Phytochemical Targeting of Mitochondria for Breast Cancer Chemoprevention,Therapy, and Sensitization

Breast cancer is a common and deadly disease that causes tremendous physical, emotional, and financial burden on patients and society. Early-stage breast cancer and less aggressive subtypes have promising prognosis for patients, but in aggressive subtypes, and as cancers progress, treatment options and responses diminish, dramatically decreasing survival. Plants are nutritionally rich and biologically diverse organisms containing thousands of metabolites, some of which have chemopreventive, therapeutic, and sensitizing properties, providing a rich source for drug discovery. In this study we review the current landscape of breast cancer with a central focus on the potential role of phytochemicals for treatment, management, and disease prevention. We discuss the relevance of phytochemical targeting of mitochondria for improved anti-breast cancer efficacy. We highlight current applications of phytochemicals and derivative structures that display anti-cancer properties and modulate cancer mitochondria, while describing future applicability and identifying areas of promise.     

The Role of TKS5 in Chromosome Stability and Bladder Cancer Progression

TKS5 promotes invasion and migration through the formation of invadopodia in some tumour cells, and it also has an important physiological function in cell migration through podosome formation in various nontumour cells. To date, the role of TKS5 in urothelial cells, and its potential role in BC initiation and progression, has not yet been addressed. Moreover, the contribution of TKS5 to ploidy control and chromosome stability has not been reported in previous studies. Therefore, in the present study, we wished to address the following questions: (i) Is TKS5 involved in the ploidy control of urothelial cells? (ii) What is the mechanism that leads to aneuploidy in response to TKS5 knockdown? (iii) Is TKS5 an oncogene or tumour-suppressor gene in the context of BC? (iv) Does TKS5 affect the proliferation, migration and invasion of BC cells? We assessed the gene and protein expressions via qPCR and Western blot analyses in a set of nontumour cell strains (Y235T, HBLAK and UROtsa) and a set of BC cell lines (RT4, T24, UMUC3 and J82). Following the shRNA knockdown in the TKS5-proficient cells and the ectopic TKS5 expression in the cell lines with low/absent TKS5 expression, we performed functional experiments, such as metaphase, invadopodia and gelatine degradation assays. Moreover, we determined the invasion and migration abilities of these genetically modified cells by using the Boyden chamber and wound-healing assays. The TKS5 expression was lower in the bladder cancer cell lines with higher invasive capacities (T24, UMUC3 and J82) compared to the nontumour cell lines from human ureter (Y235T, HBLAK and UROtsa) and the noninvasive BC cell line RT4. The reduced TKS5 expression in the Y235T cells resulted in augmented aneuploidy and impaired cell division. According to the Boyden chamber and wound-healing assays, TKS5 promotes the invasion and migration of bladder cancer cells. According to the present study, TKS5 regulates the migration and invasion processes of bladder cancer (BC) cell lines and plays an important role in genome stability.     

SARS-CoV-2 Altered Hemorheological and Hematological Parameters during One-Month Observation Period in Critically Ill COVID-19 Patients

Hematological and hemorheological parameters are known to be altered in COVID-19; however, the value of combined monitoring in order to deduce disease severity is only scarcely examined. A total of 44 acute SARS-CoV-2-infected patients (aCOV) and 44 age-matched healthy controls (Con) were included. Blood of aCOV was sampled at admission (T0), and at day 2 (T2), day 5 (T5), day 10 (T10), and day 30 (T30) while blood of Con was only sampled once. Inter- and intra-group differences were calculated for hematological and hemorheological parameters. Except for mean cellular volume and mean cellular hemoglobin, all blood cell parameters were significantly different between aCOV and Con. During the acute disease state (T0–T5), hematological and hemorheological parameters were highly altered in aCOV; in particular, anemic conditions and increased immune cell response/inflammation, oxidative/nitrosative stress, decreased deformability, as well as increased aggregation, were observed. During treatment and convalescence until T30, almost all abnormal values of aCOV improved towards Con values. During the acute state of the COVID-19 disease, the hematological, as well as the hemorheological system, show fast and potentially pathological changes that might contribute to the progression of the disease, but changes appear to be largely reversible after four weeks. Measuring RBC deformability and aggregation, as well as oxidative stress induction, may be helpful in monitoring critically ill COVID-19 patients.     

Study of the Electrochemical Behavior of N-Substituted-4-Piperidones Curcumin Analogs: A Combined Experimental and Theoretical Approach

The electrochemical behavior of N-methyl- and N-benzyl-4-piperidone curcumin analogs were studied experimentally and theoretically. The studied compounds present different substituents at the para position in the phenyl rings (-H, -Br, -Cl, -CF₃, and -OCH₃). We assessed their electrochemical behavior by differential pulse and cyclic voltammetry, while we employed density functional theory (DFT) M06 and M06-2x functionals along with 6-311+G(d,p) basis set calculations to study them theoretically. The results showed that compounds suffer a two-electron irreversible oxidation in the range of 0.72 to 0.86 V, with surface concentrations ranging from 1.72 × 10⁻⁷ to 5.01 × 10⁻⁷ mol/cm². The results also suggested that the process is diffusion-controlled for all compounds. M06 DFT calculations showed a better performance than M06-2x to obtain oxidation potentials. We found a good correlation between the experimental and theoretical oxidation potential for N-benzyl-4-piperidones (R² = 0.9846), while the correlation was poor for N-methyl-4-piperidones (R² = 0.3786), suggesting that the latter suffer a more complex oxidation process. Calculations of the BDEs for labile C-H bonds in the compounds suggested that neither of the two series of compounds has a different tendency for a proton-coupled electron transfer (PCET) oxidation process. It is proposed that irreversible behavior is due to possible dimerization of the compounds by Shono-type oxidation.     

From visionary ideas to products

This paper presents the rationale for the creation of the Microelectronics and Computer Research Corporation (MCC), to be a cooperative research organization funded by a number of U.S. computer and electronics companies.

Factors inhibiting investment in fundamental research by individual companies today are presented and analyzed, and the benefits of the consortium approach for cooperatively performing basic research and early exploratory development work are described.

The present research activities of MCC in the areas of Advanced Computer Architectures, Computer Aided Design, Software Technology, and Packaging and Interconnect technology are presented. This is followed by a discussion of future directions for research in the field of computer science.     

Ergonomics of technology transfer

It is beyond doubt that high technology has elevated the standards of living of mankind. The modern technology created and developed to a great extent by Western or developed societies is now in great demand in Eastern and developing societies who are trying to leap-frog towards advancement. But unfortunately, in the transfer of technology, both the giver and the receiver seem to make many mistakes. A technology transferred without considering the ethnic variables in the societies and differences in the climates, has found to cause problems to the acquirer. Due to the basic human factor differences such as sizes of people, physical environment, physical capacities and organizational and cultural differences, a technology which is unadapted has found to be inappropriate, harmful, hazardous and unsuccessful. In the areas of health, working conditions, production and finance, undesirable effects have resulted through haphazard technology transfer, For a successful transfer, it is therefore stressed that technology has to be adapted or modified taking into consideration the technological, anthropological and socio-economic factors of the acquiring population.     

Information technology at the National Computing Centre

An outline is given of the information services used in the National Computing Centre. An update is provided of a previous paper describing the local area network implemented in 1981. Three IT landmarks are highlighted, these include the introduction of word processing, the local area network and a digital PABX. The implications and subsequent developments are described. The facilities available on the local area network are discussed. The use of three electronic mail services are also considered, along with the use of facsimile.     

Selecting and conserving lands for biodiversity: The role of remote sensing

A major focus of conservation is on protecting areas to ensure the persistence of biological diversity. Because such areas may be large, not easily accessible, subject to change, and sensitive to the surrounding landscape, remote sensing can be a valuable tool in establishing and managing protected areas. We describe three case studies to illustrate how remote sensing can contribute to setting priorities for conservation actions, monitoring the status of conservation targets, and evaluating the effectiveness of conservation strategies. In the Connecticut River watershed, remote sensing has been used to assess flood regimes and identify key areas of floodplain forests and their context for conservation planning. At Eglin Air Force Base in Florida, remote sensing has provided information to assess the effectiveness of management strategies to restore fire to the longleaf pine sandhills ecosystem, control invasive species, and prioritize annual prescribed burns. In eastern US forests, remote sensing is being used to evaluate the ecological condition and changes at properties where direct access would be difficult.As the resolution and capacities of remote-sensing technology continue to develop, however, several issues are becoming increasingly important. It is essential that the spatial and temporal resolution of remote-sensing data be matched to the relevant scales of biodiversity, major threats, and management actions. Data layers must be compatible, both in scale and in measurement properties, and key patterns must be distinguished from irrelevant detail, especially at the finer scales of application in local management. Combining remote sensing with ground surveys can expand the array of information used in management and contribute to the ecological interpretation of remote-sensing data. Because conservation funds are always limited, remote sensing also must be cost effective. This requires balancing the wealth of detail afforded by ever-finer resolution of remote-sensing data with what is actually needed to implement sound conservation and management. Remote sensing is a valuable tool, but it is not a panacea for all of the challenges of conservation monitoring and management.     

Slicing Software for Model Construction

Applying finite-state verification techniques (e.g., model checking) to software requires that program source code be translated to a finite-state transition system that safely models program behavior. Automatically checking such a transition system for a correctness property is typically very costly, thus it is necessary to reduce the size of the transition system as much as possible. In fact, it is often the case that much of a program's source code is irrelevant for verifying a given correctness property.In this paper, we apply program slicing techniques to remove automatically such irrelevant code and thus reduce the size of the corresponding transition system models. We give a simple extension of the classical slicing definition, and prove its safety with respect to model checking of linear temporal logic (LTL) formulae. We discuss how this slicing strategy fits into a general methodology for deriving effective software models using abstraction-based program specialization.     

TWC LOGD: A portal for linked open government data ecosystems

International open government initiatives are releasing an increasing volume of raw government datasets directly to citizens via the Web. The transparency resulting from these releases not only creates new application opportunities but also imposes new burdens inherent to large-scale distributed data integration, collaborative data manipulation and transparent data consumption. The Tetherless World Constellation (TWC) at Rensselaer Polytechnic Institute (RPI) has developed the Semantic Web-based TWC LOGD portal to support the deployment of linked open government data (LOGD). The portal is both an open source infrastructure supporting linked open government data production and consumption and a vibrant community portal that educates and serves the growing international open government community of developers, data curators and end users. This paper motivates and introduces the TWC LOGD Portal and highlights innovative aspects and lessons learned.