Legitimate Target Research Articles

The metadata-driven killing apparatus: big data analytics, the target selection process, and the threat to international humanitarian law

ABSTRACT This article explores the role of metadata analytics in the target selection process to show how such analytics undermines the fundamental principle of international humanitarian law, that is, the principle of distinction between combatants and civilians. The central part of the article is divided into three sections. The first section provides a brief overview of how international humanitarian law draws the line between civilians and legitimate military targets (e.g. members of armed forces, paramilitary groups, organized armed groups, and civilians directly participating in hostilities) in both international and non-international armed conflicts. The second section explores the use of metadata analytics in the target selection process by focusing on two programs, the Real Time – Real Gateway (RT-RG) and SKYNET, developed by the United States to detect deviant ‘terrorist’ behaviour. The third section provides new insights into how metadata analytics creates the circumstances for violations of the principle of distinction. This section focuses on four characteristics of metadata analysis that undermine the principle of distinction (e.g. the inability to make qualitative distinctions between potential targets, the uncertainty of results, the incorporated margin of error, and the unpredictability of target determinations).

Hentai and the Pornification of Childhood: How the Porn Industry Just Made the Case of Regulation

One of the most popular genres of online pornography today is hentai, sexualized animation, and cartoons in the style of Japanese anime. Data from Pornhub, the world’s best-known pornography website, as well as a recent report from a British regulatory agency and our research, show that much of hentai appeals to children and depicts child-like characters engaged in sexual violence. In almost every instance, this violence targets female characters. Hentai, we show, encourages adults to see minors, especially girls, as legitimate targets of sexual violence. Until the day when these depictions of sexual violence are eradicated, we call for three ameliorative steps: age verification legislation; civil lawsuits; and sex education through a porn-critical lens.

Conservation violence: Paradoxes of “making live” and “letting die” in anti-poaching practices

Wildlife poaching has been and continues to be of significant concern to environmental sustainability. While descriptions of poaching often include vivid details about the animal victims and the heroics of those fighting to conserve biodiversity, ambiguity still surrounds ‘the poacher.’ Clarifying the identity of a poacher is necessary to expose a societal tendency to enforce stereotypes on others that perpetuate violence and inequality. Without knowing the identity of a poacher, it becomes easy for society to impose unsubstantiated beliefs upon them that legitimize unjust and violent policies. This research examines how (1) the media and (2) conservation actors construct the identity and context of the poacher to understand how and why violent protected area policies like shoot-to-kill have become accepted conservation strategies. Through a systematic analysis of news articles and primary interviews with conservation actors, we demonstrate how poachers are anonymized, dehumanized, and placed in a space of exception to become legitimate and justifiable targets of violence. We conclude by examining a central paradox that emerges from the state's biopolitical use of violent anti-poaching policies: how does a form of authority that is fundamentally justified in its claims to protect life condone the use of deadly force on its own subjects?

War and Ethics in Islamic Law: A brief Study of the Ratio of War, Rules of Conduct, and Legitimate Targets

War and Ethics in Islamic Law: A brief Study of the Ratio of War, Rules of Conduct, and Legitimate Targets

Murder in war as an ethical problem

The article is devoted to the issue of the principles of moral restraint of warfare according to the division of war participants into legitimate and illegitimate targets of military attacks, which is actively discussed in the ethics of war. The authors analyze two competing ways of differentiating this view, corresponding to two versions of the most popular contemporary ethics of war, the Just War Theory (JWT). One approach assumes symmetric rights for both combatants and non-combatants on both sides of the war, while the other approach allocates rights according to the moral significance of the war in which the actors are involved as well as their contribution to it. The authors show that in both cases an important principle of justice is violated. But the reason for this, they suggest, is that in both cases differentiation is proposed according to a certain distribution of rights. In such a case, the only moral justification for creating a lethal threat to the subject in war is that the subject does not have the right not to be so threatened independent of any of his qualities. However, the authors argue that the proposed justifications for the loss of such a right in war are not sufficient. And from this it must follow that both principles of differentiation are unjust. Nevertheless, they can be fair, according to the authors, if we refuse to consider the presence or absence of the relevant right as the only moral justification for creating a lethal or comparable threat to someone in war.

De novo designing of novel drug-like inhibitors of aldose reductase

Aldose reductase (AR, ALR2) is a member of the aldo-keto reductase superfamily. It is the first and rate-limiting enzyme of the polyol pathway. AR plays an essential role in the development of diabetic complications. It is designated as the most legitimate target for managing diabetic complications. One of the key challenges to the successful development of target-specific AR inhibitors is target selectivity. In this research, target-specific drug-like ALR2 inhibito

Marketing Practices in Small Scale Industries with Special Reference to Units in Industrial Estates Guindy Chennai

The present study is concerned with the marketing practices of the little scale industrial units. A review of the present written work on the subject reveals that the marketing issues of the little scale industrialists have remained a really unmapped extent. The purpose behind this study is to look at to what degree the little representatives get the marketing thought in their marketing decisions for fulfilling legitimate targets. The mission and vision of the affiliation includes in choosing the necessities and requirements of target markets and passing on the pined for fulfilments more effectively and profitably than contenders.

Therapeutic Targeting of TLR4 for Inflammation, Infection, and Cancer: A Perspective for Disaccharide Lipid A Mimetics.

The Toll-like receptor 4 (TLR4) signaling pathway plays a central role in the prompt defense against infectious challenge and provides immediate response to Gram-negative bacterial infection. The TLR4/MD-2 complex can sense and respond to various pathogen-associated molecular patterns (PAMPs) with bacterial lipopolysaccharide (LPS) being the most potent and the most frequently occurring activator of the TLR4-mediated inflammation. TLR4 is believed to be both a friend and foe since improperly regulated TLR4 signaling can result in the overactivation of immune responses leading to sepsis, acute lung injury, or pathologic chronic inflammation involved in cancer and autoimmune disease. TLR4 is also considered a legitimate target for vaccine adjuvant development since its activation can boost the adaptive immune responses. The dual action of the TLR4 complex justifies the efforts in the development of both TLR4 antagonists as antisepsis drug candidates or remedies for chronic inflammatory diseases and TLR4 agonists as vaccine adjuvants or immunotherapeutics. In this review, we provide a brief overview of the biochemical evidences for possible pharmacologic applications of TLR4 ligands as therapeutics and report our systematic studies on the design, synthesis, and immunobiological evaluation of carbohydrate-based TLR4 antagonists with nanomolar affinity for MD-2 as well as disaccharide-based TLR4 agonists with picomolar affinity for the TLR4/MD-2 complex.

The Shifting Face of the Enemy: ‘Less than Lethal’ Weaponry and the Criminalised Protestor

From checkpoints in Palestine and cities in other war-torn places to Istanbul, Ferguson and Paris: anti-riot and other so called ‘non-lethal’ weaponry is used worldwide against civilians by government forces. The use of such violence (even if framed as ‘non- or less-than-lethal’) against protestors in major cities, often turning the city streets into scenes from battle fields, is worrying as it shows an increasing disrespect for human and civil rights by states with an obsession with ‘keeping the order’. What is less visible, however, is how technologies and weapons that are used against protestors, and the ways they are marketed, (re)produce the image of the protestor as a legitimate target. Studying this process in more detail can help understand the criminalisation of protests and protestors along with other democratic tools. In this article I will investigate the global sale and marketing of ‘anti-riot’ or so-called ‘non-lethal’ or ‘less-than-lethal’ weaponry and technology that are used against protestors on a global security market. I will argue that this industry constructs a new enemy and by doing so criminalises our cities’ populations and the democratic tools they have at their disposal to voice their concerns. Instead of looking at police actions of repression of protest, I will thus approach this issue through the weaponry that is used against protestors and what that tells us about repression of their civil rights. I will do this by focussing on the Israeli security industry.

Troubled waters [Crimea - Infrastructure

Following the break-up of the Soviet Union in 1991, there had been protracted discussions between Russia and Ukraine aimed at reaching an agreement for the joint construction of an international road and rail link across the Kerch Strait that separates Russia from the annexed territory of Crimea. Talks eventually broke down, and after the annexation of Crimea the construction of the bridge went ahead without Ukraine's consent. The Crimean Bridge is a controversial feat of engineering, and in October 2022 it was severely damaged by an explosion. The heavily defended infrastructure is a crucial military resupply route for Russian troops and is regarded by the Ukrainian government as a legitimate military target. E&T examines the bridge's complex story, so far.

SARS-CoV-2 Antibody Effectiveness Is Influenced by Non-Epitope Mutation/Binding-Induced Denaturation of the Epitope 3D Architecture.

The public health threat from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to intensify with emerging variants of concern (VOC) aiming to render COVID-19 vaccines/infection-induced antibodies redundant. The SARS-CoV-2 spike protein is responsible for receptor binding and infection of host cells making it a legitimate antibody target. Antibodies mostly target epitopes in the receptor binding domain (RBD). Mutations occurring within epitopes influence antibody specificity and function by altering their 3D architecture. However, the mechanisms by which non-epitope mutations in the RBD influence antibody specificity and function remain a mystery. We used Protein Data Bank (PDB) deposited 3D structures for the original, Beta, Delta, BA.1, and BA.2 RBD proteins in complex with either neutralizing antibodies or Angiotensin-Converting Enzyme 2 (ACE2) to elucidate the structural and mechanistic basis for neutralizing antibody evasion driven by non-epitope amino acid substitutions in the RBD. Since the mechanism behind the extensively reported functional discrepancies between the same antibody when used individually and when used in an antibody cocktail is lacking, we explored the structural basis for this inconsistency. Finally, since SARS-CoV-2 antibodies are viral mutagens, we deciphered determinants for antibody-pressured amino acid substitutions. On the one hand, we show that non-epitope mutations in the RBD domain of SARS-CoV-2 VOC influence the formation of hydrogen bonds in the paratope-epitope interface by repositioning RBD amino-acid sidechains (AASCs). This increases the distance between complementary donor/acceptor atoms on paratope and epitope AASCs leading to weaker or the complete prevention of the formation of hydrogen bonds in the paratope-epitope interface. On the other hand, we show that SARS-CoV-2 VOC employ the same strategy to simultaneously search for complementary donor/acceptor atoms on ACE2 AASCs to form new interactions, potentially favoring increased viral transmission. Additionally, we illustrate that converting the spike protein to an RBD, a deletion mutation, also repositions epitope AASCs and that AASC interactions in the paratope-epitope interface vary when an antibody is used individually versus when utilized as a cocktail with other antibodies. Finally, we show that the process of substituting immunogenic RBD amino acids begins with the repositioning of their AASCs induced by immune/antibody pressure. We show that donor/acceptor atoms from any amino acid can determine cross-reactivity instead, provided they possess and present spatially pairing donor/acceptor atoms. By studying structural alignments for PDB deposited antibody-RBD 3D structures and relating them to published binding and neutralization profiles of the same antibodies, we demonstrate that minor structural alterations such as epitope AASC repositioning have a major impact on antibody effectiveness and, hence, should receive adequate attention given that protein structure dictates protein function.

Legitimate Targets: What is the Applicable Legal Framework Governing the Use of Force in Rio de Janeiro?

Legitimate Targets: What is the Applicable Legal Framework Governing the Use of Force in Rio de Janeiro?

Synthesis of indole derivatives as Alzheimer inhibitors and their molecular docking study

Acetylcholinesterase prevails in the healthy brain, with butyrylcholinesterase reflected to play a minor role in regulating brain acetylcholine (ACh) levels. However, BuChE activity gradually increases in patients with (AD), while AChE activity remains unaffected or decays. Both enzymes therefore represent legitimate therapeutic targets for ameliorating the cholinergic deficit considered to be responsible for the declines in cognitive, behavioural, and global functioning characteristic of AD. Current study described the synthesis of indole-based sulfonamide derivatives (1-23) and their biological activity. Synthesis of these scaffolds were achieved by mixing chloro-substituted indole bearing amine group with various substituted benzene sulfonyl chloride in pyridine, under refluxed condition to obtained desired products. All products were then evaluated for AchE and BuchE inhibitory potential compare with positive Donepezil as standard drug for both AchE and BchE having IC50 = 0.016 ± 0.12 and 0.30 ± 0.010 μM respectively. In this regard analog 9 was found potent having IC50 value 0.15 ± 0.050 μM and 0.20 ± 0.10 for both AchE and BuChE respectively. All other derivatives also found with better potential. All compounds were characterized by various techniques such as 1H, 13C-NMR and HREI-MS. In addition, biological activity was maintained to explore the bioactive nature of scaffolds and their protein-ligand interaction (PLI) was checked through molecular docking study. Communicated by Ramaswamy H. Sarma

Abstract 13344: Endothelin B Receptor Agonist, Sovateltide, Promotes Neural Regeneration by Improving Mitochondria Function in a Neonatal Rat Model of Hypoxic-Ischemic Encephalopathy

Introduction: Our preliminary studies have indicated the role of Endothelin B receptors (ETBR) stimulation in decreasing oxidative stress and cell death after sovateltide treatment following hypoxic-ischemic encephalopathy (HIE) in rat pups, which suggests the involvement of ETBR in neonatal hypoxic-ischemic injury. However, its mechanism of action is not yet established. Therefore, this study investigated the effect of sovateltide on mitochondrial dysfunction and neurogenesis in a neonatal rat model of HIE. Hypothesis : Sovateltide protects neuronal survival via preserving mitochondrial activity. Methods: Sprague-Dawley male and female rat pups grouped separately, were divided into 5 different subgroups (1) Control; (2) HIE + Vehicle; (3) HIE + Hypothermia; (4) HIE + sovateltide; and (5) HIE + sovateltide + hypothermia. HIE was induced by ligating the right carotid artery on a postnatal day (PND) 7, followed by hypoxia for 120 min and hypothermia (32-34°C) for 5 h. On PND 7, sovateltide (5 μg/kg, ICV) was injected after hypoxic-ischemic injury. Pups were euthanized on PND 10. Brains were isolated for analysis of markers for mitochondrial fission and fusion as well as neurogenesis in rat brain tissues using western blots. Results : Animals receiving sovateltide showed a significantly increased expression of neuronal differentiation marker, NeuroD1 (p<0.0001) and DoubleCortin (p<0.001) along with neural marker for mature neurons, NeuN (p<0.001) compared to vehicle. Additionally, an upregulation (p<0.0001) of mitochondrial fusion-related proteins, Mfn2, and downregulation of fission proteins, Drp1, in the sovateltide group compared to the vehicle was observed. Higher neuronal progenitor cell differentiation along with better mitochondrial biogenesis in the brain of sovateltide alone or as an adjunct to hypothermia in rat pups was noted. Similar findings were obtained in both male and female rats. Conclusion : Stimulation of ETBR by sovateltide promotes neural regeneration via maintaining mitochondrial dynamics, indicating a potential neuroprotective effect and may, therefore, offer a legitimate therapeutic target for the treatment of neonatal HI brain injury.

‘We watched his whole life unfold. . .Then you watch the death’: drone tactics, operator trauma, and hidden human costs of contemporary wartime

Scholars of war and combat posit that soldiers are more willing to execute strikes on adversaries when they perceive lower risk to themselves or less connection with their targets. Accordingly, technologies like the drone, which drastically expands the distance between adversaries, should make it easier to strike decisively and without remorse. The empirical record tells a different story. Despite operating very far away from the battle theater, drone operators suffer PTSD at the same rate as pilots of manned aircraft. We argue that this unanticipated consequence of drone warfare stems from the unique way in which drone tactics marry spatial distance and temporal duration. Drone operators surveil their targets via detailed video footage for extended periods of time, both before and after firing, in order to identify or locate potential targets, to measure collateral risks, and afterward to assess a strike’s effectiveness. We argue that the clarity and duration of this surveillance tempers any advantage derived from ‘distance’. Spatial distance protects drone operators from enemy fire but temporal proximity exposes them to greater emotional costs of killing than previously thought. Indeed, prolonged observation temporally extends ‘contact’ and mitigates the dehumanizing effects imputed to distance. This unexpected effect highlights a shifting ethical dilemma. In the formulation of the ‘naked soldier’, combatants in a just war deserve respect due to shared vulnerability. Yet while spatial distance physically protects the drone operator, it also requires that they identify vulnerable and legitimate targets through contemporary timing practices that establish intimate knowledge of that target and may thus denude and even heighten the operator’s emotional vulnerability. While others have argued that contemporary wartime features technologies and tactics that undercut conventions about legitimate combat, we uncover an emerging ethical problem in moral and psychological harms associated with the way that drone warfare trades space for time.

HONEYPOT BASED INTRUSION DETECTION SYSTEM

Honeypot is a computer security mechanism set to detect, deflect or counteract attempts at unauthorized use of information. It has enormous potential for the security community. This can be modeled after any digital asset, including software applications, servers or the network itself. It is intentionally and purposefully designed to look like a legitimate target, resembling the model in terms of structure, components and content and is meant to convince the adversary that they have accessed the actual system and encourage them to spend time within this controlled environment. It acts better than firewalls or intrusion detection system by detecting encrypted attacks in IPv6 networks to capture different types of frauds.

Charting Hinduism's rules of armed conflict: Indian sacred texts and international humanitarian law

AbstractWhat does Hinduism have to say about the rules of armed conflict? How might Hinduism enrich the modern global discourse on international humanitarian law (IHL)? What convergences might be found, and what areas of divergence? This paper examines and contextualizes the rules of armed conflict advocated in classical Hindu texts, especially in the epic Mahābhārata, where important norms of Hinduism are established. It also examines the other major epic, the Rāmāyaṇa, and the Dharmaśāstras (Law Codes), as well as the Arthaśāstra, which takes an alternative (realpolitik) approach. This paper focuses on conduct during armed conflict (jus in bello), now synonymous for many with IHL, rather than considerations leading up to war (jus ad bellum). The paper seeks to illuminate both convergences and divergences with IHL and highlight particular Hindu approaches on the righteous (dharmic) application of violence. Like IHL, classical Hinduism values (1) proportionality of force during armed engagement; (2) the minimization of human suffering during combat; (3) care for survivors of war; (4) immunity towards non-combatants, especially civilians; and (5) balancing military necessity with humanity. With respect to divergences, classical Hinduism extols non-violence in ways that critique even the warrior's duty to engage in righteous war (dharma yuddha). In contrast to IHL, the Hindu epics have some different limitations; for instance, they limit the right to combat to a particular caste, the kṣatriyas, though this concept could be modernized to mean uniformed personnel of the State. The epics also disavow certain practices that are legal under IHL, such as ambushes and surprise attacks against legitimate targets. The Hindu proportionality provision goes beyond IHL by prescribing that only warriors of the same type should fight. With its many deeply ethical considerations, Hinduism enriches modern IHL through its heightened emphasis on fair and humane conduct in battle and its call towards compassion on behalf of both combatants and non-combatants.

Against Aggression? Revisiting an Overlooked Contender for Moral Bioenhancement

In moral bioenhancement (MBE) discourse, aggression has been identified as one potential target of biomedical intervention. Early suggestions that aggression might be modulated to improve moral outcomes were met with strong opposition from those claiming it is impossible to modulate aggression without harming traits of distinct social and agential value. If we are to preclude (or endorse) particular paths to moral enhancement then we ought to establish sound reasons for doing so. However, in paying due consideration to contemporary aggression studies we will see that current efforts to rule out aggression as one such path are untenable. I argue that the rejection of aggression-reduction as a viable target of MBE is a mistake, and that this arises from a rudimentary view of aggression which is incompatible with current scientific consensus. Drawing on contemporary psychological views I argue that it is necessary to distinguish subtypes of aggression, and that once these distinctions are recognised there is a potential space for MBE to target the biological correlates of specific kinds of aggressive behaviour. Ultimately, I suggest that aggression remains a legitimate target of inquiry, and that mitigating deleterious manifestations may yet offer one prospect for MBE.

Towards the discovery of potential RdRp inhibitors for the treatment of COVID-19: structure guided virtual screening, computational ADME and molecular dynamics study.

Coronavirus disease 2019 (COVID-19) has become a major challenge affecting almost every corner of the world, with more than five million deaths worldwide. Despite several efforts, no drug or vaccine has shown the potential to check the ever-mutating SARS-COV-2. The emergence of novel variants is a major concern increasing the need for the discovery of novel therapeutics for the management of this pandemic. Out of several potential drug targets such as S protein, human ACE2, TMPRSS2 (transmembrane protease serine 2), 3CLpro, RdRp, and PLpro (papain-like protease), RNA-dependent RNA polymerase (RdRP) is a vital enzyme for viral RNA replication in the mammalian host cell and is one of the legitimate targets for the development of therapeutics against this disease. In this study, we have performed structure-based virtual screening to identify potential hit compounds against RdRp using molecular docking of a commercially available small molecule library of structurally diverse and drug-like molecules. Since non-optimal ADME properties create hurdles in the clinical development of drugs, we performed detailed in silico ADMET prediction to facilitate the selection of compounds for further studies. The results from the ADMET study indicated that most of the hit compounds had optimal properties. Moreover, to explore the conformational dynamics of protein–ligand interaction, we have performed an atomistic molecular dynamics simulation which indicated a stable interaction throughout the simulation period. We believe that the current findings may assist in the discovery of drug candidates against SARS-CoV-2.

A reflection on the use of Antidepressants to manage agitation in dementia

IntroductionAgitated behaviors is a common neuropsychiatric symptom (NPS) in dementia, defined as inappropriate verbal, vocal, or motor activity that is not thought to be caused by an unmet need. It is frequently reported as a major problem, that impairs the quality of life for the elderly themselves and for caregivers. There has been increasing interest in the use of sedative antidepressants to treat NPS due to concerns over the safety and efficacy of antipsychotics in this setting.ObjectivesWe aim to review clinical evidence of alternatives to antipsychoticst to manage agitation in dementia.MethodsWe conduct a non-systematic review of recent evidence on dementia and agitation, using PubMed/Medline database.ResultsAlthough non-pharmacological interventions are the first-line treatment for agitation, it is a legitimate target for therapeutic intervention and according to previous guidelines, antipsychotic are among the most used drugs, albeit restricted because of side-effects. A substitution strategy to avoid antipsychotic prescription was highly considered, however there is limited evidence to support the use of antidepressants as a safe and effective alternative for agitation in dementia. Studies compare Mirtazapine, Selective serotonin reuptake inhibitors (SSRIs) and Trazodone and a reduced benefit in mortality is observed. However, citalopram was more effective were more likely outpatients for moderately agitation and Mirtazapine reveals being potentially harmful, in different studies.ConclusionsMoving forward, a greater understanding of NPS neurobiology, will help to clarify the efficacy of Antedepressants for the treatment of agitation in dementia. Benefits an also the patient and caregiver preference should be kept in mind.DisclosureNo significant relationships.