Ultracold dense gas of deeply bound heteronuclear molecules

Recently, the quest for an ultracold and dense ensemble of polar molecules has attracted strong interest. Polar molecules have bright prospects for novel quantum gases with long-range and anisotropic interactions, for quantum information science, and for precision measurements. However, high-density clouds of ultracold polar molecules have so far not been produced. Here, we report a key step towards this goal. Starting from an ultracold dense gas of heteronuclear 40K-87Rb Feshbach molecules with typical binding energies of a few hundred kHz and a negligible dipole moment, we coherently transfer these molecules into a vibrational level of the ground-state molecular potential bound by >10 GHz. We thereby increase the binding energy and the expected dipole moment of the 40K-87Rb molecules by more than four orders of magnitude in a single transfer step. Starting with a single initial state prepared with Feshbach association, we achieve a transfer efficiency of 84%. While dipolar effects are not yet observable, the presented technique can be extended to access much more deeply bound vibrational levels and ultimately those exhibiting a significant dipole moment. The preparation of an ultracold quantum gas of polar molecules might therefore come within experimental reach.Comment: 5 pages, 5 figure

Searching for Exoplanets Using a Microresonator Astrocomb

Detection of weak radial velocity shifts of host stars induced by orbiting planets is an important technique for discovering and characterizing planets beyond our solar system. Optical frequency combs enable calibration of stellar radial velocity shifts at levels required for detection of Earth analogs. A new chip-based device, the Kerr soliton microcomb, has properties ideal for ubiquitous application outside the lab and even in future space-borne instruments. Moreover, microcomb spectra are ideally suited for astronomical spectrograph calibration and eliminate filtering steps required by conventional mode-locked-laser frequency combs. Here, for the calibration of astronomical spectrographs, we demonstrate an atomic/molecular line-referenced, near-infrared soliton microcomb. Efforts to search for the known exoplanet HD 187123b were conducted at the Keck-II telescope as a first in-the-field demonstration of microcombs

Findings from the Peutz-Jeghers Syndrome Registry of Uruguay

Background: Peutz-Jeghers syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased cancer risk, usually caused by mutations of the STK11 gene. This study collected epidemiological, clinical and genetic data from all Uruguayan PJS patients. Methods: Clinical data were obtained from public and private medical centers and updated annually. Sequencing of the STK11 gene in one member of each family was performed. Results and discussion: 25 cases in 11 unrelated families were registered (15 males, 10 females). The average age of diagnosis and death was 18 and 41 years respectively. All patients had characteristic PJS pigmentation and gastrointestinal polyps. 72% required urgent surgery due to intestinal obstruction. 3 families had multiple cases of seizure disorder, representing 20% of cases. 28% developed cancer and two patients had more than one cancer. An STK11 mutation was found in 8 of the 9 families analyzed. A unique M136K missense mutation was noted in one family. Comparing annual live births and PJS birth records from 1970 to 2009 yielded an incidence of 1 in 155,000. Conclusion: The Uruguayan Registry for Peutz-Jeghers patients showed a high chance of emergent surgery, epilepsy, cancer and shortened life expectancy. The M136K missense mutation is a newly reported STK 11 mutation

Continued improvement of cardiovascular mortality in Hungary - impact of increased cardio-metabolic prescriptions

<p>Abstract</p> <p>Background</p> <p>During the last 35 years the poor ranking of Hungary on the list of life expectancy at birth among European countries, has not changed. In 1970 our lag behind the leading European countries was the smallest. The gap was growing between 1970 and 1993 but from 1994 onwards the life expectancy at birth in Hungary has increased continuously and somewhat faster than in other European countries. The aim of this study was to analyze the association between decreasing cardiovascular mortality rates, as a main cause of death and the increase in cardio-metabolic prescriptions and possible changes in lifestyle behavior.</p> <p>Methods</p> <p>Analyses were conducted on national data concerning cardiovascular mortality and the number of cardio-metabolic drug prescription per capita. The association between yearly rates of cardiovascular events and changes in antihypertensive, antilipidemic and antidiabetic prescription rates was analyzed. The changes in other cardiovascular risk factors, like lifestyle were also considered.</p> <p>Results</p> <p>We observed a remarkable decline of mortality due to stroke and acute myocardial infarction (AMI). The fall was significantly associated with all prescription rates. The proportion of each treatment type responsible for suppression of specific mortality rates is different. All treatment types comparably improved stroke mortality, while antilipidemic therapy improved AMI outcome.</p> <p>Conclusions</p> <p>These results emphasize the importance of a comprehensive strategy that maximizes the population coverage of effective treatments. Hungary appears to be at the beginning of the fourth stage of epidemiologic transition, i.e. it has entered the stage of delayed chronic noninfectious diseases.</p

Cholesteryl Ester Transfer Protein (CETP) Polymorphisms Affect mRNA Splicing, HDL Levels, and Sex-Dependent Cardiovascular Risk

Polymorphisms in and around the Cholesteryl Ester Transfer Protein (CETP) gene have been associated with HDL levels, risk for coronary artery disease (CAD), and response to therapy. The mechanism of action of these polymorphisms has yet to be defined. We used mRNA allelic expression and splice isoform measurements in human liver tissues to identify the genetic variants affecting CETP levels. Allelic CETP mRNA expression ratios in 56 human livers were strongly associated with several variants 2.5–7 kb upstream of the transcription start site (e.g., rs247616 p = 6.4×10−5, allele frequency 33%). In addition, a common alternatively spliced CETP isoform lacking exon 9 (Δ9), has been shown to prevent CETP secretion in a dominant-negative manner. The Δ 9 expression ranged from 10 to 48% of total CETP mRNA in 94 livers. Increased formation of this isoform was exclusively associated with an exon 9 polymorphism rs5883-C>T (p = 6.8×10−10) and intron 8 polymorphism rs9930761-T>C (5.6×10−8) (in high linkage disequilibrium with allele frequencies 6–7%). rs9930761 changes a key splicing branch point nucleotide in intron 8, while rs5883 alters an exonic splicing enhancer sequence in exon 9

High prevalence of germline STK11 mutations in Hungarian Peutz-Jeghers Syndrome patients

<p>Abstract</p> <p>Background</p> <p>Peutz-Jeghers syndrome (PJS) is a rare autosomal dominantly inherited disease characterized by gastrointestinal hamartomatous polyposis and mucocutaneous pigmentation. The genetic predisposition for PJS has been shown to be associated with germline mutations in the <it>STK11</it>/<it>LKB1 </it>tumor suppressor gene. The aim of the present study was to characterize Hungarian PJS patients with respect to germline mutation in <it>STK11</it>/<it>LKB1 </it>and their association to disease phenotype.</p> <p>Methods</p> <p>Mutation screening of 21 patients from 13 PJS families were performed using direct DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). Comparative semi-quantitative sequencing was applied to investigate the mRNA-level effects of nonsense and splice-affecting mutations.</p> <p>Results</p> <p>Thirteen different pathogenic mutations in <it>STK11</it>, including a high frequency of large genomic deletions (38%, 5/13), were identified in the 13 unrelated families studied. One of these deletions also affects two neighboring genes (<it>SBNO2 </it>and <it>GPX4</it>), located upstream of <it>STK11</it>, with a possible modifier effect. The majority of the point mutations (88%, 7/8) can be considered novel. Quantification of the <it>STK11 </it>transcript at the mRNA-level revealed that the expression of alleles carrying a nonsense or frameshift mutation was reduced to 30-70% of that of the wild type allele. Mutations affecting splice-sites around exon 2 displayed an mRNA processing pattern indicative of co-regulated splicing of exons 2 and 3.</p> <p>Conclusions</p> <p>A combination of sensitive techniques may assure a high (100%) <it>STK11 </it>mutation detection frequency in PJS families. Characterization of mutations at mRNA level may give a deeper insight into the molecular consequences of the pathogenic mutations than predictions made solely at the genomic level.</p

Common NOD2/CARD15 variants are not associated with susceptibility or the clinicopathologic characteristics of sporadic colorectal cancer in Hungarian patients

BACKGROUND: Epidemiological observations suggest that cancer arises from chronically inflamed tissues. Inflammatory bowel disease (IBD) is a typical example as patients with longstanding IBD are at an increased risk for developing colorectal cancer (CRC) and mutations of the NOD2/CARD15 gene increase the risk for Crohn's disease (CD). Recently, NOD2/CARD15 has been associated with a risk for CRC in some studies, which stemmed from ethnically diverse populations. Our aim was to identify common NOD2/CARD15 mutations in Hungarian patients with sporadic CRC. METHODS: A total of 194 sporadic CRC patients (m/f: 108/86, age at diagnosis of CRC: 63.2 ± 9.1 years old) and 200 healthy subjects were included. DNA was screened for SNP8, SNP12 and SNP13 NOD2/CARD15 mutations by denaturing-HPLC and confirmed by direct sequencing. RESULTS: NOD2/CARD15 mutations were found in 28 patients (14.4%) and in 23 controls (11.5%, p = NS). Allele frequencies for SNP8/R702W (1.8% vs. 1.5%) SNP12/G908R (1.8% vs. 1.8%) and SNP13/3020insC (3.6% vs. 2.5%) were also not statistically different between patients and controls. The clinicopathologic characteristics of CRC patients with or without NOD2/CARD15 mutations were not significantly different. CONCLUSION: Our results suggest that common NOD2/CARD15 mutations alone do not contribute to CRC risk in the Hungarian population

Bridging ultrahigh-Q devices and photonic circuits

Optical microresonators are essential to a broad range of technologies and scientific disciplines. However, many of their applications rely on discrete devices to attain challenging combinations of ultra-low-loss performance (ultrahigh Q) and resonator design requirements. This prevents access to scalable fabrication methods for photonic integration and lithographic feature control. Indeed, finding a microfabrication bridge that connects ultrahigh-Q device functions with photonic circuits is a priority of the microcavity field. Here, an integrated resonator having a record Q factor over 200 million is presented. Its ultra-low-loss and flexible cavity design brings performance to integrated systems that has been the exclusive domain of discrete silica and crystalline microcavity devices. Two distinctly different devices are demonstrated: soliton sources with electronic repetition rates and high-coherence/low-threshold Brillouin lasers. This multi-device capability and performance from a single integrated cavity platform represents a critical advance for future photonic circuits and systems

Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins

Cotranslational protein folding can facilitate rapid formation of functional structures. However, it might also cause premature assembly of protein complexes, if two interacting nascent chains are in close proximity. By analyzing known protein structures, we show that homomeric protein contacts are enriched towards the C-termini of polypeptide chains across diverse proteomes. We hypothesize that this is the result of evolutionary constraints for folding to occur prior to assembly. Using high-throughput imaging of protein homomers in vivo in E. coli and engineered protein constructs with N- and C-terminal oligomerization domains, we show that, indeed, proteins with C-terminal homomeric interface residues consistently assemble more efficiently than those with N-terminal interface residues. Using in vivo, in vitro and in silico experiments, we identify features that govern successful assembly of homomers, which have implications for protein design and expression optimization