Electronic structure of strain-tunable Janus WSSe-ZnO heterostructures from first-principles.

The electronic structure of semiconducting 2D materials such as monolayer transition metal dichalcogenides (TMDs) are known to be tunable via environment and external fields, and van der Waals (vdW) heterostructures consisting of stacks of distinct types of 2D materials offer the possibility to further tune and optimize the electronic properties of 2D materials. In this work, we use density functional theory (DFT) calculations to calculate the structure and electronic properties of a vdW heterostructure of Janus monolayer WSSe with monolayer ZnO, both of which possess out of plane dipole moments. The effects of alignment, biaxial and uniaxial strain, orientation, and electric field on dipole moments and band edge energies of this heterostructure are calculated and examined. We find that the out of plane dipole moment of the ZnO monolayer is highly sensitive to strain, leading to the broad tunability of the heterostructure band edge energies over a range of experimentally-relevant strains. The use of strain-tunable 2D materials to control band offsets and alignment is a general strategy applicable to other vdW heterostructures, one that may be advantageous in the context of clean energy applications, including photocatalytic applications, and beyond.

Conquering the complex world of human septins: implications for health and disease.

Septins are highly conserved filamentous proteins first characterized in budding yeast and subsequently identified in must eukaryotes. Septins can bind and hydrolyze GTP, which is intrinsically related to their formation of septin hexamers and functional protein interactions. The human septin family is composed of 14 loci, SEPT1-SEPT14, which encode dozens of different septin proteins. Their central GTPase and polybasic domain regions are highly conserved but they diverge in their N-terminus and/or C-terminus. The mechanism by which the different isoforms are generated is not yet well understood, but one can hypothesize that the use of different promoters and/or alternative splicing could give rise to these variants. Septins perform diverse cellular functions according to tissue expression and their interacting partners. Functions identified to date include cell division, chromosome segregation, protein scaffolding, cellular polarity, motility, membrane dynamics, vesicle trafficking, exocytosis, apoptosis, and DNA damage response. Their expression is tightly regulated to maintain proper filament assembly and normal cellular functions. Alterations of these proteins, by mutation or expression changes, have been associated with a variety of cancers and neurological diseases. The association of septins with cancer results from alterations of expression in solid tumors or translocations in leukemias [mixed lineage leukemia (MLL)]. Expression changes in septins have also been associated with neurological conditions such as Alzheimer's and Parkinson's disease, as well as retinopathies, hepatitis C, spermatogenesis and Listeria infection. Pathogenic mutations of SEPT9 were identified in the autosomal dominant neurological disorder hereditary neuralgic amyotrophy (HNA). Human septin research over the past decade has established their importance in cell biology and human disease. Further functional characterization of septins is crucial to our understanding of their possible diagnostic, prognostic, and therapeutic applications.

Separation of nuclei representing different phases of the growth cycle from unsynchronized mammalian cell cultures.

Nuclei have been isolated from unsynchronized cultures of Chinese hamster fibroblasts after varying intervals of growth following the incorporation of thymidine (-3)H for 20 min. These nuclei were fractionated by unit gravity sedimentation in a stabilizing density gradient of sucrose, and fractions were analyzed for the concentration of nuclei, DNA, and radioactivity. A more rapidly sedimenting population of nuclei in the G(2) phase of the cell cycle was separated from a group of nuclei in the G(1) phase, and nuclei in progressive stages of DNA synthesis (S phase) were distributed between these two regions. The fractionation of intact cells by sedimentation according to their position in the cell cycle was found to be less satisfactory than the corresponding separation of nuclei. This probably results from the continuous accumulation of mass within individual cells throughout the entire cell cycle, whereas most of the mass of a nucleus is replicated during a relatively narrow interval of the total cell cycle.

Noise raises blood pressure without impairing auditory sensitivity.

Two rhesus monkeys, exposed continuously to realistic patterns and levels of noise for 9 months, exhibited sustained elevations in blood pressure that did not return to baseline values after the noise ended. Auditory brainstem responses, measured before and after exposure, indicated no change in auditory sensitivity.

Solubilization of nonhistone chromosomal proteins by carboxymethyldextran for chromatography.

Chromosomal proteins extracted from calf thymus by 0.35 M NaCl were insoluble at the low salt concentration needed initially for ion-exchange chromatography. However, the addition of high-affinity carboxymethyl-dextran rendered the precipitated proteins soluble, permitting them to be fractionated by elution from DEAE-Sephacel. In this way, the separation of HMG-1 from HMG-2 was achieved, as well as a partial fractionation of the low mobility group proteins, under conditions that did not disturb the native conformation of the proteins.

Fractionation of granule proteins of granulocytes by copper chelate chromatography.

The tendency of lactoferrin to associate with other proteins at low salt concentrations defeated attempts to fractionate the acetate-extracted granule proteins of guinea pig granulocytes by ion-exchange chromatography. This problem was overcome by using copper-chelate chromatography at high salt concentrations to separate lactoferrin from the other granule proteins. Lysozyme and a 'cationic protein' were purified to apparent homogeneity in the same operation. The chromatographic profile of proteins extracted from purified secondary granules differed from that of proteins extracted from total granules chiefly in the absence of a substantial 'cationic protein' peak.

Localization of eosinophil-derived neurotoxin and eosinophil cationic protein in neutrophilic leukocytes.

Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are generally regarded as eosinophil-specific proteins. We tested whether EDN and ECP are present in mature neutrophils. By indirect immunofluorescence, both eosinophils and neutrophils stained with antibodies to EDN and ECP. Lysates of purified (<0.1% eosinophil contamination) neutrophils contained EDN, 112+/-4 ng/10(6) cells, and ECP, 163+/-2 ng/10(6) cells, whereas eosinophil major basic protein (MBP) was not detectable. Electron microscopic examination of immunogold-labeled buffy coat cells stained with EDN antibody showed that EDN is localized to neutrophil granules. Finally, EDN mRNA was detected in lysates of highly purified neutrophils (0.001% eosinophil contamination) by the reverse transcription-polymerase chain reaction. We conclude that proteins that are either identical to or immunologically cross-reactive with EDN and ECP are present in neutrophils and that EDN is synthesized and localized to neutrophil granules. Thus, caution must be exercised in interpreting the presence of EDN and ECP as specific markers of eosinophil-associated inflammation in human disease.

Effect of inflammatory serum on 14C-glucosamine incorporation into bone marrow granulocytes in vitro.

As a preliminary approach to developing a biochemical assay for detecting humoral regulators of granulocyte maturation in the normal and inflammatory states, studies were carried out on the effects of normal and inflammatory sera on the incorporation of 14C-glucosamine into the glycoproteins of bone marrow granulocytes in vitro. We observed that, relative to normal serum, inflammatory serum had a marked stimulatory effect on 14C-glucosamine incorporation into these glycoproteins. This property of inflammatory serum reached a maximum at about 8 h after the initiation of inflammation in vivo and preceded the maximum increase in the mitotic activity of granulocyte precursors in the marrow by 18 h. It was also found that normal serum contains both dialyzable and heat-sensitive nondialyzable factors that inhibit 14C-glucosamine incorporation into bone marrow granulocytes in vitro. Data are presented which indicate that the stimulatory effect of inflammatory serum is most likely due to a nondialyzable factor which is capable of blocking the effect of the inhibitors present in normal serum.

Interplay between fibrinolysis and complement: plasmin cleavage of iC3b modulates immune responses.

BACKGROUND: The plasmin(ogen) and complement systems are simultaneously activated at sites of tissue injury, participating in hemostasis, wound healing, inflammation and immune surveillance. In particular, the C3 proteolytic fragment, iC3b, and its degradation product C3dg, which is generated by cleavage by factor I (FI) and the cofactor complement receptor CR1, are important in bridging innate and adaptive immunity. Via a thioester (TE) bond, iC3b and C3dg covalently tag pathogens, modulating phagocytosis and adaptive immune responses. OBJECTIVE: To examine plasmin-mediated proteolysis of iC3b, and to evaluate the functional consequences, comparing the effects with products generated by FI/CR1 cleavage of iC3b. METHODS: Dose-dependent and time-dependent plasmin-mediated cleavage of iC3b were characterized by analytical gel electrophoresis. The properties of the resultant TE bond-containing fragments on phagocytosis and induction of pro-inflammatory cytokines were measured in cell culture systems. RESULTS: At low concentrations, plasmin effectively cleaves iC3b, but at numerous previously undescribed sites, giving rise to novel C3c-like and C3dg-like moieties, the latter of which retain the TE bond. When attached to zymosan or erythrocytes and exposed to THP-1 macrophages, the C3dg-like proteins behave almost identically to the bona fide C3dg, yielding less phagocytosis as compared with the opsonin iC3b, and more macrophage secretion of the pro-inflammatory cytokine, IL-12. CONCLUSION: Plasmin cleavage of iC3b provides a complement regulatory pathway that is as efficient as FI/CR1 but does not require a cellular cofactor.

Quality of ambulatory care after myocardial infarction among Medicare patients by type of insurance and region.

PURPOSE: To evaluate use of effective cardiac medications and rehabilitation after myocardial infarction in the ambulatory setting in health maintenance organizations (HMOs) and fee-for-service care, and by region. SUBJECTS AND METHODS: We surveyed elderly Medicare patients during 1996 and 1997 in California (n = 516), Florida (n = 304), and the Northeast (n = 220; Massachusetts, New York, and Pennsylvania) approximately 18 months after myocardial infarction. We assessed use of cardiac medications and rehabilitation for HMO (n = 520) and fee-for-service (n = 520) patients matched by age, sex, month of infarct, and region. RESULTS: Across all regions, similar proportions of HMO and fee-for-service patients were using aspirin (72%, n = 374 vs. 74%, n = 387), beta-blockers (38%, n = 195 vs. 32%, n = 168), angiotensin-converting enzyme inhibitors (31%, n = 159 vs. 29%, n = 148), cholesterol-lowering agents (28%, n = 146 vs. 30%, n = 157), and calcium channel blockers (31%, n = 162 vs. 31%, n = 159; all P >0.07), except in California where more HMO patients received beta-blockers (36%, n = 93 vs. 26%, n = 66, P = 0.01). In adjusted analyses, use of these drugs did not differ significantly between HMO and fee-for-service patients. Substantial regional differences were evident in the use of beta-blockers (Northeast 46%, n = 102; Florida 34%, n = 102; California 31%, n = 159) and cholesterol-lowering agents (California 35%, n = 182; Florida 24%, n = 73; Northeast 22%, n = 48; each P <0.001). Fee-for-service patients were more likely than HMO patients to receive cardiac rehabilitation in unadjusted (32%, n = 167, vs. 22%, n = 141, P = 0.001) and adjusted analyses. CONCLUSIONS: Both HMO and fee-for-service patients would likely benefit from greater use of beta-blockers and cholesterol-lowering agents. Professional fees for cardiac rehabilitation may promote increased use among fee-for-service patients. Future studies should assess the quality of ambulatory cardiac care in different types of HMOs and the reasons for geographic variations in cardiac drug use.

CLONE 3: plasmid drawing and clone management software program for microcomputers.

CLONE 3 is a microcomputer software program which draws circular and linear plasmid maps, facilitates cloning operations and performs related sequence analysis and information retrieval functions. This article describes the use of the CLONE 3 program to streamline the flow of information in the research laboratory doing genetic engineering applications.

Evidence for a factor in normal human serum that induces human neutrophilic granulocyte end-stage maturation in vitro.

The end-stage maturation of neutrophilic granulocyte precursor cells isolated from normal human bone marrow by Ficoll density centrifugation was studied in a liquid culture assay system used previously to study the maturation of guinea pig granulocyte precursors. Dialyzed normal human serum induced end-stage morphological maturation of human granulocyte precursors and this induction was proportional to a serum level of up to 5.0% in the assay medium. At serum concentrations greater than 5.0% a pronounced inhibition of maturation was observed. Passage of serum through a DEAE-Fractogel 650S column equilibrated with 0.01 M phosphate buffer (pH 7.0) resulted in the binding of the end-stage granulocyte maturation factor to the column. The activity eluted from the column in a fraction containing 17% of the starting serum protein that was inhibitor-free and was also capable of inducing the appearance of granulocyte alkaline phosphatase, a specific biochemical marker for granulocyte end-stage maturation. GMF is most likely a protein since it was destroyed by protease digestion. The data also indicate that neither purified human transferrin nor human recombinant granulocyte colony-stimulating factor can substitute for human serum GMF as a granulocyte end-stage maturation factor in this assay system. It was observed, however, that purified human transferrin greatly potentiated the effect of GMF suggesting that transferrin plays a supporting role in the end-stage maturation of human granulocytes in vitro. To our knowledge the evidence presented here indicates for the first time the existence of a neutrophilic granulocyte end-stage maturation factor in normal human serum.

The effect of soap distribution on diarrhoea: Nyamithuthu Refugee Camp.

BACKGROUND: In January 1993, Nyamithuthu Camp in Malawi housed 64000 Mozambican refugees. Communicable diseases, primarily diarrhoea, pneumonia, malaria and measles, contribute to substantially higher mortality rates in refugee populations compared to similar non-displaced populations. METHOD: A systematic sample of 402 households in one portion of the camp were surveyed for diarrhoeal risk factors, and then interviewed twice weekly for 4 months regarding new diarrhoea episodes and the presence of soap in the household. Two-hundred grams of soap per person was distributed monthly. RESULTS: Households had soap on average only 38% of the interview days. Soap was used primarily for bathing and washing clothes (86%). Although 81% of mothers reported washing their children's hands, only 28% of those mothers used soap for that purpose. The presence of soap in a household showed a significant protective effect: there were 27% less episodes of diarrhoea in households when soap was present compared to when no soap was present (RR = 0.73, 95% CI: 0.54 < RR < 0.98). Potential confounding factors were assessed and did not appear to be responsible for the association between the presence of soap and reductions in diarrhoea incidence. CONCLUSION: In summary, our findings suggest that the provision of regular and adequate soap rations, even in the absence of a behaviour modification or education programme, can play an important role in reducing diarrhoea in refugee populations. If subsequent study confirms the soap as a cheap and effective measure to reduce diarrhoea, its provision in adequate amounts should be a high priority in refugee settings.

PIP: In January 1993, Nyamithuthu Camp in Malawi housed 64,000 Mozambican refugees. Communicable diseases such as diarrhea, pneumonia, malaria, and measles cause substantially higher mortality rates in refugee populations compared to similar nondisplaced populations. A sample of 402 households in one part of the camp was surveyed for diarrheal risk factors, then interviewed twice weekly for 4 months about new diarrhea episodes and the presence of soap in the household. Each refugee was routinely rationed 240 g of soap in bar form per month. Surveyed households had soap on an average of only 38% of interview days, with soap used mainly for bathing and washing clothes. While 81% of mothers reported washing their children's hands, only 28% of those mothers used soap for that purpose. There were 27% fewer episodes of diarrhea in households where soap was present compared to when soap was not present. No potential confounding factors were found to be responsible for the association between the presence of soap and reductions in the incidence of diarrhea. These findings highlight the importance of regularly providing adequate soap rations in reducing diarrhea in refugee populations.

Sarcoidosis with orbital tumor outside the lacrimal gland: initial manifestation in 2 elderly white women.

Two elderly white women (aged 72 and 87 years) were first seen with painless, unilateral orbital swelling. Orbital scanning revealed masses infiltrating the soft tissue around the eye. Biopsy results showed nodular, noncaseating granulomas consistent with sarcoidosis. One patient's workup revealed systemic manifestations of sarcoidosis at the time of examination with hilar lymphadenopathy noted on gallium scan; the other refused a complete systemic workup. The orbital tumors resolved with systemic prednisone therapy. To our knowledge, our 87-year-old patient is the oldest to be seen with orbital sarcoidosis. These 2 patients demonstrate that this diagnosis must be considered with orbital tumors in the elderly and in unusual locations, such as these which occurred outside the lacrimal gland.

Haemophilus influenzae: an important cause of maternal and neonatal infections.

Although Haemophilus influenzae is recognized as a major pathogen of infants, its role in maternal and neonatal infections is not as well appreciated. We analyzed the records of all mothers and neonates infected with H influenzae over a 10-year period. Twenty-eight mother/neonate sets were identified in which at least one had documented infection with H influenzae. Of the 18 mothers with documented infection, 13 had chorioamnionitis, endometritis, or both, and two of these mothers were bacteremic with H influenzae. Of the 23 infected neonates, 15 presented with early sepsis and/or pneumonia and nine had conjunctivitis. During the period of the study, only group B streptococci and Escherichia coli were more common as causes of early neonatal bacteremia. Under the conditions of this retrospective study, maternal infection predicted neonatal infection. However, prospective studies in which asymptomatic patients are cultured will be required to determine how well maternal colonization/infection with H influenzae predicts neonatal infection.

Mast cells, neutrophils, and eosinophils in prurigo nodularis.

BACKGROUND AND DESIGN: Prurigo nodularis is a disease of unknown cause. To characterize the involvement of mast cells, neutrophils, and eosinophils in lesional tissue, we analyzed seven skin biopsy specimens by an indirect immunofluorescence technique for localization of mast cell tryptase, neutrophil elastase, and eosinophil granule major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin. RESULTS: Mast cells were detected in all of the specimens, with prominent numbers of mast cells in three specimens; there was minimal or no extracellular deposition of tryptase in any of the tissues. Neutrophil infiltration was observed in all specimens, but few cells were observed in four; extracellular elastase was minimal or absent in all but one specimen in which prominent dermal elastase deposition was found. Scanty eosinophil infiltration was present in all specimens; however, extracellular deposition of the eosinophil granule proteins including major basic protein, eosinophil-derived neurotoxin, and eosinophil cationic protein was present in all but one specimen and striking deposition of at least one eosinophil granule protein was present in six of the seven specimens. CONCLUSIONS: These studies suggest that mast cell numbers are increased in prurigo nodularis and that eosinophil degranulation as evidenced by striking extracellular deposition of granule proteins is prominent in lesions. In contrast, extracellular deposition of mast cell and neutrophil proteins is absent. The distinctive proteins of the eosinophil granule have potent effects on tissues; the toxicity of these proteins and their deposition in lesional tissue suggest a pathogenic role for the eosinophil in prurigo nodularis.

Effect of therapeutic level ultrasound on visual evoked potentials in the hypoxic cat.

The effect of 1.0 MHz ultrasound at an intensity of 1.0 W/cm2 SATA on brain function of anaesthetized cats was assessed using Visual Evoked Potentials (VEPs). Ultrasound alone did not significantly modify the averaged VEP signals. However, acute hypoxia depressed the VEP response. When the brain was exposed to ultrasound during the hypoxic episode, the VEP response remained normal. Raising brain temperature by whole body heating could not mimic the beneficial effect of ultrasound on the VEP response during hypoxia. This suggests that therapeutic ultrasound may have a protective effect on hypoxic tissues and may have clinical applications.

Displacement chromatography of simple protein mixtures, using carboxymethyldextrans.

Simple mixtures of proteins have been used as models to demonstrate that the fractionation of proteins by carboxymethyldextrans on an anion exchanger (Peterson, E.A. (1978) Anal. Biochem. 90, 767--784) is fundamentally a displacement process. Examples include the separation of two closely similar proteins, the A and B forms of beta-lactoglobulin. The use of carboxymethyldextran spacers was essential for good separation, since resolution based on protein--protein displacement was generally inadequate. The origins and effects of heterogeneity in the preparations used as spacers are discussed.

Autocrine HBEGF expression promotes breast cancer intravasation, metastasis and macrophage-independent invasion in vivo.

Increased expression of HBEGF in estrogen receptor-negative breast tumors is correlated with enhanced metastasis to distant organ sites and more rapid disease recurrence upon removal of the primary tumor. Our previous work has demonstrated a paracrine loop between breast cancer cells and macrophages in which the tumor cells are capable of stimulating macrophages through the secretion of colony-stimulating factor-1 while the tumor-associated macrophages (TAMs), in turn, aid in tumor cell invasion by secreting epidermal growth factor. To determine how the autocrine expression of epidermal growth factor receptor (EGFR) ligands by carcinoma cells would affect this paracrine loop mechanism, and in particular whether tumor cell invasion depends on spatial ligand gradients generated by TAMs, we generated cell lines with increased HBEGF expression. We found that autocrine HBEGF expression enhanced in vivo intravasation and metastasis and resulted in a novel phenomenon in which macrophages were no longer required for in vivo invasion of breast cancer cells. In vitro studies revealed that expression of HBEGF enhanced invadopodium formation, thus providing a mechanism for cell autonomous invasion. The increased invadopodium formation was directly dependent on EGFR signaling, as demonstrated by a rapid decrease in invadopodia upon inhibition of autocrine HBEGF/EGFR signaling as well as inhibition of signaling downstream of EGFR activation. HBEGF expression also resulted in enhanced invadopodium function via upregulation of matrix metalloprotease 2 (MMP2) and MMP9 expression levels. We conclude that high levels of HBEGF expression can short-circuit the tumor cell/macrophage paracrine invasion loop, resulting in enhanced tumor invasion that is independent of macrophage signaling.