Identification and characterization of GRIP domain Golgin PpImh1 from Pichia pastoris

Budding yeast Pichia pastoris has highly advanced secretory pathways resembling mammalian systems, an advantage that makes it a suitable model system to study vesicular trafficking. Golgins are large Golgi‐resident proteins, primarily reported to play role in cargo vesicle capture, but details of such mechanisms are yet to be deciphered. Golgins that localize to the Golgi via their GRIP domain, a C‐terminal Golgi anchoring domain, are known as GRIP domain Golgins. In this present study, we have identified and functionally characterized a homologue of one such GRIP domain Golgin protein, Imh1, from the budding yeast P. pastoris. We have demonstrated that the GRIP domain present at the C‐terminal of P. pastoris Imh1 (PpImh1) functions as its Golgi‐targeting sequence. Using a combination of yeast two‐hybrid analysis, dynamic light scattering and electron microscopy, we have shown that PpImh1 can self‐associate and form a homodimer. Analysis of purified recombinant PpImh1 by CD spectroscopy indicates the presence of an 85% α‐helical structure, a characteristic of high‐content α‐helical coiled‐coil sequences normally present in other Golgin family proteins. Two‐hybrid analysis indicated self‐interaction between C‐terminal fragments, yet N‐terminal fragments do not mediate any such form of self‐interaction, suggesting that PpImh1 may form a parallel dimer. Electron microscopy data indicates that PpImh1 forms extended rod‐like homo‐dimeric molecules with splayed N‐terminal end which can act as a tether for capturing vesicles. Our study provides the first evidence in support of the dimeric Y‐shaped structure for any Golgin in the budding yeast.     

Enhanced functions of vascular and bladder cells on poly-lactic-co-glycolic acid polymers with nanostructured surfaces

Polymers currently utilized for tissue engineering applications do not possess surfaces with nanostructured features. However, the tissue that the polymers will replace is composed of proteins that have nanometer dimensions. Undoubtedly, in situ, cells are accustomed to interacting with surface roughness values in the nanometer regime due to the presence of such proteins in natural tissue. Therefore, the objective of this paper was to design, synthesize and evaluate (using in vitro cellular models) poly-lactic-co-glycolic acid (PLGA) with nanostructured surface features to serve as the next generation of more efficient tissue engineered materials. For this purpose, nanostructured PLGA was created by treating conventional PLGA with various concentrations of NaOH for select periods of time. To eliminate surface chemistry changes created though the etching process, PLGA was cast from silastic molds of NaOH-treated nanostructured PLGA. Results provided the first evidence of increased numbers of vascular cells (specifically, endothelial and aortic smooth muscle cells) and bladder smooth muscle cells on nanostructured compared with conventional PLGA substrates. For this reason, the present results suggest, for the first time, that PLGA should incorporate a high degree of nanostructured surface roughness to enhance tissue regeneration for vascular and bladder applications.     

OMNIDIRECTIONAL HIGH REFLECTOR FOR INFRARED WAVELENGTH

We have purposed the design of omnidirectional high reflectors with wide bandwidth (nearly 6300A⁰) for the infrared wavelength. Using translational matrix method for numerical calculation, it is found that a complete photonic band gap high reflector covering the wavelength region 11500A⁰ to 17800A⁰ is obtained for the quarter wave stack air / (n_L n_H)⁷ / air by using the tellurium (n=4.60) and TiO₂ (n=2.35) as material of high reflective index and SiO₂(n=1.45) low refractive index. Due to high refractive index of contrast of the structure i.e. SiO₂/tellurium, a large complete photonic band gap, omnidirectional high reflector, has been observed for the infrared wavelengths. This type of omnidirectional high reflector can be used in telecommunication. Besides this, we have studied the effective refractive indices (phase and group) of the proposed structures. It is observed that the effective refractive indices (phase and group) of the high omnidirectional reflector band are largely changed near the band edges due to the high refractive index of contrast, and the reflections from the internal interfaces of the structure.     

Adaptive thermal comfort in the residential buildings of north east India—An effect of difference in elevation

Thermal comfort standards are required not only to ensure good indoor climatic condition, but also to optimize the energy used in a building for heating or cooling purposes. Generally, Fanger’s Predicted Mean Vote–Predicted Percentage Dissatisfied (PMV–PPD) model is used by designers and architects to estimate the comfort condition and hence the setpoint temperature inside a building. However, the recent field survey based studies on adaptive thermal comfort suggests that the above used PMV model frequently either underestimates or overestimates the thermal sensation due to the non-inclusion of the adaptive opportunities that a subject may have in maintaining comfortable condition. This leads to often an estimation of higher or lower setpoint temperature than that actually required for maintaining comfort, thereby consuming higher energy. The aim of the research is to study the effect of difference in elevation which is a major factor for temperature difference in hilly terrain, on the thermal comfort of residents. We conducted a field survey in 6 residential buildings at two different elevations in the Darjeeling Himalayan Region of north east India. A total of 1017 questionnaires regarding the indoor occupant thermal comfort were collected from 46 subjects during the monthly survey held in the year 2015. Variations in clothing insulation and other thermal comfort parameters were seen both with difference in elevation and with outdoor environmental conditions.     

Efficient Field Emission from Vertically Aligned Cu2O1‐δ(111) Nanostructure Influenced by Oxygen Vacancy

In the architecture described, cuprous oxide (Cu₂O) is tamed to be highly (111) plane oriented nanostructure through adjusting the deposition postulate by glancing angle deposition technique. In the controlled atmosphere oxygen vacancy is introduced into the Cu₂O crystal subsequently fostering an impurity energy state (E_im) close to the conduction band. Our model of Cu₂O electronic structure using density functional theory suggests that oxygen vacancies enhance the electron donating ability because of unshared d‐electrons of Cu atoms (nearest to the vacancy site), allowing to pin the work function energy level around 0.28 eV compared to the bulk. This result is also complemented by Kelvin probe force microscopy analysis and X‐ray photoelectron spectroscopy method. Oxygen vacancy in Cu₂O (Cu₂O_1‐δ) exhibits promising field emission properties with interesting field electron tunneling behavior at different applied fields. The films show very low turn‐on and threshold voltages of value 0.8 and 2.4 V μm^?1 respectively which is influenced by the oxygen vacancy. Here, a correlation between the work function modulation due to the oxygen vacancy and enhancement of field emission of Cu₂O_1–δ nanostructure is demonstrated. This work reveals a promising new vision for Cu₂O as a low power field emitter device.     

Enhancement of intrinsic optical signal recording with split spectrum optical coherence tomography

Functional optical coherence tomography (OCT) of stimulus-evoked intrinsic optical signal (IOS) promises to be a new methodology for high-resolution mapping of retinal neural dysfunctions. However, its practical applications for non-invasive examination of retinal function have been hindered by the low signal-to-noise ratio (SNR) and small magnitude of IOSs. Split spectrum amplitude-decorrelation has been demonstrated to improve the image quality of OCT angiography. In this study, we exploited split spectrum strategy to improve the sensitivity of IOS recording. The full OCT spectrum was split into multiple spectral bands and IOSs from each sub-band were calculated separately and then combined to generate a single IOS image sequence. The algorithm was tested on in vivo images of frog retinas. It significantly improved both IOS magnitude and SNR, which are essential for practical applications of functional IOS imaging.     

Glycosphingolipids in Diabetes,Oxidative Stress,and Cardiovascular Disease: Prevention in Experimental Animal Models

Diabetes contributes to about 30% morbidity and mortality world-wide and has tidal wave increases in several countries in Asia. Diabetes is a multi-factorial disease compounded by inflammation, dyslipidemia, atherosclerosis, and is sometimes accompanied with gains in body weight. Sphingolipid pathways that interplay in the enhancement of the pathology of this disease may be potential therapeutic targets. Thus, the application of advanced sphingolipidomics may help predict the progression of this disease and therapeutic outcomes in man. Pre-clinical studies using various experimental animal models of diabetes provide valuable information on the role of sphingolipid signaling networks in diabetes and the efficacy of drugs to determine the translatability of innovative discoveries to man. In this review, we discuss three major concepts regarding sphingolipids and diabetes. First, we discuss a possible involvement of a monosialodihexosylceramide (GM3) in insulin–insulin receptor interactions. Second, a potential role for ceramide (Cer) and lactosylceramide (LacCer) in apoptosis and mitochondrial dysfunction is proposed. Third, a larger role of LacCer in antioxidant status and inflammation is discussed. We also discuss how inhibitors of glycosphingolipid synthesis can ameliorate diabetes in experimental animal models.     

Theranostic Small-Molecule Prodrug Conjugates for Targeted Delivery and Controlled Release of Toll-like Receptor 7 Agonists

We previously reported the design and synthesis of a small-molecule drug conjugate (SMDC) platform that demonstrated several advantages over antibody–drug conjugates (ADCs) in terms of in vivo pharmacokinetics, solid tumor penetration, definitive chemical structure, and adaptability for modular synthesis. Constructed on a tri-modal SMDC platform derived from 1,3,5-triazine (TZ) that consists of a targeting moiety (Lys-Urea-Glu) for prostate-specific membrane antigen (PSMA), here we report a novel class of chemically identical theranostic small-molecule prodrug conjugates (T-SMPDCs), [^18/19F]F-TZ(PSMA)-LEGU-TLR7, for PSMA-targeted delivery and controlled release of toll-like receptor 7 (TLR7) agonists to elicit de novo immune response for cancer immunotherapy. In vitro competitive binding assay of [¹⁹F]F-TZ(PSMA)-LEGU-TLR7 showed that the chemical modification of Lys-Urea-Glu did not compromise its binding affinity to PSMA. Receptor-mediated cell internalization upon the PSMA binding of [¹⁸F]F-TZ(PSMA)-LEGU-TLR7 showed a time-dependent increase, indicative of targeted intracellular delivery of the theranostic prodrug conjugate. The designed controlled release of gardiquimod, a TLR7 agonist, was realized by a legumain cleavable linker. We further performed an in vivo PET/CT imaging study that showed significantly higher uptake of [¹⁸F]F-TZ(PSMA)-LEGU-TLR7 in PSMA⁺ PC3-PIP tumors (1.9 ± 0.4% ID/g) than in PSMA⁻ PC3-Flu tumors (0.8 ± 0.3% ID/g) at 1 h post-injection. In addition, the conjugate showed a one-compartment kinetic profile and in vivo stability. Taken together, our proof-of-concept biological evaluation demonstrated the potential of our T-SMPDCs for cancer immunomodulatory therapies.     

A holistic perspective on the theoretical foundations for ICT4D research

ABSTRACT

While many theories have guided research Information and Communication Technologies for Development (ICT4D), we are yet to construct a clear and coherent narrative that would help us answer the question of how ICT fosters development in underdeveloped communities. In this paper, we argue that one of the main reasons for this is that our holistic understanding of ICT4D is seldom grounded in theories to understand the core areas that define the field, namely, ICT, Development, and, ‘4’ which are the transformative processes that link the two. Through a brief literature review, we list theories that have informed ICT4D research in each of these areas. We present examples of theories, namely, Capability Approach, Affordances, and Actor-Network Theory together with Social Capital and illustrate how we have used them in our research. Building on this holistic perspective on theoretical foundation, we propose five agendas for ICT4D research.     

Less is more: compressive sensing in optics and image science

We review an emerging sampling theory, namely compressive sampling, which reproduces signals or images from a much smaller set of samples than that required by the Nyquist–Shannon criterion. This review article outlines the main theoretical concepts surrounding compressive sensing and discusses the relationship among compressive sensing, signal sparsity, and sensing modalities. We also describe the applications of compressive sensing in the field of optics and image science.