Polychlorinated biphenyl contamination to the Canadian arctic from landfills and sewage treatment outlets

An investigation was undertaken in soil from the Canadian polar circle [Yellowknife (YELL), Iqaluit (IQA), and Cambridge Bay (CAM)]. Twenty four soil samples (YELL = 3, IQA = 15, CAM = 6) were collected with the depths of 0–20 cm below surface. Eighty major PCBs congeners were analyzed and twenty two PCBs were detected. Concentrations of PCBs in IQA were found to be the highest (0.11–1111 ng/g on dry weight basis), following in decreasing order: CAM (0.07–145 ng/g) and YELL (0.4–7.1 ng/g). Contamination profiles of PCB congeners were different between Iqaluit samples, while PCBs congener profiles were similar in Yellowknife and Cambridge Bay areas. The background sample sites were chosen to be representative of clean and undisturbed soils. The large difference in concentrations observed between dumpsites and background soil samples suggest PCB deposition into these dumpsites from materials discarded within. This is yet another evidence to show that previously pristine Polar Regions are increasingly getting contaminated through human activities. PCBs are excellent industrial markers in this forensic investigation

The effect of correctional facility programming on nonviolent beliefs

Gemstone Team Peace in PrisonsTo date, little research has made an effort to pinpoint measurable changes in beliefs resulting from correctional facility programming. Peace in Prisons studied the effects of the programs at the Montgomery County Correctional Facility on the inmates' beliefs regarding violence. It was hypothesized that inmates participating in programs would undergo a greater reduction in violent beliefs over time than those not in programs. The team administered the Nonviolence Test to inmates three times over a 3-month period. The primary purpose was to observe differences between those in programs and those not in programs. The team also sought to analyze the effects of other factors, including type of program, age, education, and race. The results demonstrate changes in violent beliefs due to a variety of factors, including involvement in certain types of programs, age, and the jail setting itself. What is more, these findings suggest numerous avenues for further research

Selective Deposition and Alignment of Single-Walled Carbon Nanotubes Assisted by Dielectrophoresis: From Thin Films to Individual Nanotubes

Dielectrophoresis has been used in the controlled deposition of single-walled carbon nanotubes (SWNTs) with the focus on the alignment of nanotube thin films and their applications in the last decade. In this paper, we extend the research from the selective deposition of SWNT thin films to the alignment of small nanotube bundles and individual nanotubes. Electrodes with “teeth”-like patterns are fabricated to study the influence of the electrode width on the deposition and alignment of SWNTs. The entire fabrication process is compatible with optical lithography-based techniques. Therefore, the fabrication cost is low, and the resulting devices are inexpensive. A series of SWNT solutions is prepared with concentrations ranging from 0.0125 to 0.2 mg/ml. The alignment of SWNT thin films, small bundles, and individual nanotubes is achieved under the optimized experimental conditions. The electrical properties of these samples are characterized; the linear current–voltage plots prove that the aligned SWNTs are mainly metallic nanotubes. The microscopy inspection of the samples demonstrates that the alignment of small nanotube bundles and individual nanotubes can only be achieved using narrow electrodes and low-concentration solutions. Our investigation shows that it is possible to deposit a controlled amount of SWNTs in desirable locations using dielectrophoresis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)$^{1,2}$. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive$^{1,2}$. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma$^{3}$. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy respons

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Illness Narratives of African Americans Living With Coronary Heart Disease: A Critical Interactionist Analysis.

How African American men and women respond to and manage living with coronary heart disease (CHD) is not well understood despite the well-documented disproportionate burden of CHD and its complications among African Americans in the United States. Through a critical interactionist perspective, we explore illness experiences of African Americans living with CHD and describe a broad range of micro-, meso-, and macro-contextual factors that influence their illness experiences. For participants in this study, CHD has become a "Black disease" wherein certain bodies have become historically and racially marked; a conceptualization maintained and passed on by African Americans themselves. Such findings highlight that CHD is more than a "lifestyle disease" where high-risk behaviors and lack of healthy choices are ultimate culprits. Rather, CHD is perceived by African Americans who have it as yet another product of ongoing racial and socio-structural dynamics through which their health burdens are created, sustained, and reproduced

Large-scale neural dynamics in a shared low-dimensional state space reflect cognitive and attentional dynamics

Cognition and attention arise from the adaptive coordination of neural systems in response to external and internal demands. The low-dimensional latent subspace that underlies large-scale neural dynamics and the relationships of these dynamics to cognitive and attentional states, however, are unknown. We conducted functional magnetic resonance imaging as human participants performed attention tasks, watched comedy sitcom episodes and an educational documentary, and rested. Whole-brain dynamics traversed a common set of latent states that spanned canonical gradients of functional brain organization, with global desynchronization among functional networks modulating state transitions. Neural state dynamics were synchronized across people during engaging movie watching and aligned to narrative event structures. Neural state dynamics reflected attention fluctuations such that different states indicated engaged attention in task and naturalistic contexts, whereas a common state indicated attention lapses in both contexts. Together, these results demonstrate that traversals along large-scale gradients of human brain organization reflect cognitive and attentional dynamics