Room temperature plasmon laser by total internal reflection

Plasmon lasers create and sustain intense and coherent optical fields below light's diffraction limit with the unique ability to drastically enhance light-matter interactions bringing fundamentally new capabilities to bio-sensing, data storage, photolithography and optical communications. However, these important applications require room temperature operation, which remains a major hurdle. Here, we report a room temperature semiconductor plasmon laser with both strong cavity feedback and optical confinement to 1/20th of the wavelength. The strong feedback arises from total internal reflection of surface plasmons, while the confinement enhances the spontaneous emission rate by up to 20 times.Comment: 8 Page, 2 Figure

Structure formation in active networks

Structure formation and constant reorganization of the actin cytoskeleton are key requirements for the function of living cells. Here we show that a minimal reconstituted system consisting of actin filaments, crosslinking molecules and molecular-motor filaments exhibits a generic mechanism of structure formation, characterized by a broad distribution of cluster sizes. We demonstrate that the growth of the structures depends on the intricate balance between crosslinker-induced stabilization and simultaneous destabilization by molecular motors, a mechanism analogous to nucleation and growth in passive systems. We also show that the intricate interplay between force generation, coarsening and connectivity is responsible for the highly dynamic process of structure formation in this heterogeneous active gel, and that these competing mechanisms result in anomalous transport, reminiscent of intracellular dynamics

Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain

Background: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results: In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.Bernhard T Baune, Carsten Konrad, Dominik Grotegerd, Thomas Suslow, Eva Birosova, Patricia Ohrmann, Jochen Bauer, Volker Arolt, Walter Heindel, Katharina Domschke, Sonja Schöning, Astrid V Rauch, Christina Uhlmann, Harald Kugel and Udo Dannlowsk

Single-molecule visualization reveals the damage search mechanism for the human NER protein XPC-RAD23B

DNA repair is critical for maintaining genomic integrity. Finding DNA lesions initiates the entire repair process. In human nucleotide excision repair (NER), XPC-RAD23B recognizes DNA lesions and recruits downstream factors. Although previous studies revealed the molecular features of damage identification by the yeast orthologs Rad4-Rad23, the dynamic mechanisms by which human XPC-RAD23B recognizes DNA defects have remained elusive. Here, we directly visualized the motion of XPC-RAD23B on undamaged and lesion-containing DNA using high-throughput single-molecule imaging. We observed three types of one-dimensional motion of XPC-RAD23B along DNA: diffusive, immobile and constrained. We found that consecutive AT-tracks led to increase in proteins with constrained motion. The diffusion coefficient dramatically increased according to ionic strength, suggesting that XPC-RAD23B diffuses along DNA via hopping, allowing XPC-RAD23B to bypass protein obstacles during the search for DNA damage. We also examined how XPC-RAD23B identifies cyclobutane pyrimidine dimers (CPDs) during diffusion. XPC-RAD23B makes futile attempts to bind to CPDs, consistent with low CPD recognition efficiency. Moreover, XPC-RAD23B binds CPDs in biphasic states, stable for lesion recognition and transient for lesion interrogation. Taken together, our results provide new insight into how XPC-RAD23B searches for DNA lesions in billions of base pairs in human genome

Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif

To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally “native” epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high α-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens

Acute paranoid psychosis as sole clinical presentation of hepatic artery thrombosis after living donor liver transplantation

<p>Abstract</p> <p>Background</p> <p>Hepatic artery thrombosis is a devastating complication after orthotopic liver transplantation often requiring revascularization or re-transplantation. It is associated with considerably increased morbidity and mortality. Acute cognitive dysfunction such as delirium or acute psychosis may occur after major surgery and may be associated with the advent of surgical complications.</p> <p>Case presentation</p> <p>Here we describe a case of hepatic artery thrombosis after living-donor liver transplantation which was not preceded by signs of liver failure but rather by an episode of acute psychosis. After re-transplantation the patient recovered without sequelae.</p> <p>Conclusion</p> <p>This case highlights the need to remain cautious when psychiatric disorders occur in patients after liver transplantation. The diagnostic procedures should not be restricted to medical or neurological causes of psychosis alone but should also focus vascular complications related to orthotopic liver transplantation.</p

Resorbable screws versus pins for optimal transplant fixation (SPOT) in anterior cruciate ligament replacement with autologous hamstring grafts: rationale and design of a randomized, controlled, patient and investigator blinded trial [ISRCTN17384369]

BACKGROUND: Ruptures of the anterior cruciate ligament (ACL) are common injuries to the knee joint. Arthroscopic ACL replacement by autologous tendon grafts has established itself as a standard of care. Data from both experimental and observational studies suggest that surgical reconstruction does not fully restore knee stability. Persisting anterior laxity may lead to recurrent episodes of giving-way and cartilage damage. This might at least in part depend on the method of graft fixation in the bony tunnels. Whereas resorbable screws are easy to handle, pins may better preserve graft tension. The objective of this study is to determine whether pinning of ACL grafts reduces residual anterior laxity six months after surgery as compared to screw fixation. DESIGN/ METHODS: SPOT is a randomised, controlled, patient and investigator blinded trial conducted at a single academic institution. Eligible patients are scheduled to arthroscopic ACL repair with triple-stranded hamstring grafts, conducted by a single, experienced surgeon. Intraoperatively, subjects willing to engage in this study will be randomised to transplant tethering with either resorbable screws or resorbable pins. No other changes apply to locally established treatment protocols. Patients and clinical investigators will remain blinded to the assigned fixation method until the six-month follow-up examination. The primary outcome is the side-to-side (repaired to healthy knee) difference in anterior translation as measured by the KT-1000 arthrometer at a defined load (89 N) six months after surgery. A sample size of 54 patients will yield a power of 80% to detect a difference of 1.0 mm ± standard deviation 1.2 mm at a two-sided alpha of 5% with a t-test for independent samples. Secondary outcomes (generic and disease-specific measures of quality of life, magnetic resonance imaging morphology of transplants and devices) will be handled in an exploratory fashion. CONCLUSION: SPOT aims at showing a reduction in anterior knee laxity after fixing ACL grafts by pins compared to screws

Multiple Distant Origins for Green Sea Turtles Aggregating off Gorgona Island in the Colombian Eastern Pacific

Mitochondrial DNA analyses have been useful for resolving maternal lineages and migratory behavior to foraging grounds (FG) in sea turtles. However, little is known about source rookeries and haplotype composition of foraging green turtle aggregations in the southeastern Pacific. We used mitochondrial DNA control region sequences to identify the haplotype composition of 55 green turtles, Chelonia mydas, captured in foraging grounds of Gorgona National Park in the Colombian Pacific. Amplified fragments of the control region (457 bp) revealed the presence of seven haplotypes, with haplotype (h) and nucleotide (π) diversities of h = 0.300±0.080 and π = 0.009±0.005 respectively. The most common haplotype was CMP4 observed in 83% of individuals, followed by CMP22 (5%). The genetic composition of the Gorgona foraging population primarily comprised haplotypes that have been found at eastern Pacific rookeries including Mexico and the Galapagos, as well as haplotypes of unknown stock origin that likely originated from more distant western Pacific rookeries. Mixed stock analysis suggests that the Gorgona FG population is comprised mostly of animals from the Galapagos rookery (80%). Lagrangian drifter data showed that movement of turtles along the eastern Pacific coast and eastward from distant western and central Pacific sites was possible through passive drift. Our results highlight the importance of this protected area for conservation management of green turtles recruited from distant sites along the eastern Pacific Ocean

Yeast Based Small Molecule Screen for Inhibitors of SARS-CoV

Severe acute respiratory coronavirus (SARS-CoV) emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP) is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells

Process evaluation of a blended web-based intervention on return to work for sick-listed employees with common mental health problems in the occupational health setting

Purpose A blended web-based intervention, "eHealth module embedded in collaborative occupational health care" (ECO), aimed at return to work, was developed and found effective in sick-listed employees with common mental disorders. In order to establish the feasibility of ECO, a process evaluation was conducted. Methods Seven process components were investigated: recruitment, reach, dose delivered, dose received, fidelity, satisfaction and context. Quantitative and qualitative methods were used to collect data: an online questionnaire for the employees, website data, telephonic interviews with occupational physicians (OPs) and observations of the researchers. Results Recruitment was uncomplicated for the employees, but required several steps for the OPs. Reach was 100 % at the OP level and 76.3 % at the employee level. Dose delivered and received for OPs: 91.6 % received minimally one email message. Dose delivered and received for the employees: finishing of the different modules of ECO varied between 13 and 90 %. Fidelity: the support of the OP to the employee in ECO was lower than anticipated. Satisfaction: both employees and OPs were satisfied with the intervention. However, employees reported a need for more support in ECO. The context showed that OPs had limited time to support the employees and it was impossible for the employee to contact the OP outside their regular contacts. Conclusion Feasibility of ECO and satisfaction of employees and OPs with ECO were good. Fidelity of OPs was limited. For further implementation in the occupational health setting, especially contextual barriers regarding time limitation and accessibility of OPs for employees should be addressed