Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of a new tissue plasminogen activator analogue, Fb‐Fb‐CF, on cerebral reperfusion in a rabbit embolic stroke model

Early fibrinolytic therapy with full molecular tissue plasminogen activator (t‐PA) has been observed to be both angiographically and clinically effective when employed in animal stroke models. Preliminary clinical trials with t‐PA are in progress. It is possible to refine t‐PA by developing fragments or analogues of the drug. Using recombinant DNA technology in the Escherichia coli system, a t‐PA analogue consisting of the catalytic fragment of t‐PA and a dimer of the B fragment of staphylococcal protein A (Fb‐Fb‐CF) has been produced. Because this analogue has a long serum half‐life of 90 minutes, we employed Fb‐Fb‐CF in a rabbit cerebral embolic stroke model to assess its efficacy as a reperfusion agent. When given as a bolus to 10 animals 15 minutes after embolization, Fb‐Fb‐CF produced angiographic cerebral reperfusion in 48 ± 21 minutes (± SD), while in 8 saline‐treated controls, reperfusion was not observed at 180 minutes in any animal (p < 0.01). In another experiment reperfusion was demonstrated at 66 ± 32 minutes in 11 animals treated with Fb‐Fb‐CF 90 minutes after embolization as compared with 100 ± 25 minutes in 12 saline‐treated controls (p < 0.01). A small macroscopic hemorrhage within an infarct was seen in 1 Fb‐Fb‐CF‐treated animal in the 15‐minute experiment and in none of the controls. In the 90‐minute experiment, macroscopic hemorrhagic infarction was seen in 4 Fb‐Fb‐CF‐treated animals and in 3 controls. Plasma fibrinogen levels measured in the 15‐minute Fb‐Fb‐CF treatment group declined by 16% immediately after the Fb‐Fb‐CF bolus was administered and by 19% after 180 minutes. These data demonstrate that Fb‐Fb‐CF can rapidly reestablish cerebral perfusion with only modest reductions in plasma fibrinogen when given either 15 or 90 minutes after cerebral embolization.
Assessment of three generations of mice derived by ICSI using freeze-dried sperm

Summary Although the derivation of mice by intracytoplasmic sperm injection (ICSI) using freeze-dried sperm has been demonstrated previously, a comprehensive analysis of their viability, health, and fertility has not. The purpose of the present study was to determine the extent to which ICSI using freeze-dried sperm stored at 4 °C for 1–2 months from mice on either an inbred (C57BL/6J) or hybrid (B6D2F1/J) genetic background results in genomic instability and/or phenotypic abnormality in mice and two generations of their progeny. Fertilization rates (number of 2-cells per injected oocytes) using ICSI of fresh and freeze-dried sperm were similar within and between mouse strains, although fewer freeze-dried sperm-derived embryos than fresh sperm-derived embryos developed to blastocysts in vitro (C57BL/6J and B6D2F1/J) and liveborn pups in vivo (B6D2F1/J only). Nevertheless, once born, mice derived by ICSI using freeze-dried sperm in both mouse strains were healthy and reproductively sound. No major differences in litter size, weaning rate, and sex ratio were noted in the two generations of progeny (F2 and F3) of ICSI-derived offspring using freeze-dried sperm compared with that in the natural mating (control) group. Further, there was no evidence that either ICSI or freeze drying induced genomic instability, as determined by microsatellite analysis of the derived mice and subsequent generations when compared with both parental genotypes, nor were there differences in the number or types of pathological changes in any of the three generations of progeny. We conclude that viable, healthy and genomically stable mice can be derived by ICSI using freeze-dried mouse sperm stored in the refrigerator for at least 2 months. Further, because freeze drying is a simpler and more economical technique compared with embryo and sperm cryopreservation, the results of this study justify additional research to continue to develop and enhance the technique for the preservation, storage, and sharing of genetically altered mice.
Nuclear import of the histone acetyltransferase complex SAS-I in Saccharomyces cerevisiae

The protein complex SAS-I links histone acetylation to the assembly of repressed chromatin in Saccharomyces cerevisiae. Sas2p, the histone acetyltransferase subunit of SAS-I, forms a complex with Sas4p and Sas5p, which are both required for maximal complex activity. In this study, we found that Sas4p was the central subunit of the SAS-I complex, bridging Sas2p and Sas5p. We demonstrated that the nuclear import of Sas2p and Sas5p was mediated by two karyopherins/importins, Kap123p and Pse1p, and both were associated in vivo with these importins. By contrast, Sas4p was not a substrate of Kap123p or Pse1p, suggesting that the nuclear import of the SAS-I subunits occurred independently of each other. Several other non-essential karyopherins were not involved in the nuclear import of SAS-I subunits. When the putative nuclear localization signal (NLS) of Sas2p was deleted, nuclear accumulation of Sas2p was significantly decreased. By contrast, deletion of the proposed NLS of Sas4p had no influence on its nuclear localization. An unknown signal region was located in the N-terminal domain of Sas5p and was responsible for the nuclear import by Kap123p and Pse1p. We found a striking similarity between the NLS sequences of Sas2p and those of histones H3 and H4, which were recently reported to be further import substrates of Kap123p and Pse1p. A database search based on the aligned consensus sequence revealed potential new import substrates of the Kap123p and Pse1p nuclear import pathways, which are connected to chromatin function.
Poptrie: A Compressed Trie with Population Count for Fast and Scalable Software IP Routing Table Lookup

Internet of Things leads to routing table explosion. An inexpensive approach for IP routing table lookup is required against ever growing size of the Internet. We contribute by a fast and scalable software routing lookup algorithm based on a multiway trie, called Poptrie. Named after our approach to traversing the tree, it leverages the population count instruction on bit-vector indices for the descendant nodes to compress the data structure within the CPU cache. Poptrie outperforms the state-of-the-art technologies, Tree BitMap, DXR and SAIL, in all of the evaluations using random and real destination queries on 35 routing tables, including the real global tier-1 ISP's full-route routing table. Poptrie peaks between 174 and over 240 Million lookups per second (Mlps) with a single core and tables with 500--800k routes, consistently 4--578% faster than all competing algorithms in all the tests we ran. We provide the comprehensive performance evaluation, remarkably with the CPU cycle analysis. This paper shows the suitability of Poptrie in the future Internet including IPv6, where a larger route table is expected with longer prefixes.
The septin Sept5/CDCrel-1 competes with α-SNAP for binding to the SNARE complex

SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) proteins are supposed to mediate the docking and/or fusion of the vesicle with the plasma membrane. However, it is not clearly understood how this process is regulated. In a search for potential SNARE regulators, we recently identified septin 5 (Sept5) as a novel SNARE interacting protein. Septins were first identified as filamentous proteins required for cytokinesis in yeast. Several septins have now been identified in mammals but little is known about their functions. We have previously shown that Sept5 is predominantly expressed in the brain, where it associates with vesicles and membranes through its interaction with the SNARE domain of syntaxin 1A. Furthermore, Sept5 appears to inhibit exocytosis, possibly by regulating vesicle targeting and/or fusion events. To gain insight into the role of Sept5, we have mapped the Sept5 domains important for syntaxin binding. We also investigated the ability of Sept5 to bind to syntaxin when in various protein complexes. Although Sept5 cannot bind an nSec1–syntaxin complex, it can bind syntaxin in a SNARE complex. This interaction is occluded by the binding of α-SNAP, suggesting that Sept5 may regulate the availability of SNARE proteins through its interaction with syntaxin and the 7 S complex.
Comparison of respiratory activity and culturability during monochloramine disinfection of binary population biofilms

Biofilm bacteria challenged with monochloramine retained significant respiratory activity, even though they could not be cultured on agar plates. Microbial colony counts on agar media declined by approximately 99.9% after 1 h of disinfection, whereas the number of bacteria stained by a fluorescent redox dye experienced a 93% reduction. Integrated measures of biofilm respiratory activity, including net oxygen and glucose utilization rates, showed only a 10 to 15% reduction. In this biofilm system, measures of microbial respiratory activity and culturability yielded widely differing estimates of biocide efficacy.
Polysaccharide Krestin Is a Novel TLR2 Agonist that Mediates Inhibition of Tumor Growth via Stimulation of CD8 T Cells and NK Cells

Purpose: Polysaccharide krestin (PSK) is a mushroom extract that has been long used in Asia and recently in Western countries as a treatment for cancer due to its presumed immune potentiating effects. Although there have been reports of clinical responses after patients have ingested PSK, the mechanism of action of the agent remains undefined. The current study was undertaken to investigate the mechanism of the antitumor actions of PSK. Experimental Design: The immunostimulatory effect of PSK was first evaluated in vitro using splenocytes from neu transgenic mice and Toll-like receptor (TLR) 2 knockout (TLR2−/−) mice. Then the immunostimualtory and antitumor effect of PSK was determined using tumor-bearing neu transgenic mice, TLR2−/−, and wild-type C57BL/6 mice. Results: We demonstrate that PSK is a selective TLR2 agonist, and the activation of dendritic cells (DC) and T cells by PSK is dependent on TLR2. Oral administration of PSK in neu transgenic mice significantly inhibits breast cancer growth. Selective depletion of specific cell populations suggests that the antitumor effect of PSK is dependent on both CD8+ T cell and NK cells, but not CD4+ T cells. PSK does not inhibit tumor growth in TLR2−/− mice suggesting that the antitumor effect is mediated by TLR2. Conclusion: These results demonstrate that PSK, a natural product commonly used for the treatment of cancer, is a specific TLR2 agonist and has potent antitumor effects via stimulation of both innate and adaptive immune pathways. Clin Cancer Res; 17(1); 67–76. ©2010 AACR.
Characteristics related to early secondary amenorrhoea and pregnancy among women diagnosed with systemic lupus erythematosus: an analysis using the GOAL study

Objective Systemic lupus erythematosus (SLE) disproportionately affects women and often develops during their reproductive years. Research suggests that some women who receive cyclophosphamide as treatment for SLE experience earlier decline in menstrual function, but reproductive health among women with SLE who have not taken this drug is less well understood. This study aims to better understand the relation between SLE and reproduction by assessing early secondary amenorrhoea and pregnancy in women treated with and without cyclophosphamide from a population-based cohort with large numbers of African-Americans. Methods Female patients with SLE, ages 20–40 at time of diagnosis, who were 40 years or older at the time of the survey were included in this analysis (N=147). Participants in the Georgians Organized Against Lupus (GOAL) study were asked about their reproductive histories including early secondary amenorrhoea, defined as loss of menstruation before age 40. Results Women who were cyclophosphamide naïve had an increased prevalence of early secondary amenorrhoea compared with population estimates, 13–17% compared with 1–5%. Factors associated with early secondary amenorrhoea in women not treated with cyclophosphamide were marital status and receipt of a kidney transplant. Treatment with cyclophosphamide doubled the prevalence after adjustment for patient characteristics. Over 88% of women reported being pregnant at least once, and about 83% of these had a child, but the majority of pregnancies occurred before diagnosis. Conclusions SLE diagnosed in early adulthood may affect women's reproductive health even if they are not treated with cyclophosphamide. Better understanding of other factors related to reproductive health in this population will improve clinicians' and patients' abilities to make treatment and family planning decisions.
A Systematic Review of Catechol-O-Methyltransferase Inhibitors: Efficacy and Safety in Clinical Practice

&NA;Catechol-O-methyltransferase (COMT) inhibitors are drugs commonly used in the management of patients with Parkinson disease complicated by motor fluctuations. Among them, entacapone is the most commonly used. Tolcapone has been reintroduced in patients where entacapone has proved to be ineffective after being withdrawn from the market because of sporadic cases of hepatotoxicity. The last COMT inhibitor is nebicapone, which use in clinical practice is still under study. ObjectivesThe objectives of this study were to analyze the clinical efficacy in reducing motor complications and to evaluate their use in clinical practice and the adverse events reported in the literature. MethodsScientific articles of the main previously mentioned drugs have been reviewed. ResultsAll these 3 drugs have proved to be effective in improving wearing-off and significantly reduce the daily dose of levodopa at the number of daily intakes. Tolcapone is undoubtedly the most effective drug, although in clinical practice sporadic cases of hepatotoxicity have limited its use in patients unresponsive to entacapone. Nebicapone is effective, and its safety is still under evaluation. Entacapone is generally well tolerated, and no significant adverse events are reported. ConclusionsTo manage motor fluctuations, the use of COMT inhibitors is now consolidated in the common clinical practice. Tolcapone is used as a second choice in patients with severe motor fluctuations not responsive to entacapone.
Strength and Deformation Characteristics of Lightweight Foamed Soil Using In-situ Soil

A series of unconfined compression tests were carried out firstly to investigate mechanical behaviors of Lightweight Foamed Soil (LWFS) which is composed of dredged soils, cement and air foam. And secondly, to compare the difference of mechanical characteristic of LWFS with previous research conclusions (Yoon & Kim,2004) by using different dredged soils sampled at Joong-Ma in Gwangyang harbor area. Based on numberous laboratory experiments, it was found that deformation coefficient of LWFS increases with increasing cement contents but decreases with increasing initial water contents of dredged soils. Appropriate regression formula (normalizing factor scheme) which considers relationship between LWFS composing elements, initial water contents of dredged soils, cement, air foam, and uniaxial compression strength or LWFS is proposed for practical applications. Finally, it was clear that, to apply LWFS method to practical projects, certain laboratory test would be necessary to take considerations of soil locality because mechanical charac-teristics of LWFS were surely dependent upon their sampled locations and properties.
Treatment of acute myeloid leukaemia in younger patients.

The survival of AML in younger patients has improved in the last 20 years, as a consequence of a more intensive approach to treatment. Seventy-five to eighty percent of patients will enter complete remission, so the main challenge is to prevent relapse. Several trials have assessed the value of allogeneic or autologous transplantation. When these trials have been assessed by careful statistical methods, the advantage of transplant overall is difficult to detect. Intensive consolidation can deliver a similar survival, of which high-dose Ara-C has been widely adopted, but other intensive schedules appear equivalent. It is not known how many treatment courses are required. Patients are at differing risks of relapse which may influence the choice of treatment. In trials where a risk profile is available, and where a donor versus no-donor analysis is performed, there appears to be little robust evidence to support transplant in good or poor risk disease, although the experience in the latter groups is not unanimous. Standard risk patients may be the subgroup who deliver survival benefit, but since chemotherapy continues to improve, there remains some uncertainty. It is possible that technical improvements in transplantation, such as peripheral blood as a source of stem cells, may remove this uncertainty.
CpG-B Oligodeoxynucleotide Promotes Cell Survival via Up-regulation of Hsp70 to Increase Bcl-xL and to Decrease Apoptosis-inducing Factor Translocation*

Unmethylated CpG oligodeoxynucleotides (ODNs) activate immune responses in a TLR9-dependent manner. In this study, stimulation of mouse macrophages with CpG-B ODN increased cellular Hsp70 expression and prevented apoptosis induced by serum starvation or staurosporine treatment. CpG-B ODN-induced Hsp70 expression depended on TLR9, MyD88, and phosphatidylinositol 3-kinase. Inhibition of Hsp70 synthesis by an inhibitor (quercetin) or antisense hsp70 attenuated not only Hsp70 expression but also the anti-apoptotic capacity of CpG-B ODN. Ectopic expression of Hsp70 rescued the inhibitory effect of quercetin on CpG-B ODN-induced anti-apoptosis. Additional experiments demonstrated that quercetin and anti-sense hsp70 modulated CpG-B ODN-induced anti-apoptosis via a caspase-3-independent pathway by down-regulating the survival gene bcl-xL and by increasing translocation of apoptosis-inducing factor. These findings suggest that CpG-B ODN may up-regulate Hsp70 via a TLR9/MyD88/phosphatidylinositol 3-kinase pathway to increase Bcl-xL and to decrease apoptosis-inducing factor nuclear translocation, resulting in anti-apoptosis.
Brevity is not always a virtue in primate communication

Semple et al. (Semple et al. in press, Biol. Lett. (doi:10.1098/rsbl.2009.1062)) argued that the ‘law of brevity’ (an inverse relationship between word length and frequency of use) applies not only to human language but also to vocal signalling in non-human primates, because coding efficiency is paramount in both situations. We analysed the frequency of use of signals of different duration in the vocal repertoires of two Neotropical primate species studied in the wild—the common marmoset (Callithrix jacchus) and the golden-backed uakari (Cacajao melanocephalus). The key prediction of the law of brevity was not supported in either species: although the most frequently emitted calls were relatively brief, they were not the shortest signals in the repertoire. The costs and benefits associated with signals of different duration must be appreciated to understand properly their frequency of use. Although relatively brief vocal signals may be favoured by natural selection in order to minimize energetic costs, the very briefest signals may be ambiguous, contain reduced information or be difficult to detect or locate, and may therefore be selected against. Analogies between human language and vocal communication in animals can be misleading as a basis for understanding frequency of use, because coding efficiency is not the only factor of importance in animal communication, and the costs and benefits associated with different signal durations will vary in a species-specific manner.
A New Technique to Measure the Jitter

In this paper we present a new process to measure the jitter of a telecommunication system. To understand better the new proposed technique we show others classical measurer systems. The obtained results are coherent with the well known theoretical formula of the analog PLL based on an ideal multiplier and also with the practical results obtained experimentally.
Changes in Arterial Stiffness and Wave Reflection With Advancing Age in Healthy Men and Women: The Framingham Heart Study

With advancing age, arterial stiffness and wave reflections increase and elevate systolic and pulse pressures. An elevated central pulse pressure is generally ascribed to increased wave reflection and portends an unfavorable prognosis. Using arterial tonometry, we evaluated central (carotid-femoral) and peripheral (carotid-brachial) pulse wave velocity, amplitudes of forward and reflected pressure waves, and augmentation index in 188 men and 333 women in the Framingham Heart Study offspring cohort who were free of clinical cardiovascular disease, hypertension, diabetes, smoking within the past 12 months, dyslipidemia, and obesity. In multivariable linear regression models, advancing age was the predominant correlate of higher carotid-femoral pulse wave velocity; other correlates were higher mean arterial pressure, heart rate, and triglycerides and walk test before tonometry (model R2 = 0.512, P < 0.001). A similar model was obtained for carotid-brachial pulse wave velocity (model R2 = 0.227, P < 0.001), although the increase with advancing age was smaller. Owing to different relations of age to central and peripheral stiffness measures, carotid-femoral pulse wave velocity was lower than carotid-brachial pulse wave velocity before age 50 years but exceeded it thereafter, leading to reversal of the normal central-to-peripheral arterial stiffness gradient. In this healthy cohort with a minimal burden of cardiovascular disease risk factors, an age-related increase in aortic stiffness, as compared with peripheral arterial stiffness, was associated with increasing forward wave amplitude and pulse pressure and reversal of the arterial stiffness gradient. This phenomenon may facilitate forward transmission of potentially deleterious pressure pulsations into the periphery.
Failure locus of the anterior cruciate ligament: 3D finite element analysis

Anterior cruciate ligament (ACL) disruption is a common injury that is detrimental to an athlete's quality of life. Determining the mechanisms that cause ACL injury is important in order to develop proper interventions. A failure locus defined as various combinations of loadings and movements, internal/external rotation of femur and valgus and varus moments at a 25o knee flexion angle leading to ACL failure was obtained. The results indicated that varus and valgus movements were more dominant to the ACL injury than femoral rotation. Also, Von Mises stress in the lateral tibial cartilage during the valgus ACL injury mechanism was 83% greater than that of the medial cartilage during the varus mechanism of ACL injury. The results of this study could be used to develop training programmes focused on the avoidance of the described combination of movements which may lead to ACL injury.