A portable magneto-optical trap with prospects for atom interferometry in civil engineering.

The high precision and scalable technology offered by atom interferometry has the opportunity to profoundly affect gravity surveys, enabling the detection of features of either smaller size or greater depth. While such systems are already starting to enter into the commercial market, significant reductions are required in order to reach the size, weight and power of conventional devices. In this article, the potential for atom interferometry based gravimetry is assessed, suggesting that the key opportunity resides within the development of gravity gradiometry sensors to enable drastic improvements in measurement time. To push forward in realizing more compact systems, techniques have been pursued to realize a highly portable magneto-optical trap system, which represents the core package of an atom interferometry system. This can create clouds of 107 atoms within a system package of 20 l and 10 kg, consuming 80 W of power.This article is part of the themed issue 'Quantum technology for the 21st century'.

Effects of a structured exercise programme in sedentary dogs with chronic diarrhoea.

The aim of this investigation was to evaluate the effects of a structured exercise programme in sedentary dogs with chronic diarrhoea. Twenty-two dogs were enrolled in the study. All dogs received oral prednisolone (1 mg/kg/day for 14 days, followed by a tapering dosage) for 10 weeks. After four weeks of prednisolone treatment, dogs were assigned to either the exercise or control group (n=11 each). Owners of dogs in the exercise group were instructed to guide their dogs in structured exercise training (low-intensity to moderate-intensity aerobic and resistance exercise three to five days per week). After 10 weeks of prednisolone treatment with concomitant 6 weeks of complementary exercise, the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) score had decreased significantly in the exercise group (from 8.8±1.5 at the start of the exercise programme to 2.4±1.5; P<0.001); no such change was observed in the control group (from 9.2±0.9 to 9.2±1.1). CIBDAI scores differed significantly between the groups at the end of the 10-week study period (P<0.001). The exercise programme affected all six CIBDAI parameters significantly; bodyweight (P<0.001, adjusted r2=0.722) was most affected. A structured exercise programme may have positive effects on clinical symptoms in sedentary dogs with chronic diarrhoea.

Observing coherence effects in an overdamped quantum system.

It is usually considered that the spectrum of an optical cavity coupled to an atomic medium does not exhibit a normal-mode splitting unless the system satisfies the strong coupling condition, meaning the Rabi frequency of the coherent coupling exceeds the decay rates of atom and cavity excitations. Here we show that this need not be the case, but depends on the way in which the coupled system is probed. Measurements of the reflection of a probe laser from the input mirror of an overdamped cavity reveal an avoided crossing in the spectrum that is not observed when driving the atoms directly and measuring the Purcell-enhanced cavity emission. We understand these observations by noting a formal correspondence with electromagnetically induced transparency of a three-level atom in free space, where our cavity acts as the absorbing medium and the coupled atoms play the role of the control field.

Relationships between three potentiation effects of plyometric training and performance.

UNLABELLED: This study measured the potentiation effects of plyometric training [normalized electromyography (EMG) in triceps surae, stiffness and elastic energy utilization of the Achilles tendon] and investigated the correlations between these effects and performances [voluntary electromechanical delay (EMD) and jump height]. Twenty-one subjects were randomly assigned either to the control group (10 subjects: age 22.3+/-1.6 years) or to a training group (11 subjects: age 22.1+/-1.6 years) that performed 8 weeks of plyometric training. RESULTS: As compared with the performances before training, normalized EMG in the soleus were significantly (P

Influence of oxygen defects on the crystal structure and magnetic properties of the (Tb1-xNax)MnO3-y (0

The crystallographic and magnetic behaviors of (Tb1-xNax)MnO3-y (0

Chemical size effect on the magnetic and electrical properties in the (Tb(1-)(x)Eu(x))MnO(3) (0 < or = x < or = 1.0) system.

The effect of isovalent chemical substitution of Eu3+ into the Tb3+ sites on the magnetic and electrical properties of (Tb1-xEux)MnO3 (0

Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus.

Diabetes is associated with renal calcium and magnesium wasting, but the molecular mechanisms of these defects are unknown. We measured renal calcium and magnesium handling and investigated the effects of diabetes on calcium and magnesium transporters in the thick ascending limb and distal convoluted tubule in streptozotocin (STZ)-induced diabetic rats. Rats were killed 2 weeks after inducing diabetes, gene expression of calcium and magnesium transporters in the kidney was determined by real-time polymerase chain reaction, and the abundance of protein was assessed by immunoblotting. Our results showed that diabetic rats had significant increase in the fractional excretion for calcium and magnesium (both P < 0.01), but not for sodium. Reverse transcriptase-polymerase chain reaction revealed significant increases in messenger RNA abundance of transient potential receptor (TRP) V5 (223 +/- 10%), TRPV6 (177 +/- 9%), calbindin-D28k (231 +/- 8%), and TRPM6 (165 +/- 8%) in diabetic rats. Sodium chloride cotransporter was also increased (207 +/- 10%). No change was found in paracellin-1 (cortex: 108 +/- 8%; medulla: 110 +/- 10%). Immunofluorescent studies of renal sections showed significant increase in calbindin-D28k (238 +/- 10%) and TRPV5 (211 +/- 10%), but no changes in paracellin-1 in Western blotting (cortex: 110 +/- 7%; medulla: 99 +/- 7%). Insulin administration completely corrected the hyperglycemia-associated hypercalciuria and hypermagnesiuria, and reversed the increase of calcium and magnesium transporter abundance. In conclusion, our results demonstrated increased renal calcium and magnesium transporter abundance in STZ-induced diabetic rats, which may represent a compensatory adaptation for the increased load of calcium and magnesium to the distal tubule.

Analysis of splice-site mutations of the alpha-galactosidase A gene in Fabry disease.

Fabry disease is an X-linked disease caused by a defective lysosomal enzyme, alpha-galactosidase A, and characterized by skin lesions and multiorgan involvement, including kidney, heart, and the central nervous system. Currently more than 200 genotypes have been identified, including several aberrant splicing. However, most of the mutation analyses were performed using genomic sequencing only, and therefore some of the splicing mutations were misclassified as missense mutations. In order to predict the splicing event caused by each mutation, we conducted a literature search for all published mutations located near the splice sites, including exonic point mutations, and performed a splice-site score (SSS) analysis. The literature search identified 13 donor-site mutations, including four exonic mutations (S65T, D183S, K213N, and M267I), located at the end of exons 1, 3, 4, and 5, respectively, six acceptor-site mutations, and one new exon creation. All mutated splice sites, except for the one associated with the new exon creation, had a lower SSS than their respective natural sites. Cryptic or newly created sites were identified with SSS from 0.09 to 1.0. The predictions, based on SSS analysis, are in agreement with all six mutations with known cDNA sequence from the literature, including five mutations with exon skipping and one mutation with creation of a new acceptor site. For the S65T genotype, we performed reverse transcription-polymerase chain reaction (RT-PCR) analysis using RNA isolated from the whole-blood sample. We verified that a weak cryptic site (SSS = 0.09) 14 nucleotides downstream was activated and resulted in an insertion of 14 bp and a frameshift stop at codon 106. This change is more consistent with the clinical presentation of the patient, the classical Fabry disease, than the amino acid substitution (S65T), which does not affect the enzyme function. In conclusion, the SSS analysis is very useful for predicting splicing events and genotype/phenotype correlation in Fabry disease. As different mechanisms may be involved in pre-mRNA splicing, it is important to obtain cDNA sequencing for molecular diagnosis.

Two novel mutations in the alpha-galactosidase A gene in Chinese patients with Fabry disease.

Fabry disease is an X-linked disorder caused by a deficiency of the lysosomal alpha-galactosidase A [EC 3.2.1.22]. The molecular diagnosis of Fabry disease is important for genotype/phenotype correlation, pre-natal or early diagnosis, and detection of carrier status. Although more than 200 genotypes of the alpha-galactosidase A gene have been identified, mutation data on the Chinese population is sparse. We recently identified two unrelated Chinese families with Fabry disease. Mutation analysis was performed by polymerase chain reaction (PCR) sequencing of the seven exons and adjacent introns of the alpha-galactosidase A gene. Two novel mutations were identified: in family I, a C-to-A transversion resulted in an early termination at amino acid 222 (Y222X), while in family II, an A-to-G transition resulted in a substitution of alanine for threonine at amino acid 410 (T410A). Carrier status was identified in all four females in the two families. The genotype Y222X is associated with classic Fabry disease, with unexpectedly rapid deterioration of visual acuity, while T410A is associated with a milder Fabry disease, with ventricular hypertrophy and neuropathic pain.

Therapeutic application of chimeric RNA/DNA oligonucleotide based gene therapy.

Chimeric RNA/DNA oligonucleotides, or chimera, have emerged as a breakthrough technology for treating genetic disorders. Chimera have been shown to induce correction of point mutations in several genetic disease models without utilising the viral vectors. Recent studies of chimera-based gene therapy in genetic disease models are reviewed. Chimera were delivered intravenously, intramuscularly, intradermally, or topically with or without vehicles. Correction of the mutation at genotypic and phenotypic levels was assessed using various methods. The gene correction frequency varied, ranging from 1-40%. The resulting phenotype changes lasted longer than one year in some studies. The most dramatic phenotypic change is the reduction of serum bilirubin level by 50% in the Gunn rat, a model for Crigler-Najjar syndrome. Chimera based gene therapy has the potential to develop into powerful therapeutic modality for genetic diseases.

Retropharyngeal abscess caused by group B Streptococcus in a previously healthy child.

Retropharyngeal cellulitis/abscess has not been recognized as a manifestation of group B streptococcal disease in the pediatric group beyond neonates. The purpose of this paper is to present a previously healthy 3-year-old boy with a retropharyngeal abscess due to group B Streptococcus which was successfully treated by surgical incision and drainage in combination with amoxicillin/clavulanate therapy.

Estrogen action and male fertility: roles of the sodium/hydrogen exchanger-3 and fluid reabsorption in reproductive tract function.

Estrogen receptor alpha (ER alpha) is essential for male fertility. Its activity is responsible for maintaining epithelial cytoarchitecture in efferent ductules and the reabsorption of fluid for concentrating sperm in the head of the epididymis. These discoveries and others have helped to establish estrogen's bisexual role in reproductive importance. Reported here is the molecular mechanism to explain estrogen's role in fluid reabsorption in the male reproductive tract. It is shown that estrogen regulates expression of the Na(+)/H(+) exchanger-3 (NHE3) and the rate of (22)Na(+) transport, sensitive to an NHE3 inhibitor. Immunohistochemical staining for NHE3, carbonic anhydrase II (CAII), and aquaporin-I (AQP1) was decreased in ER alpha knockout (alpha ERKO) efferent ductules. Targeted gene-deficient mice were compared with alpha ERKO, and the NHE3 knockout and CAII-deficient mice showed alpha ERKO-like fluid accumulation, but only the NHE3 knockout and alpha ERKO mice were infertile. Northern blot analysis showed decreases in mRNA for NHE3 in alpha ERKO and antiestrogen-treated mice. The changes in AQP1 and CAII in alpha ERKO seemed to be secondary because of the disruption of apical cytoarchitecture. Ductal epithelial ultrastructure was abnormal only in alpha ERKO mice. Thus, in the male, estrogen regulates one of the most important epithelial ion transporters and maintains epithelial morphological differentiation in efferent ductules of the male, independent of its regulation of Na(+) transport. Finally, these data raise the possibility of targeting ER alpha in developing a contraceptive for the male.

Renal gene therapy.

Until now there is no renal gene therapy available for clinical use, however, gene therapy for several experimental renal diseases has been tested with promising results. The kidney is a well-differentiated organ with a variety of specialized compartments, i.e., vascular, glomerular, tubular, and interstitial. Many physiological factors such as cell turnover rate, blood flow, and urine flow, as well as anatomical factors such as glomerular basement membrane and nephron segment arrangement, may affect the specificity and efficacy of gene therapy in the kidney. On the other hand, the kidney has a major advantage over other solid organs, since it is accessible by many routes, including intrarenal artery infusion, retrograde delivery through the urinary tract, direct injection into renal parenchyma, and perfusion into the donor graft prior to transplantation (1). This chapter reviews nonviral gene transfer in the different compartments of the kidney (for review of viral vectormediated renal gene transfer, see refs. 2-5), and in skeletal muscle, for renal gene therapy, and potential applications and safety concerns for renal gene therapy.

Reabsorption of betaine in Henle's loops of rat kidney in vivo.

This study was designed 1) to localize and 2) to characterize betaine reabsorption from the tubular lumen in rat kidney in vivo, and 3) to test whether reabsorption is modulated by the diuretic state. [(14)C]betaine (+ [(3)H]inulin) was microperfused through the proximal convoluted tubule (PCT) and microinfused into late proximal (LP) and early distal (ED) tubules, long loops of Henle (LLH), and vasa recta of the rat in vivo et situ, and the fractional recovery of the (14)C label was determined end proximally (PCT) and in the final urine, respectively. [(14)C]betaine was not reabsorbed during ED microinfusion, whereas fractional reabsorption during LP microinfusion was 82% at 0.06 mM betaine and decreased gradually to 4.8% at 60 mM. L-Proline had lower Michaelis-Menten constant (K(m)) and sarcosine a higher K(m) than betaine. Chronic, but not acute, diuresis inhibited betaine reabsorption in Henle's loops. Fractional [(14)C]betaine reabsorption in PCT was much smaller than that during LP microinfusion. [(14)C]betaine (7.28 mM) microinfused 1) into LLH was reabsorbed to 30% and 2) into vasa recta appeared in the ipsilateral urine to a much higher extent than contralaterally. In both cases, no saturation was detected at 70 mM. We conclude that betaine is reabsorbed by mediated transport from descending limbs of short Henle's loops by a proline-preferring carrier in a diuresis-modulated manner. In the deep medulla, bidirectional blood/urine betaine transport exists.

Long-term cyclophosphamide treatment for recurrent type I membranoproliferative glomerulonephritis after transplantation.

The incidence of recurrent type I membranoproliferative glomerulonephritis (MPGN) after renal transplant is approximately 30%, and the rate of graft loss due to recurrent MPGN type I is higher than 50%. The treatment of this disease has not been defined. We report a case of recurrent MPGN type diagnosed 4 months after a cadaveric renal transplantation. The patient was treated with cyclophosphamide and was able to maintain her graft function. Cyclophosphamide was interrupted three times during the course. Each time her renal function deteriorated and her serum albumin decreased. The patient currently has a functional renal graft 3 years after transplantation while receiving low-dose therapy with cyclophosphamide. We suggest treating recurrent type I MPGN with cyclophosphamide while continuing the calcineurin inhibitor and prednisone.

Iatrogenic hyperadrenocorticism in 28 dogs.

Twenty-eight dogs with iatrogenic hyperadrenocorticism were studied. The most common clinical signs were cutaneous lesions (27/28), polydipsia (21/28), polyuria (19/28), and lethargy (16/28). The most predominant findings on biochemical profile were elevated alkaline phosphatase (ALP, 15/28) and alanine transferase (ALT, 14/28); hypercholesterolemia (14/28); elevated aspartate transferase (AST, 12/28); and elevated triglycerides (12/18). Baseline cortisol levels of all 28 dogs were at the lower end of the reference range and exhibited suppressed or no response to adrenocorticotropic hormone (ACTH) stimulation. The mean time for each dog to show initial improvement of clinical signs after corticosteroid withdrawal was six weeks, with another mean time of 12 weeks to demonstrate complete remission.

Homologous recombination based gene therapy.

BACKGROUND/AIMS: Most of the current expression vector based gene therapy protocols fail to achieve clinically significant transgene expression required for treating genetic diseases. Homologous recombination, initially considered to be of limited use for gene therapy because of its low frequency in mammalian cells, has recently emerged as a potential strategy for developing gene therapy. METHODS: Six recent studies of homologous recombination in mammalian cells are reviewed. Different approaches have been used in these studies including RNA/DNA chimeric oligonucleotides, small or large homologous DNA fragments, or adeno-associated viral vectors. RESULTS: Most of these studies show a reasonable frequency of homologous recombination which warrants further in vivo testing. CONCLUSIONS: Homologous recombination based gene therapy has the potential to develop into a powerful therapeutic modality for genetic diseases. It can offer permanent expression and normal regulation of corrected genes in appropriate cells or organs and probably can be used for treating dominantly inherited diseases such as polycystic kidney disease.

Entering the gene therapy era.

Gene therapy is a new modality with the potential for treating a variety of diseases, inherited or acquired. Although the initial clinical trials, particularly those for cystic fibrosis, have not been successful, the preliminary results of more recent studies of gene therapy for myocardial infarction are encouraging. New plasmids, viral and nonviral vectors, and applications are being developed at a rapid pace. A switch is now inserted in the plasmids so that the therapeutic gene can be turned on and off as needed. A chimeric RNA/DNA oligonucleotide has also been designed so that mutated genes can be converted to normal sequences. These and other novel approaches soon will propel the gene therapy industry into reality. Healthcare providers and educators need to be prepared for the coming of the gene therapy era.