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.     

Regulatory RNAs: A Universal Language for Inter-Domain Communication

In eukaryotes, microRNAs (miRNAs) have roles in development, homeostasis, disease and the immune response. Recent work has shown that plant and mammalian miRNAs also mediate cross-kingdom and cross-domain communications. However, these studies remain controversial and are lacking critical mechanistic explanations. Bacteria do not produce miRNAs themselves, and therefore it is unclear how these eukaryotic RNA molecules could function in the bacterial recipient. In this review, we compare and contrast the biogenesis and functions of regulatory RNAs in eukaryotes and bacteria. As a result, we discovered several conserved features and homologous components in these distinct pathways. These findings enabled us to propose novel mechanisms to explain how eukaryotic miRNAs could function in bacteria. Further understanding in this area is necessary to validate the findings of existing studies and could facilitate the use of miRNAs as novel tools for the directed remodelling of the human microbiota.     

COVID-19 hospitalization rates rise exponentially with age,inversely proportional to thymic T-cell production

Here, we report that COVID-19 hospitalization rates follow an exponential relationship with age, doubling for every 16 years of age or equivalently increasing by 4.5% per year of life (R² = 0.98). This mirrors the well-studied exponential decline of both thymus volume and T-cell production, which halve every 16 years. COVID-19 can therefore be added to the list of other diseases with this property, including those caused by methicillin-resistant Staphylococcus aureus, MERS-CoV, West Nile virus, Streptococcus pneumoniae and certain cancers, such as chronic myeloid leukaemia and brain cancers. In addition, the incidence of severe disease and mortality due to COVID-19 are both higher in men, consistent with the degree to which thymic involution (and the decrease in T-cell production with age) is more severe in men compared to women. Since these properties are shared with some non-contagious diseases, we hypothesized that the age dependence does not come from social-mixing patterns, i.e. that the probability of hospitalization given infection rises exponentially, doubling every 16 years. A Bayesian analysis of daily hospitalizations, incorporating contact matrices, found that this relationship holds for every age group except for the under 20s. While older adults have fewer contacts than young adults, our analysis suggests that there is an approximate cancellation between the effects of fewer contacts for the elderly and higher infectiousness due to a higher probability of developing severe disease. Our model fitting suggests under 20s have 49–75% additional immune protection beyond that predicted by strong thymus function alone, consistent with increased juvenile cross-immunity from other viruses. We found no evidence for differences between age groups in susceptibility to infection or infectiousness to others (given disease state), i.e. the only important factor in the age dependence of hospitalization rates is the probability of hospitalization given infection. These findings suggest the existence of a T-cell exhaustion threshold, proportional to thymic output and that clonal expansion of peripheral T-cells does not affect disease risk. The strikingly simple inverse relationship between risk and thymic T-cell output adds to the evidence that thymic involution is an important factor in the decline of the immune system with age and may also be an important clue in understanding disease progression, not just for COVID-19 but other diseases as well.     

Food recognition using neural network classifier and multiple hypotheses image segmentation

ABSTRACT

This paper proposes the multiple-hypotheses image segmentation and feed-forward neural network classifier for food recognition to improve the performance. Initially, the food or meal image is given as input. Then, the segmentation is applied to identify the regions, where a particular food item is located using salient region detection, multi-scale segmentation, and fast rejection. Then, the features of every food item are extracted by the global feature and local feature extraction. After the features are obtained, the classification is performed for each segmented region using a feed-forward neural network model. Finally, the calorie value is computed with the aid of (i) food volume and (ii) calorie and nutrition measure based on mass value. The experimental results and performance evaluation are validated. The outcome of the proposed method attains 0.947 for Macro Average Accuracy (MAA) and 0.959 for Standard Accuracy (SA), which provides better classification performance.     

High-performance MIM capacitor using ALD high-k HfO/sub 2/-Al/sub 2/O/sub 3/ laminate dielectrics

For the first time, we successfully fabricated and demonstrated high performance metal-insulator-metal (MIM) capacitors with HfO/sub 2/-Al/sub 2/O/sub 3/ laminate dielectric using atomic layer deposition (ALD) technique. Our data indicates that the laminate MIM capacitor can provide high capacitance density of 12.8 fF//spl mu/m/sup 2/ from 10 kHz up to 20 GHz, very low leakage current of 3.2 /spl times/ 10/sup -8/ A/cm/sup 2/ at 3.3 V, small linear voltage coefficient of capacitance of 240 ppm/V together with quadratic one of 1830 ppm/V/sup 2/, temperature coefficient of capacitance of 182 ppm//spl deg/C, and high breakdown field of /spl sim/6 MV/cm as well as promising reliability. As a result, the HfO/sub 2/-Al/sub 2/O/sub 3/ laminate is a very promising candidate for next generation MIM capacitor for radio frequency and mixed signal integrated circuit applications.     

Algebraic theory of optimal filterbanks

We introduce an optimality theory for finite impulse response (FIR) filterbanks using a general algebraic point of view. We consider an admissible set /spl Lscr/ of FIR filterbanks and use scalability as the main notion based on which performance of the elements in /spl Lscr/are compared. We show that quantification of scalability leads naturally to a partial ordering on the set /spl Lscr/. An optimal solution is, therefore, represented by the greatest element in /spl Lscr/. It turns out that a greatest element does not necessarily exist in /spl Lscr/. Hence, one has to settle with one of the maximal elements that exist in /spl Lscr/. We provide a systematic way of finding a maximal element by embedding the partial ordering at hand in a total ordering. This is done by using a special class of order-preserving functions known as Schur-convex. There is, however, a price to pay for achieving a total ordering: there are infinitely many possible choices for Schur-convex functions, and the optimal solution specified in /spl Lscr/ depends on this (subjective) choice. An interesting aspect of the presented algebraic theory is that the connection between several concepts, namely, principal component filterbanks (PCFBs), filterbanks with maximum coding gain, and filterbanks with good scalability, is clearly revealed. We show that these are simply associated with different extremal elements of the partial ordering induced on /spl Lscr/ by scalability.     

PdO/Pd system equilibrium phase diagram under a gas mixture of oxygen and nitrogen

The thermal equilibrium decomposition properties of the PdO-Pd system under oxygen partial pressures ranging from 0.1 to 1.0 atm in a total combined pressure of oxygen and nitrogen of 1.0 atm were investigated by means of thermal-gravimetric analyses. The phase diagram of Pd-PdO over the range of oxygen/nitrogen gas concentration was established. The decomposition temperature of PdO to Pd was found to increase with the partial pressure of oxygen.     

Evaluation of Digitally Encoded Layer‐by‐layer Coated Microparticles as Cell Carriers

To obtain more biologically relevant data there is a growing interest in the use of living cells for assaying the biological activity of unknown chemical compounds. Density ‘multiplex’ cell‐based assays, where different cell types are mixed in one well and simultaneously investigated upon exposure to a certain compound are beginning to emerge. To be able to identify the cells they should be attached to microscopic carriers that are encoded. This paper investigates how digitally encoded microparticles can be loaded with cells while keeping the digital code in the microcarriers readable. It turns out that coating the surface of the encoded microcarriers with polyelectrolytes using the layer‐by‐layer (LbL) approach provides the microcarriers with a ‘highly functional’ surface. The polyelectrolyte layer allows the growth of the cells, allows the orientation of the cell loaded microcarriers in a magnetic field, and does not hamper the reading of the code. It has further been shown that the cells growing on the polyelectrolyte layer can become transduced by adenoviral particles hosted by the polyelectrolyte layer. It is concluded that the digitally encoded microparticles are promising materials for use in biomedical and pharmaceutical in‐vitro research where cells are used as tools.