Miracle-dz/UniFAR-FTUs huggingface dataset:
Incremental Layer Assignment for Timing Optimization

With VLSI technology nodes scaling into the nanometer regime, interconnect delay plays an increasingly critical role in timing. For layer assignment, most works deal with via counts or total net delays, ignoring critical paths of each net and resulting in potential timing issues. In this article, we propose an incremental layer assignment framework targeting delay optimization in timing the critical path of each net. A set of novel techniques are presented: self-adaptive quadruple partition based on K × K division benefits the runtime; semidefinite programming is utilized for each partition; and the sequential mapping algorithm guarantees integer solutions while satisfying edge capacities; additionally, concurrent mapping offers a global view of assignment and post delay optimization reduces the path timing violations. The effectiveness of our work is verified by ISPD’08 benchmarks.
The Role and Dynamics of β-Catenin in Precondition Induced Neuroprotection after Traumatic Brain Injury

Preconditioning via heat acclimation (34°C 30 d) results in neuroprotection from traumatic brain injury due to constitutive as well as dynamic changes triggered by the trauma. Among these changes is Akt phosphorylation, which decreases apoptosis and induces HIF1α. In the present study we investigated the Akt downstream GSK3β/β -catenin pathway and focused on post injury alternations of β catenin and its impact on the cellular response in preconditioned heat acclimated mice. We found that the reduction in motor disability is accompanied with attenuation of depressive like behavior in heat acclimated mice that correlates with the GSK3β phosphorylation state. Concomitantly, a robust β catenin phosphorylation is not followed by its degradation, or by reduced nuclear accumulation. Enhanced tyrosine phosphorylation of β catenin in the injured area weakens the β catenin-N cadherin complex. Membrane β catenin is transiently reduced in heat acclimated mice and its recovery 7 days post TBI is accompanied by induction of the synaptic marker synaptophysin. We suggest a set of cellular events following traumatic brain injury in heat acclimated mice that causes β catenin to participate in cell-cell adhesion alternations rather than in Wnt signaling. These events may contribute to synaptogenesis and the improved motor and cognitive abilities seen heat acclimated mice after traumatic brain injury.
Resource optimization for energy efficiency in multi-cell massive MIMO with MRC detectors

In this paper, resource allocation for energy-efficient communications in a pilot-contaminated uplink multi-cell massive MIMO system with MRC detectors is investigated. The problem of maximizing energy efficiency (EE) of data transmissions in the system is studied by optimizing the number of antennas per BS, the pilot signal power, and the data signal power. The considered optimization problem takes into account the circuit power consumption, pilot contamination, and budget constraints in the number of antennas per Base Station (BS) and the average transmission power per symbol. The resulting optimization problem has a non-convex fractional objective function which is difficult to solve in its original form. Therefore, principles from fractional programming are used to first transform the problem into an equivalent parametric form and then to derive an iterative resource allocation algorithm. In each iteration, an alternating optimization technique is used to solve the objective function by decomposing it into a sequence of solvable difference of convex (D.C) programming subproblems. Simulation results show that higher EE levels can be achieved by optimizing the pilot and data powers separately. Also, increasing the number of antennas per BS with the power budget may or may not be energy-efficient, depending on the range of operation.
Reverse Engineering of Design Patterns from Java Source Code

Recovering design patterns can enhance existing source code analysis tools by bringing program understanding to the design level. This paper presents a new, fully automated pattern detection approach. The new approach is based on our reclassification of the GoF patterns by their pattern intent. We argue that the GoF pattern catalog classifies design patterns in the forward-engineering sense; our reclassification is better suited for reverse engineering. Our approach uses lightweight static program analysis techniques to capture program intent. This paper also describes our tool, PINOT, that implements this new approach. PINOT detects all the GoF patterns that have concrete definitions driven by code structure or system behavior. Our tool is faster, more accurate, and targets more patterns than existing pattern detection tools. PINOT has been used successfully in detecting patterns in Java AWT, JHotDraw, Swing, Apache Ant, and many other programs and packages
Metformin Improves Immunosuppressant Induced Hyperglycemia and Exocrine Apoptosis in Rats

Background Immunosuppressants are an important cause of posttransplantation diabetes mellitus. We have shown that tacrolimus and sirolimus induce hyperglycemia and hyperinsulinemia in normal rats. We hypothesized that metformin, given concurrently with tacrolimus and/or sirolimus, prevents disturbances in glucose and insulin metabolism. Methods Eight groups (n=6) of normal Sprague-Dawley rats were studied: four groups received tacrolimus, sirolimus, tacrolimus/sirolimus, or control for 14 days, and four more groups received similar treatments along with metformin. Daily glucoses were measured. All rats were administered an oral glucose challenge before sacrifice. Pancreata were analyzed by terminal deoxynucleotide tranferase-mediated dUTP nick-end labeling staining and immunohistochemistry. Results Tacrolimus, sirolimus, and tacrolimus/sirolimus impaired glucose tolerance compared to control. Sirolimus and tacrolimus/sirolimus also increased random blood glucose levels. Sirolimus alone resulted in hyperinsulinemia after oral glucose challenge compared to control. In the sirolimus/metformin and tacrolimus/sirolimus/metformin groups, mean daily random glucose was no longer increased, although the response to glucose challenge was still impaired. Metformin decreased pancreatic exocrine and trended to decrease endocrine apoptosis in tacrolimus/sirolimus group and reduced islet insulin content in sirolimus group. Conclusions This is the first study to show that metformin can improve immunosuppressant-induced hyperglycemia, when administered concurrently, and reduces exocrine apoptosis (reducing the impact on potential islet progenitor cells).
A fast hybrid genetic algorithm for the quadratic assignment problem

Genetic algorithms (GAs) have recently become very popular by solving combinatorial optimization problems. In this paper, we propose an extension of the hybrid genetic algorithm for the well-known combinatorial optimization problem, the quadratic assignment problem (QAP). This extension is based on the "fast hybrid genetic algorithm" concept. An enhanced tabu search is used in the role of the fast local improvement of solutions, whereas a robust reconstruction (mutation) strategy is responsible for maintaining a high degree of the diversity within the population. We tested our algorithm on the instances from the QAP instance library QAPLIB. The results demonstrate promising performance of the proposed algorithm.
Sediment quality assessment of Beasley Lake: bioaccumulation and effects of pesticides in Hyalella azteca

Beasley Lake is a Conservation Effects Assessment Program (CEAP) watershed in the intensively cultivated Mississippi Delta, USA. Lake sediment quality at three sites was evaluated in 2004 and 2008 for biological impairment and uptake (animal tissue pesticide residues) from 14 pesticides and three metabolites using Hyalella azteca (Saussure). Eleven pesticides and three metabolites were detected in sediment among the three sites in 2004 and all 17 compounds examined were detected among the three sites in 2008, with the herbicide atrazine having the greatest concentrations. Twenty-eight-day H. azteca survival and growth (mg w/w) indicated no survival effects at any site for either year, but growth impairment occurred in H. azteca exposed to sediments in 2004, whereas growth enhancement occurred in H. azteca exposed to sediments at one site in 2008. Pesticides observed in animal tissue pesticide residues occurred more frequently and in greater concentrations in 2004 compared with 2008. Thirteen pesticides were detected in animal tissue pesticide residues in 2004, with chlorpyrifos occurring in the greatest concentrations, and six pesticides were detected in 2008, with p,p′-DDT occurring in the greatest concentrations. H. azteca tissue pesticide residues of seven pesticides, two herbicides, three insecticides, one insecticide metabolite, and p,p′-DDT, were associated with growth.
Pig heart short chain L‐3‐hydroxyacyl‐CoA dehydrogenase revisited: Sequence analysis and crystal structure determination

Short chain L‐3‐hydroxyacyl CoA dehydrogenase (SCHAD) is a soluble dimeric enzyme critical for oxidative metabolism of fatty acids. Its primary sequence has been reported to be conserved across numerous tissues and species with the notable exception of the pig heart homologue. Preliminary efforts to solve the crystal structure of the dimeric pig heart SCHAD suggested the unprecedented occurrence of three enzyme subunits within the asymmetric unit, a phenomenon that was thought to have hampered refinement of the initial chain tracing. The recently solved crystal coordinates of human heart SCHAD facilitated a molecular replacement solution to the pig heart SCHAD data. Refinement of the model, in conjunction with the nucleotide sequence for pig heart SCHAD determined in this paper, has demonstrated that the previously published pig heart SCHAD sequence was incorrect. Presented here are the corrected amino acid sequence and the high resolution crystal structure determined for pig heart SCHAD complexed with its NAD+ cofactor (2.8 Å; Rcryst = 22.4%, Rfree = 28.8%). In addition, the peculiar phenomenon of a dimeric enzyme crystallizing with three subunits contained in the asymmetric unit is described.
Chronic Active Hepatitis Induced by Helicobacter hepaticus in the A/JCr Mouse Is Associated with a Th1 Cell-Mediated Immune Response

ABSTRACT Helicobacter hepaticus infection in A/JCr mice results in chronic active hepatitis characterized by perivascular, periportal, and parenchymal infiltrates of mononuclear and polymorphonuclear cells. This study examined the development of hepatitis and the immune response of A/JCr mice to H. hepaticus infection. The humoral and cell-mediated T helper immune response was profiled by measuring the postinfection (p.i.) antibody response in serum, feces, and bile and by the production of cytokines and proliferative responses by splenic mononuclear cells to H. hepaticusantigens. Secretory immunoglobulin A (IgA) and systemic IgG2a antibody developed by 4 weeks p.i. and persisted through 12 months. Splenocytes from infected mice proliferated and produced more gamma interferon (IFN-γ) than interleukin-4 (IL-4) or IL-5 when cultured with H. hepaticus outer membrane proteins. The predominantly IgG2a antibody response in serum and the in vitro production of IFN-γ in excess of IL-4 or IL-5 are consistent with a Th1 immune response reported in humans and mice infected withHelicobacter pylori and Helicobacter felis, respectively. Mice infected with H. hepaticus developed progressively severe perivascular, periportal, and hepatic parenchymal lesions consisting of lymphohistiocytic and plasmacytic cellular infiltrates. In addition, transmural typhlitis was observed at 12 months p.i. The characterization of a cell-mediated Th1 immune response toH. hepaticus infection in the A/JCr mouse should prove valuable as a model for experimental regimens which manipulate the host response to Helicobacter.
Action Experience and Action Discovery in Medicated Individuals with Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disorder that markedly affects voluntary action. While regular dopamine treatment can help restore motor function, dopamine also influences cognitive portions of the action system. Previous studies have demonstrated that dopamine medication boosts action-effect associations, which are crucial for the discovery of new voluntary actions. In the present study, we investigated whether neural processes involved in the discovery of new actions are altered in PD participants on regular dopamine treatment, compared to healthy age-matched controls. We recorded brain electroencephalography (EEG) activity while PD patients and age-matched controls performed action discovery (AD) and action control tasks. We found that the novelty P3, a component normally present when there is uncertainty about the occurrence of the sensory effect, was enhanced in PD patients. However, AD was maintained in PD patients, and the novelty P3 demonstrated normal learning-related reductions. Crucially, we found that in PD patients the causal association between an action and its resulting sensory outcome did not modulate the amplitude of the feedback correct-related positivity (fCRP), an EEG component sensitive to the association between an action and its resulting effect. Collectively, these preliminary results suggest that the formation of long-term action-outcome representations may be maintained in PD patients on regular dopamine treatment, but the initial experience of action-effect association may be affected.
Hospital volume of throughput and periprocedural and medium-term adverse events after percutaneous coronary intervention: retrospective cohort study of all 17 417 procedures undertaken in Scotland, 1997–2003

Objective: To determine whether percutaneous coronary intervention (PCI) hospital volume of throughput is associated with periprocedural and medium-term events, and whether any associations are independent of differences in case mix. Design: Retrospective cohort study of all PCIs undertaken in Scottish National Health Service hospitals over a six-year period. Methods: All PCIs in Scotland during 1997–2003 were examined. Linkage to administrative databases identified events over two years’ follow up. The risk of events by hospital volume at 30 days and two years was compared by using logistic regression and Cox proportional hazards models. Results: Of the 17 417 PCIs, 4900 (28%) were in low-volume hospitals and 3242 (19%) in high-volume hospitals. After adjustment for case mix, there were no significant differences in risk of death or myocardial infarction. Patients treated in high-volume hospitals were less likely to require emergency surgery (adjusted odds ratio 0.18, 95% confidence interval (CI) 0.07 to 0.54, p = 0.002). Over two years, patients in high-volume hospitals were less likely to undergo surgery (adjusted hazard ratio 0.52, 95% CI 0.35 to 0.75, p = 0.001), but this was offset by an increased likelihood of further PCI. There was no net difference in coronary revascularisation or in overall events. Conclusion: Death and myocardial infarction were infrequent complications of PCI and did not differ significantly by volume. Emergency surgery was less common in high-volume hospitals. Over two years, patients treated in high-volume centres were as likely to undergo some form of revascularisation but less likely to undergo surgery.
RPPA-based protein profiling reveals eIF4G overexpression and 4E-BP1 serine 65 phosphorylation as molecular events that correspond with a pro-survival phenotype in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL), the most common adult leukemia, remains incurable despite advancements in treatment regimens over the past decade. Several expression profile studies have been pursued to better understand CLL pathogenesis. However, these large-scale studies only provide information at the transcriptional level. To better comprehend the differential protein changes that take place in CLL, we performed a reverse-phase protein array (RPPA) analysis using 167 different antibodies on B-cell lysates from 18 CLL patients and 6 normal donors. From our analysis, we discovered an enrichment of protein alterations involved with mRNA translation, specifically upregulation of the translation initiator eIF4G and phosphorylation of the cap-dependent translation inhibitor 4E-BP1 at serine 65. Interestingly, 4E-BP1 phosphorylation occurred independently of AKT phosphorylation, suggesting a disconnect between PI3K/AKT pathway activation and 4E-BP1 phosphorylation. Based on these results, we treated primary CLL samples with NVP-BEZ235, a PI3K/mTOR dual inhibitor, and compared its apoptotic-inducing potential against the BTK inhibitor Ibrutinib and the PI3Kδ inhibitor Idelalisib. We demonstrated that treatment with NVP-BEZ235 caused greater apoptosis, greater apoptotic cleavage of eIF4G, and greater dephosphorylation of 4E-BP1 in primary CLL cells. Taken together, these results highlight the potential dependence of eIF4G overexpression and 4E-BP1 phosphorylation in CLL survival.
Hassles with Taking Out the Garbage: Aggravating Aggresomes

Diverse human diseases ranging from amyloidosis to neurodegenerative diseases are now recognized as ‘conformational diseases’ caused by protein misfolding and protein aggregation. Misfolded and aggregated proteins are usually handled in the cell through chaperone‐mediated refolding, or when that is impossible, destroyed by proteasomal degradation. Recent evidence suggests that cells might have evolved a third pathway that involves the sequestration of aggregated proteins into specialized ‘holding stations’ called aggresomes. The aggresomal pathway provides a mechanism by which aggregated proteins form particulate (∼ 200 nm) mini‐aggregates that are transported on microtubules (MTs) towards the MT organizing center (MTOC) by a process mediated by the minus‐end motor protein dynein. Once at the MTOC, the individual particles pack into a single, usually spherical aggresome (1–3 μm) that surrounds the MTOC. Aggresomes are dynamic: they recruit various chaperones and proteasomes, presumably to aid in the disposal of the aggregated proteins. In addition, the formation of an aggresome is likely to activate the autophagic clearance mechanism that terminates in lysosomal degradation. Hence, the aggresome pathway may provide a novel system to deliver aggregated proteins from the cytoplasm to lysosomes for degradation. Although it is clear that many pathological states correlate with the formation of aggresomes, their causal relationships remain hotly debated. Here, we describe the current state of our knowledge of the aggresome pathway and outline the open questions that provide the focus of current research.
Preparation of Effective and Safe Gene Carriers by Grafting Alkyl Chains to Generation 5 Polypropyleneimine

Gene therapy is a novel method to treat a variety of diseases including genetic disorders and cancer. Nonviral gene carriers have now gained considerable attention as gene carrier systems. Polyamidoamine (PAMAM) and polypropyleneimine (PPI) are the two most widely used denderimers in gene delivery studies. The aim of the current study was to investigate the effects of modification of generation 5 polypropyleneimine (G5 PPI) dendrimers with alkanoate groups as hydrophobic moieties on DNA transfection and cytotoxicity. Six, 10, and 16 carbon derivatives of bromoalkanoic acids were conjugated onto PPI with 10%, 30%, and 50% of surface amine grafting. Ethidium bromide exclusion assay results proved the ability of modified carriers to condense DNA. Transfection assay showed higher DNA delivery potential for 30% and 50% grafting with decanoate moieties compared to native G5 PPI and SuperfectTM. 3-(4,5-Dimethylthiazol-2-yl)-2,5-di phenyltetrazolium bromide (MTT) and apoptosis experiments showed lower toxicity for modified carriers compared to unmodified PPI. The hemolytic effect of grafted carriers was not significantly different from G5 PPI. Size and zeta potential measurements revealed that polyplex size was less than 200 nm and electrical charges were in the range 14–25 mV. The hydrophobic modifications improved transfection activity and toxicity of G5 PPI without negatively affecting hemocompatibility. These modified carriers are therefore promising candidates for further in vivo investigations.
Study on characteristics of SAR imagery around the coast for shoreline detection

ABSTRACT This study investigated how the synthetic aperture radar (SAR) parameters and natural conditions affect the spatial distribution of backscattering coefficient of SAR images around the shoreline. Primary findings of this study are summarized as follows: (i) the HH polarization mode is the best mode for shoreline detection; (ii) SAR scenes with incident angle ranging from 30° to 50° under sea-to-land observation direction are recommended for shoreline detection; (iii) clear contrast of the backscattering coefficient between the beach and sea is expected when the nearshore significant wave height is smaller than 0.5 m for L-band SAR scenes; and (iv) X-band SAR scenes may be preferred to L-band SAR scenes for shoreline detection especially where the grain size of the beach material is relatively fine.
Kidney, liver and bone cadmium content in the western sandpiper in relation to migration.

Cadmium content was measured in kidney, liver and tarsus bones of western sandpipers (Calidris mauri) at a temperate migratory stopover site (Fraser Delta, British Columbia, Canada) and a wintering site (Playa el Agallito, Chitre, Panama) over a two year period. Cadmium content in liver and kidney was age and sex dependent. Adult females generally had lower kidney and liver cadmium than adult males (P < 0.05), but a sex difference was not detected in juveniles. Cadmium increased with age in kidney, liver and to a lesser extent in bone (P < 0.001) with average "steady-state" kidney and liver content being reached within the sandpipers first year. In general, tissue cadmium residues in adult males and females were independent of sampling location although for bone, site-specific differences did occur (P < 0.001). Bone cadmium was lower in females sampled from their wintering grounds as compared to temperate stopover sites suggesting that bone cadmium may be mobilized during periods of feather molt. Comparison of cadmium residues among sandpipers of increasing age suggest that exposure is occurring along the Pacific Coast, at stopover sites as the birds migrate north to Alaska and south to Panama. This study points to the importance of considering the ecology of the species (e.g., in this case migratory behavior) in interpreting trace metal residues.
The specification of neuronal identity by graded Sonic Hedgehog signalling.

During the development of vertebrate nervous system, distinct classes of motor neurons and interneurons are generated at distinct dorsoventral positions in the ventral neural tube. The differentiation of these neuronal subtypes is directed by the secreted protein Sonic Hedgehog (Shh). Shh acts in a graded manner to establish different neural progenitor cell populations, defined by the expression of homeodomain transcription factors. These factors are critical for the interpretation of graded Shh signalling and act initially both to refine progenitor domain boundaries and to maintain their integrity. Subsequently, these factors direct the expression of genes that confer neuronal subtype identity to post-mitotic neurons.