Thermal and phase transformations analysis in a PREMOMET® steel

Thermal analysis in a PREMOMET® steel has been performed by differential scanning calorimetry (DSC) and highresolution dilatometry. The phase transformation temperatures (Ac1, Ac3, Ms and Mf) of this steel were obtained by the two methods at different heating rates showing good agreement between both techniques. The enthalpy of α-γ transformation for this steel was measured using the thermograms acquired by DSC and microstructure was analyzed by scanning electron microscope (SEM). The results showed that this steel retained a martensitic structure for all conditions

Thermal and phase transformations analysis in a PREMOMET® steel

Thermal analysis in a PREMOMET® steel has been performed by differential scanning calorimetry (DSC) and highresolution dilatometry. The phase transformation temperatures (Ac1, Ac3, Ms and Mf) of this steel were obtained by the two methods at different heating rates showing good agreement between both techniques. The enthalpy of α-γ transformation for this steel was measured using the thermograms acquired by DSC and microstructure was analyzed by scanning electron microscope (SEM). The results showed that this steel retained a martensitic structure for all conditions

An investigation to enhance understanding of the stimulation of weed seedling emergence by soil disturbance

Enhanced understanding of soil disturbance effects on weed seedling recruitment will help guide improved management approaches. Field experiments were conducted at 16 site-years at 10 research farms across Europe and North America to (i) quantify superficial soil disturbance (SSD) effects onChenopodium album emergence and (ii) clarify adaptive emergence behaviour in frequently disturbed environments. Each site-year contained factorial combinations of two seed populations (local and common, with the common population studied at all site-years) and six SSD timings [0, 50, 100, 150, 200 day-degrees (d°C, base temperature 3°C) after first emergence from undisturbed soil]. Analytical units in this study were emergence flushes. Flush magnitudes (maximum weekly emergence per count flush) and flush frequencies (flushes year−1) were compared between disturbed and undisturbed seedbanks. One year after burial, SSD promoted seedling emergence relative to undisturbed seedbanks by increasing flush magnitude rather than increasing flush frequency. Two years after burial, SSD promoted emergence through increased flush magnitude and flush frequency. The promotional effects of SSD on emergence were strongest within 500 d°C following SSD; however, low levels of SSD-induced emergence were detected as late as 3000 d°C following SSD. Accordingly, stale seedbed practices that eliminate weed seedlings should occur within 500 d°C of disturbance, because few seedlings emerge after this time. However, implementation of stale seedbed practices will probably cause slight increases in weed population densities throughout the year. Compared with the common population, local populations exhibited reduced variance in total emergence measured within sites and across SSD treatments, suggesting thatC. albumadaptation to local pedo-climatic conditions involves increased consistency in SSD-induced emergence

Opciones para el control de Cyperus difformis resistente a penoxsulam

El cultivo del arroz en países mediterráneos es particularmente vulnerable a la aparición de resistencias a herbicidas. Cyperus difformis es una mala hierba problemática en este cultivo y recientemente se ha descrito la existencia de biotipos resistentes a penoxsulam. El objetivo del trabajo fue evaluar las posibilidades de varias materias activas, alternativas al penoxsulam, que pudieran ser utilizadas para controlar C. difformis. En el estudio se utilizaron 6 poblaciones, dos de las cuales eran resistentes al penoxsulam y otras dos sensibles. Los tratamientos aplicados fueron: 1) penoxsulam+triclopyr, 2) bentazona + MCPA, 3) triclopyr, 4) bentazona, 5) MCPA, 6) fluroxipyr, 7) azimsulfuron y 8) Testigo no tratado. Los resultados indican que bentazona y triclopyr son los mejores candidatos para ser incluidos en un programa de control alternativo frente a C. difformis.Options to control Cyperus difformis resistant to penoxulam Rice crop in the mediterranean countries is particularly prone to herbicide resistance. Cyperus difformis is a major weed problem in rice crop, and penoxsulam resistance has been recently reported. The aim of the paper was to evaluate the chances of several herbicides to be included in an alternative control to penoxsulam of C. difformis. Six populations of C. difformis were used. Two of them were penoxsulam resistant and two were penoxsulam susceptible. The treatments were: 1) penoxsulam+triclopyr, 2) bentazona + MCPA, 3) triclopyr, 4) bentazona, 5) MCPA, 6) fluroxipyr, 7) azimsulfuron and 8) Untreated check. Results indicate that bentazona and triclopyr are the best candidates to be included in an alternative control

Notch1 signaling in NOTCH1-mutated mantle cell lymphoma depends on Delta-Like ligand 4 and is a potential target for specific antibody therapy.

Background NOTCH1 gene mutations in mantle cell lymphoma (MCL) have been described in about 5-10% of cases and are associated with significantly shorter survival rates. The present study aimed to investigate the biological impact of this mutation in MCL and its potential as a therapeutic target. Methods Activation of Notch1 signaling upon ligand-stimulation and inhibitory effects of the monoclonal anti-Notch1 antibody OMP-52M51 in NOTCH1-mutated and -unmutated MCL cells were assessed by Western Blot and gene expression profiling. Effects of OMP-52M51 treatment on tumor cell migration and tumor angiogenesis were evaluated with chemotaxis and HUVEC tube formation assays. The expression of Delta-like ligand 4 (DLL4) in MCL lymph nodes was analyzed by immunofluorescence staining and confocal microscopy. A MCL mouse model was used to assess the activity of OMP-52M51 in vivo. Results Notch1 expression can be effectively stimulated in NOTCH1-mutated Mino cells by DLL4, whereas in the NOTCH1-unmutated cell line JeKo-1, less effect was observed upon any ligand-stimulation. DLL4 was expressed by histiocytes in both, NOTCH1-mutated and -unmutated MCL lymph nodes. Treatment of NOTCH1-mutated MCL cells with the monoclonal anti-Notch1 antibody OMP-52M51 effectively prevented DLL4-dependent activation of Notch1 and suppressed the induction of numerous direct Notch target genes involved in lymphoid biology, lymphomagenesis and disease progression. Importantly, in lymph nodes from primary MCL cases with NOTCH1/2 mutations, we detected an upregulation of the same gene sets as observed in DLL4-stimulated Mino cells. Furthermore, DLL4 stimulation of NOTCH1-mutated Mino cells enhanced tumor cell migration and angiogenesis, which could be abolished by treatment with OMP-52M51. Importantly, the effects observed were specific for NOTCH1-mutated cells as they did not occur in the NOTCH1-wt cell line JeKo-1. Finally, we confirmed the potential activity of OMP-52M51 to inhibit DLL4-induced Notch1-Signaling in vivo in a xenograft mouse model of MCL. Conclusion DLL4 effectively stimulates Notch1 signaling in NOTCH1-mutated MCL and is expressed by the microenvironment in MCL lymph nodes. Our results indicate that specific inhibition of the Notch1-ligand-receptor interaction might provide a therapeutic alternative for a subset of MCL patients

Specific NOTCH1 antibody targets DLL4-induced proliferation, migration, and angiogenesis in NOTCH1-mutated CLL cells

Targeting Notch signaling has emerged as a promising therapeutic strategy for chronic lymphocytic leukemia (CLL), particularly in NOTCH1-mutated patients. We provide first evidence that the Notch ligand DLL4 is a potent stimulator of Notch signaling in NOTCH1-mutated CLL cells while increases cell proliferation. Importantly, DLL4 is expressed in histiocytes from the lymph node, both in NOTCH1-mutated and -unmutated cases. We also show that the DLL4-induced activation of the Notch signaling pathway can be efficiently blocked with the specific anti-Notch1 antibody OMP-52M51. Accordingly, OMP-52M51 also reverses Notch-induced MYC, CCND1, and NPM1 gene expression as well as cell proliferation in NOTCH1-mutated CLL cells. In addition, DLL4 stimulation triggers the expression of protumor target genes, such as CXCR4, NRARP, and VEGFA, together with an increase in cell migration and angiogenesis. All these events can be antagonized by OMP-52M51. Collectively, our results emphasize the role of DLL4 stimulation in NOTCH1-mutated CLL and confirm the specific therapeutic targeting of Notch1 as a promising approach for this group of poor prognosis CLL patients

Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice

Background Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. Aims To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). Methods We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. Results Of 255 patients, median follow-up was 35.1 months (IQR: 20.2–53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. Conclusion Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension

Diagnóstico y tratamiento del cáncer de mama HER2+: Guía de Práctica Clínica de la Sociedad Peruana de Cancerología

Introduction. In Peru, breast cancer represents the most common type of cancer in women and the sixth most lethal type of&nbsp;cancer in the general population. Overexpression of the epidermal growth factor receptor (HER2 +) occurs in 20% to 30%&nbsp;of breast cancers, and is associated with more aggressive tumors, with greater recurrence and greater mortality. Objective.&nbsp;Prepare a set of evidence-based recommendations for the diagnosis and treatment of HER2 + breast cancer, in order to help&nbsp;reduce mortality, disease progression and improve quality of life. Methods. A panel of clinical specialists and methodologists&nbsp;was formed, who identified relevant clinical questions about the diagnosis and treatment of HER2 + breast cancer. A systematic&nbsp;search for CPGs was carried out in Medline (PubMed), and in developing and compiling agencies. For the formulation of&nbsp;recommendations, the panel of specialists discussed the evidence and elements of the context of implementation of the&nbsp;recommendation, following the methodology proposed by the Ministry of Health of Peru. Results. Nine clinical questions were&nbsp;prioritized. A total of 25 clinical recommendations were made. Conclusions. An evidence-based CPG was developed through&nbsp;a systematic, rigorous and transparent process developed by a multidisciplinary team.Introducción. En Perú, el cáncer de mama representa el tipo de cáncer más frecuente en mujeres y el sexto tipo de cáncer&nbsp;más letal en la población general. La sobreexpresión del receptor del factor de crecimiento epidérmico (HER2+) ocurre en&nbsp;20% a 30% de los cánceres de mama, y se asocia con tumores más agresivos, con mayor recurrencia y mayor mortalidad.&nbsp;Objetivo. Elaborar un conjunto de recomendaciones basadas en evidencias para el diagnóstico y tratamiento del cáncer&nbsp;de mama HER2+, con la finalidad de contribuir a reducir la mortalidad, progresión de la enfermedad y mejorar la calidad&nbsp;de vida. Métodos. Se conformó un panel de especialistas clínicos y metodólogos, quienes identificaron preguntas clínicas&nbsp;relevantes sobre el diagnóstico y tratamiento del cáncer de mama HER2+. Se desarrolló una búsqueda sistemática de&nbsp;GPC en Medline (PubMed), y en organismos elaboradores y recopiladores. Para la formulación de recomendaciones, el&nbsp;panel de especialistas discutió la evidencia y elementos del contexto de implementación de la recomendación, siguiendo&nbsp;la metodología propuesta por el Ministerio de Salud del Perú. Resultados. Se priorizó nueve preguntas clínicas. Se formuló&nbsp;un total de 25 recomendaciones clínicas. Conclusiones. Se elaboró una GPC basada en evidencias, a través de un&nbsp;proceso sistemático, riguroso y transparente desarrollado por un equipo multidisciplinario.&nbsp

Gender Dimorphism in Skeletal Muscle Leptin Receptors, Serum Leptin and Insulin Sensitivity

To determine if there is a gender dimorphism in the expression of leptin receptors (OB-R170, OB-R128 and OB-R98) and the protein suppressor of cytokine signaling 3 (SOCS3) in human skeletal muscle, the protein expression of OB-R, perilipin A, SOCS3 and alpha-tubulin was assessed by Western blot in muscle biopsies obtained from the m. vastus lateralis in thirty-four men (age = 27.1±6.8 yr) and thirty-three women (age = 26.7±6.7 yr). Basal serum insulin concentration and HOMA were similar in both genders. Serum leptin concentration was 3.4 times higher in women compared to men (P<0.05) and this difference remained significant after accounting for the differences in percentage of body fat or soluble leptin receptor. OB-R protein was 41% (OB-R170, P<0.05) and 163% (OB-R128, P<0.05) greater in women than men. There was no relationship between OB-R expression and the serum concentrations of leptin or 17β-estradiol. In men, muscle OB-R128 protein was inversely related to serum free testosterone. In women, OB-R98 and OB-R128 were inversely related to total serum testosterone concentration, and OB-R128 to serum free testosterone concentration. SOCS3 protein expression was similar in men and women and was not related to OB-R. In women, there was an inverse relationship between the logarithm of free testosterone and SCOS3 protein content in skeletal muscle (r = −0.46, P<0.05). In summary, there is a gender dimorphism in skeletal muscle leptin receptors expression, which can be partly explained by the influence of testosterone. SOCS3 expression in skeletal muscle is not up-regulated in women, despite very high serum leptin concentrations compared to men. The circulating form of the leptin receptor can not be used as a surrogate measure of the amount of leptin receptors expressed in skeletal muscles

Bone Mass and the CAG and GGN Androgen Receptor Polymorphisms in Young Men

BACKGROUND: To determine whether androgen receptor (AR) CAG (polyglutamine) and GGN (polyglycine) polymorphisms influence bone mineral density (BMD), osteocalcin and free serum testosterone concentration in young men. METHODOLOGY/PRINCIPAL FINDINGS: Whole body, lumbar spine and femoral bone mineral content (BMC) and BMD, Dual X-ray Absorptiometry (DXA), AR repeat polymorphisms (PCR), osteocalcin and free testosterone (ELISA) were determined in 282 healthy men (28.6+/-7.6 years). Individuals were grouped as CAG short (CAG(S)) if harboring repeat lengths of < or = 21 or CAG long (CAG(L)) if CAG > 21, and GGN was considered short (GGN(S)) or long (GGN(L)) if GGN < or = 23 or > 23. There was an inverse association between logarithm of CAG and GGN length and Ward's Triangle BMC (r = -0.15 and -0.15, P<0.05, age and height adjusted). No associations between CAG or GGN repeat length and regional BMC or BMD were observed after adjusting for age. Whole body and regional BMC and BMD values were similar in men harboring CAG(S), CAG(L), GGN(S) or GGN(L) AR repeat polymorphisms. Men harboring the combination CAG(L)+GGN(L) had 6.3 and 4.4% higher lumbar spine BMC and BMD than men with the haplotype CAG(S)+GGN(S) (both P<0.05). Femoral neck BMD was 4.8% higher in the CAG(S)+GGN(S) compared with the CAG(L)+GGN(S) men (P<0.05). CAG(S), CAG(L), GGN(S), GGN(L) men had similar osteocalcin concentration as well as the four CAG-GGN haplotypes studied. CONCLUSION: AR polymorphisms have an influence on BMC and BMD in healthy adult humans, which cannot be explained through effects in osteoblastic activity