cssi/SciSciGPT-SciSciNet huggingface dataset:
Psychiatric problems in breast cancer

The author discusses the prevalence of psychiatric problems in cancer, and highlights five emotional problems common to all cancer patients: the emotionally charged nature of the word cancer, the patient's perceived lack of control, the uncertainty about outcome, the discordant treatment mode, and the debilitating nature of cancer treatments. The author then divides the problems faced by breast cancer patients into three categories needing clinical intervention: (1) the psychosocial, (2) the somatic, and (3) the psychiatric. Diagnosis and treatment of the two psychiatric problems of depression and delirium is emphasized.
Reaction of Hydroxyl Radical with Nitric Acid: Insights into Its Mechanism†

The rate constant for the reaction of hydroxyl radicals with nitric acid has an unusual pressure and temperature dependence. To explore the mechanism for this reaction, we have measured rate constants for reactions of isotopically substituted species OD + DNO3, OH + DNO3, OD + HNO3, and 18OH + HNO3 and the yield of NO3 product. Deuterium substitution on nitric acid results in more than a 10-fold reduction in the rate constant, removes the pressure dependence (over the observed range of 20−200 Torr in He and SF6), and leads to a strongly curved Arrhenius temperature dependence. Deuterium substitution on hydroxyl increases the rate constant slightly but does not change the pressure dependence. There is no evidence for exchange reactions in the isotopically mixed reactions. Absorption measurements of the NO3 product yield show that the title reaction produces nitrate radical with unit efficiency over all temperatures and pressures studied. We discuss the implications of the measured rate constants, product y...
A System Dynamics Model for a Sustainable Fish Population

To visualize or address complex real world problems, eliciting and mapping of a mental model is reasonable approach but it is far from sufficient by itself. In this article we present a system dynamics model. The purpose of the model is to develop a sustainable model for fish population, growth, and harvesting. The model was run through several important tests to determine its sensitivity to changing in key parameters and initial values with different scenarios and boundary conditions. Model results show that fish birth, growth, stocks and catch can be controlled quickly in different real-world changing conditions to maintain a sustainable fish population.
Single-Cluster Monte Carlo Dynamics for the Ising Model

We present an extensive study of a new Monte Carlo acceleration algorithm introduced by Wolff for the Ising model. It differs from the Swendsen-Wang algorithm by growing and flipping single clusters at a random seed. In general, it is more efficient than Swendsen-Wang dynamics ford>2, giving zero critical slowing down in the upper critical dimension. Monte Carlo simulations give dynamical critical exponentszw=0.33±0.05 and 0.44+0.10 ind=2 and 3, respectively, and numbers consistent withzw=0 ind=4 and mean-field theory. We present scaling arguments which indicate that the Wolff mechanism for decorrelation differs substantially from Swendsen-Wang despite the apparent similarities of the two methods.
Tris(ethane-1,2-diamine-κ2N,N′)nickel(II) diiodide

The title compound, [Ni(C2H8N2)3]I2, crystallizes with an [Ni(en)32+] cation (en is ethane-1,2-diamine) and two iodide ions in the asymmetric unit. Two of the en ligands surrrounding the Ni2+ ion have disordered C atoms, while the third exhibits extensive weak N—H⋯I inter­actions with the two iodide ions that extend throughout the crystalline lattice, producing an infinite network along (011).
α-Factor inhibition of the rate of cell passage through the “start” step of cell division in Saccharomyces cerevisiae yeast: Estimation of the division delay per α-factor·receptor complex

Abstract A highly sensitive, kinetically unambiguous assay for α-factor-induced delay of cell passage through the “start” step of cell division in yeast is presented. The assay employs perfusion with periodic microscopy to monitor the bud emergence kinetics on the 20% of cells within an exponentially growing population which exist prior to the α-factor execution point of start. The t 1 2 for cell passage through start by this population of cells is 31 min in the absence of α-factor. The inhibition constant, KI, represents the α-factor concentration which produces a 50% inhibition of this rate and is equal to 2×10−10M. A second assay for maximal cell division arrest by α-factor on whole populations of cells is presented. This assay shows a maximum cell division arrest time of 125±5 h at saturating α-factor, and a K50 (that is, an α-factor concentration which produces a half-maximal response) of 2.5×10−8M. Both assays were performed in the effective absence of α-factor inactivation. Values of the dissociation constant KD and total number of receptors per cell which specifically mediate cell division arrest or delay were estimated to be 2.5×10−8M and 104, respectively. These estimates, along with the quantitative dose-response data for division arrest which are presented here, are consistent with each receptor·α-factor complex which is present on the cell at equilibrium producing a 43±10 s delay of cell passage through start. Surprisingly, this number is constant within twofold over the entire range of cellular division arrest responses to α-factor, that is, from a 1.9-fold inhibition of the rate of cell passage through start at 0.17 nM α-factor to a 125±5 h maximum arrest at saturating α-factor concentrations of >170 nM. The possible significance of this observation toward the mechanism of α-factor-induced cell division arrest is discussed.
GITR agonist enhances vaccination responses in lung cancer

An immune tolerant tumor microenvironment promotes immune evasion of lung cancer. Agents that antagonize immune tolerance will thus aid the fight against this devastating disease. Members of the tumor necrosis factor receptor (TNFR) family modulate the magnitude, duration and phenotype of immune responsiveness to antigens. Among these, GITR expressed on immune cells functions as a key regulator in inflammatory and immune responses. Here, we evaluate the GITR agonistic antibody (DTA-1) as a mono-therapy and in combination with therapeutic vaccination in murine lung cancer models. We found that DTA-1 treatment of tumor-bearing mice increased: (i) the frequency and activation of intratumoral natural killer (NK) cells and T lymphocytes, (ii) the antigen presenting cell (APC) activity in the tumor, and (iii) systemic T-cell specific tumor cell cytolysis. DTA-1 treatment enhanced tumor cell apoptosis as quantified by cleaved caspase-3 staining in the tumors. DTA-1 treatment increased expression of IFNγ, TNFα an...
Some factors involved in the dissolution of Autographa californica nuclear polyhedrosis virus polyhedra by digestive fluids of Trichoplusia ni larvae

Abstract Factors involved in the dissolution of polyhedra of Autographa californica nuclear polyhedrosis virus (AcNPV) by digestive fluid collected from fifth stage Trichoplusia ni larvae were studied in vitro. Observations were made at timed intervals using phase contrast microscopy and transmission electron microscopy. When digestive fluid was heated at 50°C proteases retained activity. Exposure of polyhedra to digestive fluid previously heated to 50°C resulted in polyhedral matrix dissolution and envelope disruption in a manner similar to that of unheated digestive fluid, only delayed slightly. After exposure of polyhedra for 3 min, only enveloped virons were observed. Heating the digestive fluid to 60° or higher inactivated the proteases and altered the effect on polyhedra. Dissolution of the occlusion body matrix occurred but the polyhedral envelope remained and only a few weakened areas were observed in its structure. Within the polyhedral envelope, enveloped virons were not observed, only nucleocapsids and capsids. Exposure of polyhedra to 0.1 m sodium carbonate buffer at p Hs of 9.5 or higher had effects similar to those of the digestive fluid with heat (60°C)-inactivated proteases. The addition of trypsin and chymotrypsin to the 0.1 m sodium carbonate buffer had no effect, while the addition of a bacterial protease ( Streptomyces griseus ) at p Hs of 9.5 or higher resulted in dissolution of the matrix and disruption of the polyhedral envelope like the digestive fluid. Material infectious to TN-368 cells was obtained by exposure of AcNPV to T. ni digestive fluid. Maximum infectivity resulted from a 5-min exposure to unheated digestive fluid, with a dramatic decrease in infectivity with longer exposure. Exposure to digestive fluid with heat (60°C)-inactivated proteases resulted in a slower release of infectious material from the occlusion body, with a steady increase in the level of infectivity throughout the 30-min digestion period.
Wood-fired power plants in the Philippines: financial and economic assessment of wood-supply strategies

Abstract To help reduce its dependence on imported oil, the Philippines is constructing over 60 wood-fired electricity generating plants. Nine power plants are now operational, but financial difficulties are hindering the development of wood-supply networks. This study found that financial and economic costs of the current strategy promoting the development of captive wood supplies exceed the costs of open-market wood at a majority of the project sites. Plantation establishment and wood transport are the most costly activities associated with producing captive wood. Sensitivity analysis indicates that the total unit costs of captive wood are most responsive to changes in plantation yields. Future changes in the costs of labor (within a reasonable range) would have little impact on wood costs. Although many open-market suppliers can provide wood at a cost lower than that produced under the current approach, any policy shift favoring open-market wood procurement must include provisions to guard against adverse environmental effects.
National cancer database report on chondrosarcoma of the head and neck.

Background Management of chondrosarcoma of the head and neck is largely based on single-institution reports with small numbers accrued over several decades. Methods The American College of Surgeons' National Cancer Data Base included 400 cases of chondrosarcoma of the head and neck diagnosed between 1985 and 1995. Chi square analyses of selected contingency tables and Wilcoxon regression analyses of selected survival stratifications were performed. Results Histologic types included conventional (80.8%), myxoid (10.5%), and mesenchymal (8.8%). The mesenchymal and myxoid subtypes were rare among white patients (17.1%) and more common among African-American (31.8%) and Hispanic patients (44.9%). Treatment was most commonly surgery alone (59.5%) and surgery with irradiation (21.0%). Disease-specific survival was 87.2% at 5 years and 70.6% at 10 years. Worse 5-year survival was associated with higher grade (67.3%), regional or distant spread (71.0%), and the myxoid (45.0%) or mesenchymal (53.2%) subtypes. Conclusions Chondrosarcoma of the head and neck encompasses a variety of lesions that differ substantially by demographic and tumor characteristics. Individual tumors can be classified further according to site of origin, histologic subtype, and tumor grade, which can be used to predict biologic behavior and prognosis. © 2000 John Wiley & Sons, Inc. Head Neck 22: 408–425, 2000.
Using Cognitive Mapping to Understand Problems Experienced by Family Caregivers of Persons with Severe Physical Disabilities

Individuals who provide ongoing care for family members who have a chronic disease or disability are likely to encounter a wide array of problems that can compromise their own health and their ability to function effectively in a caregiving role. Structured focus group meetings were conducted to elicit a comprehensive list of the problems that caregivers experienced during their first year of providing care to a person with a severe physical disability. A separate group of caregivers (N = 60) individually sorted problems into piles based on their similarity and assigned relative importance to each problem. The aggregated data were analyzed with multidimensional scaling and hierarchical cluster analysis. Results indicated that caregivers cognitively organize problems along three dimensions: I. Centeredness–caregiver versus patient-oriented; II. Relationship Demands–physical versus emotional; and III. Caregiver Burden–time versus emotional. Additionally, 6 clusters of substantively similar problems were identified and prioritized in terms of personal relevance: Basic Needs (lowest); Perceived Constraints; Caregiver Challenges; Patient Resentment; Patient Withdrawal; and Patient Intrapsychic Adjustment (highest). Further examination of the organization of problems identified by caregivers should provide important insights about the experience of caregivers and how more targeted interventions can be developed to address their specific needs.
Coupled electron/proton transfer of galvinol attached to SAMs on gold electrodes

The theory for a 1-electron, 1-proton redox couple with potential-dependent transfer coefficients is tested using a self-assembled monolayer with attached galvinol/galvinoxyl redox couples on a gold electrode. The potential dependence of the transfer coefficients is derived from the Marcus density-of-states model of heterogeneous electron transfer. The pKa of surface-attached galvinol is 11.3. The predicted asymmetry in kinetically controlled cyclic voltammograms is observed at pHs lower than 11. Apparent standard rate constants between pH 10 and 13 are fitted to the theory to yield a standard rate constant of 4.5 × 10 s−1 for the deprotonated galvinol/galvinoxyl radical redox couple; this standard rate constant is comparable to the standard rate constant for ferrocene/ferricenium with the same number of atoms linking the redox center to the electrode. Anomalous behavior is seen for the apparent standard rate constants at pHs between 7 and 9.
Measures of Cognitive Structure: Do They Assess Learning at the Level of Comprehension?.

Abstract One purpose of this study was to determine whether cognitive structure, assessed by psychometric measures of concept interrelatedness, can be developed when the students initially do not know what concept relationships exist and what they mean. The second purpose was to apply those measures to a learning situation that has produced a nonspecific transfer effect, i.e., the facilitative effect of concrete examples on learning abstract passages, to attempt to explain this effect more completely. Five groups of 20 students each read two prose passages and took recall and structure assessment tests on the second passage. Results (1) indicated that the nonspecific facilitative transfer effect was replicated and (2) offered some support for the contention that the cognitive structure which proximity measures assess can be trained to correspond to content structure, but that related recall remains low. With resolution of some of the methodological issues surrounding these measures, however, clearer explanation of transfer effects and assessment of higher order learning may be facilitated.
Identification of C-C Chemokine Receptor 1 (CCR1) as the Monocyte Hemofiltrate C-C Chemokine (HCC)-1 Receptor

Hemofiltrate C-C chemokine (HCC)-1 is a recently cloned C-C chemokine that is structurally similar to macrophage inflammatory protein (MIP)-1alpha. Unlike most chemokines, it is constitutively secreted by tissues and is present at high concentrations in normal human plasma. Also atypical for chemokines, HCC-1 is reported not to be chemotactic for leukocytes. In this paper, we have investigated the chemokine receptor usage and downstream signaling pathways of HCC-1. Cross-desensitization experiments using THP-1 cells suggested that HCC-1 and MIP-1alpha activated the same receptor. Experiments using a panel of cloned chemokine receptors revealed that HCC-1 specifically activated C-C chemokine receptor (CCR)1, but not closely related receptors, including CCR5. HCC-1 competed with MIP-1alpha for binding to CCR1-transfected cells, but with a markedly reduced affinity (IC50 = 93 nM versus 1.3 nM for MIP-1alpha). Similarly, HCC-1 was less potent than MIP-1alpha in inducing inhibition of adenylyl cyclase in CCR1-transfected cells. HCC-1 induced chemotaxis of freshly isolated human monocytes, THP-1 cells, and CCR1-transfected cells, and the optimal concentration for cell migration (100 nM) was approximately 100-fold lower than that of MIP-1alpha (1 nM). These data demonstrate that HCC-1 is a chemoattractant and identify CCR1 as a functional HCC-1 receptor on human monocytes.
Changes in Vascular Viscoelasticity Caused by Smooth Muscle Cell Tone and Pressurization Frequency

The cushioning and conduit functions of large arteries allow the body to efficiently circulate blood and perfuse organs. These functions can be characterized by quantifying the viscoelastic properties of arteries. In this study, we investigated the effects of smooth muscle cell (SMC) tone and pressurization frequency on vascular viscoelasticity using an isolated, perfused vessel test. We tested mouse carotid arteries in control, dilated (via sodium nitroprusside) and constricted (via the thromboxane receptor analogue U46619) states at 0.1, 1, 3, and 5 Hz with a pulse pressure from 90 to 120 mmHg. Dose response experiments were first performed in order to determine the optimal vasoconstrictor concentration to be used in frequency response experiments. Our results showed that energy dissipation was significantly higher and elasticity was significantly lower for vasoconstricted arteries. We also found that frequency significantly changed both energy dissipation and elasticity as the frequency was increased from 0.1 to 5 Hz. These results provide insights into the changes in vascular viscoelasticity caused by SMC tone and pressurization frequency, which have implications for vascular function in vivo.Copyright © 2007 by ASME
Bandwidth selection in local polynomial regression using eigenvalues

Summary. Local polynomial regression is commonly used for estimating regression functions. In practice, however, with rough functions or sparse data, a poor choice of bandwidth can lead to unstable estimates of the function or its derivatives. We derive a new expression for the leading term of the bias by using the eigenvalues of the weighted design matrix where the bias depends on the arrangement of the X-values in the bandwidth window. We then use this result to determine a local data-driven bandwidth selection method and to provide a diagnostic for poor bandwidths that are chosen by using other methods. We show that our data-driven bandwidth is asymptotically equivalent to the optimal local bandwidth and that it performs well for relatively small samples when compared with other methods. In addition, we provide simulation results for first-derivative estimation. We illustrate its performance with data from Mars Global Surveyor.
Transition of a microRNA from Repressing to Activating Translation Depending on the Extent of Base Pairing with the Target

MicroRNAs are major post-transcriptional regulators of gene expression. Here we show in the ancient protozoan Giardia lamblia a snoRNA-derived 26-nucleotide microRNA, miR3, which represses the translation of histone H2A mRNA containing an imperfect target but enhances translation when the target is made fully complementary. A stepwise mutational analysis of the fully complementary target showed that the activating effect of miR3 was significantly reduced when a single nucleotide at the 5′-end of the target was altered. The effect of miR3 became repressive when 12 of the nucleotides lost their complementation to miR3 with maximum repression reached when only 8 base-pairs remained between the miR3 seed sequence and the target. A synthetic 8-nucleotide RNA oligomer of the miR3 seed sequence was found capable of exerting a similar Argonaute-dependent translational repression. This is the first report showing a correlation between the extent of base-pairing with the target and a change in miRNA function.
Ubiquitin-mediated degradation of Rpn4 is controlled by a phosphorylation-dependent ubiquitylation signal.

Abstract A ubiquitylation signal of a protein substrate is defined as a short primary sequence or a structural feature recognized by a specific E3. Our previous work has mapped the ubiquitylation signal of Rpn4, the transcription activator for the Saccharomyces cerevisiae proteasome genes, to an N-terminal acidic domain (NAD) consisting of amino acids 211–229. However, the molecular mechanism by which Ubr2, the cognate E3, recognizes NAD remains unclear. Here we show that phosphorylation of either Ser-214 or Ser-220 enhances the binding of NAD to Ubr2. However, phosphorylation of Ser-220 but not Ser-214 plays a predominant role in Rpn4 ubiquitylation and degradation. Interestingly, NAD does not constitute the major Ubr2-binding site of Rpn4 even though it serves as the ubiquitylation signal essential for Rpn4 degradation. By contrast, the stable binding with Ubr2 conferred by other domains of Rpn4 is not required for Rpn4 degradation. Our results indicate that ubiquitin-mediated degradation of Rpn4 is controlled by a phosphorylation-dependent ubiquitylation signal. This study also suggests that binding to E3 may be only a part of the function of a ubiquitylation signal.
Comparative study of the effects of salinomycin and monensin on electrophysiologic and contractile properties of canine myocardium.

The effects of the monocarboxylic ionophore, salinomycin (K+-selective), on isometric twitcches, high K+-induced contracture and transmembrane action potentials were compared with those of the monocarboxylic ionophore, monensin (Na+-selective), in isolated canine right ventricular muscle. In a concentration (5 × 10−6) which did not produce changes in resting force, salinomycin increased peak active force ( P0, + 170 ± 36%, mean % change from control ±S.D., P< 0.01). and relaxation and maximal rates of force development (dP/dtmax, + 123 ± 33%, P < 0.01) and relaxation (−dP/dtmax, + 180 ± 40%, P < 0.01) of the isometric twitch. A similar response pattern was found for 5 × 10−6 M monensin (P0, + 90 ± 24%, P < 0.01; dP/dtmax, + 137 ± 19%, P < 0.01; −dP/dtmax, + 145 ± 20%, P < 0.01). In contrast to their effects on isometric twitches, salinomycin reduced peak K+ contracture force (Pc, −35 ± 14%, P < 0.01) whereas monensin increased it (Pc, +30 ± 12%, P < 0.02). Ventricular muscle action potential duration was shortened similarly by the ionophores. β-Adrenergic receptor blockade with nadolol diminished salinomycin's effects on the isometric twitch and K+ contracture, but not its effect to shorten the action potential. Monensin's actions were unaffected by nadolol. These results suggest that salinomycin's effects arise from both a direct modulation of K+ movement and the release of endogenous catecholamine. In contrast, monensin may act to alter intracellular Na+ which in turn leads to Na+Ca2+ exchange and Ca2+ -mediated modulation of K+ movement.
Sequencing and the Single Channel

Single-channel electrophysiology provides for high-resolution measurements of the dynamics of single macromolecules, the channel proteins (Neher and Sakmann, 1976). Among the measurements that have proven fruitful have been ability to monitor, in almost real time, the interactions between the channel and a blocker, or modifier, of ion permeation (Neher and Steinbach, 1978; Prod’hom et al., 1987; Hemsley and Busath, 1991). The emphasis usually has been on the channel, but different blockers/modifiers may have different characteristic “fingerprints” (Hemsley and Busath, 1991), which provides for possibilities in terms of using the characteristics of the blocking events to determine the chemical identity of the blocking species.
True confessions: Responding to psychiatric patients who report their own crimes

Abstract As long as things go well with a man, his conscience is lenient and lets the ego do all sorts of things; but when misfortune befalls him, he searches his soul, acknowledges his sinfulness, heightens the demands of his conscience, imposes abstinences on himself and punishes himself with penances. (Freud, 1930) When psychiatric patients report their own crimes, authentic confessions can easily be attributed to deviant thinking and mistakenly identified as ‘false confessions’. Four examples of pseudo-false confessions of violent crimes are described. Their relationships to specific psychopathological syndromes, and to counter-transference reactions to violent patients, are discussed. Guidelines are offered to clinicians to help them distinguish true confessions from false ones. Ethical and legal issues are reviewed.
Classes of ring galaxies generated by dynamical friction

Dynamical friction is incorporated in the numerical modeling of colliding ring galaxies. It is shown that dynamical friction may lead to the capture of an initially unbound companion into a damped oscillatory orbit before ultimately merging with the target disk. In the late stages of its motion the companion may be virtually merged with the main galaxy while rings are still propagating in the disk. This raises the possibility that there exist (at least) two classes of ring galaxies: a class of ring galaxies with separate detached companions in which dynamical friction is too weak to have captured the collider, and a second class with no apparent companion in which the latter has either merged with the target galaxy or has disrupted. These two classes could possibly be identified with O-type and P-type ring galaxies of Few and Madore (1986).
The equilibrium allocation of diffusive and jump risks with heterogeneous agents

Abstract We study a two-agent pure exchange equilibrium subject to both nondiversifiable diffusive and jump risks. Agents can trade in a financial market consisting of a stock market, a money market, and an insurance market for jump risk. Heterogeneity is introduced through different levels of relative risk aversion. In the framework of standard expected utility we find the surprising result that the less risk averse agent purchases insurance contracts against jump risk from the more risk averse agent. This equilibrium allocation is linked to the non-linear wealth sharing rule in such an economy, and preserves the wealth effects studied by Dumas [Rev. Financ. Stud. 2 (1989) 157] in the case of pure diffusive risk. Since the benchmark economy with homogeneous agents generates no excess uncertainty in the stock market, we study the effect on excess volatility and excess jump size solely due to different levels of relative risk aversion. We observe 3% excess uncertainty in jump sizes for a reasonable specification of economic fundamentals.
HEURISTIC PRINCIPLE FOR QUANTIZED HALL STATES

It is argued that the incompressibility of fractional quantized Hall states, and the qualitative form of their wavefunction, can be understood by an argument based on adiabatic localization of magnetic flux. The hierarchy of allowed filling fractions is derived in a very simple way, that makes no reference to successive condensations of quasiparticles.
The Influence of Corporate Image and Specificity of Candidate Qualifications on Response to Recruitment Advertisement

This paper reports the results of an experiment designed to examine the possible impact of (1) the corporate image of the advertiser and (2) the degree of specificity of the candidate qualifications, on the likelihood of reader response to a recruitment advertisement. The data indicated that the corporate image of the advertiser significantly influenced the likelihood of reader response, whereas the degree of specificity of the candidate qualifications did not significantly influence the likelihood of reader response to recruitment advertisement. The implications of the findings are discussed and avenues for further study are suggested.
Reefs—Challenges and Opportunities for the New Millennium

Did you ever have the feeling that keeping up with the literature in your field of specialization is practically a full-time job? And that it is even worse when including fields related to your specialty? Did you also feel that this is hopeless? My specialty is reefs. Apart from going to the library every so often, I use GeoRef® to try to keep up. If you go into the database and just ask for “reefs” and “1998,” for example, you will get more than 800 references! In the 1950's you would have gotten only around 80, and 50 years before that not more than 5 titles per year. Seeing this increase in publication, you might question whether you will have to read several thousands of papers on reefs per year in the near future. Looking at the development in more detail suggests, however, that geologic and paleontologic publications on reefs may have reached in the mid 1980's what population ecologists would call the carrying capacity level (Fig. 1). Possible reasons for this are a decreased level of research funding or simply changes in fashion—other fields of research have become more trendy in our community. Even though this topic is very interesting—I suggest you check your own specialty on GeoRef®—I won't go into detail here. More important, in my opinion, is the fact that the enormous increase in geological and paleontological publications on reefs—biology is not even considered here—and the general development of the curve show that reefs are still booming. Even though this might be an oversimplification, numbers of publications …
Allosteric Activation of the Phosphoinositide Phosphatase Sac1 by Anionic Phospholipids

Sac family phosphoinositide phosphatases comprise an evolutionarily conserved family of enzymes in eukaryotes. Our recently determined crystal structure of the Sac phosphatase domain of yeast Sac1, the founding member of the Sac family proteins, revealed a unique conformation of the catalytic P-loop and a large positively charged groove at the catalytic site. We now report a unique mechanism for the regulation of its phosphatase activity. Sac1 is an allosteric enzyme that can be activated by its product phosphatidylinositol or anionic phospholipid phosphatidylserine. The activation of Sac1 may involve conformational changes of the catalytic P-loop induced by direct binding with the regulatory anionic phospholipids in the large cationic catalytic groove. These findings highlight the fact that lipid composition of the substrate membrane plays an important role in the control of Sac1 function.
EVIDENCE FOR THE SINGLE PHASE PAIRING THEORY OF MEIOSIS

The segregation pattern of an attached X chromosome with several Y-autosome translocations conflicts with the expectations based on the distributive pairing hypothesis because the chromosomes segregating from the translocation configuration include both exchange and non-exchange chromosomes. The results of the second experiment involving three compound chromosomes go even further; they suggest that the essential association which determines the segregation of nonhomologous elements is in fact set up prior to the time of crossing over.
Leber Congenital Amaurosis Caused by Mutations in GUCY2D

Leber congenital amaurosis (LCA) is a clinically and genetically heterogeneous group of diseases that account for the most severe form of early-onset retinal dystrophy. Mutations in retinal guanylate cyclase-1 (GUCY2D) are associated with LCA1, a prevalent form. GUCY2D encodes guanylate cyclase-1 (GC1), a protein expressed in rod and cone photoreceptors that regulates cGMP and Ca(2+) levels within these cells. LCA1 patients present with severely impaired vision, reduced, or ablated electroretinogram and nystagmus. Despite a high degree of visual disturbance, LCA1 patients retain normal photoreceptor laminar architecture, except for foveal cone outer segment abnormalities and, in some patients, foveal cone loss. This article will summarize clinical characterization of patients and proof of concept gene replacement studies in several animal models of GC1 deficiency, both of which have laid the groundwork for clinical application of a gene therapy for treatment of LCA1.
Structure of Tobacco Mosaic Virus at 3.6 Å Resolution: Implications for Assembly

X-ray fiber diffraction analysis of tobacco mosaic virus (TMV) has led to the building of a molecular model of the intact virus, based on a map at 3.6 A resolution derived from five separated Bessel orders. This has been made possible by advances in the solution of the fiber diffraction phase problem. It is now possible to understand much of the chemical basis of TMV assembly, particularly in terms of intersubunit electrostatic interactions and RNA binding. Consideration of the molecular structure in conjunction with physical chemical studies by several groups of investigators suggests that the nucleating aggregate for initiation of TMV assembly is a short (about two turns) helix of protein subunits, probably inhibited from further polymerization in the absence of RNA by the disordering of peptide loop near the inner surface of the virus.
Human trypanolytic factor APOL1 forms pH-gated cation-selective channels in planar lipid bilayers: relevance to trypanosome lysis.

Apolipoprotein L-1 (APOL1), the trypanolytic factor of human serum, can lyse several African trypanosome species including Trypanosoma brucei brucei, but not the human-infective pathogens T. brucei rhodesiense and T. brucei gambiense, which are resistant to lysis by human serum. Lysis follows the uptake of APOL1 into acidic endosomes and is apparently caused by colloid-osmotic swelling due to an increased ion permeability of the plasma membrane. Here we demonstrate that nanogram quantities of full-length recombinant APOL1 induce ideally cation-selective macroscopic conductances in planar lipid bilayers. The conductances were highly sensitive to pH: their induction required acidic pH (pH 5.3), but their magnitude could be increased 3,000-fold upon alkalinization of the milieu (pKa = 7.1). We show that this phenomenon can be attributed to the association of APOL1 with the bilayer at acidic pH, followed by the opening of APOL1-induced cation-selective channels upon pH neutralization. Furthermore, the conductance increase at neutral pH (but not membrane association at acidic pH) was prevented by the interaction of APOL1 with the serum resistance-associated protein, which is produced by T. brucei rhodesiense and prevents trypanosome lysis by APOL1. These data are consistent with a model of lysis that involves endocytic recycling of APOL1 and the formation of cation-selective channels, at neutral pH, in the parasite plasma membrane.
Victims’ Voices and Victims’ Choices in Three IPV Courts

Critics of mandatory interventions for intimate partner violence (IPV) propose that the justice system disempowers victims by denying them voice and choice in legal proceedings. This exploratory study examines this claim through observations of three criminal courts. Findings show that victims are offered voice and a degree of choice in only one of the three courts. Court procedures that enhance victim voice and choice include a specialized IPV court, victim advocates trained in victims’ rights issues, and a lead judge who models respectful treatment of victims. The author proposes that voice and choice are distinct aspects of victim empowerment and that the provision of voice may have benefits to IPV victims that are distinct from the benefits of choice.
Bullous Pemphigoid in Late Childhood Successfully Treated with Mycophenolate Mofetil as an Adjuvant Therapy

: Bullous pemphigoid is an acquired subepidermal vesiculobullous disease most commonly seen in the elderly. We report a 16-year-old girl with bullous pemphigoid who achieved disease remission with mycophenolate mofetil as an adjuvant therapy.
Nitric oxide in neuronal degeneration.

SummaryNO has clearly revolutionized our thinking about aspects of neurotransmission and neuronal signaling. NO is emerging as an important regulator of a variety of physiologic processes; however, under conditions of excessive or inappropriate formation, NO is also emerging as an important mediator of pathologic nervous tissue damage. Uncovering and understanding the targets of NO that contribute to the neuropathologic process will hopefully lead to the development of selective therapeutic agents and to a better understanding of basic processes underlying normal and pathological neuronal functions.VLD is supported by grants from USPHS NS22643, NS33142, the American Foundation for AIDS Research, National Alliance for Research on Schizophrenia and Depression, American Heart Association, the Alzheimer's Association and the Muscular Dystrophy Association. T. M. D. is supported by grants from the USPHS NS01578, NS26643, NS33277, and the American Health Assistance Foundation, Paul Beeson Physician Scholars in ...
Discordance between morphological species identification and mtDNA phylogeny in the flesh fly genus Ravinia (Diptera : Sarcophagidae)

In order to better understand the phylogenetic relationships among species in the genus Ravinia Robineau-Desvoidy, 1863, we analysed data from two mitochondrial gene fragments: cytochrome oxidase I (COI) and cytochrome oxidase II (COII). We used Bayesian inference and maximum likelihood methods to infer phylogenetic relationships. Our results indicate that the genera Ravinia and Chaetoravinia, previously synonymised into the genus Ravinia (sensu lato) are each likely to be monophyletic (posterior probability 1; bootstrap support 85%). We found highly supported paraphyletic relationships among species of Ravinia, with relatively deep splits in the phylogeny. This conflict between the morphological species definitions and the mtDNA phylogeny could be indicative of the presence of cryptic species in Ravinia anxia (Walker, 1849), Ravinia floridensis (Aldrich, 1916), Ravinia lherminieri (Robineau-Desvoidy, 1830), and Ravinia querula (Walker, 1849).
Mutations in the Catalytic Domain of Prohormone Convertase 2 Result in Decreased Binding to 7B2 and Loss of Inhibition with 7B2 C-terminal Peptide

Prohormone convertases 1 (PC1) and 2 (PC2) are members of a family of subtilisin-like proprotein convertases responsible for proteolytic maturation of a number of different prohormones and proneuropeptides. Although sharing more than 50% homology in their catalytic domains, PC1 and PC2 exhibit differences in substrate specificity and susceptibility to inhibitors. In addition to these differences, PC2, unlike PC1 and other members of the family, specifically binds the neuroendocrine protein 7B2. In order to identify determinants responsible for the specific properties of the PC2 catalytic domain, we compared its primary sequence with that of other PCs. This allowed us to distinguish a PC2-specific sequence at positions 242–248. We constructed two PC2 mutants in which residues 242 and 243 and residues 242–248 were replaced with the corresponding residues of PC1. Studies of in vivo cleavage of proenkephalin, in vivo production of α-MSH from proopiomelanocortin, and in vitro cleavage of a PC2-specific artificial substrate by mutant PC2s did not reveal profound alterations. On the other hand, both mutant pro-PC2s exhibited a considerably reduced ability to bind to 21-kDa 7B2. In addition, inhibition of mutant PC2-(242–248) by the potent natural inhibitor 7B2 CT peptide was almost completely abolished. Taken together, our results show that residues 242–248 do not play a significant role in defining the substrate specificity of PC2 but do contribute greatly to binding 7B2 and are critical for inhibition with the 7B2 CT peptide.
Balancing Multiple Sources of Reward in Reinforcement Learning

For many problems which would be natural for reinforcement learning, the reward signal is not a single scalar value but has multiple scalar components. Examples of such problems include agents with multiple goals and agents with multiple users. Creating a single reward value by combining the multiple components can throw away vital information and can lead to incorrect solutions. We describe the multiple reward source problem and discuss the problems with applying traditional reinforcement learning. We then present an new algorithm for finding a solution and results on simulated environments.
Your phone or mine?: fusing body, touch and device sensing for multi-user device-display interaction

Determining who is interacting with a multi-user interactive touch display is challenging. We describe a technique for associating multi-touch interactions to individual users and their accelerometer-equipped mobile devices. Real-time device accelerometer data and depth camera-based body tracking are compared to associate each phone with a particular user, while body tracking and touch contacts positions are compared to associate a touch contact with a specific user. It is then possible to associate touch contacts with devices, allowing for more seamless device-display multi-user interactions. We detail the technique and present a user study to validate and demonstrate a content exchange application using this approach.
Magnetic Fluid and Nanoparticle Applications to Nanotechnology

Magnetic field based micro/nanoelectromechanical systems (MEMS/NEMS) devices are proposed that use 10 nm diameter magnetic particles, with and without a carrier fluid, for a new class of nanoduct flows, nanomotors, nanogenerators, nanopumps, nanoactuators, and other similar nanoscale devices. A few examples of macroscopic ferrohydrodynamic instabilities that result in patterns, lines, and structures are shown that can be scaled down to sub-micron dimensions.
Medicinal Plants of Mt. Pelion, Greece

This study focuses on plants used for medicinal purposes in the Mt. Pelion area of Greece; however other plant uses were noted when discovered. A total of 225 taxa representing 77 families are presented along with habitat data and ethnobotanical information when relevant. Some notes on related species are also included. In addition to ethnobotanical field research which included collection of voucher specimens, ancient literature pertaining to plant usage was also consulted. Local markets that sold wild plants or their products were investigated as well. Some plants not known to be ethnobotanically significant were also collected in order to learn more about species distribution on Mt. Pelion. It is possible that ancient plant usage information that was lost due to the destruction of classical literary works has survived in the oral tradition in the Mt. Pelion area and elsewhere in Greece. A number of little known psychoactive and narcotic plant uses (including ivy as an additive to wine) are reported in this publication.
Diethyl 1,1‐Cyclobutanedicarboxylate

Diethyl 1,1-cyclobutanedicarboxylate reactant: 480 g. (3.0 moles) of diethyl malonate reactant: 472 g. (3.0 moles) of trimethylene chlorobromide product: cyclobutanecarboxylic acid product: diethyl 1,1-cyclobutanedicarboxylate Keywords: alkylation, C-alkylation; annulation, carbocyclic-[4]; cyclization, condensation
Multiple Modes Of Na Channel Modulation By Divalent Cations

Ca2+ and other divalent cations exert multiple effects on voltage-gated Na channels. Although virtually i yyermeant, both extracellular and intracellular Ca ions block Na+ m vement by binding to sites within the channel. Ca*+ also competes with tetrodotoxin and saxitoxin for a blocking site near the external mouth of the pore. Both internal and external divalent cations also affect voltagedependent Na channel gating by interacting with negatively charged membrane lipids and binding sites on the channel itself. Thus, divalent cations are effective modulators of Na channels and valuable probes of channel structure and function.
High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene

The gene encoding AIB1, an estrogen receptor coactivator, is amplified in a subset of human breast cancers. Here we show that overexpression of AIB1 in transgenic mice (AIB1-tg) leads to mammary hypertrophy, hyperplasia, abnormal postweaning involution, and the development of malignant mammary tumors. Tumors are also increased in other organs, including the pituitary and uterus. AIB1 overexpression increases mammary IGF-I mRNA and serum IGF-I protein levels. In addition, IGF-I receptor and downstream signaling molecules are activated in primary mammary epithelial cells and mammary tumor cells derived from AIB1-tg mice. Knockdown of AIB1 expression in cultured AIB1-tg mammary tumor cells leads to reduced IGF-I mRNA levels and increased apoptosis, suggesting that an autocrine IGF-I loop underlies the mechanism of AIB1-induced oncogenesis.
A comparison of acquired immunodeficiency syndrome and Kaposi's sarcoma incidence rates, Atlanta, 1983-86

Recent temporal trends in incidence rates for acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma were compared in metropolitan Atlanta, Georgia. From 1983 through 1986 the age-adjusted incidence rate of Kaposi's sarcoma among White males ages 25-49 increased 11-fold (2.2-24.4/100,000 person years). The annual incidence rate of AIDS increased ten-fold (11.3-113.3/100,000). These findings do not support earlier reports that the proportion of AIDS patients with Kaposi's sarcoma has decreased over time.
Efficacy of labeling of foods and pharmaceuticals.

Over the past several decades, the US Congress and regulatory agencies have developed a complex system of informational regulations for food and drugs that goes far beyond indications such as "USDA pproved." Individual states have also begun to display increasing interest in this issue. California, for instance, has adopted its own warning system for risks of cancer and reproductive toxicity, and many other states are also considering warning measures. These efforts have diverse objectives. One function is to provide information about beneficial features, such as information about the nutritional value of foods and the medical conditions that pharmaceutical products can address. A second function is to alert the consumers to possible adverse effects of the product, for instance sodium labels for foods, health warnings for cigarettes, and information about adverse reactions to drugs. A third function of warnings is to indicate the particular types of precautions, that should be exercised, e.g. cautioning against driving after drinking alcoholic beverages, and against adverse drug interactions. Examination of food and drug warnings is instructive more generally since these warnings embody all the functions of risk communication mechanisms. Moreover, the presence of the learned intermediary--the physician in the case of prescription medications--provides an interesting variation on the context of risk communication.
Linear discriminant analysis: new formulations and overfit analysis

In this paper, we will present a unified view for LDA. We will (1) emphasize that standard LDA solutions are not unique, (2) propose several new LDA formulations: St-orthonormal LDA, Sw-orthonormal LDA and orthogonal LDA which have unique solutions, and (3) show that with St-orthonormal LDA and Sw-orthonormal LDA formulations, solutions to all four major LDA objective functions are identical. Furthermore, we perform an indepth analysis to show that the LDA sometimes performs poorly due to over-fitting, i.e., it picks up PCA dimensions with small eigenvalues. From this analysis, we propose a stable LDA which uses PCA first to reduce to a small PCA subspace and do LDA in the subspace.
An Opportunity for Change: College Accreditation and the New Library Manager

Column Editor’s Note. Accreditation is a challenging process for all librarians, but perhaps even more so at the community college level, where library leaders and librarians tend to be deeply invo...