Reading out Fisher information from the zeros of the point spread function.

We show that, for optical systems whose point spread functions exhibit isolated zeros, the information one can gain about the separation between two incoherent point light sources does not scale quadratically with the separation (which is the distinctive dependence causing Rayleigh's curse) but only linearly. Moreover, the dominant contribution to the separation information comes from regions in the vicinity of these zeros. We experimentally confirm this idea, demonstrating significant superresolution using natural or artificially created spectral doublets.

Kinetic energy release distributions from dissociative photoionization of weakly bound trimers at 14-27 eV.

The formation of the intriguing ions C4H6O+, C6H6Cl+, and C6H6O+, by dissociative ionization of heterotrimers of butadiene/sulfur dioxide, benzene/hydrogen chloride and benzene/oxygen by 14-27 eV photons, illustrates the possibility that VUV irradiation of clusters comprised of three or more molecules could provide a route to make ions containing bonds not previously accessible. Kinetic energy release distributions were measured in an attempt to understand the formation of these ions and why clusters larger than dimers are needed. Standard theory was applied to find whether more complicated theoretical treatments are needed to understand the data. It was found that all of the above ions were most likely produced by essentially the same mechanism: excitation of one moiety, transfer of its excitation energy to the moiety that dissociates, followed by slow decay of the remaining excited ion into the unexcited moiety as the "solvent" plus the ion with the new bond. The very low reaction probabilities to produce these ions, combined with very low target densities in the presence of many orders of magnitude higher densities of other molecules, precluded the usual imaging techniques. However, we found that the retarding-potential method can give useful data. Also, at present laser photon energies higher than 15 eV provide significantly smaller average intensities than are needed.

Molecular mapping and genomics of soybean seed protein: a review and perspective for the future.

KEY MESSAGE: Genetic improvement of soybean protein meal is a complex process because of negative correlation with oil, yield, and temperature. This review describes the progress in mapping and genomics, identifies knowledge gaps, and highlights the need of integrated approaches. Meal protein derived from soybean [Glycine max (L) Merr.] seed is the primary source of protein in poultry and livestock feed. Protein is a key factor that determines the nutritional and economical value of soybean. Genetic improvement of soybean seed protein content is highly desirable, and major quantitative trait loci (QTL) for soybean protein have been detected and repeatedly mapped on chromosomes (Chr.) 20 (LG-I), and 15 (LG-E). However, practical breeding progress is challenging because of seed protein content's negative genetic correlation with seed yield, other seed components such as oil and sucrose, and interaction with environmental effects such as temperature during seed development. In this review, we discuss rate-limiting factors related to soybean protein content and nutritional quality, and potential control factors regulating seed storage protein. In addition, we describe advances in next-generation sequencing technologies for precise detection of natural variants and their integration with conventional and high-throughput genotyping technologies. A syntenic analysis of QTL on Chr. 15 and 20 was performed. Finally, we discuss comprehensive approaches for integrating protein and amino acid QTL, genome-wide association studies, whole-genome resequencing, and transcriptome data to accelerate identification of genomic hot spots for allele introgression and soybean meal protein improvement.

Development of SNP Genotyping Assays for Seed Composition Traits in Soybean.

Seed composition is one of the most important determinants of the economic values in soybean. The quality and quantity of different seed components, such as oil, protein, and carbohydrates, are crucial ingredients in food, feed, and numerous industrial products. Soybean researchers have successfully developed and utilized a diverse set of molecular markers for seed trait improvement in soybean breeding programs. It is imperative to design and develop molecular assays that are accurate, robust, high-throughput, cost-effective, and available on a common genotyping platform. In the present study, we developed and validated KASP (Kompetitive allele-specific polymerase chain reaction) genotyping assays based on previously known functional mutant alleles for the seed composition traits, including fatty acids, oligosaccharides, trypsin inhibitor, and lipoxygenase. These assays were validated on mutant sources as well as mapping populations and precisely distinguish the homozygotes and heterozygotes of the mutant genes. With the obvious advantages, newly developed KASP assays in this study can substitute the genotyping assays that were previously developed for marker-assisted selection (MAS). The functional gene-based assay resource developed using common genotyping platform will be helpful to accelerate efforts to improve soybean seed composition traits.

Algal competition in a water column with excessive dioxide in the atmosphere.

This paper deals with a resource competition model of two algal species in a water column with excessive dioxide in the atmosphere. First, the uniqueness of positive steady state solutions to the single-species model with two resources is established by the application of the degree theory and the strong maximum principle for the cooperative system. Second, some asymptotic behavior of the single-species model is given by comparison principle and uniform persistence theory. Third, the coexistence solutions to the competition system of two species with two substitutable resources are obtained by global bifurcation theory, various estimates and the strong maximum principle for the cooperative system. Numerical simulations are used to illustrate the outcomes of coexistence and competitive exclusion.

Evaluation of high yielding soybean germplasm under water limitation.

Limited information is available for soybean root traits and their plasticity under drought stress. To date, no studies have focused on examining diverse soybean germplasm for regulation of shoot and root response under water limited conditions across varying soil types. In this study, 17 genetically diverse soybean germplasm lines were selected to study root response to water limited conditions in clay (trial 1) and sandy soil (trial 2) in two target environments. Physiological data on shoot traits was measured at multiple crop stages ranging from early vegetative to pod filling. The phenotypic root traits, and biomass accumulation data are collected at pod filling stage. In trial 1, the number of lateral roots and forks were positively correlated with plot yield under water limitation and in trial 2, lateral root thickness was positively correlated with the hill plot yield. Plant Introduction (PI) 578477A and 088444 were found to have higher later root number and forks in clay soil with higher yield under water limitation. In sandy soil, PI458020 was found to have a thicker lateral root system and higher yield under water limitation. The genotypes identified in this study could be used to enhance drought tolerance of elite soybean cultivars through improved root traits specific to target environments.

Atropine-resistant bradycardia due to hyperkalaemia.

Symptomatic sinus bradycardia is routinely treated in the emergency department with atropine and pacing. Two cases are presented that illustrate the importance of considering hyperkalaemia, particularly in the presence of atropine-resistant symptomatic bradycardia. The administration of calcium in such cases acts to stabilise the myocardium and resolve the bradycardia. Blood gas analysis provides a rapid estimate of serum potassium concentrations, facilitating timely treatment.

Jejunal atresia associated with idiopathic ileal perforation.

Jejunoileal atresia is one of the common causes of neonatal intestinal obstruction. Intestinal perforation with meconium peritonitis in the neonatal period, which carries a high mortality rate, is also common. The association of jejunal atresia with idiopathic ileal perforation is very rare.

The consequence of PRELP overexpression on skin.

PRELP is a member of the small leucine-rich repeat proteoglycan family that is abundantly expressed in many cartilages compared to other connective tissues. To study the consequence of PRELP overexpression in tissues where it is normally expressed at low abundance, transgenic mice were generated in which the human PRELP transgene was placed under control of the CMV promoter. A connective tissue phenotype was observed in the skin, where the organization of collagen fibrils in the dermis was perturbed and the thickness of the hypodermal fat layer was diminished.

Phase I trial of oral MAC-321 in subjects with advanced malignant solid tumors.

PURPOSE: MAC-321 is a novel taxane that has demonstrated exceptional activity in human xenograft models when administered intravenously and orally. Preclinical studies of MAC-321 have shown antitumor activity in MDR-expressing and paclitaxel-resistant tumors. This phase I dose escalation study was performed to determine the safety, tolerability, and pharmacokinetic profile of orally administered MAC-321 given once every 21 days. Preliminary antitumor activity of MAC-321 was also examined. METHODS: Key eligibility criteria included adult subjects with refractory solid tumors or solid tumors for which conventional therapy was unsuitable or did not exist, good performance status (ECOG ( 2), and adequate hematologic, hepatic, and renal functions. Plasma pharmacokinetic (PK) sampling was performed during the first cycle of therapy. RESULTS: Five dose levels of MAC-321 ranging from 25 to 75 mg/m(2) were evaluated in 18 subjects (four women and 14 men). MAC-321 was well tolerated at the first three dose levels (25, 37, 50 mg/m(2)). Two subjects developed dose-limiting toxicities (DLTs) at 75 mg/m(2); one subject with grade 3 and one subject with grade 4 neutropenia with fever. Three subjects treated at an intermediate dose level of 60 mg/m(2) had no DLTs. However, the study was terminated prior to completion of the maximal tolerated dose cohort after subjects treated with intravenous MAC-321 in a concurrent study experienced life-threatening toxicities. Other common toxicities included grades 1-2 fatigue and grades 1-2 diarrhea. There was substantial interpatient variability in the PK parameters. MAC-321 was rapidly absorbed with a mean C (max) value of less than 1 h. Mean C (max) and AUC values generally increased in a dose-related manner. The median terminal phase elimination half-life was 45 h (range 20-228 h). Disease stabilization was seen in four subjects with the following tumors: mesothelioma (14 cycles), chondrosarcoma (12 cycles), small cell carcinoma (10 cycles), and prostate carcinoma (6 cycles). CONCLUSIONS: MAC-321 can be safely administered orally once every 21 days up to a dose of 60 mg/m(2). The major DLT was neutropenic fever. Four subjects had disease stabilization.

Long term use of thalidomide: safe and effective.

PURPOSE: To assess the efficacy and safety of high dose thalidomide therapy for longer duration of time in relapsed or refractory Multiple Myeloma (MM) patients. MATERIALS AND METHODS: Twelve relapsed/refractory MM patients (7 Males, 5 Females), who received thalidomide for more than 2 years were selected from the Out Patient Department of Institute Rotary Cancer Hospital (IRCH), AIIMS, India. Patients received thalidomide beginning at a dose of 200 mg/day with fortnightly increment to a maximum dose of 800 mg/day. Patients were assessed for response on the basis of M proteins (MP), bone marrow biopsy with touch preparation and skeletal X-rays. RESULTS: Nine patients tolerated a maximum dose of 800 mg/day whereas three patients were given 600 mg/day. All patients showed > or = 25-50% decline in serum /urine M proteins. Complete response/ near complete response was seen in 50%, partial response in 17% and minimal response (SD) in 34% patients. Median duration of thalidomide therapy was 47 months (range 29-60 months). Currently 11 patients are alive. TOXICITY: Varying degree of constipation and sedation were seen universally. One patient had DVT, which responded to anti-coagulant therapy. Other toxic effects included infections, skin reactions. There was no toxic death. CONCLUSION: Long-term use of thalidomide is safe, effective and feasible. We feel that this is one of few reports describing safety and efficacy of long-term thalidomide in relapsed and refractory MM.

Pterocarpus marsupium extract (Vijayasar) prevented the alteration in metabolic patterns induced in the normal rat by feeding an adequate diet containing fructose as sole carbohydrate.

Insulin resistance (hyperinsulinaemia) is now recognized as a major contributor to the development of glucose intolerance, dyslipidaemia and hypertension in non-insulin-dependent diabetes mellitus (NIDDM) patients. Sedentary lifestyle, consumption of energy-rich diet, obesity, longer lifespan, etc., are important reasons for this rise (J. R. Turtle, Int J Clin Prac 2000; 113: 23). Aqueous extracts of Pterocarpus marsupium Linn bark (PM), Ocimum sanctum Linn leaves (OS) and Trigonella foenumgraecum Linn seeds (FG) have been shown to exert hypoglycaemic/antihyperglycaemic effect in experimental as well as clinical setting. As no work has been carried out so far to assess the effect of PM, OS and FG on fructose-induced hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia, we undertook this study to assess whether these extracts attenuate the metabolic alteration induced by fructose-rich diet in rats. Five groups of rats (eight each) were fed chow diet, 66% fructose diet, 66% fructose diet + PM leaves extract (1 g/kg/day), 66% fructose diet + OS leaves extract (200 mg/kg/day) and 66% fructose diet + FG seeds extract (2 g/kg/day) for 30 days. Fructose feeding to normal rats for 30 days significantly increased serum glucose, insulin and triglyceride levels in comparison with control. Treatment with all the three plants extract for 30 days significantly lowered the serum glucose levels in comparison with control group. However, only PM extract substantially prevented hypertriglyceridaemia and hyperinsulinaemia, while OS and FG had no significant effect on these parameters. Results of this study, in addition to previous clinical benefits of PM seen in NIDDM subjects, are suggestive of usefulness of PM bark (Vijayasar) in insulin resistance, the associated disorder of type 2 diabetes; however, OS and FG may not be useful. Though several antidiabetic principles (-epicatechin, pterosupin, marsupin and pterostilbene) have been identified in the PM, yet future studies are required to certify their efficacy and safety before clinical scenario.

Use of simple hematological, biochemical and clinical parameters to monitor response of multiple myeloma patients on high dose thalidomide therapy.

BACKGROUND: Evidence of increased bone marrow vascularity in multiple myeloma (MM) has led to the use of anti-angiogenic drugs especially thalidomide in relapsed or refractory patients. Currently, parameters such as serum/ urine electrophoresis for M (monoclonal) proteins, bone marrow biopsy with touch preparation and b2 microglobulin are routinely used to assess response to therapy. These investigations are expensive, invasive and require high technical setup. AIM: To correlate simple and routine hematological and biochemical parameters with the key marker of disease i.e. M proteins. SETTINGS AND DESIGN: This is an open label, uncontrolled, single-arm study. MATERIALS AND METHODS: Twenty nine refractory or relapsed multiple myeloma patients of both sexes (M=20, F=9) with age ranging between 35-72 years were initiated on 200 mg/day of thalidomide with fortnightly increments of 200 mg to a maximum tolerated dose not exceeding 800 mg/day. All hematological and biochemical parameters were monitored at monthly intervals for one year. STATISTICAL ANALYSIS: Correlation analysis was performed between hemoglobin (Hb), total leukocyte count (TLC), absolute neutrophil count (ANC), platelet count (PC), total proteins (TP), serum albumin and serum globulin on one hand and M protein levels on the other using Pearsons Correlation test by SPSS version 7.5. RESULT: Hb, TLC, ANC, PC and serum albumin levels showed a significant negative correlation with M proteins. A highly significant positive correlation existed between M proteins on one hand and TP and globulin levels on the other. Dryness of skin indicated positive response to therapy. These correlations were found to be significant at the end of one month of therapy in all the above-mentioned parameters except in TLC where it was significant after 2 months of thalidomide therapy. CONCLUSION: Results suggest that sustained efficacy of thalidomide therapy may be amenable to monitoring by these simple, inexpensive and easily available investigations after ascertaining an initial response by M protein and marrow plasmacytosis as these parameters closely follow M protein levels. However more studies are required to further substantiate these findings.

Appearance potential of CF3+ in the dissociative photoionization of CF3Br.

Measurements of the appearance potential for the production of CF3+ in the photoionization of CF3Br are in sharp disagreement, contributing to controversy in the heat of formation of CF3+. We reexamine our previous work and add additional experiments, obtaining AP(CF3+/CF3Br) = 11.64 +/- 0.04 eV as the average of four measurements made under widely different conditions. This is higher by 0.08 eV than the value we reported previously. Our new value for Delta(f)H0 degrees (CF3+) is now 88.0 +/- 0.9 kcal mol(-1). We compare our method with other techniques.

Anti-cataract activity of Pterocarpus marsupium bark and Trigonella foenum-graecum seeds extract in alloxan diabetic rats.

Long-term complications are frequently encountered in diabetes mellitus and are difficult to treat. This study was undertaken to assess the effect of three antidiabetic plants on the development of cataract in rats. An aqueous extract of Pterocarpus marsupium Linn bark (PM, Hindi name: Vijaysar) (1 g kg(-1) day(-1)), Ocimum sanctum Linn leaves (OS, Hindi name, Tulsi) (200 mg kg(-1) day(-1)) and alcoholic extract of Trigonella foenum-graecum Linn seeds (FG, Hindi name, Methi) (2 g kg(-1) day(-1)) were given to alloxan (120 mg kg(-1)) diabetic rats until the development of cataract. Serum glucose and body weight were monitored at regular intervals while cataract was examined through naked eye as well as slit lamp at 75, 100 and 115 days after alloxan administration. Administration of all the three plant extracts exerted a favorable effect on body weight and blood glucose, the effects were best with PM followed by FG and OS. On the course of cataract development, PM followed by FG exerted anti-cataract effect evident from decreased opacity index while OS failed to produce any anti-cataract effect in spite of significant antihyperglycemic activity.

Brassica juncea (Rai) significantly prevented the development of insulin resistance in rats fed fructose-enriched diet.

Brassica juncea (BJ; Hindi name: Rai) seeds and Murraya koenigii (MK; English names: Curry leaves) leaves, used as food ingredients and also by diabetics in India, were assessed in a fructose-mediated non-genetic model of insulin resistance. Feeding of fructose rich diet for 30 days resulted in rise in blood glucose by 29.4%, insulin by 101.2% and cholesterol by 26.7% indicating development of insulin resistance. However, feeding of a fructose diet containing 10% Brassica juncea seeds powder for 30 days significantly decreased fasting serum glucose, insulin and cholesterol levels but did not normalize them. On the other hand, a diet containing 15% Murraya koenigii leaves powder failed to exert any effect on these parameters. Results of the present study suggests that BJ can play a role in management of pre-diabetic state of insulin resistance and should be promoted for use in patients prone to diabetes.

Pharmacological actions and potential uses of Momordica charantia: a review.

Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in last few decades has certified several such claims of use of several plants of traditional medicine. Popularity of Momordica charantia (MC) in various systems of traditional medicine for several ailments (antidiabetic, abortifacient, anthelmintic, contraceptive, dysmenorrhea, eczema, emmenagogue, antimalarial, galactagogue, gout, jaundice, abdominal pain, kidney (stone), laxative, leprosy, leucorrhea, piles, pneumonia, psoriasis, purgative, rheumatism, fever and scabies) focused the investigator's attention on this plant. Over 100 studies using modern techniques have authenticated its use in diabetes and its complications (nephropathy, cataract, insulin resistance), as antibacterial as well as antiviral agent (including HIV infection), as anthelmintic and abortifacient. Traditionally it has also been used in treating peptic ulcers, interestingly in a recent experimental studies have exhibited its potential against Helicobacter pylori. Most importantly, the studies have shown its efficacy in various cancers (lymphoid leukemia, lymphoma, choriocarcinoma, melanoma, breast cancer, skin tumor, prostatic cancer, squamous carcinoma of tongue and larynx, human bladder carcinomas and Hodgkin's disease). There are few reports available on clinical use of MC in diabetes and cancer patients that have shown promising results.

Ethanolic extract of Ocimum sanctum leaves partially attenuates streptozotocin-induced alterations in glycogen content and carbohydrate metabolism in rats.

Ocimum sanctum (OS) has been mentioned in Indian system of traditional medicine to be of value in the treatment of diabetes mellitus. We have previously shown that OS shows a dose-dependent hypoglycemic effect and prevented rise in plasma glucose in normal rats. It also showed significant antihyperglycemic effect in STZ-induced diabetes. The present study was undertaken to assess the effect of OS on three important enzymes of carbohydrate metabolism [glucokinase (GK) (EC 2.7.1.2), hexokinase (HK) (EC 2.7.1.1) and phosphofructokinase (PFK) (EC 2.7.1.11)] along with glycogen content of insulin-dependent (skeletal muscle and liver) and insulin-independent tissues (kidneys and brain) in STZ (65 mg/kg) induced model of diabetes for 30 days. Administration of OS extract 200mg/kg for 30 days led to decrease in plasma glucose levels by approximately 9.06 and 26.4% on 15th and 30th day of the experiment. Liver and two-kidney weight expressed as percentage of body weight significantly increased in diabetics (P<0.0005) versus normal controls. OS significantly decreased renal (P<0.0005) but not liver weight. Renal glycogen content increased by over 10 folds while hepatic and skeletal muscle glycogen content decreased by 75 and 68% in diabetic controls versus controls. OS did not affect glycogen content in any tissue. Activity of HK, GK and PFK in diabetic controls was 35, 50 and 60% of the controls and OS partially corrected this alteration.

Cyclo-oxygenase 2 inhibitors: emerging roles in the gut.

BACKGROUND AND AIMS: Discovery of an isoform of Cyclo-oxygenase (COX) 1, the inducible COX-2, has made it possible to avoid some side effects of non-specific COX inhibitors. The COX-2 gene is over-expressed in reflux oesophagitis, Barrett's oesophagus, gastric and colon cancer, familial adenomatous polyposis, pancreatic cancer, hepatocellular carcinoma, hepatotoxicity, cirrhosis, and inflammatory bowel disease, and specific COX-2 inhibitors have been tried experimentally and clinically and found effective. METHODS: A Medline search was performed of English-language experimental studies and controlled clinical trials from January 1980 to January 2002, and relevant citations were noted. RESULTS: Review of available literature shows that sulindac and COX-2 inhibitors are effective in preventing as well as regressing familial adenomatous polyposis. However, they have not been shown to prevent cancer in these patients. Studies evaluating NSAIDs and COX-2 inhibitors in carcinogen-induced and genetically manipulated animal models of various cancers have been promising especially in conditions such as Barrett's oesophagus, oesophageal and hepatocellular carcinoma and pancreatic cancer. COX-2 inhibitors may be of value in the treatment of reflux oesophagitis, pancreatitis and hepatitis, although carefully planned randomized controlled clinical trials demonstrating their efficacy need to be conducted. At present NSAIDs and COX-2 inhibitors cannot be recommended for average-risk individuals or for those with sporadic colorectal neoplasia (or other forms of cancers) as chemo-preventive agents. CONCLUSION: COX-2 inhibitors may open up a new therapeutic era in which these drugs can be used for chemo-prophylaxis. However, COX-2 selective inhibitors retain renal adverse effects of the non-selective inhibitors and the concern regarding the pro-thrombotic potential of COX-2 inhibitors will limit their value as chemo-preventive agents.

Effect of T. foenumgraecum on glycogen content of tissues and the key enzymes of carbohydrate metabolism.

The Indian traditional system of medicine prescribed plant therapies for diseases including diabetes mellitus called madhumeh in Sanskrit. One such plant mentioned in Ayurveda is Trigonella foenumgraecum (FG). In the present study, FG (1g/kg PO) was assessed for its effect on glycogen levels of insulin dependent (skeletal muscle and liver), insulin independent tissues (kidneys and brain) and enzymes such as glucokinase (GK), hexokinase (HK), and phosphofructokinase (PFK). Administration of FG led to decrease in blood glucose levels by 14.4 and 46.64% on 15th and 30th day of the experiment. Liver and 2-kidney weight expressed as percentage of body weight was significantly increased in diabetics (P<0.0005) versus normal controls and this alteration in the renal weight (P<0.0005) but not liver weight was normalized by feeding of FG. Renal glycogen content increased by over 10 folds while hepatic and skeletal muscle glycogen content decreased by 75 and 68% in diabetic controls versus controls and these alteration in glycogen content was partly prevented by FG. Activity of HK, GK and PFK in diabetic controls was 35, 50 and 60% of the controls and FG partially corrected this alteration in PFK, HK and GK.