A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.     

Development of low-alcohol isotonic beer by interrupted fermentation

Alcohol-free beer with isotonic properties is getting more popular and its production can be carried out by different production strategies; however, interrupted fermentation is still a challenge. Therefore, the objective of this study was to develop a low-alcohol isotonic beer (<0.5% v/v) by interrupted fermentation. Moreover, the major objective is to compare the developed product to commercial beverages (sports drinks, ‘Pilsen' regular beer, alcohol-free beers and low-alcohol isotonic beer). The beverages were evaluated based on pH, alcohol content (% v/v), total titratable acidity (mEq L⁻¹), osmolality (mOsmol kg⁻¹), bitterness International Bitterness Units, colour European Brewery Convention, total phenolic compounds (mg L⁻¹ gallic acid), reducing and total sugars (%) and Na and K contents (mg L⁻¹). The developed low-alcohol isotonic beer presented characteristics similar to sports drinks, with the advantage of being richer in phenolic compounds and suitable osmolality. Despite salts were added in its formulation, the grades attributed to all beers employed in the sensory evaluation, as well as the purchase intention did not present significant differences.     

Toward optimization of a robust low-cost sulfonated-polyethersulfone containing layered double hydroxide for PEM fuel cells

Polyethersulphone (PES) is an aromatic thermoplastic, at low environmental impact, evaluated in this work as a promising candidate for new polymer electrolytes in the PEMFCs technology. A sulfonation procedure has been tuned in order to graft sulfonic acid groups on the polymer chains (sPES) and to make it hydrophilic. Homogeneous membranes with different polymer's sulfonation degrees (SD%) have demonstrated excellent mechanical properties and very low permeability toward methanol (important in the DMFCs), even if low proton conductivity. Nanocomposite sPES membranes were prepared by dispersion of highly hydrophilic lamellar particles such as layered double hydroxide (LDH) in the polymer. Deep investigations performed by a combination of PFG-NMR, EIS, XRD, DMA, and scanning electron microscopy have evidenced the exfoliation of the lamellae in polymer matrix. However, a certain anisotropy was evidenced both in the morphology and molecular diffusion, favored in the longitudinal direction (parallel to surface), while completely inhibited in the cross-section. This finding is most likely induced by the polymer structure, therefore particular attention must be paid to the choice of the filler and preparation of the composites. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47884.     

Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug–drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.     

GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation

Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.     

Predictive equation for acquisition of hepatitis B in hospital workers in a general hospital

A cross-sectional study was performed to obtain risk factors for hepatitis B disease, HBsAg carriers and immunised personnel, among 2470 workers in a general hospital in Madrid, Spain. The data obtained were analyzed with multiple logistic regression to obtain beta coefficients for variables. The results of the analysis show that being a nurse or being regularly exposed to blood are the most important risk factors for hepatitis B acquisition. The length of time working at the same job activity was also a risk factor. The resulting beta coefficients allow the construction for a hepatitis non-immunised, HBsAg carrier and immunised HBV status, which can select subjects for a hepatitis B vaccination program.     

Pulse-stream VLSI neural networks mixing analog and digitaltechniques

The pulse-stream technique, which represents neural states as sequences of pulses, is reviewed. Several general issues are raised, and generic methods appraised, for pulsed encoding, arithmetic, and intercommunication schemes. Two contrasting synapse designs are presented and compared. The first is based on a fully analog computational form in which the only digital component is the signaling mechanism itself-asynchronous, pulse-rate encoded digital voltage pulses. In this circuit, multiplication occurs in the voltage/current domain. The second design uses more conventional digital memory for weight storage, with synapse circuits based on pulse stretching. Integrated circuits implementing up to 15000 analog, fully programmable synaptic connections are described. A demonstrator project is described in which a small robot localization network is implemented using asynchronous, analog, pulse-stream devices.     

Fast Parallel Reordering and Isomorphism Testing of k -Trees

In this paper two problems on the class of k -trees, a subclass of the class of chordal graphs, are considered: the fast reordering problem and the isomorphism problem. An O(log ² n) time parallel algorithm for the fast reordering problem is described that uses O(nk(n-k)/\kern -1ptlog n) processors on a CRCW PRAM proving membership in the class NC for fixed k . An O(nk(k+1)!) time sequential algorithm for the isomorphism problem is obtained representing an improvement over the O(n ² k(k+1)!) algorithm of Sekharan (the second author) [10]. A parallel version of this sequential algorithm is presented that runs in O(log ² n) time using O((nk((k+1)!+n-k))/log n) processors improving on a parallel algorithm of Sekharan for the isomorphism problem [10]. Both the sequential and parallel algorithms use a concept introduced in this paper called the kernel of a k -tree.