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.

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.

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.

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.

Mechanism of efflux of melphalan from L5178Y lymphoblasts in vitro.

The mechanism of efflux of melphalan from L5178Y lymphoblasts in vitro was investigated. Evidence was obtained that drug efflux occurs by a process different from the influx mechanism. A time course of efflux followed a first-order process for at least 5 min, with a rate constant K of 0.13 +/- 0.05 (S.D.) min-1, and approximately 80% of drug taken up by the cells was exchangeable. From a kinetic analysis of melphalan efflux, it was not possible to determine if the mechanism of drug efflux was simple diffusion or a technically nonsaturable carrier-mediated process. The Q10 for drug efflux varied from 1.2 to 1.8, values intermediate between those expected for simple diffusion and a carrier-mediated process. Furthermore, drug efflux was sodium independent and was not inhibited by the presence of amino acids on the same side of the membrane, findings which support the concept that efflux was by simple diffusion. The presence of a wide variety of amino acids in the extracellular medium was found to stimulate melphalan efflux. An evaluation of the structure-activity relationship disclosed that amino acids containing hydroxyl, acidic, or amide side chains were most active; however, a distinct pattern between amino acid structure and stimulation of efflux was not established. The stimulation process was concentration dependent and was not restricted to either L5178Y cells or to melphalan as transport substrate.

Effects of ramipril on coronary events in high-risk persons: results of the Heart Outcomes Prevention Evaluation Study.

BACKGROUND: In trials of patients with left ventricular dysfunction or heart failure, ACE inhibitor use was unexpectedly associated with reduced myocardial infarction (MI). Using the Heart Outcomes Prevention Evaluation (HOPE) trial data, we tested prospectively whether ramipril, an ACE inhibitor, could reduce coronary events and revascularization procedures among patients with normal left ventricular function. METHODS AND RESULTS: In the HOPE trial, 9297 high-risk men and women, >/=55 years of age with previous cardiovascular disease or diabetes plus 1 risk factor, were randomly assigned to ramipril (up to 10 mg/d), vitamin E (400 IU/d), their combination, or matching placebos. During the mean follow-up of 4.5 years, there were 482 (10.4%) patients with clinical MI and unexpected cardiovascular death in the ramipril group compared with 604 (12.9%) in the placebo group [relative risk reduction (RRR), 21% (95% CI) (11,30); P<0.0003]. Ramipril was associated with a trend toward less fatal MI and unexpected death [4.0% versus 4.7%; RRR, 16% (-3, 31)] and with a significant reduction in nonfatal MI [5.6% versus 7.2%; RRR, 23% (9,34)]. Risk reductions in MI were documented in participants taking or not taking beta-blockers, lipid lowering, and/or antiplatelet agents. Although ramipril had no impact on hospitalizations for unstable angina [11.9% versus 12.2%; RRR, 3% (-9,14)], it reduced the risk of worsening and new angina [27.2% versus 30.0%; RRR, 12% (5,18); P<0.0014] and coronary revascularizations [12.5% versus 14.8%; RRR, 18%; (8,26) P<0.0005]. CONCLUSIONS: In this high-risk cohort, ramipril reduced the risk of MI, worsening and new angina, and the occurrence of coronary revascularizations.

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.

Characterization and expression of murine PRELP.

The cDNA sequence of the murine proline/arginine-rich end leucine-rich repeat protein (PRELP) gene was cloned by PCR-based techniques. The gene encodes a protein of 378 amino acids, which is four amino acid residues shorter than its human counterpart. This difference resides mainly in the amino terminal region of the mature protein, which is five amino acids shorter in the mouse than the human and has a lower arginine content. The remainder of the protein, including the structure of the leucine-rich repeats, the potential sites for N-linked glycosylation, and the disulfide-bonded domains are well conserved between species. In common with humans, the murine gene possesses three exons, with the translation initiation codon residing in exon 2 and the termination codon in exon 3. Exons 1 and 2 are separated by an intron of approximately 6.7 kbp, whereas exons 2 and 3 are separated by an intron of approximately 1.7 kbp. Western blot analysis of mouse cartilage extracts indicates that PRELP exists as a glycoprotein of approximately 55 kDa, as in human cartilage. Immunohistochemical and in situ hybridization analysis reveal that PRELP is expressed in cartilage throughout both fetal development and post-natal life, in contrast to the human where expression in cartilage is not apparent prior to birth. Northern blot analysis indicates that PRELP mRNA is also expressed in the developing embryo prior to skeletogenesis. The promoter region of the mouse PRELP gene possesses no TATA box in its proximal region, in common with humans, and shows differences in the conservation of elements known to be involved in regulating expression of the human PRELP gene.

Competition along a spatial gradient of resource supply: a microbial experimental model.

In a set of laboratory experiments, we examined competition for phosphorus between algae and bacteria under various carbon:phosphorus (C:P) supply ratios in spatially homogeneous and heterogeneous microcosms. Experimental results were compared to those predicted by theoretical models of resource competition. In the spatially heterogeneous microcosm, algae that were inferior competitors for P persisted in vessels with high local C:P supply ratios that would cause exclusion in the spatially homogeneous microcosms. Resource competition theory, adapted to this system, provided a starting point for explaining these results. Spatial structure can enhance local diversity because locally inferior competitors are transported from source habitats into sink habitats where they would otherwise be excluded. Such local sources were determined by their resource supply ratios. These results verify the hypothesis that spatial processes enhance local diversity when a system of local habitats is divided into sources and sinks in such a way that each persisting species has at least one source within the system. However, existing theoretical models did not accurately predict distributions of competitor abundance within this experimental system.

Monoclonal antibody associated with a lymphocyte subpopulation in chronic lymphocytic leukemia.

An IgG monoclonal antibody that detects a subpopulation of lymphocytes found in peripheral blood and bone marrow of patients with CLL and malignant lymphoma is described. The initial immunization used to achieve the resultant monoclonal antibody included the use of cells obtained by DNA transformation of mouse L-cells with the DNA obtained from a morphologically altered somatic cell hybrid between primary human CLL peripheral lymphocytes and a flat-revertant Chinese hamster ovary (CHO) cell line designated GRC+L-73. Hybridomas were thus selected as potentially recognizing antigens associated with the morphological transformation induced by hybridization of CHO cells with lymphocytes from lymphocytic malignancies. One such hybridoma, designated 37-28, was selected for further investigation. The monoclonal antibody produced was IgG (gamma G2a) and detects a subpopulation of lymphocytes present in hematological specimens of some of the lymphocytic malignancies.

Rat kidney 25-hydroxyvitamin D3 1 alpha- and 24-hydroxylases: evidence for two distinct gene products.

Total RNA was isolated from kidneys of Sprague-Dawley rats. Oligo (dT)-primed single-stranded cDNA was obtained by the reverse transcriptase reaction from which a 285 bp cDNA probe coding for 25-hydroxyvitamin D3-24-hydroxylase [25(OH)D3-24-OHase] was generated by the polymerase chain reaction. Northern blotting performed with kidney poly (A)+ RNA isolated from rats (1) fed a standard diet, (2) depleted in D3 and hypocalcemic, and (3) fed a standard diet and injected intraperitoneally with 50,000 IU of vitamin D3 for 5 days showed that the transcript for 24-OHase was weakly expressed in control, and highly induced in vitamin D3-treated animals. No transcript could be elicited in vitamin D-depleted hypocalcemic animals in which 25(OH)D3-1 alpha-OHase was maximally induced. The data show that 24-OHase is independently regulated of 1 alpha-OHase, strongly suggestive of the enzymes being encoded by two distinct genes.

Three-dimensional method for determination of amniotic fluid volume in intrauterine pockets.

BACKGROUND: Although current ultrasound techniques provide a linear (amniotic fluid index; AFI) or two-dimensional area index of amniotic fluid (AF), these indices have limited correlation with actual AF volume. We sought to quantify the three-dimensional volume of ultrasound-identified AF pockets, as assessed by the AFI and two-dimensional area methods. The BVI 2500 (Bladder Volume Instrument 2500; Diagnostic Ultrasound Corp., Redmond, WA) has been used to quantify the volume of residual urine in the bladder. INSTRUMENT AND METHOD: The BVI 2500 (Diagnostic Ultrasound Corp.) ultrasound uses a rotating 2-MHz transducer, computer-defined fluid interface, and computer integration of 12 cross-sectional images to calculate three-dimensional fluid volume. After providing written informed consent, 14 term pregnant patients (36-42 weeks) were evaluated using the BVI 2500 and an Ultramark 8 sector scan (Advanced Technology Laboratory, Bothell, WA). The largest vertical fluid pocket in each quadrant of the abdomen was identified with the sector scan, and vertical and horizontal measurements for AFI and two-dimensional area were recorded. Simultaneous AF volume measurements of each pocket were performed three times with the bladder volume instrument, and maximum values were used. Three-dimensional volume, two-dimensional area, and AFI values were compared by correlation analysis, with P < or = .05 considered statistically significant. EXPERIENCE: Among all patients, the average (+/- standard deviation) AFI was 7.6 +/- 4.1 (range 1.5-16.4) cm, and the average two-dimensional area was 30.9 +/- 21.1 (range 4.3-81.3) cm2. This corresponded to an average three-dimensional volume of 215 +/- 134 (range 23-497) cm3. Three-dimensional volume correlated highly with both AFI (r = 0.9; P < .001) and two-dimensional area (r = 0.86; P < .001). One AFI centimeter was equivalent to a volume of 30 cm3. CONCLUSION: There are highly significant linear correlations of three-dimensional amniotic fluid volumes with AFI and two-dimensional area. The four pockets used in AFI determination account for only 50% of total AF volume. Three-dimensional determinations may aid in clinical assessments of AF volume.

Lisinopril versus placebo in the treatment of heart failure: the Lisinopril Heart Failure Study Group.

Lisinopril, a long-acting, angiotensin-converting enzyme inhibitor, was compared with placebo in a randomized, parallel, double-blind, 12-week study of 193 patients with heart failure. All patients were New York Heart Association Functional Class II, III, or IV and had remained symptomatic despite optimal dosing with digoxin and diuretics. After 12 weeks of therapy, the improvement in treadmill exercise duration was greater in the lisinopril group (113 seconds) compared with the placebo group (86 seconds). This improvement in exercise duration was particularly evident in patients with left ventricular ejection fractions less than 35% (lisinopril = 130 seconds; placebo = 94 seconds). In patients receiving lisinopril, the increase in exercise duration was accompanied by an improvement in quality of life as measured by the Yale Scale Dyspnea/Fatigue Index and in signs and symptoms of heart failure. In addition, the lisinopril group had a larger mean increase (3.7%) in left ventricular ejection fraction when compared with the placebo group (1.3%). Thus, lisinopril, administered once daily for 12 weeks, was well tolerated and efficacious in the treatment of heart failure when used concomitantly with diuretics and digoxin.

Hospitalizing the suicidal adolescent: decision-making criteria of psychiatric residents.

OBJECTIVE: The primary purpose of this research is to investigate the criteria used by general psychiatric residents in determining the appropriateness of hospitalization. METHOD: A questionnaire containing 64 vignettes describing adolescent suicide attempts was completed by a sample of 33 residents from a general psychiatry training program. Six variables known to relate to lethality of attempt were systematically varied within the vignettes: gender, depression, conduct disorder/substance abuse, previous attempts, suicidal relative, and family supports. Respondents were asked to judge the appropriateness of hospitalization for each vignette. RESULTS: Hospitalization preference was significantly predicted by all risk factors except for gender, with the presence of depression emerging as the most important predictor of hospitalization. Residents recommended hospitalization more frequently than did experienced child and adolescent clinicians. In comparison with experienced clinicians, residents placed more importance on depression, and less importance on conduct disorder/substance abuse, in making decisions to hospitalize. CONCLUSIONS: Although psychiatric residents use known risk factors for adolescent suicide in assessing need for hospitalization, there was clear support for further training initiatives for psychiatric residents concerning the assessment of suicidal adolescents.