Progressive Pattern Interleaver with Multi-Carrier Modulation Schemes and Iterative Multi-User Detection in IoT 6G Environments with Multipath Channels.

Sixth-generation (6G) wireless networks demand a more efficient implementation of non-orthogonal multiple access (NOMA) schemes for severe multipath fading environments to serve multiple users. Using non-orthogonal multiple access (NOMA) schemes in IoT 6G networks is a promising solution to allow multiple users to share the same spectral and temporal resource, increasing spectral efficiency and improving the network's capacity. In this work, we have evaluated the performance of a novel progressive pattern interleaver (PPI) employed to distinguish the users in interleaved division multiple access (IDMA) schemes, suggested by 3GPP guidelines as a NOMA scheme, with two multi-carrier modulation schemes known as single-carrier frequency-division multiple access (SC-FDMA) and orthogonal frequency-division multiplexing (OFDM), resulting in SC-FDMA-IDMA and OFDM-IDMA schemes. Both schemes are multi-carrier schemes with orthogonal sub-carriers to deal against inter-symbol interference (ISI) and orthogonal interleavers for the simultaneous access of multiple users. It has been suggested through simulation outcomes that PPI performance is adequate with SC-FDMA-IDMA and OFDM-IDMA schemes in terms of bit error rate (BER) under multipath channel conditions. Moreover, regarding bandwidth requirement and the implementation complexity of the transmitted interleaver structure, PPI is superior to the conventional random interleaver (RI).

Engineered Skin Tissue Equivalents for Product Evaluation and Therapeutic Applications.

The current status of skin tissue equivalents that have emerged as relevant tools in commercial and therapeutic product development applications is reviewed. Due to the rise of animal welfare concerns, numerous companies have designed skin model alternatives to assess the efficacy of pharmaceutical, skincare, and cosmetic products in an in vitro setting, decreasing the dependency on such methods. Skin models have also made an impact in determining the root causes of skin diseases. When designing a skin model, there are various chemical and physical considerations that need to be considered to produce a biomimetic design. This includes designing a structure that mimics the structural characteristics and mechanical strength needed for tribological property measurement and toxicological testing. Recently, various commercial products have made significant progress towards achieving a native skin alternative. Further research involve the development of a functional bilayered model that mimics the constituent properties of the native epidermis and dermis. In this article, the skin models are divided into three categories: in vitro epidermal skin equivalents, in vitro full-thickness skin equivalents, and clinical skin equivalents. A description of skin model characteristics, testing methods, applications, and potential improvements is presented.

Quantification of Lipid Phase Order of In Vivo Human Skin Using Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy and Multivariate Curve Resolution Analysis.

A new analysis methodology utilizing multivariate curve resolution (MCR) has been successfully combined with Fourier transform infrared (FT-IR) measurement of in vivo human skin to resolve lipid phase constituents in the spectra relative to high and low chain ordering. A clinical study was performed to measure lipid order through different depths of stratum corneum of human subjects. Fourier transform IR spectra were collected through the top 10 layers of the skin on four sites on the left and right forearm of 12 individuals. Depth profiling was achieved by tape stripping to remove layers of skin with 10 successive tapes from each site. In vivo ATR FT-IR spectra were collected after removing each tape. Three isolated spectral regions were analyzed, centered around 2850 cm-1, 1460-1480 cm-1, and 730 cm-1, corresponding to stretching, scissoring, and rocking -CH2 vibrational modes, respectively. Both traditional lipid conformation analysis and MCR analysis were performed on the same spectral data. The lipid order ratio, expressed as the fraction of highly ordered orthorhombic (OR) lipids to the total lipids content (orthorhombic + hexagonal [HEX] + liquid crystal [LC]), was assessed as function of depth. Lipid order depth profiles (LODP) show an increase in order with the stratum corneum depth which can be adequately described by an exponential function for the data obtained in this study. The LODP derived from the three vibrational modes show very similar trends, although the absolute order ratios are somewhat different. The variance of the skin LODP across individuals is much greater than between sites within the same individual. The higher arm sites closer to the elbow on the left and right arm show no statistically significant difference and are recommended for use in comparative studies. The scissoring mode shows the highest sensitivity for determination of LODP value.

In vivo multiphoton microscopy of melasma.

Melasma is a skin disorder characterized by hyperpigmented patches due to increased melanin production and deposition. In this pilot study, we evaluate the potential of multiphoton microscopy (MPM) to characterize non-invasively the melanin content, location, and distribution in melasma and assess the elastosis severity. We employed a clinical MPM tomograph to image in vivo morphological features in melasma lesions and adjacent normal skin in 12 patients. We imaged dermal melanophages in most dermal melasma lesions and occasionally in epidermal melasma. The melanin volume fraction values measured in epidermal melasma (14% ± 4%) were significantly higher (p < 0.05) than the values measured in perilesional skin (11% ± 3%). The basal keratinocytes of melasma and perilesions showed different melanin distribution. Elastosis was predominantly more severe in lesions than in perilesions and was associated with changes in melanin distribution of the basal keratinocytes. These results demonstrate that MPM may be a non-invasive imaging tool for characterizing melasma.

Comparative in vitro toxicity profile of electronic and tobacco cigarettes, smokeless tobacco and nicotine replacement therapy products: e-liquids, extracts and collected aerosols.

The use of electronic cigarettes (e-cigs) continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT) products and a nicotine replacement therapy (NRT) product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic.

Three-dimensional chemical imaging of skin using stimulated Raman scattering microscopy.

Stimulated Raman scattering (SRS) microscopy is used to generate structural and chemical three-dimensional images of native skin. We employed SRS microscopy to investigate the microanatomical features of skin and penetration of topically applied materials. Image depth stacks are collected at distinct wavelengths corresponding to vibrational modes of proteins, lipids, and water in the skin. We observed that corneocytes in stratum corneum are grouped together in clusters, 100 to 250 µm in diameter, separated by 10- to 25-µm-wide microanatomical skin-folds called canyons. These canyons occasionally extend down to depths comparable to that of the dermal-epidermal junction below the flat surface regions in porcine and human skin. SRS imaging shows the distribution of chemical species within cell clusters and canyons. Water is predominately located within the cell clusters, and its concentration rapidly increases at the transition from stratum corneum to viable epidermis. Canyons do not contain detectable levels of water and are rich in lipid material. Oleic acid-d34 applied to the skin surface lines the canyons down to a depth of 50 µm below the surface of the skin. This observation could have implications on the evaluation of penetration profiles of bioactive materials measured using traditional methods, such as tape-stripping.

Improved modeling of in vivo confocal Raman data using multivariate curve resolution (MCR) augmentation of ordinary least squares models.

In vivo confocal Raman spectroscopy has become the measurement technique of choice for skin health and skin care related communities as a way of measuring functional chemistry aspects of skin that are key indicators for care and treatment of various skin conditions. Chief among these techniques are stratum corneum water content, a critical health indicator for severe skin condition related to dryness, and natural moisturizing factor components that are associated with skin protection and barrier health. In addition, in vivo Raman spectroscopy has proven to be a rapid and effective method for quantifying component penetration in skin for topically applied skin care formulations. The benefit of such a capability is that noninvasive analytical chemistry can be performed in vivo in a clinical setting, significantly simplifying studies aimed at evaluating product performance. This presumes, however, that the data and analysis methods used are compatible and appropriate for the intended purpose. The standard analysis method used by most researchers for in vivo Raman data is ordinary least squares (OLS) regression. The focus of work described in this paper is the applicability of OLS for in vivo Raman analysis with particular attention given to use for non-ideal data that often violate the inherent limitations and deficiencies associated with proper application of OLS. We then describe a newly developed in vivo Raman spectroscopic analysis methodology called multivariate curve resolution-augmented ordinary least squares (MCR-OLS), a relatively simple route to addressing many of the issues with OLS. The method is compared with the standard OLS method using the same in vivo Raman data set and using both qualitative and quantitative comparisons based on model fit error, adherence to known data constraints, and performance against calibration samples. A clear improvement is shown in each comparison for MCR-OLS over standard OLS, thus supporting the premise that the MCR-OLS method is better suited for general-purpose multicomponent analysis of in vivo Raman spectral data. This suggests that the methodology is more readily adaptable to a wide range of component systems and is thus more generally applicable than standard OLS.

Tracheal Morphologic and Protein Alterations FollowingShort-Term Cigarette Mainstream Smoke Exposure to Rats.

A short-term 5-day nose-only cigarette smoke exposure study was conducted in Fisher 344 rats to identify smoke-induced tracheal protein changes. Groups of 10 male and female 5 week old rats were assigned to 1 of 4 exposure groups. Animals received filtered air, or 75, 200 or 400 mg total particulate matter (TPM)/m(3) of diluted 3R4F Kentucky reference cigarette mainstream smoke. Exposures were conducted for 3 hrs/day, for 5 consecutive days. Tracheas from half the rats were processed for pathology, and tracheas from the other half of the rats frozen immediately for proteomics. We hypothesized that smoke will activate tracheal inflammatory, apoptotic, proliferative, and stress-induced pathways. Mucosal epithelial toxicity from the inhaled material was evidenced by cilia shortening and loss of tracheal mucosal epithelium in smoke-exposed animals. Mucosal thinning occurred in all smoke-exposed groups with hyperplastic reparative responses in the 200 and 400 mg TPM/m(3) groups. Tracheal lysates from control vs. treated animals were screened for 800 proteins using antibody-based microarray technology and subsequently the most changed proteins evaluated by Western blot. Tracheal proteins expressed at high levels that were markedly increased or decreased by smoke exposure depended on dose and gender and included caspase 5, ERK 1/2 and p38. Signaling pathways common between the morphologic and protein changes were stress, apoptosis, cell cycle control, cell proliferation and survival. Changes in identified proteins affected by smoke exposure were associated with tracheal mucosal pathology, may induce functional tracheal changes, and could serve as early indicators of tracheal damage and associated disease.

Proteomic analyses of lung lysates from short-term exposure of Fischer 344 rats to cigarette smoke.

A short-term 5 day mainstream cigarette smoke exposure study was conducted in Fischer 344 rats to identify changes in lung proteins. Groups of 10 male and female rats at 5 weeks of age were assigned to one of four exposure groups. Animals received either nose-only filtered air (Air Control) or 75, 200, or 400 mg total particulate matter (TPM)/m(3) of diluted cigarette smoke. Exposures were conducted for 3 h per day, for 5 consecutive days. One lung per animal was frozen in liquid nitrogen and processed for proteomic analyses. Lung lysates from control verses treated animals were screened with 650 antibodies for changes in signaling protein levels and phosphorylation using antibody microarray technology, and then over 100 of the top protein hits were assessed by immunoblotting. The top smoke-altered proteins were further evaluated using reverse lysate microarrays. Major protein changes showed medium to strong bands on Western blots, depended on dose and gender, and included protein-serine kinases (Cot/Tpl2, ERK1/2, GSK3α/ß, MEK6, PKCα/γ, RSK1), protein phosphatases (PP4/A'2, PP1Cß), and other proteins (caspase 5, CRMP2, Hsc70, Hsp60, Rac1 and STAT2). The most pronounced changes occurred with 75 mg TPM/m(3) exposed females and 200 mg TPM/m(3) exposed males. Smoke-altered proteins regulate apoptosis, stress response, cell structure, and inflammation. Changes in identified proteins may serve as early indicators of lung damage.

Quantitative nanoscale water mapping in frozen-hydrated skin by low-loss electron energy-loss spectroscopy.

Spatially resolved low-loss electron energy-loss spectroscopy (EELS) is a powerful method to quantitatively determine the water distribution in frozen-hydrated biological materials at high spatial resolution. However, hydrated tissue, particularly its hydrophilic protein-rich component, is very sensitive to electron radiation. This sensitivity has traditionally limited the achievable spatial resolution because of the relatively high noise associated with low-dose data acquisition. We show that the damage caused by high-dose data acquisition affects the accuracy of a multiple-least-squares (MLS) compositional analysis because of inaccuracies in the reference spectrum used to represent the protein. Higher spatial resolution combined with more accurate compositional analysis can be achieved if a reference spectrum is used that better represents the electron-beam-damaged protein component under frozen-hydrated conditions rather than one separately collected from dry protein under low-dose conditions. We thus introduce a method to extract the best-fitting protein reference spectrum from an experimental spectrum dataset. This method can be used when the MLS-fitting problem is sufficiently constrained so that the only unknown is the reference spectrum for the protein component. We apply this approach to map the distribution of water in cryo-sections obtained from frozen-hydrated tissue of porcine skin. The raw spectral data were collected at doses up to 10(5)e/nm(2) despite the fact that observable damage begins at doses as low as 10(3)e/nm(2). The resulting spatial resolution of 10nm is 5-10 times better than that in previous studies of frozen-hydrated tissue and is sufficient to resolve sub-cellular water fluctuations as well as the inter-cellular lipid-rich regions of skin where water-mediated processes are believed to play a significant role in the phenotype of keratinocytes in the stratum corneum.

Effects of short-term cigarette smoke exposure on Fischer 344 rats and on selected lung proteins.

A short-term 5-day cigarette smoke exposure study was conducted in Fischer 344 rats to identify smoke-induced lung protein changes. Groups of 10 male and 10 female rats at 5 weeks of age were randomly assigned to one of four exposure groups. Animals received filtered air (control) or 75, 200, or 400 mg total particulate matter (TPM)/m(3) of diluted Kentucky reference 3R4F cigarette smoke. Nose-only exposures were conducted for 3 hours/day for 5 consecutive days. Mean body weights were significantly reduced only in male rats exposed to 400 mg TPM/m(3). Body weight gains were significantly reduced in 200- and 400-mg TPM/m(3)-exposed males and in all smoke-exposed females compared with controls. Alveolar histiocytosis increased slightly in all smoke exposed-females and 200- and 400-mg TPM/m(3)-exposed males. Cyclooxygenase-2 staining increased at 400 mg TPM/m(3). Matrix metalloproteinase-12 staining of alveolar macrophages and bronchiolar epithelia increased in smoke-exposed animals, especially 400-mg TPM/m(3)-exposed females. Protein kinase C-alpha staining increased in macrophages at 200- and 400-mg TPM/m(3) doses. c-Jun NH(2)-terminal kinases staining decreased in smoke-exposed tissues. The identified changed proteins play roles in inflammation, transformation, proliferation, stress activation, and apoptosis.

Effects of mainstream cigarette smoke on the global metabolome of human lung epithelial cells.

Metabolomics is a technology for identifying and quantifying numerous biochemicals across metabolic pathways. Using this approach, we explored changes in biochemical profiles of human alveolar epithelial carcinoma (A549) cells following in vitro exposure to mainstream whole smoke (WS) aerosol as well as to wet total particulate matter (WTPM) or gas/vapor phase (GVP), the two constituent phases of WS from 2R4F Kentucky reference cigarettes. A549 cells were exposed to WTPM or GVP (expressed as WTPM mass equivalent GVP volumes) at 0, 5, 25, or 50 microg/mL or to WS from zero, two, four, and six cigarettes for 1 or 24 h. Cell pellets were analyzed for perturbations in biochemical profiles, with named biochemicals measured, analyzed, and reported in a heat map format, along with biochemical and physiological interpretations (mSelect, Metabolon Inc.). Both WTPM and GVP exposures likely decreased glycolysis (based on decreased glycolytic intermediaries) and increased oxidative stress and cell damage. Alterations in the Krebs cycle and the urea cycle were unique to WTPM exposure, while induction of hexosamines and alterations in lipid metabolism were unique to GVP exposure. WS altered glutathione (GSH) levels, enhanced polyamine and pantothenate levels, likely increased beta-oxidation of fatty acids, and increased phospholipid degradation marked by an increase in phosphoethanolamine. GSH, glutamine, and pantothenate showed the most significant changes with cigarette smoke exposure in A549 cells based on principal component analysis. Many of the changed biochemicals were previously reported to be altered by cigarette exposure, but the global metabolomic approach offers the advantage of observing changes to hundreds of biochemicals in a single experiment and the possibility for new discoveries. The metabolomic approach may thus be used as a screening tool to evaluate conventional and novel tobacco products offering the potential to reduce risks of smoking.

Cleansing without compromise: the impact of cleansers on the skin barrier and the technology of mild cleansing.

Cleanser technology has come a long way from merely cleansing to providing mildness and moisturizing benefits as well. It is known that harsh surfactants in cleansers can cause damage to skin proteins and lipids, leading to after-wash tightness, dryness, barrier damage, irritation, and even itch. In order for cleansers to provide skin-care benefits, they first must minimize surfactant damage to skin proteins and lipids. Secondly, they must deposit and deliver beneficial agents such as occlusives, skin lipids, and humectants under wash conditions to improve skin hydration, as well as mechanical and visual properties. While all surfactants tend to interact to some degree with lipids, their interaction with proteins can vary significantly, depending upon the nature of their functional head group. In vitro, ex vivo, and in vivo studies have shown that surfactants that cause significant skin irritation interact strongly with skin proteins. Based on this understanding, several surfactants and surfactant mixtures have been identified as "less irritating" mild surfactants because of their diminished interactions with skin proteins. Surfactants that interact minimally with both skin lipids and proteins are especially mild. Another factor that can aggravate surfactant-induced dryness and irritation is the pH of the cleanser. The present authors' recent studies demonstrate that high pH (pH 10) solutions, even in the absence of surfactants, can increase stratum corneum (SC) swelling and alter lipid rigidity, thereby suggesting that cleansers with neutral or acidic pH, close to SC-normal pH 5.5, may be potentially less damaging to the skin. Mildness enhancers and moisturizing agents such as lipids, occlusives, and humectants minimize damaging interactions between surfactants, and skin proteins and lipids, and thereby, reduce skin damage. In addition, these agents play an ameliorative role, replenishing the skin lipids lost during the wash period. The present review discusses the benefits of such agents and their respective roles in improving the overall health of the skin barrier.