Single-cell transcriptomic and T cell antigen receptor analysis of human cytomegalovirus (hCMV)-specific memory T cells reveals effectors and pre-effectors of CD8+- and CD4+-cytotoxic T cells.

Latent human cytomegalovirus (hCMV) infection can pose a serious threat of reactivation and disease occurrence in immune-compromised individuals. Although T cells are at the core of the protective immune response to hCMV infection, a detailed characterization of different T cell subsets involved in hCMV immunity is lacking. Here, in an unbiased manner, we characterized over 8000 hCMV-reactive peripheral memory T cells isolated from seropositive human donors, at a single-cell resolution by analysing their single-cell transcriptomes paired with the T cell antigen receptor (TCR) repertoires. The hCMV-reactive T cells were highly heterogeneous and consisted of different developmental and functional memory T cell subsets such as, long-term memory precursors and effectors, T helper-17, T regulatory cells (TREGs) and cytotoxic T lymphocytes (CTLs) of both CD4 and CD8 origin. The hCMV-specific TREGs, in addition to being enriched for molecules known for their suppressive functions, showed enrichment for the interferon response signature gene sets. The hCMV-specific CTLs were of two types, the pre-effector- and effector-like. The co-clustering of hCMV-specific CD4-CTLs and CD8-CTLs in both pre-effector as well as effector clusters suggest shared transcriptomic signatures between them. The huge TCR clonal expansion of cytotoxic clusters suggests a dominant role in the protective immune response to CMV. The study uncovers the heterogeneity in the hCMV-specific memory T cells revealing many functional subsets with potential implications in better understanding of hCMV-specific T cell immunity. The data presented can serve as a knowledge base for designing vaccines and therapeutics.

Condensed-phase isomerization through tunnelling gateways.

Quantum mechanical tunnelling describes transmission of matter waves through a barrier with height larger than the energy of the wave1. Tunnelling becomes important when the de Broglie wavelength of the particle exceeds the barrier thickness; because wavelength increases with decreasing mass, lighter particles tunnel more efficiently than heavier ones. However, there exist examples in condensed-phase chemistry where increasing mass leads to increased tunnelling rates2. In contrast to the textbook approach, which considers transitions between continuum states, condensed-phase reactions involve transitions between bound states of reactants and products. Here this conceptual distinction is highlighted by experimental measurements of isotopologue-specific tunnelling rates for CO rotational isomerization at an NaCl surface3,4, showing nonmonotonic mass dependence. A quantum rate theory of isomerization is developed wherein transitions between sub-barrier reactant and product states occur through interaction with the environment. Tunnelling is fastest for specific pairs of states (gateways), the quantum mechanical details of which lead to enhanced cross-barrier coupling; the energies of these gateways arise nonsystematically, giving an erratic mass dependence. Gateways also accelerate ground-state isomerization, acting as leaky holes through the reaction barrier. This simple model provides a way to account for tunnelling in condensed-phase chemistry, and indicates that heavy-atom tunnelling may be more important than typically assumed.

Fluorescence Quenching in J-Aggregates through the Formation of Unusual Metastable Dimers.

Molecular aggregation alters the optical properties of a system as fluorescence may be activated or quenched. This is usually described within the well-established framework of H- and J-aggregates. While H-aggregates show nonfluorescent blueshifted absorption bands with respect to the isolated monomer, J-aggregates are fluorescent displaying a redshifted peak. In this publication, we employ a combined approach of experiment and theory to study the complex aggregation features and photophysical properties of diaminodicyanoquinone derivatives, which show unusual and puzzling nonfluorescent redshifted absorption bands upon aggregation. Our theoretical analysis demonstrates that stable aggregates do not account for the experimental observations. Instead, we propose an unprecedented mechanism involving metastable dimeric species formed from stable dimers to generate nonfluorescent J-aggregates. These results represent a novel kind of aggregation-induced optical effect and may have broad implications for the photophysics of dye aggregates.

Blockchain in manufacturing quality control: A computer simulation study.

Blockchain has been applied to quality control in manufacturing, but the problems of false defect detections and lack of data transparency remain. This paper proposes a framework, Blockchain Quality Controller (BCQC), to overcome these limitations while fortifying data security. BCQC utilizes blockchain and Internet-of-Things to form a peer-to-peer supervision network. This paper also proposes a consensus algorithm, Quality Defect Tolerance (QDT), to adopt blockchain for during-production quality control. Simulation results show that BCQC enhances data security and improves defect detections. Although the time taken for the quality control process increases with the number of nodes in blockchain, the application of QDT allows multiple inspections on a workpiece to be consolidated at a faster pace, effectively speeding up the entire quality control process. The BCQC and QDT can improve the quality of parts produced for mass personalization manufacturing.

"Inverted" CO molecules on NaCl(100): a quantum mechanical study.

Somewhat surprisingly, inverted ("O-down") CO adsorbates on NaCl(100) were recently observed experimentally after infrared vibrational excitation (Lau et al., Science, 2020, 367, 175-178). Here we characterize these species using periodic density functional theory and a quantum mechanical description of vibrations. We determine stationary points and minimum energy paths for CO inversion, for low (1/8 and 1/4 monolayers (ML)) and high (1 ML) coverages. Transition state theory is applied to estimate thermal rates for "C-down" to "O-down" isomerization and the reverse process. For the 1/4 ML p(1 × 1) structure, two-dimensional and three-dimensional potential energy surfaces and corresponding anharmonic vibrational eigenstates obtained from the time-independent nuclear Schrödinger equation are presented. We find (i) rather coverage-independent CO inversion energies (of about 0.08 eV or 8 kJ mol-1 per CO) and corresponding classical activation energies for "C-down" to "O-down" isomerization (of about 0.15 eV or 14 kJ mol-1 per CO); (ii) thermal isomerization rates at 22 K which are vanishingly small for the "C-down" to "O-down" isomerization but non-negligible for the back reaction; (iii) several "accidentally degenerate" pairs of eigenstates well below the barrier, each pair describing "C-down" to "O-down" localized states.

Introduction: Covid-19 and the conditions and struggles of agrarian classes of labour.

Covid-19 generated a crisis in capitalism, but not of capitalism. Capitalism reproduces itself in crisis and in ways that have significant but uneven impacts on the conditions and struggles of agrarian classes of labour. This article explores preliminary studies of how Covid-19 has affected agrarian social formations in Africa, Asia and Latin America and the farmers, petty commodity producers, labourers and agribusinesses who populate them. It considers some of the implications for wage-labour, agriculture, accumulation and social reproduction including care work. And it briefly considers Covid-19's political impacts-in terms of the role of the state and possibilities for challenging capitalism, its violence and its ecological crisis.

Role of Endoscopic Resection Versus Surgical Resection in Management of Malignant Colon Polyps: a National Cancer Database Analysis.

BACKGROUND: Endoscopic resection (polypectomy) or surgery, are the main approaches in management of malignant colon polyps. There are very few large population-based studies comparing outcomes between the two. METHODS: Using the National Cancer Database, we identified patients ≥ 18 years with the first diagnosis of T1N0M0 malignant polyp from 2004 to 2015. Patients with a positive resection margin were excluded. Outcomes were compared between those who had surgery versus those who had polypectomy. Overall survival was compared using Kaplan-Meier curves. Multivariate Cox proportional hazards analysis was performed to generate hazard ratios, adjusted for patient, demographic, and tumor factors. RESULTS: A total of 31,062 patients met the inclusion criteria, out of which 2593 (8.3%) underwent polypectomy alone and 28,469 (91.7%) had surgery. Overall survival was significantly better in the surgical group compared with the polypectomy group. One-year and 5-year survival for surgery were 95.8% and 86.1% respectively compared with 94.2% and 80.6% for polypectomy (p < .0001). Hazard ratio for surgery after adjusting for various clinical-, demographic-, and tumor-level factors was 0.53 (p < .0001). CONCLUSION: Our study is the largest population-based analysis of patients with T1N0M0 malignant colon polyps. Overall survival was higher in patients who underwent surgery compared with polypectomy. This remained consistent even after adjusting for multiple patient and tumor factors between the two groups.

Impact of Pharmacy Student-Driven Postdischarge Telephone Calls on Heart Failure Hospital Readmission Rates: A Pilot Program.

Background: Heart failure (HF) hospitalization rates have remained high in the past 10 years. Numerous studies have shown significant improvement in HF readmission rates when pharmacists or pharmacy residents conduct postdischarge telephone calls. Objective: The purpose of this retrospective review of a pilot program was to evaluate the impact of pharmacy student-driven postdischarge phone calls on 30- and 90-day hospital readmission rates in patients recently discharged with HF. Methods: A retrospective manual chart review was conducted for all patients who received a telephone call from the pharmacy students. The primary endpoint compared historical readmissions, 30 and 90 days prior to hospital discharge, with 30 and 90 days post discharge readmissions. For the secondary endpoints, historical and postdischarge 30-day and 90-day readmission rates were compared for patients with a primary diagnosis of HF and for patients with a secondary diagnosis of HF. Descriptive statistics were calculated in the form of means and standard deviations for continuous variables and frequencies and percentages for categorical variables. Results: Statistically significant decrease was observed for both the 30-day (P = .006) and 90-day (P = .007) readmission periods. Prior to the pharmacy students' phone calls, the overall group of 131 patients had historical readmission rates of 24.43% within 30 days and 38.17% within 90 days after hospital discharge. After the postdischarge phone calls, the readmission rates decreased to 11.45%, for 30 days, and 22.90%, for 90 days. Conclusion: Postdischarge phone calls, specifically made by pharmacy students, demonstrated a positive impact on reducing HF-associated hospital readmissions, adding to the growing body of evidence of different methods of pharmacy interventions and highlighting the clinical impact pharmacy students may have in transition of care services.

Navigating the Challenges of Adjuvant Chemotherapy in Older Patients with Early-Stage Non-Small-Cell Lung Cancer.

Lung cancer is a disease of older adults. In the US and worldwide, more than 60% of patients being diagnosed are over the age of 65 years. The preferred treatment of stage I-II non-small-cell lung cancer (NSCLC) is surgical resection. Adjuvant chemotherapy with a platinum-based combination is the standard of care for patients with early-stage NSCLC after surgery. However, there have been no large prospective studies to test the efficacy of adjuvant chemotherapy in the elderly, the population most affected by lung cancer. The available evidence is limited to retrospective reviews of large population databases or post hoc analyses of prospective studies in age-unselected populations. This review aims to address the knowledge gap pertaining to the use of adjuvant chemotherapy in older patients with resected NSCLC. There are many barriers to use of adjuvant chemotherapy in older adults with NSCLC. The utilization of adjuvant chemotherapy amongst older adults has been slow but is improving. While the elderly may tolerate a lower dose intensity of chemotherapy compared with younger patients, they do garner benefit from adjuvant chemotherapy. There is a lack of a standardized tool to risk-stratify older patients for adjuvant chemotherapy after resection. Geriatric assessment may help guide decision making in the clinical practice setting. The principles of geriatric assessment and commonly employed tools for such assessment will be reviewed. Further, the emerging therapies in adjuvant treatment of lung cancer based on genetic mutations will be discussed.

Is There a Correlation Between Footstep Length, Lower Extremities, and Stature?

A probable correlation between stature and footstep length is expected, and consequently, the stature may be estimated from footstep length. The present research was conducted to study the correlation of footstep length with length of the lower extremities and stature. The study participants (n=142) were asked to walk on a paper sheet with inked feet and footstep length was measured. Mean stature and lower limb length were significantly larger in males. Sex differences were not observed in the average footstep length. Average footstep length and lower limb length did not show a significant correlation among the participants. A statistically significant correlation was observed between average footstep length and stature only among females. Our observations suggest that the length of the lower limb may not be a major factor in determining the footstep length of a person and that the forensic utility of stature estimation from footstep length may be limited.

Elevated level of prostate specific antigen among prostate cancer patients and high prevalence in the Gangetic zone of Bihar, India.

Prostate cancer (CaP) is a common reproductive cancer among men. This study was conducted to correlate the cancer incidence with Gangetic zone and to correlate the tumor marker prostate specific antigen (PSA) level in serum with different age groups and stage of malignancy. Patients suffering from CaP in the pathology unit of Mahavir Cancer Sansthan (Hospital and Research Centre), Patna, Bihar, India were studied from June 2009 to May 2010. PSA level in the serum of CaP patients was estimated by ELISA method. CaP incidence was highly recorded in Gangetic zone than the non-Gangetic zone. Maximum patients were in the 56 - 75 years age group with a marked predominance. Results of PSA examination showed that serum PSA level was not correlating with the age of patient and stage of malignancy. Significantly, elevated level of more than 10 ng/ml of PSA was recorded among the studied cancer patients. In this study, it is concluded that Gangetic zone habitat have high risk of CaP and elevated level of PSA was marked in Bihar, India.