canal are innervated by afferent fibers in the hypogastric and pelvic nerves. Four studies compared the innervation territory and sensitivity to peripheral stimuli of the two sets of fibers in adult virgin rats. 2. Innervation territory was studied anatomically by injecting different fluorescent dyes into different parts of the reproductive, lower urinary, and lower digestive tracts and examining retrogradely labeled neurons in dorsal root ganglia. It was also studied electrophysiologically in anesthetized rats by summing potentials evoked in branches of the two nerves by electrical stimulation of different parts of the reproductive tract. 3. In both studies sensory innervation of the reproductive tract shifted from the pelvic to the hypogastric nerve (i.e., shifted entry into the spinal cord from the L6-S1 to the T13-L3 dorsal root ganglia, respectively) as the dye or stimulating electrode shifted from the vaginal entrance to the uterine horns, with fibers from both nerves densely innervating the cervix region (i.e., entering the spinal cord through both sets of ganglia). The anatomic results suggested that the regions innervated by fibers in one nerve might also be innervated by a small component of normally quiescent fibers in the other nerve. 4. Response sensitivity was studied electrophysiologically by simultaneously recording multiunit activity in branches of the hypogastric and pelvic nerves in two ways. First, in intact, anesthetized rats, activity was recorded during mechanical stimulation of the reproductive tract (distension of the vagina and uterus, probing the cervix). Second, in an in vitro organ preparation of the uterus and vagina, activity was recorded during chemical stimulation through the uterine artery with bradykinin, serotonin, NaCN, CO2, and KCl. 5. Pelvic nerve fibers were markedly more sensitive than hypogastric nerve fibers to uterine and cervical mechanostimulation. Similarly, pelvic nerve fibers were more likely to respond or responded more vigorously than hypogastric nerve fibers to all chemical stimuli (except KCl). 6. These results provide strong evidence that afferent fibers in the pelvic and hypogastric nerves of nulliparous adult rats subserve different functions in reproduction and sensation. Pelvic nerve fibers seem closely tied to sensory and behavioral processes associated with mating and conception, whereas hypogastric fibers seem closely tied to pregnancy and nociception, with fibers in both nerves serving functions during parturition.
Sixteen Years of Change for Australian Female Academics: Progress or Segmentation?.

Quantitative methods and secondary data informed by critical realism and a feminist standpoint provide a contemporary snapshot of academic gender ratios in Australian universities, along with historical data, for the entire population of interest. The study is set in the context of the well-researched, worldwide gendered nature of higher education and focuses on female academics in teaching due to the teaching-research status divide and systemic changes such as managerialism that bring teaching into the limelight. Findings reveal that women's overall status continues to improve, albeit slowly. For example, parity in the teaching professoriate may not be achieved until 2033. Apparent gains are patchy in that women tend to be confined to 'bad' jobs as casual teachers and males still constitute a large majority of the academic professoriate. Overall, the increasing numbers of women mask segmentation and marginalisation. The pipeline and critical mass theories are useful explanations for this gender imbalance. The main policy recommendation is to create and privilege ongoing, teaching specialist roles.
Structural Analyses of gp45 Sliding Clamp Interactions during Assembly of the Bacteriophage T4 DNA Polymerase Holoenzyme

In the preceding paper (Latham, G. J., Bacheller, D. J., Pietroni, P., and von Hippel, P. H. (1997)J. Biol. Chem. 272, 31677–31684), we demonstrated that the T4 gp44/62-ATP clamp loader binds to the C-terminal face of the gp45 sliding clamp. Here we extend these results by exploring the structural relationship between the gp43 polymerase and the gp45 sliding clamp. Using fluorescence intensity and polarization techniques, as well as photo-cross-linking methods, we present evidence that gp43, like gp44/62, binds to the C-terminal face of gp45. In addition, we show that g43 binds to the gp45 clamp in two distinct interaction modes, depending on the presence or absence of template-primer DNA. When template-primer DNA is present, gp43 binds tightly to gp45 to form the highly processive DNA polymerase holoenzyme. Gp43 also binds to gp45 in the absence of template-primer DNA, but this interaction is more than 100 times weaker than gp43-gp45 binding on DNA. Specific interactions between gp43 and the C-terminal face of gp45 are maintained in both modes of binding. These results underscore the pivotal role of template-primer DNA in modulating the strength of protein-protein interactions during DNA synthesis and provide additional insight into the structural requirements of the replication process.
Predicting long‐term outcome in schizophrenia

Prediction of 14‐ to 17‐year outcome from symptoms present at admission and psychosocial and personality data was attempted among the 92 survivors of a group of 110 first‐admitted schizophrenic patients. Three different outcome criteria were used and the correlations between these varied from low to high. Using a discriminant analytical approach where all 107 predictor variables were used to predict a combination of outcome criteria, 23% of outcome variance could be explained, which should be compared with 49% in a previous 5‐ to 9‐year outcome study on the same material. At least one outcome variable ‐ economic self‐support ‐ could not at all be predicted. “Atypical” symptoms were associated with favourable outcome and longitudinal variables indicative of “high‐risk personality”, or duration and severity of illness, were related to bad prognosis. Overt psychotic symptoms had no significant correlation with outcome.
An Additive Wiener Process-Based Prognostic Model for Hybrid Deteriorating Systems

Hybrid deteriorating systems, which are made up of both linear and nonlinear degradation parts, are often encountered in engineering practice, such as gyroscopes which are frequently utilized in ships, aircraft, and weapon systems. However, little reported literature can be found addressing the degradation modeling for a system of this type. This paper proposes a general degradation modeling framework for hybrid deteriorating systems by employing an additive Wiener process model that consists of a linear degradation part and a nonlinear part. Furthermore, we derive the analytical solution of the remaining useful life distribution approximately for the presented model. For a specific system in service, the posterior estimates of the stochastic parameters in the model are updated recursively by using the condition monitoring observations based on a Bayesian framework with the consideration that the stochastic parameters in the linear and nonlinear deteriorating parts are correlated. Thereafter, the posterior distribution of stochastic parameters is used to update in real-time the distribution of the remaining useful life where the uncertainties in the estimated stochastic parameters are incorporated. Finally, a numerical example and a practical case study are provided to verify the effectiveness of the proposed method. Compared with two existing methods in literature, our proposed degradation modeling method increases the one-step prediction accuracy slightly in terms of mean squared error, but gains significant improvements in the estimated remaining useful life.
Dynamic Shared SPM Reuse for Real-Time Multicore Embedded Systems

Allocating the scratchpad memory (SPM) space to tasks is a challenging problem in real-time multicore embedded systems that use shared SPM. Proper SPM space allocation is important, as it considerably influences the application worst-case execution time (WCET), which is of great importance in real-time applications. To address this problem, in this article we present a dynamic SPM reuse scheme, where SPM space can be reused by other tasks during runtime without requiring any static SPM partitioning. Although the proposed scheme is applied dynamically at runtime, the required decision making is fairly complex and hence cannot be performed at runtime. We have developed techniques to perform the decision making offline at design time in the form of optimization problems combined with task scheduling/mapping. The proposed work is unlike previous works that either exploit static schemes for SPM space allocation or perform task scheduling/mapping and SPM space allocation incoherently. The experimental results show that our dynamic SPM reuse scheme can reduce WCET by up to 55% as compared to recent previous works on SPM allocation in real-time multicore embedded systems.
Inactivation of the Medial Prefrontal Cortex Interferes with the Expression But Not the Acquisition of Differential Fear Conditioning in Rats

The medial prefrontal cortex (mPFC) has been implicated in the processing of emotionally significant stimuli, particularly the inhibition of inappropriate responses. We examined the role of the mPFC in regulation of fear responses using a differential fear conditioning procedure in which the excitatory conditioned stimulus (CS+) was paired with an aversive footshock and intermixed with the inhibitory conditioned stimulus (CS-). In the first experiment, using rats as subjects, muscimol, a gamma-amino-butyric acid type A (GABAA) receptor agonist, or artificial cerebrospinal fluid (aCSF) was infused intracranially into the mPFC across three conditioning sessions. Twenty-four hours after the last conditioning session, freezing response of the rats was tested in a drug-free state. Neither the muscimol nor the aCSF infusion had any effect on differential responding. In the second experiment, the same experimental procedure was used except that the infusion was made before the testing session rather than the conditioning sessions. The results showed that muscimol infusion impaired differential responding: the level of freezing to CS- was indiscriminable from that to CS+. Taken together, these results suggest that the mPFC is responsible for the regulation of fear response by inhibiting inappropriate fear expressions.
Analysis of Mistakes as a Method to Improve Test Case Design

Test Design -- how test specifications and test cases are created -- inherently determines the success of testing. However, test design techniques are not always properly applied, leading to poor testing. We have developed an analysis method based on identifying mistakes made when designing the test cases. Using an extended test case template and an expert review, the method provides a systematic categorization of mistakes in the test design. The detailed categorization of mistakes provides a basis for improvement of the Test Case Design, resulting in better tests. In developing our method we have investigated over 500 test cases created by novice testers. In a comparison with industrial test cases we could confirm that many of these mistake categories remain relevant also in an industrial context. Our contribution is a new method to improve the effectiveness of test case construction through proper application of test design techniques, leading to an improved coverage without loss of efficiency.
Boosted Convolutional Neural Networks

In this work, we propose a new algorithm for boosting Deep Convolutional Neural Networks (BoostCNN) to combine the merits of boosting and modern neural networks. To learn this new model, we propose a novel algorithm to incorporate boosting weights into the deep learning architecture based on least squares objective function. We also show that it is possible to use networks of different structures within the proposed boosting framework and BoostCNN is able to select the best network structure in each iteration. This not only results in superior performance but also reduces the required manual effort for finding the right network structure. Experiments show that the proposed method is able to achieve state-of-the-art performance on several fine-grained classification tasks such as bird, car, and aircraft classification.
Easily refutable subformulas of large random 3CNF formulas

A simple nonconstructive argument shows that most 3CNF formulas with cn clauses (where c is a large enough constant) are not satisfiable. It is an open question whether there is an efficient refutation algorithm that for most formulas with cn clauses proves that they are not satisfiable. We present a polynomial time algorithm that for most 3CNF formulas with cn 3/2 clauses (where c is a large enough constant) finds a subformula with O(c 2 n) clauses and then proves that this subformula is not satisfiable (and hence that the original formula is not satisfiable). Previously, it was only known how to efficiently certify the unsatisfiability of random 3CNF formulas with at least poly(log(n)) · n 3/2 clauses. Our algorithm is simple enough to run in practice. We present some preliminary experimental results.
Value Orientations to Explain Beliefs Related to Environmental Significant Behavior

In environmental literature it is argued that three different value orientations may be relevant for understanding environmental beliefs and intentions: egoistic, altruistic, and biospheric. Until now, the distinction between altruistic and biospheric value orientations has hardly been supported empirically. In this article, three studies are reported aimed to examine whether an egoistic, altruistic, and biospheric value orientation can indeed be distinguished empirically by using an adapted value instrument. Also, it is examined whether these value orientations are differently and uniquely related to general and specific beliefs and behavioral intention. Results provide support for the reliability and validity of the value instrument. All studies replicated the distinction into three value orientations, with sufficient internal consistency. Furthermore, when altruistic and biospheric goals conflict, they seem to provide a distinct basis for proenvironmental intentions. The value instrument could therefore be useful to better understand relationships between values, beliefs, and intentions related to environmentally significant behavior.
Visual gaze control during peering flight manoeuvres in honeybees

As animals travel through the environment, powerful reflexes help stabilize their gaze by actively maintaining head and eyes in a level orientation. Gaze stabilization reduces motion blur and prevents image rotations. It also assists in depth perception based on translational optic flow. Here we describe side-to-side flight manoeuvres in honeybees and investigate how the bees’ gaze is stabilized against rotations during these movements. We used high-speed video equipment to record flight paths and head movements in honeybees visiting a feeder. We show that during their approach, bees generate lateral movements with a median amplitude of about 20 mm. These movements occur with a frequency of up to 7 Hz and are generated by periodic roll movements of the thorax with amplitudes of up to ±60°. During such thorax roll oscillations, the head is held close to horizontal, thereby minimizing rotational optic flow. By having bees fly through an oscillating, patterned drum, we show that head stabilization is based mainly on visual motion cues. Bees exposed to a continuously rotating drum, however, hold their head fixed at an oblique angle. This result shows that although gaze stabilization is driven by visual motion cues, it is limited by other mechanisms, such as the dorsal light response or gravity reception.
Serum interleukin 18 and interleukin 18 binding protein in rheumatoid arthritis

Objective: To measure serum interleukin 18 (IL18) and IL18 binding protein (IL18BP) levels in patients with inflammatory arthropathies, and to identify associations with disease status and the response to treatment. Methods: Serum samples were obtained before and after methotrexate treatment from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) attending an early arthritis clinic. IL18 and IL18BP were measured by enzyme linked immunosorbent assay (ELISA). Results: Sixty patients with RA and 13 with PsA were evaluated. Serum IL18 levels were significantly higher in RA than in PsA (p<0.001). After six months' treatment with methotrexate, IL18 levels were reduced, but the differences were not significant (p=0.052). In cross sectional analyses, no correlations between IL18 levels and measures of disease activity or structural damage in RA were found. In longitudinal analyses, no correlations between IL18 levels and the response to treatment or the degree of progressive joint damage were found. Similarly, IL18BP levels were raised in RA, and were not associated with measures of the clinical status or the response to treatment. Conclusion: Raised serum levels of IL18 are consistent with a pathophysiological role in RA. However, in this study measurement of circulating IL18 and IL18BP did not correlate significantly with clinical measures of disease activity or the response to treatment in patients with early RA.
Do Individuals with Low Cognitive Control Benefit from Digitised Support? An individual differences study on workload, situational awareness, performance and communication

Cognitive control serves goal directed behaviour and entails the ability to 1) inhibit dominant or prepotent responses, 2) switch between tasks and mindsets and 3) update working memory. Previous research on individual differences in cognitive control and task performance mainly focused on finding relations between these different components of cognitive control and rather abstract experimental tasks. In contrast, in this thesis an applied method is adopted. To investigate the relation between individual differences in cognitive control and experienced workload, situational awareness (sa), performance and communication in an online coordination task, I joined the running "Commander Zone Management system" project of Thales Netherlands in cooperation with TNO. Sixteen participants performed a coordination task, in which they had to remotely coordinate and support three groups of gold prospectors. Participants performed the task twice: once supported by a paper map and once supported by a digitised support system providing up to date information about the current location of each group. The results suggested that, first, people with low cognitive control benefit from a digitised support system regarding experienced workload. Second, people with high switching capacity communicate more (but shorter) when incidents occur in the paper map condition, leading to better performance. Third, there were indications that digitised support as well as a high inhibiting capacity are associated with a higher level of sa in general and especially with the level of sa concerning the projection of future actions of elements in the environment. Due to some complications during the experiment some results remained unexplained or less interpretable. However, the results from this study clearly show the importance of including individual differences in cognitive control in future development of support systems and future studies on high workload situations.