Miracle-dz/UniFAR-FTUs huggingface dataset:
Citadel

Stacked memory modules are likely to be tightly integrated with the processor. It is vital that these memory modules operate reliably, as memory failure can require the replacement of the entire socket. To make matters worse, stacked memory designs are susceptible to newer failure modes (e.g., due to faulty through-silicon vias, or TSVs) that can cause large portions of memory, such as a bank, to become faulty. To avoid data loss from large-granularity failures, the memory system may use symbol-based codes that stripe the data for a cache line across several banks (or channels). Unfortunately, such data-striping reduces memory-level parallelism, causing significant slowdown and higher power consumption. This article proposes Citadel, a robust memory architecture that allows the memory system to retain each cache line within one bank. By retaining cache lines within banks, Citadel enables a high-performance and low-power memory system and also efficiently protects the stacked memory system from large-granularity failures. Citadel consists of three components; TSV-Swap, which can tolerate both faulty data-TSVs and faulty address-TSVs; Tri-Dimensional Parity (3DP), which can tolerate column failures, row failures, and bank failures; and Dynamic Dual-Granularity Sparing (DDS), which can mitigate permanent faults by dynamically sparing faulty memory regions either at a row granularity or at a bank granularity. Our evaluations with real-world data for DRAM failures show that Citadel provides performance and power similar to maintaining the entire cache line in the same bank, and yet provides 700 × higher reliability than ChipKill-like ECC codes.
Comparative analysis of genetic diversity and differentiation of cauliflower (Brassica oleracea var. botrytis) accessions from two ex situ genebanks

Cauliflower (Brassica oleracea var. botrytis) is an important vegetable crop for human nutrition. We characterized 192 cauliflower accessions from the USDA and IPK genebanks with genotyping by sequencing (GBS). They originated from 26 different countries and represent about 44% of all cauliflower accessions in both genebanks. The analysis of genetic diversity revealed that accessions formed two major groups that represented the two genebanks and were not related to the country of origin. This differentiation was robust with respect to the analysis methods that included principal component analysis, ADMIXTURE and neighbor-joining trees. Genetic diversity was higher in the USDA collection and significant phenotypic differences between the two genebanks were found in three out of six traits investigated. GBS data have a high proportion of missing data, but we observed that the exclusion of single nucleotide polymorphisms (SNPs) with missing data or the imputation of missing SNP alleles produced very similar results. The results indicate that the composition and type of accessions have a strong effect on the structure of genetic diversity of ex situ collections, although regeneration procedures and local adaptation to regeneration conditions may also contribute to a divergence. Fst-based outlier tests of genetic differentiation identified only a small proportion (<1%) of SNPs that are highly differentiated between the two genebanks, which indicates that selection during seed regeneration is not a major cause of differentiation between genebanks. Seed regeneration procedures of both genebanks do not result in different levels of genetic drift and loss of genetic variation. We therefore conclude that the composition and type of accessions mainly influence the level of genetic diversity and explain the strong genetic differentiation between the two ex situ collections. In summary, GBS is a useful method for characterizing genetic diversity in cauliflower genebank material and our results suggest that it may be useful to incorporate routine genotyping into accession management and seed regeneration to monitor the diversity present in ex situ collections and to reduce the loss of genetic diversity during seed regeneration.
Interactions between Ions and Lysenin Nanochannels and their Potential Applications as Biosensors

Lysenin is classified as a pore-forming toxin protein that is isolated from the earthworm Eisenia fetida and consists of 297 amino acids [1]. Lysenin inserts large conducting pores (3.04.7 nm in diameter) into artificial membranes (BLM) which include sphingomyelin. These pores (channels) are open and oriented upon insertion into the bilayer lipid membrane. Lysenin channels gate at positive voltages (voltage-induced gating), but not at negative voltages. Lysenin pores also exhibit activity modulation in response to changes in ionic strength and pH, indicating that electrostatic interaction is responsible for Lysenin conductance activities. In this line of inquiries, and by modulating Lysenin electrostatic interactions, it was hypothesized that the electrical properties of Lysenin pores (channels) could be influenced by multivalent ions. The macroscopic conductance of Lysenin channels was inhibited by addition of multivalent ions. The inhibition was concentration dependent and reversible by addition of chelating or precipitating agents. The ability of the examined multivalent ions to inhibit pore conductance depended on ionic charge and size. Taken together, these results indicate that the Lysenin channel has a binding site that is placed inside the channel and interacts electrostatically with multivalent ions resulting in a conductance response related to ionic number and size. The high sensitivity of Lysenin pores toward trivalent ions indicates that Lysenin channels could be used to develop novel biosensors for multivalent ion detection in environmental samples. The dynamic interaction of Lysenin with multivalent ions was modeled based on the conductivity of the bulk solution and the status of Lysenin channels. The purpose of the model was to provide a mechanistic understanding of Lysenin gating. Using the experimental data, an equilibrium rate constant of the interaction between Lysenin and each multivalent ion was estimated. Each rate constant was related to the binding affinity of each ion with the binding site. This dissertation is approved for recommendation to the Graduate Council. Dissertation Director: _______________________________________ Prof. Gregory Salamo Dissertation Committee: _______________________________________ Prof. William F. Oliver III _______________________________________ Prof. Laurent Bellaiche _______________________________________ Prof. Ralph Henry _______________________________________ Prof. Woodrow Shew _______________________________________ Prof. Daniel Fologea Dissertation Duplication Release I hereby authorize the University of Arkansas Libraries to duplicate this dissertation when needed for research and/or scholarship. Agreed __________________________________________ Radwan Awwad Al Faouri Refused __________________________________________ Radwan Awwad Al Faouri
Mathematical Model for Detecting Diabetes

Diabetes is a syndrome of disordered metabolism, usually due to a combination of hereditary and environmental causes, resulting in abnormally high blood sugar levels. Various hormones in our body such as insulin, growth hormone, glucagon control blood glucose levels, epinephrine best know as adrenaline, glucocorticoids and thyroxine. The two most common forms of diabetes are due to either a diminished production of insulin (Type 1 diabetes), or diminished response by the body to insulin (Type 2 and gestational diabetes). Both lead to hyperglycemia, which largely causes the acute signs of diabetes: excessive urine production, resulting compensatory thirst and increased fluid intake, blurred vision, unexplained weight loss, lethargy, and changes in energy metabolism. We will explain how each hormone is activated and how it affects glucose levels in blood. We present a mathematical model that determines diabetes in patients based in the results on the glucose intolerance test of 5 hours. Our model extends the one proposed by E. Ackerman 2 (1969) to include three instead of two hormones concentrations. In particular we include concentrations for glucose, glucagon and a global variable that includes other hormones such as insulin. The model is based on a 3x3 system of non-homogenous ordinary differential equations. A nonlinear least square method is used to determine the coefficient parameters of the system based on actual data from GTT. The simulations also provide an indicator similar to the one proposed by E. Ackerman (1969), to diagnose a diabetic condition. Additionally, we develop a graphical user interface to facilitate the entering of the patient's data and the visualization of the results.
Metabolomic biomarkers as strong correlates of Parkinson disease progression

Objective: To determine whether a Parkinson disease (PD)-specific biochemical signature might be found in the total body metabolic milieu or in the CSF compartment, especially since this disorder has systemic manifestations beyond the progressive loss of dopaminergic nigrostriatal neurons. Methods: Our goal was to discover biomarkers of PD progression. Using ultra-high-performance liquid chromatography linked to gas chromatography and tandem mass spectrometry, we measured concentrations of small-molecule (≤1.5 kDa) constituents of plasma and CSF from 49 unmedicated, mildly affected patients with PD (mean age 61.4 years; mean duration of PD 11.4 months). Specimens were collected twice (baseline and final) at intervals up to 24 months. During this time, mean Unified Parkinson’s Disease Rating Scale (UPDRS) parts 2 + 3 scores increased 47% (from 28.8 to 42.2). Measured compounds underwent unbiased univariate and multivariate analyses, including fitting data into multiple linear regression with variable selection using least absolute shrinkage and selection operator (LASSO). Results: Of 575 identified plasma and 383 CSF biochemicals, LASSO led to selection of 15 baseline plasma constituents with high positive correlation (0.87, p = 2.2e−16) to baseline-to-final change in UPDRS parts 2 + 3 scores. Three of the compounds had xanthine structures, and 4 were either medium- or long-chain fatty acids. For the 15 LASSO-selected biomarkers, pathway enrichment software found no overrepresentation among metabolic pathways. CSF concentrations of the dopamine metabolite homovanillate showed little change between baseline and final collections and minimal correlation with worsening UPDRS parts 2 + 3 scores (0.29, p = 0.041). Conclusions: Metabolomic profiling of plasma yielded strong prediction of PD progression and offered biomarkers that may provide new insights into PD pathogenesis.
Cytoplasmic streaming in Drosophila oocytes varies with kinesin activity and correlates with the microtubule cytoskeleton architecture

Cells can localize molecules asymmetrically through the combined action of cytoplasmic streaming, which circulates their fluid contents, and specific anchoring mechanisms. Streaming also contributes to the distribution of nutrients and organelles such as chloroplasts in plants, the asymmetric position of the meiotic spindle in mammalian embryos, and the developmental potential of the zygote, yet little is known quantitatively about the relationship between streaming and the motor activity which drives it. Here we use Particle Image Velocimetry to quantify the statistical properties of Kinesin-dependent streaming during mid-oogenesis in Drosophila. We find that streaming can be used to detect subtle changes in Kinesin activity and that the flows reflect the architecture of the microtubule cytoskeleton. Furthermore, based on characterization of the rheology of the cytoplasm in vivo, we establish estimates of the number of Kinesins required to drive the observed streaming. Using this in vivo data as the basis of a model for transport, we suggest that the disordered character of transport at mid-oogenesis, as revealed by streaming, is an important component of the localization dynamics of the body plan determinant oskar mRNA.
Proton gradients at the origin of life

Chemiosmotic coupling − the harnessing of electrochemical ion gradients across membranes to drive metabolism − is as universally conserved as the genetic code. As argued previously in these pages, such deep conservation suggests that ion gradients arose early in evolution, and might have played a role in the origin of life. Alkaline hydrothermal vents harbour pH gradients of similar polarity and magnitude to those employed by modern cells, one of many properties that make them attractive models for life's origin. Their congruence with the physiology of anaerobic autotrophs that use the acetyl CoA pathway to fix CO2 gives the alkaline vent model broad appeal to biologists. Recently, however, a paper by Baz Jackson criticized the hypothesis, concluding that natural pH gradients were unlikely to have played any role in the origin of life. Unfortunately, Jackson mainly criticized his own interpretations of the theory, not what the literature says. This counterpoint is intended to set the record straight.
Response to comment on ‘Randomization inference for treatment effects on a binary outcome’

We would like to thank Professor Yasutaka Chiba [1] for his comments on Rigdon and Hudgens (RH) [2]. In this response, we compare Chiba’s approach to constructing confidence intervals (CIs), as described in [3], with the approach in RH. First, we explain that despite the different parameterizations, both approaches test the same null hypotheses for the average causal effect of treatment, using the same randomization distributions to carry out the permutation tests. The difference between the two methods lies in the choice of whether to invert and combine two one-sided tests as Chiba proposed or to invert a single two-sided test as in RH. Next, we present a more computationally efficient method Rigdon, Loh, and Hudgens (RLH) for computing the RH intervals based on Chiba’s principal stratification formulation of the problem. We also propose a third method based on Blaker [4], which inverts a single two-sided test but forms a CI that is at least as narrow as Chiba’s method. Our simulation results show the RLH intervals tend to be narrowest on average among the three methods, but the differences between the methods are reduced either as the magnitude of the average causal effect increases or as the population size increases. Finally, we provide a simple explanation why a certain CI reported in RH was described by Chiba as ‘somewhat unnatural’ [1]. As the original formulation of the RH approach could be computationally intensive, Monte Carlo sampling was used to approximate p-values when carrying out the hypothesis tests. The interval reported in RH appeared ‘unnatural’ because of the Monte Carlo approximation. Using the RLH approach without Monte Carlo sampling, we obtain the same interval as Chiba [1, 3].
A systematic review and meta-analysis of bidirectional effect of arsenic on ERK signaling pathway

Arsenic is a toxic metal, which ultimately leads to cell apoptosis. ERK is considered a key transcriptional regulator of arsenic-induced apoptosis. Due to a few controversial issues about arsenic-mediated extracellular signal-regulated MAP kinases (ERK) signaling, a meta-analysis was performed. Subgroup analyses demonstrated that high doses (≥2 µmol/l) of arsenic increased the expression of Ras, ERK, ERK1, ERK2, phosphorylated (p)-ERK, p-ERK1, and p-ERK2, while low doses (<2 µmol/l) decreased the expression of Ras, ERK1, p-ERK, and p-ERK2 when compared to control groups. Long term exposure (>24 h) to arsenic led to inhibition of expression of ERK1, p-ERK1, and p-ERK2, whereas short-term exposure (≤24 h) triggered the expression of ERK1, ERK2, p-ERK, p-ERK1, and p-ERK2. Furthermore, normal cells exposed to arsenic exhibited higher production levels of Ras and p-ERK. Conversely, exposure of cancer cells to arsenic showed a lower level of production of Ras and p-ERK as well as higher level of p-ERK1 and p-ERK2 as compared to control group. Short-term exposure of normal cells to high doses of arsenic may promote ERK signaling pathway. In contrast, long-term exposure of cancer cells to low doses of arsenic may inhibit ERK signaling pathway. This study may be helpful in providing a theoretical basis for the diverging result of arsenic adverse effects on one hand and therapeutic mechanisms on the other concerning arsenic-induced apoptosis.
Rac1/WAVE2 and Cdc42/N-WASP Participation in Actin-Dependent Host Cell Invasion by Extracellular Amastigotes of Trypanosoma cruzi

This study evaluated the participation of host cell Rho-family GTPases and their effector proteins in the actin-dependent invasion by Trypanosoma cruzi extracellular amastigotes (EAs). We observed that all proteins were recruited and colocalized with actin at EA invasion sites in live or fixed cells. EA internalization was inhibited in cells depleted in Rac1, N-WASP, and WAVE2. Time-lapse experiments with Rac1, N-WASP and WAVE2 depleted cells revealed that EA internalization kinetics is delayed even though no differences were observed in the proportion of EA-induced actin recruitment in these groups. Overexpression of constitutively active constructs of Rac1 and RhoA altered the morphology of actin recruitments to EA invasion sites. Additionally, EA internalization was increased in cells overexpressing CA-Rac1 but inhibited in cells overexpressing CA-RhoA. WT-Cdc42 expression increased EA internalization, but curiously, CA-Cdc42 inhibited it. Altogether, these results corroborate the hypothesis of EA internalization in non-phagocytic cells by a phagocytosis-like mechanism and present Rac1 as the key Rho-family GTPase in this process.
Meta-analysis reveals that reproductive strategies are associated with sexual differences in oxidative balance across vertebrates

Abstract Oxidative stress is a key physiological mechanism underlying life-history tradeoffs. Here, I use meta-analytic techniques to test whether sexual differences in oxidative balance are common in vertebrates and to identify which factors are associated with such differences. The dataset included 732 effect size estimates from 100 articles (82 species). Larger unsigned effect size (meaning larger sexual differences in a given marker) occurred in: reptiles and fish; those species that do not provide parental care; and oviparous species. Estimates of signed effect size (positive values meaning higher oxidative stress in males) indicated that females were less resistant to oxidative stress than males in: reptiles while males and females were similar in fish, birds, and mammals; those species that do not provide parental care; and oviparous species. There was no evidence for a significant sexual differentiation in oxidative balance in fish, birds, and mammals. Effect size was not associated with: the number of offspring; whether the experimental animals were reproducing or not; biomarker (oxidative damage, non-enzymatic, or enzymatic antioxidant), the species body mass; the strain (wild vs. domestic); or the study environment (wild vs. captivity). Oxidative stress tended to be higher in females than males across most of the tissues analyzed. Levels of residual heterogeneity were high in all models tested. The findings of this meta-analysis indicate that diversification of reproductive strategies might be associated with sexual differences in oxidative balance. This explorative meta-analysis offers a starting platform for future research to investigate the relationship between sex and oxidative balance further.
The CURE

VLIW processors typically deliver high performance on limited budget making them ideal for a variety of communication and signal processing solutions. These processors typically need large multi-ported register files that can have side effects of increased cycle time and high power consumption. The access delay and energy of these register files can also become prohibitive when increasing the register count or the access ports, thus limiting the overall performance of the processor. Most prior art circumvent this problem by using multiple clusters with private register files, to lower the access delay and reduce energy consumption. However, clustering artifacts, like increased inter--cluster communication operations and spill-recovery code, result in a performance penalty. This paper proposes CURE — a novel technique to considerably reduce the negative effects of clustering. CURE augments the ISA to expose the communication registers to the compilers to increase availability of architectural register state to all functional units. The inter--cluster communication operations are integrated into regular ALU and memory operations to improve instruction encoding efficiency. We also propose a new code scheduling heuristic to handle the ISA changes, and to realize the improvements in processor’s performance and energy consumption. Our quantitative analysis estimates that CURE, when compared to the baseline 8--issue uni--cluster processor, boosts average performance by 61% while reducing the average register dynamic energy by 77%.
Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group.

OBJECTIVE Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken. METHOD T1-weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume. RESULTS In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33. CONCLUSIONS The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.