Miracle-dz/UniFAR-FTUs huggingface dataset:
An EST‐based genome scan using 454 sequencing in the marine snail Littorina saxatilis

Genome scans have been used in the studies of ecological speciation to find genomic regions (‘outlier loci’) showing reduced gene flow between divergent populations/species. High‐throughput sequencing (‘454’) offers new opportunities in this field via transcriptome sequencing. Divergent ecotypes of the marine gastropod Littorina saxatilis represent a good example of incipient ecological speciation. We performed a 454‐based genome scan between H and M ecotypes of L. saxatilis from the British Isles using cDNA of pooled individuals. Allele frequencies were calculated for 2454 single nucleotide polymorphisms (SNPs), within 572 contigs, and 7% of loci were detected as outliers. Functional annotation of the contigs containing outlier SNPs showed that they included shell matrix and muscle proteins (lithostathine, mucin, titin), proteins involved in energetic metabolism (arginine kinase, NADH dehydrogenase) and reverse transcriptases. Follow‐up investigations into these proteins and unannotated outliers will be a promising route in the study of ecological speciation in L. saxatilis.
Device-guided breathing exercises in the control of human blood pressure: systematic review and meta-analysis

Objective: To evaluate whether device-guided breathing (DGB) lowers blood pressure (BP) in adults. Design: Systematic review and meta-analysis. Data sources: We searched Medline (1950–2010), Embase (1980–2010), the Cochrane Library including the Cochrane Central register of Controlled Trials (CENTRAL), AMED (1985–2010), CINAHL (1980–2010) and the Current Controlled Trials registry (as of October 2010). Outcome measures: Primary outcomes included the mean change in SBP and DBP. Secondary outcomes included change in heart rate, quality of life, compliance with the device and any side effects of the device. Results: We included eight trials of the Resperate device (InterCure Ltd, Lod, Israel), consisting of 494 adult patients. Use of this device resulted in significantly reduced SBP by 3.67 mmHg [95% confidence interval (CI) = −5.99 to −1.39; P = 0.002] and decreased DBP by 2.51 mmHg (95% CI = −4.15 to −0.87; P = 0.003). However, sensitivity analysis was carried out excluding the five trials sponsored by or involving the manufacturers of the device, which revealed no overall effect on BP using the device. The maximum trial duration was 9 weeks and no overall effect was seen on heart rate or quality of life using the device. Conclusion: There is evidence that short-term use of DGB may reduce both DBP and DBP. However, five of the eight trials were sponsored by or involved the manufactures of the device. When these trials were excluded we found no overall effect. We conclude that longer term, independent trials are required to validate this intervention.
Bioresorbable Collagen Membranes for Guided Bone Regeneration

Localized lack of bone volume in the jaws may be due to congenital, post-traumatic, postsurgical defects or different disease processes. Increasing the bone volume has long been an attractive field of basic and clinical research. The introduction of implant therapy, and the proven relationship between long-term prognosis of dental implants and adequate bone volume at the implant site (Lekholm et al. 1986), dramatically increased the interest of both clinicians and scientists in this field, making augmentation procedures an important part of contemporary implant therapy. Basically, four methods have been described to augment bone volume: a. osteoinduction, using appropriate growth factors (Reddi 1981; Urist 1965); b. osteoconduction, using grafting materials that serve as scaffolds for new bone growth (Buch et al. 1986; Reddi et al. 1987); c. distraction osteogenesis, by which a surgically induced bone fracture enables slow controlled pulling apart of the separated bone fragments (Ilizarov 1989a,b); d. guided bone regeneration, which allows selective bone tissue growth into a space maintained by tissue barriers (Dahlin et al. 1988, 1991a; Kostopoulos & Karring 1994; Nyman & Lang 1994). Among the different methods, guided bone regeneration (GBR) is the most popular and best documented for the treatment of localized bone defects in the jaws, probably due to its relative simplicity of use while allowing the placement of endosseous implants in areas of the jaw with bony defects and/or insufficient bone volume. Highly predictable success rates can be achieved using GBR; in fact, it has been shown that success rates of implants placed at GBR treated sites and sites without bone augmentation are comparable (Hammerle et al. 2002).
Evolution of host specialization in gut microbes: the bee gut as a model

Bacterial symbionts of eukaryotes often give up generalist lifestyles to specialize to particular hosts. The eusocial honey bees and bumble bees harbor two such specialized gut symbionts, Snodgrassella alvi and Gilliamella apicola. Not only are these microorganisms specific to bees, but different strains of these bacteria tend to assort according to host species. By using in-vivo microbial transplant experiments, we show that the observed specificity is, at least in part, due to evolved physiological barriers that limit compatibility between a host and a potential gut colonizer. How and why such specialization occurs is largely unstudied for gut microbes, despite strong evidence that it is a general feature in many gut communities. Here, we discuss the potential factors that favor the evolution of host specialization, and the parallels that can be drawn with parasites and other symbiont systems. We also address the potential of the bee gut as a model for exploring gut community evolution.
Ranking information resources in peer-to-peer text retrieval: an experimental study

This paper experimentally studies approaches to the problem of ranking information resources w.r. t. user queries in peer-to-peer information retrieval. In distributed environments, for each given user query and a set of information resources that are available, we need to select the right subset of these resources to forward the query to. Here, we study the problem of pruning descriptions of resources to acceptable lengths in a peer-to-peer scenario and two approaches to overcome the mismatch problem that may arise as a consequence of the pruning, namely query expansion and learning better resource descriptions from query streams. The results show that resource descriptions can be pruned to a large extent without ill effects and that learning better descriptions from query streams works much better than query expansion.
Clinical role of multidrug resistance protein 1 expression in chemotherapy resistance in early-stage breast cancer: the Austrian Breast and Colorectal Cancer Study Group.

PURPOSE The multidrug resistance protein 1 (MRP1) is expressed in human breast cancer cells and may contribute to the clinical drug resistance of breast cancer patients. Therefore, we determined the impact of MRP1 expression on the clinical outcome of adjuvant therapy in patients with early-stage breast cancer. PATIENTS AND METHODS Immunostaining for MRP1 was performed on tissue sections from 516 premenopausal, hormone receptor-positive breast cancer patients with stage I and II disease. Statistical analyses were performed to assess the effect of MRP1 expression on survival and to test for interaction between MRP1 expression and treatment. RESULTS MRP1 expression independently predicted shorter relapse-free survival (RFS) and overall survival (OS) in patients treated with cyclophosphamide, methotrexate, and fluorouracil (CMF; RFS: hazard ratio [HR] = 1.48; 95% CI, 1.16 to 1.88; P = .002; OS: HR = 1.82; 95% CI, 1.10 to 3.01; P = .02), but it did not predict shorter RFS and OS in patients who received tamoxifen plus goserelin (RFS: HR = 0.99; 95% CI, 0.74 to 1.31; P = .9; OS: HR = 0.68; 95% CI, 0.40 to 1.15; P = .1). Tests for interaction between MRP1 expression and treatment were statistically significant for both RFS (P = .04) and OS (P = .006). CONCLUSION Our data suggest that MRP1 expression plays an important role in the clinical resistance to adjuvant CMF chemotherapy but does not seem to affect response to adjuvant endocrine treatment with tamoxifen plus goserelin. Thus, MRP1 may be a useful marker for the selection of patients with early-stage breast cancer for the appropriate adjuvant therapy after prospective confirmatory evaluation.
Secure Communication Over Parallel Relay Channel

We investigate the problem of secure communication over parallel relay channel in the presence of a passive eavesdropper. We consider a four-terminal relay-eavesdropper channel which consists of multiple relay-eavesdropper channels as subchannels. For the discrete memoryless model, we establish outer and inner bounds on the rate-equivocation region. The inner bound allows mode selection at the relay. For each subchannel, secure transmission is obtained through one of two coding schemes at the relay: decoding-and-forwarding the source message or confusing the eavesdropper through noise injection. For the Gaussian memoryless channel, we establish lower and upper bounds on the perfect secrecy rate. Furthermore, we study a special case in which the relay does not hear the source and show that under certain conditions the lower and upper bounds coincide. The results established for the parallel Gaussian relay-eavesdropper channel are then applied to study the fading relay-eavesdropper channel. Analytical results are illustrated through some numerical examples.
Imaging Approaches for Dementia

SUMMARY: Brain imaging has progressed from exclusion of rare treatable mass lesions to a specific antemortem diagnosis. MR imaging−derived hippocampal atrophy and WMH are regarded as imaging biomarkers of AD and CVD respectively. Abnormal FP-CIT SPECT or cardiac iodobenzamide SPECT is a useful supportive imaging feature in the diagnosis of DLB. Frontal and/or anterior temporal atrophy and anterior defects on molecular imaging with FDG-PET or perfusion SPECT are characteristic of FTDs. Whole-body FDG-PET may be helpful in patients with rapidly progressing “autoimmune dementias,” and FLAIR and DWI are indicated in suspected CJD. A major role of imaging is in the development of new drugs and less costly biomarkers.
C.E.R.A. once every 4 weeks corrects anaemia and maintains haemoglobin in patients with chronic kidney disease not on dialysis

Background. No previous randomized controlled studies have been reported examining de novo, once every 4 weeks (Q4W) administration of erythropoiesis-stimulating agents in chronic kidney disease (CKD) patients. We report results from a randomized multinational study that compared continuous erythropoietin receptor activator (C.E.R.A.) Q4W with darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) for the correction of anaemia in non-dialysis CKD patients. Methods. Patients were randomized (1:1) to receive either 1.2 μg/kg C.E. R.A. Q4W or darbepoetin alfa QW/Q2W during a 20-week correction period and an 8-week evaluation period. Two primary end points were assessed: the haemoglobin (Hb) response rate and the change in average Hb concentration between baseline and evaluation. Results. The Hb response rate for C.E. R.A. was 94.1%, significantly higher than the protocol-specified 60% response rate [95% confidence interval (CI): 89.1, 97.3; P < 0.0001] and comparable with darbepoetin alfa (93.5%; 95% CI: 88.4, 96.8; P < 0.0001). C.E. R.A. Q4W was non-inferior to darbepoetin alfa QW/Q2W, with similar mean Hb changes from baseline of 1.62 g/dL and 1.66 g/dL, respectively. Patients receiving C.E. R.A. showed a steady rise in Hb, with fewer patients above the target range during the first 8 weeks compared with darbepoetin alfa [39 patients (25.8%) versus 72 patients (47.7%); P < 0.0001]. Adverse event rates were comparable between the treatment groups. Conclusion. C.E. R.A. Q4W successfully corrects anaemia and maintains stable Hb levels within the recommended target range in non-dialysis CKD patients.
High-speed parallel implementation of a modified PBR algorithm on DSP-based EH topology

Algebraic Reconstruction Technique (ART) is an age-old method used for solving the problem of three-dimensional (3-D) reconstruction from projections in electron microscopy and radiology. In medical applications, direct 3-D reconstruction is at the forefront of investigation. The simultaneous iterative reconstruction technique (SIRT) is an ART-type algorithm with the potential of generating in a few iterations tomographic images of a quality comparable to that of convolution backprojection (CBP) methods. Pixel-based reconstruction (PBR) is similar to SIRT reconstruction, and it has been shown that PBR algorithms give better quality pictures compared to those produced by SIRT algorithms. In this work, we propose a few modifications to the PBR algorithms. The modified algorithms are shown to give better quality pictures compared to PBR algorithms. The PBR algorithm and the modified PBR algorithms are highly compute intensive, Not many attempts have been made to reconstruct objects in the true 3-D sense because of the high computational overhead. In this study, we have developed parallel two-dimensional (2-D) and 3-D reconstruction algorithms based on modified PBR. We attempt to solve the two problems encountered by the PBR and modified PBR algorithms, i.e., the long computational time and the large memory requirements, by parallelizing the algorithm on a multiprocessor system. We investigate the possible task and data partitioning schemes by exploiting the potential parallelism in the PBR algorithm subject to minimizing the memory requirement. We have implemented an extended hypercube (EH) architecture for the high-speed execution of the 3-D reconstruction algorithm using the commercially available fast floating point digital signal processor (DSP) chips as the processing elements (PEs) and dual-port random access memories (DPR) as channels between the PEs. We discuss and compare the performances of the PBR algorithm on an IBM 6000 RISC workstation, on a Silicon Graphics Indigo 2 workstation, and on an EH system. The results show that an EH(3,1) using DSP chips as PEs executes the modified PBR algorithm about 100 times faster than an LBM 6000 RISC workstation. We have executed the algorithms on a 4-node IBM SP2 parallel computer. The results show that execution time of the algorithm on an EH(3,1) is better than that of a 4-node IBM SP2 system. The speed-up of an EH(3,1) system with eight PEs and one network controller is approximately 7.85.
Defects in Stratum Corneum Desquamation Are the Predominant Effect of Impaired ABCA12 Function in a Novel Mouse Model of Harlequin Ichthyosis

Harlequin Ichthyosis is a severe skin disease caused by mutations in the human gene encoding ABCA12. Here, we characterize a novel mutation in intron 29 of the mouse Abca12 gene that leads to the loss of a 5’ splice donor site and truncation of the Abca12 RNA transcript. Homozygous mutants of this smooth skin or smsk allele die perinatally with shiny translucent skin, typical of animal models of Harlequin Ichthyosis. Characterization of smsk mutant skin showed that the delivery of glucosylceramides and CORNEODESMOSIN was defective, while ultrastructural analysis revealed abnormal lamellar bodies and the absence of lipid lamellae in smsk epidermis. Unexpectedly, mutant stratum corneum remained intact when subjected to harsh chemical dissociation procedures. Moreover, both KALLIKREIN 5 and -7 were drastically decreased, with retention of desmoplakin in mutant SC. In cultured wild type keratinocytes, both KALLIKREIN 5 and -7 colocalized with ceramide metabolites following calcium-induced differentiation. Reducing the intracellular levels of glucosylceramide with a glucosylceramide synthase inhibitor resulted in decreased secretion of KALLIKREIN proteases by wild type keratinocytes, but not by smsk mutant keratinocytes. Together, these findings suggest an essential role for ABCA12 in transferring not only lipids, which are required for the formation of multilamellar structures in the stratum corneum, but also proteolytic enzymes that are required for normal desquamation. Smsk mutant mice recapitulate many of the pathological features of HI and can be used to explore novel topical therapies against a potentially lethal and debilitating neonatal disease.
Cable-net supported glass facade systems

Cable-net supported glass facade systems that comprise of pre-stressed cable-net, glass panes and glass support attachments; are commonly used in airport terminals, hotel lobbies, and trade centres. Glass used in building facade presents an aesthetic feature as well as contributes to the structural stiffness of the whole structural system of the building. In this research, the performance of cable-net supported glass facade systems was investigated via experiments and finite element analysis using the Abaqus v6.9 software. Two generic configurations of cable-net system were considered, namely flat and curved cable-net system, both with and without glass panes. For the curved cable-nets, two different curvatures were considered. Each system was subjected to three tests: static, impact and cable anchorage failure test. The results indicated that the glass panes made significant contributions to the stiffness of the whole structural system. The glass stiffness contribution for flat cable-net system was high at the early stage of loading (approximately 30%) but reduced when the load was increased. However, the glass stiffness contribution for curved cable-net increased gradually as the load was increased. For both configurations, the glass stiffness contribution remained steady at about 20% of the whole structural stiffness as the cables in the cable-net stiffened until the maximum load was applied to the system. Based on the static tests, the pre-stress force in the cables in the cable-net systems can possibly be reduced by approximately 50% of the initial pre-stress force; should the glass be considered in the analysis design of cable-net structure. Moreover, the curved cable-net could be designed to have lower pre-stress force in cables compared to that of flat cable-net to meet the deflection criterion of the cable-net structure. Consequently, in the impact test, the glass supported by cable-net structure was deflected at the same level as the cable-net when subjected to impact force. Although the deflection of cable-net is large, the deflection of individual glass was very shallow compared to the allowable deflection of glass pane. Despite the cable-net structure having the capability in reducing the impact force on the glass pane, it has no capability to prevent glass breakage when the impact hit the glass at its edge. Another effect of impact test was the corner node of the cable-net structure had almost the same deflection when the ball bearing hit the glass at the centre of glass facade; although it was found to be very stiff in the static test. The corner node was deflected excessively although the impact was farther from the node. The sudden failure of cable anchorage had no dramatic effects such as progressive collapse or glass breakage even though the cable forces in the curved cable-net oscillated about ±20% of the initial pre-stressed force. Finite element (FE) models were developed for flat cable-nets with and without glass panes using the Abaqus v6.9 software. The FE results were in good agreement with the experimental results with only 1% difference between the two sets of results.
Competing Death Programs in Poliovirus-Infected Cells: Commitment Switch in the Middle of the Infectious Cycle

ABSTRACT Productive poliovirus infection of HeLa cells leads to the canonical cytopathic effect (CPE), whereas certain types of abortive infection result in apoptosis. To define the time course of commitment to the different types of poliovirus-induced death, inhibitors of viral replication (guanidine HCl) or translation (cycloheximide) were added at different times postinfection (p.i.). Early in the infection (during the first ∼2 h p.i.), predominantly proapoptotic viral function was expressed, rendering the cells committed to apoptosis, which developed several hours after viral expression was arrested. In the middle of infection, concomitantly with the onset of fast generation of viral progeny, the implementation of the viral apoptotic program was abruptly interrupted. In particular, activation of an Asp-Glu-Val-Asp (DEVD)-specific caspase(s) occurring in the apoptosis-committed cells was prevented by the ongoing productive infection. Simultaneously, the cells retaining normal or nearly normal morphology became committed to CPE, which eventually developed regardless of whether or not further viral expression was allowed to proceed. The implementation of the poliovirus-induced apoptotic program was suppressed in HeLa cells overexpressing the Bcl-2 protein, indicating that the fate of poliovirus-infected cells depends on the balance of host and viral pro- and antiapoptotic factors.
Synthesis and immunosuppressive activity of new cyclolinopeptide A analogs modified with β‐prolines

Immune response suppressors are used in the medical praxis to prevent graft rejection after organ transplantation and in the therapy of some autoimmune diseases. As a continuation of our previous work searching for new, effective suppressors devoid of toxicity, we present the synthesis, conformational analysis, and biological activity of nonapeptides 1–6, analogs of naturally existing immunomodulatory peptide CLA. New CLA analogs were modified with (S)‐β2‐iso‐proline 7 or (S)‐β3‐homo‐proline 8, respectively. The conformational influence of the β‐iso‐proline and β‐homo‐proline building blocks was analyzed by NMR spectroscopy. Peptides 1–6 exist as a mixture of four isomers due to cis/trans isomerization of the Xxx–Pro peptide bond. The major isomers of peptides 1, 3, and 4 contain all peptide bonds of the trans geometry. The geometry of the proline–proline bond of the second populated isomer of peptides 3 and 4 is cis. The proline–proline peptide bond is cis for the major isomers of peptides 2, 5, and 6. The peptides were tested for their ability to suppress the proliferative response of mouse splenocytes to T‐ and B‐cell mitogens and the secondary humoral immune response to sheep erythrocytes in vitro in parallel with a reference drug—cyclosporine A. The immunoregulatory actions of the peptides depended on the position and content of proline isomers and were, with some exceptions, strongly inhibitory at the highest dose tested (100 µg/ml). In addition, the peptides were practically devoid of toxicity at that dose. In conclusion, the replacement of Pro by β‐Pro may be useful for fine‐tuning CLA immunosuppressive potency and undesirable toxicity. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
High temperature sensitivity is intrinsic to voltage-gated potassium channels

Temperature-sensitive transient receptor potential (TRP) ion channels are members of the large tetrameric cation channels superfamily but are considered to be uniquely sensitive to heat, which has been presumed to be due to the existence of an unidentified temperature-sensing domain. Here we report that the homologous voltage-gated potassium (Kv) channels also exhibit high temperature sensitivity comparable to that of TRPV1, which is detectable under specific conditions when the voltage sensor is functionally decoupled from the activation gate through either intrinsic mechanisms or mutations. Interestingly, mutations could tune Shaker channel to be either heat-activated or heat-deactivated. Therefore, high temperature sensitivity is intrinsic to both TRP and Kv channels. Our findings suggest important physiological roles of heat-induced variation in Kv channel activities. Mechanistically our findings indicate that temperature-sensing TRP channels may not contain a specialized heat-sensor domain; instead, non-obligatory allosteric gating permits the intrinsic heat sensitivity to drive channel activation, allowing temperature-sensitive TRP channels to function as polymodal nociceptors. DOI: http://dx.doi. org/10.7554/eLife.03255. 001