cssi/SciSciGPT-SciSciNet huggingface dataset:
Mechanism of Inhibition of Estrogen Biosynthesis by Azole Fungicides

Biosynthesis of estrogens from androgens is catalyzed by cytochrome P450 aromatase. Aromatase inhibition by the triazole compounds letrozole (LTZ) and anastrozole is a prevalent therapy for estrogen-dependent postmenopausal breast cancer. Azoles are widely used as agricultural fungicides and antimycotic drugs that target 14α-demethylase. Some were previously shown to inhibit aromatase, thereby raising the possibility of endocrine disruptive effects. However, mechanistic analysis of their inhibition has never been undertaken. We have evaluated the inhibitory effects of 3 common fungicides, bifonazole, imazalil, and flusilazole, in human aromatase purified from placenta and compared them with LTZ, the most potent inhibitor of aromatase. Bifonazole exhibits strong inhibitory effects with an IC50 of 270nM and Ki (Michaeles-Menten inhibition constant) of 68nM, compared with 10nM and 13nM, respectively, for LTZ. The IC50 and Ki are 1100nM and 278nM for imazilil and 3200nM and 547nM for flusilazole, respectively...
Review of equine piroplasmosis.

Equine piroplasmosis is caused by one of 2 erythrocytic parasites Babesia caballi or Theileria equi. Although the genus of the latter remains controversial, the most recent designation, Theileria, is utilized in this review. Shared pathogenesis includes tick-borne transmission and erythrolysis leading to anemia as the primary clinical outcome. Although both parasites are able to persist indefinitely in their equid hosts, thus far, only B. caballi transmits across tick generations. Pathogenesis further diverges after transmission to equids in that B. caballi immediately infects erythrocytes, whereas T. equi infects peripheral blood mononuclear cells. The recent re-emergence of T. equi in the United States has increased awareness of these tick-borne pathogens, especially in terms of diagnosis and control. This review focuses in part on factors leading to the re-emergence of infection and disease of these globally important pathogens.
Adrenocorticotropin increases interleukin-6 release from rat adrenal zona glomerulosa cells.

Interleukin-6 (IL-6) is produced by adrenal zona glomerulosa cells; its release is stimulated by several secretagogues, including IL-1 alpha, IL-1 beta, and angiotensin II. The present study reports that ACTH (0.1-100 nM) increased the release of IL-6 from primary cultures of rat adrenal cells in a concentration-dependent manner. This increase was accompanied by an increase in cAMP content in cell extracts and in the incubation medium. The dynamics of IL-6 release from the adrenal cells also were investigated using a perifusion system; approximately 50 min were required for the effects of IL-1 alpha, IL-1 beta, and ACTH on IL-6 release to become apparent. Following withdrawal of the secretagogues, IL-6 release returned to basal levels within 90-120 min. In some experiments, the adrenal zona glomerulosa was separated from the zona fasciculata/reticularis to determine the origin of secretagogue-stimulated IL-6 release. PGE2 and forskolin increased IL-6 release from both cell types, but maximal release from ...
Evidence of ambiguous differentiation and mTOR pathway dysregulation in subependymal giant cell astrocytoma.

Objective The exact cell of origin of subependymal giant cell astrocytoma is debated but most currently consider the tumor in the astrocytic category. Mutations and subsequent biallelic inactivation of TSC1 encoding hamartin, or TSC2 encoding tuberin appear to be the underlying genetic aberrations. Inactivation leads to loss of proteins that inhibit mammalian target of rapamycin (mTOR ) disrupting tightly regulated cell functions. Material and method We analyzed the expression of tuberin and hamartin along with an array of neuroepithelial markers in 9 subependymal giant cell astrocytomas. In addition, RPS6 and 4EBP1 regulatory proteins that are downstream in the mTOR pathway were also evaluated. Results While hamartin and tuberin expression levels were relatively decreased compared to control tissue, this was not of particular practical use to detect the mutated gene since low levels of positivity could be detected throughout the central nervous system. As expected, the levels of RPS6 and 4EBP1 were increased, further confirming the activation of the mTOR pathway. GFAP was positive in 5 cases, while Synaptophysin positivity was found in all tumors. CD34 (a marker often observed in well differentiated glio-neuronal tumors), Olig2 (a nuclear marker present in most gliomas), IDH1 and IDH2 were entirely negative in all tumor cells. Ki67 (MIB-1) showed a low proliferation rate ranging from 2% to 8%. Conclusion Staining with neuroepithelial markers supports the suggestion of ambiguous differentiation. Subependymal giant cell astrocytomas do not appear to have the typical expression profiles of astrocytic tumors, under which they have been classified.
Pancreas acinar cell differentiation. 8. Effect of methionine on DNA synthesis of pancreas anlage in organ culture.

Abstract Rat pancreas embryonic rudiments incubated in a control chemically-defined (CD) medium grew and differentiated during 9 days of organ culture to adult acinar cells characterized by zymogen granules and relatively high levels of enzyme activity. Incubation of the anlagen in a chemically-defined medium with a lower methionine concentration (CD-MD) gave growth to a comparable size but no acinar cell formation, no zymogen granules and no increases of enzyme activity. Anlagen incubated in the CD medium showed a marked decrease of the autoradio-graphic labeling index of acinar cell nuclei after exposure to 3H-thymidine during the period of organ culture, whereas culture of anlagen in the CD-MD medium led to far less decrease of the acinar cell labeling index. When anlagen which had been grown in the CD-MD medium for 9 days were incubated for 3 additional days in the CD medium there was a highly significant drop in the previously high labeling index. The higher level of methionine in the CD medium may have been involved in the synthesis of, or the methylation of, an inhibitor of DNA synthesis.
A relationship between the 11-2--ball property and the strong 11-2--ball property

Abstract The 1 1 2 -ball property and the strong 1 1 2 -ball property in a Banach space were studied by D. Yost [Bull. Austral. Math. Soc. 20 (1979) , 285–300; Math. Scand. 50 (1982) , 100–110]. G. Godini [“Banach Space Theory and Its Applications” (A. Pietsch, N. Popa and I. Singer, Eds.), Vol. 991, Springer-Verlag, New York/Berlin, 1983 ], gave geometrical characterizations of the subspaces with property (∗), as well as with the 1 1 2 -ball property. D. Yost [Math. Scand. 50 (1982) , 100–110] gave an example that has the 1 1 2 -ball property but not the strong 1 1 2 -ball property. In the present paper, property (S) is introduced and characterizations of the strong 1 1 2 -ball property are given. The subspaces of C(T) which have the 1 1 2 -ball property are characterized, where T is compact and connected.
An Extension of the REA Framework to Support Balanced Scorecard Information Requirements.

In this paper, we propose extensions to the resource‐event‐agent (REA) framework to encompass the information requirements of the balanced scorecard and other management systems that incorporate nonfinancial measures. The REA conceptual accounting framework was designed to describe the information architecture related to an organization's economic activity (e.g., McCarthy 1982; Dunn et al. 2005). Geerts and McCarthy (2001b, 2002) extended the original REA to include value‐chain level configurations, task‐level configurations, and encompass a broader array of business economic phenomena. Yet, the REA framework remains closely tied to its accounting roots, with a focus on economic events and financial resources. A substantial number of organizations are adopting strategic management systems that include both financial and nonfinancial measures to overcome known limitations of systems based on traditional financial data alone (e.g., Said et al. 2003; Eccles et al. 2001; Ittner et al. 2003). We therefore exam...
Leucine Aminopeptidase, β-Glucosidase and Alkaline Phosphatase Activity Rates and Their Significance in Nutrient Cycles in Some Coastal Mediterranean Sites

In aquatic microbial ecology, knowledge of the processes involved in the turnover of organic matter is of utmost importance to understand ecosystem functioning. Microorganisms are major players in the cycling of nutrients (nitrogen, phosphorus) and carbon, thanks to their enzymatic activities (leucine aminopeptidase, LAP, alkaline phosphatase, AP, and β-glucosidase, β-GLU) on organic polymers (proteins, organic phosphates and polysaccharides, respectively). Estimates of the decomposition rates of organic polymers are performed using fluorogenic compounds, whose hydrolysis rate allow us to obtain information on the “potential” metabolic activity of the prokaryotic community. This paper refers the enzyme patterns measured during recent oceanographic cruises performed in some coastal Mediterranean sites, not yet fully investigated in terms of microbial biogeochemical processes. Mean enzyme activity rates ranged from 5.24 to 5558.1 nM/h, from 12.68 to 244.73 nM/h and from 0.006 to 9.51 nM/h for LAP, AP and β-GLU, respectively. The highest LAP and AP activity rates were measured in the Gulf of Milazzo (Tyrrhenian Sea) and in the Straits of Messina, in association with the lowest bacterioplankton abundance; in contrast, the lowest ones were found in the northern Adriatic Sea. β-GLU was more active in the Straits of Messina. Activity rates were analysed in relation to the main environmental variables. Along the northern Adriatic coastal side affected by the Po river, significant inverse relationships linked LAP and AP with salinity, pointing out that fluvial inputs provided organic substrates for microbial metabolism. Both in the Gulf of Manfredonia and in the Straits of Messina, LAP and AP levels were inversely related with the concentration of nitrate and inorganic phosphorus, respectively. In the Gulf of Milazzo, high cell-specific AP measured in spite of phosphorus availability suggested the role of this enzyme not only in phosphorus, but also in carbon release.
Charged fraction and electrostatic collection of ultrafine and submicrometer particles formed during O2–CO2 coal combustion

Abstract The charged fraction of submicrometer and ultrafine particles generated during bench scale coal combustion and the subsequent penetration of particles through a cylindrical-wire electrostatic precipitator (ESP) in O 2 –CO 2 and O 2 –N 2 environments were measured. In all combustion environments, natural particle charging within the combustor was not adequate for high efficiency particle collection in the ESP; thus, corona generation was necessary for enhanced particle charging. With a positive applied potential, the corona inception voltage and voltage required to reach a given current level in the ESP in gas mixtures composed of O 2 and CO 2 were higher than those composed of O 2 and N 2 , while similar voltages were needed for negative corona generation. In positive coronas, particle penetration through the ESP in O 2 –CO 2 environments was 1–2 orders of magnitude higher than in O 2 –N 2 environments. Little difference in particle penetration between O 2 –N 2 and O 2 –CO 2 was seen in negative coronas.
Direct clinician-to-patient feedback discussion of inhaled steroid use: its effect on adherence.

Study Objectives To evaluate whether direct feedback discussion on inhaled steroid use might influence subsequent adherence with this therapy. Design and Setting A 10-week, single-blind, randomized trial in asthma patients. Inclusion criteria included forced expiratory volume in 1 second Measures Mean weekly inhaled steroid adherence [(number of actuations/prescribed number of actuations) · 100]; 2) number of days with overuse of inhaled steroids; 3) 24-hour and nighttime albuterol use; 4) included forced expiratory volume in 1 second; and 5) Asthma Quality of Life Questionnaire total score. Results Ten treatment and nine control patients completed the study. Mean weekly inhaled steroid adherence over the first week was not significantly different in the treatment and control groups: 61 ± 9% versus 51 ± 5%, respectively. However, by the second week, adherence increased to 81 ± 7% in the treatment group, whereas it decreased to 47 ± 7% in the control group ( P = 0.003). Adherence remained above 70% in the treatment group for the entire trial, but continued to decrease in the control group. Overuse of inhaled steroids was low in both groups. There were no group differences in any of the asthma outcomes. Conclusions Direct clinician-to-patient feedback discussion on inhaled steroid use using electronic printouts did improve adherence in the short-term in asthma patients at high-risk for poor adherence.
The growth hormone-releasing activity of a synthetic hexapeptide in normal men and short statured children after oral administration.

It has been shown that iv GH-releasing peptide (GHRP; His-DTrp-Ala-Trp-DPhe-Lys-NH2) specifically releases GH in man. Because of the clinical value of having an orally active peptide to release GH, five normal men were given GHRP orally at dosages of 100 and 300 micrograms/kg. At the 300 micrograms/kg dosage, the GH rise was detectable at 30 min, peaked between 60-75 min, and gradually declined to the baseline level between 150-180 min. Peak GH levels rose 63- and 202-fold above the baseline after administration of 100 and 300 micrograms/kg GHRP, respectively. Nine short stature children with varying degrees of GH deficiency were also included in this study. All children had short stature, slow growth, and delayed bone age and were being treated with biosynthetic human GH. The studies were performed after stopping GH treatment for 2-3 weeks. The oral GHRP dose administered to all of the children was 300 micrograms/kg, because this dosage was found to consistently increase GH levels in adults. The magnitud...
Presidential address: Outcome assessment in vascular surgery — Results mean everything☆☆☆★

I always wanted to be a surgeon. Surgeons were able to help people in a uniquely direct way, and the surgeons I most admired were willing to sacrifice something of themselves to do it. Good surgeons could look anyone squarely in the eye because they had invested their lives in a career that made a difference. They acted decisively when the best interests of their patients hung in the balance. They elevated their professio n. I wanted to be one of them, and so did you. These are the reasons most of us became surgeons in the first place. The time again has come to embrace them because nearly every surgeon now must also contend with the incidental uncertainties imposed by a sputtering economy, runaway healthcare expenses, a contentious bureaucracy, and a concerned public. Those who say they want to make things better through reform often mean that they only want to make them cheaper. Better, it seems to me, still is up to us. I f we can distance ourselves for a moment from the daily confusion regarding healthcare and how to finance it, the present debate about quality and cost offers an unmistakable opportunity for us to make vascular surgery better than it ever has been. We just have to get back to those fundamentals. What do we really stand for as surgeons? I think we stand for results.
Capacity versus robustness: a tradeoff for link restoration in mesh networks

Link recovery in high-speed four-fiber networks can be achieved using dynamic searches, covers of rings, or generalized loopback. We present a method to provide link recovery for all links in a network without using all links for backup traffic transmission. The method extends generalized loopback to operate on a subgraph of the full backup graph. The backup capacity on such links can then be used to carry unprotected traffic, i.e., traffic that is not recovered in case of a failure, while primary fibers on the links retain failure protection. Although all primary fibers remain fully robust to single-link failures, reserving links for unprotected traffic reduces a network's ability to recover from multiple failures. We explore the tradeoff between capacity and robustness to two-link failures for several typical high-speed optical fiber networks, comparing the properties of three link-restoration algorithms based on generalized loopback with the properties of covers of rings. Our results demonstrate robustness comparable or superior to that available with covers of rings while providing an additional unprotected traffic capacity of roughly 20% of the network's primary capacity.
Reconstitution of the Biochemical Activities of the AttJ Repressor and the AttK, AttL, and AttM Catabolic Enzymes of Agrobacterium tumefaciens

The attKLM operon encodes a lactonase (AttM) that hydrolyzes acylhomoserine lactone autoinducers, as well as two putative dehydrogenases (AttK and AttL). Here we show that AttK, AttL, and AttM collectively covert gamma-butyrolactone to succinate. Two metabolic intermediates, gamma-hydroxybutyrate and succinic semialdehyde, inactivated the AttJ repressor in vitro and induced attKLM transcription in vivo.
Transposon and Deletion Mutagenesis of Genes Involved in Perchlorate Reduction in Azospira suillum PS

ABSTRACT Although much work on the biochemistry of the key enzymes of bacterial perchlorate reduction, chlorite dismutase, and perchlorate reductase has been published, understanding of the molecular mechanisms of this metabolism has been somewhat hampered by the lack of a clear model system amenable to genetic manipulation. Using transposon mutagenesis and clean deletions, genes important for perchlorate reduction in Azospira suillum PS have been identified both inside and outside the previously described perchlorate reduction genomic island (PRI). Transposon mutagenesis identified 18 insertions in 11 genes that completely abrogate growth via reduction of perchlorate but have no phenotype during denitrification. Of the mutants deficient in perchlorate reduction, 14 had insertions that were mapped to eight different genes within the PRI, highlighting its importance in this metabolism. To further explore the role of these genes, we also developed systems for constructing unmarked deletions and for complementing these deletions. Using these tools, every core gene in the PRI was systematically deleted; 8 of the 17 genes conserved in the PRI are essential for perchlorate respiration, including 3 genes that comprise a unique histidine kinase system. Interestingly, the other 9 genes in the PRI are not essential for perchlorate reduction and may thus have unknown functions during this metabolism. We present a model detailing our current understanding of perchlorate reduction that incorporates new concepts about this metabolism. IMPORTANCE Although perchlorate is generated naturally in the environment, groundwater contamination is largely a result of industrial activity. Bacteria capable of respiring perchlorate and remediating contaminated water have been isolated, but relatively little is known about the biochemistry and genetics of this process. Here we used two complementary approaches to identify genes involved in perchlorate reduction. Most of these genes are located on a genomic island, which is potentially capable of moving between organisms. Some of the genes identified are known to be directly involved in the metabolism of perchlorate, but other new genes likely regulate the metabolism in response to environmental signals. This work has uncovered new questions about the regulation, energetics, and evolution of perchlorate reduction but also presents the tools to address them.
Regulation of the autophagy protein LC3 by phosphorylation

Macroautophagy is a major catabolic pathway that impacts cell survival, differentiation, tumorigenesis, and neurodegeneration. Although bulk degradation sustains carbon sources during starvation, autophagy contributes to shrinkage of differentiated neuronal processes. Identification of autophagy-related genes has spurred rapid advances in understanding the recruitment of microtubule-associated protein 1 light chain 3 (LC3) in autophagy induction, although braking mechanisms remain less understood. Using mass spectrometry, we identified a direct protein kinase A (PKA) phosphorylation site on LC3 that regulates its participation in autophagy. Both metabolic (rapamycin) and pathological (MPP+) inducers of autophagy caused dephosphorylation of endogenous LC3. The pseudophosphorylated LC3 mutant showed reduced recruitment to autophagosomes, whereas the nonphosphorylatable mutant exhibited enhanced puncta formation. Finally, autophagy-dependent neurite shortening induced by expression of a Parkinson disease–associated G2019S mutation in leucine-rich repeat kinase 2 was inhibited by dibutyryl–cyclic adenosine monophosphate, cytoplasmic expression of the PKA catalytic subunit, or the LC3 phosphorylation mimic. These data demonstrate a role for phosphorylation in regulating LC3 activity.
SIRT1 contains N- and C-terminal regions that potentiate deacetylase activity

SIRT1 is one of seven mammalian sirtuin (silent information regulator 2-related) proteins that harbor NAD+-dependent protein deacetylase activity and is implicated in multiple metabolic and age-associated pathways and disorders. The sirtuin proteins contain a central region of high sequence conservation that is required for catalytic activity, but more variable N- and C-terminal regions have been proposed to mediate protein specific activities. Here we show that the conserved catalytic core domain of SIRT1 has very low catalytic activity toward several known protein substrates, but that regions N- and C-terminal to the catalytic core potentiate catalytic efficiency by between 12- and 45-fold, with the N-terminal domain contributing predominantly to catalytic rate, relatively independent of the nature of the acetyl-lysine protein substrate, and the C-terminal domain contributing significantly to the Km for NAD+. We show that the N- and C-terminal regions stimulate SIRT1 deacetylase activity intramolecularly and that the C-terminal region stably associates with the catalytic core domain to form a SIRT1 holoenzyme. We also demonstrate that the C-terminal region of SIRT1 can influence the inhibitory activity of some sirtuin inhibitors that are known to function through the catalytic core domain. Together, these studies highlight the unique properties of the SIRT1 member of the sirtuin proteins and have implications for the development of SIRT1-specific regulatory molecules.
Perry Miller's Rehabilitation of the Puritans: A Critique

In the era between the Civil War and the Depression the mythical character called the “American Mind” was troubled. All was well during the day when prosperity and success faced him at every turn, but at night he would sometimes dream of his childhood and awake feeling strangely uneasy. His analyst explained that this tension was the product of latent guilt feelings and suggested for therapy that he read himself to sleep with recent studies of the oppressive effects of Puritanism on young national minds. Turning to these works, the “American Mind” found that the analyst had been quite right. The source of the guilt feelings, he discovered, was an irrational phase of his development called the Reformation. This phase had been dominant when he lived in New England (he since had moved to the Midwest), but he was assured that the latest scholarship had discovered its influence to be harsh, grotesque, superstitious, narrowminded, illiberal, and worst of all intolerant.1 The problem was, one expert informed him, that this era “was unleavened by the spirit of the Renaissance.” Another observed that the Reformation attitudes were a “subtle poison” flowing thorugh the veins of the entire social organism. Still another implied that the “splendor of the Renaissance” had been delayed three hundred years by Reformation intolerance. Convinced that the open-mindedness of the Renaissance was healthier than the irrational bigotry of the Reformation, the “American Mind” of this era began to feel easier about his past. He resolved to tolerate everyone, except of course his more conservative enemies whom he damned as “Puritan.”
A productivity centered application performance tuning framework

In response to the productivity challenge of the U.S. DARPA HPCS initiative, we have developed a methodology that provides an extremely simple and pain-free interface through which scientists can collect rich performance data from selected parts of an execution, digest the data at a very high level, and plan for improvements. This process can be easily repeated, each time refining the selection of parts of the application and revising the granularity of data collected, until complete insight is gained about bottlenecks. A distinct feature of our approach is that the framework is independent of the features being examined. Recognizing that the features to be examined change with systems/applications and also with depth at which an aspect is being examined, our framework provides an easy interface to continually add new features for examination. Furthermore, many different features can be collected simultaneously and examined in a non-interfering manner. Finally, all this is accomplished without changing the source code in any manner. We believe that this is an ideal platform for building knowledge-based repositories for automatic performance tuning, which is the subject of our future study.In this paper, we describe our productivity centered framework for application performance tuning. It comprises of three features: an unique source code and binary instrumentation feature, a versatile user-interface that brings all the sophisticated capabilities of the binary instrumentation to the user at a higher level of abstraction, and the functionality to collect different dimensions of performance data. The results of execution are all in terms of source level names and at no point does the scientist needs to worry about low-level details of instrumentation. We believe that it is this ability, of deciphering performance impacts at source level, that leads to high productivity of scientists to understand, direct and tune the behavior of the computing system.
Donor states and donee states: investigating geographic redistribution of the US federal-aid highway program 1974–2008

In 2009, the US government spent more than $42 billion on the federal-aid highway program. Most of this money was raised from motor vehicle taxes, whose proceeds are deposited in the highway trust fund. Federal motor vehicle user taxes flow into the fund and aid expenditures flow out from it to build and maintain highways and other transportation infrastructure. With so much money at stake it should be no surprise that expenditure decisions are the subject of intense political debate. Chief among these debates is the conflict between donor states, whose residents pay more in highway user taxes than the state receives in federal highway aid and donee states, whose residents pay less in highway user taxes than the state receives in highway aid. While this geographic redistribution has been masked recently by infusions of general fund revenue into the trust fund, the debate nevertheless continues. This paper attempts to understand why some states are donors and others are donees by simultaneously testing four hypotheses about the geographic redistribution of federal highway dollars that relate to a state’s highway need, economic condition, level of urbanization, and representation on the key Congressional oversight committees. The analyses show that redistribution does not favor states with larger highway systems, more highway use, or lower median incomes, all of which are different indicators of need. Instead, states that are less urban and better represented on the four key Congressional committees generally benefit from redistribution. These findings indicate that the user tax revenues are not used in places where they are most needed. Thus they provide little empirical support for any compelling policy argument for continued geographic redistribution of federal highway user tax dollars.
Experimental Validation of Conditioned Inhibition

24 naive albino rats were run down a straight alley 30 trials a day. Half were fed 10 gm. per day and half 12. Half were run under spaced conditions and half under massed. All Ss stopped running although they were rewarded on every trial. Drive level was significantly related to days to extinction, and massing of trials was significantly related to running time. Implications of these findings were discussed.
Self-Stabilization in Amorphous Silicon Circuits

Thin-film transistors (TFTs) based on disordered semiconductors such as amorphous hydrogenated silicon (a-Si:H) experience a threshold voltage (VT) shift with time in the presence of a gate bias. The VT shift needs to be compensated for circuit applications. We study an interesting property of self-compensation in fundamental analog TFT circuits with one a part of the circuit compensating for the effects of VT shift in the other and vice versa.
The Design of a Single Cavity Harmonic Buncher for Argonne's Low Beta Heavy Ion Linac

In order to increase the beam capture efficiency of Argonne's heavy ion linac to over 70%, a single cavity harmonic buncher has been designed as a replacement for the existing fundamental frequency buncher Because the beam line space between the 1.5 MeV Xe+1 preaccelerator and first accelerating cavity is at a premium, especially in the tunnel area near the preaccelerator, a single cavity design was undertaken. In addition, to further conserve access space, the cavity was designed to fit directly beneath the beam line. The cavity is designed to resonate at the fundamental linac frequency of 12.5 MHz and its first harmonic, 25 MHz. This was accomplished by nesting the 25 MHz resonant section inside the larger 12.5 MHz resonant section. Both sections are heavily capacitively loaded, folded coaxial lines with two 0.008 m accelerating gaps per section. The cavity was designed using a transmission line model taking account of the capacitances of each discontinuity and by use of the RF cavity computer program "Superfish." The transit time factor for the cavity gaps was calculated using the computer program "Poisson" and are 0.44 for the 25 MHz section and 0.70 for the 12.5 MHz section. The transit time factors are "poor" because of the large linac aperture of 0.049 m.
Single Molecule Study of the Motion of Matrix Metalloprotease MMP1 on Type I Collagen Fiber Shows Proteolysis Driven Hindered Biased Diffusion

Diffusion plays an important role in many biological processes. Using single molecule fluorescence techniques, we have studied the diffusive motion of matrix metalloprotease MMP1 on Type I collagen fiber from rat tail. Collagen is the most abundant protein in humans. Fibril forming Type I collagen is the main component of the extracellular matrix (ECM) that supports and defines most tissues. Degradation of collagen in the ECM by matrix metalloproteases (MMPs) is an important process in tissue remodeling. By tracking single fluorescently labeled MMPs moving on a collagen substrate, we were able to characterize the diffusive motion with high temporal resolution. These measurements suggest that proteolytic cleavage of the collagen substrate by Wild Type MMP1 (WT MMP1) both biases and hinders the diffusive motion of MMP1 on the collagen fiber. Both bias and hindrance are temperature dependent for WT MMP1. The diffusion was neither hindered nor biased for a point-mutant MMP1 and for MMP9, both of which are incapable of cleaving native Type I collagen from rat tail. To separate the effects of hindrance and bias, we specifically created hindrance by incubating collagen with WT MMP1 prior to measuring the motion of a catalytically inactive mutant MMP1. The resulting nonlinear diffusion of mutant MMP1 was characteristic of diffusion in hindered space. These results provide insight into the process of collagen degradation.
Training skills for illness self-management in the rehabilitation of schizophrenia. A Family-assisted Program for Latinos in California

SUMMARY This study evaluated the effectiveness of a skills training program designed to teach disease management to Latinos with schizophrenia treated at a community mental health center. Ninety-two Latino outpatients with schizophrenia and their designated relatives were randomly assigned to three months of skills training (ST) versus customary outpatient care (CC) and followed for a total of nine months. The skills training approach was culturally adapted by including the active participation of key relatives to facilitate the acquisition and generalization of disease management skills into the patients’ natural environment. There was a significant advantage for the ST group over the CC group on several symptom measures, skill acquisition and generalization, level of functioning and rates of rehospitalization. There were no significant differences between the groups on quality of life or caregiver burden. Skills training had a direct effect on skill acquisition and generalization and utilization of disease management skills led to decreased rates of rehospitalization. Incorporating an intensive, culturally relevant generalization effort into skills training for Latinos with schizophrenia and their families was effective in teaching disease management and viable in a community mental health center.
Vocal Nodules and Edema May Be Due to Vibration-Induced Rises in Capillary Pressure

Hypothesis: Vocal fold vibration may physically raise intravascular pressure to levels high enough to damage capillaries and result in leakage of erythrocytes. This type of injury is commonly seen in benign vocal fold lesions and is not well explained. Study Design: Theoretical, retrospective. Methods: The relationship of intravascular pressure to vibration frequency and amplitude is derived and confirmed with a physical blood vessel model, then applied to published human measurements to estimate human intravascular pressures. Results: Vocal fold intravascular pressure is predicted to have a quadratic dependence on both frequency and amplitude. During speaking, the pressure may rise to over 20 cmH2O, and may reach levels far higher for screaming and singing. Such pressure magnitudes are known to trigger inflammatory cascades and can lead to fluid leakage. They also have the potential for pharmacologic control with β-agonists. Conclusions: Intravascular pressure likely rises significantly during vocal fold vibration and may lead to the type of injury seen in benign vocal fold lesions. The results support voice therapy aimed at reducing vibratory amplitude. More vibratory amplitude measurements need to be performed in a wider range of subjects before the full range of human vocal fold vascular pressures can be estimated.
Neuropsychological patterns in magnetic resonance imaging-defined subgroups of patients with degenerative dementia.

We hypothesized that specific neuropsychological deficits were associated with specific patterns of atrophy. A magnetic resonance imaging volumetric study and a neuropsychological protocol were obtained for patients with several frontotemporal lobar dementia phenotypes including a social/dysexecutive (SOC/EXEC, n = 17), progressive nonfluent aphasia (n = 9), semantic dementia (n = 7), corticobasal syndrome (n = 9), and Alzheimer’s disease (n = 21). Blinded to testing results, patients were partitioned according to pattern of predominant cortical atrophy; our partitioning algorithm had been derived using seriation, a hierarchical classification technique. Neuropsychological test scores were regressed versus these atrophy patterns as fixed effects using the covariate total atrophy as marker for disease severity. The results showed the model accounted for substantial variance. Furthermore, the “large-scale networks” associated with each neuropsychological test conformed well to the known literature. For example, bilateral prefrontal cortical atrophy was exclusively associated with SOC/EXEC dysfunction. The neuropsychological principle of “double dissociation” was supported not just by such active associations but also by the “silence” of locations not previously implicated by the literature. We conclude that classifying patients with degenerative dementia by specific pattern of cortical atrophy has the potential to predict individual patterns of cognitive deficits. (JINS, 2009, 15, 459–470.)
Human-machine co-construct intelligence on horizon year load in long term spatial load forecasting

Horizon year load (HYL) is an important parameter in load forecasting algorithms that involve the Gompertz functions. Land use information has been utilized to determine HYL by computerized program. However, this approach fails when computer tries to seek optimal solution but ignores the physical meaning of the data, which can be overcome by the planners. This paper proposes and implements a methodology to determine horizon year load using land use information and planners' domain knowledge. The proposed methodology has been implemented and applied to several US utility companies to calculate the HYL of the small areas in the service territory. The resulting HYL has been used to drive the long-term electric load growth forecasting and to get satisfying forecast.
Book tagging on LibraryThing: How, why, and what are in the tags?

The purpose of this exploratory study is to understand book tagging by investigating LibraryThing (LT) members' purposes for tagging; exploring how tags are used; and comparing member assigned tags with terms in corresponding MARC records. The results show that LT members tag mostly for personal reasons, especially to manage their own collection, but they also tag to assist others to find a book. Once assigned, LT members use the tags to search and retrieve books, to gain information about books, and most importantly, to assist with personal collection management. Contrary to users of other popular tagging systems such as Flickr, LT members do not perceive social networking as an important factor when assigning and using the tags. The study also reveals that book tags by users vary greatly from MARC records. When tags overlapped with the terms used in MARC records, the majority of the matching occurred in the fields of 600s (Subject Access Fields) and 245 (Title Statement). The findings of the study contribute to the understanding of how books are represented in LT members' conceptual spaces, and have implications on how libraries could employ user created tags in OPACs.
Caught in the act: the dialogue between bacteriophage R17 and the type IV secretion machine of plasmid R1.

Summary Bacteria communicate with each other through contact-independent and -dependent signalling mechanisms. Sensory perception of both types of signals is needed for conjugative transfer of mobile DNA elements via type IV secretion systems (T4SSs) to bacterial or eukaryotic target cells. While the regulatory circuitries coupling extracellular quorum and environmental signals to transcription of T4SS genes are increasingly understood, it remains fundamentally unknown how a potential recipient cell stimulates donor conjugative DNA transfer upon contact. In this issue, Lang et al. (2011) report use of the male-specific bacteriophage R17, a phage that binds conjugative pili elaborated by IncF plasmid R1, to define requirements for phage-contact-mediated T4SS activation and phage penetration. They report that R17 penetrates only through T4SS channels engaged for delivery of their plasmid cargo to recipient cells. Engagement requires docking of catalytically active relaxase TraI bound at oriT with the TraD substrate receptor (also termed the T4CP). The data, together with recent ultrastructural and biochemical findings, support an intriguing new model that the T4CP cumulatively senses an intracellular signal (substrate docking) and an extracellular signal (pilus bound by phage or a recipient cell) to co-ordinate a late stage morphogenetic or gating reaction that enables bidirectional transmission of nucleoprotein substrates through the T4SS.
Impact of initial muscle length on force deficit following lengthening contractions in mammalian skeletal muscle.

The purpose of this study was to determine whether initial muscle length influenced the extent of isometric force deficit following 20 in vitro lengthening contractions of the soleus muscle from Fischer 344 rats. Force deficit was evaluated following one of five protocols: (1) lengthening contractions from optimal muscle length (Lo) to 120% Lo; (2) lengthening contractions from 80% Lo to Lo; (3) lengthening contractions from Lo to 120% Lo but with a stimulation frequency that elicited the same force as protocol 2; (4) 20 isometric contractions at Lo; (5) 20 stretches +/- 20% Lo in inactive muscle. Following lengthening contractions, extent of force deficit significantly differed between protocols 1, 2, and 3 (P < 0.05). Maximal isometric force (Po) was decreased by approximately 32%, approximately 8%, and approximately 15% in protocols 1, 2, and 3, respectively. In contrast, neither isometric contractions nor passive stretching (protocols 4 and 5) resulted in any reduction in Po. Irrespective of muscle length, the extent of force deficit was highly correlated (R = -0.774, P < 0.001) with peak force during active lengthening. Thus, the magnitude of isometric force deficit following lengthening contractions is influenced by both initial muscle length and peak force development. These findings have important practical implications for both exercise conditioning and rehabilitation, which are discussed.
Informational Leverage and the Endogenous Timing of Product Introductions

This paper provides a new rationale for bundling based on informational leverage. It is demonstrated that physically tying a product of established quality to one of unknown quality may mitigate the problem of asymmetric information encountered in the latter market. Leveraging reputation in one market to provide information about product quality in a second market can have profound implications for the timing of new product introductions. Bundling motivated by informational leverage can enhance efficiency by increasing consumer's access to costly information. When the possibility of endogenous timing of product introduction is considered, however, the welfare consequences of bundling are ambiguous. The positive effect of market creation must be weighed against the negative effect of market delay.
Sources of Bias in Teacher Ratings of Adolescents with ADHD

Best practice assessment of childhood ADHD includes behavior ratings from multiple sources across multiple environments. However, adolescents in secondary schools interact with several teachers each day, and research has shown that teacher perceptions of the same child can be highly inconsistent. As a result, rating scale data can be equivocal, depending on which teachers are selected. The intent of the present study was two-fold: 1) to assess the consistency between teacher behavior ratings of adolescents with ADHD, and 2) to explore predictors of rater leniency or severity (i.e., sources of bias). Results suggest that interrater reliability within our sample was moderate, consistent with previous research. Further, teacher characteristics, including sex and age, were related to biases on ratings of student hyperactivity-impulsivity. Specifically, women and younger teachers provided significantly more severe ratings on average than did men and older teachers. Implications for the interpretation and statistical norming of ADHD rating scales are discussed.
The impact of α-toxin on host cell plasma membrane permeability and cytokine expression during human blood infection by CA-MRSA USA300.

This investigation examines the influence of α-toxin (Hla) expression by CA-MRSA on host immune cell integrity and cytokine expression during infection of human blood. Flow cytometry analysis of human blood infected by Staphylococcus aureus PFGE type USA300 or a USA300Δhla demonstrated that Hla expression significantly increased plasma membrane permeability of human CD14+ monocytes. The increased susceptibility of human CD14+ monocytes to Hla toxicity paralleled the high cell-surface expression on these cell types of ADAM10. USA300 rapidly associated with PMNs and monocytes but not T cells following inoculation of human blood. Transcription analysis indicated a strong up-regulation of proinflammatory cytokine transcription following infection of human blood by USA300 and USA300Δhla. CBAs and ELISAs determined that IL-6, IL-10, TNF-α, IFN-γ, IL-1β, IL-8, and IL-4 are significantly up-regulated during the initial phases of human blood infection by USA300 relative to mock-infected blood but failed to distinguish any significant differences in secreted cytokine protein concentrations during infection by USA300Δhla relative to USA300. Collectively, these findings demonstrate that expression of Hla by USA300 has a significant impact on human CD14+ monocyte plasma membrane integrity but is not exclusively responsible for the proinflammatory cytokine profile induced by USA300 during the initial stages of human blood infection.
Floristic Quality as an Indicator of Native Species Diversity in Managed Grasslands

We undertook floristic studies of 104 grasslands in the tallgrass prairie region of Kansas to examine differences in the floristic quality of five common grassland management systems. The different grasslands were warm-season prairie hay meadows, warm-season native pastures, cool-season planted hay fields, cool-season planted pastures, and Conservation Reserve Program (CRP) fields. We recorded 383 vascular plant taxa of which 79% were native and 21% were non-native. Species richness at our sites ranged from seven for a cool season pasture to 109 for a warm-season hay meadow. Our results show that warm-season hay meadows exhibit highest species richness (256 taxa) and are habitats for highly conservative native taxa, while degraded grasslands have a higher number of alien taxa (29% in cool season planted hay fields) and lower species richness (136 for cool season hay fields). We computed Floristic Quality Assessment Index (FQI) values, which ranged from 0.3 for a cool-season pasture to 41 for warm-season prairie hay meadows while modified FQI ranged from 0.09 for a cool-season pasture to 4.48 for a warm-season prairie hay meadow. FQI values across management types differed significantly from each other (p=0.000). We conclude that native prairie hay meadows are significant reservoirs of conservative grassland species. In addition, the FQI can be a useful tool for discerning effects of land management on grassland vegetation.
A NEW PARALLEL IDENTIFICATION ALGORITHM FOR LINEAR TIME-INVARIANT SYSTEMS: PRELIMINARY RESULTS

This papers develops a new algorithm for parameter identificain linear time invariant systems. This algorithm uses an algebraic representation of parameter sensitivity variables in linear time-invariant systems[8,9], and thereby offers the potential for considerably reducing the computational burden in cases where there are a large number of unknown parameters. Additionally, this algorithm is particularly well suited to parallel computation.
Leisure Experience and Identity: What Difference Does Difference Make?

(2000). Leisure Experience and Identity: What Difference Does Difference Make? Journal of Leisure Research: Vol. 32, No. 1, pp. 79-81.