Low-threshold ultraviolet solid-state laser based on a Ce3+:LiCaAlF6 crystal resonator.

A low-threshold solid-state UV laser using a whispering gallery mode (WGM) resonator constructed from UV transparent crystalline material is demonstrated. Using a Ce3+:LiCaAlF6 resonator, we observe broad bandwidth lasing (280-330 nm) with a low threshold intensity of 7.5×10(9) W/m(2) and an effective slope efficiency of ~25%.

Multiplex epitope mapping using bacterial surface display reveals both linear and conformational epitopes.

As antibody-based diagnosis and therapy grow at an increased pace, there is a need for methods which rapidly and accurately determine antibody-antigen interactions. Here, we report a method for the multiplex determination of antibody epitopes using bacterial cell-surface display. A protein-fragment library with 10(7) cell clones, covering 60 clinically-relevant protein targets, was created and characterized with massively parallel sequencing.

Identification of multiple 5-HT₄ partial agonist clinical candidates for the treatment of Alzheimer's disease.

The cognitive impairments observed in Alzheimer's disease (AD) are in part a consequence of reduced acetylcholine (ACh) levels resulting from a loss of cholinergic neurons. Preclinically, serotonin 4 receptor (5-HT(4)) agonists are reported to modulate cholinergic function and therefore may provide a new mechanistic approach for treating cognitive deficits associated with AD. Herein we communicate the design and synthesis of potent, selective, and brain penetrant 5-HT(4) agonists.

Automated solid-phase subcloning based on beads brought into proximity by magnetic force.

In the fields of proteomics, metabolic engineering and synthetic biology there is a need for high-throughput and reliable cloning methods to facilitate construction of expression vectors and genetic pathways. Here, we describe a new approach for solid-phase cloning in which both the vector and the gene are immobilized to separate paramagnetic beads and brought into proximity by magnetic force. Ligation events were directly evaluated using fluorescent-based microscopy and flow cytometry.

Scanning tunnelling microscopy imaging of symmetry-breaking structural distortion in the bismuth-based cuprate superconductors.

A complicating factor in unravelling the theory of high-temperature (high-T(c)) superconductivity is the presence of a 'pseudogap' in the density of states, the origin of which has been debated since its discovery. Some believe the pseudogap is a broken symmetry state distinct from superconductivity, whereas others believe it arises from short-range correlations without symmetry breaking. A number of broken symmetries have been imaged and identified with the pseudogap state, but it remains crucial to disentangle any electronic symmetry breaking from the pre-existing structural symmetry of the crystal.

An integrated ion trap and time-of-flight mass spectrometer for chemical and photo- reaction dynamics studies.

We demonstrate the integration of a linear quadrupole trap with a simple time-of-flight mass spectrometer with medium-mass resolution (m/Δm ∼ 50) geared towards the demands of atomic, molecular, and chemical physics experiments. By utilizing a novel radial ion extraction scheme from the linear quadrupole trap into the mass analyzer, a device with large trap capacity and high optical access is realized without sacrificing mass resolution. This provides the ability to address trapped ions with laser light and facilitates interactions with neutral background gases prior to analyzing the trapped ions.

Feasibility of initiating and sustaining registry-based immunization recall in private practices.

Objective: To assess the feasibility of initiating and sustaining immunization recall by private practices, including the barriers and costs, using a statewide immunization information system (IIS).

Methods: Private practices in southeast Michigan were recruited in 2007 to perform IIS-based immunization recalls. Enrolled practices were provided with training and asked to conduct 4 recalls during the course of 12 months of children 19 to 35 months of age.

Measurement of a large chemical reaction rate between ultracold closed-shell 40Ca atoms and open-shell 174Yb+ ions held in a hybrid atom-ion trap.

Ultracold 174Yb+ ions and 40Ca atoms are confined in a hybrid trap. The charge exchange chemical reaction rate constant between these two species is measured and found to be 4 orders of magnitude larger than recent measurements in other heteronuclear systems. The structure of the CaYb+ molecule is determined and used in a calculation that explains the fast chemical reaction as a consequence of strong radiative charge transfer.

VAMP8 is a vesicle SNARE that regulates mucin secretion in airway goblet cells.

Mucin secretion is an innate defence mechanism, which is noxiously upregulated in obstructive lung diseases (e.g. chronic obstructive pulmonary disease (COPD), cystic fibrosis and asthma).

Parental weight (mis)perceptions: factors influencing parents' ability to correctly categorise their child's weight status.

This study investigates parents' ability to correctly classify their child's weight status. The influence of parent and child socio-demographic and lifestyle factors on parental misclassification of their child's weight status is explored. A representative sample of Irish children (aged 5-12 (n = 596) years, aged 13-17 years (n = 441)) and their parents (n = 1885) were recruited to participate in a national dietary survey.

Quality of induced sputum using a human-powered nebuliser in a mobile human immunodeficiency virus testing service in South Africa.

Objectives: To investigate the quality of induced sputum samples using a human-powered (HPN) and an electric-powered nebuliser (EPN).

Methods: For each participant two sputum samples were induced using the HPN and the EPN. The sequence of the two nebulisers was allocated at random.

Trapping molecular ions formed via photo-associative ionization of ultracold atoms.

The formation of (40)Ca(2)(+) molecular ions is observed in a hybrid (40)Ca magneto-optical and ion trap system. The molecular ion formation process is determined to be photo-associative ionization of ultracold (40)Ca atoms. A lower bound for the two-body rate constant is found to be beta ≥ 2 ± 1 × 10(-15) cm(3) Hz.

Identification of a lysosomal pathway that modulates glucocorticoid signaling and the inflammatory response.

The antimalaria drug chloroquine has been used as an anti-inflammatory agent for treating systemic lupus erythematosus and rheumatoid arthritis. We report that chloroquine promoted the transrepression of proinflammatory cytokines by the glucocorticoid receptor (GR). In a mouse collagen-induced arthritis model, chloroquine enhanced the therapeutic effects of glucocorticoid treatment.

Reduction of protein adsorption and macrophage and astrocyte adhesion on ventricular catheters by polyethylene glycol and N-acetyl-L-cysteine.

Cellular obstruction of poly(dimethyl)siloxane (PDMS) catheters is one of the most prevalent causes of shunt failure in the treatment of hydrocephalus. By modifying PDMS using short- and long-chain mono-functional polyethylene glycol (PEG604 and PEG5K, respectively) and N-acetyl-L-cysteine via adsorption and covalent binding (NAC and NAC/EDC/NHS, respectively), we increased surface wettability. We hypothesized that these surface modifications would inhibit protein adsorption and decrease host macrophage and astrocyte adhesion.

Effects of surface wettability, flow, and protein concentration on macrophage and astrocyte adhesion in an in vitro model of central nervous system catheter obstruction.

While silicone devices have vastly improved an array of medical treatments, reactions at the tissue-substrate interface often impede their functionality. Insertion of a poly(dimethyl)siloxane (PDMS) catheter into the cerebral ventricles to drain excess cerebrospinal fluid (CSF) is the most common treatment of hydrocephalus, but shunting often fails because inflammatory tissue, choroid plexus cells, and debris grow into these central nervous system catheters and obstruct flow. We hypothesized that plasma oxidation of PDMS would inhibit macrophage and astrocyte adhesion under flow (0 to 0.

Successful treatment of metastatic hepatic epithelioid hemangioendothelioma with thalidomide: a case report.

Introduction: Hepatic epithelioid hemangioendothelioma is a rare malignancy arising from the vascular endothelial cells within the liver. Historically, the disease is characterized as being poorly responsive to both chemotherapy and radiotherapy, with liver resection or transplantation the treatment of choice when feasible. For patients with advanced disease, reports of long-term therapeutic benefits from conventional cytotoxic treatments are very limited.

Development and evaluation of monoclonal antibodies against phosphatidylethanolamine binding protein 1 in pancreatic cancer patients.

Phosphatidylethanolamine binding protein 1 (PEBP1), also known as Raf kinase inhibitor protein (RKIP), has been considered as a suppressor of metastasis and a prognostic marker in prostate cancer, breast cancer, gastrointestinal stromal tumors, melanoma, and epithelial ovarian cancer. In this report, recombinant PEBP1 was successfully expressed in an Escherichia coli system. A panel of monoclonal antibodies (mAbs) against PEBP1 with high specificity and affinity was generated and characterized using ELISA, western blot analysis, immunofluorescent staining and immunohistochemical staining.

Constraining the evolution of the fundamental constants with a solid-state optical frequency reference based on the 229Th nucleus.

We describe a novel approach to directly measure the energy of the narrow, low-lying isomeric state in 229Th. Since nuclear transitions are far less sensitive to environmental conditions than atomic transitions, we argue that the 229Th optical nuclear transition may be driven inside a host crystal with a high transition Q. This technique might also allow for the construction of a solid-state optical frequency reference that surpasses the short-term stability of current optical clocks, as well as improved limits on the variability of fundamental constants.

Genotyping three SNPs affecting warfarin drug response by isothermal real-time HDA assays.

Background: The response to the anticoagulant drug warfarin is greatly affected by genetic polymorphisms in the VKORC1 and CYP2C9 genes. Genotyping these polymorphisms has been shown to be important in reducing the time of the trial and error process for finding the maintenance dose of warfarin thus reducing the risk of adverse effects of the drug.

Method: We developed a real-time isothermal DNA amplification system for genotyping three single nucleotide polymorphisms (SNPs) that influence warfarin response.

Mechanical contributions to astrocyte adhesion using a novel in vitro model of catheter obstruction.

Drainage and diversion of cerebrospinal fluid (CSF) through shunt systems is the most common treatment for hydrocephalus, but complications due to tissue obstruction of the catheter occur in up to 61% of patients. Although shunt systems have undergone limited technological advancements to resist mammalian cell adhesion, there is a need to further reduce adhesion that can exacerbate obstruction. The high intrinsic variability in clinical studies and an inability to predict chronic adhesion of host cells in vitro while maintaining the environmental conditions observed in hydrocephalus have impeded progress.

Gemcitabine and carboplatin in the treatment of transitional cell carcinoma of the urothelium: a single centre experience and review of the literature.

The objectives of this study are to evaluate patient outcomes in clinical practice using gemcitabine and carboplatin (GCarbo) as first-line treatment in metastatic transitional cell carcinoma (TCC) of the urothelium, and to review the published evidence on the use of GCarbo in this setting. From July 2003, all cases of metastatic TCC of the urothelium referred to a single consultant were treated using 3-weekly gemcitabine 1200 mg/m(2) i.v.

Induction chemotherapy followed by chemoradiation in locally advanced pancreatic cancer: an effective and well-tolerated treatment.

Aims: The treatment of locally advanced pancreatic cancer varies enormously both within the UK and internationally. Although chemoradiation is the treatment of choice in the USA, in the UK this modality is used infrequently because of concerns regarding both its efficacy and its toxicity. We reviewed our experience with induction chemotherapy and selective chemoradiation in an attempt to show that it is a well-tolerated treatment that may be superior to chemotherapy alone.

An auxiliary capacitor based ultrafast drive circuit for shear piezoelectric motors.

Shear piezoelectric motors frequently require large voltage changes on very short time scales. Since piezos behave electrically as capacitors, this requires a drive circuit capable of quickly sourcing or sinking a large amount of current at high voltages. Here we describe a novel circuit design using a high voltage amplifier, transistor switching stage, and auxiliary capacitor.

Effect of potassium citrate therapy on the risk of renal stone formation during spaceflight.

Purpose: Exposure to microgravity affects human physiology and results in changes in urinary chemical composition during and after spaceflight, favoring an increased risk of renal stones. We assessed the efficacy of potassium citrate to decrease the stone risk during and after spaceflight.

Materials And Methods: The study was done in 30 long duration spaceflight crew members to the space stations Mir and International Space Station.

Computer modelling of thorium doping in LiCaAlF(6) and LiSrAlF(6): application to the development of solid state optical frequency devices.

This paper describes computer modelling of thorium doping in crystalline LiCaAlF(6) and LiSrAlF(6). The study has been motivated by the interest in using these materials as hosts for (229)Th nuclei, which are being investigated for use as frequency standards. The dopant sites and form of charge compensation are obtained; this information is essential for the further development and optimization of these devices.