An Overview of Partial Least Squares

Partial least squares analysis is a multivariate statistical technique that allows comparison between multiple response variables and multiple explanatory variables. Partial least squares is one of a number of covariance-based statistical methods which are often referred to as structural equation modeling or SEM. It was designed to deal with multiple regression when data has small sample, missing values, or multicollinearity. Partial least squares regression has been demonstrated on both real data and in simulations (Garthwaite, 1994, Tennenhaus, 1998). It has been very popular in hard science, especially chemistry and chemometrics, where there is a big problem with a high number of correlated variables and a limited number of observations. Its use in marketing has been more limited although data has similar problems (Ryan, Rayner, & Morrison, 1999). This paper provides a brief overview of partial least squares (PLS) and its use as an analytical method in marketing research

MAD2L2 promotes open chromatin in embryonic stem cells and derepresses the Dppa3 locus.

The chromatin of naive embryonic stem cells (ESCs) has a largely open configuration, as evident by the lack of condensed heterochromatin and the hypomethylation of DNA. Several molecular mechanisms promoting this constellation were previously identified. Here we present evidence for an important epigenetic function of MAD2L2, a protein originally known for its role in DNA damage repair, and for its requirement in germ cell development. We demonstrate using super-resolution microscopy that numerous MAD2L2 microfoci are exclusively associated with euchromatin, similar to other factors of the DNA damage response. In the absence of MAD2L2 the amount of heterochromatin demarcated by H3K9me2 was significantly increased. Among the most strongly suppressed genes was Dppa3, an ESC- and germ-cell-specific gene regulating DNA methylation. In Mad2l2-deficient ESCs 5-methylcytosine levels were globally increased, while several imprinted genes became hypomethylated and transcriptionally activated. Our results emphasize the important function of MAD2L2 for the open chromatin configuration of ESCs

A user-friendly and accurate machine learning tool for the evaluation of the worldwide yearly photovoltaic electricity production

While traditional methods for modelling the thermal and electrical behaviour of photovoltaic (PV) modules rely on analytical and empirical techniques, machine learning is gaining interest as a way to reduce the time, expertise, and tools required by designers or experts while maintaining high accuracy and reliability. This research presents a data-driven machine learning tool based on artificial neural networks (ANNs) that can forecast yearly PV electricity directly at the optimal PV inclination angle without geographic restrictions and is valid for a wide range of electrical characteristics of PV modules. Additionally, empirical correlations were developed to easily determine the optimal PV inclination angle worldwide. The ANN algorithm, developed in Matlab, systematically and quantitatively summarizes the behaviour of eight PV modules in 48 worldwide climatic conditions. The algorithm's applicability and robustness were proven by considering two different PV modules in the same 48 locations. Yearly climatic variables and electrical/thermal PV module parameters serve as input training data. The yearly PV electricity is derived using dynamic simulations in the TRNSYS environment, which is a simulation program primarily and extensively used in the fields of renewable energy engineering and building simulation for passive as well as active solar design. Multiple performance metrics validate that the ANN-based machine learning tool demonstrates high reliability and accuracy in the PV energy production forecasting for all weather conditions and PV module characteristics. In particular, by using 20 neurons, the highest value of R-square of 0.9797 and the lowest values of the root mean square error and coefficient of variance of 14.67 kWh and 3.8%, respectively, were obtained in the training phase. This high accuracy was confirmed in the ANN validation phase considering other PV modules. An R-square of 0.9218 and values of the root mean square error and coefficient of variance of 31.95 kWh and 7.8%, respectively, were obtained. The results demonstrate the algorithm's vast potential to enhance the worldwide diffusion and economic growth of solar energy, aligned with the seventh sustainable development goal

Front-end electronics for cable reduction in Intracardiac Echocardiography (ICE) catheters

3-D imaging ICE catheters with large element counts present design challenges in achieving simultaneous data readout from all elements while significantly reducing cable count for a small catheter diameter. Current approaches such as microbeamformer techniques tend to rely on area and power hungry circuits, making them undesirable for ICE catheters. In this paper, a system which uses are an efficient real-time programmable on-chip transmit (TX) beamformer circuitry to reduce the cable count on the TX side and analog 8/1 Time Division Multiplexing (TDM) with Direct Digital Demodulation (DDD) to reduce the cable count on the receive (RX) side is presented

Red-Shifted Aequorin Variants Incorporating Non-Canonical Amino Acids: Applications in \u3cem\u3eIn Vivo\u3c/em\u3e Imaging

The increased importance of in vivo diagnostics has posed new demands for imaging technologies. In that regard, there is a need for imaging molecules capable of expanding the applications of current state-of-the-art imaging in vivo diagnostics. To that end, there is a desire for new reporter molecules capable of providing strong signals, are non-toxic, and can be tailored to diagnose or monitor the progression of a number of diseases. Aequorin is a non-toxic photoprotein that can be used as a sensitive marker for bioluminescence in vivo imaging. The sensitivity of aequorin is due to the fact that bioluminescence is a rare phenomenon in nature and, therefore, it does not suffer from autofluorescence, which contributes to background emission. Emission of bioluminescence in the blue-region of the spectrum by aequorin only occurs when calcium, and its luciferin coelenterazine, are bound to the protein and trigger a biochemical reaction that results in light generation. It is this reaction that endows aequorin with unique characteristics, making it ideally suited for a number of applications in bioanalysis and imaging. Herein we report the site-specific incorporation of non-canonical or non-natural amino acids and several coelenterazine analogues, resulting in a catalog of 72 cysteine-free, aequorin variants which expand the potential applications of these photoproteins by providing several red-shifted mutants better suited to use in vivo. In vivo studies in mouse models using the transparent tissue of the eye confirmed the activity of the aequorin variants incorporating L-4-iodophehylalanine and L-4-methoxyphenylalanine after injection into the eye and topical addition of coelenterazine. The signal also remained localized within the eye. This is the first time that aequorin variants incorporating non-canonical amino acids have shown to be active in vivo and useful as reporters in bioluminescence imaging

Single-Chip Reduced-Wire CMUT-on-CMOS System for Intracardiac Echocardiography

CMUT-on-CMOS integration is particularly suitable for catheter based ultrasound imaging applications, where electronics integration enables multiplexing capabilities to reduce the number of electrical connections leading to smaller catheter cable profiles. Here, a single-chip CMUT-on-CMOS system for intracardiac echocardiography (ICE) is presented. In this system, a 64 element 1-D CMUT array is fabricated over an application specific integrated circuit (ASIC) that features a programmable transmit beamformer with high voltage (HV) pulsers and receive circuits using 8:1 time division multiplexing (TDM). Integration of pitch matched 64 channel front-end circuits with CMUT arrays in a single-chip configuration allows for implementation of catheter probes with miniaturization, reduced number of cables, and better mechanical flexibility. The ASIC is implemented in 60 V 0.18 μm HV process. It occupies 2.6×11 mm 2 which can fit in the catheter size of 9F, and reduces the number of wires from more than 64 to 22. This system is used for B-mode imaging of imaging phantoms and its potential application for 2D CMUT-on-CMOS arrays is discussed

Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax(®)

BACKGROUND: Melanoma tumors are known to express antigens that usually induce weak immune responses of short duration. Expression of both tumor-associated antigens p53 and TRP2 by melanoma cells raises the possibility of simultaneously targeting more than one antigen in a therapeutic vaccine. In this report, we show that VacciMax(® )(VM), a novel liposome-based vaccine delivery platform, can increase the immunogenicity of melanoma associated antigens, resulting in tumor elimination. METHODS: C57BL/6 mice bearing B16-F10 melanoma tumors were vaccinated subcutaneously 6 days post tumor implantation with a mixture of synthetic peptides (modified p53: 232–240, TRP-2: 181–188 and PADRE) and CpG. Tumor growth was monitored and antigen-specific splenocyte responses were assayed by ELISPOT. RESULTS: Vaccine formulated in VM increased the number of both TRP2- and p53-specific IFN-γ producing splenocytes following a single vaccination. Vaccine formulated without VM resulted only in enhanced IFN-γ producing splenocytes to one CTL epitopes (TRP2:180–188), suggesting that VM overcomes antigen dominance and enhances immunogenicity of multiple epitopes. Vaccination of mice bearing 6-day old B16-F10 tumors with both TRP2 and p53-peptides formulated in VM successfully eradicated tumors in all mice. A control vaccine which contained all ingredients except liposomes resulted in eradication of tumors in no more than 20% of mice. CONCLUSION: A single administration of VM is capable of inducing an effective CTL response to multiple tumor-associated antigens. The responses generated were able to reject 6-day old B16-F10 tumors

Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax® encapsulated CTL/T helper peptides

The incidence of cancer increases significantly in later life, yet few pre-clinical studies of cancer immunotherapy use mice of advanced age. A novel vaccine delivery platform (VacciMax®,VM) is described that encapsulates antigens and adjuvants in multilamellar liposomes in a water-in-oil emulsion. The therapeutic potential of VM-based vaccines administered as a single dose was tested in HLA-A2 transgenic mice of advanced age (48–58 weeks old) bearing large palpable TC1/A2 tumors. The VM-based vaccines contained one or more peptides having human CTL epitopes derived from HPV 16 E6 and E7. VM formulations contained a single peptide, a mixture of four peptides or the same four peptides linked together in a single long peptide. All VM formulations contained PADRE and CpG as adjuvants and ISA51 as the hydrophobic component of the water-in-oil emulsion. VM-formulated vaccines containing the four peptides as a mixture or linked together in one long peptide eradicated 19-day old established tumors within 21 days of immunization. Peptide-specific cytotoxic cellular responses were confirmed by ELISPOT and intracellular staining for IFN-γ producing CD8+ T cells. Mice rendered tumor-free by vaccination were re-challenged in the opposite flank with 10 million HLF-16 tumor cells, another HLA-A2/E6/E7 expressing tumor cell line. None of these mice developed tumors following the re-challenge. In summary, this report describes a VM-formulated therapeutic vaccine with the following unprecedented outcome: a) eradication of large tumors (> 700 mm3) b) in mice of advanced age c) in less than three weeks post-immunization d) following a single vaccination

Capillary filling with wall corrugations] Capillary filling in microchannels with wall corrugations: A comparative study of the Concus-Finn criterion by continuum, kinetic and atomistic approaches

We study the impact of wall corrugations in microchannels on the process of capillary filling by means of three broadly used methods - Computational Fluid Dynamics (CFD), Lattice-Boltzmann Equations (LBE) and Molecular Dynamics (MD). The numerical results of these approaches are compared and tested against the Concus-Finn (CF) criterion, which predicts pinning of the contact line at rectangular ridges perpendicular to flow for contact angles theta > 45. While for theta = 30, theta = 40 (no flow) and theta = 60 (flow) all methods are found to produce data consistent with the CF criterion, at theta = 50 the numerical experiments provide different results. Whilst pinning of the liquid front is observed both in the LB and CFD simulations, MD simulations show that molecular fluctuations allow front propagation even above the critical value predicted by the deterministic CF criterion, thereby introducing a sensitivity to the obstacle heigth.Comment: 25 pages, 8 figures, Langmuir in pres