Miracle-dz/UniFAR-FTUs huggingface dataset:
On the diameter of the symmetric group: polynomial bounds

We address the long-standing conjecture that all permutations have polynomially bounded word length in terms of any set of generators of the symmetric group. The best available bound on the maximum required word length is exponential in n log n. Polynomial bounds on the word length have previously been established for very special classes of generating sets only.In this paper we give a polynomial bound on the word length under the sole condition that one of the generators fix at least 67% of the domain. Words of the length claimed can be found in Las Vegas polynomial time.The proof involves a Markov chain mixing estimate which permits us, apparently for the first time, to break the "element order bottleneck. "As a corollary, we obtain the following average-case result: for a 1 -- Δ fraction of the pairs of generators for the symmetric group, the word length is polynomially bounded. It is known that for almost all pairs of generators, the word length is less than exp(√n ln n(1 + o(1))).
Efficiency enhancement of Raman microspectroscopy at long working distance by parabolic reflector

Raman microspectroscopy is well suited for readily revealing information about bio-samples. As such, this technique has been applied to a wide range of areas, especially in bio-medical diagnosis. However, bio-samples typically suffer from low Raman signal level due to the nature of inelastic scattering of photons, To achieve a decent signal level, usually a high numerical aperture is employed. One drawback with these objectives is that their working distance is very short. In many cases of clinic diagnosis, a long working distance is always desired which limits the usage of these objectives. We propose a practical solution to this problem by enhancing the Raman/fluorescence signal by a parabolic reflector. On one hand, the high signal level is achieved by the large solid angle of collection of the parabolic reflector. On the other hand, the long working distance is guaranteed by the novel design of our microscope. The enhancement-capability is demonstrated through five types of samples among which we found the method is most applicable for turbid samples.
Implementation and comparison of power definitions using a DSP based prototyping system

This work presents and compares the outcome of the two most elaborated power definitions in the frequency domain. For this study the electrical power quantities proposed in the new IEEE Standard 1459-2000 and developed by L. Czarnecki are considered. These definitions are implemented and applied to some case studies in real life measurements. The general structure of the in-house DSP/FPGA based system used for the prototyping of the measurement device and the software environment used to support power measuring algorithms performed on a low voltage distribution grid are discussed. Finally, a THD decomposition depending on the distortion origin will be presented.
Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD) model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs.
Heparan Sulfate Sugar Modifications Mediate the Functions of Slits and Other Factors Needed for Mouse Forebrain Commissure Development

Heparan sulfate proteoglycans are cell surface and secretory proteins that modulate intercellular signaling pathways including Slit/Robo and FGF/FGFR. The heparan sulfate sugar moieties on HSPGs are subject to extensive postsynthetic modification, generating enormous molecular complexity that has been postulated to provide increased diversity in the ability of individual cells to respond to specific signaling molecules. This diversity could help explain how a relatively small number of axon guidance molecules are able to instruct the extremely complex connectivity of the mammalian brain. Consistent with this hypothesis, we previously showed that mutant mice lacking the heparan sulfotransferases (Hsts) Hs2st or Hs6st1 display major axon guidance defects at the developing optic chiasm. Here we further explore the role of these Hsts at the optic chiasm and investigate their function in corpus callosum development. Each Hst is expressed in a distinct pattern and each mutant displays a specific spectrum of axon guidance defects. Particular Hs2st−/− and Hs6st1−/− phenotypes closely match those of Slit1−/− and Slit2−/− embryos respectively, suggesting possible functional relationships. To test functional interactions between Hs2st or Hs6st1 and Slits we examined optic chiasm and corpus callosum phenotypes in a panel of genotypes where Hs2st or Hs6st1 and Slit1 or Slit2 function were simultaneously reduced or absent. We find examples of Hs2st and Hs6st1 having epistatic, synergistic, and antagonistic genetic relationships with Slit1 and/or Slit2 depending on the context. At the corpus callosum we find that Hs6st1 has Slit-independent functions and our data indicate additional roles in FGF signaling.
Precision Matrix Estimation in High Dimensional Gaussian Graphical Models with Faster Rates

We present a new estimator for precision matrix in high dimensional Gaussian graphical models. At the core of the proposed estimator is a collection of node-wise linear regression with nonconvex penalty. In contrast to existing estimators for Gaussian graphical models with O(s √ log d/n) estimation error bound in terms of spectral norm, where s is the maximum degree of a graph, the proposed estimator could attain O(s/ √ n+ √ log d/n) spectral norm based convergence rate in the best case, and it is no worse than exiting estimators in general. In addition, our proposed estimator enjoys the oracle property under a milder condition than existing estimators. We show through extensive experiments on both synthetic and real datasets that our estimator outperforms the state-of-the-art estimators.
Transaction Healing: Scaling Optimistic Concurrency Control on Multicores

Today's main-memory databases can support very high transaction rate for OLTP applications. However, when a large number of concurrent transactions contend on the same data records, the system performance can deteriorate significantly. This is especially the case when scaling transaction processing with optimistic concurrency control (OCC) on multicore machines. In this paper, we propose a new concurrency-control mechanism, called transaction healing, that exploits program semantics to scale the conventional OCC towards dozens of cores even under highly contended workloads. Transaction healing captures the dependencies across operations within a transaction prior to its execution. Instead of blindly rejecting a transaction once its validation fails, the proposed mechanism judiciously restores any non-serializable operation and heals inconsistent transaction states as well as query results according to the extracted dependencies. Transaction healing can partially update the membership of read/write sets when processing dependent transactions. Such overhead, however, is largely reduced by carefully avoiding false aborts and rearranging validation orders. We implemented the idea of transaction healing in TheDB, a main-memory database prototype that provides full ACID guarantee with a scalable commit protocol. By evaluating TheDB on a 48-core machine with two widely-used benchmarks, we confirm that transaction healing can scale near-linearly, yielding significantly higher transaction rate than the state-of-the-art OCC implementations.
Discovery, Characterization, and Antiparkinsonian Effect of Novel Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4

Parkinson's disease (PD) is caused by the death of dopamine neurons in the basal ganglia and results in motor symptoms such as tremor and bradykinesia. Activation of metabotropic glutamate receptor 4 (mGluR4) has been shown to modulate neurotransmission in the basal ganglia and results in antiparkinsonian effects in rodent PD models. N-Phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) is a positive allosteric modulator (PAM) of mGluR4 that has been used to further validate the role of mGluR4 in PD, but the compound suffers from a lack of selectivity, relatively low potency, and poor solubility. Via high-throughput screening, we discovered more than 400 novel PAMs of mGluR4. Compounds derived from a novel chemical scaffold were characterized in vitro at both rat and human mGluR4 using two distinct assays of mGluR4 function. The lead compound was approximately 8-fold more potent than PHCCC, enhanced the potency of glutamate at mGluR4 by 8-fold, and did not show any significant potentiator or antagonist activity at other mGluR subtypes. Resolution of the regioisomers of the lead revealed that the cis regioisomer, (±)-cis-2-(3,5-dichlorphenylcarbamoyl)cyclohexanecarboxylic acid (VU0155041), contained the majority of the mGluR4 PAM activity and also exhibited partial agonist activity at mGluR4 at a site that was distinct from the glutamate binding site, suggesting that this compound is a mixed allosteric agonist/PAM of mGluR4. VU0155041 was soluble in an aqueous vehicle, and intracerebroventricular administration of 31 to 316 nmol of VU0155041 dose-dependently decreased haloperidol-induced catalepsy and reserpine-induced akinesia in rats. These exciting results provide continued support for mGluR4 as a therapeutic target in PD.
A linkage study between bipolar disorder and genes involved in dopaminergic and GABAergic neurotransmission

Neurobiological studies indicate a dysregulation of the dopaminergic and GABAergic neurotransmission in bipolar disorder. We examined two large families segregating bipolar disorder, for linkage with the genes encoding dopamine beta-hydroxylase, the dopamine transporter DAT1, the dopamine D2, D3 and D5 receptors, and the alpha-1, alpha-5 and beta-1 subunits of the GABAA receptor. Under at least one diagnostic model one of the two families provided evidence to exclude linkage for the DAT1, DRD2, DRD3, DRD5, DBH, GABRA1 and GABARB1 genes but could not exclude the GABRA5 locus. A second family excluded only the GABRA1 and GABRA5 loci at zero recombination and could not formally reject linkage at the DBH, DRD2, DRD3, DRD5, DAT1 and GABARB1 loci. Further analyses at these loci are warranted.
Heart Rate Power Spectrum and Plasma Catecholamine Levels after Postural Change and Cold Pressor Test

ABSTRACT: During stress, low-frequency (0.01–0.15 Hz) heart rate power and plasma catecholamine levels increase in response to increased sympathetic efferent activity. To test the hypothesis that low-frequency heart rate power, a measure of sympathetic control of heart rate, directly correlates with plasma catecholamine concentrations during periods of increased sympathetic tone, we compared heart rate power spectral measures with antecubital vein norepinephrine, epinephrine, and dopamine concentrations during postural change and after cold pressor testing. We analyzed absolute levels and changes in mean heart rate, respiratory rate, blood pressure, heart rate power spectra, and concentration of norepinephrine, epinephrine, and dopamine in 14 healthy volunteers (seven female/seven male) after postural change and in six (three female/three male) during cold pressor testing. Postural change from supine to standing position resulted in increased heart rate [61 ± 8 versus 83 + 11 (SD) bpm, p < 0.05], diastolic (68 ± 7 versus 11 ± 6 mm Hg, p < 0.05) and mean blood pressures (84 ± 6 versus 91 ± 9 mm Hg, p < 0.05), norepinephrine concentration (2.09 ± 1.11 versus 3.23 ± 1.62 nmol/L, p < 0.05), and low-frequency heart rate power (7.55 ± 5.63 versus 33.79 ± 23.55 bpm2, p < 0.05). High-frequency heart rate power, a measure of parasympathetic control of heart rate, decreased with standing (5.38 ± 4.22 versus 2.94 ± 2.69 bpm2, p < 0.05). Diastolic (66 ± 7 versus 81 ± 9 mm Hg,p < 0.05) and mean (83 ± 9 versus 97 ± 11 mm Hg, p < 0.05) blood pressures and norepinephrine concentration (1.21 ± 0.40 versus 1.77 ± 0.79 nmol/L,/ p < 0.05) increased with cold pressor testing. We found no correlation between absolute levels or changes in low-frequency heart rate power and norepinephrine, epinephrine, or dopamine concentration. Thus, we conclude that low-frequency heart rate power and plasma catecholamines are significantly affected by physiologic changes but arc likely regulated by different areas within the sympathetic nervous system.
Treatment of hyperthyroidism in pregnancy

One hundred and five consecutive pregnancies in 79 women affected by hyperthyroidism were observed during an 8‐year period. AH had received treatment either with carbimazole alone (Group I) or with the combination of carbimazole and propranolol (Group II). There were 72 pregnancies in Group I, 33 in Group II. Seventy‐five pregnancies occurred whilst the mother was receiving antithyroid therapy and in the other 30 the diagnosis of hyperthyroidism was made following conception. The total fetal loss was 17.1%, with a spontaneous abortion rate of 5.5% in Group I and 24.2% in Group II. No congenital malformation or maternal deaths occurred. Carbimazole is safe and effective during pregnancy. Adding propranolol offers no further advantage and may indeed be detrimental.
Methylocystis bryophila sp. nov., a facultatively methanotrophic bacterium from acidic Sphagnum peat, and emended description of the genus Methylocystis (ex Whittenbury et al. 1970) Bowman et al. 1993.

A novel species is proposed for two facultatively methanotrophic representatives of the genus Methylocystis, strains H2s(T) and S284, which were isolated from an acidic (pH 4.3) Sphagnum peat-bog lake (Teufelssee, Germany) and an acidic (pH 3.8) peat bog (European North Russia), respectively. Cells of strains H2s(T) and S284 are aerobic, Gram-negative, non-motile, curved coccoids or short rods that contain an intracytoplasmic membrane system typical of type-II methanotrophs. They possess both a soluble and a particulate methane monooxygenase (MMO); the latter is represented by two isozymes, pMMO1 and pMMO2. The preferred growth substrates are methane and methanol. In the absence of C1 substrates, however, these methanotrophs are capable of slow growth on acetate. Atmospheric nitrogen is fixed by means of an aerotolerant nitrogenase. Strains H2s(T) and S284 grow between pH 4.2 and 7.6 (optimum pH 6.0-6.5) and at 8-37 °C (optimum 25-30 °C). The major fatty acids are C18 : 1ω8c, C18 : 1ω7c and C16 : 1ω7c; the major quinone is Q-8. The DNA G+C content is 62.0-62.3 mol%. Strains H2s(T) and S284 share identical 16S rRNA gene sequences, which displayed 96.6-97.3 % similarity to sequences of other taxonomically characterized members of the genus Methylocystis. Therefore, strains H2s(T) and S284 are classified as members of a novel species, for which the name Methylocystis bryophila sp. nov. is proposed; strain H2s(T) ( = DSM 21852(T) = VKM B-2545(T)) is the type strain.
A Fully Integrated HF-Band Passive RFID Tag IC Using 0.18- $\mu\hbox{m}$ CMOS Technology for Low-Cost Security Applications

We present a fully integrated small-size HF-band passive RF identification (RFID) tag chip with authentication and security functions. The design of the RF transceiver and digital control of the tag IC is based on the International Organization for Standardization-14443 type-B protocol. The design of the key analog part of the tag IC is presented, which includes a robust demodulator for 10% amplitude shift keying envelope detection, a high-quality random number generator, and a voltage regulator that can handle a range of output load currents. To implement the secure data transaction with a reader, a 128-b advanced encryption standard (AES) with a new cyclic key generation is used for the data encryption and decryption. An on-chip 4-kb electrically erasable programmable ROM (EEPROM) is used to support the AES operation, tag identification, and tag self-destruction. The read and write accesses of the EEPROM are performed using a 128-b wide buffer with self-timed bursts. The tag chip is fabricated in a one-poly six-metal low-power 0.18-μm CMOS process with a CoSi2 Schottky diode and EEPROM process. Using the scaled-down CMOS technology, the size of the tag chip is only 1.1 × 1 mm2, providing a cost-effective solution for everyday RFID applications.
Proteomic characterization of EL4 lymphoma‐derived tumors upon chemotherapy treatment reveals potential roles for lysosomes and caspase‐6 during tumor cell death in vivo

The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an established in vivo apoptosis model for the investigation of novel cancer imaging agents and immunological treatments due to the rapid and significant response of the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy. Despite the utility of this model system in cancer research, little is known regarding the molecular details of in vivo tumor cell death. Here, we report the first in‐depth quantitative proteomic analysis of the changes that occur in these tumors upon cyclophosphamide and etoposide treatment in vivo. Using a label‐free quantitative proteomic approach a total of 5838 proteins were identified in the treated and untreated tumors, of which 875 were determined to change in abundance with statistical significance. Initial analysis of the data reveals changes that may have been predicted, such as the downregulation of ribosomes, but demonstrates the robustness of the dataset. Analysis of the dataset also reveals the unexpected downregulation of caspase‐3 and an upregulation of caspase‐6 in addition to a global upregulation of lysosomal proteins in the bulk of the tumor.
Tensor Products of Sup-Lattices and Generalized Sup-Arrows

An alternative description of the tensor product of sup-lattices is given with yet another description provided for the tensor product in the special case of CCD sup-lattices. In the course of developing the latter, properties of sup-preserving functions and the totally below relation are generalized to not-necessarily-complete ordered sets.
MAPK-Activated Protein Kinase-2 in Cardiac Hypertrophy and Cyclooxygenase-2 Regulation in Heart

Rationale: Activation of p38 mitogen-activated protein kinase (MAPK) has a significant impact on cardiac gene expression, contractility, extracellular matrix remodeling, and inflammatory response in heart. The p38 kinase pathway also has a controversial role in cardiac hypertrophy. MAPK-activated protein kinase-2 (MK2) is a well-established p38 downstream kinase, yet its contribution to p38-mediated pathological response in heart has not been investigated. Objective: We examined the specific contribution of MK2 to the pathological remodeling induced by p38. Methods and Results: We used a cardiomyocyte specific and inducible transgenic approach to determine the functional and molecular impact of acute activation of the p38 pathway in heart in either a MK2 wild-type or a MK2-null background. p38 activation in wild-type mice led to a rapid onset of lethal cardiomyopathy associated with cardiomyocyte hypertrophy, interstitial fibrosis, and contractile dysfunction. Inactivation of MK2 partially but significantly reduced cardiomyocyte hypertrophy, improved contractile performance, and prevented early lethality. MK2 inactivation had no effect on the mRNA levels of hypertrophic marker genes or the proinflammatory gene cyclooxygenase (COX)-2. However, MK2 had a major role in COX-2 protein synthesis without affecting the mRNA level or protein stability. Conclusions: p38 activity in adult myocytes can contribute to pathological hypertrophy and remodeling in adult heart and that MK2 is an important downstream molecule responsible for specific features of p38-induced cardiac pathology.
A Procedure to Find Discrete Representations of the Efficient Set with Specified Coverage Errors

An important issue in multiple objective mathematical programming is finding discrete representations of the efficient set. Because discrete points can be directly studied by a decision maker, a discrete representation can serve as the solution to the multiple objective problem at hand. However, the discrete representation must be of acceptable quality to ensure that a most--preferred solution identified by a decision maker is of acceptable quality. Recently, attributes for measuring the quality of discrete representations have been proposed. Although discrete representations can be obtained in many different ways, and their quality evaluated afterwards, the ultimate goal should be to find such representations so as to conform to specified quality standards. We present a method that can find discrete representations of the efficient set according to a specified level of quality. The procedure is based on mathematical programming tools and can be implemented relatively easily when the domain of interest is a polyhedron. The nonconvexity of the efficient set is dealt with through a coordinated decomposition approach. We conduct computational experiments and report results.
Scalable and Energy Efficient Execution Methods for Multicore Systems

Multicore architectures impose great pressure on resource management. The exploration spaces available for resource management increase explosively, especially for large-scale highend computing systems. The availability of abundant parallelism causes scalability concerns at all levels. Multicore architectures also impose pressure on power management. Growth in the number of cores causes continuous growth in power. In this dissertation, we introduce methods and techniques to enable scalable and energy efficient execution of parallel applications on multicore architectures. We study strategies and methodologies that combine DCT and DVFS for the hybrid MPI/OpenMP programming model. Our algorithms yield substantial energy saving (8.74% on average and up to 13.8%) with either negligible performance loss or performance gain (up to 7.5%). To save additional energy for high-end computing systems, we propose a power-aware MPI task aggregation framework. The framework predicts the performance effect of task aggregation in both computation and communication phases and its impact in terms of execution time and energy of MPI programs. Our framework provides accurate predictions that lead to substantial energy saving through aggregation (64.87% on average and up to 70.03%) with tolerable performance loss (under 5%). As we aggregate multiple MPI tasks within the same node, we have the scalability concern of memory registration for high performance networking. We propose a new memory registration/deregistration strategy to reduce registered memory on multicore architectures with helper threads. We investigate design polices and performance implications of the helper thread approach. Our method efficiently reduces registered memory (23.62% on average and up to 49.39%) and avoids memory registration/deregistration costs for reused communication memory. Our system enables the execution of application input sets that could not run to the completion with the memory registration limitation.