Miracle-dz/UniFAR-FTUs huggingface dataset:
Revealing the paradox of drug reward in human evolution

Neurobiological models of drug abuse propose that drug use is initiated and maintained by rewarding feedback mechanisms. However, the most commonly used drugs are plant neurotoxins that evolved to punish, not reward, consumption by animal herbivores. Reward models therefore implicitly assume an evolutionary mismatch between recent drug-profligate environments and a relatively drug-free past in which a reward centre, incidentally vulnerable to neurotoxins, could evolve. By contrast, emerging insights from plant evolutionary ecology and the genetics of hepatic enzymes, particularly cytochrome P450, indicate that animal and hominid taxa have been exposed to plant toxins throughout their evolution. Specifically, evidence of conserved function, stabilizing selection, and population-specific selection of human cytochrome P450 genes indicate recent evolutionary exposure to plant toxins, including those that affect animal nervous systems. Thus, the human propensity to seek out and consume plant neurotoxins is a paradox with far-reaching implications for current drug-reward theory. We sketch some potential resolutions of the paradox, including the possibility that humans may have evolved to counter-exploit plant neurotoxins. Resolving the paradox of drug reward will require a synthesis of ecological and neurobiological perspectives of drug seeking and use.
Robust adaptive beamforming for general-rank signal models using positive semi-definite covariance constraint

In this paper, we develop an improved approach to the worst- case robust adaptive beamforming for general-rank signal models by means of taking into account the positive semi-definite constraint for the mismatched signal covariance matrix. The resulting robust adaptive beamforming problem is solved in an iterative way using semi-definite programming (SDP) at each iteration. Simulation results show that the proposed technique achieves a substantially improved performance as compared to the current robust adaptive beamforming techniques developed for the general-rank signal environments.
Discrete Molecular Dynamics Study of Aβ 16-22 Folding and Aggregation

Alzheimer’s disease (AD) is the most common cause of late life dementia. Substantial clinical and experimental evidence supports the hypothesis that amyloid β-protein (Aβ) aggregation produces assemblies with potent neurotoxic properties that cause AD. For this reason, it is important to elucidate the structural dynamics of Aβ aggregation at atomic level. We apply the discrete molecular dynamics method coupled with a four-bead protein model to study the aggregation of Aβ16-22, a peptide that contains the Aβ central hydrophobic cluster, Leu17–Ala21, found to be crucial in mediating Aβ assembly. Backbone hydrogen bond interactions are incorporated into the model. Effective hydrophobic and electrostatic interactions between side-chains are parameterized using amino acid-specific hydropathies and net charges. The aggregation of up to 16 Aβ16-22 peptides is studied. The results show that randomly-oriented monomers can aggregate into fibrillar subunits. These subunits consist of multi-layer β-sheets that resemble the well-known cross-β structure as revealed by X-ray diffraction studies of amyloid fibrils. An antiparallel arrangement of β-strands is observed within each β-sheet, which agrees with solid-state NMR studies. In the absence of electrostatic interactions the peptides aggregate into amorphous (disordered) structure, 2 suggesting that the electrostatic interactions are crucial to the antiparallel βsheet organization. Heat capacity calculations show that Aβ16-22 assembly and melting are two-stage processes, a prediction that can be tested experimentally using differential scanning calorimetry. Continued investigation of intermediate assembly states along the fibril formation pathway promises to reveal mechanistic features of Aβ assembly of value in the design of therapeutic agents.
BRAF mutations in chronic lymphocytic leukemia

Abstract BRAF mutations have been shown to occur at a high frequency in melanoma and thyroid cancer, but also at lower frequencies in hematological malignancies. To assess the potential role of BRAF, we have sequenced exons 11 and 15 of BRAF in 138 cases with chronic lymphocytic leukemia (CLL) and 32 cases of B-cell prolymphocytic leukemia (B-PLL). We found an incidence of BRAF mutations of 2.8% in CLL (4/138), while no cases with B-PLL showed BRAF mutations. The analysis of a cohort of patients with fludarabine-refractory disease (n = 87) showed no increase in the mutation incidence, suggesting that this mutation is not selected for during the disease progression. A limited analysis of the effect of BRAF inhibition in primary CLL cells showed no cell death induction in CLL samples with and without BRAF mutations. Our analysis suggests that BRAF mutations occur at a low frequency in CLL. The pharmacological inhibition of MEK/ERK signaling using the mutant BRAF inhibitor PLX4720 showed no effect on viability in vitro in CLL cases.
Regularity and Related Problems for Deterministic Pushdown Automata

It ~S shown that to decide whether the language accepted by an arbitrary deterministic pushdown automaton is LL (k), or whether ~t m accepted by some one-counter or finite-turn pushdown machine, must be at least as difficult as to decide whether it is regular. The regularity problem itself is analyzed in detail, and Stearns' dec~mon procedure for this as improved by one level of exponentiatlon Upper bounds, close to known lower bounds, are obtained for the succinctness with which a pushdown automaton, and various restrictions of it, can express equivalent fimte-state machines
The real-time link between person perception and action: Brain potential evidence for dynamic continuity

Using event-related potentials, we investigated how the brain extracts information from another's face and translates it into relevant action in real time. In Study 1, participants made between-hand sex categorizations of sex-typical and sex-atypical faces. Sex-atypical faces evoked negativity between 250 and 550 ms (N300/N400 effects), reflecting the integration of accumulating sex-category knowledge into a coherent sex-category interpretation. Additionally, the lateralized readiness potential revealed that the motor cortex began preparing for a correct hand response while social category knowledge was still gradually evolving in parallel. In Study 2, participants made between-hand eye-color categorizations as part of go/no-go trials that were contingent on a target's sex. On no-go trials, although the hand did not actually move, information about eye color partially prepared the motor cortex to move the hand before perception of sex had finalized. Together, these findings demonstrate the dynamic continuity between person perception and action, such that ongoing results from face processing are immediately and continuously cascaded into the motor system over time. The preparation of action begins based on tentative perceptions of another's face before perceivers have finished interpreting what they just saw.
Haptic Invitation of Textures: Perceptually Prominent Properties of Materials Determine Human Touch Motions

In daily life, certain textures and materials invite our touch motions. To seek the nature of such haptic invitation, we conducted a series of experiments consisting of sensory evaluations and ranking tasks for 36 materials to ascertain their perceptual properties and their degrees of haptic invitation. In addition, we recorded the human touch motions elicited by these materials. The results showed high degrees of haptic invitation for materials with perceptually prominent textures, which indicates that such textures frequently invite human touch motions. We also developed a Bayesian network model that represented the probabilistic relationships between invited touch motions and the properties of textures. The model substantiated the observation that different types of textural prominence led to different types of invited touch motions. These results collectively suggest that materials with prominent textures frequently encourage humans to touch them, using appropriate or specified touch motions.
Human Embryonic Mesenchymal Stem Cell-Derived Conditioned Medium Rescues Kidney Function in Rats with Established Chronic Kidney Disease

Chronic kidney disease (CKD) is a major health care problem, affecting more than 35% of the elderly population worldwide. New interventions to slow or prevent disease progression are urgently needed. Beneficial effects of mesenchymal stem cells (MSC) have been described, however it is unclear whether the MSCs themselves or their secretome is required. We hypothesized that MSC-derived conditioned medium (CM) reduces progression of CKD and studied functional and structural effects in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX) combined with L-NNA and 6% NaCl diet in Lewis rats. Six weeks after SNX, CKD rats received either 50 µg CM or 50 µg non-CM (NCM) twice daily intravenously for four consecutive days. Six weeks after treatment CM administration was functionally effective: glomerular filtration rate (inulin clearance) and effective renal plasma flow (PAH clearance) were significantly higher in CM vs. NCM-treatment. Systolic blood pressure was lower in CM compared to NCM. Proteinuria tended to be lower after CM. Tubular and glomerular damage were reduced and more glomerular endothelial cells were found after CM. DNA damage repair was increased after CM. MSC-CM derived exosomes, tested in the same experimental setting, showed no protective effect on the kidney. In a rat model of established CKD, we demonstrated that administration of MSC-CM has a long-lasting therapeutic rescue function shown by decreased progression of CKD and reduced hypertension and glomerular injury.
DYNAMIC AXIAL RESPONSE OF SINGLE PILES EMBEDDED IN TRANSVERSELY ISOTROPIC SOILS

The response of piles with circular section embedded in transversely isotropic half spaces to timeharmonic axial loads is analyzed. The pile is modeled by the Finite Element technique as a series of bar elements. The soil is modeled by an indirect formulation of the Boundary Element Method. The BEM formulation uses influence functions which are displacements and stresses due to loads distributed along circular and cylindrical surfaces inside a transversely isotropic elastic half space. This approach has two main advantages: only the soil-pile interface needs discretization and the load sources can be applied directly along the true pile surface. The coupling between the two models is set at the middle point of the bar elements, rather than at the end points. This leads to a much more stable numeric solution and to a smoother load transfer profile. The results for the isotropic case are compared with numerical values obtained by other researchers. The influence of the soil anisotropy is addressed.
Option Contracts and Capacity Management—Enabling Price Discrimination under Demand Uncertainty

We explore using an option contract as a price discrimination tool under demand uncertainty. In our capacity game model, a monopolistic supplier has to build capacity before observing the uncertain demand. The demand is generated by two potential customers, who privately know their own types. The types could be either high or low, differing in willingness to pay for each unit of demand. To discriminate between the customer types, the supplier designs option contracts so that only the high type will buy options in advance. The high type will do so because the options can hedge their risk of demand loss when capacity is tight. The supplier profits in three ways. First, the high type customers pay higher marginal prices on average. Second, the high type customers' demand is satisfied as a first priority, guaranteeing allocation efficiency. Third, the supplier can observe the number of options being purchased and so determine customer types, improving capacity investment efficiency. We compare our results to those of classical second degree price discrimination. We show that our proposed framework guarantees the same level of supplier profit even when the supplier cannot discriminate between the customers by bundling products.
Sideways Camera Rotations of 90° and 135° Result in Poorer Performance of Laparoscopic Tasks for Novices

Objective: The aim of this study was to determine the impact of sideways visuomotor rotations between 0° and 180° on novice performance in a laparoscopic simulator. Background: The laparoscopic surgical environment often involves visuomotor rotations because the laparoscope may be placed to the surgeon’s side. Basic research by Cunningham indicated that visuomotor rotations between 90° and 135° result in peak performance decrements. Research by Ames and colleagues failed to replicate Cunningham’s results in the laparoscopic environment, possibly due to (a) confounds from carryover effects or (b) use of an alternative laparoscopic training task rather than the straight-line pointing task used by Cunningham. Two experiments were conducted to determine if Cunningham’s results generalize to the laparoscopic environment when controlling for carryover effects for a three-dimensional “straight-line” pointing task (Experiment 1) and a laparoscopic training task (Experiment 2). Method: In Experiments 1 and 2, participants were assigned to one of five visuomotor rotations: 0°, 45°, 90°, 135°, or 180°. Utilizing a laparoscopic simulator, participants performed either a three-dimensional pointing task (Experiment 1) or a peg transfer task (Experiment 2). Results: In both experiments, visuomotor rotations of 90° or 135° resulted in the poorest performance. Conclusion: When controlling for carryover effects, Cunningham’s results generalize to novices’ performance of a pointing and a peg transfer task in the laparoscopic environment. Applications: The results indicate that 90° and 135° sideways laparoscope placements may result in worse performance for novices in the laparoscopic environment, indicating potentially longer learning curves for these conditions in the laparoscopic as well as other teleoperation environments.
The vasopressin Avprlb receptor: Molecular and pharmacological studies

The distribution, pharmacology and function of the arginine vasopressin (Avp) 1b receptor subtype (Avpr1b) has proved more challenging to investigate compared to other members of the Avp receptor family. Avp is increasingly recognised as an important modulator of the hypothalamic–pituitary–adrenal (HPA) axis, an action mediated by the Avpr1b present on anterior pituitary corticotrophs. The Avpr1b is also expressed in some peripheral tissues including pancreas and adrenal, and in the hippocampus (HIP), paraventricular nucleus and olfactory bulb of the rodent brain where its function is unknown. The central distribution of Avpr1bs is far more restricted than that of the Avpr1a, the main Avp receptor subtype found in the brain. Whether Avpr1b expression in rodent tissues is dependent on differences in the length of microsatellite dinucleotide repeats present in the 5′ promoter region of the Avpr1b gene remains to be determined. One difficulty of functional studies on the Avpr1b, especially its involvement in the HPA axis response to stress, which prompted the generation of Avpr1b knockout (KO) mouse models, was the shortage of commercially available Avpr1b ligands, particularly antagonists. Research on mice lacking functional Avpr1bs has highlighted behavioural deficits in social memory and aggression. The Avpr1b KO also appears to be an excellent model to study the contribution of the Avpr1b in the HPA axis response to acute and perhaps some chronic (repeated) stressors where corticotrophin-releasing hormone and other genes involved in the HPA axis response to stress do not appear to compensate for the loss of the Avpr1b.
Investigating Philosophies Underpinning Dietetic Private Practice

There is limited theory or knowledge regarding dietitians’ practice philosophies and how these philosophies are generated and incorporated into their professional practices. For the purposes of this study, a conceptual framework will explain and define the ‘philosophies’ as three different types of knowledge; episteme, techne, and phronesis. This study aimed to develop an explanatory theory of how dietitians in private practice source, utilise, and integrate practice philosophies. A grounded theory qualitative methodology was used to inform the sampling strategy, data collection, and analytical processes. Semi-structured interviews with dietitians in private practice were undertaken and data were collected and analysed concurrently. The results show that dietitians form collaborative relationships with their clients, in order to nurture change over time. They use intrinsic and intertwined forms of episteme, techne, and phronesis, which allow them to respond both practically and sensitively to their clients’ needs. The learning and integration of these forms of knowledge are situated in their own practice experience. Dietitians adapt through experience, feedback, and reflection. This study highlights that private practice offers a unique context in which dietitians deal with complex issues, by utilising and adapting their philosophies.
Antimicrobial effect of Pistacia atlantica leaf extract

The antimicrobial effect of the mastic tree (Pistacia atlantica) under in vitro conditions has been reported. Therefore, it is of interest to evaluate the effect of the plant leaf extract (aqueous) on bacterial load in mouth and saliva. The leaf of the Pistacia atlantica plant was collected and cleaned, dried at 40⁰c and then powdered. The extraction was carried out using the maceration method in vacuum with the rotary evaporator device. Bacterial inhibition (Streptococcus species) by the leaf extract was studied using the disc diffusion and embedding sink diffusion methods. The values of MIC and MBC were determined. The collected data was further analyzed using t-test and repeated measure statistical tests. The disc diffusion technique showed a significant inhibitory effect for Pistacia atlantica leaf extract on S. mutans (ATCC 35668) and S. mitis (ATCC 49456) with inhibition zones of 19 and 25 millimeters, respectively. This is for the highest leaf extract concentration used in this study (p<0.01). The values of MIC and MBC for S.mutans was 60, 90 μg/ml and for S. mitis was 75, 110 μg/ml (p<0.01 significance). The leaf extract has no significant effect on S. salivarius (ATCC 13419). Thus, the antimicrobial properties of the aqueous leaf extract from Pistacia atlantica is demonstrated in this study.
Bispecific Antibodies as a Development Platform for New Concepts and Treatment Strategies

With the development of molecular cloning technology and the deep understanding of antibody engineering, there are diverse bispecific antibody formats from which to choose to pursue the optimal biological activity and clinical purpose. The single-chain-based bispecific antibodies usually bridge tumor cells with immune cells and form an immunological synapse because of their relatively small size. Bispecific antibodies in the IgG format include asymmetric bispecific antibodies and homodimerized bispecific antibodies, all of which have an extended blood half-life and their own crystalline fragment (Fc)-mediated functions. Besides retargeting effector cells to the site of cancer, new applications were established for bispecific antibodies. Bispecific antibodies that can simultaneously bind to cell surface antigens and payloads are a very ideal delivery system for therapeutic use. Bispecific antibodies that can inhibit two correlated signaling molecules at the same time can be developed to overcome inherent or acquired resistance and to be more efficient angiogenesis inhibitors. Bispecific antibodies can also be used to treat hemophilia A by mimicking the function of factor VIII. Bispecific antibodies also have broad application prospects in bone disorders and infections and diseases of the central nervous system. The latest developments of the formats and application of bispecific antibodies will be reviewed. Furthermore, the challenges and perspectives are summarized in this review.
Incremental Learning of Local Linear Mappings

A new incremental network model for supervised learning is proposed. The model builds up a structure of units each of which has an associated local linear mapping (LLM). Error information obtained during training is used to determine where to insert new units whose LLMs are interpolated from their neighbors. Simulation results for several classiication tasks indicate fast convergence as well as good generalization. The ability of the model to also perform function approximation is demonstrated by an example.
Disentangling the Quantum World

Correlations related to related to quantum entanglement have convinced many physicists that there must be some at-a-distance connection between separated events, at the quantum level. In the late 1940s, however, O. Costa de Beauregard proposed that such correlations can be explained without action at a distance, so long as the influence takes a zigzag path, via the intersecting past lightcones of the events in question. Costa de Beauregard's proposal is related to what has come to be called the retrocausal loophole in Bell's Theorem, but -- like that loophole -- it receives little attention, and remains poorly understood. Here we propose a new way to explain and motivate the idea. We exploit some simple symmetries to show how Costa de Beauregard's zigzag needs to work, to explain the correlations at the core of Bell's Theorem. As a bonus, the explanation shows how entanglement might be a much simpler matter than the orthodox view assumes -- not a puzzling feature of quantum reality itself, but an entirely unpuzzling feature of our knowledge of reality, once zigzags are in play.
A statistical word-level translation model for comparable corpora

In this paper, we present a model of statistical word-level mapping for comparable corpora. The approach is based on the assumption that if two terms have close distributional profiles, their corresponding translations' distributional profiles should be close in a comparable corpus. The proposed model is described. A preliminary investigation on intralanguage comparable corpora is laid out. The preliminary results are >92% accurate, suggesting the feasibility of the model. The model needs to undergo some improvements and should be tested cross linguistically before assessing its significance.
3D Spatial Interaction with the Wii Remote for Head-Mounted Display Virtual Reality

This research investigates the design of a low-cost 3D spatial interaction approach using the Wii Remote for immersive Head-Mounted Display (HMD) virtual reality. Current virtual reality applications that incorporate the Wii Remote are either desktop virtual reality applications or systems that use large screen displays. However, the requirements for an HMD virtual reality system differ from such systems. This is mainly because in HMD virtual reality, the display screen does not remain at a fixed location. The user views the virtual environment through display screens that are in front of the user’s eyes and when the user moves his/her head, these screens move as well. This means that the display has to be updated in realtime based on where the user is currently looking. Normal usage of the Wii Remote requires the controller to be pointed in a certain direction, typically towards the display. This is too restrictive for HMD virtual reality systems that ideally require the user to be able to turn around in the virtual environment. Previous work proposed a design to achieve this, however it suffered from a number of drawbacks. The aim of this study is to look into a suitable method of using the Wii Remote for 3D interaction in a space around the user for HMD virtual reality. This paper presents an overview of issues that had to be considered, the system design as well as experimental results.