Is the Chemical Strategy for Imbuing "Polyene" Character in Diketopyrrolopyrrole-Based Chromophores Sufficient for Singlet Fission?

In this work, we have rationally designed and synthesized a novel thiophene-diketopyrrolopyrrole (TDPP)-vinyl-based dimer. We have investigated the optical and electronic properties and have probed the photophysical dynamics using transient absorption to investigate the possibility of singlet exciton fission. These revealed extremely rapid decay to the ground state (<50 ps), which we confirm is due to intramolecular excitonic processes rather than large-scale conformational change enabled by the vinyl linker. In all cases, the main excited state appears to be “dark”, suggesting rapid internal conversion into a dark 2A$_{g}$-type singlet state. We found no evidence of triplet formation in TDPP-V-TDPP under direct photoexcitation. This may be a consequence of significant singlet stabilization in the dimer, bringing it below the energy needed to form two triplets. Our studies on this model compound set valuable lessons for design of novel triplet-forming materials and highlight the need for more broadly applicable design principles.We thank the NMR Research Centre, Indian Institute of Science, Bangalore for the NMR facility. S.P., R.H.F., and A.J.M. thank UKIERI, British Council for a research grant. T.M. thanks IISc for a Senior Research Fellowship. This work was supported by the Engineering and Physical Sciences Research Council, U.K. (Grant Numbers EP/M005143/1, EP/ G060738/1, and EP/M025330/1: “Hybrid Polaritonics”)

DESIGN AND IN VITRO EVALUATION OF FAST DISSOLVING FILMS CONTAINING HP ß CD INCLUSION COMPLEXES OF LAMOTRIGINE

Objectives: The objectives of the present study is to design and evaluate fast dissolving films of lamotrigine using HP ß CD inclusion complexes with an aim to achieve rapid drug release thereby controlling the seizures in the shortest possible time. Design: Inclusion complexes of lamotrigine were prepared with hydroxypropyl β cyclodextrin (HP β CD) employing different methods to improve the solubility and mask the bitter taste of the drug. Fast dissolving films were prepared by incorporating the developed inclusion complexes and using hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) as film forming agents and other suitable excipients by solvent casting method. Results: Inclusion complexes prepared by ultrasonication method resulted in better solubility and dissolution rate compared to other methods studied. The fast dissolving films prepared using inclusion complexes were found to be transparent and smooth in texture. The thickness, drug content, % moisture absorption and moisture loss, folding endurance and weight variation was found to be uniform. In vitro release profiles were inversely proportional to the polymer and directly proportional to superdisintegrant and plasticizer concentration. Optimized formulations (F8 and F12) were subjected for fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) which revealed the absence of any chemical interactions between the excipients of the formulation. The formulations were found to be stable without any significant changes during the stability studies carried out as per the ICH guidelines. Conclusion: The study revealed the successful development of fast dissolving films of lamotrigine with promising results thereby suggesting the possible use of the developed films in the rapid management of epileptic seizures. Keywords: Fast dissolving films; epilepsy; lamotrigine; inclusion complex; HPMC; PVA; physico-chemical characterization

A Terminal Velocity on the Landscape: Particle Production near Extra Species Loci in Higher Dimensions

We investigate particle production near extra species loci (ESL) in a higher dimensional field space and derive a speed limit in moduli space at weak coupling. This terminal velocity is set by the characteristic ESL-separation and the coupling of the extra degrees of freedom to the moduli, but it is independent of the moduli's potential if the dimensionality of the field space is considerably larger than the dimensionality of the loci, D >> d. Once the terminal velocity is approached, particles are produced at a plethora of nearby ESLs, preventing a further increase in speed via their backreaction. It is possible to drive inflation at the terminal velocity, providing a generalization of trapped inflation with attractive features: we find that more than sixty e-folds of inflation for sub-Planckian excursions in field space are possible if ESLs are ubiquitous, without fine tuning of initial conditions and less tuned potentials. We construct a simple, observationally viable model with a slightly red scalar power-spectrum and suppressed gravitational waves; we comment on the presence of additional observational signatures originating from IR-cascading and individual massive particles. We also show that moduli-trapping at an ESL is suppressed for D >> d, hindering dynamical selection of high-symmetry vacua on the landscape based on this mechanism.Comment: 46 pages, 6 figures. V3: typos corrected compared to JHEP version, conclusions unchange

A cross-sectional comparative study of gut bacterial community of Indian and Finnish children

The human gut microbiome plays a crucial role in the compositional development of gut microbiota. Though well documented in western pediatrics population, little is known about how various host conditions affect populations in different geographic locations such as the Indian subcontinent. Given the impact of distinct environmental conditions, our study assess the gut bacterial diversity of a small cohort of Indian and Finnish children and investigated the influence of FUT2 secretor status and birth mode on the gut microbiome of these populations. Using multiple profiling techniques, we show that the gut bacterial community structure in 13-14-year-old Indian (n = 47) and Finnish (n = 52) children differs significantly. Specifically, Finnish children possessed higher Blautia and Bifidobacterium, while genera Prevotella and Megasphaera were predominant in Indian children. Our study also demonstrates a strong influence of FUT2 and birth mode variants on specific gut bacterial taxa, influence of which was noticed to differ between the two populations under study

Functional mapping of hospitals by diagnosis-dominant case-mix analysis

BACKGROUND: Principles and methods for the allocation of healthcare resources among healthcare providers have long been health policy research issues in many countries. Healthcare reforms including the development of a new case-mix system, Diagnosis Procedure Combination (DPC), and the introduction of a DPC-based payment system are currently underway in Japan, and a methodology for adequately assessing the functions of healthcare providers is needed to determine healthcare resource allocations. METHODS: By two-dimensional mapping of the rarity and complexity of diagnoses for patients receiving treatment, we were able to quantitatively demonstrate differences in the functions of different healthcare service provider groups. RESULTS: On average, inpatients had diseases that were 3.6-times rarer than those seen in outpatients, while major teaching hospitals treated inpatients with diseases 3.0-times rarer on average than those seen at small hospitals. CONCLUSION: We created and evaluated a new indicator for DPC, the diagnosis-dominant case-mix system developed in Japan, whereby the system was used to assess the functions of healthcare service providers. The results suggest that it is possible to apply the case-mix system to the integrated evaluation of outpatient and inpatient healthcare services and to the appropriate allocation of healthcare resources among health service providers

Feasibility of the porous zone approach to modelling vegetation in CFD

Vegetation within stormwater ponds varies seasonly and its presence affects the flow field, which in turn affects the pond’s Residence Time Distribution and its effectiveness at pollutant removal. Vegetated flows are complex and, as a result, few suitable tools exist for evaluating realistic stormwater pond designs. Recent research has suggested using a porous zone to represent vegetation within a CFD model, and this paper investigates the feasibility of this approach using ANSYS Fluent. One of the main benefits of using a porous zone is the ability to derive the relevant parameters from the known physical characteristics of stem diameter and porosity using the Ergun equation. A sensitivity analysis on the viscous resistance factor 1/α1/α and the inertial resistance factor C2C2 has been undertaken by comparing model results to data collected from an experimental vegetated channel. Best fit values of C2C2 were obtained for a range of flow conditions including emergent and submerged vegetation. Results show the CFD model to be insensitive to 1/α1/α but very sensitive to values of C2C2. For submerged vegetation, values of C2C2 derived from the Ergun equation are under-predictions of best-fit C2C2 values as only the turbulence due to the shear layer is represented. The porous zone approach does not take into account turbulence generated from stem wakes such that no meaningful predictions for emergent vegetation were obtained. C2C2 values calculated using a force balance show better agreement with best-fit C2C2 values than those derived from the Ergun equation. Manually fixing values of kk and εε within the porous zone of the model shows initial promise as a means of taking stem wakes into account

Tissue sparing surgery in knee reconstruction: unicompartmental (UKA), patellofemoral (PFA), UKA + PFA, bi-unicompartmental (Bi-UKA) arthroplasties

Recently mini-invasive joint replacement has become one of the hottest topics in the orthopaedic world. However, these terms have been improperly misunderstood as a “key-hole” surgery where traditional components are implanted with shorter surgical approaches, with few benefits and several possible dangers. Small implants as unicompartmental knee prostheses, patellofemoral prostheses and bi-unicompartmental knee prostheses might represent real less invasive procedures: Tissue sparing surgery, the Italian way to minimally invasive surgery (MIS). According to their experience the authors go through this real tissue sparing surgery not limited only to a small incision, but where the surgeons can respect the physiological joint biomechanics

Semaphorin 3A Suppresses Tumor Growth and Metastasis in Mice Melanoma Model

<div><h3>Background</h3><p>Recent understanding on cancer therapy indicated that targeting metastatic signature or angiogenic switch could be a promising and rational approach to combat cancer. Advancement in cancer research has demonstrated the potential role of various tumor suppressor proteins in inhibition of cancer progression. Current studies have shown that axonal sprouting inhibitor, semaphorin 3A (Sema 3A) acts as a potent suppressor of tumor angiogenesis in various cancer models. However, the function of Sema 3A in regulation of melanoma progression is not well studied, and yet to be the subject of intense investigation.</p> <h3>Methodology/Principal Findings</h3><p>In this study, using multiple <em>in vitro</em> and <em>in vivo</em> approaches we have demonstrated that Sema 3A acts as a potent tumor suppressor <em>in vitro</em> and <em>in vivo</em> mice (C57BL/6) models. Mouse melanoma (B16F10) cells overexpressed with Sema 3A resulted in significant inhibition of cell motility, invasiveness and proliferation as well as suppression of <em>in vivo</em> tumor growth, angiogenesis and metastasis in mice models. Moreover, we have observed that Sema 3A overexpressed melanoma clone showed increased sensitivity towards curcumin and Dacarbazine, anti-cancer agents.</p> <h3>Conclusions</h3><p>Our results demonstrate, at least in part, the functional approach underlying Sema 3A mediated inhibition of tumorigenesis and angiogenesis and a clear understanding of such a process may facilitate the development of novel therapeutic strategy for the treatment of cancer.</p> </div

Innovations in total knee replacement: new trends in operative treatment and changes in peri-operative management

The human knee joint can sustain damage due to injury, or more usually osteoarthritis, to one, two or all three of the knee compartments: the medial femorotibial, the lateral femorotibial and the patellofemoral compartments. When pain associated with this damage is unmanageable using nonsurgical techniques, knee replacement surgery might be the most appropriate course of action. This procedure aims to restore a pain-free, fully functional and durable knee joint. Total knee replacement is a well-established treatment modality, and more recently, partial knee replacement—more commonly known as bi- or unicompartmental knee replacement—has seen resurgence in interest and popularity. Combined with the use of minimally invasive surgery (MIS) techniques, gender-specific prosthetics and computer-assisted navigation systems, orthopaedic surgeons are now able to offer patients knee replacement procedures that are associated with (1) minimal risks during and after surgery by avoiding fat embolism, reducing blood loss and minimising soft tissue disruption; (2) smaller incisions; (3) faster and less painful rehabilitation; (4) reduced hospital stay and faster return to normal activities of daily living; (5) an improved range of motion; (6) less requirement for analgesics; and (7) a durable, well-aligned, highly functional knee. With the ongoing advancements in surgical technique, medical technology and prosthesis design, knee replacement surgery is constantly evolving. This review provides a personal account of the recent innovations that have been made, with a particular emphasis on the potential use of MIS techniques combined with computer-assisted navigation systems to treat younger, more physically active patients with resurfacing partial/total implant knee arthroplasty