Vulnerable warriors: the atmospheric marketing of military and policing equipment before and after 9/11

In this article, we analyse changes in the circulation of advertisements of policing products at security expos between 1995 and 2013. While the initial aim of the research was to evidence shifts in terrorist frames in the marketing of policing equipment before and after 9/11, our findings instead suggested that what we are seeing is the rise of marketing to police as “vulnerable warriors”, law enforcement officers in need of military weapons both for their offensive capabilities and for the protection they can offer to a police force that is always under threat

Антимікробна активність in vitro нанодисперсного кремнезему і композиту полігексаметиленгуанідину гідрохлориду для лікування місцевих інфекцій

The problem of antimicrobial drug resistance can be solved through the development of novel antimicrobial compounds and combination drugs. In order to enhance polyhexamethyleneguanidine hydrochloride (PHMG-HC) therapeutic benefits, a composite (code name CMU-211) of PHMG-HC with a nanoparticle-based sorbent of highly dispersed silica (HDS) was developed.Aim. To evaluate in vitro antimicrobial activity of highly dispersed silica and PHMG-HC (HDS + PHMG-HC) composite (CMU-211), highly dispersed silica (HDS) suspension (CMU-212), and PHMG-HC solution as a reference against standard test-strains.Materials and methods. HDS + PHMG-HC composite, HDS suspension, and PHMG-HC solution. Microbial test-strains (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella enterica, Klebsiella pneumoniae, and Candida albicans). An antimicrobial activity of substances was studied with broth dilution method in LB liquid medium, minimum inhibitory concentrations (MIC) were obtained.Results. CMU-211 has been shown to have high activity against C. albicans and S. aureus with a minimum inhibitory concentration (MIC) of 48.83/9.77 μg/mL (HDS/PHMG-HC) and marked effect on E. coli (MIC of 97.66/19.53 μg/mL) and S. enterica (MIC of 195.31/39.06 μg/mL). The relatively low activity of CMU-211 was reported against K. pneumoniae (MIC of 390.63/78.13 μg/mL) and P. aeruginosa (MIC of 195.31/39.06 μg/mL), however, the effect on P. aeruginosa was consistent with the activity of PHMG-HC applied alone. The concentrations of CMU-211 had to be twice as high as the MICs to ensure bactericidal (fungicidal) effect on microorganisms studied, except of S. enterica and K. pneumoniae for which bacteriostatic concentration was also proved to be bactericidal.Conclusions. These results taken together with previous findings on CMU-211 high sorption activity suggest that the composite has double therapeutic activity and may be beneficial for local infections treatment.Резистентность к антимикробным препаратам является актуальной проблемой для всего мира, которая негативно влияет на результаты лечения больных. Решить поставленную проблему можно путем создания и внедрения новых антимикробных соединений и комплексных лекарственных средств. Актуальным остается разработка комбинированного антимикробного средства, которое бы проявляло выраженное антимикробное действие и сорбционные свойства. В качестве противомикробного компонента был избран полигексаметиленгуанидина гидрохлорид (ПГМГ-ГХ), который является высокомолекулярным катионным поверхностно-активным веществом группы гуанидина.Цель. Определить противомикробную активность суспензии нанодисперсного кремнезема (НДК), композита НДК и ПГМГ-ГХ и раствора полимера ПГМГ-ГХ.Материалы и методы. В работе были использованы 5 % суспензия НДК, модифицированная полимером ПГМГ-ГХ; 5 % суспензия НДК и 20 % водный раствор полигексаметиленгуанидина гидрохлорида. Исследование антимикробной активности веществ проводили на микроорганизмах: Escherichia coli; Staphylococcus aureus; Pseudomonas aeruginosa; Salmonella enterica; Klebsiella pneumoniae; Candida albicans.Результаты. Композит НДК/ПГМГ-ГХ обладает высокой активностью против C. albicans и S. aureus с МИК ~10 мкг/мл (в пересчете на ПГМГ-ГХ) и выраженной активностью против Е. coli (MIC ~20 мкг/мл), S. enterica (MIC ~40 мкг/мл) и P. aeruginosa (MIC ~40 мкг/мл). Относительно низкую активность композит НДК/ПГМГ-ГХ проявил к K. pneumoniae (MIC ~ 80 мкг/мл). Активность композита НДК/ПГМГ-ГХ была сходна с таковой у ПГМГ-ГХ.Выводы. Разработанный композит НДК/ПГМГ-ГХ проявляет выраженное антибактериальное действие по отношению к грамположительным, грамотрицательным микроорганизмам, а также C. albicans.Резистентність до антимікробних препаратів є актуальною проблемою для всіх країн світу, що негативно впливає на результати лікування хворих. Вирішити поставлену проблему можна шляхом створення та впровадження нових антимікробних сполук та комплексних лікарських засобів. Актуальним залишається розробка комбінованого антимікробного засобу, який би проявляв виражену антимікробну дію та сорбційні властивості. В якості антимікробного компоненту було обрано полігексаметиленгуанідину гідрохлорид (ПГМГ-ГХ), що є високомолекулярною катіонною поверхнево-активною речовиною групи гуанідинів.Мета. Визначити антимікробну активність суспензії нанодисперсного кремнезему (НДК), композиту НДК та ПГМГ-ГХ і розчину полімера ПГМГ-ГХ.Матеріали та методи. В роботі була використана 5 % суспензія НДК, модифікована полімером ПГМГ-ГХ; 5 % суспензія НДК та 20 % водний розчин полігексаметиленгуанідину гідрохлориду. Дослідження антимікробної активності речовин проводили на мікроорганізмах: Escherichia coli; Staphylococcus aureus; Pseudomonas aeruginosa; Salmonella enterica; Klebsiella pneumoniae; Candida albicans.Результати. Композит НДК/ПГМГ-ГХ має високу активність проти C. albicans і S. aureus з МІК ~10 мкг/мл (у перерахунку на ПГМГ-ГХ) і виражену активність проти Е. coli (MIC ~20 мкг/мл), S. enterica (MIC ~40 мкг/мл) і P. aeruginosa (MIC ~40 мкг/мл). Відносно низьку активність композит НДК/ПГМГ-ГХ проявив щодо K. pneumoniae (MIC ~80 мкг/мл). Активність композиту НДК/ПГМГ-ГХ була подібна до такої ж у ПГМГ-ГХ.Висновки. Розроблений композит НДК/ПГМГ-ГХ проявляє виражену антибактеріальну дію щодо грампозитивних, грамнегативних мікроорганізмів, а також C. albicans

M\"ossbauer Antineutrinos: Recoilless Resonant Emission and Absorption of Electron Antineutrinos

Basic questions concerning phononless resonant capture of monoenergetic electron antineutrinos (M\"ossbauer antineutrinos) emitted in bound-state beta-decay in the 3H - 3He system are discussed. It is shown that lattice expansion and contraction after the transformation of the nucleus will drastically reduce the probability of phononless transitions and that various solid-state effects will cause large line broadening. As a possible alternative, the rare-earth system 163Ho - 163Dy is favoured. M\"ossbauer-antineutrino experiments could be used to gain new and deep insights into several basic problems in neutrino physics

If we build it they will come: targeting the immune response to breast cancer.

Historically, breast cancer tumors have been considered immunologically quiescent, with the majority of tumors demonstrating low lymphocyte infiltration, low mutational burden, and modest objective response rates to anti-PD-1/PD-L1 monotherapy. Tumor and immunologic profiling has shed light on potential mechanisms of immune evasion in breast cancer, as well as unique aspects of the tumor microenvironment (TME). These include elements associated with antigen processing and presentation as well as immunosuppressive elements, which may be targeted therapeutically. Examples of such therapeutic strategies include efforts to (1) expand effector T-cells, natural killer (NK) cells and immunostimulatory dendritic cells (DCs), (2) improve antigen presentation, and (3) decrease inhibitory cytokines, tumor-associated M2 macrophages, regulatory T- and B-cells and myeloid derived suppressor cells (MDSCs). The goal of these approaches is to alter the TME, thereby making breast tumors more responsive to immunotherapy. In this review, we summarize key developments in our understanding of antitumor immunity in breast cancer, as well as emerging therapeutic modalities that may leverage that understanding to overcome immunologic resistance

Identifying Resistance Mechanisms against Five Tyrosine Kinase Inhibitors Targeting the ERBB/RAS Pathway in 45 Cancer Cell Lines

Because of the low overall response rates of 10-47% to targeted cancer therapeutics, there is an increasing need for predictive biomarkers. We aimed to identify genes predicting response to five already approved tyrosine kinase inhibitors. We tested 45 cancer cell lines for sensitivity to sunitinib, erlotinib, lapatinib, sorafenib and gefitinib at the clinically administered doses. A resistance matrix was determined, and gene expression profiles of the subsets of resistant vs. sensitive cell lines were compared. Triplicate gene expression signatures were obtained from the caArray project. Significance analysis of microarrays and rank products were applied for feature selection. Ninety-five genes were also measured by RT-PCR. In case of four sunitinib resistance associated genes, the results were validated in clinical samples by immunohistochemistry. A list of 63 top genes associated with resistance against the five tyrosine kinase inhibitors was identified. Quantitative RT-PCR analysis confirmed 45 of 63 genes identified by microarray analysis. Only two genes (ANXA3 and RAB25) were related to sensitivity against more than three inhibitors. The immunohistochemical analysis of sunitinib-treated metastatic renal cell carcinomas confirmed the correlation between RAB17, LGALS8, and EPCAM and overall survival. In summary, we determined predictive biomarkers for five tyrosine kinase inhibitors, and validated sunitinib resistance biomarkers by immunohistochemistry in an independent patient cohort. © 2013 Pénzváltó et al

Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies

Human epidermal growth factor receptor 2 (HER2; ERBB2) amplification and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations often co-occur in breast cancer. Aberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway has been shown to correlate with a diminished response to HER2-directed therapies. We generated a mouse model of HER2-overexpressing (HER2+), PIK3CAH1047R-mutant breast cancer. Mice expressing both human HER2 and mutant PIK3CA in the mammary epithelium developed tumors with shorter latencies compared with mice expressing either oncogene alone. HER2 and mutant PIK3CA also cooperated to promote lung metastases. By microarray analysis, HER2-driven tumors clustered with luminal breast cancers, whereas mutant PIK3CA tumors were associated with claudin-low breast cancers. PIK3CA and HER2+/PIK3CA tumors expressed elevated transcripts encoding markers of epithelial-to-mesenchymal transition and stem cells. Cells from HER2+/PIK3CA tumors more efficiently formed mammospheres and lung metastases. Finally, HER2+/PIK3CA tumors were resistant to trastuzumab alone and in combination with lapatinib or pertuzumab. Both drug resistance and enhanced mammosphere formation were reversed by treatment with a PI3K inhibitor. In sum, PIK3CAH1047R accelerates HER2-mediated breast epithelial transformation and metastatic progression, alters the intrinsic phenotype of HER2-overexpressing cancers, and generates resistance to approved combinations of anti-HER2 therapies

Co-expression of nuclear and cytoplasmic HMGB1 is inversely associated with infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer

<p>Abstract</p> <p>Background</p> <p>The intratumoral infiltration of T cells, especially memory T cells, is associated with a favorable prognosis in early colorectal cancers. However, the mechanism underlying this process remains elusive. This study examined whether high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecule, is involved in the infiltration of T cells and disease progression in locally advanced colon cancer.</p> <p>Methods</p> <p>Seventy-two cases of pathologically-confirmed specimens were obtained from patients with stage IIIB (T3N1M0) colon cancer who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University. The density of tumor-infiltrating lymphocytes (TILs) within the tumor tissue and the expression of HMGB1 in the cancer cells were examined via immunohistochemical analysis. The phenotype of CD45RO+ cells was confirmed using a flow cytometric assay. The association between HMGB1 expression, the density of TILs, and the 5-year survival rate were analyzed.</p> <p>Results</p> <p>The density of CD45RO+ T cells within the tumor was independently prognostic, although a higher density of CD3+ T cells was also associated with a favorable prognosis. More importantly, the expression of HMGB1 was observed in both the nucleus and the cytoplasm (co-expression pattern) in a subset of colon cancer tissues, whereas nuclear-only expression of HMGB1 (nuclear expression pattern) existed in most of the cancer tissues and normal mucosa. The co-expression pattern of HMGB1 in colon cancer cells was inversely associated with the infiltration of both CD3+ and CD45RO+ T cells and 5-year survival rates.</p> <p>Conclusions</p> <p>This study revealed that the co-expression of HMGB1 is inversely associated with the infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer, indicating that the distribution patterns of HMGB1 might contribute to the progression of colon cancer via modulation of the local immune response.</p