A one-dimensional spot welding model

A one-dimensional model is proposed for the simulations of resistance spot welding, which is a common industrial method used to join metallic plates by electrical heating. The model consists of the Stefan problem, in enthalpy form, coupled with the equation of charge conservation for the electrical potential. The temperature dependence of the density, thermal conductivity, specific heat, and electrical conductivity are taken into account, since the process generally involves a large temperature range, on the order of 1000 K. The model is general enough to allow for the welding of plates of different thicknesses or dissimilar materials and to account for variations in the Joule heating through the material thickness due to the dependence of electrical resistivity on the temperature. A novel feature in the model is the inclusion of the effects of interface resistance between the plates which is also assumed to be temperature dependent. In addition to constructing the model, a finite difference scheme for its numerical approximations is described, and representative computer simulations are depicted. These describe welding processes involving different interface resistances, different thicknesses, different materials, and different voltage forms. The differences in the process due to AC or DC currents are depicted as well

Genetic approaches for assessment of phosphorus use efficiency in groundnut (Arachis hypogaea L.)

Production of phosphorus efficient genotypes can reduce environmental pollution. Identification of P-efficient groundnut genotypes is a need of the hour to sustain in P-deficient soils. The pot experiment showed significant differences between genotypes (G) and treatments (T) for all the traits and G × T interaction for majority of traits. The G × T × Y interaction effects were also significant for all the traits except leaf P% (LP%), leaf acid phosphatase (LAP) and root dry weight (RDW). In lysimeter experiment, the effect of G, T and G × T were significant for leaf dry weight (LDW), stem dry weight (SDW), total transpiration (TT) and transpiration efficiency (TE). For traits, LDW, SDW, TT, TE, ICGV 00351 and ICGS 76; for SDW, TT, ICGV 02266 are best performers under both P-sufficient and deficient conditions. Based on P-efficiency indices and surrogate traits of P-uptake, ICGV’s 02266, 05155, 00308, 06040 and 06146 were considered as efficient P-responding genotypes. From GGE biplot, ICGV 06146 under P-deficient and TAG 24 under both P-sufficient and deficient conditions are portrayed as best performer. ICGV 06146 was identified as stable pod yielder and a promising genotype for P-deficient soils. The genotypes identified in this study can be used as a parent in developing mapping population to decipher the genetics and to devleop groundnut breeding lines suitable to P-deficient soils

Late symptoms in long-term gynaecological cancer survivors after radiation therapy: a population-based cohort study.

BACKGROUND: We surveyed the occurrence of physical symptoms among long-term gynaecological cancer survivors after pelvic radiation therapy, and compared with population-based control women. METHODS: We identified a cohort of 789 eligible gynaecological cancer survivors treated with pelvic radiation therapy alone or combined with surgery in Stockholm or Gothenburg, Sweden. A control group of 478 women was randomly sampled from the Swedish Population Registry. Data were collected through a study-specific validated postal questionnaire with 351 questions concerning gastrointestinal and urinary tract function, lymph oedema, pelvic bones and sexuality. Clinical characteristics and treatment details were retrieved from medical records. RESULTS: Participation rate was 78% for gynaecological cancer survivors and 72% for control women. Median follow-up time after treatment was 74 months. Cancer survivors reported a higher occurrence of symptoms from all organs studied. The highest age-adjusted relative risk (RR) was found for emptying of all stools into clothing without forewarning (RR 12.7), defaecation urgency (RR 5.7), difficulty feeling the need to empty the bladder (RR 2.8), protracted genital pain (RR 5.0), pubic pain when walking indoors (RR 4.9) and erysipelas on abdomen or legs at least once during the past 6 months (RR 3.6). Survivors treated with radiation therapy alone showed in general higher rates of symptoms. CONCLUSION: Gynaecological cancer survivors previously treated with pelvic radiation report a higher occurrence of symptoms from the urinary and gastrointestinal tract as well as lymph oedema, sexual dysfunction and pelvic pain compared with non-irradiated control women. Health-care providers need to actively ask patients about specific symptoms in order to provide proper diagnostic investigations and management

Distinct Patterns of DNA Damage Response and Apoptosis Correlate with Jak/Stat and PI3Kinase Response Profiles in Human Acute Myelogenous Leukemia

BACKGROUND:Single cell network profiling (SCNP) utilizing flow cytometry measures alterations in intracellular signaling responses. Here SCNP was used to characterize Acute Myeloid Leukemia (AML) disease subtypes based on survival, DNA damage response and apoptosis pathways. METHODOLOGY AND PRINCIPAL FINDINGS:Thirty four diagnostic non-M3 AML samples from patients with known clinical outcome were treated with a panel of myeloid growth factors and cytokines, as well as with apoptosis-inducing agents. Analysis of induced Jak/Stat and PI3K pathway responses in blasts from individual patient samples identified subgroups with distinct signaling profiles that were not seen in the absence of a modulator. In vitro exposure of patient samples to etoposide, a DNA damaging agent, revealed three distinct "DNA damage response (DDR)/apoptosis" profiles: 1) AML blasts with a defective DDR and failure to undergo apoptosis; 2) AML blasts with proficient DDR and failure to undergo apoptosis; 3) AML blasts with proficiency in both DDR and apoptosis pathways. Notably, AML samples from clinical responders fell within the "DDR/apoptosis" proficient profile and, as well, had low PI3K and Jak/Stat signaling responses. In contrast, samples from clinical non responders had variable signaling profiles often with in vitro apoptotic failure and elevated PI3K pathway activity. Individual patient samples often harbored multiple, distinct, leukemia-associated cell populations identifiable by their surface marker expression, functional performance of signaling pathway in the face of cytokine or growth factor stimulation, as well as their response to apoptosis-inducing agents. CONCLUSIONS AND SIGNIFICANCE:Characterizing and tracking changes in intracellular pathway profiles in cell subpopulations both at baseline and under therapeutic pressure will likely have important clinical applications, potentially informing the selection of beneficial targeted agents, used either alone or in combination with chemotherapy

Transforming Growth Factor: β Signaling Is Essential for Limb Regeneration in Axolotls

Axolotls (urodele amphibians) have the unique ability, among vertebrates, to perfectly regenerate many parts of their body including limbs, tail, jaw and spinal cord following injury or amputation. The axolotl limb is the most widely used structure as an experimental model to study tissue regeneration. The process is well characterized, requiring multiple cellular and molecular mechanisms. The preparation phase represents the first part of the regeneration process which includes wound healing, cellular migration, dedifferentiation and proliferation. The redevelopment phase represents the second part when dedifferentiated cells stop proliferating and redifferentiate to give rise to all missing structures. In the axolotl, when a limb is amputated, the missing or wounded part is regenerated perfectly without scar formation between the stump and the regenerated structure. Multiple authors have recently highlighted the similarities between the early phases of mammalian wound healing and urodele limb regeneration. In mammals, one very important family of growth factors implicated in the control of almost all aspects of wound healing is the transforming growth factor-beta family (TGF-β). In the present study, the full length sequence of the axolotl TGF-β1 cDNA was isolated. The spatio-temporal expression pattern of TGF-β1 in regenerating limbs shows that this gene is up-regulated during the preparation phase of regeneration. Our results also demonstrate the presence of multiple components of the TGF-β signaling machinery in axolotl cells. By using a specific pharmacological inhibitor of TGF-β type I receptor, SB-431542, we show that TGF-β signaling is required for axolotl limb regeneration. Treatment of regenerating limbs with SB-431542 reveals that cellular proliferation during limb regeneration as well as the expression of genes directly dependent on TGF-β signaling are down-regulated. These data directly implicate TGF-β signaling in the initiation and control of the regeneration process in axolotls

Functional Characterization of FLT3 Receptor Signaling Deregulation in Acute Myeloid Leukemia by Single Cell Network Profiling (SCNP)

Molecular characterization of the FMS-like tyrosine kinase 3 receptor (FLT3) in cytogenetically normal acute myeloid leukemia (AML) has recently been incorporated into clinical guidelines based on correlations between FLT3 internal tandem duplications (FLT3-ITD) and decreased disease-free and overall survival. These mutations result in constitutive activation of FLT3, and FLT3 inhibitors are currently undergoing trials in AML patients selected on FLT3 molecular status. However, the transient and partial responses observed suggest that FLT3 mutational status alone does not provide complete information on FLT3 biological activity at the individual patient level. Examination of variation in cellular responsiveness to signaling modulation may be more informative.Using single cell network profiling (SCNP), cells were treated with extracellular modulators and their functional responses were quantified by multiparametric flow cytometry. Intracellular signaling responses were compared between healthy bone marrow myeloblasts (BMMb) and AML leukemic blasts characterized as FLT3 wild type (FLT3-WT) or FLT3-ITD. Compared to healthy BMMb, FLT3-WT leukemic blasts demonstrated a wide range of signaling responses to FLT3 ligand (FLT3L), including elevated and sustained PI3K and Ras/Raf/Erk signaling. Distinct signaling and apoptosis profiles were observed in FLT3-WT and FLT3-ITD AML samples, with more uniform signaling observed in FLT3-ITD AML samples. Specifically, increased basal p-Stat5 levels, decreased FLT3L induced activation of the PI3K and Ras/Raf/Erk pathways, decreased IL-27 induced activation of the Jak/Stat pathway, and heightened apoptotic responses to agents inducing DNA damage were observed in FLT3-ITD AML samples. Preliminary analysis correlating these findings with clinical outcomes suggests that classification of patient samples based on signaling profiles may more accurately reflect FLT3 signaling deregulation and provide additional information for disease characterization and management.These studies show the feasibility of SCNP to assess modulated intracellular signaling pathways and characterize the biology of individual AML samples in the context of genetic alterations

Virtual genome walking across the 32 Gb Ambystoma mexicanum genome; assembling gene models and intronic sequence

Large repeat rich genomes present challenges for assembly using short read technologies. The 32 Gb axolotl genome is estimated to contain ~19 Gb of repetitive DNA making an assembly from short reads alone effectively impossible. Indeed, this model species has been sequenced to 20× coverage but the reads could not be conventionally assembled. Using an alternative strategy, we have assembled subsets of these reads into scaffolds describing over 19,000 gene models. We call this method Virtual Genome Walking as it locally assembles whole genome reads based on a reference transcriptome, identifying exons and iteratively extending them into surrounding genomic sequence. These assemblies are then linked and refined to generate gene models including upstream and downstream genomic, and intronic, sequence. Our assemblies are validated by comparison with previously published axolotl bacterial artificial chromosome (BAC) sequences. Our analyses of axolotl intron length, intron-exon structure, repeat content and synteny provide novel insights into the genic structure of this model species. This resource will enable new experimental approaches in axolotl, such as ChIP-Seq and CRISPR and aid in future whole genome sequencing efforts. The assembled sequences and annotations presented here are freely available for download from https://tinyurl.com/y8gydc6n. The software pipeline is available from https://github.com/LooseLab/iterassemble

Author Correction: Genetic approaches for assessment of phosphorus use efficiency in groundnut (Arachis hypogaea L.)

Production of phosphorus efficient genotypes can reduce environmental pollution. Identification of P-efficient groundnut genotypes is a need of the hour to sustain in P-deficient soils. The pot experiment showed significant differences between genotypes (G) and treatments (T) for all the traits and G × T interaction for majority of traits. The G × T × Y interaction effects were also significant for all the traits except leaf P% (LP%), leaf acid phosphatase (LAP) and root dry weight (RDW). In lysimeter experiment, the effect of G, T and G × T were significant for leaf dry weight (LDW), stem dry weight (SDW), total transpiration (TT) and transpiration efficiency (TE). For traits, LDW, SDW, TT, TE, ICGV 00351 and ICGS 76; for SDW, TT, ICGV 02266 are best performers under both P-sufficient and deficient conditions. Based on P-efficiency indices and surrogate traits of P-uptake, ICGV’s 02266, 05155, 00308, 06040 and 06146 were considered as efficient P-responding genotypes. From GGE biplot, ICGV 06146 under P-deficient and TAG 24 under both P-sufficient and deficient conditions are portrayed as best performer. ICGV 06146 was identified as stable pod yielder and a promising genotype for P-deficient soils. The genotypes identified in this study can be used as a parent in developing mapping population to decipher the genetics and to devleop groundnut breeding lines suitable to P-deficient soils

Systematic Agile Development in Regulated Environments

International audienc