A microfluidic oligonucleotide synthesizer

De novo gene and genome synthesis enables the design of any sequence without the requirement of a pre-existing template as in traditional genetic engineering methods. The ability to mass produce synthetic genes holds great potential for biological research, but widespread availability of de novo DNA constructs is currently hampered by their high cost. In this work, we describe a microfluidic platform for parallel solid phase synthesis of oligonucleotides that can greatly reduce the cost of gene synthesis by reducing reagent consumption (by 100-fold) while maintaining a 100 pmol synthesis scale so there is no need for amplification before assembly. Sixteen oligonucleotides were synthesized in parallel on this platform and then successfully used in a ligation-mediated assembly method to generate DNA constructs 200 bp in length

The impact of exchanges rates on international real estate portfolio allocation

This paper, examines whether the asset holdings and weights of an international real estate portfolio using exchange rate adjusted returns are essentially the same or radically different from those based on unadjusted returns. The results indicate that the portfolio compositions produced by exchange rate adjusted returns are markedly different from those based on unadjusted returns. However following the introduction of the single currency the differences in portfolio composition are much less pronounced. The findings have a practical consequence for the investor because they suggest that following the introduction of the single currency international investors can concentrate on the real estate fundamentals when making their portfolio choices, rather than worry about the implications of exchange rate risk

Judging Ordinary Meaning

Judges generally begin their interpretive task by looking for the ordinary meaning of the language of the law. And they often end there - out of respect for the notice function of the law or deference to the presumed intent of the lawmaker. Most everyone agrees on the primacy of the ordinary meaning rule. Yet scholars roundly bemoan the indeterminacy of the communicative content of the language of the law. And they pivot quickly to other grounds for interpretation

Iterative approach to computational enzyme design

A general approach for the computational design of enzymes to catalyze arbitrary reactions is a goal at the forefront of the field of protein design. Recently, computationally designed enzymes have been produced for three chemical reactions through the synthesis and screening of a large number of variants. Here, we present an iterative approach that has led to the development of the most catalytically efficient computationally designed enzyme for the Kemp elimination to date. Previously established computational techniques were used to generate an initial design, HG-1, which was catalytically inactive. Analysis of HG-1 with molecular dynamics simulations (MD) and X-ray crystallography indicated that the inactivity might be due to bound waters and high flexibility of residues within the active site. This analysis guided changes to our design procedure, moved the design deeper into the interior of the protein, and resulted in an active Kemp eliminase, HG-2. The cocrystal structure of this enzyme with a transition state analog (TSA) revealed that the TSA was bound in the active site, interacted with the intended catalytic base in a catalytically relevant manner, but was flipped relative to the design model. MD analysis of HG-2 led to an additional point mutation, HG-3, that produced a further threefold improvement in activity. This iterative approach to computational enzyme design, including detailed MD and structural analysis of both active and inactive designs, promises a more complete understanding of the underlying principles of enzymatic catalysis and furthers progress toward reliably producing active enzymes

RPCs Considered Harmful

Scholars agree that amphibious configurations are an interesting new topic in the field of cryp- toanalysis, and mathematicians concur. After years of structured research into gigabit switches, we argue the improvement of forward-error correction, which embodies the private principles of cryptography. In our research, we use authenticated modalities to demonstrate that digital-to-analog converters and evolutionary programming can collude to address this question. Such a hypothesis at first glance seems unexpected but is derived from known results

Letter to editor: A new core gross anatomy syllabus for medicine

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Influence of wheel size on muscle activity and tri-axial accelerations during Cross-Country mountain biking

This study aimed to investigate the influence of different mountain bike wheel diameters on muscle activity and whether larger diameter wheels attenuate muscle vibrations during cross-country riding. Nine male competitive mountain bikers (age 34.7 ± 10.7 years; stature 177.7 ± 5.6 cm; body mass 73.2 ± 8.6 kg) participated in the study. Riders performed one lap at race pace on 26, 27.5 and 29 inch wheeled mountain bikes. sEMG and acceleration (RMS) were recorded for the full lap and during ascent and descent phases at the gastrocnemius, vastus lateralis, biceps brachii and triceps brachii. No significant main effects were found by wheel size for each of the four muscle groups for sEMG or acceleration during the full lap and for ascent and descent (P > .05). When data were analysed between muscle groups, significant differences were found between biceps brachii and triceps brachii (P < .05) for all wheel sizes and all phases of the lap with the exception of for the 26 inch wheel during the descent. Findings suggest wheel diameter has no influence on muscle activity and vibration during mountain biking. However, more activity was observed in the biceps brachii during 26 inch wheel descending. This is possibly due to an increased need to manoeuvre the front wheel over obstacles

Severity of disease and mortality for hospitalized patients with community-acquired viral pneumonia compared to patients with community-acquired bacterial pneumonia

Background: There exists a large body of literature to help identify, diagnose, treat, and manage community-acquired pneumonia (CAP). Despite this, there is little data that directly compares the clinical syndromes and complications of pure bacterial pneumonia to pure viral pneumonia. Our study compares the clinical presentation, morbidity and mortality of viral vs. bacterial etiologies of CAP. Methods: This was a secondary data analysis of the Community-Acquired Pneumonia Organization (CAPO) international study database. Data was collected concerning patient demographics, physical examination findings, laboratory findings, radiological findings, severity of illness, and clinical outcomes and stratified according to the two study groups, CAVP and CABP. A microbiological diagnosis of CABP was based on the isolation of a bacterium from a respiratory sample, blood culture and/or identification of a urinary antigen for Streptococcus or Legionella; microbiological diagnosis of CAVP was based on polymerase chain reaction or antigen detection from respiratory samples. Results: Our study included 1,913 patients. Of these, 286 (15.0%) had viral infection, while 1,627 (85.0%) had CAVP. We found that bacterial CAP patients are older, more frequently male, and suffer from a higher proportion of comorbidities when compared to viral CAP patients. Comparison of physical exam findings and laboratory values failed to find a clinically significant difference between bacterial and viral CAP patients. When comparing severity of illness, bacterial CAP patients had greater frequency of PSI ≥ class IV; however, viral CAP patients more frequently needed ICU admission, ventilator support, vasopressor support, and had higher rate of in hospital mortality. Conclusions: Our study confirms the extreme difficulty differentiating CABP from CAVP using demographics, physical exam, or x-ray findings. We found no major clinical or laboratory findings distinguishing CABP from CAVP. The increased severity of illness of CAVP compared to bacterial etiologies shows that PSI scores may not be an accurate indicator of severity of disease. More studies are needed to identify the best process of care for patients with CAP, including the potential benefits of routine respiratory viral panel testing and empiric antiviral therapy

Single cell analysis reveals immune cell-adipocyte crosstalk regulating the transcription of thermogenic adipocytes.

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function

Cavity-enabled high-dimensional quantum key distribution

High-dimensional quantum key distribution (QKD) offers the possibility of encoding multiple bits of key on a single entangled photon pair. An experimentally promising approach to realizing this is to use energy–time entanglement. Currently, however, the control of very high-dimensional entangled photons is challenging. We present a simple and experimentally compact approach, which is based on a cavity that allows one to measure two different bases: the time of arrival and another that is approximately mutually unbiased to the arrival time. We quantify the errors in the setup, due both to the approximate nature of the mutually unbiased measurement and as a result of experimental errors. It is shown that the protocol can be adapted using a cut-off so that it is robust against the considered errors, even within the regime of up to 10 bits per photon pair