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Mesoporous silica nanoparticles (MSNPs) are inorganic nanoparticles that have been comprehensively investigated and are intended to deliver therapeutic agents. MSNPs have revolutionized the therapy for various conditions, especially cancer and infectious diseases. In this article, the viability of MSNPs' administration for lung cancer therapy has been reviewed. However, certain challenges lay ahead in the successful translation such as toxicology, immunology, large-scale production, and regulatory matters have made it extremely difficult to translate such discoveries from the bench to the bedside. This review highlights recent developments, characteristics, mechanism of action and customization for targeted delivery. This review also covers the most recent data that sheds light on MSNPs' extraordinary therapeutic potential in fighting lung cancer as well as future hurdles. Article highlights Background Lung cancer (LC) is one of the leading causes of cancer-related mortality worldwide. It has been estimated that 19.5 million novel tumor instances and 6.09 million fatalities happened in 2022. The conventional therapies are not successful in the treatment of LC, because of the resistance of LC cells against the usual chemotherapeutic agents. There is an urgent need for the development of innovative illness treatment techniques. This paper highlights the potential of mesoporous silica nanoparticles (MSNPs) in LC. Molecular mechanism of LC & inhibitory pathways LC is characterized by a neoplastic metamorphosis of epithelial cells of the lungs. LC is not only induced by mutations, but molecular alterations of the anaplastic lymphoma kinase gene are also the prevalent inducer of LC. The article highlights the mechanism and various inhibitory pathways in LC. Diagnosis & treatment methods for LC The article highlights various diagnosis strategies including physical evaluation, analysis of blood and urine samples, x-ray, MRI, computed tomography scan, positron emission tomography (PET) scan, etc. The multifactorial treatments including surgery, chemotherapy, radiotherapy, radiosurgery, and immunotherapy for LC have also been discussed in the article. Two potential targeting strategies, i.e., passive targeting and active targeting are employed as a potential approach to anticancer therapy. Emergence of nanomaterials & role of MSNPs in LC MSNPs have revolutionized the therapy for various conditions, especially cancer and infectious diseases. MSNPs are excellent and unique carriers for drug delivery and cancer therapy owing to their suitable features. The surface functionalization of MSNPs is extremely crucial to increase their effectiveness in vivo while lowering their toxicity. MSNPs are typically employed in pulmonary drug-delivery systems through the process of passive diffusion. Advantages & disadvantages of MSNPs MSNPs possess an ordered structure which is very appropriate for packing high amounts of drug moieties. The toxicology of MSNPs toward specific cell lines may be due to the presence of surface silanolates and/or the formation of silica reactive oxygen species. The structural modifications of MSNPs minimize their toxicities and influence the accumulation and biodegradation rate. Conclusion & Future Perspective MSNPs have demonstrated significant benefits over other nanocarriers in terms of anticancer drug delivery. Employing MSNPs and the EPR effect, neoteric therapeutic strategies can be used to alleviate LC. Prior to clinical trials, it is also essential to standardize any exterior functionalization approaches. [ABSTRACT FROM AUTHOR]

Over the recent years, responsiveness has gained importance as it is a critical element of public governance processes and acts as a driving factor for supporting the achievement of governance objectives, especially in the implementation phases. In this study, we identify the knowledge gaps in the realm of responsive governance based on a systematic literature review. Based on our analysis, we propose a conceptual framework of major building blocks (input, process and outcomes) for the development and implementation of responsive governance at the local, regional and national levels of administrative hierarchy. [ABSTRACT FROM AUTHOR]

Tofacitinib is a first-generation JAK inhibitor approved by the US FDA for treating rheumatoid arthritis. It exhibits a broad-spectrum inhibitory effect with abilities to block JAK-STAT signalling. The primary objective of this review is to obtain knowledge about cutting-edge methods for effectively treating a variety of skin problems by including tofacitinib into formulations that are based on nanocarriers. The review also highlights clinical trials and offers an update on published clinical patents. Nanocarriers provide superior performance compared to conventional treatments in terms of efficacy, stability, drug bioavailability, target selectivity and sustained drug release. Current review has the potential to make significant contributions to the ongoing discussion involving dermatological treatments and the prospective impact of nanotechnology on transforming healthcare within this field. [ABSTRACT FROM AUTHOR]

We present Locksynth, a tool that automatically derives synchronization needed for destructive updates to concurrent data structures that involve a constant number of shared heap memory write operations. Locksynth serves as the implementation of our prior work on deriving abstract synchronization code. Designing concurrent data structures involves inferring correct synchronization code starting with a prior understanding of the sequential data structure's operations. Further, an understanding of shared memory model and the synchronization primitives is also required. The reasoning involved transforming a sequential data structure into its concurrent version can be performed using Answer Set Programming, and we mechanized our approach in previous work. The reasoning involves deduction and abduction that can be succinctly modeled in ASP. We assume that the abstract sequential code of the data structure's operations is provided, alongside axioms that describe concurrent behavior. This information is used to automatically derive concurrent code for that data structure, such as dictionary operations for linked lists and binary search trees that involve a constant number of destructive update operations. We also are able to infer the correct set of locks (but not code synthesis) for external height-balanced binary search trees that involve left/right tree rotations. Locksynth performs the analyses required to infer correct sets of locks and as a final step, also derives the C++ synchronization code for the synthesized data structures. We also provide a performance analysis of the C++ code synthesized by Locksynth with the hand-crafted versions available from the Synchrobench microbenchmark suite. To the best of our knowledge, our tool is the first to employ ASP as a backend reasoner to perform concurrent data structure synthesis. [ABSTRACT FROM AUTHOR]

A cross-sectional, representative sample from adolescent girls of higher senior secondary schools was collected for the study. We analyzed the data from 600 Punjabi Indian female adolescents (200 from humanities, 200 from commerce, and 200 from science stream) aged 15-17 years who were randomly selected from government and private schools. The symptoms of depression, anxiety, and stress were assessed by the DAS questionnaire. Overall prevalence was 50.8%, 58.7%, and 68% for depression, anxiety, and stress, respectively. A significant difference was reported for depression (.000), anxiety (.000), and stress (.002) between adolescents of three streams. The results of the study point out that there is a necessity for some interventions to educate adolescent girls about the negative effects of stress, depression, and anxiety on their body. [ABSTRACT FROM AUTHOR]

In the present investigation, an attempt was made to formulate timolol maleate (TML) loaded polymeric nanoparticles of flax seed gum (FX) and chitosan (CH) for ocular delivery using ionic gelation method. The process of nanoparticle preparation was optimized using 2-factor, 3-level central composite experimental design. The optimal concentration of FX and CH that yielded nanoparticles with minimum particle size (267.06 ± 8.65 nm) and maximum encapsulation efficiency (74.96 ± 4.78%) was found to be 0.10% w/v and 0.08% w/v, respectively. The formulated nanoparticles revealed considerable bioadhesive strength and exhibited sustained release of drug in in vitro diffusion studies. The ex vivo transcorneal penetration study revealed higher corneal penetration of TML compared to marketed eye drops. The confocal scanning laser microscopy (CSLM) studies also confirmed the ability of nanoparticles to penetrate into deeper layers of cornea. The histopathological studies revealed corneal biocompatibility of nanoparticles. The nanoparticles were found to reduce the intra ocular pressure (IOP) in rabbits for prolonged period when compared to conventional eye drops. The results of the present study suggested a promising role of polymeric nanoparticles for ocular drug delivery in treatment of glaucoma. [ABSTRACT FROM AUTHOR]

Currently, biomedical, food, and pharmaceutical industries are exploring biocompatible, biodegradable, and readily available polymers as an alternative to synthetic polymers. The naturally occurring galactomannans comprising of galactopyranosyl (Gal) and mannopyranosyl (Man) residues are an attractive alternative to synthetic polymers due to their wide availability, and easily maniputable physical, and chemical properties. In the present study, a natural polymer, Leucaenea leucocephala galactomannan (LLG) was extracted from the seeds of Leucaenea leucocephala by an aqueous method, derivatized by reductive amination process using ethylene diamine as aminating agent to form aminated LLG (AMLLG). The conditions for amination were optimized by varying the concentration of aminating agent, temperature of the reaction mixture and time of reaction and their effect on degree of substitution was determined. The derivatized galactomannan was characterized by FTIR, DSC, XRD, SEM and zeta potential analysis. The texture properties (firmness, consistency, and cohesiveness) and bioadhesive strength of AMLLG was also determined. Furthermore, the antimicrobial potential of AMLLG was evaluated against Escherichia coli and Staphylococcus aureus suggesting better antibacterial activity of AMLLG than chitosan (standard). Overall, the study highlights that the amine derivative of LLG could be a promising candidate as preservative in food industry and as a drug delivery vehicle in pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this paper is to demonstrate the development of key supply chain capabilities in the Indian public sector-run liquefied petroleum gas (LPG) supply chain. This case study has relevance to emerging markets grappling with problems caused by monopolies and subsidies. Furthermore, this case study not only aims to improve operations of the LPG supply chain, but also re-designs its supply network to meet customers’ expectations. It illustrates value creation through growth in non-domestic sales, a reduction in consumption of subsidized LPG as a consequence of better understanding of customer needs and customer diversity, process re-engineering and deployment of ICT systems, and change management and capability building across various LPG stakeholders.Design/methodology/approach An interpretive research methodology is applied, using an illustrative single case study of the Indian public sector-run LPG supply chain. The research methodology is iterative and exploratory in nature, consisting of a back and forth process between extant literature and the field, as well as in-depth discussions/interviews with senior management, distributors, and consumers.Findings Key supply chain capabilities of an integrated and seamless ICT system, detection and blocking of duplicate/ghost connections, the capping of entitlements, and coordination and collaboration across various stakeholders result in value creation for all stakeholders. When such collaboration across stakeholders’ spans both vertically and horizontally through the supply chain, change management and capability building drive value creation through policy interventions and initiatives.Practical implications This study provides an illustrative example of meeting customers’ expectations, increasing consumer convenience, and improving service levels, amidst the complex subsidy challenges in LPG distribution in India. The economic and environmental benefits, as well as increased customer satisfaction, from policy interventions regarding value creation in supply chains, have implications for similar public sector-run schemes.Social implications As a result of the various policy changes, the LPG subsidy was restricted to legitimate customers, reducing the fiscal burden on the Indian Government. Furthermore, seamless ICT-introduced efficiencies for government, distributers, and customers were attained.Originality/value This research articulates the capture, creation, and appropriation of value through the deployment of new supply chain initiatives in a large, complex environment, in particular the public sector-run LPG supply chain. [ABSTRACT FROM AUTHOR]

We use the under-recognized income accounting identity to provide an important theoretical basis for using the Cobb-Douglas production function in IT productivity analyses. Within the income accounting identity we partition capital into non-IT and IT capital and analytically derive an accounting identity (AI)-based Cobb-Douglas form that both nests the three-input Cobb-Douglas and provides additional terms based on wage rates and rates of return to non-IT and IT capital. To empirically confirm the theoretical derivation, we use a specially constructed data set from a subset of the U.S. manufacturing industry that involve elaborate calculations of rates of return—a data set that is infeasible to obtain for most productivity studies—to estimate the standard Cobb-Douglas and our AI-based form. We find that estimates from our AI-based form correspond with those of the Cobb-Douglas, and our AI-based form has significantly greater explanatory power. In addition, empirical estimation of both forms is relatively robust to the assumption of intertemporally stable input shares required to derive the AI-based form, although there may be limits. Thus, in the context of future research the Cobb-Douglas form and its application in IT productivity work have a theoretically and empirically supported basis in the accounting identity. A poor fit to data or unexpected coefficient estimates suggests problems with data quality or intertemporally unstable input shares. Our work also shows how some returns to IT that do not show up in output elasticities can be found in total factor productivity (TFP)—the novel ways inputs are combined to produce output. The critical insight for future research is that many unobservables that have been considered part of TFP can be manifested in rates of return to IT capital, non-IT capital, and labor—rates of return that are separated from TFP in our AI-based form. Finally, finding that the additional rates of return terms partially explain TFP confirms the need for future IT productivity researchers to incorporate time-varying TFP in their models. [ABSTRACT FROM AUTHOR]

ABSTRACT Designing a drug delivery system to target the eye is an interesting and challenging endeavor faced by scientists because of the critical and pharmacokinetically-specific environment that exists in the eye. Topical administration of ophthalmic drugs is used to alleviate the symptoms and signs caused by ocular surface inflammatory disorders, to treat infections, for glaucoma or intraocular inflammation (uveitis). However, the responsiveness toward the conventionally developed drug delivery system is limited because of the presence of several types of barriers in the eye that impede the effective passage of many drugs leading to minimal dose absorption. Ion activated in situ gelling ocular systems undergo phase transition in the presence of cations (present in the tear fluid), thus enhancing the residence time of drug in the cornea. In the present study natural polysaccharides (pectin alone or in combination with sodium alginate) or a pectin derivative (thiolated pectin [TP] alone or in combination with sodium alginate) were used to formulate in situ gelling eye drops. The formulations were evaluated for their gelling capacity, rheological studies, spreadability, bioadhesion strength, and in vitro drug release. Thiolation of pectin was observed to result in an increase in the gelling behavior, viscosity, and bioadhesive strength. The formulations comprising pectin alone (P7), combination of pectin and sodium alginate (P5SA1) or TP6 demonstrated good in vitro release characteristics. The optimized formulations displayed a significant decrease in the intraocular pressure as compared to the marketed formulation upon instillation in rabbit eye. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39788. [ABSTRACT FROM AUTHOR]

The gag reflex is a normal involuntary defense mechanism that prevents foreign bodies from entering the trachea, pharynx or larynx. The patient who gags may present with a range of disruptive reaction, from simple contraction of palatal or circumoral musculature to spasm of the pharyngeal structures, accompanied by vomiting. Factors that are believed to be important in etiology are; Local and systemic disorders, Anatomic factors, Psychological factors, Iatrogenic factors. Management of gagging includes-Clinical techniques, Psychological technique, Surgical technique, and Pharmacological management. [ABSTRACT FROM AUTHOR]

Many studies measure the value of information technology (IT) by focusing on how much value is added rather than on the mechanisms that drive value addition. We argue that value from IT arises not only directly through changes in the factor input mix but also indirectly through IT-enabled augmentation of non-IT inputs and changes in the underlying production technology. We develop an augmented form of the Cobb- Douglas production function to separate and measure different productivity-enhancing effects of IT. Using industry-level data from the manufacturing sector, we find evidence that both direct and indirect effects of IT are significant. Partitioning industries into IT-intensive and non-IT-intensive, we find that the indirect effects of IT predominate in the IT-intensive sector. In contrast, the direct effects of IT predominate in the non-IT intensive sector. These results indicate structural differences in the role of IT in production between industries that are IT-intensive and those that are not. The implication for decision-makers is that for IT-intensive industries the gains from IT come primarily through indirect effects such as the augmentation of non-IT capital and labor. [ABSTRACT FROM AUTHOR]

Given a distributed computation and a global predicate, predicate detection involves determining whether there exists at least one consistent cut (or global state) of the computation that satisfies the predicate. On the other hand, computation slicing is concerned with computing the smallest subcomputation (with the least number of consistent cuts) that contains all consistent cuts of the computation satisfying the predicate. In this paper, we investigate the relationship between predicate detection and computation slicing and show that the two problems are actually equivalent. Specifically, given an algorithm to detect a predicate b in a computation C, we derive an algorithm to compute the slice of C with respect to b. The time complexity of the (derived) slicing algorithm is O(n∣E∣T), where n is the number of processes, E is the set of events, and O(T) is the time complexity of the detection algorithm. We discuss how the "equivalence" result of this paper can be utilized to derive a faster algorithm for solving the genera/predicate detection problem in many cases. Slicing algorithms described in our earlier papers are all offline in nature. In this paper, we also present two online algorithms for computing the slice. The first algorithm can be used to compute the slice for a general predicate. Its amortized time complexity is O(n(c+n)T) per event, where c is the average concurrency in the computation and O(T) is the time complexity of the detection algorithm. The second algorithm can be used to compute the slice for a regular predicate. Its amortized time complexity is only O(n2) per event. [ABSTRACT FROM AUTHOR]

The group mutual exclusion problem extends the traditional mutual exclusion problem by associating a type (or a group) with each critical section. In this problem, processes requesting critical sections of the same type can execute their critical sections concurrently. However, processes requesting critical sections of different types must execute their critical sections in a mutually exclusive manner. We present a distributed algorithm for solving the group mutual exclusion problem based on the notion of surrogate-quorum. Intuitively, our algorithm uses the quorum that has been successfully locked by a request as a surrogate to service other compatible requests for the same type of critical section. Unlike the existing quorum-based algorithms for group mutual exclusion, our algorithm achieves a low message complexity of O(q) and a low (amortized) bit-message complexity of O(bqr), where q is the maximum size of a quorum, b is the maximum number of processes from which a node can receive critical section requests, and r is the maximum size of a request while maintaining both synchronization delay and waiting time at two message hops. As opposed to some existing quorum-based algorithms, our algorithm can adapt without performance penalties to dynamic changes in the set of groups. Our simulation results indicate that our algorithm outperforms the existing quorum-based algorithms for group mutual exclusion by as much as 45 percent in some cases. We also discuss how our algorithm can be extended to satisfy certain desirable properties such as concurrent entry and unnecessary blocking freedom. [ABSTRACT FROM AUTHOR]

An important problem in distributed systems is to detect termination of a distributed computation. A computation is said to have terminated when all processes have become passive and all channels have become empty. In this paper, we present a suite of algorithms for detecting termination of a non-diffusing computation for an arbitrary communication topology under a variety of conditions. All our termination detection algorithms have optimal message complexity. Furthermore, they have optimal detection latency when message processing time is ignored. [ABSTRACT FROM AUTHOR]

Determining order relationship between events of a distributed computation is a fundamental problem in distributed systems which has applications in many areas including debugging, visualization, checkpointing and recovery. Fidge/Mattern’s vector-clock mechanism captures the order relationship using a vector of size N in a system consisting of N processes. As a result, it incurs message and space overhead of N integers. Many distributed applications use synchronous messages for communication. It is therefore natural to ask whether it is possible to reduce the timestamping overhead for such applications. In this paper, we present a new approach for timestamping messages and events of a synchronously ordered computation, that is, when processes communicate using synchronous messages. Our approach depends on decomposing edges in the communication topology into mutually disjoint edge groups such that each edge group either forms a star or a triangle. We show that, to accurately capture the order relationship between synchronous messages, it is sufficient to use one component per edge group in the vector instead of one component per process. Timestamps for events are only slightly bigger than timestamps for messages. Many common communication topologies such as ring, grid and hypercube can be decomposed into $${\lceil N/2 \rceil}$$ edge groups, resulting in almost 50% improvement in both space and communication overheads. We prove that the problem of computing an optimal edge decomposition of a communication topology is NP-complete in general. We also present a heuristic algorithm for computing an edge decomposition whose size is within a factor of two of the optimal. We prove that, in the worst case, it is not possible to timestamp messages of a synchronously ordered computation using a vector containing fewer than $${2 \lfloor N/6 \rfloor}$$ components when N ≥ 2. Finally, we show that messages in a synchronously ordered computation can always be timestamped in an offline manner using a vector of size at most $${\lfloor N/2 \rfloor}$$ . [ABSTRACT FROM AUTHOR]

Writing correct distributed programs is hard. In spite of extensive testing and debugging, software faults persist even in commercial grade software. Many distributed systems should be able to operate properly even in the presence of software faults. Monitoring the execution of a distributed system, and, on detecting a fault, initiating the appropriate corrective action is an important way to tolerate such faults. This gives rise to the predicate detection problem which requires finding whether there exists a consistent cut of a given computation that satisfies a given global predicate.Detecting a predicate in a computation is, however, an NP-complete problem in general. In order to ameliorate the associated combinatorial explosion problem, we introduce the notion of computation slice. Formally, the slice of a computation with respect to a predicate is a (sub)computation with the least number of consistent cuts that contains all consistent cuts of the computation satisfying the predicate. Intuitively, slice is a concise representation of those consistent cuts of a computation that satisfy a certain condition. To detect a predicate, rather than searching the state-space of the computation, it is much more efficient to search the state-space of the slice.We prove that the slice of a computation is uniquely defined for all predicates. We also present efficient algorithms for computing the slice for several useful classes of predicates. For an arbitrary predicate, we establish that the problem of computing the slice is NP-complete in general. Nonetheless, for such a predicate, we develop an efficient heuristic algorithm for computing anapproximateslice. Our experimental results demonstrate that slicing can lead to an exponential improvement over existing techniques for predicate detection in terms of time and space. [ABSTRACT FROM AUTHOR]

Correct distributed programs are hard to write. Not surprisingly, distributed systems are especially vulnerable to software faults. Testing and debugging is an important way to improve the reliability of distributed systems. A distributed debugger equipped with the mechanism to re-execute the traced computation in a controlled fashion can greatly facilitate the detection and localization of bugs. This approach gives rise to a general problem of predicate control, which takes a computation and a safety property specified on the computation as inputs, and produces a controlled computation, with added synchronization, that maintains the given safety property as output. We devise efficient control algorithms for two classes of useful predicates, namely region predicates and disjunctive predicates. For the former, we prove that the control algorithm is optimal in the sense that it guarantees maximum concurrency possible in the controlled computation. For the latter, we prove that our control algorithm generates the least number of synchronization dependencies and therefore has optimal message-complexity. Furthermore, we provide a necessary and sufficient condition under which it is possible to efficiently compute a minimal controlling synchronization for a general predicate. We also give an algorithm to compute such a synchronization under the condition provided. [ABSTRACT FROM AUTHOR]

This article presents an outline of the procedures involved in constructing an ear prosthesis employing a customised three-piece stone mould for processing room temperature vulcanized silicone. The critical steps are emphasized in making the impression, sculpturing, and processing procedures to insure the quality of the prosthetic replacement. [ABSTRACT FROM AUTHOR]

We present a novel key predistribution scheme that uses deployment knowledge to divide deployment regions into overlapping clusters, each of which has its own distinct key space. Through careful construction of these clusters, network resilience is improved, without compromising connectivity or communications overhead. Experimental results show significant improvement in performance over existing schemes based on deployment knowledge. [ABSTRACT FROM AUTHOR]