Lagrangian coherent structure assisted path planning for transoceanic autonomous underwater vehicle missions.

Transoceanic Gliders are Autonomous Underwater Vehicles (AUVs) for which there is a developing and expanding range of applications in open-seas research, technology and underwater clean transport. Mature glider autonomy, operating depth (0-1000 meters) and low energy consumption without a CO2 footprint enable evolutionary access across ocean basins. Pursuant to the first successful transatlantic glider crossing in December 2009, the Challenger Mission has opened the door to long-term, long-distance routine transoceanic AUV missions. These vehicles, which glide through the water column between 0 and 1000 meters depth, are highly sensitive to the ocean current field. Consequently, it is essential to exploit the complex space-time structure of the ocean current field in order to plan a path that optimizes scientific payoff and navigation efficiency. This letter demonstrates the capability of dynamical system theory for achieving this goal by realizing the real-time navigation strategy for the transoceanic AUV named Silbo, which is a Slocum deep-glider (0-1000 m), that crossed the North Atlantic from April 2016 to March 2017. Path planning in real time based on this approach has facilitated an impressive speed up of the AUV to unprecedented velocities resulting in major battery savings on the mission, offering the potential for routine transoceanic long duration missions.

Stratified coastal ocean interactions with tropical cyclones.

Hurricane-intensity forecast improvements currently lag the progress achieved for hurricane tracks. Integrated ocean observations and simulations during hurricane Irene (2011) reveal that the wind-forced two-layer circulation of the stratified coastal ocean, and resultant shear-induced mixing, led to significant and rapid ahead-of-eye-centre cooling (at least 6 °C and up to 11 °C) over a wide swath of the continental shelf. Atmospheric simulations establish this cooling as the missing contribution required to reproduce Irene's accelerated intensity reduction. Historical buoys from 1985 to 2015 show that ahead-of-eye-centre cooling occurred beneath all 11 tropical cyclones that traversed the Mid-Atlantic Bight continental shelf during stratified summer conditions. A Yellow Sea buoy similarly revealed significant and rapid ahead-of-eye-centre cooling during Typhoon Muifa (2011). These findings establish that including realistic coastal baroclinic processes in forecasts of storm intensity and impacts will be increasingly critical to mid-latitude population centres as sea levels rise and tropical cyclone maximum intensities migrate poleward.

The role of calbindin and 1,25dihydroxyvitamin D3 in the kidney.

The identification of a putative apical Ca++ channel in 1,25dihydroxyvitamin D3 responsive epithelia (proximal intestine and the distal nephron) as well as recent studies using calbindin-D28k knock-out mice indicating the first direct in-vivo evidence for a role for this calcium-binding protein in renal calcium absorption suggest mechanisms, which had remained incomplete, related to the control of renal calcium absorption.

Preoperative volume expansion improves tolerance to carotid artery cross-clamping during endarterectomy.

OBJECTIVE: The benefit of carotid endarterectomy for carotid artery stenosis relates to both appropriate patient selection and careful surgical technique. Critical to the latter is the ability to afford intraoperative neuroprotection during carotid cross-clamping, although the optimal strategy to assure this protection remains debated. This report describes the impact of adding preoperative colloid volume expansion to a surgical algorithm that includes electroencephalographic (EEG) monitoring and barbiturate-induced burst suppression for EEG lateralization refractory to hypertension. METHODS: The incidence of ischemic EEG change during carotid cross-clamping was observed. The results of an initial series of patients (n = 45) reported before incorporation of volume expansion were compared with the results of the current series (n = 155) of carotid endarterectomies, which included preoperative volume expansion with 6% hetastarch (500 or 1000 cc). RESULTS: With preoperative volume expansion, there was a 40% decrease in the incidence of EEG lateralization during carotid cross-clamping (17.4 versus 28.9%, P < 0.05) and a 63% decrease in the EEG lateralization refractory to induced hypertension (5.8 versus 15.6%, P < 0.05). The combined perioperative stroke and death rate was 1.3%. CONCLUSION: These results support the use of preoperative colloid volume expansion in carotid endarterectomy as a means of increasing the cerebral tolerance to carotid cross-clamping.

IB4, a monoclonal antibody against the CD18 leukocyte adhesion protein, reduces intracranial pressure following thromboembolic stroke in the rabbit.

Neutrophil activation and accumulation as a consequence of cerebral ischemia-reperfusion has been suggested to exacerbate tissue injury. The current study is designed to examine the effect of IB4, a monoclonal antibody directed against the neutrophil adhesion protein, CD18, in a rabbit model of thromboembolic stroke. New Zealand rabbits (3-3.5 kg n=8 each group), were given an autologous clot embolus, delivered to the anterior circulation of the brain via the internal carotid artery. Immediately following thromboembolism, the mean arterial pressure in all animals was reduced to 30 mmHg by controlled exsanguination for a period of 45 min. All animals were mechanically ventilated and following parameters were monitored hourly: arterial blood gases, intracranial pressure, regional cerebral blood flow, hematocrit, and core temperature. Rabbits were given either IB4 (1 mg kg(-1)), or vehicle (1 percent albumin, IV) 30 min following the thromboembolic event. The mean arterial pressure of all animals was restored to the baseline value of 50-60 mmHg for the remainder of the 4-h experiment. Following the thromboembolic event, the intracranial pressure rose in both groups, although this was significantly less in the IB4-treated group, with the final values being 195.9 +/- 38.3 vs. 135.5 +/- 26.0 percent of baseline (mean +/- SEM, p < 0.05). However, regional cerebral blood flow and infarct size (TTC staining) were virtually identical in both groups. It is concluded that blockade of the neutrophil adhesion protein, CD18, may contribute to a reduction in the intracranial pressure following cerebral ischemia and reperfusion, providing further evidence that activated neutrophils may contribute to cerebral edema.

Contamination of human ovarian follicular fluid and serum by chlorinated organic compounds in three Canadian cities.

OBJECTIVES: To determine the extent of contamination of ovarian follicular fluid and serum samples in women undergoing in-vitro fertilization and to study the effect of the contaminants on reproductive outcome. DESIGN: Inception cohort study. PATIENTS: Seventy-four women undergoing in-vitro fertilization at three regional clinics in Halifax, Hamilton, Ont., and Vancouver. MAIN OUTCOME MEASURES: Follicular fluid and serum levels of contaminants, cleavage rates and time to cleavage of first egg. RESULTS: Five chlorinated organic chemicals were frequently found in the two types of samples: alpha-chlordane (ALCH), dichlorochlorophenylethylene (DDE), heptachloroepoxide-oxychlordane (OXCH), hexachlorobenzene (HCB) and polychlorinated biphenyl (PCB). The levels were generally low. Regional differences between the three clinics were present. Samples from the Halifax clinic had the lowest frequency and level of contamination. The source of drinking water (well, bottled or municipal) was an important confounder. The concentrations of the five contaminants did not affect the cleavage rate or the time to cleavage of the first egg. CONCLUSION: Trace amounts of toxic and persistent chlorinated organic chemicals found in the follicular fluid of Canadian women undergoing in-vitro fertilization did not seem to have any adverse biologic effect on the rate of fertilization and the time to cleavage. Reasons for regional differences in the concentrations of contaminants require further study.

In vitro evidence supporting two mechanisms of action for the anion transport inhibitor L-644,711 in cerebral ischaemia.

L-644,711 is a novel anion channel inhibitor which has previously been shown to decrease brain injury in two related rabbit models of cerebral ischaemia. We hypothesize two mechanisms of action of L-644,711 for its salutary effects on cerebral ischaemia: inhibition of neutrophil function and prevention of excitotoxin release from astrocytes. We present in vitro evidence supporting these two mechanisms of action. L-644,711 demonstrated a dose dependent inhibition of fMLP-induced neutrophil aggregation and superoxide anion release. In addition, L-644,711 demonstrated a dose dependent inhibition of glutamate release from swollen astrocytes in primary culture. We conclude that L-644,711 may prevent brain injury in cerebral ischaemia by inhibiting neutrophil function and preventing release of glutamate from swollen astrocytes.

Reduction in ischemic brain injury in rabbits by the anion transport inhibitor L-644,711.

BACKGROUND AND PURPOSE: We studied the anion transport inhibitor L-644,711, which is known to reduce astrocyte swelling and excitotoxin release in primary astrocyte culture, in two models of thromboembolic stroke to assess its capacity to influence ischemic brain injury. METHODS: New Zealand White rabbits were used in this study. The two models include autologous clot embolized to the brain via the carotid artery, with one model using a transient period of systemic hypotension. Cerebral blood flow was determined by the hydrogen clearance method, intracranial pressure was measured with a fiberoptic transducer, and infarct size was assessed with triphenyltetrazolium chloride staining of the coronally sectioned brain. Both models received a 2-hour infusion of L-644,711 (total dose, 12 mg/kg) beginning 20 minutes before embolization. RESULTS: In both the normotensive (p less than 0.01) and the hypotensive (p less than 0.05) model, treatment with L-644,711 resulted in a significant reduction in infarct size and a significant improvement in regional cerebral blood flow (p less than 0.03, normotensive model, and p less than 0.05, hypotensive model). Raised intracranial pressure, unique to the hypotensive model, was abolished by the administration of L-644,711 (p less than 0.05). A hyperglycemic response associated with embolization, also unique to the hypotensive model, was significantly reduced by the administration of L-644,711 (p less than 0.05). CONCLUSIONS: The ability of L-644,711 to limit brain injury in two related models of thromboembolic stroke suggests a potential therapeutic role for anion channel blockers in cerebral ischemia.

Increased cerebral blood flow in idiopathic pseudotumour cerebri.

Cerebral blood flow was studied in nine patients with idiopathic pseudotumour and one patient with cortical vein thrombosis in Denver, Colorado using the 133Xe inhalation method. Globally elevated blood flows were found in all of the idiopathic pseudotumour patients averaging 149% of control values generated in the same setting. The patient with the cortical vein thrombosis demonstrated normal global flows. Possible pathophysiological mechanisms for these findings are discussed.

Influence of blood clots in the cumulus complex on oocyte fertilization and cleavage.

Since multiple ovarian punctures are performed during oocyte retrieval, the likelihood of blood contaminating the follicular fluid is high. The purpose of this study was to determine whether the presence of blood clots, which are frequently seen in the cumulus of oocytes retrieved under ultrasound guidance, has any effect on fertilization and subsequent embryo cleavage and to identify oocyte characteristics which may predict these events. Oocytes were morphologically graded and the presence of blood clots in the cumulus was recorded. Cases in which the male partner had a total motile sperm count less than 20 x 10(6) on the day of insemination were excluded from the logistic regression analysis. The presence of blood clots in the cumulus was a negative predictor of cleavage [odds ratio (OR) = 0.54]. The results indicate that an oocyte with optimal quality is one which is spherical (OR = 5.45), has an expanded corona (OR = 3.80) and has no blood clots in the cumulus complex.

The value of semen analysis and sperm function assays in predicting pregnancy among infertile couples.

Over a 2-year period, 227 couples were evaluated by an extended assessment of the male partner's ejaculate. This extended assessment comprised sperm penetration of denuded hamster oocytes, ability of sperm to penetrate synthetic mucus, and the adenosine triphosphate (ATP) content of whole semen. In proportional hazards analysis adjusting for the contribution of clinical and other seminal variables, the sperm penetration assay (SPA) test was a predictor of pregnancy in the subgroup with normal conventional seminal variables (greater than 40 million motile sperm per ejaculate). When the SPA result was 20% or more the probability of pregnancy was 3.7 times higher; the performance of the SPA as a diagnostic test was better in the couples with treated tubal disease than in other diagnostic categories.

Semen predictors of in vitro fertilization and embryo cleavage.

In vitro fertilization treatment for male infertility is not very successful because fertilization is known to be affected by semen quality. Information on fertilizing ability may provide prognostic information for couples contemplating such treatment. The purpose of this study was to identify semen variables that would predict fertilization and embryo cleavage. Sperm was prepared by the swim-up method before insemination of oocytes obtained by laparoscopy after ovulation induction. Routine semen analysis and the hypoosmotic swelling test for assessment of sperm membrane integrity were performed on aliquots of prepared sperm. Logistic regression and receiver-operator characteristic curve analyses were performed to determine the overall best-fitting model and discriminatory level of variables that would predict cleavage. The results indicate that after the swim-up procedure, at least 10 million sperm/ml, capable of undergoing swelling in hypoosmotic medium, are necessary to increase the likelihood of in vitro fertilization and cleavage.

Does dihydrotestosterone induce atresia in the hypophysectomized immature female rat treated with pregnant mare's serum gonadotropin?

This study was originally designed to test the hypothesis that the binding of luteinizing hormone in granulosa cells decreases with atresia. The hypophysectomized immature female rat that was primed with pregnant mare's serum gonadotropin and treated with dihydrotestosterone was used as a model for atresia. Histochemical analysis of acid phosphatase was used as a marker for atresia and topical autoradiography with iodine 125-labeled human chorionic gonadotropin for binding of luteinizing hormone. Histologically, there was no significant difference in atresia, acid phosphatase, or 125I-labeled human chorionic gonadotropin binding in antral follicles between control animals given pregnant mare's serum gonadotropin and animals treated with pregnant mare's serum gonadotropin and dihydrotestosterone. Assessment of the total follicular population, however, showed that dihydrotestosterone at dosages of 1 and 5 mg/kg resulted in decreases in atresia of 48% and 58%, respectively. Although these data disprove our hypothesis, they strongly suggest that dihydrotestosterone decreases follicular atresia by increasing the number of small preantral follicles.

Covalent cross-linking of transfer ribonucleic acid to the ribosomal P site. Mechanism and site of reaction in transfer ribonucleic acid.

The covalent cross-linking of unmodified Escherichia coli N-acetylvalyl-tRNA to the 16S RNA of Escherichia coli ribosomes upon near-UV irradiation previously reported by us [Schwartz, I., & Ofengand, J. (1978) Biochemistry 17, 2524--2530] has been studied further. Up to 70% of the unmodified tRNA, nonenzymatically bound to tight-couple ribosomes at 7 mM Mg2+, could be cross-linked by 310--335-nm light. Covalent attachment was solely to the 16S RNA. It was dependent upon both irradiation and the presence of mRNA but was unaffected by the presence or absence of 4-thiouridine in the tRNA. The kinetics of cross-linking showed single-hit behavior. Twofold more cross-linking was obtained w-th tight-couple ribosomes than with salt-washed particles. Puromycin treatment after irradiation released the bound N-acetyl[3H]valine, demonstrating that the tRNA was covalently bound at the P site and that irradiation and covalent linking did not affect the peptidyl transferase reaction. Cross-linking was unaffected by the presence of O2, argon, ascorbate (1 mM), or mercaptoethanol (10 mM). Prephotolysis of a mixture of tRNA and ribosomes in the absence of puly(U2,G) did not block subsequent cross-linking in its presence nor did it generate any long-lived chemically reactive species. There was a strong tRNA specificity. E. coli tRNA1Val and tRNA1Ser and Bacillus subtilis tRNAVal and tRNAThr could be cross-linked, but E. coli tRNA2Val, 5-fluorouracil-substituted tRNA1Val, tRNAPhe, or tRNAFMet could not. By sequence comparison of the reactive and nonreactive tRNAs, the site of attachment in the tRNA was deduced to be the 5'-anticodon base, cmo5U, or ,o5U in all of the reactive tRNAs. The attachment site in 16S RNA is described in the accompanying paper [Zimmerman, R. A., Gates, S. M., Schwartz, I., & Ofengand, J. (1979) Biochemistry (following paper in this issue)]. The link between tRNA and 16S RNA is either direct or involves mRNA bases at most two nucleotides apart since use of the trinucleotide GpUpU in place of poly(U2,G) to direct the binding and cross-linking of N-acetylvalyl-tRNA to the P site did not affect either the rate or yield of cross-linking. Both B. subtilis tRNAVal (mo5U) and E. coli tRNA1Val (cmo5U) gave the same rate and yield of cross-linking when directed by the trinucleotide GpUpU. Therefore, the presence of the charged carboxyl group in the cmo5U-containing tRNA apparently does not markedly perturb the orientation of this base with respect to its reaction partner in the 16S RNA. The cross-linking of AcVal-tRNA only takes place from the P site. At 75 mM KCl and 75 mM NH4Cl, less than 0.4% cross-linking was found at the A site, while 55.5% was obtained at the P site. However, when the salt concentration was lowered to 50 mM NH4Cl, 5% cross-linking to the A site was detected, compared to 49% at the P site. Thus, a simple change in the ionic strength of the incubation mixture was able to alter the affinity labeling pattern of the ribosome.

Synthesis and properties of nucleoside 5'-phosphoazidates derived from guanosine and adenosine nucleotides: effective on elongation factors G and Tu dependent reactions.

A new type of nucleoside poly (5'-phosphate) analogue, nucleoside 5"-phosphoazidate, with an azido group on the terminal phosphate of GTP, ATP, GDP, GMP, AND AMP, has been synthesized by nucleophilic displacement of the corresponding activated nucleosides by azide ion in yields of 25-45%. Guanosine 5-phosphoazidates is readily photolyzed by ultraviolet light; the corresponding adenosine derivative photolyzes more slowly. Guanosine 5'-O-(2-azidodiphosphate) and guanosine 5"-O-(3-azidotrophosphate) are competitive inhibitors of the formation of the ribosome-EF-G-GDP-fusidic acid complex and of the ribosome-EF-G GTPase. The dissociation constants of the former reaction are calculated to be 27 and 7 micrometer, respectively, or 270 and 73 times that of GDP. In the latter reaction, which is conducted in the absence of fusidic acid, the Ki values are 330 and 28 micrometer, respectively, or 12 and 1 times that of GDP. Guanosine 5"-O-(2-azidodiphosphate) and guanosine 5'-O-(3-azidotriphosphate) also complete with GTP in the formation of the binary complex. EF-Tu-GTP, with respective Kd values of 750 and 75 relative to GTP.