Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Sequence and Structural Polymorphism on the Mechanical Properties of Amyloid Fibrils

Amyloid fibrils playing a critical role in disease expression, have recently been found to exhibit the excellent mechanical properties such as elastic modulus in the order of 10 GPa, which is comparable to that of other mechanical proteins such as microtubule, actin filament, and spider silk. These remarkable mechanical properties of amyloid fibrils are correlated with their functional role in disease expression. This suggests the importance in understanding how these excellent mechanical properties are originated through self-assembly process that may depend on the amino acid sequence. However, the sequence-structure-property relationship of amyloid fibrils has not been fully understood yet. In this work, we characterize the mechanical properties of human islet amyloid polypeptide (hIAPP) fibrils with respect to their molecular structures as well as their amino acid sequence by using all-atom explicit water molecular dynamics (MD) simulation. The simulation result suggests that the remarkable bending rigidity of amyloid fibrils can be achieved through a specific self-aggregation pattern such as antiparallel stacking of β strands (peptide chain). Moreover, we have shown that a single point mutation of hIAPP chain constituting a hIAPP fibril significantly affects the thermodynamic stability of hIAPP fibril formed by parallel stacking of peptide chain, and that a single point mutation results in a significant change in the bending rigidity of hIAPP fibrils formed by antiparallel stacking of β strands. This clearly elucidates the role of amino acid sequence on not only the equilibrium conformations of amyloid fibrils but also their mechanical properties. Our study sheds light on sequence-structure-property relationships of amyloid fibrils, which suggests that the mechanical properties of amyloid fibrils are encoded in their sequence-dependent molecular architecture.
Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone: a proof of concept trial.

STUDY QUESTION Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care? SUMMARY ANSWER Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support with exogenous progesterone. WHAT IS KNOWN ALREADY A bolus of hCG for final maturation of follicles in connection with COS may induce the risk of OHSS and the luteal phase progesterone levels rise very abruptly in the early luteal phase. STUDY DESIGN, SIZE, DURATION This is a proof-of-concept study conducted as a three arm RCT with a total of 93 patients. First patient enrolled in January 2012 and the study finished in January 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS Normal responder women undergoing IVF/ICSI treatment in a university hospital. One arm served as control, where women followed a standard antagonist protocol. Two study arms were included both having 125 IU hCG daily for luteal phase support without exogenous progesterone after using a GnRHa trigger for ovulation induction. In both study arms exogenous FSH was stopped on stimulation day 6 and replaced by exogenous hCG that was initiated on either stimulation day 2 or day 6. Blood samples were obtained on the day of ovulation induction, on the day of oocyte pickup (OPU) and day OPU + 7. MAIN RESULTS AND THE ROLE OF CHANCE The mean serum levels of hCG did not exceeded the normal physiological range of LH activity in any samples. Mid-luteal progesterone levels were significantly higher in the two study groups receiving daily low-dose hCG for luteal phase support as compared with the control group (control group: 177 ± 27 nmol/l; study group 1: 334 ± 42 nmol/l; study group 2: 277 ± 27 nmol/l; (mean ± SEM). No differences in reproductive outcome were seen between groups. LIMITATIONS, REASONS FOR CAUTION The number of patients included is limited and conclusions need to be verified in a larger RCT. WIDER IMPLICATIONS OF THE FINDINGS Endogenous production of progesterone may become more attractive as the luteal phase support with levels of LH-like activity only in the physiological range and may, from the patients' point of view, replace inconvenient exogenous progesterone preparation. Further hCG may reduce the cost of stimulation and may collectively be used for stimulation of the follicular phase, ovulation induction and for luteal phase support. STUDY FUNDING/COMPETING INTERESTS An unrestricted grant from ARTS Biologics made this study possible. None of the authors has any competing interests to declare. TRIAL REGISTRATION NUMBER ClinicalTrial.gov number: NCT01504139. TRIAL REGISTRATION DATE 28 December 2011.
Does Entitlement Crowd Out Efficiency or Equality Seeking? - Selling the Roles in Generosity Game Experiments -

In generosity games, one agreement payoff is exogenously given, whereas the other is endogenously determined by the proposer's choice of the "pie" size. This has been shown to induce pie choices which are either efficiency or equality seeking. In our experiment, before playing the generosity game, participants are asked to buy their role via a random price mechanism. This should entitle them to exploit the chances which their role provides and at the same time avoid the selection bias of competitive auctions. We find that entitlement crowds out equality seeking and strengthens efficiency seeking. Interpreting participants' willingness to pay as an aspiration level of how much they want to earn, our design further allows us to test for satisficing behavior. Indeed, we find evidence for satisficing behavior in the data.
Towards Predictable, High-Performance Memory Hierarchies in Fixed-Priority Preemptive Multitasking Real-Time Systems

Cache memories are crucial to obtain high performance on contemporary computing systems. However, sometimes they have been avoided in real-time systems due to their lack of determinism. Unfortunately, most of the published techniques to attain predictability when using cache memories are complex to apply, precluding their use on real applications. This paper proposes a memory hierarchy such that, when combined with a careful pre-existing selection of the instruction cache contents, it brings an easy way to obtain predictable yet high-performance results. The purpose is to make possible the use of instruction caches in realistic realtime systems, with the ease of use in mind. The hierarchy is founded on a conventional instruction cache based scheme plus a simple memory assist, whose operation offers a very predictable behaviour and good performance thanks to the addition of a dedicated locking state memory.
An Influence of Nonlinearities to Storage Capacity of Neural Networks

The more realistic neural soma and synaptic nonlinear relations and an alternative mean field theory (MFT) approach relevant for strongly interconnected systems as a cortical matter are considered. The general procedure of averaging the quenched random states in the fully-connected networks for MFT, as usually, is based on the Boltzmann Machine learning. But this approach requires an unrealistically large number of samples to provide a reliable performance. We suppose an alternative MFT with deterministic features instead of stochastic nature of searching a solution a set of large number equations. Of course, this alternative theory will not be strictly valid for infinite number of elements. Another property of generalization is an inclusion of the additional member in the effective Hamiltonian allowing to improve the stochastic hill-climbing search of the solution not dropping into local minima of the energy function. Especially, we pay attention to increasing of neural networks retrieval capability transforming the replica-symmetry model by including of different nonlinear elements. Some results of numerical modeling as well as the wide discussion of neural systems storage capacity are presented.
Multimodal Coding of Three-Dimensional Rotation and Translation in Area MSTd: Comparison of Visual and Vestibular Selectivity

Recent studies have shown that most neurons in the dorsal medial superior temporal area (MSTd) signal the direction of self-translation (i.e., heading) in response to both optic flow and inertial motion. Much less is currently known about the response properties of MSTd neurons during self-rotation. We have characterized the three-dimensional tuning of MSTd neurons while monkeys passively fixated a central, head-fixed target. Rotational stimuli were either presented using a motion platform or simulated visually using optic flow. Nearly all MSTd cells were significantly tuned for the direction of rotation in the absence of optic flow, with more neurons preferring roll than pitch or yaw rotations. The preferred rotation axis in response to optic flow was generally the opposite of that during physical rotation. This result differs sharply from our findings for translational motion, where approximately half of MSTd neurons have congruent visual and vestibular preferences. By testing a subset of neurons with combined visual and vestibular stimulation, we also show that the contributions of visual and vestibular cues to MSTd responses depend on the relative reliabilities of the two stimulus modalities. Previous studies of MSTd responses to motion in darkness have assumed a vestibular origin for the activity observed. We have directly verified this assumption by recording from MSTd neurons after bilateral labyrinthectomy. Selectivity for physical rotation and translation stimuli was eliminated after labyrinthectomy, whereas selectivity to optic flow was unaffected. Overall, the lack of MSTd neurons with congruent rotation tuning for visual and vestibular stimuli suggests that MSTd does not integrate these signals to produce a robust perception of self-rotation. Vestibular rotation signals in MSTd may instead be used to compensate for the confounding effects of rotatory head movements on optic flow.
Comparative Metabolic Analysis of CHO Cell Clones Obtained through Cell Engineering, for IgG Productivity, Growth and Cell Longevity

Cell engineering has been used to improve animal cells’ central carbon metabolism. Due to the central carbon metabolism’s inefficiency and limiting input of carbons into the TCA cycle, key reactions belonging to these pathways have been targeted to improve cultures’ performance. Previous works have shown the positive effects of overexpressing PYC2, MDH II and fructose transporter. Since each of these modifications was performed in different cell lines and culture conditions, no comparisons between these modifications can be made. In this work we aim at contrasting the effect of each of the modifications by comparing pools of transfected IgG producing CHO cells cultivated in batch cultures. Results of the culture performance of engineered clones indicate that even though all studied clones had a more efficient metabolism, not all of them showed the expected improvement on cell proliferation and/or specific productivity. CHO cells overexpressing PYC2 were able to improve their exponential growth rate but IgG synthesis was decreased, MDH II overexpression lead to a reduction in cell growth and protein production, and cells transfected with the fructose transporter gene were able to increase cell density and reach the same volumetric protein production as parental CHO cells in glucose. We propose that a redox unbalance caused by the new metabolic flux distribution could affect IgG assembly and protein secretion. In addition to reaction dynamics, thermodynamic aspects of metabolism are also discussed to further understand the effect of these modifications over central carbon metabolism.
A Map of Local Adaptation in Arabidopsis thaliana

Field experiments identify loci associated with fitness and local adaptation in Arabidopsis. Local adaptation is critical for species persistence in the face of rapid environmental change, but its genetic basis is not well understood. Growing the model plant Arabidopsis thaliana in field experiments in four sites across the species’ native range, we identified candidate loci for local adaptation from a genome-wide association study of lifetime fitness in geographically diverse accessions. Fitness-associated loci exhibited both geographic and climatic signatures of local adaptation. Relative to genomic controls, high-fitness alleles were generally distributed closer to the site where they increased fitness, occupying specific and distinct climate spaces. Independent loci with different molecular functions contributed most strongly to fitness variation in each site. Independent local adaptation by distinct genetic mechanisms may facilitate a flexible evolutionary response to changing environment across a species range.
A positive approach to management education: The relationship between academic PsyCap and student engagement

Purpose The purpose of this paper is to examine the relationship between the positive psychological strengths of undergraduate business students, collectively known as positive psychological capital (PsyCap), and their levels of engagement. Design/methodology/approach This study has a cross-sectional design in which students from two Midwestern universities were surveyed regarding their levels of PsyCap and levels of engagement in educationally sound activities. Item response theory (IRT) and hierarchical regression were used to test study hypotheses. The authors assessed measurement validity using confirmatory factor analyses in MPLUS 7.0 using four-category 2PL graded response models with a weighted least squares means and variance adjusted estimator. Hierarchical regression was used to control for alternative explanations of variance in assessing the effects of PsyCap on student engagement. Findings Using measures of student engagement drawn from the National Survey of Student Engagement, the analysis indicated significant positive relationships between the academic PsyCap of 323 undergraduate business students and their levels of student-faculty engagement (SFE; r=0.30, p<0.01), community-based activities (CBA; r=0.28, p<0.01), and transformational learning opportunities (TLO; r=0.19, p<0.01). A series of hierarchical regressions also indicated that PsyCap is a significant predictor of student engagement as assessed against SFE, CBA, and TLO. Research limitations/implications The findings from this study suggest that further research examining the relationship between PsyCap development and student engagement could have significant implications for management educators. The positive associations found between these key variables could be utilized by management educators to implement novel and effective teaching interventions for developing the PsyCap of their students and, ultimately, increase their students’ levels of engagement. Originality/value Although extant research has demonstrated connections between positive psychological constructs (i.e. hope, self-efficacy, resilience, optimism) and student engagement, this is the first study to take a holistic view of developable, positive psychological capacities, collectively assessed as PsyCap, and examine the potential impact on three recognized dimensions of student engagement.
Identification of Gene Modules Associated with Low Temperatures Response in Bambara Groundnut by Network-Based Analysis

Bambara groundnut (Vigna subterranea (L.) Verdc. ) is an African legume and is a promising underutilized crop with good seed nutritional values. Low temperature stress in a number of African countries at night, such as Botswana, can effect the growth and development of bambara groundnut, leading to losses in potential crop yield. Therefore, in this study we developed a computational pipeline to identify and analyze the genes and gene modules associated with low temperature stress responses in bambara groundnut using the cross-species microarray technique (as bambara groundnut has no microarray chip) coupled with network-based analysis. Analyses of the bambara groundnut transcriptome using cross-species gene expression data resulted in the identification of 375 and 659 differentially expressed genes (p<0.01) under the sub-optimal (23°C) and very sub-optimal (18°C) temperatures, respectively, of which 110 genes are commonly shared between the two stress conditions. The construction of a Highest Reciprocal Rank-based gene co-expression network, followed by its partition using a Heuristic Cluster Chiseling Algorithm resulted in 6 and 7 gene modules in sub-optimal and very sub-optimal temperature stresses being identified, respectively. Modules of sub-optimal temperature stress are principally enriched with carbohydrate and lipid metabolic processes, while most of the modules of very sub-optimal temperature stress are significantly enriched with responses to stimuli and various metabolic processes. Several transcription factors (from MYB, NAC, WRKY, WHIRLY & GATA classes) that may regulate the downstream genes involved in response to stimulus in order for the plant to withstand very sub-optimal temperature stress were highlighted. The identified gene modules could be useful in breeding for low-temperature stress tolerant bambara groundnut varieties.
Efficacy of Multidetector-Row Computed Tomography as a Practical Tool in Comparison to Invasive Procedures for Visualization of the Biliary Obstruction

Introduction: Recently, multidetector computed tomography (MDCT) has been introduced into clinical practice. MDCT has become the noninvasive diagnostic test of choice for detailed evaluation of biliary obstruction. Aim: the main objective of the present study was to evaluate the diagnostic value of MDCT compared to invasive procedures for detecting biliary obstruction causes. Material and Methods: Since February 2009 until May 2011 fifty biliary obstruction patients based on clinical, laboratory or ultrasonographic findings, were evaluated by Multidetector-row computed tomography. The causes of biliary obstruction, which was identified using. MDCT were classified into three categories: calculus, benign stricture, and malignancy. Final diagnosis was conducted based on percutaneous transhepatic cholangiography (PTC), endoscopic retrograde cholangiopancreatography, biopsy, or surgery. The MDCT diagnosis and were compared with the final diagnosis. Results: A correct diagnosis of causes of biliaryobstruction was made on the basis of MDCT findings for 44 of the total 50 patients. Two patients with chronic pancreatitis were incorrectly diagnosed with a pancreatic head adenocarcinoma on the basis of MDCT findings. One patient with biliary stone was incorrectly diagnosed with a periampullary adenocarcinoma on the basis of MDCT findings. The Sensitivity, specificity and accuracy of MDCT in the diagnosis of causes of biliary obstruction were 94.12% and87.87% and94.6% respectively. Conclusion: Based on the findings of this study MDCT has an excellent image quality, providing valuable information about the biliary tree and other abdominal organs. The use of advanced image processing, including maximum intensity projection and multiplanar reconstruction (especially coronal or sagittal reformatted images), allows superior visualization of the biliary tree and vascular structures. Three-dimensional reconstruction images complement axial images by providing a more anatomically meaningful display of the lesion and its relationship to adjacent structures, and accurate determining the craniocaudal extent of the lesion. High accuracy, wide availability and ease of use, make the MDCT the imaging modality of choice for evaluation of biliary obstruction.
A case series of the safety and efficacy of testosterone replacement therapy in renal failure and kidney transplant patients

Background Hypogonadism is common in patients with renal dysfunction and does not always correct following transplantation. Recent studies show increased mortality for dialysis and transplant patients with low testosterone (T). These patients are often not treated due to concerns over efficacy and complications (both real and imagined). There is surprisingly scant literature supporting the use of T therapy in these patients. We wished to examine the results of T therapy in our patients with renal failure or following transplant. Methods We identified 15 men in our Men’s Health Registry treated with T who either were on dialysis or had a functioning transplant at time of therapy. Demographic, laboratory and clinical outcome data were collected from the electronic medical record. Results There were 3 men on dialysis and 12 with a functioning transplant. Mean age was 53.7 years (range, 39–71 years) and mean total serum T was 207.9 ng/mL (range, 45–330 ng/mL). All had bothersome symptoms including fatigue (15/15) and erectile dysfunction (ED) (14/15). Mean hematocrit was 35.8% and 9/15 were anemic. Therapy included patches in 1, topical gels in 6 and testopel pellets in 8. With a mean follow-up of 22.7 months (range, 11–58 months), mean T post therapy was 528 (range, 226–869). Mean hematocrit improved to 42.6% and 7/9 anemic patients improved out of the anemic range. There were no cardiovascular or infectious complications. Conclusions Symptomatic hypogonadism is common in dialysis and transplant patients and T replacement therapy can be safely given with improvement in T values and symptoms in most patients. Anemia is usually improved. Testopel pellets can be used in immunosuppressed transplant recipients without infectious complications.
Suppression of the immune response by alpha-fetoprotein on the primary and secondary antibody response

Mouse amniotic fluid was shown to contain a noncytotoxic inhibitor of primary gammaM and secondary gammaM, gammaG subclass splenic plaque forming cells in vitro to SRBC. The suppressive effect was not abolished by exhaustive dialysis or by absorption of mouse amniotic fluid (MAF) with SRBC. Polyacrylamide gel analysis showed that dialyzed MAF was composed of three major protein components, transferrin, albumin, and alpha-fetoprotein (AFP). The selective removal of each of these patients from MAF by affinity chromatography suggested that AFP was the immunosuppressive substance in MAF. This conclusion was verified by the demonstration that pure AFP suppressed in vitro antibody synthesis in microgram quantities whereas equivalent amounts of normal mouse serum, transferrin, or albumin did not. Dose-response studies showed that the effect of AFP in the isolated form was equivalent to the suppressive effect of comparable amounts of AFP in MAF. gammaA and gammaG plaque-forming cell (PFC) responses were suppressed by a significantly lower concentration of AFP than was the gammaM PFC response. The degree of suppression watration of AFP than was the gammaM PFC response. The degree of suppression was dependent on the time at which AFP was added to the cultures; MAF added to antigen- stimulated cultures up to 24 h after initiation of cultures was immunosuppressive whereas similar additions of MAF at 48 h after initiation or later did not suppress. The duration of exposure of spleen cells to MAF in cultures without antigen necessary to achieve suppression of a subsequent primary immune response was determine-d to be approximately 8 h. The results suggest that AFP may have an immunoregulatry function. This has potentially important implications in the maternal-fetal relationship, the immune capabilities of the fetus and newborn, and in certain malignant and nonmalignant diseases in which AFP is elevated.