Asymptotic analysis of the dominant mechanisms in the coffee extraction process

peer-reviewedExtraction of coffee solubles from roast and ground coffee is a highly complex process, depending on a large number of brewing parameters. We consider a recent, experimentally validated, model of coffee extraction, describing extraction from a coffee bed using a double porosity model, which includes dissolution and transport of coffee. It was shown that this model can accurately describe coffee extraction in two situations: extraction from a dilute suspension of coffee grains and extraction from a packed coffee bed. Despite being based on some simplifying assumptions, this model can only be solved numerically. In this paper we consider asymptotic solutions of the model describing extraction from a packed coffee bed. Such solutions can explicitly relate coffee concentration to the process parameters. For an individual coffee grain, extraction is controlled by a rapid dissolution of coffee from the surface of the grain, in conjunction with a slower diffusion of coffee through the intragranular pore network to the grain surface. Extraction of coffee from the bed also depends on the speed of advection of coffee from the bed. We utilize the small parameter resulting from the ratio of the advection timescale to the grain diffusion timescale to construct asymptotic solutions using the method of matched asymptotic expansions. The asymptotic solutions are compared to numerical solutions and data from coffee extraction experiments. The asymptotic solutions depend on a small number of dimensionless parameters and so are useful to quickly fit extraction curves and investigate the influence of various process parameters on the extraction.PUBLISHEDpeer-reviewe

Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

Objective To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. Design Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1). Setting Reproductive medicine clinics. Patient(s) A total of 1,329 women (aged 18â40 years). Intervention(s) Follitropin delta (AMH <15 pmol/L: 12 μg/d; AMH â¥15 pmol/L: 0.10â0.19 μg/kg/d; maximum 12 μg/d), or follitropin alfa (150 IU/d for 5 days, potential subsequent dose adjustments; maximum 450 IU/d). Main Outcomes Measure(s) Ongoing pregnancy and ongoing implantation rates; noninferiority margins â8.0%. Result(s) Ongoing pregnancy (30.7% vs. 31.6%; difference â0.9% [95% confidence interval (CI) â5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; â0.6% [95% CI â6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; â0.9% [95% CI â5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8â14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH <15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (â¥15 or â¥20 oocytes in patients with AMH â¥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6 μg). Conclusion(s) Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation. Clinical Trial Registration Number NCT01956110

MicroRNA-135b Regulates Leucine Zipper Tumor Suppressor 1 in Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and it presents a therapeutic challenge in organ transplant recipient patients. Despite the need, there are only a few targeted drug treatment options. Recent studies have revealed a pivotal role played by microRNAs (miRNAs) in multiple cancers, but only a few studies tested their function in cSCC. Here, we analyzed differential expression of 88 cancer related miRNAs in 43 study participants with cSCC; 32 immunocompetent, 11 OTR patients, and 15 non-lesional skin samples by microarray analysis. Of the examined miRNAs, miR-135b was the most upregulated (13.3-fold, 21.5-fold; p=0.0001) in both patient groups. Similarly, the miR-135b expression was also upregulated in three cSCC cell lines when evaluated by quantitative real-time PCR. In functional studies, inhibition of miR-135b by specific anti-miR oligonucleotides resulted in upregulation of its target gene LZTS1 mRNA and protein levels and led to decreased cell motility and invasion of both primary and metastatic cSCC cell lines. In contrast, miR-135b overexpression by synthetic miR-135b mimic induced further down-regulation of LZTS1 mRNA in vitro and increased cancer cell motility and invasiveness. Immunohistochemical evaluation of 67 cSCC tumor tissues demonstrated that miR-135b expression inversely correlated with LZTS1 staining intensity and the tumor grade. These results indicate that miR-135b functions as an oncogene in cSCC and provide new understanding into its pathological role in cSCC progression and invasiveness

Extraction of coffee antioxidants: impact of brewing time and method

The aim of this work was to study the extraction behavior of the main coffee antioxidants (caffeoylquinic acids, melanoidins and caffeine) and the antioxidant capacity, during brewing time in the most widely consumed coffee brew methods (filter and espresso) in coffee. Antioxidant capacity by colorimetric assays (Folin-Ciocalteau, ABTS and DPPH) and electron spin resonance spectroscopy techniques (Fremy's salt and TEMPO) were analyzed. In espresso coffee, more than 70% of the antioxidants (except dicaffeoylquinic acids, diCQA) of a coffee brew were extracted during the first 8s. In filter coffee, a U-shape antioxidants extraction profile was observed, starting later (after 75 s) in Vietnam coffee than in Guatemala one, probably due to different wettability. Other technological parameters, such as turbulences and a longer contact time between water and ground coffee in filter coffeemaker, increased extraction efficiency, mainly in less polar antioxidant compounds as diCQA. In conclusion, these technological factors should be considered to optimize coffee antioxidants extraction that can be used as ingredients for functional foods

miRNA-135a promotes breast cancer cell migration and invasion by targeting HOXA10

<p>Abstract</p> <p>Background</p> <p>miRNAs are a group of small RNA molecules regulating target genes by inducing mRNA degradation or translational repression. Aberrant expression of miRNAs correlates with various cancers. Although miR-135a has been implicated in several other cancers, its role in breast cancer is unknown. <it>HOXA10 </it>however, is associated with multiple cancer types and was recently shown to induce p53 expression in breast cancer cells and reduce their invasive ability. Because <it>HOXA10 </it>is a confirmed miR-135a target in more than one tissue, we examined miR-135a levels in relation to breast cancer phenotypes to determine if miR-135a plays role in this cancer type.</p> <p>Methods</p> <p>Expression levels of miR-135a in tissues and cells were determined by poly (A)-RT PCR. The effect of miR-135a on proliferation was evaluated by CCK8 assay, cell migration and invasion were evaluated by transwell migration and invasion assays, and target protein expression was determined by western blotting. GFP and luciferase reporter plasmids were constructed to confirm the action of miR-135a on downstream target genes including <it>HOXA10</it>. Results are reported as means ± S.D. and differences were tested for significance using 2-sided Student"s t-test.</p> <p>Results</p> <p>Here we report that miR-135a was highly expressed in metastatic breast tumors. We found that the expression of miR-135a was required for the migration and invasion of breast cancer cells, but not their proliferation. <it>HOXA10</it>, which encodes a transcription factor required for embryonic development and is a metastasis suppressor in breast cancer, was shown to be a direct target of miR-135a in breast cancer cells. Our analysis showed that miR-135a suppressed the expression of <it>HOXA10 </it>both at the mRNA and protein level, and its ability to promote cellular migration and invasion was partially reversed by overexpression of <it>HOXA10</it>.</p> <p>Conclusions</p> <p>In summary, our results indicate that miR-135a is an onco-miRNA that can promote breast cancer cell migration and invasion. <it>HOXA10 </it>is a target gene for miR-135a in breast cancer cells and overexpression of <it>HOXA10 </it>can partially reverse the miR-135a invasive phenotype.</p