cssi/SciSciGPT-SciSciNet huggingface dataset:
SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the gut microbiota in type 2 diabetic mice

Type 2 diabetes (T2D) is associated with generalized vascular dysfunction characterized by increases in large artery stiffness, endothelial dysfunction, and vascular smooth muscle dysfunction. Sodium glucose cotransporter 2 inhibitors (SGLT2i) represent the most recently approved class of oral medications for the treatment of T2D, and have been shown to reduce cardiovascular and overall mortality. Although it is currently unclear how SGLT2i decrease cardiovascular risk, an improvement in vascular function is one potential mechanism. The aim of the current study was to examine if dapagliflozin, a widely prescribed STLT2i, improves generalized vascular dysfunction in type 2 diabetic mice. In light of several studies demonstrating a bi-directional relation between orally ingested medications and the gut microbiota, a secondary aim was to determine the effects of dapagliflozin on the gut microbiota. Male diabetic mice (Db, n = 24) and control littermates (Con; n = 23) were randomized to receive either a standard diet or a standard diet containing dapagliflozin (60 mg dapagliflozin/kg diet; 0.006%) for 8 weeks. Arterial stiffness was assessed by aortic pulse wave velocity; endothelial function and vascular smooth muscle dysfunction were assessed by dilatory responses to acetylcholine and sodium nitroprusside, respectively. Compared to untreated diabetic mice, diabetic mice treated with dapagliflozin displayed significantly lower arterial stiffness (Db = 469 cm/s vs. Db + dapa = 435 cm/s, p < 0.05), and improvements in endothelial dysfunction (area under the curve [AUC] Db = 57.2 vs. Db + dapa = 117.0, p < 0.05) and vascular smooth muscle dysfunction (AUC, Db = 201.7 vs. Db + dapa = 285.5, p < 0.05). These vascular improvements were accompanied by reductions in hyperglycemia and circulating markers of inflammation. The microbiota of Db and Con mice were distinctly different, and dapagliflozin treatment was associated with minor alterations in gut microbiota composition, particularly in Db mice, although these effects did not conclusively mediate the improvements in vascular function. Dapagliflozin treatment improves arterial stiffness, endothelial dysfunction and vascular smooth muscle dysfunction, and subtly alters microbiota composition in type 2 diabetic mice. Collectively, the improvements in generalized vascular function may represent an important mechanism underlying the cardiovascular benefits of SGLT2i treatment.
Disorders of Tyrosine Metabolism

Five inherited disorders of tyrosine catabolism are known and depicted in Fig. 15.1. Hereditary tyrosinaemia type I is characterized by progressive liver disease and renal tubular dysfunction with rickets. Hereditary tyrosinaemia type II (Richner-Hanhart syndrome) presents with keratitis and blisterous lesions of the palms and soles. Tyrosinaemia type III may be asymptomatic or associated with mental retardation. Hawkinsinuria may be asymptomatic or presents with failure to thrive and metabolic acidosis in infancy. In alkaptonuria symptoms of osteoarthritis usually appear at an advanced age. Other inborn errors of tyrosine metabolism include oculocutaneous albinism caused by a deficiency of melanocyte-specific tyrosinase, converting tyrosine into DOPA-quinone; the deficiency of tyrosine hydroxylase, the first enzyme in the synthesis of dopamine from tyrosine; and the deficiency of aromatic l-amino acid decarboxylase, which also affects tryptophan metabolism. The latter two disorders are covered in Chap. 26.
Evaluation of feather meal as a source of sulfur amino acids for growing steers.

In situ and digestion studies were conducted to evaluate feather meal (FTH), blood meal (BM), and meat and bone meal (MBM) for escape protein content, amino acid composition of the escape protein, true protein digestibility, and digestibility of the individual amino acids. Following 12 h of ruminal incubation, escape protein values were 73.5, 92.4, and 60.8% of CP for FTH, BM, and MBM, respectively. Blood meal and MBM were poor sources of sulfur amino acids (SAA), whereas FTH was a good source. Most of the SAA of FTH, however, was Cys, with very little Met. True protein digestibilities were not different for the protein sources (P > .15), ranging from 86.7 to 94.0% of the CP. However, digestibilities of the individual amino acids were quite different. Two growth studies were conducted to evaluate FTH as a source of SAA for growing cattle. The first study used 120 steers (228 +/- 15 kg) supplemented with urea, MBM, MBM plus 1% FTH, or MBM plus 2% FTH. Additionally, incremental amounts of rumen-protected Met were added to treatments containing MBM. Supplementation of MBM increased (P < .05) ADG compared with the urea control. Addition of FTH to MBM resulted in a linear (P < .01) increase in ADG. However, addition of rumen-protected Met to MBM plus FTH treatments further improved gains. Although FTH is an effective source of SAA, Met probably was first-limiting. The second study used 90 steers (243 +/- 18 kg) supplemented with BM plus incremental amounts of SAA from either FTH or rumen-protected Met. Addition of SAA improved ADG compared with BM alone (P < .05). Rumen-protected Met as a source of SAA improved ADG compared with FTH (P < .05). The SAA from FTH promoted a gain response equal to 50% of the response obtained with rumen-protected Met. Formulation of ruminant diets for metabolizable amino acids must account for escape value and digestibility of each individual amino acid. Feather meal is an effective source of SAA; however, Cys supplies over five times the amount supplied by Met.
OXIDATION AND HEAT TRANSFER STUDIES IN GRAPHITE CHANNELS: V. THERMAL PROPERTIES OF AIR-COOLED GRAPHITE CHANNELS**Work performed under the auspices of the United States Atomic Energy Commission.

A summary is given of the work done on the thermal behavior of air-cooled graphite channels. The differences in results between this work and work done in the United Kingdom appear to arise from the different models used. The recent results and re-evaluation of the previous experiments indicate that the model used in the United Kingdom work is not experimentally supported.
ACTIVATION OF TYROSINE HYDROXYLASE AND DOPAMINE METABOLITE ACCUMULATION IN THE PRIMATE CINGULATE CORTEX FOLLOWING CHRONIC HALOPERIDOL

A kinetic activation of tyrosine hydroxylase (TH) and an increase in dopamine (DA) metabolite concentration were observed in the basal ganglia of the vervet monkey after a single dose of haloperidol. Tolerance developed to this response after chronic haloperidol treatment. In contrast, in the frontal and cingulate cortex the activation of TH and DA metabolite accumulation was minimal after a single dose of haloperidol, administered to naive animals, but increased significantly when the same dose of haloperidol was administered to animals chronically treated with haloperidol.
Anneliese Maier: Galileo and Theories of Impetus

In one of her late essays Anneliese Maier took up a theme that had interested her throughout a good part of her life and attempted to clarify, once again, the extent to which Galileo was indebted to fourteenth-century theories of impetus for the elaboration of his “new science” of motion (1967, pp. 465–490).1 In the course of her exposition she pointed out how Galileo’s concept of impetus changed from his earliest writings on motion to his more mature works, but that even when such changes are taken into account, the way in which he thought of impetus was quite different from the view of the four-teenth-century Scholastics. She also raised a question about his reading of Aristotle’s texts bearing on this subject, suggesting that he might have gotten his knowledge of Aristotle “at second hand,” and so implying that the ideas about impetus being entertained in the latter part of the sixteenth century were different from those that were current in the fourteenth century (ibid., p. 468). Regardless of how Galileo came by his understanding of impetus, however, Maier contended that even his earlier view was closer than the medievals’ to the modern concept of inertia, and thus that it was easier for him to make the transition to the “new science” than it would have been had he well understood and subscribed to the fourteenth-century concept (ibid., pp. 468–469).
Birds and Butterflies Along Urban Gradients in Two Ecoregions of the United States: Is Urbanization Creating a Homogeneous Fauna?

Humans are transforming Earth’s landscape to an unprecedented degree in both magnitude and rate (Meyer and Turner 1992). We alter the landscape through the extraction of resources, the development of industry, the practice of agriculture, the pursuit of recreation, and the building of structures. These alterations affect every ecosystem on Earth (Vitousek et al. 1997).
Rising mortality in patients with combined burn and trauma

Combined trauma in the burn patient has been previously shown to have higher mortality. With improved critical care and multidisciplinary approach, we hypothesized the risk of mortality in combined burn and trauma has decreased. A retrospective analysis of trauma, burn and combined burn-trauma patients in the National Trauma Data Bank was performed comparing years 2007-2015 to years 1994-2002. The impact of burn injuries on mortality in patients with minor trauma has decreased (OR 2.45, CI 2.26-2.66, p<0.001 compared to OR 4.04, CI 4.51-4.66, p<0.001) in years 2007-2015 while the impact of burn injuries on mortality in patients with severe trauma has increased (OR 1.37, CI 1.29-1.47, p<0.001 compared to OR 1.26, CI 1.05-1.51, p<0.001). When controlling for known risk factors of mortality in burn and trauma, the contribution of the severity of trauma on mortality in combined burn-trauma patients with total body surface area ≥20% is negligible. In contrast, an increase in percentage of total body surface area burned is associated with a step-wise increase in mortality for all combined burn-trauma patients. However, the largest impact is seen in patients with minor trauma. This population represents a unique overlap of patients where future collaborative research can help identify best practices and improve outcomes.
Mathematics of dengue transmission dynamics: Roles of vector vertical transmission and temperature fluctuations.

Abstract A new deterministic model is designed and used to gain insight into the effect of seasonal variations in temperature and vector vertical transmission on the transmission dynamics of dengue disease. The model, which incorporates (among many other features) the dynamics of the immature dengue-competent mosquitoes, vertical transmission in the vector population, density-dependent larval mortality and temperature effects, is rigorously analysed and simulated using data relevant to the disease dynamics in Chiang Mai province of Thailand. The non-trivial disease-free equilibrium of the model is shown to be globally-asymptotically stable when the associated basic reproduction number of the model is less than unity. Numerical simulations of the model, using data relevant to the disease dynamics in the Chiang Mai province of Thailand, show that vertical transmission in the vector population has only marginal impact on the disease dynamics, and that the effect of vertical transmission is temperature-dependent (in particular, the effect of vertical transmission on the disease dynamics increases for values of the mean monthly temperature in the range [ 16 − 28 ] ∘ C, and decreases with increasing mean monthly temperature thereafter). It is further shown that dengue burden (as measured in terms of disease incidence) is maximized when the mean monthly temperature is in the range [ 26 − 28 ] ∘ C (and dengue burden decreases for mean monthly temperature values above 28 ∘ C). Thus, this study suggests that anti-dengue control efforts should be intensified during the period when this temperature range is recorded in the Chiang Mai province (this occurs between June and August).
Collaborative Learning Exercises for Teaching Protein Mass Spectrometry

A collaborative learning module for teaching protein mass spectrometry has been developed to overcome common obstacles to incorporating the modern topic of biological mass spectrometry into the undergraduate chemistry curriculum. Protein mass spectrometry data is provided to eliminate the need for expensive instrumentation, and an instructor’s manual gives necessary details for those unfamiliar with the topic. The first section provides background information on proteins and the field of proteomics. The second section describes the use of electrospray ionization to determine the molecular weight of a protein. The third section shows how to identify a protein using peptide mass mapping, and the fourth section describes tandem MS experiments for de novo peptide sequencing. Each section also includes lessons on the analytical instrumentation used to make mass measurements including electrospray ionization, matrix assisted laser desorption ionization, and time-of-flight mass spectrometry. The module includes ...
The (Deep) End of Empathy

Following an overview of the trends in contemporary scholarship on empathy, this article describes the lived experience of individuals with deep empathic sensitivity. Narrative accounts were drawn ...
The importance of patch attributes and context to the management and recovery of an endangered lagomorph

We investigated the role of patch attributes and context on patch occupancy of the Lower Keys marsh rabbit (Sylvilagus palustris hefneri). The Lower Keys marsh rabbit is a federally endangered lagomorph endemic to the Lower Keys of Florida. The marsh rabbit occurs in subpopulations on patches of high marsh that interact to form a metapopulation. Between March 1991 and July 1993, all known patches of high marsh in the Lower Keys were surveyed for presence or absence of marsh rabbit pellets three times per year. Of the 59 habitat patches, 20 had pellets present during all of the surveys (occupied patches), 22 had pellets present during at least one survey (variable patches), and 17 never had any pellets present (empty). Ten variables were measured at each of the 59 patches; seven of these variables concerned attributes of the patch (food, cover, patch size), and three were patch context variables (distance of patch to other patches, distance of patch to other features). Two discriminant function analysis (DFA) were performed. The first DFA compared empty patches to occupied patches (both variably and consistently occupied). Patch isolation explained the most variation in patch occupancy followed by area. The second DFA compared the variably occupied sites with the consistently occupied sites, and patch attributes variables involving the type and height of vegetation were significant. Management efforts for the Lower Keys marsh rabbit should be aimed at both improving habitat quality and decreasing distance between patches.
Performance Enhancement of Ag/HfO 2 Metal Ion Threshold Switch Cross-Point Selectors

A metal ion threshold switch (MITS) based on an Ag/TiN/HfO2/Pt stack is experimentally demonstrated with improved endurance. The incorporation of a low-temperature atomic layer deposition (ALD) TiN layer as an efficient diffusion barrier enables optimum Ag infiltration during the electroforming step. Further, the tunability of the threshold voltage (VTS) from 0.25 to 1.1V via bottom electrode (BE) work function engineering is demonstrated. The Ag/TiN/HfO2/Al MITS selector exhibits a 4.4x increase in VTS, $100~\mu \text{A}$ ON-current handling capability, low leakage (~10 pA), $10^{{7}}$ half-bias non-linearity and fast (<30 ns) turn-ON switching speed. The turn-OFF speed of the selector device is independent of the built-in field, indicating that the latter does not influence ionic relaxation during the filament rupture process.
Time sequence gamma-spectrometry of irradiated salt

Abstract Persisted Memory Mapping File (MMF) techniques have been developed for the processing and analysis of time-stamped list (TLIST) mode data collected from an irradiated salt sample. This is a new technique that is unique to this research and enables additional information to be obtained from a conventional pulse height analysis (PHA) gamma-spectrometry acquisition. A salt sample was irradiated using a DT neutron generator and immediately measured using TLIST acquisition for 1 month to generate a 22 GB data file. MMF techniques were used to process the file without size restrictions at a rate of 388.5 MB minute−1, with instant access to any position within the file, separating the file into a series of time sequenced spectra suitable for PHA analysis. This enabled 14 activation products to be identified at different time intervals (41Ar, 80Br, 80m Br, 47Ca, 34m Cl, 38Cl, 42K, 43K, 56Mn, 22 Na, 24 Na, 85Sr, 87m Sr and 69m Zn), and 6 radionuclides (80Br, 47Ca, 34m Cl, 56Mn, 24Na and 87m Sr) to be definitively confirmed based upon their measured half-life. Using this technique, the detection of 47Ca, and in-growth of its 47Sc progeny, was demonstrated as useful for calculating the time since irradiation.
Intraoperative Air Leak, Colonic Ischemia, or Tension: How to Salvage the Failed Anastomosis

Anastomotic leak rates in colorectal surgery remain persistently high despite increased awareness of contributing factors, low threshold for proximal fecal diversion, and modern technologies to better assess bowel perfusion. Leak rates for low colorectal anastomoses range 3–30% with risk factors including malnutrition, smoking, immunosuppression, prior radiation therapy, obesity, and male gender. Technical factors such as tension on the anastomosis and adequacy of the blood supply also play a critical role in the occurrence of leaks. This chapter will review intraoperative strategies to assess the integrity of colorectal anastomoses, reduce the risk of anastomotic leaks, and salvage a failed anastomosis and ischemic colonic conduit. Reconstructive techniques to salvage intraoperative and postoperative anastomotic leaks will also be reviewed.
Effects of the government's ban in Ghana on women in artisanal and small-scale gold mining

Abstract Artisanal and small-scale gold mining operations have been conducted in Ghana for centuries. Over time, technological advances in the industry occurred and miners separated from large-scale mining and applied this knowledge to small-scale or individual mining practices. In March 2017, the government responded to a media campaign against environmental degradation and placed a ban against water pollution; this ban affected all informal gold mining operations because of the chronic use of mercury in gold extraction, which contributes to water contamination. The unintended consequences of this ban were that approximately 1 million people lost their jobs. A qualitative study was conducted to understand how small-scale gold mining affected female miners and in turn, the implications of the ban on these women and their families. There were 21 illegal female miners interviewed in Akwatia, Ghana. The results from this study confirmed that many female miners used their mining money to support their families. Because the ban blocked mining employment opportunities, the women were forced into unreliable and low-paying alternative jobs and were unable to pay for school fees and food. Unfortunately, while the ban may have improved the environment, it also contributed to adverse outcomes related to women and children's development, like inadequate nutritional needs and school dropout rates; thus, bans like this need to be reconsidered and readapted to address these immeasurable consequences.
Assessing Introspective Awareness of Attention Capture

Visual attention can sometimes be involuntarily captured by salient stimuli, and this may lead to impaired performance in a variety of real-world tasks. If observers were aware that their attention was being captured, they might be able to exert control and avoid subsequent distraction. However, it is unknown whether observers can detect attention capture when it occurs. In the current study, participants searched for a target shape and attempted to ignore a salient color distractor. On a subset of trials, participants then immediately classified whether the salient distractor captured their attention (“capture” vs. “no capture”). Participants were slower and less accurate at detecting the target on trials on which they reported “capture” than “no capture.” Follow-up experiments revealed that participants specifically detected covert shifts of attention to the salient item. Altogether, these results indicate that observers can have immediate awareness of visual distraction, at least under certain circumstances.
Non-covalent interactions of hydrogen cyanide and acetonitrile with the quinoline radical cation via ionic hydrogen bonding

Abstract Non-covalent interactions of HCN and CH3CN with the quinoline radical cation (C9H7N+•) through carbon-based ionic hydrogen bonds in the gas phase result in binding energies of 8.1 and 11.5 kcal/mol, respectively. The quinoline cation can be externally solvated with HCN molecules which tend to favor the formation of hydrogen bonding chains rather than multiple direct attachments to the quinoline cation. The solvated structures allow the exposure of the quinoline ion on the surface of cold grains of meteorites and comets to reactive space molecules which could result in the formation of nitrogen-containing complex organic ions in space.
Utilization of the large-bore Penumbra JET 7 reperfusion catheter in thrombectomy for acute ischemic stroke: A single-center experience.

Background and PurposeThe Penumbra JET 7 reperfusion catheter is used in the revascularization of large vessel occlusions in acute ischemic stroke. Description of its use in clinical practice remai...
Dengue - Perils and Prevention.

Dengue virus (DENV) is responsible for an estimated 100 million symptomatic cases of infection and 10,000 deaths annually. The incidence of dengue has been doubling every decade since 1990.1 Dengue...
A pilot study on the feasibility of testing residential tap water in North Carolina: implications for environmental justice and health.

Background In 2015 alone, community water systems serving about 21 million Americans violated the United States Environmental Protection Agency's (US-EPA) water quality standards. While water at community treatment and distribution centers is regularly monitored and tested, little is known about pollutants in the water systems at the household level. Aims This pilot study assessed the feasibility of (1) testing for the presence and concentration of 14 contaminants and physicochemical parameters in household tap water in a low-income neighborhood and (2) using community engagement for recruitment and citizen science approaches to data collection. Methods We used a multistage approach that included geo-mapping to delineate testing sites, community engagement for recruitment and citizen science approaches to increase the response rate. We used a 14-in-one dipstick test designed to measure trace amounts of heavy metals, non-metallic elements, and physicochemical water properties in drinking water in a sample of 70 homes. Results In 50%, 25%, and 7% of water samples tested, the concentration of mercury, lead, and chromium, respectively, were higher than US-EPA drinking water standards. Citizen science approaches were effective for increasing response rates and low-income household participation in water quality testing. Significance The overlap between poverty, older homes, and high concentrations of potentially toxic metals in drinking water presents concerns for community health. Our pilot community engagement and citizen science approaches are likely scalable and would be of benefit to both the scientific community and to municipalities with constrained budgets. Future studies may examine the role of the principles of environmental justice in the distribution and prevalence of toxic elements in drinking water.
Effects of participation in a U.S. trial of newborn genomic sequencing on parents at risk for depression

Much emphasis has been placed on participant's psychological safety within genomic research studies; however, few studies have addressed parental psychological health effects associated with their child's participation in genomic studies, particularly when parents meet the threshold for clinical concern for depression. We aimed to determine if parents' depressive symptoms were associated with their child's participation in a randomized-controlled trial of newborn exome sequencing. Parents completed the Edinburgh Postnatal Depression Scale (EPDS) at baseline, immediately post-disclosure, and 3 months post-disclosure. Mothers and fathers scoring at or above thresholds for clinical concern on the EPDS, 12 and 10, respectively, indicating possible Major Depressive Disorder with Peripartum Onset, were contacted by study staff for mental health screening. Parental concerns identified in follow-up conversations were coded for themes. Forty-five parents had EPDS scores above the clinical threshold at baseline, which decreased by an average of 2.9 points immediately post-disclosure and another 1.1 points 3 months post-disclosure (both p ≤ .014). For 28 parents, EPDS scores were below the threshold for clinical concern at baseline, increased by an average of 4.7 points into the elevated range immediately post-disclosure, and decreased by 3.8 points at 3 months post-disclosure (both p < .001). Nine parents scored above thresholds only at 3 months post-disclosure after increasing an average of 5.7 points from immediately post-disclosure (p < .001). Of the 82 parents who scored above the threshold at any time point, 43 (52.4%) were reached and 30 (69.7%) of these 43 parents attributed their elevated scores to parenting stress, balancing work and family responsibilities, and/or child health concerns. Only three parents (7.0%) raised concerns about their participation in the trial, particularly their randomization to the control arm. Elevated scores on the EPDS were typically transient and parents attributed their symptomatology to life stressors in the postpartum period rather than participation in a trial of newborn exome sequencing.
Recent developments in sample preparation techniques combined with high-performance liquid chromatography: A critical review

This review article compares and contrasts sample preparation techniques coupled with high-performance liquid chromatography (HPLC) and describes applications developed in biomedical, forensics, and environmental/industrial hygiene in the last two decades. The proper sample preparation technique can offer valued data for a targeted application when coupled to HPLC and a suitable detector. Improvements in sample preparation techniques in the last two decades have resulted in efficient extraction, cleanup, and preconcentration in a single step, thus providing a pathway to tackle complex matrix applications. Applications such as biological therapeutics, proteomics, lipidomics, metabolomics, environmental/industrial hygiene, forensics, glycan cleanup, etc., have been significantly enhanced due to improved sample preparation techniques. This review looks at the early sample preparation techniques. Further, it describes eight sample preparation technique coupled to HPLC that has gained prominence in the last two decades. They are (1) solid-phase extraction (SPE), (2) liquid-liquid extraction (LLE), (3) gel permeation chromatography (GPC), (4) Quick Easy Cheap Effective Rugged, Safe (QuEChERS), (5) solid-phase microextraction (SPME), (6) ultrasonic-assisted solvent extraction (UASE), and (7) microwave-assisted solvent extraction (MWASE). SPE, LLE, GPC, QuEChERS, and SPME can be used offline and online with HPLC. UASE and MWASE can be used offline with HPLC but have also been combined with the online automated techniques of SPE, LLE, GPC, or QuEChERS for targeted analysis. Three application areas of biomedical, forensics, and environmental/industrial hygiene are reviewed for the eight sample preparation techniques. Three hundred and twenty references on the eight sample preparation techniques published over the last two decades (2001-2021) are provided. Other older references were included to illustrate the historical development of sample preparation techniques.
Interleukin-36 Cytokines in Infectious and Non-Infectious Lung Diseases

The IL-36 family of cytokines were identified in the early 2000’s as a new subfamily of the IL-1 cytokine family, and since then, the role of IL-36 cytokines during various inflammatory processes has been characterized. While most of the research has focused on the role of these cytokines in autoimmune skin diseases such as psoriasis and dermatitis, recent studies have also shown the importance of IL-36 cytokines in the lung inflammatory response during infectious and non-infectious diseases. In this review, we discuss the biology of IL-36 cytokines in terms of how they are produced and activated, as well as their effects on myeloid and lymphoid cells during inflammation. We also discuss the role of these cytokines during lung infectious diseases caused by bacteria and influenza virus, as well as other inflammatory conditions in the lungs such as allergic asthma, lung fibrosis, chronic obstructive pulmonary disease, cystic fibrosis and cancer. Finally, we discuss the current therapeutic advances that target the IL-36 pathway and the possibility to extend these tools to treat lung inflammatory diseases.
Isolation of normal and tumor-specific Pvt-1 cDNA clones.

One of the first examples of activation of a proto-oncogene by direct chromosomal translocation was identified in lymphoid malignancies with the aberrant association between c-myc and antigen receptor genes, i.e. immunoglobulin (Ig) or T- cell receptor (TCR) (reviewed in Cory 1986). More recently, a number of genes i.e. Bcl-2 (Cleary et al. 1986; Tsujimoto and Croce 1986), Bcl-3 (Ohno et al. 1990), Lyl-1 (Cleary et al. 1988), Ttg (McGuire et al. 1989) E2A (Nourse et al. 1990) and Il-3 (Grimaldi and Meeker 1989), have also been found associated with Ig or TCR in hematopoietic malignancies as a result of aberrant chromosomal translocation. Nearly 80% of mouse plasmacytomas contain a rcpt(12;15) chromosomal translocation which juxtapositions c-myc and Ig heavy chain genes and ultimately results in deregulation of c-myc gene expression (reviewed in Potter et al. 1984). Another 10–20% of mouse plasma cell tumors exhibit a rcpt (6;15) chromosomal translocation which results in the aberrant association of an Ig light chain gene with a region located more than 100kb distal to c-myc. Nevertheless, northern blot analysis of these tumors reveals similar levels of c-myc deregulation despite the enormous distance between this cluster of breakpoints, termed Pvt-1, and c-myc (Mushinski 1988). Pvt-1 is consistently found 100– 300kb distal to c-myc in rat, mouse and humans and, therefore, represents a conserved linkage group among these species (Fig. 1). In studies of rat thymomas, a region of common integration sites (Mis-1, Mlvi-1) for the Moloney murine leukemia virus (Mo-MuLV) were discovered which proved to be equivalent to mouse Pvt-1 (Tsichlis et al. 1983; Villeneuve et al. 1986; Koehne et al. 1989). In fact, Mo-MuLV or MCF proviral integration sites in the region of Pvt-1 have been found in 25–50% of rat thymomas (Lemay and Jolicoeur 1984) or murine T lymphomas (Graham et al. 1985). The translocation in the t(2;8) Burkitt’s lymphoma, JBL2, juxtaposes an Ig’ light chain to a region homologous to mouse Pvt-1 (Graham and Adams 1986). While many Burkitt’s lymphomas with t(2;8) or t(8;22) translocations contain chromosomal breakpoints which map 3′ of c-myc, most appear to cluster closer to c-myc than Pvt-1 (Henglein et al. 1989)(Fig. 1).
Simultaneous exploitation of the fundamental and higher order wineglass modes in a vibratory gyro

This paper reports the first step towards simultaneously operating the n = 2 and n = 3 pairs of modes in a disk resonator for two independent measurements of angular rate. A model based approach is adopted to estimate the resonator imbalance parameters and an iterative mass perturbation technique is developed to simultaneously reduce the frequency mismatch of the n = 2 mode pair as well as the n = 3 mode pair. At the termination of mass deposition process, each pair of modes exhibits a residual frequency mismatch of approximately 100 mHz.
Design of enhancement current-balanced logic for mixed-signal ICs

The dual-V/sub T/ and negative feedback mechanisms have been proposed to enhance Current Balanced Logic (CBL) for low noise IC design. The detailed circuit analysis and SPICE simulations show that the dual-V/sub T/ structure has advantages over the conventional CBL design in many design aspects, such as gate area, delay, power dissipation, and switching noise. The negative feedback can further reduce the current spike with some tradeoffs. The design procedures of the enhancement CBL are discussed in detail. The proposed methods give the designer a better control of the current spike for mixed-signal integrated circuits.
New methods for alkaloid synthesis : Generation of indole-2, 3-diquinomethanes as a route to indole alkaloids

Abstract The generation of an indole-2,3-quinodimethane intermediate and its use for the synthesis of indole alkaloids is described.
Distorted Mirrors: Americans and Their Relations with Russia and China in the Twentieth Century

As the United States enters the twenty-first century, it confronts two powers that loomed less large on the world stage a century before. Yet American policies toward Russia and China have been shaped by attitudes going back even further, as this new book relates. ""Distorted Mirrors"" traces American prejudices toward the two countries by focusing on the views of influential writers and politicians over the course of the twentieth century. Donald Davis and Eugene Trani show where American images of Russia and China originated, how they evolved, and how they have often helped sustain foreign policies generally negative toward the former and positive toward the latter. This wide-ranging survey draws on memoirs, archives, and interviews, much of it appearing in print for the first time, to show how influential individuals shaped these perceptions and policies based on what they saw - or thought they saw - in those two countries.Through a series of tableaux that traces America's relations with Russia and China through the twentieth century, the authors show how the personalities of certain players impacted the interpretation of key situations and conflicts and how cultural attitudes toward Russia and China became ingrained and difficult to dislodge. The book traces formative attitudes back to two late-nineteenth-century books, with George Kennan's ""Siberia and the Exile System"" painting a grim picture of tsarist penal colonies and William Rockhill's ""Land of the Lamas"" depicting China as an exotic Shangri-la.Davis and Trani show how these images were sustained over the years: for Russia, by Slavic expert Samuel Harper, State Department official Robert Kelley, journalist Eugene Lyons, ambassador William Bullitt, President Franklin D. Roosevelt, and policymakers George F. Kennan and Paul Nitze; and for China, by President Woodrow Wilson, philosopher John Dewey, journalist Edgar Snow, novelist Pearl S. Buck, ambassador Nelson T. Johnson, FDR, journalist Theodore White, and statesman Henry Kissinger. They also relate how Ronald Reagan and George H. W. Bush tried to replace these misconceptions with a policy of accommodation, and they assess the state of current U.S. attitudes and policies.""Distorted Mirrors"" marks a fresh approach to U.S. relations with these countries, emphasizing long-term attitudes that influenced policies rather than the reverse. It shows us that perceptions shaped over the course of the twentieth century are crucial for their bearing on the twenty-first, particularly if those unrestrained prejudices reemerge.
Ammonium Chloride Alters Secretory Protein Sorting within the Maturing Exocrine Storage Compartment

Abstract Addition of 20 mM ammonium chloride during in vitro chase incubation of [35S]methionine pulse-labeled parotid tissue does not perturb the magnitude or radiochemical composition of secretion stimulated by isoproterenol. An apparent inhibition of stimulated output of radiolabeled secretory proteins that was observed when ammonium chloride was added immediately postpulse (but not at later time points prior to stimulation) could be accounted for by slowdown in Golgi transit of exocrine secretory protein at a stage prior to completion of terminal glycosylation. Thus, ammonium chloride does not block entry of newly synthesized secretory proteins into the secretagogue-releasable storage granule compartment. By contrast, ammonium chloride increases the output and substantially alters the relative composition of newly synthesized protein in unstimulated secretion. The latter effects could be assigned to stages of intracellular transport that normally occur at chase times greater than 60 min postpulse and thus are focused within the maturing acinar storage granule. Notably, the compositional alterations cannot reflect the preferential exocytosis of immature granules. Taken together, these results suggest that the sorting of exocrine secretory proteins into the secretagogue-regulated pathway may not involve positive selection by a pH-based process initiated in a pregranule compartment. Rather, unstimulated secretion may arise by a negative sorting (or exclusion) process that occurs during compaction of proteins for storage within maturing granules and that is perturbed by weak base addition. Sorted (or excluded) proteins would appear to follow the vesicular (nongranular) secretory pathway that originates in maturing granules (von Zastrow, M., and Castle, J.D. (1987) J. Cell Biol. 105, 2675-2684).
High-Affinity [3H]THA (Tetrahydroaminoacridine) Binding Sites in Rat Brain

Tetrahydroaminoacridine (THA), an acetylcholinesterase inhibitor that is reported to have significant effects on cognition and memory in Alzheimer’s disease patients, binds to rat brain membranes in a saturable and reversible manner. Computer analysis of the binding data revealed high- and low-affinity sites with Kd values of 97.8 nM and 4.65 µM and Bmax values of 4.13 and 114 pmol/mg protein. Autoradiographic studies show that these binding sites are not co-localized with acetylcholinesterase activity. The binding of [3H]THA to membranes does not appear to be related to receptors for several neurotransmitters/neuromodulators, including acetylcholine and other acetylcholinesterase inhibitors. Amiridin, a closely related acetylcholinesterase inhibitor, was able to block specific [3H]THA binding (IC50 = 1.05 µM). While the function of THA mediated by these sites is unknown, they may be responsible in part for the distinct clinical effects of tetrahydroaminoacridine compared to other acetylcholinesterase inhibitors.
Electron-Lattice Interactions in Manganese-Oxide Perovskites

The virial theorem is invoked to argue for a first-order transition from localized to itinerant electronic behavior. A competition between localized and itinerant electronic behavior leads to phase segregation via cooperative oxygen displacements that may be manifest either as a stationary charge-density wave or as a condensation of two-manganese polarons into ferromagnetic, conductive clusters in a paramagnetic, polaronic matrix. Growth in a magnetic field of the ferromagnetic clusters to beyond their percolation threshold gives the intrinsic colossal magnetoresistance (CMR) found above Tc and the transition to a “bad metal” below T with increasing (180° φ c. A rapid rise in Tc ) Mn O Mn bond angle at cross-over where the CMR is found is attributed to an angle-dependent oxygen-vibration frequency ω φ o( ), a prediction that can be checked experimentally.
Experimental Inoculation of Egyptian Rousette Bats (Rousettus aegyptiacus) with Viruses of the Ebolavirus and Marburgvirus Genera

The Egyptian rousette bat (Rousettus aegyptiacus) is a natural reservoir for marburgviruses and a consistent source of virus spillover to humans. Cumulative evidence suggests various bat species may also transmit ebolaviruses. We investigated the susceptibility of Egyptian rousettes to each of the five known ebolaviruses (Sudan, Ebola, Bundibugyo, Tai Forest, and Reston), and compared findings with Marburg virus. In a pilot study, groups of four juvenile bats were inoculated with one of the ebolaviruses or Marburg virus. In ebolavirus groups, viral RNA tissue distribution was limited, and no bat became viremic. Sudan viral RNA was slightly more widespread, spurring a second, 15-day Sudan virus serial euthanasia study. Low levels of Sudan viral RNA disseminated to multiple tissues at early time points, but there was no viremia or shedding. In contrast, Marburg virus RNA was widely disseminated, with viremia, oral and rectal shedding, and antigen in spleen and liver. This is the first experimental infection study comparing tissue tropism, viral shedding, and clinical and pathologic effects of six different filoviruses in the Egyptian rousette, a known marburgvirus reservoir. Our results suggest Egyptian rousettes are unlikely sources for ebolaviruses in nature, and support a possible single filovirus—single reservoir host relationship.
Carbon as reducing agent for the precipitation of plasmonic Cu particles in glass

Abstract The first investigation on the use of carbon to produce metal nanocomposite glasses with plasmonic properties is reported. It is demonstrated how the reducing properties of graphite powder allow for producing Cu nanocomposite glasses in a controlled manner during heat treatment. Cu–C containing phosphate glasses were prepared by melting in ambient atmosphere having copper introduced in its highest oxidation state as CuO. Optical absorption and photoluminescence spectroscopy were employed in assessing material optical properties as a function of graphite contents and thermal processing. The processes likely resulting in copper valence state changes leading to the plasmonic material are discussed.
Genetically determined spontaneous and pentylenetetrazol-induced brief spindle episodes in mice.

Abstract Regular 7 s , 1- to 5-s bursts of high-amplitude spindles were observed in the cortical electroencephalogram of DBA mice. We named these bursts “brief spindle episodes” (BSE). The BSEs were bilaterally symmetrical and could be seen to occur earlier in more frontal derivations. BSEs appeared to actively suppress overt body movement, though some facial twitching could be observed. Two convulsant agents, pentylenetetrazol (PTZ) and picrotoxin, provoked BSE activity; a third, nicotine, suppressed BSE activity at both sub- and supraconvulsant doses. Three other inbred mouse strains were also tested for BSE occurrence. Two, C57BL 6 and BALB c mice, failed to show BSE activity either spontaneously or after PTZ. The third strain, C3H, showed lower-amplitude, shorter-duration, and less well-organized BSE activity spontaneously and after PTZ. Juvenile DBA mice (21 to 25 days) showed slower, lower-amplitude, shorter-duration BSEs than did adults. Older mice (31 to 36 days) showed more adult BSEs. The possibility that BSEs are an epileptic phenomenon is discussed. It is clear that they are a genetically determined electroencephalographic characteristic that may provide a useful tool for studying genetic determination of nervous system functioning as well as mechanisms of cortical hypersynchrony.
The Early Demise of the “Stronger” Sex: Gender-Related Causes of Sex Differences in Longevity:

It is well documented that males die at younger ages than females. Although the sex differential in longevity has some basis in biology, many gender-related socialization practices in place in American culture build on existing genetic predispositions to cause males to be more vulnerable than females to early death, especially violent death and death from heart disease. Demographic data are presented to document premature death rates for men relative to women, especially violent death from accidents, suicide, and homicide. A hierarchy of causes of death that is increasingly subject to human influence is presented along with a multidimensional model for understanding early death among males. Conclusions are offered for some reconsiderations of masculinity that would be helpful in reducing the sex differential in longevity.
State of the art treatment of nasal polyposis

BackgroundNasal polyposis represents the end point of multiple inflammatory pathways and controversy continues as to the exact roles of medical and surgical approaches in the management of nasal po...
Single-Molecule Tracking of Nanorobots on Pseudo-One-Dimensional DNA Origami Tracks

A synthetic molecular nanorobot dubbed a "spider" composed of a streptavidin protein "body" bound to three biotinylated 8-17 deoxyribozyme-bearing "legs" completes the programmed task of traversing a predetermined DNA origami track. The track is assembled by folding and holding in place a long single-stranded DNA molecule into a two-dimensional landscape by using hundreds of short oligonucleotides ("staples") and hybridizing chimeric DNA-RNA substrates to specific staples to realize a pseudo-one-dimensional track. Spiders are designed to undergo a biased random walk as their legs repeatedly cleave oligonucleotide substrates on a track, causing the legs to more readily dissociate from the cleaved product and progress towards the uncleaved substrate. We image Cy3-labeled spiders and Cy5-labeled origami using total internal reflection fluorescence microscopy (TIRFM). By fitting Gaussian functions to the imaged point spread functions, we are able to monitor with nanometer spatial precision the real-time motion of the spiders along DNA origami tracks.
Linkage Problem, Distribution Estimation, and Bayesian Networks

This paper proposes an algorithm that uses an estimation of the joint distribution of promising solutions in order to generate new candidate solutions. The algorithm is settled into the context of genetic and evolutionary computation and the algorithms based on the estimation of distributions. The proposed algorithm is called the Bayesian Optimization Algorithm (BOA). To estimate the distribution of promising solutions, the techniques for modeling multivariate data by Bayesian networks are used. The BOA identifies, reproduces, and mixes building blocks up to a specified order. It is independent of the ordering of the variables in strings representing the solutions. Moreover, prior information about the problem can be incorporated into the algorithm, but it is not essential. First experiments were done with additively decomposable problems with both nonoverlapping as well as overlapping building blocks. The proposed algorithm is able to solve all but one of the tested problems in linear or close to linear time with respect to the problem size. Except for the maximal order of interactions to be covered, the algorithm does not use any prior knowledge about the problem. The BOA represents a step toward alleviating the problem of identifying and mixing building blocks correctly to obtain good solutions for problems with very limited domain information.
Proteomic toolbox for autoimmunity research

Autoimmune diseases are genetically complex and poorly understood, and may lead to clinically severe consequences including end-organ damage. Given this scenario, early biomarker discovery is becoming increasingly important for early diagnosis and treatment in these diseases. Among the different approaches tried, the application of proteomic analysis of body fluids has great potential as a non-invasive tool for early diagnosis in many different disease settings. During the past 10 years, proteomics-based approaches have made steady inroads into the study of various autoimmune diseases. In this review, we summarize the highlights of various traditional as well as novel proteomic methods, including 2D-MS/MS, multi-dimensional HPLC-MS/MS, CE-MS/MS, SELDI-TOF-MS/MS, iTRAQ and a variety of targeted antibody-based protein arrays, which have been particularly informative in the field of autoimmunity.