Anomalous Antiferromagnetism in Metallic RuO_{2} Determined by Resonant X-ray Scattering.

We studied the magnetic ordering of thin films and bulk crystals of rutile RuO_{2} using resonant x-ray scattering across the Ru L_{2} absorption edge. Combining polarization analysis and azimuthal angle dependence of the magnetic Bragg signal, we have established the presence and characteristic of collinear antiferromagnetism in RuO_{2} with T_{N}>300 K. In addition to revealing a spin-ordered ground state in the simplest ruthenium oxide compound, the persistence of magnetic order even in nanometer-thick films lays the ground for potential applications of RuO_{2} in antiferromagnetic spintronics.

Differential bleaching of corals based on El Niño type and intensity in the Andaman Sea, southeast Bay of Bengal.

The Andaman coral reef region experienced mass bleaching events during 1998 and 2010. The purpose of this study is to investigate the role of the El Niño in the coral reef bleaching events of the Andaman region. Both Niño 3.4 and 3 indices were examined to find out the relationship between the mass bleaching events and El Niño, and correlated with sea surface temperature (SST) anomalies in the Andaman Sea. The result shows that abnormal warming and mass bleaching events in the Andaman Sea were seen only during strong El Niño years of 1997-1998 and 2009-2010. The Andaman Sea SST was more elevated and associated with El Niño Modoki (central Pacific El Niño) than conventional El Niño (eastern Pacific El Niño) occurrences. It is suggested that the development of hot spot patterns around the Andaman Islands during May 1998 and April-May 2010 may be attributed to zonal shifts in the Walker circulation driven by El Niño during the corresponding period.

Vasculogenesis and Angiogenesis in Modular Collagen-Fibrin Microtissues.

The process of new blood vessel formation is critical in tissue development, remodeling and regeneration. Modular tissue engineering approaches have been developed to enable the bottom-up assembly of more complex tissues, including vascular networks. In this study, collagen-fibrin composite microbeads (100-300 µm in diameter) were fabricated using a water-in-oil emulsion technique. Human endothelial cells and human fibroblasts were embedded directly in the microbead matrix at the time of fabrication. Microbead populations were characterized and cultured for 14 days either as free-floating populations or embedded in a surrounding fibrin gel. The collagen-fibrin matrix efficiently entrapped cells and supported their viability and spreading. By 7 days in culture, endothelial cell networks were evident within microbeads, and these structures became more prominent by day 14. Fibroblasts co-localized with endothelial cells, suggesting a pericyte-like function, and laminin deposition indicated maturation of the vessel networks over time. Microbeads embedded in a fibrin gel immediately after fabrication showed the emergence of cells and the coalescence of vessel structures in the surrounding matrix by day 7. By day 14, inosculation of neighboring cords and prominent vessel structures were observed. Microbeads pre-cultured for 7 days prior to embedding in fibrin gave rise to vessel networks that emanated radially from the microbead by day 7, and developed into connected networks by day 14. Lumen formation in endothelial cell networks was confirmed using confocal sectioning. These data show that collagen-fibrin composite microbeads support vascular network formation. Microbeads embedded directly after fabrication emulated the process of vasculogenesis, while the branching and joining of vessels from pre-cultured microbeads resembled angiogenesis. This modular microtissue system has utility in studying the processes involved in new vessel formation, and may be developed into a therapy for the treatment of ischemic conditions.

Mitochondrial gene replacement in human pluripotent stem cell-derived neural progenitors.

Human pluripotent stem cell-derived neural progenitor (hNP) cells are an excellent resource for understanding early neural development and neurodegenerative disorders. Given that many neurodegenerative disorders can be correlated with defects in the mitochondrial genome, optimal utilization of hNP cells requires an ability to manipulate and monitor changes in the mitochondria. Here, we describe a novel approach that uses recombinant human mitochondrial transcription factor A (rhTFAM) protein to transfect and express a pathogenic mitochondrial genome (mtDNA) carrying the G11778A mutation associated with Leber's hereditary optic neuropathy (LHON) disease, into dideoxycytidine (ddC)-treated hNPs. Treatment with ddC reduced endogenous mtDNA and gene expression, without loss of hNP phenotypic markers. Entry of G11778A mtDNA complexed with the rhTFAM was observed in mitochondria of ddC-hNPs. Expression of the pathogenic RNA was confirmed by restriction enzyme analysis of the SfaN1-digested cDNA. On the basis of the expression of neuron-specific class III beta-tubulin, neuronal differentiation occurred. Our results show for the first time that pathogenic mtDNA can be introduced and expressed into hNPs without loss of phenotype or neuronal differentiation potential. This mitochondrial gene replacement technology allows for creation of in vitro stem cell-based models useful for understanding neuronal development and treatment of neurodegenerative disorders.

KIT ligand and bone morphogenetic protein signaling enhances human embryonic stem cell to germ-like cell differentiation.

BACKGROUND: Signaling mechanisms involved in early human germ cell development are largely unknown and believed to be similar to mouse germ cell development; however, there may be species specific differences. KIT ligand (KITL) and Bone morphogenetic protein 4 (BMP4) are necessary in mouse germ cell development and may play an important role in human germ cell development. METHODS: KITL signaling studies were conducted by differentiating human embryonic stem cells (hESCs) on KITL wild-type, hetero- or homozygous knockout feeders for 10 days, and the effects of BMP signaling was determined by differentiation in the presence of BMP4 or its antagonist, Noggin. The formation of germ-like cells was ascertained by immunocytochemistry, flow cytometry and quantitative RT-PCR for germ cell markers. RESULTS: The loss of KITL in enrichment and differentiation cultures resulted in significant down-regulation of germ cell genes and a 70.5% decrease in germ-like (DDX4+ POU5F1+) cells, indicating that KITL is involved in human germ cell development. Moreover, endogenous BMP signaling caused germ-like (DDX4+ POU5F1+) cell differentiation, and the inhibition of this pathway caused a significant decrease in germ cell gene expression and in the number of DDX4+ POU5F1+ cells. Further, we demonstrated that eliminating feeders but maintaining their secreted extracellular matrix is sufficient to sustain the increased numbers of DDX4+ POU5F1+ cells in culture. However, this resulted in decreased germ cell gene expression. CONCLUSIONS: From these studies, we establish that KITL and BMP4 germ cell signaling affects in vitro formation of hESC derived germ-like cells and we suggest that they may play an important role in normal human germ cell development.

BMP4 promotes formation of primitive vascular networks in human embryonic stem cell-derived embryoid bodies.

The vasculature develops primarily through two processes, vasculogenesis and angiogenesis. Although much work has been published on angiogenesis, less is known of the mechanisms regulating the de novo formation of the vasculature commonly called vasculogenesis. Human embryonic stem cells (hESC) have the capability to produce all of the cells of the body and have been used as in vitro models to study the molecular signals controlling differentiation and vessel assembly. One such regulatory molecule is bone morphogenetic protein-4 (BMP4), which is required for mesoderm formation and vascular/hematopoietic specification in several species. However, hESC grown in feeder-free conditions and treated with BMP4 differentiate into a cellular phenotype highly expressing a trophoblast gene profile. Therefore, it is unclear what role, if any, BMP4 plays in regulating vascular development in hESC. Here we show in two National Institutes of Health-registered hESC lines (BG02 and WA09) cultured on a 3D substrate of Matrigel in endothelial cell growth medium-2 that the addition of BMP4 (100 ng/ml) for 3 days significantly increases the formation and outgrowth of a network of cells reminiscent of capillary-like structures formed by mature endothelial cells (P<0.05). Analysis of the expression of 45 genes by quantitative real time-polymerase chain reaction on a low-density array of the entire culture indicates a rapid and significant downregulation of pluripotent and most ectodermal markers with a general upregulation of endoderm, mesoderm, and endothelial markers. Of the genes assayed, BMPR2 and RUNX1 were differentially affected by exposure to BMP4 in both cell lines. Immunocytochemistry indicates the morphological structures formed were negative for the mature endothelial markers CD31 and CD146 as well as the neural marker SOX2, yet positive for the early vascular markers of endothelium (KDR, NESTIN) and smooth muscle cells (alpha-smooth muscle actin [alpha SMA]). Together, these data suggest BMP4 can enhance the formation and outgrowth of an immature vascular system.

Correction of limb-length inequality during total hip arthroplasty.

Although several methods of intraoperative limb-length measurements have been described, their success in predicting the limb-length correction is not well documented. A new technique of measuring intraoperative limb lengthening using a vertical Steinmann pin at the infracotyloid groove of the acetabulum was studied in 100 consecutive primary total hip arthroplasties. Correlation of the predicted intraoperative correction was done with the postoperative radiographic measurements. Preoperative limb-length inequality ranged from -24 mm (short) to +2 mm (long) (mean, -4.2 mm). Intraoperative measurement of lengthening ranged from 0 to 15 mm (mean, 5.9 mm). Radiographic measurements of postoperative radiographs showed lengthening ranging from 0 to 17 mm (mean, 7.4 mm). There was significant correlation between the 2 values (r =.84). Postoperative limb-length inequality ranged from -7 mm to +8 mm (mean, 1.9 mm). None of the patients had to use shoe lifts for equalization of limb lengths.

Simultaneous regulation of hemodynamic and anesthetic states: a simulation study.

A model predictive control strategy to simultaneously regulate hemodynamic and anesthetic variables in critical care patients is presented. A nonlinear canine circulatory model, which has been used to study the effect of inotropic and vasoactive drugs on hemodynamic variables, has been extended to include propofol pharmacokinetics and pharmacodynamics. Propofol blood concentration is used as a measure for depth of anesthesia. The simulation model is used to design and test the control strategy. The optimization-based model predictive control strategy assures that constraints imposed on the drug infusion rates are met. The physician always remains "in the loop" and serves as the "primary controller" by making propofol blood concentration setpoint changes based on observations about anesthetic depth. Results are shown for three simulated cases: (i) congestive heart failure, (ii) postcoronary artery bypass, and (iii) acute changes in hemodynamic variables.

Efficacy of lincomycin against the strains of Staphylococcus aureus isolated from various types of pyodermas in children : in vitro and in vivo study.

Lincomycin is chemically distinct from all other available antibiotics except its semi-synthetic derivative clindamycin. Though it has been in the market for over three decades, there were not many clinical studies in India. This study has been undertaken to know its efficacy against Staphylococcus aureus, commonest organism of pyodermas in children. Material was taken from the lesions of 100 fresh cases of various types of pyodermas in children and studied by Gram stain and in 50% human blood agar and nutrient agar according to standard methods. The staphylococci thus isolated were tested for linocomycin susceptibility by using the disc diffusion technique. Lincomycin was given to all these children in a daily dose of 30 mg/kg 5 - 10 days. Treatment failure was defined as persistence of lesions after 10 days of treatment. 75% strains of staphylococci were susceptible to lincomycin in vitro and 95% of the patients responded to 5-10 days treatment. Five out of 100 children did not respond to treatment even after 10 days. No case of relapse was noticed among these 95 children for a period of 2 weeks. No side effects were observed and the drug was very well tolerated. Being highly effective and least toxic linomycin deserves a place in the antimicrobial arsenal of the modern dermatologists.

Control of a nonsquare drug infusion system: A simulation study.

A model predictive control strategy was developed and tested on a nonlinear canine circulatory model for the regulation of hemodynamic variables under critical care conditions. Different patient conditions such as congestive heart failure, post-operative hypertension, and sepsis shock were studied in closed-loop simulations. The model predictive controller, which uses a different linear model depending on the patient condition, allowed constraints to be explicitly enforced. The controller was initially tuned on the basis of a linear plant model, then tested on the nonlinear physiological model; the simulations demonstrated the ability to handle constraints, such as drug dosage specifications, commonly desired by critical care physicians.

Immediate weightbearing after uncemented total hip arthroplasty.

Radiographic subsidence of the femoral prosthesis and clinical results after unilateral and simultaneous bilateral uncemented total hip arthroplasty were compared. Patients who had bilateral total hip arthroplasty began weight-bearing as tolerated on both lower extremities the day after surgery. Patients who had undergone unilateral total hip arthroplasty were maintained at 10% weightbearing on the operative limb for 6 weeks after surgery. Patients in both groups were matched for age, gender, and weight. Minimal followup was 2 years. There was no difference between the two groups in terms of clinical results. Radiographic assessments were performed immediately after surgery, 6 weeks after surgery, and again at 2 years after surgery. Radiographs were reviewed by a single observer and analyzed with a digitized data recorder. Increased subsidence of the femoral prosthesis within the bilateral group was found at 6 weeks. The mean subsidence of the femoral prosthesis at 6 weeks for the bilateral total hip arthroplasty group was 0.86 mm (range, 0.18-2.60 mm) and for the unilateral group was 0.39 mm (range, 0.07-1.46 mm). However, subsidence occurring between 6 weeks and 2 years averaged 0.50 mm (range, 0.09-1.10 mm) for the bilateral group and 0.54 mm (range, 0.03-0.99 mm) for the unilateral group. This difference was not significant. At the 2-year followup, all femoral prostheses in both groups appeared radiographically stable with evidence of bone ingrowth and no indications of loosening. Thus, immediate weightbearing after bilateral total hip arthroplasty in this study resulted in more initial subsidence (during the first 6 weeks after surgery) of the femoral prosthesis but did not preclude the prosthesis from becoming stable and achieving bone ingrowth. Patients in both groups obtained satisfactory clinical results. Because initial stability and bone ingrowth are factors influenced by prosthesis design, the results of this study may not be applicable to all implants.

Clinical profile of cutaneous leishmaniasis in Faifa-Gizan, South west province of Kingdom of Saudi Arabia (A study of 140 cases).

A preliminary study was conducted to know the age, sex distribution and clinical pattern of cutaneous leishmaniasis (CL) in a remote hilly area, Faifa, Gizan situated in the South West region of the Kingdom of Saudi Arabia. C L accounted for nearly 5% of the new outpatient attendance in the study period (1988-90) of 20 months. Out of the 140 new patients who formed the study group, 82 were males (58.57%) and 58 females (41.43%) in the age range of 9 months to 60 years. Ninety two patients were children (65.71%) below 15 years. including 58 boys and 34 girls and CL is a major public health problem in children of this area. The fact that out of 140 affected individuals, 134 were local Saudis and 6 non-Saudis reveals the autochthonous nature of the disease in this region. The clinical spectrum included dry crusted ulcers, erythematous indurated plaques, nodules, papules, and oozing shallow ulcers. The lesions were distributed mostly on face and extremities. Response to pentostam (Sodium stibogluconate) was highly satisfactory.

Solid state synthesis and thermal stability of HAP and HAP - beta-TCP composite ceramic powders.

Powders of pure beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HAP) and a biphasic composite mixture of HAP+beta-TCP were prepared by solid state reaction between two commercially available calcium-based precursors namely, tricalcium phosphate (TCP) and calcium hydroxide (Ca(OH)2). These reactants mixed in the molar ratios ranging from 3 : 0 to 3 : 4 (designated T0 to T4) in deionized water, milled and slip-cast into discs were heat treated in the temperature range of 600 degrees C to 1250 degrees C. The products formed were characterized by X-ray diffraction (XRD) and i.r. spectroscopic techniques for identification of phases formed and functional groups present in them. While tricalcium phosphate and calcium hydroxide taken in the molar ratio of 3 : 2 and 3 : 3 resulted in pure HAP when heat treated at 1000 degrees C for 8 h, the 3 : 1 and 3 : 1.5 molar ratio compositions resulted in a biphasic mixture of HAP+beta-TCP for similar heat treatments. Heat treatment of 3 : 4 molar ratio composition of tricalcium phosphate and calcium hydroxide at 1000 degrees C yielded HAP with free CaO as the secondary phase. Products of heat treatment at higher temperatures (1150 and 1250 degrees C) for even shorter duration (2 h) while not differing from the products obtained from T0 and T2 cases at 1000 degrees C (pure beta-TCP and pure HAP), change in the case of T1, T1.5, T3 and T4 to products with lesser percentages of HAP containing beta-TCP (in the case of T1 and T1.5) or CaO (in the case of T3 and T4) as the secondary phase.

Pilot study of labelling bovine muscle tissue with 14C.

A pilot study has been performed to assess the feasibility of labelling bovine muscle tissue with 14C, in order to produce material suitable for intercomparison exercises. Approximately 1 kg of tissue was prepared by grinding, blending, labelling with 14C-methylated bovine haemoglobin and thoroughly mixing by repeated blending. The product was sealed in cans and sterilized to preserve it. Portions of raw material were dried to test the homogeneity of moisture content. Homogeneity of 14C in the natural and labelled materials was tested by analyzing sub-samples of 2-3 g in weight of the freeze-dried materials. The 14C content was determined by combusting and collecting the CO2 for liquid scintillation counting. The material was found to be homogeneous to the extent of 2-4% (R.S.D.), which is comparable with the R.S.D. of the 14C measurements. The 14C concentration in the labelled material was 8190 +/- 220 Bq.kg-1 of carbon. It was concluded that bovine muscle prepared in this manner would be suitable for intercomparison exercises. The 14C level in unlabelled tissue was found to be 260 +/- 7 Bq.kg-1 of carbon, which is similar to the level of 14C previously determined in milk and both are consistent with levels measured in vegetation in Eastern Ontario.

Integrated approach to the management of patients with advanced germ cell tumors of the testis.

Between 1985 and 1991, 63 patients with disseminated germ cell tumors of the testis were treated with initial cisplatin based combination chemotherapy. Complete response was seen in 38% of patients. Adjunctive surgical resection of residual disease was carried out in 26 patients (41%), including the use of intraoperative radiation therapy in two patients with seminoma. Furthermore, two other patients with seminoma and residual mass underwent retroperitoneal irradiation. Salvage chemotherapy was administered to five patients with progressive disease, and only one of these could be salvaged with adjunctive surgery. A disease-free state was achieved in 75% of patients at a mean follow-up period of 30 months.

Determination of nanogram amounts of iodine in foods by radiochemical neutron activation analysis.

Three different neutron activation analysis methods have been developed for the determination of ppb levels of iodine in food samples. The methods are based on the separation of iodine using (i) toluene extraction followed by bismuth sulfide coprecipitation; (ii) bismuth sulfide coprecipitation followed by radiochemical purification with palladium iodide; and (iii) radiochemical isolation by bismuth sulfide coprecipitation. The accuracy of these methods was evaluated by analysing replicate samples of reference materials. The measured values of iodine in A-11 Milk Powder, H-4 Animal Muscle and H-9 Mixed Human Diet from the International Atomic Energy Agency (IAEA) are statistically indistinguishable from the IAEA recommended values, and those for the Standard Reference Materials 1571 Orchard Leaves and 1577 Bovine Liver from the National Institute of Standards and Technology (NIST) are in good agreement with the NIST information values. The precision, in terms of relative standard deviation, is 5% at 50-100 ppb and 10% at 5-20 ppb levels of iodine. The absolute detection limits of these methods vary between 0.5 and 10 ng of iodine. All three methods were used to measure the iodine content of several food samples. The method involving bismuth sulfide coprecipitation followed by radiochemical purification provides the best detection limit and highest precision.