The Jericho Option: Al-Qa'ida and Attacks on Critical Infrastructure

There is no doubt that al-Qaida and its affiliates have displayed, and continue to display, an acute interest in attacking targets that are considered to be important components of the infrastructure of the United States. What has not thus far been carried out, however, is an in-depth examination of the basic nature, historical evolution, and present scope of the organization's objectives that might help government personnel develop sound policy recommendations and analytical indicators to assist in detecting and interdicting plots of this nature. This study was completed with the financial support of the Lawrence Livermore National Laboratory, through a project sponsored by the U.S. Department of Homeland Security, Science and Technology Directorate. It is specifically intended to increase counterterrorism analysts understanding of certain features of al-Qaida's strategy and operations in order to facilitate the anticipation and prevention of attacks directed against our most critical infrastructures. The procedure adopted herein has involved consulting a wide variety of source materials that bear on the topic, ranging from sacred religious texts and historical accounts to al-Qaida-linked materials and the firsthand testimony of captured members of the group. It has also intentionally combined multiple approaches, including exploring the more esoteric religion-historical referents that have served to influence al-Qaida's behavior, providing a strategic analysis of its objectives and targeting rationales, closely examining the statements and writings of al-Qaida leaders and spokesmen (in part on the basis of material translated from primary sources), offering a descriptive analysis of its past global attack patterns, and producing concise but nonetheless in-depth case studies of its previous ''infrastructural'' attacks on U.S. soil. The analyses contained herein tend to support the preliminary assessment made by some of the authors in an earlier report, namely, that transnational jihadist organizations are amongst the extremist groups that are most likely to carry out successful attacks against targets that U.S. officials would categorize as elements of this country's critical infrastructure. These networks clearly have the operational capabilities to conduct these types of attacks, even on a large scale, and they display a number of ideological proclivities that may incline them to attack such targets. Although this seems self-evident, this study has also yielded more detailed insights into the behavior and orientation of al-Qaida and its affiliated networks

High expression of focal adhesion kinase (p125(FAK)) in node-negative breast cancer is related to overexpression of HER-2/neu and activated Akt kinase but does not predict outcome

INTRODUCTION: Focal adhesion kinase (FAK) regulates multiple cellular processes including growth, differentiation, adhesion, motility and apoptosis. In breast carcinoma, FAK overexpression has been linked to cancer progression but the prognostic relevance remains unknown. In particular, with regard to lymph node-negative breast cancer it is important to identify high-risk patients who would benefit from further adjuvant therapy. METHODS: We analyzed 162 node-negative breast cancer cases to determine the prognostic relevance of FAK expression, and we investigated the relationship of FAK with major associated signaling pathways (HER2, Src, Akt and extracellular regulated kinases) by immunohistochemistry and western blot analysis. RESULTS: Elevated FAK expression did not predict patient outcome, in contrast to tumor grading (P = 0.005), Akt activation (P = 0.0383) and estrogen receptor status (P = 0.0033). Significant positive correlations were observed between elevated FAK expression and HER2 overexpression (P = 0.001), as well as phospho-Src Tyr-215 (P = 0.021) and phospho-Akt (P < 0.001), but not with phospho-ERK1/2 (P = 0.108). Western blot analysis showed a significant correlation of FAK Tyr-861 activation and HER2 overexpression (P = 0.01). CONCLUSIONS: Immunohistochemical detection of FAK expression is of no prognostic significance in node-negative breast cancer but provides evidence that HER2 is involved in tumor malignancy and metastatic ability of breast cancer through a novel signaling pathway participating FAK and Src

Biocontrol of charcoal-rot of sorghum by actinomycetes isolated from herbal vermicompost

A total of 137 actinomycetes, isolated from 25 different herbal vermicomposts, were characterized for their antagonistic potential against Macrophomina phaseolina by dual-culture assay. Of them, eight most promising isolates (CAI-17, CAI-21, CAI-26, CAI-68, CAI-78, KAI-26, KAI-27 and MMA-32) were characterized for the production of siderophore, chitinase, protease, hydrocyanic acid (HCN), indole acetic acid (IAA) and further evaluated for their antagonistic potential against M. phaseolina by blotter-paper assay and in greenhouse. All the eight isolates produced HCN and IAA, seven produced siderophore (except CAI-78) and protease (except KAI-27) and four produced chitinase (CAI-26, KAI-26, KAI-27 and MMA-32). In the blotter-paper assay, no charcoal-rot infection was observed in KAI-26 and KAI-27-treated sorghum roots, indicating complete inhibition of the pathogen, while the other isolates showed 47 to 88% lesser charcoal-rot infection compared to the control. In the antifungal activity test against M. phaseolina (in greenhouse on sorghum), all the isolates increased in shoot dry mass by 28 to 53% and root dry mass by 5 to 21%, over the control. In order to confirm the plant growth promoting (PGP) traits of the isolates, the green house experiment was repeated, but in the absence of M. phaseolina. The results further confirmed the PGP traits of the isolates as evidenced by 15 to 34% increase in shoot dry mass on six isolates (except CAI-26 and KAI-27), 14 to 57% increase in root dry mass on five isolates (except CAI-68, KAI-26 and KAI-27), 17 to 60% increase in root length on five isolates (except CAI-17, CAI-21 and CAI-68) and 10 to 64% increase in root volume on six isolates (except CAI-17 and CAI-68). Culture filtrate of three potential actinomycetes (CAI-21, CAI-26 and MMA-32) at 0.5% inhibited the growth of M. phaseolina, indicating that the metabolites of these actinomycetes were responsible for the inhibition. The sequences of 16S rDNA gene of the isolates matched with Streptomyces but with different species in BLAST analysis. This study indicates that the selected actinomycetes have the potential for PGP and control of charcoal-rot disease in sorghum

Tamoxifen resistance in breast cancer is regulated by the EZH2–ERa–GREB1 transcriptional axis

Resistance to cancer treatment can be driven by epigenetic reprogramming of specific transcriptomes in favor of the refractory phenotypes. Here we discover that tamoxifen resistance in breast cancer is driven by a regulatory axis consisting of a master transcription factor, its cofactor, and an epigenetic regulator. The oncogenic histone methyltransferase EZH2 conferred tamoxifen resistance by silencing the expression of the estrogen receptor a (ERa) cofactor GREB1. In clinical specimens, induction of DNA methylation of a particular CpG-enriched region at the GREB1 promoter negatively correlated with GREB1 levels and cell sensitivity to endocrine agents. GREB1 also ensured proper cellular reactions to different ligands by recruiting distinct sets of ERa cofactors to cis-regulatory elements, which explains the contradictory biological effects of GREB1 on breast cancer cell growth in response to estrogen or antiestrogen. In refractory cells, EZH2-dependent repression of GREB1 triggered chromatin reallocation of ERa coregulators, converting the antiestrogen into an agonist. In clinical specimens from patients receiving adjuvant tamoxifen treatment, expression levels of EZH2 and GREB1 were correlated negatively, and taken together better predicted patient responses to endocrine therapy. Overall, our work suggests a new strategy to overcome endocrine resistance in metastatic breast cancer by targeting a particular epigenetic program. Significance: This study suggests a new strategy to overcome endocrine resistance in metastatic breast cancer by targeting a particular epigenetic program defined within.Fil: Wu, Yanming. University of Texas at San Antonio; Estados UnidosFil: Zhang, Zhao. University of Texas at San Antonio; Estados UnidosFil: Cenciarini, Mauro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Amasino, Matías Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Hong, Tao. University of Texas at San Antonio; Estados Unidos. Central South University; ChinaFil: Yang, Mei. University of Texas at San Antonio; Estados UnidosFil: Liao, Yiji. University of Texas at San Antonio; Estados UnidosFil: Chiang, Huai-Chin. University of Texas at San Antonio; Estados Unidos. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: Kaklamani, Virginia G.. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: Jeselsohn, Rinath. Dana-farber Cancer Institute; Estados UnidosFil: Vadlamudi, Ratna K.. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: Huang, Tim Hui Ming. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: Li, Rong. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: De Angelis, Carmine. Baylor College Of Medicine; Estados UnidosFil: Fu, Xiaoyong. Baylor College Of Medicine; Estados UnidosFil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Schiff, Rachel. Baylor College Of Medicine; Estados UnidosFil: Brown, Myles. Dana farber Cancer Institute; Estados UnidosFil: Xu, Kexin. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio

Assessing Terrorist Motivations for Attacking Critical Infrastructure

Certain types of infrastructure--critical infrastructure (CI)--play vital roles in underpinning our economy, security and way of life. These complex and often interconnected systems have become so ubiquitous and essential to day-to-day life that they are easily taken for granted. Often it is only when the important services provided by such infrastructure are interrupted--when we lose easy access to electricity, health care, telecommunications, transportation or water, for example--that we are conscious of our great dependence on these networks and of the vulnerabilities that stem from such dependence. Unfortunately, it must be assumed that many terrorists are all too aware that CI facilities pose high-value targets that, if successfully attacked, have the potential to dramatically disrupt the normal rhythm of society, cause public fear and intimidation, and generate significant publicity. Indeed, revelations emerging at the time of this writing about Al Qaida's efforts to prepare for possible attacks on major financial facilities in New York, New Jersey, and the District of Columbia remind us just how real and immediate such threats to CI may be. Simply being aware that our nation's critical infrastructure presents terrorists with a plethora of targets, however, does little to mitigate the dangers of CI attacks. In order to prevent and preempt such terrorist acts, better understanding of the threats and vulnerabilities relating to critical infrastructure is required. The Center for Nonproliferation Studies (CNS) presents this document as both a contribution to the understanding of such threats and an initial effort at ''operationalizing'' its findings for use by analysts who work on issues of critical infrastructure protection. Specifically, this study focuses on a subsidiary aspect of CI threat assessment that has thus far remained largely unaddressed by contemporary terrorism research: the motivations and related factors that determine whether a terrorist organization will attack critical infrastructure. In other words, this research investigates: (1) why terrorists choose to attack critical infrastructure rather than other targets; (2) how groups make such decisions; (3) what, if any, types of groups are most inclined to attack critical infrastructure targets; and (4) which types of critical infrastructure terrorists prefer to attack and why. In an effort to address the above questions as comprehensively as possible, the project team employed four discrete investigative approaches in its research design. These include: (1) a review of existing terrorism and threat assessment literature to glean expert consensus regarding terrorist target selection, as well as to identify theoretical approaches that might be valuable to analysts and decision-makers who are seeking to understand such terrorist group decision-making processes; (2) the preparation of several concise case studies to help identify internal group factors and contextual influences that have played significant roles in leading some terrorist groups to attack critical infrastructure; (3) the creation of a new database--the Critical Infrastructure Terrorist Incident Catalog (CrITC)--to capture a large sample of empirical CI attack data that might be used to illuminate the nature of such attacks to date; and (4) the development of a new analytical framework--the Determinants Effecting Critical Infrastructure Decisions (DECIDe) Framework--designed to make the factors and dynamics identified by the study more ''usable'' in any future efforts to assess terrorist intentions to target critical infrastructure. Although each is addressed separately in the following chapters, none of the four aspects of this study were developed in isolation. Rather, all the constituent elements of the project informed--and were informed by--the others. For example, the review of the available literature on terrorist target selection made possible the identification of several target selection factors that were both important in the development of the analytical framework and subsequently validated by the case studies. Similarly, statistical analysis of the CrITIC data yielded measurable evidence that supported hypotheses derived from the framework, the case studies, and the writings of various experts. Besides providing an important mechanism of self-reinforcement and validation, the project's multifaceted nature made it possible to discern aspects of CI attack motivations that would likely have been missed if any single approach had been adopted

Racial Disparities and Risk for COVID-19 Among Pregnant Patients: Results from the Michigan Statewide Collaborative

Objective: Previous studies have looked at COVID-19 outcomes in pregnancy and racial disparities among patients with COVID-19, but few have studied racial disparities among pregnant patients with COVID-19. Our goal in this study is to analyze the relationship between race and disparate COVID-19 risk in pregnancy. Study Design: A retrospective cohort analysis was performed on data collected as part of the COVID-19 in Pregnancy and The Newborn: State of Michigan Collaborative, a database of pregnant patients admitted to 14 institutions in Southern Michigan. Cases were defined as patients with a positive SARS-CoV-2 test result. Controls, those with suspicion of COVID-19 prior to universal screening or a negative PCR test, were matched to cases on the same unit within 30 days of each case. For this analysis, the two primary groups of interest were non-Hispanic Black (Black) vs. non-Hispanic White (White) patients. Potential covariates were age, body mass index (BMI), chronic hypertension, diabetes, asthma, substance use, and smoking; the dependent variable was COVID/non-COVID in a robust Poisson regression model. In addition, 18 symptoms and disease severity (mild/moderate/severe) were compared between the Black and White groups using the same statistical method. Results: Of 1,131 gravidas, 42.9%(n=485) were Black. These patients were at two-fold greater risk for COVID-19 compared with their White counterparts [35.9% vs. 18.3%, RR=1.96(1.6-2.4)]. After adjusting for obesity and diabetes, the risk of COVID-19 in Black patients remained higher compared to the risk among White patients (aRR=2.46 [1.87-3.24]). There were no differences in symptoms nor severity of disease presentation between the groups. Conclusion: In our population, Black patients are more likely to be diagnosed with COVID-19 infection during pregnancy. This finding is not explained by a range of covariates. Other factors, such as social determinants of health, may be important to understand this disparity and warrant further examination

COVID-19 is associated with early emergence of preeclampsia: results from a large regional collaborative

Objective: To examine the relationship between COVID-19 and preeclampsia (PreE) in a large, diverse population. Study Design: The COVID-19 in Pregnancy and The Newborn: State of Michigan Collaborative established a database of pregnant patients admitted to 14 institutions in Southern Michigan. Patients with COVID-19 (cases) were matched to 2 or 3 non-COVID patients (controls) on the same unit within 30 days of each case. Relative Risks (RR) were calculated using robust Poisson regression models with adjustment for covariates. Chi-squared test for trend was used to assess the increase in risk with the severity of disease. Results: 369 cases and 1,090 controls were delivered between March - October 2020. An increased risk of PreE (RR=1.8), driven almost entirely by an increase in preterm PreE (pretermPreE) (RR=2.85) was observed in COVID pregnancies (Table 1), with a dose-response relationship with symptomatology and severity (Table 2). The associations between COVID-19 disease and PreE or pretermPreE were independent of other risk factors, as demonstrated by the minimal changes in RR after adjustment for confounders (Table 1). However, African American (AA) COVID patients experienced pretermPreE 1.9 times more than COVID patients of other races (10.1 vs 5.3), an increase not observed in control patients. The strength of the association for COVID with PreE was comparable to the association of PreE with chronic hypertension and nulliparity (data not shown). Increasing symptoms and severity of COVID-19 were associated with an increased risk for PreE with placental lesions, even after adjustment for relevant covariates (Tables 1 & 2). Non-PreE COVID patients had an increased trend of placental lesions compared to non-COVID patients, reaching significance for intravillous thrombin. Conclusion: COVID-19 is significantly associated with early emergence of PreE, independent of known risk factors other than AA race. Our study shows that among patients predisposed to PreE, COVID-19 impacts PreE severity in that it leads to pretermPreE. Further studies on COVID-19 and PreE, with a focus on racial disparities, is warranted

Plant growth-promoting traits of biocontrol potential bacteria isolated from rice rhizosphere

Seven isolates of bacteria (SRI-156, SRI-158, SRI-178, SRI-211, SRI-229, SRI-305 and SRI-360) were earlier reported by us as having potential for biocontrol of charcoal rot of sorghum and plant growth promotion (PGP) of the plant. In the present study, the seven isolates were characterized for their physiological traits (tolerance to salinity, pH, temperature and resistance to antibiotics and fungicides) and further evaluated in the field for their PGP of rice. All the seven isolates were able to grow at pH values between 5 and 13, in NaCl concentrations of up to 8% (except SRI-156 and SRI-360), temperatures between 20 and 40?C and were resistant to ampicillin (>100 ppm; except SRI-158 and SRI-178) but sensitive (<10 ppm) to chloramphenicol, kanamycin, nalidixic acid, streptomycin (except SRI-156 and SRI-211) and tetracycline. They were tolerant to fungicides benlate and captan, except SRI-158 and SRI-178, bavistin and sensitive to thiram (except SRI-156 and SRI-211) at field application level. In the field, four of the seven isolates (SRI-158, SRI-211, SRI-229 and SRI-360) significantly enhanced the tiller numbers, stover and grain yields, total dry matter, root length, volume and dry weight over the un-inoculated control. In the rhizosphere soil at harvest, all the isolates significantly enhanced microbial biomass carbon (except SRI-156), microbial biomass nitrogen and dehydrogenase activity (up to 33%, 36% and 39%, respectively) and total N, available P and% organic carbon (up to 10%, 38% and 10%, respectively) compared to the control. This investigation further confirms that the SRI isolates have PGP properties

Essential function for ErbB3 in breast cancer proliferation

The overexpression of the ErbB family of tyrosine kinase receptors is thought to be important in the development of many breast tumours. To date, most attention has focused on the ErbB2 receptor. Now, in a recent report, it has been shown that ErbB3 is a critical partner for the transforming activity of ErbB2 in breast cancer cells. Importantly, the proliferative signals from this transforming complex appear to act via the PI-3 kinase pathway