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Helicity in solids often arises from the precise ordering of cooperative intra- and intermolecular interactions unique to natural, organic or molecular systems. This exclusivity limited the realization of helicity and its ensuing properties in dense inorganic solids. Here we report that Ga atoms in GaSeI, a representative III–VI–VII one-dimensional (1D) van der Waals crystal, manifest the rare Boerdijk–Coxeter helix motif. This motif is a non-repeating geometric pattern characterized by 1D face-sharing tetrahedra whose adjacent vertices are rotated by an irrational angle. Using InSeI and GaSeI, we show that the modularity of 1D van der Waals lattices accommodates the systematic twisting of a periodic tetrahelix with a 41screw axis in InSeI to an infinitely extending Boerdijk–Coxeter helix in GaSeI. GaSeI crystals are non-centrosymmetric, optically active and exfoliable to a single chain. These results present a materials platform towards understanding the origin and physical manifestation of aperiodic helicity in low-dimensional solids.

The rediscovery of one-dimensional (1D) and quasi-1D (q-1D) van der Waals (vdW) crystals ushered the realization of nascent physical properties in 1D that are suitable for applications in photonics, electronics, and sensing. However, despite renewed interest in the creation and understanding of the physical properties of 1D and q-1D vdW crystals, the lack of accessible synthetic pathways for growing well-defined nanostructures that extend across several length scales remains. Using the highly anisotropic 1D vdW NbS3–I crystal as a model phase, we present a catalyst-free and bottom-up synthetic approach to access ultralong nanowires, with lengths reaching up to 7.9 mm and with uniform thicknesses ranging from 13 to 160 nm between individual nanowires. Control over the synthetic parameters enabled the modulation of intra- and interchain growth modalities to selectively yield only 1D nanowires or quasi-2D nanoribbons. Comparative synthetic and density functional theory (DFT) studies with a closely related nondimerized phase, ZrS3, show that the unusual preferential growth along 1D can be correlated to the strongly anisotropic bonding and dimeric nature of NbS3–I.

Background: US racial and ethnic minorities have well-established elevated rates of comorbidities, which, compounded with healthcare access inequity, often lead to worse health outcomes. In the current COVID-19 pandemic, it is important to understand existing disparities in minority groups’ critical care outcomes and mechanisms behind these—topics that have yet to be well-explored. Objective: Assess for disparities in racial and ethnic minority groups’ COVID-19 critical care outcomes. Design: Retrospective cohort study. Participants: A total of 2125 adult patients who tested positive for COVID-19 via RT-PCR between March and December 2020 and required ICU admission at the Cleveland Clinic Hospital Systems were included. Main Measures: Primary outcomes were mortality and hospital length of stay. Cohort-wide analysis and subgroup analyses by pandemic wave were performed. Multivariable logistic regression models were built to study the associations between mortality and covariates. Key Results: While crude mortality was increased in White as compared to Black patients (37.5% vs. 30.5%, respectively; p= 0.002), no significant differences were appraised after adjustment or across pandemic waves. Although median hospital length of stay was comparable between these groups, ICU stay was significantly different (4.4 vs. 3.4, p= 0.003). Mortality and median hospital and ICU length of stay did not differ significantly between Hispanic and non-Hispanic patients. Neither race nor ethnicity was associated with mortality due to COVID-19, although APACHE score, CKD, malignant neoplasms, antibiotic use, vasopressor requirement, and age were. Conclusions: We found no significant differences in mortality or hospital length of stay between different races and ethnicities. In a pandemic-influenced critical care setting that operated outside conditions of ICU strain and implemented standardized protocol enabling equitable resource distribution, disparities in outcomes often seen among racial and ethnic minority groups were successfully mitigated.

This article describes the process of review and modification of a Doctor of Pharmacy didactic course remediation process. A highlight of the new process includes early intervention with a Learning Specialist, creating the opportunity for students to address learning issues earlier in the courses.

Computational methods can potentially accelerate development of more efficient organic materials for second harmonic generation. Here, we test the method that includes the evolutionary algorithm for predicting crystal structure and prognosis of nonlinear optical properties based on the predicted structure. For this test, we selected 2-iodo-3-hydroxypyridine, which exhibits second harmonic generation intensity comparable to that of urea. We performed global minimization of the lattice energy and found the experimental structure when many-body dispersion correction is added to the density functional theory values. We analyzed geometric preferences of the halogen bonding in predicted virtual polymorphs. We also found linear correlation between the lengths of the iodine–iodine halogen bonds and calculated second order susceptibilities.

Genetically predisposed CTLA4 insufficiency in humans is associated with gastric cancer development, which is paradoxical to the prototypical role of CTLA4 in suppressing antitumor immunity. CTLA4 is a critical immune checkpoint against autoimmune disorders. Autoimmunity has been implicated in protumor or antitumor activities. Here, we show that CTLA4 insufficiency initiates de novo tumorigenesis in the mouse stomach through inflammation triggered by host-intrinsic immune dysregulation rather than microbiota, with age-associated progression to malignancy accompanied by epigenetic dysregulation. The inflammatory tumorigenesis required CD4 T cells, but not the TH1 or TH17 subsets. Deficiencies in IL-4 and IL-13 or IL-4 receptor α broke the link between inflammation and initiation of tumorigenesis. This study establishes the causality of CTLA4 insufficiency in gastric cancer and uncovers a role of type 2 inflammation in initiating gastric epithelial transformation. These findings suggest possible improvement of immune therapies by blocking tumorigenic type 2 inflammation while preserving antitumor type 1 immunity.

The University of British Columbia has an interest in incorporating life cycle environmental impacts and financial information into project planning, as well as research and teaching. As part of a tall wood building research program with the UBC Sustainability Initiative and Dept. of Civil Engineering, a comprehensive life cycle assessment (LCA) and life cycle costing (LCC) study was done of two student high-rise residential buildings, based on the result of whole building LCA done by Athena Sustainable Materials Institute and whole building LCC done by Sensible Building Science. These buildings are of similar design but Brock Commons Tallwood House has a hybrid mass-timber structure and Ponderosa Commons Cedar House has a more traditional concrete structure. This paper will include a brief overview of the research process, data collection, analysis, and key results. The paper will then focus on the main opportunities, challenges, and lessons learned from both the results of the LCA/LCC projects and the process of conducting the study.

As nurses, we influence every aspect of our patients' care and are shaped ourselves by all that we experience in the course of our daily practice.

Introduction:The epidemiology of coronary artery disease (CAD) has shifted, with increasing cardiometabolic (CM) disease and decreasing obstructive CAD in patients referred for myocardial perfusion imaging (MPI). Coronary microvascular dysfunction, defined as impaired coronary flow reserve (CFR) by positron emission tomography (PET), has emerged as a key mediator of risk. Our objective was to assess whether CFR provides additive value to identify low-risk CM disease patients compared with single-photon emission computed tomography (SPECT) MPI.Methods:We retrospectively studied patients with CM disease (obesity, diabetes, or chronic kidney disease (CKD) stage ≥3) and without known CAD referred for PET or SPECT MPI at our center from 2006 to 2020. Annualized all-cause and cardiac mortality was determined from death certificates, and propensity-matched low-risk PET and SPECT patients were compared using Poisson and Cox regression.Results:CM disease was prevalent in consecutive MPI referrals without CAD including obesity (N=8869), diabetes (N=4896) and CKD (N=3555), and higher among PET MPI (p <0.001). Prevalence of summed stress score (SSS) >3 reflecting obstructive CAD was low (12%, 15% and 16%). Conversely, prevalence of CFR <2 was high (52%, 61% and 69%), reflecting impaired myocardial perfusion. In adjusted hazard analysis, normal MPI was associated with lower risk of all-cause and cardiac death (p <0.001). Normal PET (SSS ≤3 and CFR >2) was associated with lower all-cause death compared to normal SPECT (Figure, A).Normal PET and SPECT identified low-risk (<1%/year cardiac death) patients with obesity and diabetes, however those with CKD remained moderate-risk (1-3%/year) (Figure, B).Conclusion:CM disease is common among patients without CAD referred for MPI. Normal PET and SPECT MPI identify a low-risk group for obesity and diabetes, but not CKD. PET with CFR has additive prognostic utility to identify low-risk individuals compared to SPECT.

The transmembrane isoform of mucin 1 (MUC1/TM) is a well-recognized tumor antigen, contributing to tumorigenesis and immune evasion. Although MUC1/TM has been correlated with malignancy, we have previously reported on antitumor properties and prevention of tumor development by a secreted splice variant of MUC1 (MUC1/sec). Because myeloid-derived suppressor cells (MDSCs) play a critical role in tumor-induced immunosuppression, we investigated their recruitment by tumor cells expressing either MUC1/TM or MUC1/sec. DA-3 tumor cells expressing MUC1/sec recruit dramatically lower levels of MDSCs, relative to MUC1/TM-expressing DA-3 cells. Because MUC1/sec was previously shown to down-regulate tumor expression of urokinase plasminogen activator (uPA), a protease linked to tumor aggressiveness and metastasis, the potential role of uPA in MDSC recruitment was investigated. Tumor-derived uPA is capable of recruiting MDSCs, and correlates with tumor development. In addition to diminishing recruitment of MDSCs, the effect of MUC1/sec on MDSC-suppressive mechanisms was investigated. MUC1/sec, or its unique immunoenhancing peptide, is capable of blocking expression of arginase 1 and production of reactive oxygen species in MDSCs, implicated in the suppression of T cells. These findings demonstrate a new mechanism of MDSC recruitment, and provide evidence that MUC1/sec has antitumor properties affecting MDSCs.

The transmembrane isoform of mucin 1 (MUC1/TM) is a well-recognized tumor antigen, contributing to tumorigenesis and immune evasion. Although MUC1/TM has been correlated with malignancy, we have previously reported on antitumor properties and prevention of tumor development by a secreted splice variant of MUC1 (MUC1/sec). Because myeloid-derived suppressor cells (MDSCs) play a critical role in tumor-induced immunosuppression, we investigated their recruitment by tumor cells expressing either MUC1/TM or MUC1/sec. DA-3 tumor cells expressing MUC1/sec recruit dramatically lower levels of MDSCs, relative to MUC1/TM-expressing DA-3 cells. Because MUC1/sec was previously shown to down-regulate tumor expression of urokinase plasminogen activator (uPA), a protease linked to tumor aggressiveness and metastasis, the potential role of uPA in MDSC recruitment was investigated. Tumor-derived uPA is capable of recruiting MDSCs, and correlates with tumor development. In addition to diminishing recruitment of MDSCs, the effect of MUC1/sec on MDSC-suppressive mechanisms was investigated. MUC1/sec, or its unique immunoenhancing peptide, is capable of blocking expression of arginase 1 and production of reactive oxygen species in MDSCs, implicated in the suppression of T cells. These findings demonstrate a new mechanism of MDSC recruitment, and provide evidence that MUC1/sec has antitumor properties affecting MDSCs.

The thymus is the major site of T cell maturation; extensive proliferation, differentiation, and apoptosis occur in this organ. During mammary tumorigenesis, there is a profound involution of the thymus associated with a severe depletion of the most abundant subset of thymocytes, CD4+8+immature cells. Experiments to investigate the mechanism of loss of the CD4+8+population indicated that there was no increase in the systemic levels of glucocorticoids, no loss of bone marrow precursors, and no decrease in precursor seeding of the thymus. Likewise, no enhanced emigration of thymocytes from the thymus to the periphery was observed in tumor-bearing mice. A slight increase in apoptosis was found in tumor bearers' thymi, but there was no apparent decrease in the proliferation of early thymic precursors CD4−8−cells. Importantly, severely altered levels of subpopulations of the CD4−8−precursors, consistent with an arrest in differentiation at an early stage of development, were detected. Moreover, thymic stromal cell function appeared to become impaired during tumorigenesis, possibly due to the action of tumor-derived factors. Thus, downregulation of cell-mediated immune functions occurring at late stages of the disease may be causally related to the thymic involution occurring during mammary tumorigenesis.

Performance of triboelectric nanogenerators for harvesting mechanical energy from the ambient environment has been limited by structural complexity, cost‐effectiveness, and mechanical weakness of materials. Herein, a cost‐effective vertical contact separation mode triboelectric nanogenerator using polyethylene (PE) and polycarbonate (PC) in a regular digital versatile disc is reported. This cost‐effective nanogenerator with simplified structures is able to generate an open‐circuit voltage of 215.3 V and short‐circuit current of 80 μA. The effects of the distance of impact and the air gap between the triboelectric layers have also been tested from 3 to 9 cm, and 0.25 to 1 cm, respectively. It is determined that 0.5 cm is the optimal air gap. The nanogenerator is also tested in different real‐life scenarios including stresses produced by a moving car, walking, and a rolling skateboard over the nanogenerator. The surfaces of the triboelectric layers are further modified by surface‐charge engineering which induced a 460% increase in the output power. These tests reveal a significant electrical response and mechanical stability under stress. In summary, this study demonstrates that the relatively inexpensive PE and PC triboelectric pair has the potential to be used for highly efficient, mechanically robust triboelectric nanogenerators. A cost‐effective triboelectric nanogenerator has been designed and fabricated that scavenges energy from human footsteps and vehicle motion. The device has been tested considering real‐world scenarios and has been finely tuned by testing variable impact distance, load frequency, and triboelectric air gap. The device has been further enhanced by surface‐charge engineering that resulted in higher output.

Differential expression of antibody dependent cellular cytotoxicity (ADCC) effectors was studied in normal Balb/cCrgl mice and those bearing a chemically induced 7, 12 dimethylbenzanthracene mammary adenocarcinoma. Depletion of macrophages from normal mouse splenocytes by Sephadex G‐10 columns resulted in elimination of ADCC. Further separation of the normal G‐10 nonadherent splenocytes on nylon wool columns did not result in any population with significant cytotoxicity. However, Balb/c mice bearing mammary tumors showed enhanced levels of ADCC which were not eliminated by macrophage removal. Lymphocytes from tumor bearers further separated on nylon wool yielded nonadherent and adherent populations both capable of effecting significant ADCC. Treatment of the nylon nonadherent cells of both normal and tumor bearing mice with anti‐asialo GM1(AGM1) and complement decreased the ADCC responses. The same treatment only marginally affected cytotoxic levels of nylon adherent cells from tumor bearers, indicating that these effectors are primarily of non‐NK lineage. In addition, G‐10 nonadherent, nylon adherent cells from tumor bearers separated on a fluorescence activated cell sorter based on the presence of surface immunoglobulins (slg) revealed that both the slg‐and slg+(98% pure) sorted cells were capable of functioning in ADCC. To determine whether in the tumor mice the 2% of slg‐cells present in the slg+sorted population were the ADCC effectors, mixing experiments were done in which up to 10% of slg‐cells from tumor bearers were added to nylon adherent cells from normal mice. No significant increases in ADCC levels were found over that of normal mice. These experiments indicate that the 2% slg‐cells were not the ADCC effectors nor were they inducing normal B cells to exert this type of cytotoxic reaction in vitro. To further substantiate the B cell lineage of the slg+ADCC effectors, surface immunoglobulins were removed with protease treatment. After a 36 hr incubation, 92% of the cells had regenerated their slg. The results presented in this paper demonstrate that various splenic lymphoreticular populations from tumor bearers possess an enhanced cytolytic activity against antibody coated target cells. Among these is a unique nylon adherent slg+cell that is capable of functioning as an ADCC effector.

Tumor burden has been shown to induce a variety of phenotypic and functional changes in the cellular constituents of the host's immune system. These changes have been implicated as mechanisms by which tumors avoid rejection. Studies of BALB/c mice bearing a D1‐DMBA‐3 mammary adenocarcinoma showed alterations of the splenocyte populations. There was a five‐fold increase of macrophages (Mφ) that were phenotypically and functionally analyzed to establish their role in tumor‐induced modifications of the host's immune response. Monoclonal antibody staining defined a Mac‐1+2+population which comprised up to 20% of the splenocytes in tumor‐bearers (TB), but is negligible in spleens from normal mice. These Mao‐1+2+Mφ were found to mediate down‐regulation of both polyclonal and antigen‐specific T and B cell responses in vitro and in vivo. Although B cell responses were suppressed via prostaglandin E2(PGE2) production by the TB Mφ, T cell responses were relatively refractory to PGE2‐mediated down‐regulation. Instead, they were suppressed by a contact‐dependent T cell‐Mφ interaction. Furthermore, tumor‐derived factors such as granulocyte‐Mφ colony‐stimulating factor (GM‐CSF) seem to play an important role in the induction and expansion of the Mac‐1+2+Mφ. These cells appear to mediate down‐regulation of the host immune responses by at least two distinct mechanisms: 1) PGE2production and 2) a cell contact‐dependent, but non‐major‐histocompatibility‐complex‐specific, interaction.

Previous studies demonstrated that despite freedom from MTV and mammary tumors early in life Balb/cCrgl mice possess lymphocytes sensitive to mouse mammary tumor antigen(s) within 2-3 weeks of life. This sensitivity was manifested in blastogenic transformation and migration inhibition reactions using RIII milk and purified MTV from RIII milk. These reactions were not elicited with the MTV-negative milk from NIH Swiss mice. Preincubation of MTV with anti-MTV antibody inhibited the blastogenic reaction. In contrast, antibody raised against a type C murine oncornavirus had no inhibitory effect and did not by itself induce blastogenic transformation. The nature of the virus-related antigen responsible for the lymphocyte sensitivity has not been ascertained, nor has its location in the animals' tissue been determined. However, radioimmune assays for p14 antigen in multiple tissues of Balb/c mice have yielded insignificant values suggesting either incomplete expression of the genome and/or different levels of the diverse mouse mammary tumor virus antigenic components.MTV-induced lymphocyte transformation is observed at low levels and in a small percentage of Balb/cCrgl mice as early as two weeks after birth in the blastogenic assay. At 8 weeks of age the responses in the lymphocyte transformation and migration inhibition assays are intermediate in frequency and/or intensity; by 16 weeks essentially maximal responses are noted.

Lymphocytes of MTV-negative Balb/c mice are sensitive to one or more antigens of MTV as determined by blastogenic transformation and migration inhibition assays. The lymphocytes from MTV-positive Balb/cfC3H mice are nonre-sponsive in these assays but become responsive after the mice have been implanted with MTV-positive tumors. The latter findings imply that there may be either a state of tolerance to MTV antigens which is broken by the tumor transplant or that the responses are directed towards antigens to which the host is not tolerant. The cause of the sensitivity of lymphocytes from MTV-negative Balb/c mice to MTV antigens has not been determined but two possible explanations are discussed: horizontal transmission and derepression of genetic information for viral antigen.Supported by contract NO1 CP 43358 from the Virus Cancer Program of the National Cancer Institute, U. S. Public Health Service.We gratefully acknowledge the valuable and efficient technical assistance of Mr. Mantley Dorsey and Mr. Jan Stern.

Exposure of lymphoid cells from normal and mammary tumor-bearing Balb/cCrgl mice to MMTV antigens result in positive responses in blastogenic transformation and migration inhibition reactions. The levels of these responses appear to depend on the murine strain source of the viral preparations. Enhanced reactivities were observed in cultures exposed to purified MMTV from culture fluids of mammary tumor cells of spontaneous origin in the C3H strain when compared to purified MMTV derived from milk of mice from the RIII strain. To ensure the virus relatedness of the differences observed, MMTVs obtained from a common source, i.e., the Crandall feline embryo kidney cell line, were employed in blastogenesis assays. Parallel testing of feline cell-derived C3H, RIII, and GR mammary tumor viruses resulted in different levels of [3H]thymidine incorporation by spleen cells from Balb/cCrgl mice over a range of viral concentrations. These results indicate that it is possible to detect various types of MMTV variants with cell-mediated immune assays. The diverse functional reactivities elicited by these viruses may be related to the differences observed in their bioactivities as determined by incidence and development of mammary tumors and the potential of causing metastases.

The presence of antigen(s) related to the exogenous milk-transmitted murine mammary tumor virus on the surface of BALB/c splenic lymphocytes has been documented previously. Since the BALB/c strain lacks murine mammary tumor virus, the presence of murine mammary tumor virus-related antigen(s) on lymphocytes has been ascribed to expression of germinally transmitted Mtvtranscripts and proviruses were characterized to evaluate this hypothesis. Transcripts from genomic size Mtvprovirus(es) accumulated in the spleen in an age-dependent manner. Two novel Mtvtranscripts of 7.8 and 6.4 kb were observed in the spleen. These observations indicate that the transcriptional and translational expression of an endogenous Mtvoccurs in normal cells of the lymphoreticular lineage.

Normal murine B lymphocytes are not known to be effectors of the Fc receptor‐mediated, antibody‐dependent cellular cytotoxicity (ADCC). In contrast, we report here that highly purified splenic B cells from mammary tumor‐bearing mice develop the potential of lysing antibody‐coated target cells. These lymphocytes are characterized by being G‐10 nonadherent, nylon wool adherent, sIg∗, FcR+, Thy 1.2−, asialo GM1−, and the immunoglobulin heavy‐chain genes of both chromosomes are rearranged. The lytic reaction is characterized by a noninterdigitating binding and by the appearance of endocytotic vesicles in the target cells. Nuclear disintegration occurs 18 h after initial effector‐target cell conjugate formation. At such time, only minor cytoplasmic membrane alterations are evident. The emergence of killer B cells in tumor‐bearing hosts indicates that all lymphoreticular cell types bearing Fc receptors are capable of mediating ADCC.— Lopez, D. M.; Blomberg, B. B.; Padmanabhan, R. R.; Bourguignon, L. Y. W. Nuclear disintegration of target cells by killer B lymphocytes from tumor‐bearing mice. FASEB J.3: 37‐43; 1989.

Minor lymphocyte-stimulating antigens and other superantigens have been shown to be encoded by the 3' long terminal repeat (LTR) open reading frame (ORF) of the endogenous and exogenous mammary tumor viruses. We have previously reported the presence of an antigen(s) related to mouse mammary tumor virus (MMTV) envproducts in splenic B cells of BALB/c mice. By Western blots an MMTV-related molecule of 68 kDa was detected in splenic preparations of B lymphocytes, but not in T cells. Antibodies against the MMTV envelope proteins gp52 and gp36, obtained by elution after binding to nitrocellulose in the presence of purified MMTV, reacted in Western blots with a 68-kDa protein present in B cells, indicating that this molecule is related to both MMTV envelope proteins. Using antibody against the MMTV 3' LTR ORF coding sequence, 10-15% of splenic B cells reacted by immunoperoxidase staining with this reagent, while no such staining was observed in splenic T cell preparations. Furthermore, in preparations of splenic B cells, but not T cells, two bands of 68 and 33 kDa, respectively, were detected by Western blots using the anti-ORF. These results demonstrate that the superantigen protein is present in B cells of BALB/c mice in two distinct forms, i.e., as a 68-kDa molecule, possibly associated with products of the envgene, and as a 33-kDa form.

Aqueous ethanol extract of a tunicate which was previously found to exert antitumor and immunosuppressive activities in vivowas tested for its effect on normal human lymphocytes in vitro.The extract suppressed the uptake of tritiated thymidine by lymphocytes stimulated with mitogen. This suppressive effect did not require continuous presence of the extract. Treatment of lymphocytes prior to mitogenic stimulation resulted in suppressive effect. The fact that suppression by the extract could also be achieved 24 hr after exposure to mitogen, an interval which was found to suffice for the attainment of maximal commitment for blastogenic transformation indicates that Ete can act at a stage subsequent to the binding of the lectin and elicitation of a mitogenic signal(s).

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The article focuses on the Salvation Army relief agency which is known for its service before, during and after an emergency without an exit plan neither an intention to leave.

The article offers information on the relief efforts taken by the Salvation Army in response to the September 11, 2001 attacks at Ground Zero in New York City, called as Compassion Under Fire and was granted full control of the feeding operation for rescue and response workers at Ground Zero.