cssi/SciSciGPT-SciSciNet huggingface dataset:
TRIM67 Regulates Exocytic Mode and Neuronal Morphogenesis via SNAP47

Abstract Morphogenesis in developing neurons involves dramatic plasma membrane expansion, which classic hypotheses suggest is fueled by SNARE-mediated exocytosis. Distinct modes of fusion have been described; during full vesicle fusion (FVF) the entirety of vesicle contents are secreted and the vesicle membrane incorporates into the plasma membrane. In contrast, a transient fusion pore secretes lumenal cargo, but closes without membrane addition in kiss and run fusion (KNR). If exocytosis provides material for neuronal morphogenesis, this would suggest FVF predominates, although this has not been examined. Fortuitously in developing neurons, exocytic events are spatially and temporally discrete, unlike exocytic events at the neuronal synapse, allowing resolution of single vesicle fusion events although they are diffraction-limited. Here, we resolve individual exocytic events in developing murine cortical neurons, and use a newly developed classification tool to differentiate and quantify different modes of fusion. We identify four distinct modes of fusion: two FVF-like modes that insert membrane material and two KNR-like modes that do not. Within the FVF-like and KNR-like modes, discrete fluorescence profiles suggest distinct behavior of the fusion pore. Consistent with our hypothesis, FVF-like exocytosis predominates. Simulations and experimental manipulations agree that exocytosis provides sufficient amounts of membrane material for neuronal morphogenesis. Mechanistically we identify that the E3 ubiquitin ligase TRIM67 promotes FVF-like exocytosis by limiting incorporation of the Qb/Qc SNARE SNAP47 into SNARE complexes and thus, SNAP47 involvement in exocytosis. Our data suggest that SNAP47 regulates behavior of the fusion pore between the vesicle and plasma membrane, temporarily arresting the pore in an open state.
Correction for Wertz et al., "Genomic and Physiological Characterization of the Verrucomicrobia Isolate Geminisphaera colitermitum gen. nov., sp. nov., Reveals Microaerophily and Nitrogen Fixation Genes".

Author(s): Wertz, John T; Kim, Eunji; Breznak, John A; Schmidt, Thomas M; Rodrigues, Jorge LM | Abstract: Description of Didymococcus gen. nov. Didymococcus gen. nov. (Di.dy.mo.coc'cus. Gr. fem. n. didymos pair; N.L. masc. n. coccus (from Gr. masc. n. kokkos, grain, seed), coccus; N.L. masc. n. Didymococcus a coccus in pairs). Description of Didymococcus colitermitum sp. nov. Didymococcus colitermitum sp. nov. (co.li.ter'mi.tum. L. n. colon, colon, part of the large intestine; L. n. termes -itis, wood-eating worm, termite; N.L. gen. pl. n. colitermitum, of the gut of termites). Cells are coccoid (0.25 μm to 0.5 μm in diameter) and occur almost exclusively in pairs, with a Gram-negative cell wall morphology that includes an outer membrane. Cells are nonmotile, obligate aerobes and are microaerophilic. The shortest generation times occur in liquid medium under an atmosphere of 2 to 8% O2 (balance N2). On solid R2A medium, colonies are 2 to 4 mm in diameter, have an entire margin and a low convex, mucoid morphology, and are cream colored. Cells do not possess catalase or NADH/ NADPH peroxidase activity. Nitrogenase activity is inferred through growth on nitrogen-free medium. Growth occurs in liquid media between 15 and 35°C (optimum, 30°C); there is no growth at 37°C or 4°C. Growth occurs at a pH range of 5.5 to 7.5 (optimum, 7.0); there is no growth at a pH of ≤5 or ≥8. Substrates utilized as energy sources include starch, D-cellobiose, D-maltose, D-glucose, D-galactose, and one or more components present in yeast extract. Microcrystalline cellulose, methylcellulose, carboxy methylcellulose, xylan, D-fructose, D-mannose, D-trehalose, sucrose, D-ribose, D-xylose, L-arabinose, D-mannitol, D-sorbitol, D-raffinose, DL-lactate, sodium pyruvate, sodium fumarate, sodium acetate, allantoin, D-glucuronate, D-galacturonate, D-gluconic acid, xanthine, tannic acid, resourcinol, vanillic acid, sodium benzoate, and trimethylbenzoate are not utilized. The genome of type strain TAV2 is 5.2 Mb in size, contains 60.5 mol% G+C, and possesses one 16S rRNA gene copy. The type strain, isolated from guts of Reticulitermes flavipes (Kollar) collected in Dansville, MI, is TAV2 (ATCC BAA-2264; DSM 25453).
Pancreatic cancer: Do disparities in mortality rates exist with respect to socioeconomic status?

e19007Background: Pancreatic cancer continues to have one of the highest mortality rates among major cancer diagnoses with rates greater than 90 percent for all stages and with five year survival r...
Change in stage of presentation of head and neck cancer in the United States before and after the affordable care act.

Abstract Objective/Hypothesis Early diagnosis and stage at presentation, two prognostic factors for survival among patients with head and neck cancer (HNC), are significantly impacted by a patient’s health insurance status. We aimed to assess the impact of the Patient Protection and Affordable Care Act (ACA) on stage at presentation across socioeconomic and demographic subpopulations of HNC patients in the United States. Study Design Retrospective data analysis. Methods The National Cancer Database, a hospital-based cancer database (2011–2015), was queried for adults aged 18–64 years and diagnosed with a malignant primary HNC. The outcome of interest was change in early-stage diagnoses between 2011–2013 (pre-ACA) and 2014–2015 (post-ACA) using logistic regression models. Results A total of 91,137 HNC cases were identified in the pre-ACA (n = 53,726) and post-ACA (n = 37,411) years. Overall, the odds of early-stage diagnoses did not change significantly post-ACA (aOR = 0.97, 95 % CI 0.94, 1.00; p = 0.081). However, based on health insurance status, HNC patients with Medicaid were significantly more likely to present with early-stage disease post-ACA (aOR = 1.12, 95 % CI 1.03, 1.21; p = 0.007). We did not observe increased odds of early-stage presentation for other insurance types. Males were less likely to present with early-stage disease, pre- or post-ACA. Conclusions We demonstrate a significant association between ACA implementation and increased early-stage presentation among Medicaid-enrolled HNC patients. This suggests that coverage expansions through the ACA may be associated with increased access to care and may yield greater benefits among low-income HNC patients.
COVID-19 Is Straining Mental Health—Could Technology Be the Answer?

One of the most pernicious side effects of the COVID-19 pandemic is a steep rise in stress and mental health problems. According to a poll by the Kaiser Family Foundation, nearly half of American adults say that worry and stress about the pandemic is hurting their mental health [1] . There are plenty of factors feeding into this phenomenon. People are anxious about getting sick, grieving lost loved ones, and experiencing financial stress, parental stress, and loneliness. The pandemic places additional burdens on essential workers and people of color, both of whom are at greater risk of dying from the disease. COVID-19 itself has been linked to neurological problems as well as anxiety, depression, and sleep disorders [2] .
Thiolated Thermoresponsive Polymer Scaffolds with Tunable Mucoadhesivity for Intestinal Applications.

Treatments for inflammatory bowel disease (IBD) largely involve lifelong drug prescriptions or surgical intervention that can lead to poor quality of life for patients. Regenerative therapies invol...
Using the Supply-Side Approach to Understand and Estimate Equity Returns

A supply-side analysis of the average stock returns over 1926-2004 helps us see how components that include real earnings growth and the price-earnings ratio have contributed to the average total return. The long-run sustainable average equity return can be expressed as a benchmark expected equity return. An innovation is that investors can use a supply-side model as a disciplined framework for estimating average equity returns over much shorter periods than the 80-year sample analyzed.
Exploring Policy Implications of Ethics of Care and Justice in Care Work and Human Services Organizations

Much attention has recently been focused on the efficacy of cross-sector collaboration within the field of human services in response to increasing rates of child maltreatment and subsequent foster...
Covid-19 Intervention Policy Optimization Using a Multi-population Evolutionary Algorithm

The rapid spread of COVID-19, caused by the SARS-CoV-2 virus, has resulted in and continues to pose a significant threat to global health. We proposed a predictive model based on the gated recurrent unit (GRU) that investigates the influence of non-pharmaceutical interventions (NPIs) on the progression of COVID-19. The proposed model is validated by applying in different states in the United States, although it can be generalized to any region of interest in the world. The results show that the predictive model can achieve accurate forecasts across the entire US. The forecast is then utilized to identify the optimal mitigation policies. The goal is to find the best stringency level for each policy that can minimize the total number of new Covid-19 cases while minimizing the mitigation costs. A meta-heuristics method, named multi-population evolutionary algorithm with differential evolution (MPEA-DE), has been developed. The goal is to identify optimal mitigation strategies that minimize COVID-19 infection cases while controlling the costs and other negative impacts. We compared the optimal mitigation strategies identified by the MPEA-DE model with the random search and the blind greedy search strategies. The results show that MPEA-DE performs better than other baseline models based on prescription dominance.
Association of Preoperative Chemosensitivity With Postoperative Survival in Patients With Resected Gastric Adenocarcinoma.

Importance Considering its low completion rate, the survival benefit associated with postoperative chemotherapy (PC) is unclear in patients with resectable gastric adenocarcinoma who received preoperative chemotherapy. Objective To determine whether preoperative chemosensitivity is associated with postoperative survival among patients with resectable gastric adenocarcinoma who receive PC. Design, Setting, and Participants This national, hospital-based cohort study used data from the National Cancer Database, which covers more than 70% newly diagnosed gastric adenocarcinomas in the US, between 2006 and 2017. Participants included patients with clinical stage II or III disease treated with preoperative chemotherapy and curative-intent resection, excluding radiotherapy. Preoperative chemosensitivity was defined as very sensitive (ypT0N0), sensitive (pathological TNM stage less than clinical, excluding ypT0N0), and refractory (pathological greater than or equal to clinical). Data were analyzed in April 2021. Exposures Receipt of PC or not. Main Outcomes and Measures Overall survival from surgical discharge. Results This study included 2382 patients (1599 men [67%]; median [IQR] age, 63 [54-70] years). Most patients (1524 patients [64%]) received no PC. Most patients (1483 patients [62%]) had refractory disease, followed by sensitive disease (727 patients [31%]) and very sensitive disease (172 patients [7%]). Patients with older age (odds ratio [OR], 0.99; 95% CI, 0.97-1.00), comorbidity (OR, 0.71; 95% CI, 0.57-0.90), longer time from chemotherapy initiation to surgery (OR, 0.99; 95% CI, 0.97-1.00), less sensitivity to preoperative chemotherapy (very sensitive vs refractory OR, 0.58; 95% CI, 0.37-0.89; sensitive vs refractory OR, 0.96; 95% CI, 0.76-1.20), and longer surgical hospitalization (OR, 0.95; 95% CI, 0.93-0.97) had a significantly lower likelihood of receiving PC. PC was not associated with improved survival in the whole group (hazard ratio [HR], 0.88; 95% CI, 0.75-1.02). Patients with refractory disease had the worst survival compared with patients with sensitive disease (HR, 0.39; 95% CI, 0.32-0.46) and those with very sensitive disease (HR, 0.12; 95% CI, 0.07-0.20). Preoperative chemosensitivity was significantly associated with the survival benefit from PC (P for interaction = .03). PC was significantly associated with longer survival in patients with sensitive disease (5-year survival rate, 73.8% in the PC group vs 65.0% in the no PC group; HR, 0.64; 95% CI, 0.46-0.91), but not in those with very sensitive disease (5-year survival rate, 80.0% in the PC group vs 90.8% in the no PC group; HR, 2.45; 95% CI, 0.81-7.43) and those with refractory disease (5-year survival rate, 41.8% in the PC group vs 40.7% in the no PC group; HR, 0.93; 95% CI, 0.79-1.10). Conclusions and Relevance In this cohort study, preoperative chemosensitivity was associated with survival among patients with resectable gastric adenocarcinoma who received PC. These findings may help inform future studies to personalize postoperative therapy.
Alumni-Student Differences in the Level and Components of Satisfaction with a College’s Offering

The marketing task of colleges and universities is complicated by the fact that each must serve many different publics or customer groups: students, faculty, alumni, governing bodies, potential employers, etc. These groups frequently seek directly conflicting benefit bundles or products from the institution. For example, students’ desires for low fees, small classes and personal attention may not be compatible with a faculty’s interest in higher salaries, low teaching loads and the opportunity to do research. Pragmatically oriented governing bodies may attach a low, or even negative value to the output of faculty research efforts.
Opportunities for NASA Aerospace Related Funding and Collaboration

This presentation describes the different opportunities that NASA offers for effective collaboration with Academia and Industry. In particular, the presentation includes a general overview of opportunities such as SBIRs, STTRs, Educational Programs and NASA Research Announcements. A general description of forthcoming competitive opportunities under the Exploration Systems Mission Directorate (ESMD) as well as the Science Mission Directorate (SMD) are also provided.
Resistance Exercise Reduces Body Fat and Insulin During Androgen-Deprivation Therapy for Prostate Cancer

PURPOSE/OBJECTIVES To determine whether exercise could reduce biomarkers of cancer progression in prostate cancer survivors (PCSs) on androgen-deprivation therapy (ADT). DESIGN Randomized, controlled trial. SETTING Oregon Health and Science University School of Nursing. SAMPLE 51 PCSs randomized to one year of resistance and impact training or a stretching control group. METHODS The authors investigated changes in body composition and cancer-related biomarkers, and the influence of age and fat loss on changes in biomarkers. MAIN RESEARCH VARIABLES Body composition (total fat, trunk fat, and lean mass), insulin, insulin-like growth factor-1, and sex hormone-binding globulin. FINDINGS In the 36 PCSs with baseline and 12-month data, total fat (p = 0.02) and trunk fat (p = 0.06) mass decreased in the training group compared to gains in controls. Loss of total and trunk fat each mediated the relationship between groups and one-year change in insulin (p < 0.05). Age moderated the insulin response to exercise where insulin reductions were smaller with increasing age (p = 0.03). CONCLUSIONS Resistance and impact exercise may reduce body fat among PCSs undergoing ADT, in turn exerting an insulin-lowering effect. IMPLICATIONS FOR NURSING Nurses should counsel PCSs to exercise to reduce the risk of obesity and associated conditions, including cancer progression.
Use of plastic bags to maintain a humidified atmosphere for animal cell cultures.

A technique is described which allows incubation of petri dish tissue cultures in a dry incubator.
Intrinsic Human Immunodeficiency Virus Type 1 Resistance of Hematopoietic Stem Cells Despite Coreceptor Expression

Interactions of human immunodeficiency virus type 1 (HIV-1) with hematopoietic stem cells may define restrictions on immune reconstitution following effective antiretroviral therapy and affect stem cell gene therapy strategies for AIDS. In the present study, we demonstrated mRNA and cell surface expression of HIV-1 receptors CD4 and the chemokine receptors CCR-5 and CXCR-4 in fractionated cells representing multiple stages of hematopoietic development. Chemokine receptor function was documented in subsets of cells by calcium flux in response to a cognate ligand. Productive infection by HIV-1 via these receptors was observed with the notable exception of stem cells, in which case the presence of CD4, CXCR-4, and CCR-5, as documented by single-cell analysis for expression and function, was insufficient for infection. Neither productive infection, transgene expression, nor virus entry was detectable following exposure of stem cells to either wild-type HIV-1 or lentivirus constructs pseudotyped in HIV-1 envelopes of macrophage-tropic, T-cell-tropic, or dualtropic specificity. Successful entry into stem cells of a vesicular stomatitis virus G protein-pseudotyped HIV-1 construct demonstrated that the resistance to HIV-1 was mediated at the level of virus-cell membrane fusion and entry. These data define the hematopoietic stem cell as a sanctuary cell which is resistant to HIV-1 infection by a mechanism independent of receptor and coreceptor expression that suggests a novel means of cellular protection from HIV-1.
Webster and the politics of abortion.

Recent legal disputes regarding the constitutionality of statutes restricting abortion in the US center around whether women and their physicians will make decisions about abortions or whether such decisions will be the domain of state legislatures. In 1989 the Missouri 8th Circuit Court of Appeals heard a case (Webster) involving a state statute designed to restrict access to abortion. The statute under question included an assumption that life begins at conception a hospitalization requirement the requirement that a physician determine viability a ban on use of public funds for abortion and restrictions on the use of public facilities for pregnancy terminations. A federal trial court declared these provisions unconstitutional; however Missouri is seeking Supreme Court review of the Webster decision. Since abortion has become the most frequently performed medical procedure in the US it is unlikely to be outlawed. However a narrowing of abortion rights seems inevitable. In addition to further restrictions on indirect government support in terms of facilities and funding there will likely be efforts to add restrictions to minors seeking abortions and to confine abortions to earlier points in pregnancy.
EMG-force relation in the first dorsal interosseous muscle of patients with amyotrophic lateral sclerosis.

Background and purpose The relationship between surface electromyography (EMG) and muscle force is essential to assess muscle function and its deficits. However, few studies have explored the EMG-force relation in patients with amyotrophic lateral sclerosis (ALS). The purpose of this study was to examine the EMG-force relation in ALS subjects and its alteration in comparison with healthy control subjects. Methods Surface EMG and force signals were recorded while 10 ALS and 10 age-matched healthy control subjects produced isometric voluntary contractions in the first dorsal interosseous (FDI) muscle over the full range of activation. A linear fit of the EMG-force relation was evaluated through the normalized root mean square error (RMSE) between the experimental and predicted EMG amplitudes. The EMG-force relation was compared between the ALS and the healthy control subjects. Results With a linear fit, the normalized RMSE between the experimental and predicted EMG amplitudes was 9.6 ± 3.6% for the healthy control subjects and 12.3 ± 8.0% for the ALS subjects. The slope of the linear fit was 2.9 ± 2.2 μVN-1 for the ALS subjects and was significantly shallower (p 0.05). Conclusions A linear fit can be used to well describe the EMG-force relation for the FDI muscle of both ALS and healthy control subjects. A variety of processes may work together in ALS that can adversely affect the EMG-force relation.
RKIP Contributes to IFN-γ Synthesis by CD8+ T Cells after Serial TCR Triggering in Systemic Inflammatory Response Syndrome

Systemic inflammatory response syndrome (SIRS) is associated with the development of severe medical complications, including progression to multiple organ dysfunction syndrome and even death. To date, only marginal improvements in terms of therapeutic options have been established for patients affected by SIRS. Raf kinase inhibitor protein (RKIP) is a regulator of MAPK and NF-κB signaling cascades, which are both critical for production of the proinflammatory cytokines responsible for SIRS initiation. By testing a T cell-dependent mouse model of SIRS that utilizes staphylococcal enterotoxin A specific for Vβ3(+) T cells, we show that RKIP is necessary for the exaggerated production of IFN-γ from SIRS splenocytes. This effect was not due to differences in T cell expansion, IL-10 production, or APC priming, but rather a cell-intrinsic defect lying downstream of the TCR in staphylococcal enterotoxin A-specific CD8(+) T cells. Importantly, mice lacking RKIP were still able to proliferate, survive, and contribute to cytokine production in response to pathogen associated molecular pattern-TLR-mediated stimuli, despite the TCR-dependent defects seen in our SIRS model. Finally, by blocking RKIP in wild-type SIRS splenocytes, the IFN-γ response by CD8(+) Vβ3(+) T cells was significantly diminished. These data suggest that RKIP may be a potential therapeutic target in SIRS by curbing effector cytokine production from CD8(+) T cells during serial TCR triggering.
White matter bundle registration and population analysis based on Gaussian processes

This paper proposes a method for the registration of white matter tract bundles traced from diffusion images and its extension to atlas generation. Our framework is based on a Gaussian process representation of tract density maps. Such a representation avoids the need for point-to-point correspondences, is robust to tract interruptions and reconnections and seamlessly handles the comparison and combination of white matter tract bundles. Moreover, being a parametric model, this approach has the potential to be defined in the Gaussian processes' parameter space, without the need for resampling the fiber bundles during the registration process. We use the similarity measure of our Gaussian process framework, which is in fact an inner product, to drive a diffeomorphic registration algorithm between two sets of homologous bundles which is not biased by point-to-point correspondences or the parametrization of the tracts. We estimate a dense deformation of the underlying white matter using the bundles as anatomical landmarks and obtain a population atlas of those fiber bundles. Finally we test our results in several different bundles obtained from in-vivo data.
Coiled bodies in the nucleolus of breast cancer cells

Coiled bodies are a special type of small round nuclear body, composed of coiled fibers and granules, especially prominent in the nucleoplasm of highly active cells (Brasch and Ochs (1992) Exp. Cell Res. 202, 211-223). Although no specific function has been assigned to coiled bodies, they contain spliceosome snRNAs and proteins, as well as the nucleolar U3 RNA-associated protein fibrillarin. In the present study, we have used antibodies to the coiled body-specific protein p80-coilin, together with double-label immunofluorescence, confocal microscopy and immunoelectron microscopy, to examine the distribution of coiled bodies in a number of different breast cancer cell lines. By immunofluorescence, all cell lines had prominent coiled bodies in the nucleoplasm and several cell lines appeared to have coiled bodies within the nucleolus itself. Double-label immunofluorescence and confocal laser scanning microscopy confirmed the nucleolar localization of coiled bodies. Besides containing p80-coilin, nucleoplasmic and nucleolar coiled bodies contained fibrillarin and Sm proteins. By conventional and immunoelectron microscopy, nucleolar coiled bodies appeared as discrete structures within the nucleolus in a number of different morphotypes, distinct from the normal nucleolar domains of granular component, dense fibrillar component, and fibrillar centers. While the significance of finding coiled bodies in the nucleolus of certain breast cancer cell lines is at present unknown, this represents the first report of coiled bodies and Sm staining in the nucleolus of mammalian cells.
Female convict cichlids (Archocentrus nigrofasciatus) prefer to consort with same-sized males

In the monogamous cichlid fish Archocentrus nigrofasciatus, the convict cichlid, males have been shown to prefer large females, even females larger than themselves. However, convict cichlids normally form male-larger assortative pairs, with males approximately 30% larger than their mates. We tested female preference for male body size by examining their allocation of visiting behavior (consorting) in a laboratory three way choice experiment. Females consorted most with the smallest of three available males, and the preferred males were usually closely matched in size to the choosing female. The most discriminating females exhibited greater concordance in preference than the least discriminating females. Female consorting behavior in the lab differs dramatically from that of males and female mate preferences may be similarly different from those of males.
InAs avalanche photodiode with improved electric field uniformity

A new class of avalanche photodiodes (APD) characterized by exclusive electron impact ionization and known as electron avalanche photodiodes (e-APD), have received considerable attention recently due to their ideal gain and excess noise characteristics. HgCdTe, the first material system in which exclusive electron impact ionization was demonstrated, has been the subject of substantial research and development for applications requiring mid and long wavelength infrared photodetectors with high sensitivity, including remote gas sensing, light detection and ranging (LIDAR), and both active and passive imaging. More recently, InAs has also been shown to demonstrate exclusive electron impact ionization and has subsequently come under intense study. Although InAs APD's have not yet reached the multiplication gains achievable in HgCdTe, the advantages inherent to III–V materials, including mature device fabrication and improved compositional uniformity, make InAs APD's particularly attractive for mid-infrared focal plane arrays (FPA). Here, we report a significant, ∼5x, increase in the room temperature multiplication gain for InAs APD's, as compared to the state-of-the-art at 10 V reverse bias.
Water Dispersion Interactions Strongly Influence Simulated Structural Properties of Disordered Protein States

Many proteins can be partially or completely disordered under physiological conditions. Structural characterization of these disordered states using experimental methods can be challenging, since they are composed of a structurally heterogeneous ensemble of conformations rather than a single dominant conformation. Molecular dynamics (MD) simulations should in principle provide an ideal tool for elucidating the composition and behavior of disordered states at an atomic level of detail. Unfortunately, MD simulations using current physics-based models tend to produce disordered-state ensembles that are structurally too compact relative to experiments. We find that the water models typically used in MD simulations significantly underestimate London dispersion interactions, and speculate that this may be a possible reason for these erroneous results. To test this hypothesis, we create a new water model, TIP4P-D, that approximately corrects for these deficiencies in modeling water dispersion interactions while ...
Magnetic-field pinning of a dynamic electron-spin-resonance line in a GaAs/Al x Ga 1-x As heterostructure

Electrically detected electron spin resonance (ESR) is used to study the hyperfine interaction of the two-dimensional electrons and the nuclei of the host lattice in a GaAs/AlGaAs heterostructure. Under the microwave and radio- frequency double excitations, we have observed that the ESR line can be pinned in a very narrow range of magnetic field - in the vicinity of the nuclear magnetic resonance (NMR) of the nuclei of the GaAs crystal. Our observations suggest that this pinning effect is the result of a competition process between the ESR induced dynamic nuclear polarization and the NMR induced depolarization.
Rapid Isolation of the 7S‐Nerve Growth Factor Complex and Its Subunits from Murine Submaxillary Glands and Saliva

7S-Nerve growth factor (NGF) and its alpha, beta-NGF, and gamma subunits have been purified from murine submaxillary glands and saliva by a combination of gel filtration on rigid polyvinyl gels, reversed-phase liquid chromatography on short alkyl chain supports (C4 columns), and ion-exchange chromatography on silica-based carboxymethyl columns. This technique is superior to previously used methods in that it is much more rapid and allows the purification of larger quantities of polypeptide from the same amount of starting material. Beta-NGF prepared with this method elicits the outgrowth of fibers of cells of a pheochromocytoma cell line (PC 12) in vitro, indicating that the biological activity is not impaired by the organic solvents and strong acids utilized for its isolation.
Performance Characterization of Watson Ahumada Motion Detector Using Random Dot Rotary Motion Stimuli

The performance of Watson & Ahumada's model of human visual motion sensing is compared against human psychophysical performance. The stimulus consists of random dots undergoing rotary motion, displayed in a circular annulus. The model matches psychophysical observer performance with respect to most parameters. It is able to replicate some key psychophysical findings such as invariance of observer performance to dot density in the display, and decrease of observer performance with frame duration of the display.Associated with the concept of rotary motion is the notion of a center about which rotation occurs. One might think that for accurate estimation of rotary motion in the display, this center must be accurately known. A simple vector analysis reveals that this need not be the case. Numerical simulations confirm this result, and may explain the position invariance of MST(d) cells. Position invariance is the experimental finding that rotary motion sensitive cells are insensitive to where in their receptive field rotation occurs.When all the dots in the display are randomly drawn from a uniform distribution, illusory rotary motion is perceived. This case was investigated by Rose & Blake previously, who termed the illusory rotary motion the omega effect. Two important experimental findings are reported concerning this effect. First, although the display of random dots evokes perception of rotary motion, the direction of motion perceived does not depend on what dot pattern is shown. Second, the time interval between spontaneous flips in perceived direction is lognormally distributed (mode approximately 2 s). These findings suggest the omega effect fits in the category of a typical bistable illusion, and therefore the processes that give rise to this illusion may be the same processes that underlie much of other bistable phenomenon.
Simulation of heat pipe-assisted latent heat thermal energy storage with simultaneous charging and discharging

Abstract Melting and solidification of a phase change material (PCM) held within a vertical cylindrical enclosure that is integrated with a heat pipe (HP) is simulated as a single module. The HP is heated from the bottom to melt (charge) the PCM that is positioned in the middle of the HP length, and is cooled from the top to solidify (discharge) the PCM. Three modes of operation are considered in this study (i) charging-only, (ii) simultaneous charging and discharging, and (iii) discharging-only. All modes of operation are handled with a single HP within a PCM (single HP-PCM) of which the top and bottom sections are inactivated during charging-only and discharging-only modes, respectively. A parametric study of the influence of the PCM enclosure height and input/output heat transfer rates shows that, for the same mass of PCM, a longer enclosure exhibits a lower HP bottom average wall temperature and relatively more PCM melting during simultaneous charging and discharging. Increasing either the input, output, or both heat transfer rates has a significant effect on the temperature of the HP bottom and top sections, but only a minor impact on the temperature of the HP middle section.
3-Deoxyglucosone-collagen alters human dermal fibroblast migration and adhesion: Implications for impaired wound healing in patients with diabetes

The interaction of fibroblasts with the extracellular matrix is critical for wound healing. Advanced glycation end products (AGEs) occur through nonenzymatic glycation of long-lived proteins such as collagens. One precursor to these modifications, 3-deoxyglucosone (3DG), is elevated in patients with diabetes and contributes to the accumulation of AGEs on collagen with increasing chronological age. Because wound repair is dependent on fibroblast migration, proliferation, and expression of extracellular matrix proteins, we examined the role of 3DG-treated collagen and the subsequent response of fibroblasts to this modification. We found that fibroblasts adhere more strongly to 3DG-treated collagen and do not migrate efficiently into the wound site. We further show that 3DG-treated collagen induces perinuclear localization of focal adhesion kinase and paxillin, indicative of decreased association of these proteins with the cytoskeleton. Additionally, these cells expressed higher levels of the misfolded indicator protein growth arrest and DNA damage inducible gene 153. These data suggest that fibroblast/matrix interactions are altered as AGEs accumulate and affect focal adhesion formation. Furthermore, 3DG may be a factor mediating chronic wounds observed in patients with diabetes and in the elderly by altering the signaling within the fibroblast and inducing the misfolding of proteins.
Differential effects of 2,3,7,8-tetrachlorodibenzo-dioxin on responsiveness of male rats to androgens, 17ß-estradiol, luteinizing hormone, gonadotropin-releasing hormone, and progesterone

Abstract Effects of 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) on the responsiveness of male rats to hormones were investigated. TCDD treatment of postpubescent rats increased the potencies of both androgens [testosterone and 5α-dihydrotestosterone (DHT)] and estrogens (17s-estradiol) as feedback inhibitors of luteinizing hormone (LH) secretion. These increases were due, at least in part, to a TCDD-induced alteration in the regulation of pituitary responsiveness to gonadotropin-releasing hormone (GnRH). Trophic responsiveness of the seminal vesicles and ventral prostate to testosterone and DHT was unaffected by TCDD, while steroidogenic responsiveness of the testis to LH was decreased. In utero and lactational exposure to TCDD increased both LH secretory responsiveness to progesterone and progesterone-induced sexual receptivity in adulthood, while trophic responsiveness of the ventral prostate and seminal vesicles to androgens was inhibited. Thus, effects of TCDD on hormonal responsiveness in male rats are complex and depend on the hormone, the target organ, and the stage of development at which TCDD exposure occurs.
Angular fuzzy set models for linguistic values

Abstract In this paper, an angular fuzzy set model is introduced. The model uses an angle to determine a line that represents a linguistic value. Therefore, the membership value is a function of the angle a. This angular fuzzy set model can be applied to fuzzy logic modusponensand modus tollensdeduction techniques. In relation to these techniques, we employ fuzzy logic operations, such as the truth functional modification and inverse truth functional modification. A relatively simple calculation procedure is required to perform these operations. The conventional models that are represented graphically could pose difficulties during the interpretation of the graphs. The angular models, on the other hand, depend only on the angle. They are solved numerically, and therefore are easier to interpret. Illustrations using this model and comparison with conventional models are presented in this paper.
Unusual structural features of hydantoin lesions translate into efficient recognition by Escherichia coli Fpg.

Oxidation of guanine (G) and 8-oxoguanine (OG) with a wide variety of oxidants yields the hydantoin lesions, guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp). These two lesions have garnered much recent attention due to their unusual structures and high mutagenic potential. We have previously shown that duplexes containing Gh and Sp are substrates for the base excision repair glycosylase Escherichia coli Fpg (EcFpg). In order to evaluate the recognition features of these unusual lesions, binding and footprinting experiments were performed using a glycosylase inactive variant, E3Q EcFpg and 30 bp duplexes containing the embedded lesions. Surprisingly, E3Q EcFpg was found to bind significantly more tightly (~1000-fold) to duplexes containing Gh or Sp over the corresponding duplexes containing OG. This may be a consequence of the helixdestabilizing nature of the hydantoin lesions that facilitates their recognition within duplex DNA. Though DNA binding affinities of E3Q EcFpg with Gh- and Sp- containing duplexes were found to be similar to each other, hydroxyl radical footprinting using methidium-propyl-EDTA (MPE)- Fe(II) revealed subtle differences between binding of E3Q EcFpg with the two lesions. Most notably, in the presence of E3Q EcFpg, the Sp nucleotide (nt) is hyperreactive towards cleavage by MPE-Fe(II) generated hydroxyl radicals suggestive of the formation of an intercalation site for the MPE-Fe(II) reagent at the Sp nt. Interestingly, increasing the duplex length from 18 to 30 bp enhanced the excision efficiency of Gh and Sp paired with C, G or T by EcFpg such that these substrates are processed as efficiently as the signature substrate lesion OG. Moreover, the base removal activity with these two lesions was more efficient than removal of OG when in a base pairing context opposite A. The high affinity and efficient activity of EcFpg towards the hydantoin lesions suggests that EcFpg mediates repair of the lesions in vivo. Notably, the facile activity of EcFpg towards Gh and Sp in base pairing contexts with G and A, which are likely to be present after DNA replication, would be detrimental and enhance mutagenesis.
Ebolavirus vaccines for humans and apes

Because of high case fatality proportions, person-to-person transmission, and potential use in bioterrorism, the development of a vaccine against ebolavirus remains a top priority. Although no licensed vaccine or treatment against ebolavirus is currently available, progress in preclinical testing of countermeasures has been made. Here, we will review ebolavirus vaccine candidates and considerations for their use in humans and wild apes.
Time differential g-factor measurement of the 7+ isomer in 204Tl

Abstract The g-factor of the 1.118 MeV 7+level in 204Tl T 1 2 = 63 μ s was measured as g = +0.1696±0.0010n.m. by time-differential observation of the perturbed angular distribution of the de-exciting α-rays. The isomer was excited by a pulsed deuteron beam through the 204Hg(d, 2n)204Tl reaction. The meaning of the result for the structure of the level is discussed.
Mammalian Oocyte Activation by the Synergistic Action of Discrete Sperm Head Components: Induction of Calcium Transients and Involvement of Proteolysis

Sperm-borne oocyte-activating factor (SOAF) elicits activation sufficient for full development and originates from sperm head submembrane matrices. SOAF comprises discrete, heat-sensitive and -stable components (referred to here respectively as SOAF-I and -II) which are each necessary but not sufficient to activate oocytes. The heat-sensitive SOAF component, SOAF-I(m), becomes solubilized from the perinuclear matrix under reducing conditions (the SOAF transition) to generate SOAF-I(s). Although calcium transients likely play an important role in oocyte activation at fertilization, the question is open as to whether demembranated heads or SOAF-I(s) and/or SOAF-II can induce calcium transients. We now report that injection of demembranated sperm heads into mouse oocytes efficiently induced Ca(2+) oscillations. When injected independently, SOAF-I(s) and demembranated heads heated to 48 degrees C failed to generate Ca(2+) oscillations. However, co-injection of SOAF-I(s) and 48 degrees C-heated heads induced oscillations, mirroring their synergistic ability to activate oocytes. This suggests that SOAF-mediated activation proceeds via pathways resembling those at fertilization and provides the first direct evidence that multiple sperm components are required to induce Ca(2+) oscillations. We probed the SOAF-I(s) liberation at the center of this activation and show that in vitro it was sensitive to a profile of serine protease inhibitors. These findings support a model in which mammalian oocyte activation, including the induction of calcium transients, involves proteolytic processing of SOAF from sperm head submembrane compartments.
A comparison of ultrasound to goniometric and inclinometer measurements of torsion in the tibia and femur.

Abstract Background Torsions in the tibia and femur are important measurements for clinicians and researchers. A safe, accurate and time efficient tool is needed to advance the study of torsion. This study compared ultrasound and goniometric measures of torsion and also determined the repeatability of the goniometric techniques. Methods 19 females and 15 males (68 limbs) aged 19–69 years were studied. The transmalleolar axis, thigh–foot angle, and femoral torsion were measured with goniometers and compared to ultrasound measurements of tibial and femoral torsion using simple regression. Goniometric measures were measured twice to determine reliability. Results Goniometric measures of torsion were found to be reliable (intraclass correlation coefficients range: 0.84–0.90). Goniometric measurements had a weak to moderate significant relationship to ultrasound measures (standardized beta coefficient range: 0.56–0.70). Discussion Ultrasound and goniometric methods both provide useful measures of torsion; ultrasound may be more suitable for research and pre-operative planning.
α- Addition des amines sur les glycosyl isonitriles.

Abstract α-Addition reactions of glycosyl isonitriles with primary and secondary amines allowed to prepare substituted glycosyl formamidines representing good precursors in the synthesis of nucleosides.
Local anesthetic-phospholipid interactions. The pH dependence of the binding of dibucaine to dimyristoylphosphatidylcholine vesicles.

Abstract The interaction of the local anesthetic dibucaine with unilamellar vesicles of dimyristoylphosphatidylcholine was studied by equilibrium dialysis. Saturating binding profiles (as a function of dibucaine) were found, with apparent association constant ranging from 1.26·103 M -1 to 2.57·103 M-1 as pH is increased from 5.0 to 7.5. The number of phospholipid molecules comprising a binding site was found to be about 5 at each pH. Analysis of the data was also achieved using the Stern model, which takes into account the electrostatic effect on binding of the cationic drug due to the build up of a surface potential.
Update on rituximab.

Rituximab is a chimeric monoclonal antibody that was developed for the treatment of B cell lymphomas.1 It is directed against the CD20 cell surface molecule.2 CD20 is a tetraspan membrane protein that is present only on B cells, and is expressed initially at the immature B cell stage, remaining until the final differentiation into plasma cells. The function of CD20 is not clear, although it may play some role in signalling or in calcium mobilisation.3 Curiously, mice that were genetically engineered to lack CD20 (CD20 knockout mice) have not shown any clear defects in their B cells.4 Nevertheless, the specificity of CD20 for the B cell lineage, and its failure to be easily shed or internalised, has made it an excellent target for depletion by monoclonal antibodies. Not only does rituximab kill CD20+ lymphoma cells, but it also substantially depletes normal B cells from the peripheral blood.5 Tissue depletion also occurs, but is perhaps less profound, and in any case has been little documented in patients.6 The mechanism of B cell depletion appears to be a combination of FcRγ dependent ADCC (antibody dependent cell mediated cytotoxocity), complement mediated lysis, and apoptosis,7 although the relative contributions of these mechanisms in vivo remains to be determined, In addition, stimulation of the inhibitory FcRγIIB may also play a role in rituximab therapeutic effects.8 In 1997, the US Food and Drug Administration (FDA) approved rituximab for the treatment of low grade non-Hodgkin’s B cell lymphomas.9 Since that time, it has been used in over 500 000 patients with generally excellent tolerability. Largely through a series of investigator sponsored trials supported in part by Genentech (South San Francisco, CA), the use of rituximab has been extended to a much wider spectrum of B cell malignancies, and strikingly, …
Stimulation of secretion of pig thyrocalcitonin by gastrin and related hormonal peptides.

The secretion of thyrocalcitonin (TC) was measured in young pigs by radioimmunoassay of thyroid venous effluent blood. Systemic iv injection of synthetic pentagastrin and tetragastrin and of native porcine gastrin in doses of 0.034–3.4 nmoles/kg rapidly increased TC concentrations 3–20-fold in a dose-related fashion. Pancreozymin/ cholecystokinin (PZ/CCK, 7.3–12 Crick U/kg) also stimulated TC secretion, while betazole (2 mg/kg) and pancreatic glucagon (68–204 μg/kg) were essentially ineffective. Prolonged infusion of pentagastrin caused initial stimulation of TC secretion, but thereafter TC secretion fell progressively despite continued infusion. Administration of pentagastrin or gastrin directly into the thyroid artery at dose levels ineffective systemically stimulated secretion of TC, indicating a direct action on the thyroid gland. Since tetragastrin as well as pentagastrin stimulated TC secretion and since the tetrapeptide sequence comprises the carboxyl terminus of both gastrin and PZ/CCK and is the ...
Elimination of Mechanical Failure of the Hickman Right Atrial Catheter

Abstract The double lumen Hickman right atrial catheter (Evermed Co., Palo Alto, Calif.) is usually inserted through an open venous cutdown into the internal jugular or cephalic vein. It is difficult to mechanically secure. Tight ligatures around the vein opening and catheter occlude the lumen of the Silastic rubber catheter while loose ligatures allow slippage. Migration of the tip into the vena cava or innominate vein causes fibrin sleeve formation and occlusion. Because of problems during the initial use of this catheter, we modified a subsequent series by placing a Silastic rubber bead on the catheter. The catheter is carefully trimmed so that the tip will lie in the right atrium and the bead is placed into the vein proximal to the securing ligature. Comparison of the two series of primarily leukemic patients revealed complete elimination of mechanical problems in patients with beaded catheters ( 0 18 ), and significant mechanical failure in unbeaded catheters ( 7 23 ). These data indicate that adequate fixation of the Hickman catheter at the level of the venotomy and placement of the tip in the right atrium eliminates mechanical failure and markedly improves catheter function.