Role of the Central Metal Ion and Ligand Charge in the DNA Binding and Modification by Metallosalen Complexes

Several metal complexes of three different functionalized salen derivatives have been synthesized. The salens differ in terms of the electrostatic character and the location of the charges. The interactions of such complexes with DNA were first investigated in detail by UV−vis absorption titrimetry. It appears that the DNA binding by most of these compounds is primarily due to a combination of electrostatic and other modes of interactions. The melting temperatures of DNA in the presence of various metal complexes were higher than that of the pure DNA. The presence of additional charge on the central metal ion core in the complex, however, alters the nature of binding. Bis-cationic salen complexes containing central Ni(II) or Mn(III) were found to induce DNA strand scission, especially in the presence of co-oxidant as revealed by plasmid DNA cleavage assay and also on the basis of the autoradiogram obtained from their respective high-resolution sequencing gels. Modest base selectivity was observed in the DNA cleavage reactions. Comparisons of the linearized and supercoiled forms of DNA in the metal complex-mediated cleavage reactions reveal that the supercoiled forms are more susceptible to DNA scission. Under suitable conditions, the DNA cleavage reactions can be induced either by preformed metal complexes or by in situ complexation of the ligand in the presence of the appropriate metal ion. Also revealed was the fact that the analogous complexes containing Cu(II) or Cr(III) did not effect any DNA strand scission under comparable conditions. Salens with pendant negative charges on either side of the precursor salicylaldehyde or ethylenediamine fragments did not bind with DNA. Similarly, metallosalen complexes with net anionic character also failed to induce any DNA modification activities.

The C-terminal domain is sufficient for endonuclease activity of Neisseria gonorrhoeae MutL

The mutL gene of Neisseria gonorrhoeae has been cloned and the gene product purified. We have found that the homodimeric N. gonorrhoeae MutL (NgoL) protein displays an endonuclease activity that incises covalently closed circular DNA in the presence of Mn2+, Mg2+ or Ca2+ ions, unlike human MutL alpha which shows endonuclease activity only in the presence of Mn2+. We report in the present paper that the C-terminal domain of N. gonorrhoeae MutL (NgoL-CTD) consisting of amino acids 460-658 exhibits Mn2+-dependent endonuclease activity. Sedimentation velocity, sedimentation equilibrium and dynamic light scattering experiments show NgoL-CTD to be a dimer. The probable endonucleolytic active site is localized to a metal-binding motif, DMHAX(2)EX(4)E, and the nicking endonuclease activity is dependent on the integrity of this motif. By in vitro comparison of wild-type and it mutant NgoL-CTD protein, we show that the latter protein exhibits highly reduced endonuclease activity. We therefore suggest that the mode of excision initiation in DNA mismatch repair may be different in organisms that lack MutH protein, but have MutL proteins that harbour the D[M/Q]HAX(2)EX(4)E motif.

Surveillance of Surgical Site Infections following Major Hip and Knee Surgery in Finland

Background and aims. Since 1999, hospitals in the Finnish Hospital Infection Program (SIRO) have reported data on surgical site infections (SSI) following major hip and knee surgery. The purpose of this study was to obtain detailed information to support prevention efforts by analyzing SIRO data on SSIs, to evaluate possible factors affecting the surveillance results, and to assess the disease burden of postoperative prosthetic joint infections in Finland. Methods. Procedures under surveillance included total hip (THA) and total knee arthroplasties (TKA), and the open reduction and internal fixation (ORIF) of femur fractures. Hospitals prospectively collected data using common definitions and written protocol, and also performed postdischarge surveillance. In the validation study, a blinded retrospective chart review was performed and infection control nurses were interviewed. Patient charts of deep incisional and organ/space SSIs were reviewed, and data from three sources (SIRO, the Finnish Arthroplasty Register, and the Finnish Patient Insurance Centre) were linked for capture-recapture analyses. Results. During 1999-2002, the overall SSI rate was 3.3% after 11,812 orthopedic procedures (median length of stay, eight days). Of all SSIs, 56% were detected after discharge. The majority of deep incisional and organ/space SSIs (65/108, 60%) were detected on readmission. Positive and negative predictive values, sensitivity, and specificity for SIRO surveillance were 94% (95% CI, 89-99%), 99% (99-100%), 75% (56-93%), and 100% (97-100%), respectively. Of the 9,831 total joint replacements performed during 2001-2004, 7.2% (THA 5.2% and TKA 9.9%) of the implants were inserted in a simultaneous bilateral operation. Patients who underwent bilateral operations were younger, healthier, and more often males than those who underwent unilateral procedures. The rates of deep SSIs or mortality did not differ between bi- and uni-lateral THAs or TKAs. Four deep SSIs were reported following bilateral operations (antimicrobial prophylaxis administered 48-218 minutes before incision). In the three registers, altogether 129 prosthetic joint infections were identified after 13,482 THA and TKA during 1999-2004. After correction with the positive predictive value of SIRO (91%), a log-linear model provided an estimated overall prosthetic joint infection rate of 1.6% after THA and 1.3% after TKA. The sensitivity of the SIRO surveillance ranged from 36% to 57%. According to the estimation, nearly 200 prosthetic joint infections could occur in Finland each year (the average from 1999 to 2004) after THA and TKA. Conclusions. Postdischarge surveillance had a major impact on SSI rates after major hip and knee surgery. A minority of deep incisional and organ/space SSIs would be missed, however, if postdischarge surveillance by questionnaire was not performed. According to the validation study, most SSIs reported to SIRO were true infections. Some SSIs were missed, revealing some weakness in case finding. Variation in diagnostic practices may also affect SSI rates. No differences were found in deep SSI rates or mortality between bi- and unilateral THA and TKA. However, patient materials between these two groups differed. Bilateral operations require specific attention paid to their antimicrobial prophylaxis as well as to data management in the surveillance database. The true disease burden of prosthetic joint infections may be heavier than the rates from national nosocomial surveillance systems usually suggest.

Bismuth sulfide: A high-capacity anode for sodium-ion batteries

Exploring high-performance anode materials is currently one of the most urgent issues towards practical sodium-ion batteries (SIBs). In this work, Bi2S3 is demonstrated to be a high-capacity anode for SIBs for the first time. The specific capacity of Bi2S3 nanorods achieves up to 658 and 264 mAh g-1 at a current density of 100 and 2000 mA g-1, respectively. A full cell with Na3V2(PO4)3-based cathode is also assembled as a proof of concept and delivers 340 mAh g-1 at 100 mA g-1. The sodium storage mechanism of Bi2S3 is investigated by ex-situ XRD coupled with high-resolution TEM (HRTEM), and it is found that sodium storage is achieved by a combined conversion-intercalation mechanism.

Clinical Phenotype and Genetic Epidemiology of Schizophrenia in a Finnish Isolate

This study is part of the joint project "The Genetic Epidemiology and Molecular Genetics of schizophrenia in Finland" between the Departments of Mental Health and Alcohol Research, and Molecular Medicine at the National Public Health Institute. In the study, we utilized three nationwide health care registers: 1) the Hospital Discharge Register, 2) the Free Medication Register, and 3) the Disability Pension Register, plus the National Population Register, in order to identify all patients with schizophrenia born from 1940 to 1976 (N=33,731) in Finland, and their first degree-relatives. 658 patients with at least one parent born in a homogeneous isolate in northeastern Finland were identified, as well as 4904 familial schizophrenia patients with at least two affected siblings from the whole country. The comparison group was derived from the Health 2000 Study. We collected case records and reassessed the register diagnosis. Were contacted the isolate patients and a random sample of patients from the whole country to make diagnostic clinical interviews and to assess the negative and positive symptoms and signs of schizophrenia. In addition to these patients, we interviewed siblings who were initially healthy according to the Hospital Discharge Register. Of those with a register diagnosis of schizophrenia, schizoaffective or schizophreniform disorder, 69% received a record-based consensus diagnosis and 63% an interview-based diagnosis of schizophrenia. Patients with schizophrenia having first-degree relatives with psychotic disorder had more severe affective flattening and alogia than those who were the only affected individuals in their family. The novel findings were: 1) The prevalence of schizophrenia in the isolate was relatively high based on register (1.5%), case record (0.9-1.3%), and interview (0.7-1.2%) data. 2) Isolate patients, regardless of their familial loading for schizophrenia, had less delusions and hallucinations than the whole country familial patients, which may be related to the genetic homogeneity in the isolate. This phenotype encourages the use of endophenotypes in genetic analyses instead of diagnoses alone. 3) The absence of register diagnosis does not confirm that siblings are healthy, because 7.7% of siblings had psychotic symptoms already before the register diagnoses were identified in 1991. For genetic research, the register diagnosis should therefore be reassessed using either a structured interview or a best- estimate case note consensus diagnosis. Structured clinical interview methods need be considered also in clinical practice.

The Line Spectral Frequency Model of a Finite-Length Sequence

The line spectral frequency (LSF) of a causal finite length sequence is a frequency at which the spectrum of the sequence annihilates or the magnitude spectrum has a spectral null. A causal finite-length sequencewith (L + 1) samples having exactly L-LSFs, is referred as an Annihilating (AH) sequence. Using some spectral properties of finite-length sequences, and some model parameters, we develop spectral decomposition structures, which are used to translate any finite-length sequence to an equivalent set of AH-sequences defined by LSFs and some complex constants. This alternate representation format of any finite-length sequence is referred as its LSF-Model. For a finite-length sequence, one can obtain multiple LSF-Models by varying the model parameters. The LSF-Model, in time domain can be used to synthesize any arbitrary causal finite-length sequence in terms of its characteristic AH-sequences. In the frequency domain, the LSF-Model can be used to obtain the spectral samples of the sequence as a linear combination of spectra of its characteristic AH-sequences. We also summarize the utility of the LSF-Model in practical discrete signal processing systems.

Porphyrin synthesis in drug induced hepatic porphyria

Liver δ-aminolaevulate (ALA) synthetase and ALA dehydratase are induced to a greater extent in 3,5-diethoxy carbonyl-1,4-dihydrocollidine (DDC) injected mice as compared to the allyl isopropyl acetamide (AIA) injected rats. DDC treated mice do not show an increase in porphobilinogen (PEG) levels commensurate with the increase in ALA levels and the two enzyme activities, but accumulate enormous quantities of protoporphyrin in the liver. Normal mouse liver has an inherent greater capacity to convert PBG to porphyrins as compared to that of the rat. This together with the inhibition of iron incorporation into protoporphyrin in vivo at later stages of DDC administration can account for the large accumulation of protoporphyrin in these animals.

Hirsitaloteollisuuden kehityshaasteet

Pientalobarometri 2/2008 ennustaa omakotitalorakentamisen jatkavan laskuaan rakentamiskustannusten kasvamisesta, kaavoituksesta, tonttitarjonnasta ja talouden tilasta johtuen. Kustannusten odotetaan edelleen nousevan mm. energia­tehokkuuden kohentumisen myötä. Työ- ja elinkeinoministeriön Puutalojen ja rakennuspuusepäntuotteiden valmistus –toimialaraportissa 2008 oletetaan myös, että lämmöneristysvaatimukset ovat saattaneet lisätä massiivihirsitalojen kysyntää, koska uusien määräysten voimaantulon jälkeen niitä ei mahdollisesti enää tehdä. Kehityksen voidaan olettaa johtavan rakennusten koon ja varustetason järkevöittämiseen. Oma­koti­talorakentamisen tarpeeksi pientalobarometri laskee 20 000 asuntoaloitusta, mutta toimialaraportissa määrän arvioidaan vuonna 2008 jäävän 12 500 oma­kotitalon aloitukseen. Avaimet käteen –rakentaminen on kasvusuunnassa ja talo­paketit ovat kehittymässä selvemmiksi rakennusosakokonaisuuksiksi. Pientalobarometri kertoo suomalaisten toivovan yksilöllisyyttä. Talotehtaiden toimituksista yksilöllisiä suunnitteluratkaisuja on kolmannes ja tyyppimuunnoksia puolet. Valmisosatalojen osuus asunnoista on noin 68 % ja teollisen hirren osuus valmisosatalojen markkinoista on nyt kutakuinkin samoissa 10 % lukemissa kuin 20 vuotta sitten. Korkeimmillaan teollisen hirren osuus valmisosataloista kävi 17 % tasolla kymmenen vuotta sitten, vuosina 1995 ja 1996. Siporex-, betoni,- tiili- ja harkkotalojen osuus on noussut kahdessakymmenessä vuodessa 4 %:sta 12 %:iin ja precut-talojen osuus 2 %:sta 16 %:iin, kun taas puuelementtien osuus on laskenut 85 %:sta 62 %:iin. Talopaketin keskimääräinen kuluttajahinta on Toimialaraportin mukaan noin 83 000 euroa ja niitä valmistuu vuodessa alle 10 000. Talopakettimarkkinat ovat Pientalobarometrin mukaan vuonna 2008 hieman laskeneet vuosien 2006 ja 2007 huippulukemista alle 800 miljoonan euron. Teollisten hirsivalmistajien liikevaihto laski myös vuodesta 2007 alle 350 miljoonan. Toimialaraportin mukaan puutalojen valmistus työllistää vajaa 4000 henkeä 251 toimipaikassa (2006). Alan liikevaihto vuonna 2006 oli 812 miljoonaa euroa ja viennin arvo 178 miljoonaa euroa. Viennin kasvun todettiin riippuvan hirsitaloteollisuudesta. Viennin kannalta tärkeitä alueita ovat Keski-Eurooppa, Venäjä, Japani ja Pohjoismaat. Puutalojen vienti on Toimialaraportin mukaan kohonnut 90-luvun alun noin 30 miljoonasta yli 200 miljoonaan euroon, josta hirsitalojen viennin arvo ylittää 160 miljoonaa. Tutkimus- ja kehittämiskuluiksi arvioidaan puutalon valmistajilla 0–2 % tuotannon arvosta. Puutalojen mediaanikäyttökate oli Toimialaraportin mukaan vuonna 2006 noin 6 % kun teollisuuden vastaava luku on 10 %. Finnveran tilastointi hirsitalojen kustannusrakenteesta ja kannattavuudesta ei poikkea tästä, vaan hirsitalojen käyttökatteeksi ilmoitetaan 6,4 % ja kokonaistulokseksi 3,4 % vuonna 2007. Toimialaraportin mukaan teollisuuden omavaraisuusaste on noin 43 % kun taas puutaloteollisuuden omavaraisuusaste jää 26,5 %:iin ja hirsitalojen Finnveran mukaan 27,7 %:iin. Hirsitaloja valmistaa Toimialaraportin mukaan noin 150 yritystä. Alan kahden suurimman yrityksen osuus on lähes puolet koko alan liikevaihdosta.

Two-way converter logic for positive and negative binary numbers

This paper describes a hardware implementation of a two-way converter logic by which conversion between numbers from positive to negative binary representation is possible. Index terms: (i) Negative radix, (ii) Positive radix, (iii) Two-way conversion.

Studies on induction of delta-aminolevulinic acid synthetase in mouse liver

Administration of 3,5-diethoxy carbonyl-1,4-dihydrocollidine (DDC) to mice resulted in a striking increase in the level of δ-aminolevulinic acid (ALA) synthetase in liver. Although the enzyme activity was primarily localized in mitochondria and postmicrosomal supernatant fluid, a significant level of activity was also detected in purified nuclei. The time course of induction showed a close parallelism between the bound and free enzyme activities with the former always accounting for a higher percentage of the total activity as compared to the latter. Studies with cycloheximide indicated a half-life of around 3 hr for both the bound and free ALA synthetase. Actinomycin D and hemin prevented enzyme induction when administered along with DDC, but when administered 12 hr after DDC treatment Actinomycin D did not lead to a decay of either the bound or free enzyme activity and hemin inhibited the bound enzyme activity but not the free enzyme level. The molecular sizes of the mitochondrial and cytosolic ALA synthetase(s) were found to be similar on sephadex columns.

The Electronic Journal of Information Technology in Construction (ITcon): An Open Access Journal Using an Un-paid, Volunteer-Based Organization

Introduction This case study is based on the experiences with the Electronic Journal of Information Technology in Construction (ITcon), founded in 1995. Development This journal is an example of a particular category of open access journals, which use neither author charges nor subscriptions to finance their operations, but rely largely on unpaid voluntary work in the spirit of the open source movement. The journal has, after some initial struggle, survived its first decade and is now established as one of half-a-dozen peer reviewed journals in its field. Operations The journal publishes articles as they become ready, but creates virtual issues through alerting messages to “subscribers”. It has also started to publish special issues, since this helps in attracting submissions, and also helps in sharing the work-load of review management. From the start the journal adopted a rather traditional layout of the articles. After the first few years the HTML version was dropped and papers are only published in PDF format. Performance The journal has recently been benchmarked against the competing journals in its field. Its acceptance rate of 53% is slightly higher and its average turnaround time of seven months almost a year faster compared to those journals in the sample for which data could be obtained. The server log files for the past three years have also been studied. Conclusions Our overall experience demonstrates that it is possible to publish this type of OA journal, with a yearly publishing volume equal to a quarterly journal and involving the processing of some fifty submissions a year, using a networked volunteer-based organization.

Optimum Design for External Seismic Stability of Geosynthetic Reinforced Soil Walls: Reliability Based Approach

In this paper, an analytical study considering the effect of uncertainties in the seismic analysis of geosynthetic-reinforced soil (GRS) walls is presented. Using limit equilibrium method and assuming sliding wedge failure mechanism, analysis is conducted to evaluate the external stability of GRS walls when subjected to earthquake loads. Target reliability based approach is used to estimate the probability of failure in three modes of failure, viz., sliding, bearing, and eccentricity failure. The properties of reinforced backfill, retained backfill, foundation soil, and geosynthetic reinforcement are treated as random variables. In addition, the uncertainties associated with horizontal seismic acceleration and surcharge load acting on the wall are considered. The optimum length of reinforcement needed to maintain the stability against three modes of failure by targeting various component and system reliability indices is obtained. Studies have also been made to study the influence of various parameters on the seismic stability in three failure modes. The results are compared with those given by first-order second moment method and Monte Carlo simulation methods. In the illustrative example, external stability of the two walls, Gould and Valencia walls, subjected to Northridge earthquake is reexamined.

Optimum Design for External Seismic Stability of Geosynthetic Reinforced Soil Walls: Reliability Based Approach

In this paper, an analytical study considering the effect of uncertainties in the seismic analysis of geosynthetic-reinforced soil (GRS) walls is presented. Using limit equilibrium method and assuming sliding wedge failure mechanism, analysis is conducted to evaluate the external stability of GRS walls when subjected to earthquake loads. Target reliability based approach is used to estimate the probability of failure in three modes of failure, viz., sliding, bearing, and eccentricity failure. The properties of reinforced backfill, retained backfill, foundation soil, and geosynthetic reinforcement are treated as random variables. In addition, the uncertainties associated with horizontal seismic acceleration and surcharge load acting on the wall are considered. The optimum length of reinforcement needed to maintain the stability against three modes of failure by targeting various component and system reliability indices is obtained. Studies have also been made to study the influence of various parameters on the seismic stability in three failure modes. The results are compared with those given by first-order second moment method and Monte Carlo simulation methods. In the illustrative example, external stability of the two walls, Gould and Valencia walls, subjected to Northridge earthquake is reexamined.

When sharing becomes a liability: An intellectual capital approach to describing the dichotomy of knowledge protection versus sharing in intra- and interorganizational relationships

The tension created when companies are collaborating with competitors – sometimes termed co-opetition - has been subject of research within the network approach. As companies are collaborating with competitors, they need to simultaneously share and protect knowledge. The opportunistic behavior and learning intent of the partner may be underestimated, and collaboration may involve significant risks of loss of competitive edge. Contrastingly, the central tenet within the Intellectual Capital approach is that knowledge grows as it flows. The person sharing does not lose the knowledge and therefore knowledge has doubled from a company’s point of view. Value is created through the interplay of knowledge flows between and within three forms of intellectual capital: human, structural and relational capital. These are the points of departure for the research conducted in this thesis. The thesis investigates the tension between collaboration and competition through an Intellectual Capital lens, by identifying the actions taken to share and protect knowledge in interorganizational collaborative relationships. More specifically, it explores the tension in knowledge flows aimed at protecting and sharing knowledge, and their effect on the value creation of a company. It is assumed, that as two companies work closely together, the collaborative relationship becomes intertwined between the two partners and the intellectual capital flows of both companies are affected. The research finds that companies commonly protect knowledge also in close and long-term collaborative relationships. The knowledge flows identified are both collaborative and protective, with the result that they sometimes are counteracting and neutralize each other. The thesis contributes to the intellectual capital approach by expanding the understanding of knowledge protection in interorganizational relationships in three ways. First, departing from the research on co-opetition it shifts the focus from the internal view of the company as a repository of intellectual capital onto the collaborative relationships between competing companies. Second, instead of the traditional collaborative and sharing point of departure, it takes a competitive and protective perspective. Third, it identifies the intellectual capital flows as assets or liabilities depending on their effect on the value creation of the company. The actions taken to protect knowledge in an interorganizational relationship may decrease the value created in the company, which would make them liabilities.

Panel Cointegration of Chinese A and B Shares

This paper uses panel unit root and cointegration methods to test the stationarity of the premium on domestic investors’ A shares over foreign investors’ B shares and cointegration between the A and B share prices on the Chinese stock exchanges. We find that the A share price premium is nonstationary until 2001, when the A and B share markets were partially merged, and that the A and B share prices are cointegrated in the panel.Cointegration is more likely to be found for firms in the service sector and for firms that issued B shares recently.