Miracle-dz/UniFAR-FTUs huggingface dataset:
Common Neural Substrates for Response Selection across Modalities and Mapping Paradigms

In many situations, people can only compute one stimulus-to-response mapping at a time, suggesting that response selection constitutes a central processing bottleneck in human information processing. Using fMRI, we tested whether common or distinct brain regions were involved in response selection across visual and auditory inputs, and across spatial and nonspatial mapping rules. We isolated brain regions involved in response selection by comparing two conditions that were identical in perceptual input and motor output, but differed in the complexity of the mapping rule. In the visualmanual task of Experiment 1, four vertical lines were positioned from left to right, and subjects pressed one of four keys to report which line was unique in length. In the auditorymanual task of Experiment 2, four tones were presented in succession, and subjects pressed one of four keys to report which tone was unique in duration. For both visual and auditory tasks, the mapping between target position and key position was either spatially compatible or incompatible. In the verbal task of Experiment 3, subjects used nonspatial mappings that were either compatible (same if colors matched; different if they mismatched) or incompatible (the opposite). Extensive activation overlap was observed across all three experiments for incompatible versus compatible mapping in bilateral parietal and frontal regions. Our results indicate that common neural substrates are involved in response selection across input modalities and across spatial and nonspatial domains of stimulus-to-response mapping, consistent with behavioral evidence that response selection is a central process.
Plate-fin and Tube Heat Exchangers Refrigerant Circuiting Optimization in Vapor Compression Refrigeration Systems

Refrigerant circuitry in condensers and evaporators has a significant effect in the performance of refrigeration systems. The optimized project of the refrigerant circuits in refrigeration systems with plate-fin heat exchangers is not trivial, due to the complexity of their representation as well as the high number of possible combinations, even when methodologies of intelligent optimization are used. The present work proposes a new methodology for the simultaneous optimization of refrigerant circuiting in air-air refrigeration systems with plate-fin and tube heat exchangers. This new methodology proved to be more efficient than traditional methods. The method was applied, in conjunction with a full refrigeration system simulator for the optimization of a high performance commercial air- conditioning unit, considering the use of heat exchangers with tubes of different diameters. Overall, a predicted COP enhancement between 5.5% and 8.3% for system with R-22, and 6% - 6.5% for R410A, was observed with the optimization method.
Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma

Lobular carcinoma in situ (LCIS) of the breast is considered a marker for an increased risk of carcinoma in both breasts. However, the frequent association of LCIS with invasive lobular carcinoma (ILC) suggests a precursor‐product relation. The possible genomic relation between synchronous LCIS and ILC was analyzed using the technique of array‐based comparative genomic hybridization (CGH).
Adaptive biased-coin designs for clinical trials with several treatments

Adaptive designs are used in phase III clinical trials for skewing the allocation pattern towards the better treatments. We use optimum design theory to provide a skewed biased-coin procedure for sequential designs with continuous responses. The skewed designs are used to provide adaptive designs, the performance of which is studied numerically for designs with three treatments. Important properties are loss and the proportion of allocation to inferior treatments. Regularisation to provide consistent parameter estimates greatly improves both these properties.
Immunogenic Chemotherapy Sensitizes Renal Cancer to Immune Checkpoint Blockade Therapy in Preclinical Models

Background Renal cell carcinoma (RCC) is among the most common malignant cancers of males worldwide. For advanced RCC patients, there still is no effective therapy. Immune checkpoint blockade therapies have shown benefits for many cancers, but previous clinical trials of immune checkpoint blockade therapies in RCC patients achieved only modest results. Material/Methods We explored the effects of combining chemotherapy with immune checkpoint blockade therapy in RCC xenograft mouse models. We also studied the potential mechanisms by which chemotherapy might enhance the efficacy of immune checkpoint blockade therapy, both in vitro and in vivo. Results Our results showed that many commonly used chemotherapy agents can induce immunogenic marker release in RCC cell lines. Importantly, the RCC xenograft mouse model mice who received the combination treatment of 5-fluorouracil (5-FU) and anti-programmed cell death-ligand 1 (PD-L1) antibodies (Abs) had longer survival times compared to those who received 5-FU or anti-PD-L1 Abs alone. Also, increased key cytokines that promote tumor immunity, such as IL-2, IFN-γ, and TNF-α, as well as tumor-infiltrating cytotoxic T cells, were also increased after the combination treatment. Conclusions We conclude that 5-FU can sensitize RCC to anti-PD-L1 treatment by releasing the immune suppression in the tumor microenvironment.
A continuation method for semi-supervised SVMs

Semi-Supervised Support Vector Machines (S3VMs) are an appealing method for using unlabeled data in classification: their objective function favors decision boundaries which do not cut clusters. However their main problem is that the optimization problem is non-convex and has many local minima, which often results in suboptimal performances. In this paper we propose to use a global optimization technique known as continuation to alleviate this problem. Compared to other algorithms minimizing the same objective function, our continuation method often leads to lower test errors.
The Influence of Annotation, Corpus Design, and Evaluation on the Outcome of Automatic Classification of Human Emotions

The integration of emotions into human computer interaction applications promises a more natural dialog between the user and the technical system he operates. In order to construct such machinery, continuous measuring of the affective state of the user becomes essential. While basic research that is aimed to capture and classify affective signals has progressed, many issues are still prevailing that hinder easy integration of affective signals into human-computer interaction. In this paper, we identify and investigate pitfalls in three steps of the work-flow of affective classification studies. It starts with the process of collecting affective data for the purpose of training suitable classifiers. Emotional data has to be created in which the target emotions are present. Therefore, human participants have to be stimulated suitably. We discuss the nature of these stimuli, their relevance to human-computer interaction and the repeatability of the data recording setting. Second, aspects of annotation procedures are investigated, which include the variances of individual raters, annotation delay, the impact of the used annotation tool and how individual ratings are combined to a unified label. Finally, the evaluation protocol is examined which includes, amongst others, the impact of the performance measure on the accuracy of a classification model. We hereby focus especially on the evaluation of classifier outputs against continuously annotated dimensions. Alongside the discussed problems and pitfalls and the ways how they affect the outcome, we provide solutions and alternatives to overcome these issues. As a final part of the paper we sketch a recording scenario and a set of supporting technologies that can contribute to solve many of the issues mentioned above.
Subsumption, a Sometimes Undervalued Procedure

Rarely do circumstances permit one to simultaneously acknowledge a colleague's contributions, evaluate the relative importance of the basic elements of a field, and compare various paradigms for attacking a class of problems. However, through a fortuitous set of occurrences, we have that opportunity. We shall, therefore, take full advantage of the situation by presenting an evaluation of J. A. Robinson's contribution of
Association of CMV-Specific T Cell-Mediated Immunity with CMV DNAemia and Development of CMV Disease in HIV-1–Infected Individuals

Background Among HIV-1–infected individuals, cytomegalovirus (CMV) reactivation and disease occur in the setting of advanced immunosuppression. The value of a standardized assessment of CMV-specific T-cell mediated immunity by the CMV QuantiFERON assay (CMV-QFT) has not yet been thoroughly investigated in HIV-1–infected subjects. Methods Prospective, longitudinal study in 153 HIV-1–infected subjects with a CD4+ T cell count < 350/μL who simultaneously underwent CMV-QFT, CMV serology testing and CMV-DNA quantification. Factors associated with CMV-QFT were evaluated. Clinical screening for CMV manifestations was then performed every 3 months. Results Among the 141 CMV IgG-seropositive individuals the CMV-QFT assay yielded reactive results in 84% (118/141), negative results in 15% (21/141) and indeterminate (negative mitogen IFN-gamma response) results in 1% (2/141) of subjects. The mean actual CD4+ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015). A significantly lower proportion of CMV-QFT reactive vs. non-reactive patients displayed CMV DNAemia > 100 copies/mL (23% (27/118) vs. 48% (11/23), P = 0.02). Furthermore, a statistically significant inverse association between mitogen IFN-gamma response and CMV-DNAemia > 1000 copies/mL was observed (P < 0.001). During the observational period, 5 CMV end-organ manifestations were observed. In three of the CMV cases the CMV-QFT yielded indeterminate results. Conclusions While CMV-QFT reactivity indicates CMV-specific immunity, indeterminate results due to negative mitogen IFN-gamma response might reflect HIV-1-induced immunodeficiency. Thus, dependency upon CD4+ T cell count should be considered when interpreting CMV-QFT results.
The effect of a shear force on the cell shedding rate of the corneal epithelium.

PURPOSE During blinking the lids apply a shear force to the corneal epithelium. The aim of this study was to determine if a shear force applied to the epithelial surface increases the rate at which cells shed. METHODS The shedding rate was studied in perfused whole rabbit eyes, and the effect of a shear force examined by exposing the corneas to a stirred solution. Control corneas were exposed to a static solution. The shedding rate and size of shed cells were measured, and the number of terminally differentiated cells on the corneal surface determined after 6 h of perfusion using ethidium bromide. RESULTS Compared with controls, the shear force increased the cell shedding rate from the corneal surface significantly (p < 0.01, paired t-test). The increase was due to small cells with a longest dimension less than 25 microm. The number of terminally differentiated cells on the epithelial surface did not increase. CONCLUSION Because of the decrease in size, and the change in appearance of shedding cells, it is proposed that the increase in cell shedding rate was due to an increase in the number of apoptotic cells, and not to an increase in terminally differentiated cells. It is suggested that in the human eye, under adverse conditions, shear forces due to blinking may play a role in creating apoptotic cells.
Suppression outside the classical cortical receptive field

The important visual stimulus parameters for a given cell are defined by the classical receptive field (CRF). However, cells are also influenced by visual stimuli presented in areas surrounding the CRF. The experiments described here were conducted to determine the incidence and nature of CRF surround influences in the primary visual cortex. From extracellular recordings in the cat's striate cortex, we find that for over half of the cells investigated (56%, 153/271), the effect of stimulation in the surround of the CRF is to suppress the neuron's activity by at least 10% compared to the response to a grating presented within the CRF alone. For the remainder of the cells, the interactions were minimal and a few were of a facilitatory nature. In this paper, we focus on the suppressive interactions. Simple and complex cell types exhibit equal incidences of surround suppression. Suppression is observed for cells in all layers, and its degree is strongly correlated between the two eyes for binocular neurons. These results show that surround suppression is a prevalent form of inhibition and may play an important role in visual processing.
Modelling anaerobic digestion process with multiple-model

The anaerobic digestion is a wastewater treatment process without oxygen. It is a very complex process with a nonlinear model of six variables. This model is complex for state estimation and automatic control. We propose a nonlinear equivalent model but for which the theories developed for the linear case can be applied easily using the LMI tools.
Angiotensin IV AT4-receptor system in the rat kidney.

Angiotensin IV, {[des-Asp1,Arg2]ANG II or ANG-(3-8)}, has been shown to preferentially bind to a novel angiotensin binding site (AT4receptor). The cellular location and function of this receptor in the rat kidney is unknown. Autoradiography localized AT4 receptors to the cell body and apical membrane of convoluted and straight proximal tubules in the cortex and outer stripe of the outer medulla. ANG IV (0.1 pM-1 μM) elicited a concentration-dependent decrease in transcellular Na+ transport (as measured by proximal tubule O2 consumption rates) in fresh suspensions of control or nystatin-stimulated (bypasses rate-limiting step of apical Na+entry) rat proximal tubules. The inhibitory effect of 1 pM ANG IV was unaltered by either 1 μM losartan (AT1-receptor antagonist) or 1 μM PD-123319 (AT2-receptor antagonist) and yet was abolished by 1 μM divalinal-ANG IV (AT4-receptor antagonist) or ouabain pretreatment. These results demonstrate that the kidney AT4-receptor system is localized to the proximal tubule and suggests that one potential biological role of this system is in the regulation of Na+ transport by inhibiting a ouabain-sensitive component of Na+-K+-adenosinetriphosphatase activity in the rat.
Technology Dominance in Complex Decision Making: The Case of Aided Credibility Assessment

Decision aids have long been an important source of help in making structured decisions. However, decision support for more complex problems has been much more difficult to create. Decision aids are now being developed for very complex problems, and their effects among low- and high-task-knowledge individuals are still being explored. One such task is credibility assessment, in which message recipients or observers must determine a message's veracity and trustworthiness. Credibility assessment is made difficult by lack of constraints, hidden or incomplete information, and mistaken beliefs of the assessor. The theory of technology dominance (TTD) proposes that technology is most effectively applied in intelligent decision aids when an experienced user is paired with a sophisticated decision aid. This work examines TT D in the complex task of credibility assessment. To assist in credibility assessment, we created a decision aid that augments the capabilities of the user—whether novice or professional. Using hypotheses based on TT D, we tested the decision aid using high-stakes deception in recorded interviews and involved both student (novice) and law enforcement (professional) users. Both professionals and novices improved their assessment accuracy by using the decision aid. Consistent with TTD, novices were more reliant on the decision aid than were professionals. However, contrary to TTD, there was no significant difference in the way novices and professionals interacted with the system, and the decision aid was not more beneficial to professionals. Novices and professionals frequently discounted the aid's recommendations, and in many cases professionals did not view explanations when the decision aid contradicted their assessments. Potential reasons for these findings, as well as limitations and future research opportunities, are discussed.
Abnormalities in Brainstem Auditory Evoked Potentials in Sheep with Transmissible Spongiform Encephalopathies and Lack of a Clear Pathological Relationship

Scrapie is transmissible spongiform encephalopathy (TSE), which causes neurological signs in sheep, but confirmatory diagnosis is usually made postmortem on examination of the brain for TSE-associated markers like vacuolar changes and disease-associated prion protein (PrPSc). The objective of this study was to evaluate whether testing of brainstem auditory evoked potentials (BAEPs) at two different sound levels could aid in the clinical diagnosis of TSEs in sheep naturally or experimentally infected with different TSE strains [classical and atypical scrapie and bovine spongiform encephalopathy (BSE)] and whether any BAEP abnormalities were associated with TSE-associated markers in the auditory pathways. BAEPs were recorded from 141 clinically healthy sheep of different breeds and ages that tested negative for TSEs on postmortem tests to establish a reference range and to allow comparison with 30 sheep clinically affected or exposed to classical scrapie (CS) without disease confirmation (test group 1) and 182 clinically affected sheep with disease confirmation (test group 2). Abnormal BAEPs were found in 7 sheep (23%) of group 1 and 42 sheep (23%) of group 2. The proportion of sheep with abnormalities did not appear to be influenced by TSE strain or PrPSc gene polymorphisms. When the magnitude of TSE-associated markers in the auditory pathways was compared between a subset of 12 sheep with and 12 sheep without BAEP abnormalities in group 2, no significant differences in the total PrPSc or vacuolation scores in the auditory pathways could be found. However, the data suggested that there was a difference in the PrPSc scores depending on the TSE strain because PrPSc scores were significantly higher in sheep with BAEP abnormalities infected with classical and L-type BSE, but not with CS. The results indicated that BAEPs may be abnormal in sheep infected with TSEs but the test is not specific for TSEs and that neither vacuolation nor PrPSc accumulation appears to be responsible for the clinical abnormalities.
Inhibition of Wild-Type p53-Expressing AML by the Novel Small Molecule HDM2 Inhibitor CGM097

The tumor suppressor p53 is a key regulator of apoptosis and functions upstream in the apoptotic cascade by both indirectly and directly regulating Bcl-2 family proteins. In cells expressing wild-type (WT) p53, the HDM2 protein binds to p53 and blocks its activity. Inhibition of HDM2:p53 interaction activates p53 and causes apoptosis or cell-cycle arrest. Here, we investigated the ability of the novel HDM2 inhibitor CGM097 to potently and selectively kill WT p53-expressing AML cells. The antileukemic effects of CGM097 were studied using cell-based proliferation assays (human AML cell lines, primary AML patient cells, and normal bone marrow samples), apoptosis, and cell-cycle assays, ELISA, immunoblotting, and an AML patient–derived in vivo mouse model. CGM097 potently and selectively inhibited the proliferation of human AML cell lines and the majority of primary AML cells expressing WT p53, but not mutant p53, in a target-specific manner. Several patient samples that harbored mutant p53 were comparatively unresponsive to CGM097. Synergy was observed when CGM097 was combined with FLT3 inhibition against oncogenic FLT3-expressing cells cultured both in the absence as well as the presence of cytoprotective stromal-secreted cytokines, as well as when combined with MEK inhibition in cells with activated MAPK signaling. Finally, CGM097 was effective in reducing leukemia burden in vivo. These data suggest that CGM097 is a promising treatment for AML characterized as harboring WT p53 as a single agent, as well as in combination with other therapies targeting oncogene-activated pathways that drive AML. Mol Cancer Ther; 14(10); 2249–59. ©2015 AACR.
ACRYLIC BONE CEMENT REINFORCED WITH GLASS SPHERES

A commercial acrylic bone cement was modified by the incorporation of different weight fractions of glass spheres. The influence of the filler proportion on the mechanical behavior was assessed. Composite cements were prepared by replacing part of the powder phase of the cement by an equivalent weight of glass particles which resulted in an increase in the liquid to powder (L/P) ratio of the polymeric matrix. Dynamic mechanical analysis revealed an increase in residual monomer content with increasing filler proportion as a consequence of the increase in L/P. Flexural, compressive and fracture properties of the cement with varying amounts of glass particles were measured. It was found that up to 50 wt% glass particles could be added with significant increases in flexural modulus and fracture toughness. The mechanical behavior was explained in terms of both, the reinforcing effect of the filler and the plastizicing effect of the monomer.
Vam7p, a vacuolar SNAP‐25 homolog, is required for SNARE complex integrity and vacuole docking and fusion

The vacuole v‐t‐SNARE complex is disassembled by Sec17p/α‐SNAP and Sec18p/NSF prior to vacuole docking and fusion. We now report a functional characterization of the vacuolar SNARE Vam7p, a SNAP‐25 homolog. Although Vam7p has no hydrophobic domains, it is tightly associated with the vacuolar membrane. Vam7p is a constituent of the vacuole SNARE complex and is released from this complex by the Sec17p/Sec18p/ATP‐mediated priming of the vacuoles. Even in the absence of the vacuolar v‐SNARE Nyv1p, a subcomplex which includes Vam7p and the t‐SNARE Vam3p is preserved. Vam7p is necessary for the stability of the vacuolar SNARE complex, since vacuoles from mutants deleted in VAM7 do not have a Vam3p–Nyv1p complex. Furthermore, Vam7p alone, in the absence of Nyv1p and Vam3p, cannot mediate fusion with wild‐type vacuoles, whereas vacuoles with only Nyv1p or Vam3p alone can fuse with wild‐type vacuoles in the absence of the other two SNAREs. Thus, Vam7p is important for the stable assembly and efficient function of the vacuolar SNARE complex and maintenance of the vacuolar morphology. This functional characterization of Vam7p suggests a general role for SNAP‐25 homologs, not only on the plasma membrane but along the secretory pathway.