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One of the most important decisions related to the efficient management of testing phase of software development life cycle is to determine when to stop testing and release the software in the market. Most of the testing processes are imperfect once. In this paper first we have discussed an optimal release time problem for an imperfect faultdebugging model due to Kapur et al considering effect of perfect and imperfect debugging separately on the total expected software cost. Next, we proposed a SRGM incorporating the effect of imperfect fault debugging and error generation. The proposed model is validated on a data set cited in literature and a release time problem is formulated minimizing the expected cost subject to a minimum reliability level to be achieved by the release time using the proposed model. Solution method is discussed to solve such class of problem. A numerical illustration is given for both type of release problem and finally a sensitivity analysis is performed.

Testing phase of a software begins with module testing. During this period modules are tested independently to remove maximum possible number of faults within a specified time limit or testing resource budget. This gives rise to some interesting optimization problems, which are discussed in this paper. Two Optimization models are proposed for optimal allocation of testing resources among the modules of a Software. In the first model, we maximize the total fault removal, subject to budgetary Constraint. In the second model, additional constraint representing aspiration level for fault removals for each module of the software is added. These models are solved using dynamic programming technique. The methods have been illustrated through numerical examples.

ENGLISH ABSTRACT: Numerous Software Reliability Growth Models (SRGMs) have been discussed in the literature. These models are used to predict fault content and reliability of software. It has been observed that the relationship between testing time and the corresponding number of faults removed is either exponential or S-shaped, or a mix of the two. Another important class of SRGMs, known as flexible SRGMs, can depict both exponential and S-shaped growth curves. The paper introduces a new concept of power logistic learning function that proves to be very flexible, in the sense that it represents various curve types – exponential, Rayleigh, Weibull or simple logistic. The flexible nature of the power logistic function gives the flexible SRGM a higher degree of accuracy and wider applicability.AFRIKAANSE OPSOMMING: Verskeie voorbeelde van Betroubaarheidsgroeimodelle vir programmatuur word in die literatuur beskryf. Die modelle word gebruik vir die voorspelling van foutinhoud en programmatuurbetroubaarheid. Daar word waargeneem dat die verband tussen toetstyd en die resulterende foutverwydering eksponensiaal of S-vormig of ‘n kombinasie daarvan is. Aanpasbare modelle insluitende diskrete ekwivalente word ook behandel. Die publikasie ontleed vervolgens algemene plooibare maglogistieke leerkromme met wye toepasbaarheid wat slaan op eksponensiële, Rayleigh-, Weilbull- en logistieke funksies. Die plooibaarheid van die model waarborg akkuraatheid en wye toepasbaarheid met die verlangde gehalte van voorspelbaarheid.

ENGLISH ABSTRACTA Non-Homogenous Poisson Process (NHPP) model whose failure intensity function has the same mathematical form as that of a generalized exponential function was proposed for application as a Software Reliability Growth Model (SRGM). However, in order to facilitate collecting quality metrics pertaining to the degree of imperfect or efficient debugging phenomena and the number of faults left in the software, in this paper the authors propose an extension to the above SRGM. This SRGM enables adequate goodness of fit statistic and predictive validity, even when the software projects witness learning phenomenon of the testing team, either imperfect or perfect or efficient software debugging phenomenon, as well as wide fluctuations in time between failures – either occurring alone or in combinations thereof.AFRIKAANSE OPSOMMING: 'n Nie-homogene Poissonproses (NHPP) waarvan die mislukkingsdigtheidsfunksie soortgelyk is aan 'n algemene eksponensiële funksie word voorgehou as 'n programmatuur-betroubaarheidsgroeimodel (PBGM). Die model lewer toereikende passingsgoedheid en voorspellingsgeldigheid onder uiteenlopende leereienskappe van toetsers, swak of goeie ontfouting van programmatuur, en groot verskille tussen waardes van tyd tussen mislukkings. Die outeurs stel ook voor dat die goedheid van ontfoutingsaksies gemeet word met behulp van 'n uitbreiding van die PBGM-model.

Recent times have witnessed remarkable progress in cancer immunotherapy, drastically changing the cancer treatment landscape. Among the various immunotherapeutic approaches, adoptive cell therapy (ACT), particularly chimeric antigen receptor (CAR) T cell therapy, has emerged as a promising strategy to tackle cancer. CAR-T cells are genetically engineered T cells with synthetic receptors capable of recognising and targeting tumour-specific or tumour-associated antigens. By leveraging the intrinsic cytotoxicity of T cells and enhancing their tumour-targeting specificity, CAR-T cell therapy holds immense potential in achieving long-term remission for cancer patients. However, challenges such as antigen escape and cytokine release syndrome underscore the need for the continued optimisation and refinement of CAR-T cell therapy. Here, we report on the challenges of CAR-T cell therapies and on the efforts focused on innovative CAR design, on diverse therapeutic strategies, and on future directions for this emerging and fast-growing field. The review highlights the significant advances and changes in CAR-T cell therapy, focusing on the design and function of CAR constructs, systematically categorising the different CARs based on their structures and concepts to guide researchers interested in ACT through an ever-changing and complex scenario. UNIVERSAL CARs, engineered to recognise multiple tumour antigens simultaneously, DUAL CARs, and SUPRA CARs are some of the most advanced instances. Non-molecular variant categories including CARs capable of secreting enzymes, such as catalase to reduce oxidative stress in situ, and heparanase to promote infiltration by degrading the extracellular matrix, are also explained. Additionally, we report on CARs influenced or activated by external stimuli like light, heat, oxygen, or nanomaterials. Those strategies and improved CAR constructs in combination with further genetic engineering through CRISPR/Cas9- and TALEN-based approaches for genome editing will pave the way for successful clinical applications that today are just starting to scratch the surface. The frontier lies in bringing those approaches into clinical assessment, aiming for more regulated, safer, and effective CAR-T therapies for cancer patients. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory autoimmune neurological disease characterized by the recurrent appearance of demyelinating lesions and progressive disability. Currently, there are multiple disease-modifying treatments, however, there is a significant need to develop new therapeutic targets, especially for the progressive forms of the disease. This review article provides an overview of the most recent studies aimed at understanding the inflammatory processes that are activated in response to the accumulation of kynurenine pathway (KP) metabolites, which exacerbate an imbalance between immune system cells (e.g., Th1, Th2, and T reg) and promote the release of pro-inflammatory interleukins that modulate different mechanisms: membrane-receptors function; nuclear factors expression; and cellular signals. Together, these alterations trigger cell death mechanisms in brain cells and promote neuron loss and axon demyelination. This hypothesis could represent a remarkable approach for disease-modifying therapies for MS. Here, we also provide a perspective on the repositioning of some already approved drugs involved in other signaling pathways, which could represent new therapeutic strategies for MS treatment. [ABSTRACT FROM AUTHOR]

Introduction: Children born prematurely (<37 weeks' gestation) are at increased risk of perinatal complications, comorbidities, and iron deficiency. Iron deficiency is associated with restless legs syndrome and periodic limb movement disorder. In this study, we assessed the prevalence of restless sleep disorder (RSD) and elevated periodic limb movements during sleep (PLMS) in children born prematurely who underwent polysomnography. Methods: A retrospective chart review of sleep studies was conducted in children aged 1–18 years (median age 4 years) with a history of premature birth. Children with genetic syndrome, airway surgery, or tracheostomy were excluded. Three groups were compared: children with PLMS index >5, children with RSD, and children with neither elevated PLMS index nor RSD. Results: During the study, 2577 sleep studies were reviewed. Ninety-two studies fit our criteria and were included in the analysis. The median age at birth was 31 weeks, and the interquartile range (IQR) was 27–34 weeks. A total of 32 (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring. After polysomnography, 18% were found to have a PLMS index >5/h, and 14% fit the criteria for restless sleep disorder (RSD). There were no statistically significant differences in PSG parameters among the children with RSD, PLMS, and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal–Wallis ANOVA 8.621, p = 0.0135) in the RSD group (median 0.7, IQR 0.3–0.9) than in the PLMS (median 1.7, IQR 0.7–3.5) or the non-RSD/non-PLMS (median 2.0, IQR 0.8–4.5) groups. Conclusions: There was an elevated frequency of RSD and elevated PLMS in our cohort of children born prematurely. Children born prematurely are at higher risk of iron deficiency which can be a contributor factor to sleep -related movement disorders. These results add new knowledge regarding the prevalence of RSD and PLMS in these children. [ABSTRACT FROM AUTHOR]

Our study employs multi-level agent-based modeling and computational techniques to explore education as a complex system. With an underlying focus that education should be underpinned by a scientific understanding of student learning, we created computational models that simulated learning dynamics in classrooms, integrating both quantitative and qualitative insights. Through these models, we conducted experiments aligned with real classroom data to address key questions, such as "How can we effectively support the academic progress of underperforming students, who are disproportionately from low socio-economic status (SES) backgrounds, to close their multi-year achievement gap in mathematics?" Our study analyzes various instructional approaches for mathematical learning, and our findings highlight the potential effectiveness of Productive Failure as an instructional approach. Considerations of the broader applicability of computational methods in advancing educational research are also provided. [ABSTRACT FROM AUTHOR]

Neuroinflammation, a pivotal factor in the pathogenesis of various brain disorders, including neurodegenerative diseases, has become a focal point for therapeutic exploration. This review highlights neuroinflammatory mechanisms that hallmark neurodegenerative diseases and the potential benefits of essential oils in counteracting neuroinflammation and oxidative stress, thereby offering a novel strategy for managing and mitigating the impact of various brain disorders. Essential oils, derived from aromatic plants, have emerged as versatile compounds with a myriad of health benefits. Essential oils exhibit robust antioxidant activity, serving as scavengers of free radicals and contributing to cellular defense against oxidative stress. Furthermore, essential oils showcase anti-inflammatory properties, modulating immune responses and mitigating inflammatory processes implicated in various chronic diseases. The intricate mechanisms by which essential oils and phytomolecules exert their anti-inflammatory and antioxidant effects were explored, shedding light on their multifaceted properties. Notably, we discussed their ability to modulate diverse pathways crucial in maintaining oxidative homeostasis and suppressing inflammatory responses, and their capacity to rescue cognitive deficits observed in preclinical models of neurotoxicity and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Schizophrenia is traditionally associated with the presence of psychotic symptoms. In addition to these, cognitive symptoms precede them and are present during the entire course of the schizophrenia process. The present study aims to establish the relationship between working memory (short-term memory and attention), the features of the clinical picture, and the course of the schizophrenic process, gender distribution and resistance to treatment. Methods: In total, 105 patients with schizophrenia were observed. Of these, 66 were women and 39 men. Clinical status was assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), Dimensional Obsessive–Compulsive Symptom Scale (DOCS), scale for dissociative experiences (DES) and Hamilton Depression Rating Scale (HAM-D)—cognitive functions using the Luria 10-word test with fixation assessment, reproduction and attention analysis. The clinical evaluation of resistance to the treatment showed that 45 patients were resistant to the ongoing medical treatment and the remaining 60 had an effect from the therapy. Results: Our study showed that, in most patients, we found disorders of working memory and attention. In 69.82% of the patients, we found problems with fixation; in 38.1%, problems with reproduction; and in 62.86%, attention disorders. Conducting a regression analysis showed that memory and attention disorders were mainly related to the highly disorganized symptoms scale, the duration of the schizophrenic process and the dissociation scale. It was found that there was a weaker but significant association between the age of onset of schizophrenia and negative symptoms. In the patients with resistant schizophrenia, much greater violations of the studied parameters working memory and attention were found compared to the patients with an effect from the treatment. Conclusion: Impairments in working memory and attention are severely affected in the majority of patients with schizophrenia. Their involvement is most significant in patients with resistance to therapy. Factors associated with the highest degree of memory and attention impairment were disorganized symptoms, duration of schizophrenia, dissociative symptoms and, to a lesser extent, onset of illness. This analysis gives us the right to consider that the early and systematic analysis of cognition is a reliable marker for tracking both clinical dynamics and the effect of treatment. [ABSTRACT FROM AUTHOR]

Metabolic endotoxemia (ME) is characterized by a 2–3-fold increase in blood endotoxin levels and low-grade systemic inflammation without apparent infection. ME is usually accompanied by metabolic syndrome, characterized by central obesity and hyperlipidemia. According to numerous studies, ME may lead to functional brain disorders, including cognitive decline, depression, and dementia. In the current in vitro study, we aimed to determine the direct and indirect impact of endotoxin (LPS) and palmitic acid (PA), representing saturated fatty acids, on the inflammatory and oxidative stress response in the human microglial HMC3 cells unstimulated and stimulated with IFNγ. The study's results revealed that direct HMC3 cell exposition to endotoxin and PA increased inflammatory response measured as levels of IL-6 and MCP-1 released into the medium and PGE2 levels in cell lysates. Moreover, direct HMC3 cell treatment with PA and LPS induced oxidative stress, i.e., ROS and COX-2 production and lipid peroxidation. On the contrary, an indirect effect of LPS and PA on microglial cells, assessed as the impact of macrophage metabolites, was much lower regarding the inflammatory response, although still associated with oxidative stress. Interestingly, IFNγ had a protective effect on microglial cells, reducing the production of pro-inflammatory mediators and oxidative stress in HMC3 cells treated directly and indirectly with LPS and PA. [ABSTRACT FROM AUTHOR]

Schizophrenia is a chronic neuropsychiatric syndrome that significantly impacts daily function and quality of life. All of the available guidelines suggest a combined treatment approach with pharmacologic agents and psychological interventions. However, one in three patients is a non-responder, the effect on negative and cognitive symptoms is limited, and many drug-related adverse effects complicate clinical management. As a result, discovering novel drugs for schizophrenia presents a significant challenge for psychopharmacology. This selective review of the literature aims to outline the current knowledge on the aetiopathogenesis of schizophrenia and to present the recently approved and newly discovered pharmacological substances in treating schizophrenia. We discuss ten novel drugs, three of which have been approved by the FDA (Olanzapine/Samidorphan, Lumateperone, and Pimavanserin). The rest are under clinical trial investigation (Brilaroxazine, Xanomeline/Trospium, Emraclidine, Ulotaront, Sodium Benzoate, Luvadaxistat, and Iclepertin). However, additional basic and clinical research is required not only to improve our understanding of the neurobiology and the potential novel targets in the treatment of schizophrenia, but also to establish more effective therapeutical interventions for the syndrome, including the attenuation of negative and cognitive symptoms and avoiding dopamine blockade-related adverse effects. [ABSTRACT FROM AUTHOR]

We are surrounded by factors called free radicals (FR), which attach to the molecules our body is made of, first among them the endothelium. Even though FR are to a certain extent a normal factor, nowadays we face an escalating increase in these biologically aggressive molecules. The escalating formation of FR is linked to the increased usage of man-made chemicals for personal care (toothpaste, shampoo, bubble bath, etc.), domestic laundry and dish-washer detergents, and also an ever wider usage of drugs (both prescription and over the counter), especially if they are to be used long-term (years). In addition, tobacco smoking, processed foods, pesticides, various chronic infectious microbes, nutritional deficiencies, lack of sun exposure, and, finally, with a markedly increasing impact, electromagnetic pollution (a terribly destructive factor), can increase the risk of cancer, as well as endothelial dysfunction, owing to the increased production of FR that they cause. All these factors create endothelial damage, but the organism may be able to repair such damage thanks to the intervention of the immune system supported by antioxidants. However, one other factor can perpetuate the state of inflammation, namely obesity and metabolic syndrome with associated hyperinsulinemia. In this review, the role of FR, with a special emphasis on their origin, and of antioxidants, is explored from the perspective of their role in causing atherosclerosis, in particular at the coronary level. [ABSTRACT FROM AUTHOR]

Despite the use of highly active antiretroviral therapy approved by the United States Food and Drug Administration (FDA) for the treatment of human immunodeficiency virus (HIV) infection, HIV remains a public health concern due to the inability of the treatment to eradicate the virus. In this study, N-methyl-N-phenyl dithiocarbamate complexes of indium(III), bismuth(III), antimony(III), silver(I), and copper(II) were synthesized. The complexes were characterized by thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). The N-methyl-N-phenyl dithiocarbamate complexes were then evaluated for their antiviral effects against HIV-1 subtypes A (Q168), B (QHO.168), and C (CAP210 and ZM53). The results showed that the copper(II)-bis (N-methyl-N-phenyl dithiocarbamate) complex had a neutralization efficiency of 94% for CAP210, 54% for ZM53, 45% for Q168, and 63% for QHO.168. The silver(I)-bis (N-methyl-N-phenyl dithiocarbamate) complex showed minimal neutralization efficiency against HIV, while indium(III) and antimony(III) N-methyl-N-phenyl dithiocarbamate complexes had no antiviral activity against HIV-1. The findings revealed that copper(II)-bis (N-methyl-N-phenyl dithiocarbamate), with further improvement, could be explored as an alternative entry inhibitor for HIV. [ABSTRACT FROM AUTHOR]

Treatment resistant schizophrenia (TRS) is characterized by a lack of, or suboptimal response to, antipsychotic agents. The biological underpinnings of this clinical condition are still scarcely understood. Since all antipsychotics block dopamine D2 receptors (D2R), dopamine-related mechanisms should be considered the main candidates in the neurobiology of antipsychotic non-response, although other neurotransmitter systems play a role. The aims of this review are: (i) to recapitulate and critically appraise the relevant literature on dopamine-related mechanisms of TRS; (ii) to discuss the methodological limitations of the studies so far conducted and delineate a theoretical framework on dopamine mechanisms of TRS; and (iii) to highlight future perspectives of research and unmet needs. Dopamine-related neurobiological mechanisms of TRS may be multiple and putatively subdivided into three biological points: (1) D2R-related, including increased D2R levels; increased density of D2Rs in the high-affinity state; aberrant D2R dimer or heteromer formation; imbalance between D2R short and long variants; extrastriatal D2Rs; (2) presynaptic dopamine, including low or normal dopamine synthesis and/or release compared to responder patients; and (3) exaggerated postsynaptic D2R-mediated neurotransmission. Future points to be addressed are: (i) a more neurobiologically-oriented phenotypic categorization of TRS; (ii) implementation of neurobiological studies by directly comparing treatment resistant vs. treatment responder patients; (iii) development of a reliable animal model of non-response to antipsychotics. [ABSTRACT FROM AUTHOR]

Antioxidants in sports exercise training remain a debated research topic. Plant-derived polyphenol supplements are frequently used by athletes to reduce the negative effects of exercise-induced oxidative stress, accelerate the recovery of muscular function, and enhance performance. These processes can be efficiently modulated by antioxidant supplementation. The existing literature has failed to provide unequivocal evidence that dietary polyphenols should be promoted specifically among athletes. This narrative review summarizes the current knowledge regarding polyphenols' bioavailability, their role in exercise-induced oxidative stress, antioxidant status, and supplementation strategies in athletes. Overall, we draw attention to the paucity of available evidence suggesting that most antioxidant substances are beneficial to athletes. Additional research is necessary to reveal more fully their impact on exercise-induced oxidative stress and athletes' antioxidant status, as well as optimal dosing methods. [ABSTRACT FROM AUTHOR]

Antioxidants have been widely studied in the fields of biology, medicine, food, and nutrition sciences. There has been extensive work on developing assays for foods and biological systems. The scientific communities have well-accepted the effectiveness of endogenous antioxidants generated in the body. However, the health efficacy and the possible action of exogenous dietary antioxidants are still questionable. This may be attributed to several factors, including a lack of basic understanding of the interaction of exogenous antioxidants in the body, the lack of agreement of the different antioxidant assays, and the lack of specificity of the assays, which leads to an inability to relate specific dietary antioxidants to health outcomes. Hence, there is significant doubt regarding the relationship between dietary antioxidants to human health. In this review, we documented the variations in the current methodologies, their mechanisms, and the highly varying values for six common food substrates (fruits, vegetables, processed foods, grains, legumes, milk, and dairy-related products). Finally, we discuss the strengths and weaknesses of the antioxidant assays and examine the challenges in correlating the antioxidant activity of foods to human health. [ABSTRACT FROM AUTHOR]

Global climate change is rightly receiving increasing attention, including in the field of education. Climate change education (CCE) is becoming one of the key areas of education in general and it is therefore not surprising that more attention is also being paid to climate education research. This review study presents an analysis of papers focusing on climate education for ISCED (International Standard Classification of Education) 1 and 2 students. The selection of the analyzed sources follows the PRISMA 2020 statement; out of 850 identified records, 43 made it into the analysis. Articles that met each of the following criteria were included in the analysis: (i) the impact of the article meets the inclusion in the Web of Science Core Collection service, (ii) the article was published in the period 2001–2020, (iii) the central theme of the article is CCE, (iv) the target audience is ISCED 1, ISCED 2 students or their teachers, (v) the article has a research character with the presentation of methodology and results, or it is a review study that includes an analysis of the records meeting the criteria described above. The quantitative description of the results shows the diversity in journals publishing studies, the exponential increase in their number in recent years, and the hegemony of the United States in this field of research. The qualitative content analysis shows that the most frequently addressed topics focus on knowledge, behavior, actions, experiences, and attitudes. The results show that as the urgency of climate change increases, so do the number and diversity of research studies on climate education for the target group. Most of these studies focus on the mitigation behaviors and willingness to act of students. [ABSTRACT FROM AUTHOR]

Background: Good knowledge and appropriate attitude and practice about antibiotic use and resistance among the general population, are significant contributors to minimize the development of antibiotic resistance. We aimed to study the knowledge, attitude, and practice (KAP) regarding antibiotic use, resistance to upper respiratory tract infections (URTI), and associated factors with KAP, among the population attending a mass gathering in India. Methods: A cross-sectional study was conducted in 2016 during a mass gathering held in Ujjain city of Central India. A self-administered, pre-tested questionnaire consisting of 28 questions was used to collect data on demographic characteristics, KAP related to antibiotic use, resistance, and URTI. Descriptive analyses were used to describe participants' responses. Participants were divided into poor or good knowledge and appropriate or inappropriate groups of attitude and practice. Multivariable logistic regression models were used to examine the associations between demographic characteristics, URTI knowledge, and each domain of KAP. All statistical analyses were performed using Stata 16.0. The significance level was set at 5%. Results: A total of 1915 participants consented to participate (response rate 92.7%) with a mean age of 39.3 (±14.7). Complete data on socio-demographics were available for 1619 participants. Of these, 59% were male, and 61% had an education level below high school. Eighty-nine percent of participants had poor knowledge about URTI. A majority of the respondents defined antibiotics incorrectly (93%) and were classified as having poor knowledge (97%). Most of the participants (63%) could not mention any contributors to the irrational use of antibiotics. Appropriate attitudes were observed in 40% of participants, 87% denied to comply with the prescribed course of antibiotics and 88.5% had inappropriate responses for practice. Age of the respondent, sex, education, occupation, and knowledge about URTI, were the main factors associated with the KAP. Conclusions: KAP about antibiotic use and resistance among the general population in India was poor. Knowledge about URTI is strongly associated with KAP. Community interventions, i.e., educational campaigns, should be designed and implemented promptly considering the differences in demographics of the target audience. [ABSTRACT FROM AUTHOR]

Although schizophrenia is currently conceptualized as being characterized as a syndrome that includes a collection of signs and symptoms, there is strong evidence of heterogeneous and complex underpinned etiological, etiopathogenetic, and psychopathological mechanisms, which are still under investigation. Therefore, the present viewpoint review is aimed at providing some insights into the recently investigated schizophrenia research fields in order to discuss the potential future research directions in schizophrenia research. The traditional schizophrenia construct and diagnosis were progressively revised and revisited, based on the recently emerging neurobiological, genetic, and epidemiological research. Moreover, innovative diagnostic and therapeutic approaches are pointed to build a new construct, allowing the development of better clinical and treatment outcomes and characterization for schizophrenic individuals, considering a more patient-centered, personalized, and tailored-based dimensional approach. Further translational studies are needed in order to integrate neurobiological, genetic, and environmental studies into clinical practice and to help clinicians and researchers to understand how to redesign a new schizophrenia construct. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus (HIV) is one of the most prevalent diseases globally. It is estimated that 37.7 million people are infected with HIV globally, and 8.2 million persons are infected with the virus in South Africa. The highly active antiretroviral therapy (HAART) involves combining various types of antiretroviral drugs that are dependent on the infected person's viral load. HAART helps regulate the viral load and prevents its associated symptoms from progressing into acquired immune deficiency syndrome (AIDS). Despite its success in prolonging HIV-infected patients' lifespans, the use of HAART promotes metabolic syndrome (MetS) through an inflammatory pathway, excess production of reactive oxygen species (ROS), and mitochondrial dysfunction. Interestingly, Spirulina platensis (SP), a blue-green microalgae commonly used as a traditional food by Mexican and African people, has been demonstrated to mitigate MetS by regulating oxidative and inflammatory pathways. SP is also a potent antioxidant that has been shown to exhibit immunological, anticancer, anti-inflammatory, anti-aging, antidiabetic, antibacterial, and antiviral properties. This review is aimed at highlighting the biochemical mechanism of SP with a focus on studies linking SP to the inhibition of HIV, inflammation, and oxidative stress. Further, we propose SP as a potential supplement for HIV-infected persons on lifelong HAART. [ABSTRACT FROM AUTHOR]

The complexity of the retinal structure reflects on the difficulty to describe its composite cell interactions. Microglia is responsible for the immune reaction to inflammatory stimuli during diabetic retinopathy (DR), but most studies still use rodent cells. We characterized a commercially available immortalized human microglial line and tested its susceptibility to inflammation, to study the interactions between the neuro-vascular retinal portions in species-specific models. After checking the expression of microglial markers, we tried lipopolysaccharide (LPS) stimulation and several pro-inflammatory cocktails to select the best combination able to induce a significant M1 (inflammatory) response. We measured M1 induction through the expression of pro- and anti-inflammatory molecules and performed morphologic and functional assays. Marker expression confirmed the human microglial derivation of these cells. Differently from rodents, LPS did not induce a M1 profile. The best pro-inflammatory stimulus was an interleukin-1β + tumor necrosis factor-α + interferon-γ cocktail, which induced morphology changes and increased proliferation, apoptosis, migration, reactive oxygen species, and the expression of inflammatory cytokines and miRNAs. In conclusion, this microglial line proved potentially useful to investigate the cascade of events leading to DR. In perspective, co-culture models involving microvascular cells will help in the understanding of multifaceted interactions of the neurovascular unit. [ABSTRACT FROM AUTHOR]

Psychedelics such as lysergic acid diethylamide (LSD), psilocybin (magic mushrooms), and mescaline exhibit intense effects on the human brain and behaviour. In recent years, there has been a surge in studies investigating these drugs because clinical studies have shown that these once banned drugs are well tolerated and efficacious in medically supervised low doses called microdosing. Psychedelics have demonstrated efficacy in treating neuropsychiatric maladies such as difficult to treat anxiety, depression, mood disorders, obsessive compulsive disorders, suicidal ideation, posttraumatic stress disorder, and also in treating substance use disorders. The primary mode of action of psychedelics is activation of serotonin 5-HT2A receptors affecting cognition and brain connectivity through the modulation of several downstream signalling pathways via complex molecular mechanisms. Some atypical antipsychotic drugs (APDs) primarily exhibit pharmacological actions through 5-HT2A receptors, which are also the target of psychedelic drugs. Psychedelic drugs including the newer second generation along with the glutamatergic APDs are thought to mediate pharmacological actions through a common pathway, i.e., a complex serotonin–glutamate receptor interaction in cortical neurons of pyramidal origin. Furthermore, psychedelic drugs have been reported to act via a complex interplay between 5HT2A, mGlu2/3, and NMDA receptors to mediate neurobehavioral and pharmacological actions. Findings from recent studies have suggested that serotoninergic and glutamatergic neurotransmissions are very closely connected in producing pharmacological responses to psychedelics and antipsychotic medication. Emerging hypotheses suggest that psychedelics work through brain resetting mechanisms. Hence, there is a need to dig deeply into psychedelic neurobiology to uncover how psychedelics could best be used as scientific tools to benefit psychiatric disorders including schizophrenia. [ABSTRACT FROM AUTHOR]

Software reliability growth models (SRGM) are used to assess modular software quantitatively and predict the reliability of each of the modules during module testing phase. In the last few decades various SRGM's have been proposed in literature. However, it is difficult to select the best model from a plethora of models available. To reduce this difficulty, unified modeling approaches have been proposed by many researchers. In this paper we present a generalized framework for software reliability growth modeling with respect to testing effort expenditure and incorporate the faults of different severity. We have used different standard probability distribution functions for representing failure observation and fault detection/ correction times. The faults in the software are labeled as simple, hard and complex faults. Developing reliable modular software is necessary. But, at the same time the testing effort available during the testing time is limited. Consequently, it is important for the project manager to allocate these limited resources among the modules optimally during the testing process. In this paper we have formulated an optimization problem in which the total number of faults removed from modular software is (which include simple, hard and complex faults) maximized subject to budgetary and reliability constraints. To solve the optimization problem we have used genetic algorithm. One numerical example has been discussed to illustrate the solution of the formulated optimal effort allocation problem. [ABSTRACT FROM AUTHOR]

Purpose: Software testing is needed to produce extremely reliable software products. A crucial decision problem that the software developer encounters is to ascertain when to terminate the testing process and when to release the software system in the market. With the growing need to deliver quality software, the critical assessment of reliability, cost of testing and release time strategy is requisite for project managers. This study seeks to examine the reliability of the software system by proposing a generalized testing coverage-based software reliability growth model (SRGM) that incorporates the effect of testing efforts and change point. Moreover, the strategic software time-to-market policy based on costreliability criteria is suggested. Design/methodology/approach: The fault detection process is modeled as a composite function of testing coverage, testing efforts and the continuation time of the testing process. Also, to assimilate factual scenarios, the current research exhibits the influence of software users refer as reporters in the fault detection process. Thus, this study models the reliability growth phenomenon by integrating the number of reporters and the number of instructions executed in the field environment. Besides, it is presumed that the managers release the software early to capture maximum market share and continue the testing process for an added period in the user environment. The multiattribute utility theory (MAUT) is applied to solve the optimization model with release time and testing termination time as two decision variables. Findings: The practical applicability and performance of the proposed methodology are demonstrated through real-life software failure data. The findings of the empirical analysis have shown the superiority of the present study as compared to conventional approaches. Originality/value: This study is the first attempt to assimilate testing coverage phenomenon in joint optimization of software time to market and testing duration. [ABSTRACT FROM AUTHOR]

Growth of automobile industry plays a significant role in the Indian Economy. Global warming and increased pollution levels force all countries to revisit their environmental policies towards achieving sustainability. In this view, the automobile industry is under tremendous pressure from both customers and government for sustainable development. Therefore, Indian automobile industry focuses on business improvement through profitability enhancement as well as environmental development through sustainable lean manufacturing. Critical success factors (CSFs) for sustainable lean manufacturing are identified from existing literature, and experts' guidance has been considered to carry out the inter-relationship between CSFs in sustainable lean manufacturing implementation using Interpretive Structural Modelling (ISM) methodology. Top management identified as the influential CSFs, which help in implementation of SLM and leading other CSFs. Driving and dependent factors are also summarized in an Indian automobile industry perspective. The result of research based on data collection from small-, medium- and large-scale automobile sectors. It has been analysed earlier that sustainable manufacturing (lean and green practices) delivers superior results. Hence, the automobile industry needs to adopt sustainable lean manufacturing for achieving economy, social and environmental growth. lean manufacturing. Critical success factors (CSFs) for sustainable lean manufacturing are identified from existing literature, and experts' guidance has been considered to carry out the inter-relationship between CSFs in sustainable lean manufacturing implementation using Interpretive Structural Modelling (ISM) methodology. Top management identified as the influential CSFs, which help in implementation of SLM and leading other CSFs. Driving and dependent factors are also summarized in an Indian automobile industry perspective. The result of research based on data collection from small-, medium- and large-scale automobile sectors. It has been analysed earlier that sustainable manufacturing (lean and green practices) delivers superior results. Hence, the automobile industry needs to adopt sustainable lean manufacturing for achieving economy, social and environmental growth. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to develop a parsimonious and innovative model that captures the dynamics of new product diffusion in the recent high-technology markets and thus assist both academicians and practitioners who are eager to understand the diffusion phenomena. Accordingly, this study develops a novel diffusion model to forecast the demand by centering on the dynamic state of the product's adoption rate. The proposed study also integrates the consumer's psychological point of view on price change and goodwill of the innovation in the diffusion process. Design/methodology/approach: In this study, a two-dimensional distribution function has been derived using Cobb–Douglas's production function to combine the effect of price change and continuation time (goodwill) of the technology in the market. Focused on the realistic scenario of sales growth, the model also assimilates the time-to-time variation in the adoption rate (hazard rate) of the innovation owing to companies changing marketing and pricing strategies. The time-instance upon which the adoption rate alters is termed as change-point. Findings: For validation purpose, the developed model is fitted on the actual sales and price data set of dynamic random access memory (DRAM) semiconductors, liquid crystal display (LCD) monitors and room air-conditioners using non-linear least squares estimation procedure. The results indicate that the proposed model has better forecasting efficiency than the conventional diffusion models. Research limitations/implications: The developed model is intrinsically restricted to a single generation diffusion process. However, technological innovations appear in generations. Therefore, this study also yields additional plausible directions for future analysis by extending the diffusion process in a multi-generational environment. Practical implications: This study aims to assist marketing managers in determining the long-term performance of the technology innovation and examine the influence of fluctuating price on product demand. Besides, it also incorporates the dynamic tendency of adoption rate in modeling the diffusion process of technological innovations. This will support the managers in understanding the practical implications of different marketing and promotional strategies on the adoption rate. Originality/value: This is the first attempt to study the value-based diffusion model that includes key interactions between goodwill of the innovation, price dynamics and change-point for anticipating the sales behavior of technological products. [ABSTRACT FROM AUTHOR]

The article reveals information on guest editors who gave their valuable contribution towards publication of the periodical "International Journal of Reliability, Quality & Safety Engineering." The two guest editors are--P.K. Kapur, who is a Professor and the Head in the Department of Operational Research, University of Delhi. The other editor is Ajit Kumar Verma, who has been with IIT Bombay as a faculty since 1988. His areas of research in reliability engineering are interdisciplinary applications in software engineering, computing, maintenance and power systems.

The article features a calendar of events in the period of December 2, 2006 up to November 7, 2007. Topics for the conferences will include quality, reliability, Infocom technology, system integration, reliability improvements, reliability and safety engineering, maintainability, European safety and reliability, and mathematical methods in reliability.

The article presents a calendar of events in different countries. A conference titled "Third International Conference on Quality, Reliability and Infocom Technology (ICQRIT-2006)" is scheduled on December 2-4, 2006 at the Indian National Science Academy in New Delhi, India. The "European Safety and Reliability Conference (ESREL 2007)" is slated on June 25-27, 2007 in Stavanger, Norway.

Strategic innovation diffusion converts newly created knowledge into increasing a firm’s value primarily through innovative product offerings. In this paper, we present a time-based adoption pattern with pricing and promotional expenditure as a three-dimensional innovation diffusion model (3D-IDM). In our proposed 3D-IDM, we assume that value of the product plays a crucial role of being the major driver of diffusion, and is classified into the following three main factors: (1) continuation time of the product in the market - representing goodwill of the product; (2) price of the product - indicating consumers’ buying behaviour; and (3) marketing efforts of the firm. A special form of the Cobb-Douglas production function is used to design the three-dimensional framework. An empirical study is performed on number of consumer-durable sales data to validate and compare the proposed model. Various performance measures are treated uniquely using the Mahalanobis distance-based approach (DBA) to determine the relative strength of each model. [ABSTRACT FROM AUTHOR]

In this paper, a two-warehouse inventory problem has been investigated under inflation with different deterioration effects in two separate warehouses (rented warehouse, RW, and owned warehouse, OW). The objective of this investigation is to determine the lot-size of the cycle of the two-warehouse inventory system by minimizing the average cost of the system. Considering different inventory policies, the corresponding models have been formulated for linear trend in demand and interval valued cost parameters. In OW, shortages, if any, are allowed and partially backlogged with a variable rate dependent on the duration of the waiting time up to the arrival of the next lot. The corresponding optimization problems have been formulated as non-linear constrained optimization problems with interval parameters. These problems have been solved by an efficient soft computing method, viz. practical swarm optimization. To illustrate the model, a numerical example has been solved with different partially backlogging rates. Then to study the effect of changes of different system parameters on the optimal policy, sensitivity analyses have been carried out graphically by changing one parameter at a time and keeping the others at their original values. Finally, a fruitful conclusion has been reached regarding the selection of an appropriate inventory policy of the two-warehouse system. [ABSTRACT FROM PUBLISHER]