Defense Program Research Articles

Reluctant and Illegal Migrants in Mao's China: Civil Defense Evacuation in the Tianjin Region, 1969–1980

AbstractMore than 100,000 people from the city of Tianjin were evacuated to the countryside in a civil defense program during the 1970s. Many evacuees refused to submit to state migration mandates, instead sneaking back to the city illegally or petitioning to regain urban residency. City officials responded flexibly to the evacuees’ pleas, sympathizing with family reunification and treating suburban districts (jiaoqu) on the outskirts of Tianjin as a buffer zone between city and countryside. Dominated by agriculture but home to a growing number of factories, workshops, and offices during the 1970s, jiaoqu became a solution to evacuation headaches. When compared with the recent coerced movement of hundreds of thousands of Chinese citizens on national security grounds, the civil defense evacuations of the 1970s suggest that it may be misguided to think of the Mao Zedong years as a faraway time that was more radical or repressive than China today.

Human guanylate binding proteins: nanomachines orchestrating host defense.

Disease-causing microorganisms not only breach anatomical barriers and invade tissues but also frequently enter host cells, nutrient-enriched environments amenable to support parasitic microbial growth. Protection from many infectious diseases is therefore reliant on the ability of individual host cells to combat intracellular infections through the execution of cell-autonomous defense programs. Central players in human cell-autonomous immunity are members of the family of dynamin-related guanylate binding proteins (GBPs). The importance of these interferon-inducible GTPases in host defense to viral, bacterial, and protozoan pathogens has been established for some time; only recently, cell biological and biochemical studies that largely focused on the prenylated paralogs GBP1, GBP2, and GBP5 have provided us with robust molecular frameworks for GBP-mediated immunity. Specifically, the recent characterization of GBP1 as a bona fide pattern recognition receptor for bacterial lipopolysaccharide (LPS) disrupting the integrity of bacterial outer membranes through LPS aggregation, the discovery of a link between hydrolysis-induced GMP production by GBP1 and inflammasome activation, and the classification of GBP2 and GBP5 as inhibitors of viral envelope glycoprotein processing via suppression of the host endoprotease furin have paved the way for a vastly improved conceptual understanding of the molecular mechanisms by which GBP nanomachines execute cell-autonomous immunity. The herein discussed models incorporate our current knowledge of the antimicrobial, proinflammatory, and biochemical properties of human GBPs and thereby provide testable hypotheses that will guide future studies into the intricacies of GBP-controlled host defense and their role in human disease.

Readiness of rural schoolchildrenfor delivery of norms “Ready for labor and defense”

The question of theoretical and practical readiness of rural schoolchildren to pass the norms of the All-Russian physical culture and sports complex for work and defense. The results of a questionnaire conducted among students of a rural school, as well as pedagogical testing data, are presented. The significance of the program-normative basis for the development of mass sports and the improvement of the nation is quite large. The implementation of the “Ready for Labor and Defense” complex should cover all sectors of the population, especially the younger generation. The implementation of the complex has difficulties in educational organizations, including in rural schools. The following methods were used to solve the tasks: the method of analysis of literary sources, the method of questioning (questionnaire), pedagogical testing. The study was conducted on the basis of the Andogo Secondary School Municipal budgetary educational institution (Kaduy district of the Vologda region). In total, 60 rural school students took part in the study (55 % were boys, 45 % were girls). An analysis of literary sources has shown that the problem of implementing the “TRP” program in rural schools is relevant. Identified gaps in the development of physical qualities of students. The analysis of the results of a survey of students. It has been established that the implementation of the All-Russian sports complex Ready for work and defense program in a rural school is not sufficiently effective. Not all students are involved in the process of passing standards. There are gaps in theoretical knowledge on the main issues of this program for the development of mass sports and the improvement of the nation. Students showed low interest in passing the “Ready for work and defense” standards. Based on pedagogical testing, it was revealed that the indicators of development of students' physical qualities were reduced. The study made it possible to establish that the readiness of rural schoolchildren to pass the standards of the All-Russian physical culture and sports complex for work and defense is at a low level.

Twenty first century development in the Hungarian Defence Forces : The KC-390 tactical military transport aircraft

The paper gives a short historical overview of the types of aircraft representing airlift capabilities in certain periods of the life of the Hungarian Defence Forces and pays tribute to air and ground operations personnel. Describing the military transport aircraft capabilities to be developed within the framework of the Zrínyi Defence and Military Development Program, the reader will gain insight into the ever evolving he reader will gain insight into the ever evolving nature of complex airlift capabilities and the tasks resulting from participation in Alliance, international and domestic missions. The article provides a detailed description of the new, soon to be acquired military transport aircraft Embraer KC-390 Millennium.

The Human Challenges of Modernising the Air Force

The aim of my article is to provide an overview of the capability development of the Air Force’s fleet within the framework of the Zrínyi National Defence and Armed Forces Development Program and the effects of the related tasks that fundamentally affect the operator and maintenance personnel. The article briefly describes the peculiarities of the organisational culture of the Air Force, the age and position of the available personnel, which is the initial knowledge necessary for the planning of the recruitment. The article covers the complex security policy, social and technological environment to which the selection system applied by the Hungarian Armed Forces must be adapted, and which is the key to successful training and success indicators. Through personal reports, the article seeks to present a real situation about the challenges and motivations and path-finding of the personnel currently serving in military aviation.

Challenges of the Application of Lynx KF-41 Infantry Fighting Vehicle in the Hungarian Defence Forces

Continuous changes in the world and Europe have posed new challenges to NATO. The Russian–Ukrainian conflict that began in 2014 has shown that, in addition to the fight against terrorism and peace operations, the possibility of procedures and confrontations in the traditional sense must not be forgotten either. In the 21st century, the battlefield conflicts are already taking place in a complex and rapidly changing environment that requires forces to keep pace with change because that is the only way they can perform their duties successfully. In response to the challenges listed, the Hungarian Government launched the Zrínyi 2026 Defence and Armed Forces Development Program, a full-spectrum force development program aimed at making the Hungarian Armed Forces a dominant force in the region. Among the developments affecting the shooting range of the program, the regularisation of the Lynx KF-41 infantry fighting vehicle should be highlighted. Due to its capabilities, the new Western instrument is sufficiently feasible for the battlefields of the future, but the procedures that we used before IFOR, i.e. the Eastern military equipment can no longer be applied. In our study, we present the features, modern challenges that a modern battlefield poses for a combat vehicle. We analyse the unique features of the Lynx Kf-41 and the challenges that will require vehicle application and team training in the future.

The Effect of National Weekly COVID-19 Screening Testing of All Workers in Long-Term Care Facilities: A Decrease in Mortality

Background: Outbreaks of Coronavirus 2019 (COVID-19) in Long-Term Care Facilities (LTCFs) have resulted mainly from disease transmission by asymptomatic health care workers (HCW's). It is not known whether routine COVID-19 screening tests carried out on HCW's would reduce mortality of LTCF residents. Since mid-July 2020, the Israeli national LTCF defense program – "Senior Shield" - has used weekly COVID-19 PCR tests on all LTCF employees. Methods: A nationwide, government funded, screening program on all LTCF personnel for four months during the second COVID-19 wave. We evaluated differences between the two waves in the national LTCF's system with regard to hospitalizations and mortality. Estimation of national health system predicted outcomes, in the absence of this weekly screening plan, was calculated. Findings: COVID-19 tests were taken weekly in all 1,107 LTCFs which includes 62,159 HCWs and 100,046 residents. A median of 55,282 (range – 16,249) tests were performed each week. Turnaround time from sampling to result was less than 24 hours in 95% of tests. Compared to the first wave, in which 45.3% of national mortality was attributed to the LTCF's, the second wave saw a 33.8% reduction in this mortality ratio. Estimation of national health system outcomes during the second wave showed that the activation of the screening program reduced hospital load by 35% and prevented 30% of national mortality from COVID-19.Interpretation: Routine weekly COVID-19 PCR testing of all LTCF employees may reduce national hospitalizations and mortality.Funding Statement: None to declare. Declaration of Interests: None to declare.Ethics Approval Statement: The study was determined to be exempt by the Institutional Review Board of Soroka University Medical Center and thus informed consent was not required (0429-20-SOR).

Tourism Village Government Program, Characterized By State Defense as the Economic Foundation of National Defense

Abstract: The Covid-19 pandemic has impacted the global, regional and national strategic environment. the economic sector is an area that is greatly affected as a whole. The current condition must immediately find an effective and efficient solution so that it does not become a more serious threat to the defense of the State. The method used in this paper is descriptive qualitative henomenology using the theory of defense policy implementation by Lukman Yudho Prakoso which states that defense policy implementation can run well if you pay attention to the factors of Integrative, Interactive, Transparency, Controling and Accountability (IITCA). The results showed that the economic handling between the central and regional governments had not yet been integrated, interactive communication was still a major obstacle, with the arrest of the Minister of Social Affairs showing that there were still major problems related to transparency, controlling and accountability factors. The tourism village is one of the programs initiated by the government in the midst of the Covid-19 pandemic, which is expected to cause economic activity, especially in the field, so that this program is considered optimal as well to equip the state defense program for all parties involved, so that it is not vulnerable to being infiltrated by parties - irresponsible parties. The conclusion of this paper is in accordance with the theory of Kasih Prihantoro, so that the tourism village program with the character of defending the country as the foundation of the defense economy can run well, an effective and efficient netwok must be built and there must be a party acting as a driver force Keywords: State Defense, Covid-19, Tourism Village, Defense Economy

DEVELOPMENT STRATEGIC OF SIMULATOR TECHNOLOGY 4.5 GENERATION FIGHTER AIRCRAFT FOR SUPPORTING NATIONAL DEFENSE SYSTEM

<div><p class="Els-history-head">The fighter aircraft project is one of the defense and security equipment (alpalhankam or alat peralatan pertahanan dan keamanan) priority programs contained in the defense industry roadmap. Indonesia and South Korea undertook a joint development program in developing 4.5 generation fighter aircraft. However, Indonesia experiences several obstacles in the development of fighter aircraft, one of which is the ability of disparity and mastery of fighter technology. One of the critical components used as one of the development programs is simulator technology development. Mastery of simulator technology can improve the ability of Technology Readiness Level (TRL) from technology development fighter aircraft and can cause multiplier effects in other fields. Therefore we need a development strategy that is appropriate for the development of simulator technology. This study aims to analyze and define the benchmark level of performance or from the critical components which will then be used as a reference for the development strategy of the 4.5 generation fighter simulator for joint development projects. The method used in this study is a mixed-method with an approach system engineering uses quality function deployment tools and Critical Technology Element (CTE) technology assessment to identify which CTE then used as a reference strategy for the development of fighter simulator technology. The results of the study show that there are several CTE values along with simulator technology performance scores, among others mission 92.5%, data 83.56%, motion 52.51%, and strategic options that can be used in the technological development of fighter simulator generation 4.5 such as strategic joint development, self-development, and local content/offset.</p></div><div> </div>

Bioshield: Linking Bioscience, Biosecurity and Strategic Plan for Biodefense in Pandemics

Biological threats, whether intentional, unintentional or natural are considered most dangerous hazards worldwide, seriously affecting the health system and global economy. In 21st century where scientists were busy to create superhuman, COVID-19 outbreak spread to 212 countries, struck the world and we found ourselves ill equipped as international comity to defeat the virus. The economic, health and political foundation were shacked globally and exposed the global health security system due to poor implementations of the policy guidelines. Similarly, Pakistan being an endemic region for emerging and reemerging infectious diseases, encountered badly by numerous different outbreaks in past. Pakistan share border with China, India, Iran and Afghanistan and increase influx of travelers through both air and land route puts Pakistan at high risk to the infectious agents. In 21st century the game of bio warfare cannot be eliminated and pose significant challenges to the security. Countries who learned from past like Korea, China with best preparedness readiness and response tackled the situation as they have best biosecurity, biorisk management system. Biosecurity as biodefense against outbreaks, pandemics, biological warfare and bioterrorism has been underestimated in developing countries like Pakistan and therefore need to highlight the urgency at national level to cope with any future outbreaks. Risk assessment, and mitigation strategies through collaborative work should need to adopt by stakeholders for strategic plan of biosecurity. Better means to protect military, health care workers operating in difficult environment are also needed. A national biosecurity system in response to outbreaks, prioritizing the emergency R&D in diagnostics, establishing high containment facilities, vaccination should be initiated. Moreover, a permanent national defense force or bio-umbrella on biosecurity should be established to shield the country from biological, chemical, nuclear and radiological threat agents. National Biological Defense Program (NBDP) should be initiated to train and protect military personnel against wide range of biological threat.

A Network-Based Analysis Reveals the Mechanism Underlying Vitamin D in Suppressing Cytokine Storm and Virus in SARS-CoV-2 Infection.

BackgroundSARS-CoV-2 causes ongoing pandemic coronavirus disease of 2019 (COVID-19), infects the cells of the lower respiratory tract that leads to a cytokine storm in a significant number of patients resulting in severe pneumonia, shortness of breathing, respiratory and organ failure. Extensive studies suggested the role of Vitamin D in suppressing cytokine storm in COVID-19 and reducing viral infection; however, the precise molecular mechanism is not clearly known. In this work, bioinformatics and systems biology approaches were used to understand SARS-CoV-2 induced cytokine pathways and the potential mechanism of Vitamin D in suppressing cytokine storm and enhancing antiviral response.ResultsThis study used transcriptome data and identified 108 differentially expressed host genes (DEHGs) in SARS-CoV-2 infected normal human bronchial epithelial (NHBE) cells compared to control. Then, the DEHGs was integrated with the human protein-protein interaction data to generate a SARS-CoV-2 induced host gene regulatory network (SiHgrn). Analysis of SiHgrn identified a sub-network “Cluster 1” with the highest MCODE score, 31 up-regulated genes, and predominantly associated immune and inflammatory response. Interestingly, the iRegulone tool identified that “Cluster 1” is under the regulation of transcription factors STAT1, STAT2, STAT3, POU2F2, and NFkB1, collectively referred to as “host response signature network”. Functional enrichment analysis with NDEx revealed that the “host response signature network” is predominantly associated with critical pathways, including “cytokines and inflammatory response”, “non-genomic action of Vitamin D”, “the human immune response to tuberculosis”, and “lung fibrosis”. Finally, in-depth analysis and literature mining revealed that Vitamin D binds with its receptor and could work through two different pathways: (i) it inhibits the expression of pro-inflammatory cytokines through blocking the TNF induced NFkB1 signaling pathway; and (ii) it initiates the expression of interferon-stimulating genes (ISGs) for antiviral defense program through activating the IFN-α induced Jak-STAT signaling pathway.ConclusionThis comprehensive study identified the pathways associated with cytokine storm in SARS-CoV-2 infection. The proposed underlying mechanism of Vitamin D could be promising in suppressing the cytokine storm and inducing a robust antiviral response in severe COVID-19 patients. The finding in this study urgently needs further experimental validations for the suitability of Vitamin D in combination with IFN-α to control severe COVID-19.

Spies and the Virus: The COVID-19 Pandemic and Intelligence Communication in the United States

This paper introduces a crucial parameter to the novel coronavirus response in the United States, by shedding light on the early-warning role of intelligence agencies. It argues that the intelligence components of the federal government's Biological Defense Program offered actionable forewarning about an impending pandemic in the years leading to the COVID-19 outbreak. Yet, almost from the opening stages of the pandemic, senior US government officials, including President Donald Trump, have repeatedly claimed that the virus “came out of nowhere” and that “nobody saw it coming.” We show that these assertions contradict more than 15 years of pandemic preparedness warnings by intelligence professionals, and disregard the existence of intelligence-led federal pandemic response strategies of every US administration in our time. However, rather than simply placing blame on the White House for discounting these warnings, we advance a conceptual analysis of what many in the US Intelligence Community view as a critical breakdown in strategic communication between intelligence professionals and key government decision-makers. This study agrees with those who suggest that the White House disregarded its own pandemic experts. However, it also posits that the means of strategic communication employed by intelligence experts to alert the White House to the threat were unproductive. These alerts were communicated largely through the President's Daily Brief, an archaic, and ineffectual method of communication that is not designed to facilitate the kind of laser-focused, unequivocal exchange of information needed when potentially catastrophic threats confront the world. This study suggests that the Intelligence Community must implement more direct, immediate and conclusive methods of communicating intelligence to decision-makers, and should seriously consider creating a new line of products that addresses existential challenges to national security. Lastly, we contend it is time to re-evaluate existing rules that prevent intelligence analysts from offering advice on policy. Although we agree that intelligence professionals should refrain from providing policy advice on routine matters, we question the value of preventing these highly knowledgeable experts from communicating strategic policy advice to decision-makers when it comes to threats of a catastrophic nature, which may prove potentially existential for the US, its allies, and the world.

Implications of the Defense Program in the Context of National Economic Progress (Case Study of Development in East Indonesia)

The eastern part of Indonesia is one of the strategic areas where this region is nationally concerned with the lives of many people, from the point of view of political, economic, social, cultural, environmental, and defense and security interests. From a regional development point of view, there are still many areas in Eastern Indonesia that are developing slowly with low accessibility and are dominated by underdeveloped regions with very limited social and economic facilities and infrastructure. According to the defense economy, the impact of the use of the defense budget on the economy can be viewed from the demand or consumption and supply or production approaches. From the consumption side, the defense can protect national resources against various threats, so that national consumption becomes stable and even increases. On the other hand, this paper wants to see the defense program from the production side. By using qualitative methods through literature review, this paper aims to look at infrastructure development carried out by the TNI, with a case study of locations in Papua. The construction of the Trans Papua road which is covered in forests and security threats is the main obstacle. A trained Engineer Unit can do it well, which civilian agencies cannot afford. Apart from eliminating threats, defense programs must also be able to provide a multiplier effect on the welfare of the community, as has been done by the TNI in assisting infrastructure development in Papua. This shows an example that a productive defense program can boost the economy and welfare in a region, where the private sector cannot / dare to enter due to various constraints in the region.

Influenza virus-mediated suppression of bronchial Chitinase-3-like 1 secretion promotes secondary pneumococcal infection.

Infections of the lung are among the leading causes of death worldwide. Despite the preactivation of innate defense programs during viral infection, secondary bacterial infection substantially elevates morbidity and mortality rates. Particularly problematic are co-infections with influenza A virus (IAV) and the major bacterial pathogen Streptococcus pneumoniae. However, the molecular processes underlying the severe course of such co-infections are not fully understood. Previously, the absence of secreted glycoprotein Chitinase-3-like 1 (CHI3L1) was shown to increase pneumococcal replication in mice. We therefore hypothesized that an IAV preinfection decreases CHI3L1 levels to promote pneumococcal infection. Indeed, in an air-liquid interface model of primary human bronchial epithelial cells (hBECs), IAV preinfection interfered with apical but not basolateral CHI3L1 release. Confocal time-lapse microscopy revealed that the gradual loss of apical CHI3L1 localization during co-infection with influenza and S. pneumoniae coincided with the disappearance of goblet as well as ciliated cells and increased S. pneumoniae replication. Importantly, extracellular restoration of CHI3L1 levels using recombinant protein significantly reduced bacterial load in influenza preinfected bronchial models. Thus, recombinant CHI3L1 may provide a novel therapeutic means to lower morbidity and mortality associated with post-influenza pneumococcal infections.

A Praise for Defensive Programming: Leveraging Uncertainty for Effective Malware Mitigation

A promising avenue for improving the effectiveness of behavioral-based malware detectors is to leverage two-phase detection mechanisms. Existing problem in two-phase detection is that after the first phase produces borderline decision, suspicious behaviors are not well contained before the second phase completes. This paper improves CHAMELEON, a framework to realize the uncertain environment. CHAMELEON offers two environments: standard–for software identified as benign by the first phase, and uncertain–for software received borderline classification from the first phase. The uncertain environment adds obstacles to software execution through random perturbations applied probabilistically. We introduce a dynamic perturbation threshold that can target malware disproportionately more than benign software. We analyzed the effects of the uncertain environment by manually studying 113 software and 100 malware, and found that 92% malware and 10% benign software disrupted during execution. The results were then corroborated by an extended dataset (5,679 Linux malware samples) on a newer system. Finally, a careful inspection of the benign software crashes revealed some software bugs, highlighting CHAMELEON's potential as a practical complementary antimalware solution.

Fever and a Multifocal, Erythematous, Nodular Rash in an 18-month-old Boy

1. Angelique E. Boutzoukas, MD* 2. Jared Kusma, MD* 3. Joshua R. Watson, MD† 4. Bonita Fung, MD‡ 5. Christopher P. Ouellette, MD†,§ 1. *Pediatric Residency Program, 2. †Division of Infectious Diseases, 3. ‡Department of Anatomic Pathology and Laboratory Medicine, and 4. §Host Defense Program, Nationwide Children’s Hospital, Columbus, OH A previously healthy 18-month-old boy presents to the emergency department after 6 days of cough, rhinorrhea, daily fever, irritability, and progressive rash with extremity swelling. On admission, he is febrile to 38.2°C and ill-appearing. Physical examination is notable for lip and tongue erythema, a sandpaper-like exanthem on his back and extremities with scattered petechiae, and tense bilateral hand and feet edema and erythema. In addition, multiple erythematous, tender, indurated, nodular lesions (2 to 3 cm in diameter) are present on the chest, abdomen, right arm, and left hand (Fig 1). Figure 1. Numerous, tender erythematous nodular lesions localized to chest and abdomen. Laboratory evaluation is notable for leukocytosis (white blood cell count of 40,000/mm3 [40 × 109/L] with 49% segmented neutrophils, 41% band forms) and an elevated erythrocyte sedimentation rate (103 mm/hour), C-reactive protein (25.9 mg/dL [2,466.7 nmol/L]), aspartate aminotransferase (63 U/L [1.05 ukat/L]), and alanine aminotransferase (46 U/L [0.77 ukat/L]). Urinalysis shows evidence of pyuria (18 white blood cell/high power field) and proteinuria (100 mg/dL). A blood culture is obtained, and intravenous clindamycin 10 mg/kg every 8 hours is initiated to target typical skin organisms. Given the unusual nodular rash, dermatology is consulted and performs a skin biopsy of a nodule on the abdomen. Blood culture results reveal the first clue, and histopathologic analysis of the skin biopsy reveals the diagnosis. Given the initial presentation, he was hospitalized with an initial differential diagnosis including Kawasaki disease (KD), toxic shock syndrome (TSS), a serum sickness-like reaction, native valve infective endocarditis with cutaneous emboli, …

SAFETY CULTURE IN TECHNOLOGIES FOR HANDLING NUCLEAR WASTE AND NUCLEAR FUEL

The safety culture in the elimination of the nuclear legacy from the defense and civil programs of the former USSR is demonstrated by the example of three different technologies for handling nuclear waste and spent nuclear fuel. These technologies have been implemented by RFNC-VNIITF together with RFNC-VNIIEF, OJSC RI, JSC NIKIET, and the National Nuclear Center of the Republic of Kazakhstan (NCC RK). The export of nuclear fuel from the NCC RK research reactors to Russia is considered. The key aspects of eliminating access to nuclear waste at the former Semipalatinsk Test Site in the interests of the non-proliferation regime are discussed. The set of activities associated with the export of the spent fuel assemblies (SFAs) of reactors AMB-100 and AMB-200 as the nuclear legacy of the first civil nuclear power facilities to the “Mayak” PA is shown. It is noted that compliance with the national laws, regulatory documents, and safety culture has made it possible to successfully perform unique technical and organizational tasks. As a result, the Republic of Kazakhstan has met all the requirements for a non-nuclear state when staging research reactor complexes under the IAEA safeguards; the Russian Federation, the Republic of Kazakhstan, and the United States have jointly eliminated the threat to non-proliferation regime at the former Semipalatinsk Test Site, the State Atomic Energy Corporation “Rosatom” has eliminated the “sluggish accident” at one of the sites of the nuclear legacy of the civil nuclear power engineering.

Accounting for violent conflict risk in planetary defense decisions

This paper provides the first-ever survey of the implications of violent conflict risk for planetary defense program decisions. Arguably, the aim of planetary defense should be to make Earth safer from all threats, including but not limited to threats from near-Earth objects (NEOs). Insofar as planetary defense projects affect other risks besides NEOs, these other risks should be taken into account. This paper evaluates three potential effects of planetary defense programs on violent conflict risk. First, planetary defense may offer a constructive model for addressing a major global risk. By documenting the history of its successes and failures, the planetary defense community can aid efforts to address other global risks, including but not limited to violent conflict. Second, the proposed use of nuclear explosions for NEO deflection and disruption could affect the role of nuclear weapons in violent conflict risk. The effect may be such that nuclear deflection/disruption would increase aggregate risks to human society. However, the effect is difficult to assess, mainly due to ambiguities in violent conflict risk. Third, planetary defense could reduce violent conflict risk by addressing the possibility of NEO collisions being mistaken as violent attacks and inadvertently triggering violent conflict. False alarms mistaken as real attacks are a major concern, especially as a cause of nuclear war. Improved awareness of NEOs and communication between astronomers and military officials could help resolve NEO false alarms. Each of these three effects of planetary defense programs on violent conflict risk can benefit from interaction between the communities that study and address NEO and violent conflict risks.

Guanylate Binding Proteins Restrict Leishmania donovani Growth in Nonphagocytic Cells Independent of Parasitophorous Vacuolar Targeting.

Interferon (IFN)-inducible guanylate binding proteins (GBPs) play important roles in host defense against many intracellular pathogens that reside within pathogen-containing vacuoles (PVs). For instance, members of the GBP family translocate to PVs occupied by the protozoan pathogen Toxoplasma and facilitate PV disruption and lytic parasite killing. While the GBP defense program targeting Toxoplasma has been studied in some detail, the role of GBPs in host defense to other protozoan pathogens is poorly characterized. Here, we report a critical role for both mouse and human GBPs in the cell-autonomous immune response against the vector-borne parasite Leishmania donovani Although L. donovani can infect both phagocytic and nonphagocytic cells, it predominantly replicates inside professional phagocytes. The underlying basis for this cell type tropism is unclear. Here, we demonstrate that GBPs restrict growth of L. donovani in both mouse and human nonphagocytic cells. GBP-mediated restriction of L. donovani replication occurs via a noncanonical pathway that operates independent of detectable translocation of GBPs to L. donovan-containing vacuoles (LCVs). Instead of promoting the lytic destruction of PVs, as reported for GBP-mediated killing of Toxoplasma in phagocytic cells, GBPs facilitate the delivery of L. donovani into autolysosomal-marker-positive compartments in mouse embryonic fibroblasts as well as the human epithelial cell line A549. Together our results show that GBPs control a novel cell-autonomous host defense program, which renders nonphagocytic cells nonpermissible for efficient Leishmania replication.IMPORTANCE The obligate intracellular parasite Leishmania causes the disease leishmaniasis, which is transmitted to mammalian hosts, including humans, via the sandfly vector. Following the bite-induced breach of the skin barrier, Leishmania is known to live and replicate predominantly inside professional phagocytes. Although Leishmania is also able to infect nonphagocytic cells, nonphagocytic cells support limited parasitic replication for unknown reasons. In this study, we show that nonphagocytic cells possess an intrinsic property to restrict Leishmania growth. Our study defines a novel role for a family of host defense proteins, the guanylate binding proteins (GBPs), in antileishmanial immunity. Mechanistically, our data indicate that GBPs facilitate the delivery of Leishmania into antimicrobial autolysosomes, thereby enhancing parasite clearance in nonphagocytic cells. We propose that this GBP-dependent host defense program makes nonphagocytic cells an inhospitable host cell type for Leishmania growth.

GM-CSF Calibrates Macrophage Defense and Wound Healing Programs during Intestinal Infection and Inflammation

SummaryMacrophages play a central role in intestinal immunity, but inappropriate macrophage activation is associated with inflammatory bowel disease (IBD). Here, we identify granulocyte-macrophage colony stimulating factor (GM-CSF) as a critical regulator of intestinal macrophage activation in patients with IBD and mice with dextran sodium sulfate (DSS)-induced colitis. We find that GM-CSF drives the maturation and polarization of inflammatory intestinal macrophages, promoting anti-microbial functions while suppressing wound-healing transcriptional programs. Group 3 innate lymphoid cells (ILC3s) are a major source of GM-CSF in intestinal inflammation, with a strong positive correlation observed between ILC or CSF2 transcripts and M1 macrophage signatures in IBD mucosal biopsies. Furthermore, GM-CSF-dependent macrophage polarization results in a positive feedback loop that augmented ILC3 activation and type 17 immunity. Together, our data reveal an important role for GM-CSF-mediated ILC-macrophage crosstalk in calibrating intestinal macrophage phenotype to enhance anti-bacterial responses, while inhibiting pro-repair functions associated with fibrosis and stricturing, with important clinical implications.