U ovom radu istražuju se mogućnosti vođenja kompleksne konfiguracije destilacijske kolone s razdjelnim stijenkama (KRS) za četiri proizvoda. Simulacijski su ispitane dvije izvedbe sustava za vođenje. ...Na temelju statičkog modela destilacijske kolone razvijene su dinamičke simulacije tih dviju izvedba, a njihov učinak testiran je uvođenjem poremećaja u sustav. Rezultati pokazuju da je za uspješno vođenje i postizanje zahtijevane kvalitete proizvoda potrebna vrlo čvrsta regulacija temperaturnih profila unutar kolone, ali i da je to moguće postići konvencionalnim metodama vođenja, odnosno primjenom regulacije PID.
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From 2002 to 2007, the International Berlin-Frankfurt-Münster Study Group conducted a prospective randomized clinical trial (ALL IC-BFM 2002) for the management of childhood acute lymphoblastic ...leukemia (ALL) in 15 countries on three continents. The aim of this trial was to explore the impact of differential delayed intensification (DI) on outcome in all risk groups.
For this trial, 5,060 eligible patients were divided into three risk groups according to age, WBC, early treatment response, and unfavorable genetic aberrations. DI was randomized as follows: standard risk (SR), two 4-week intensive elements (protocol III) versus one 7-week protocol II; intermediate risk (IR), protocol III × 3 versus protocol II × 1; high risk (HR), protocol III × 3 versus either protocol II × 2 (Associazione Italiana Ematologia Oncologia Pediatrica AIEOP option), or 3 HR blocks plus single protocol II (Berlin-Frankfurt-Münster BFM option).
At 5 years, the probabilities of event-free survival and survival were 74% (± 1%) and 82% (± 1%) for all 5,060 eligible patients, 81% and 90% for the SR (n = 1,564), 75% and 83% for the IR (n = 2,650), and 55% and 62% for the HR (n = 846) groups, respectively. No improvement was accomplished by more intense and/or prolonged DI.
The ALL IC-BFM 2002 trial is a good example of international collaboration in pediatric oncology. A wide platform of countries able to run randomized studies in ALL has been established. Although the alternative DI did not improve outcome compared with standard treatment and the overall results are worse than those achieved by longer established leukemia groups, the national results have generally improved.
Like other pentameric ligand-gated channels, glycine receptors (GlyRs) contain long intracellular domains (ICDs) between transmembrane helices 3 and 4. Structurally characterized GlyRs are generally ...engineered to have a very short ICD. We show here that for one such construct, zebrafish GlyREM, the agonists glycine, β-alanine, taurine, and GABA have high efficacy and produce maximum single-channel open probabilities greater than 0.9. In contrast, for full-length human α1 GlyR, taurine and GABA were clearly partial agonists, with maximum open probabilities of 0.46 and 0.09, respectively. We found that the elevated open probabilities in GlyREM are not due to the limited sequence differences between the human and zebrafish orthologs, but rather to replacement of the native ICD with a short tripeptide ICD. Consistent with this interpretation, shortening the ICD in the human GlyR increased the maximum open probability produced by taurine and GABA to 0.90 and 0.70, respectively, but further engineering it to resemble GlyREM (by introducing the zebrafish transmembrane helix 4 and C terminus) had no effect. Furthermore, reinstating the native ICD to GlyREM converted taurine and GABA to partial agonists, with maximum open probabilities of 0.66 and 0.40, respectively. Structural comparison of transmembrane helices 3 and 4 in short- and long-ICD GlyR subunits revealed that ICD shortening does not distort the orientation of these helices within each subunit. This suggests that the effects of shortening the ICD stem from removing a modulatory effect of the native ICD on GlyR gating, revealing a new role for the ICD in pentameric ligand-gated channels.
This research analyzed the motivating and demotivating factors amongst employees in a wood processing and furniture manufacturing company. Research was conducted over the year 2010, during the time ...of a full economic crisis and before the restructuring of the company was done. Analysis also was conducted in 2014, during the beginning of the economic recovery and after the restructuring of the company. Research was conducted with a survey using a questionnaire containing six questions with multiple choice statements. The questions were closed-ended, and respondents used the Likert four-level scale of importance for each statement. A total of 180 employees were surveyed, and results were statistically processed by using the χ2- test and cluster analysis. This study established that the motivation factors most important to employees in a company are significantly different during the time of an economic crisis, and in the period of economic recovery, i.e. before and after restructuring of the company. Employees were most concerned about physiological needs in the time of a crisis, whereas in the time of an economic recovery, employees consider social needs to be of more importance. Also, employees consider psychological circumstances of work to be more important in the year 2014 than in the year 2010. Employees’ overall motivation can be linked to higher efficiency and higher quality production and business results, and such research should be conducted more often.
Like other pentameric ligand-gated channels, glycine receptors (GlyRs) contain long intracellular domains (ICDs) between transmembrane helices 3 and 4. Structurally characterized GlyRs are generally ...engineered to have a very short ICD. We show here that for one such construct, zebrafish GlyR
, the agonists glycine, β-alanine, taurine, and GABA have high efficacy and produce maximum single-channel open probabilities greater than 0.9. In contrast, for full-length human α1 GlyR, taurine and GABA were clearly partial agonists, with maximum open probabilities of 0.46 and 0.09, respectively. We found that the elevated open probabilities in GlyR
are not due to the limited sequence differences between the human and zebrafish orthologs, but rather to replacement of the native ICD with a short tripeptide ICD. Consistent with this interpretation, shortening the ICD in the human GlyR increased the maximum open probability produced by taurine and GABA to 0.90 and 0.70, respectively, but further engineering it to resemble GlyR
(by introducing the zebrafish transmembrane helix 4 and C terminus) had no effect. Furthermore, reinstating the native ICD to GlyR
converted taurine and GABA to partial agonists, with maximum open probabilities of 0.66 and 0.40, respectively. Structural comparison of transmembrane helices 3 and 4 in short- and long-ICD GlyR subunits revealed that ICD shortening does not distort the orientation of these helices within each subunit. This suggests that the effects of shortening the ICD stem from removing a modulatory effect of the native ICD on GlyR gating, revealing a new role for ICD in pentameric ligand-gated channels.
The use of cytogenetic assays in the surveillance of populations occupationally exposed to genotoxic carcinogens originates from the assumption that chromosomal alterations might be causally involved ...in early stages of carcinogenesis. Historical cohort studies have since 1990s consistently reported an association between the level of chromosomal aberrations (CA) in peripheral lymphocytes of healthy subjects and the risk of cancer. Only in few cases, have these results been transformed into a regulatory tool for improving occupational safety. The cytogenetic surveillance program adopted for more than two decades in the Republic of Croatia is one of these few examples. Croatian workers exposed to genotoxic agents were systematically screened for CA, to identify occupational settings needing a priority intervention. Significant increases of mean CA frequency were observed in groups exposed to ionizing radiation, chemical agents, and mixed exposures when compared with a group of unexposed referents. CA data on 736 men and 584 women, monitored between 1987 and 2000, have been associated with cancer incidence. Although the small size of the cohort did not allow for reaching statistical significance, the medium tertile of the CA frequency distribution was associated with a doubling of cancer incidence rate ratio (IRR
=
2.40; 95% CI 0.85–6.77) when compared with the lowest tertile. For chromosome-type CA, IRR was non-significantly increased for both the medium (IRR 1.53, 95% CI 0.58–3.99) and high categories (IRR 1.69; 95% CI 0.61–4.72). Recommendations for future strategies comprise the inclusion of predictive biomarkers in surveillance programs, the definition of a regulatory framework, and their possible use for the identification of individual risk profiles.
Abstract 872
ALL IC-BFM 2002 is one of the most successful projects developed by the I-BFM-SG, which is one of the world largest societies involving national leukemia groups. The trial evaluated in a ...randomized manner the impact on outcome of intensified late reinduction in the context of a newly developed risk stratification. The main goal of the trial was improvement of outcome of children with ALL in each of the 3 risk groups (RG).
From Nov 2002-Nov 2007, 5060 eligible pts aged 0–18 yrs with newly diagnosed ALL from Argentina (1270), Chile (558), Croatia (122), Cuba (151), Czech Republic (291), Hong Kong (155), Hungary (259), Israel (292), Poland (908), Serbia (266), Slovakia (137), Slovenia (36), Ukraine (421), Uruguay (96), and Moscow (98) were enrolled in the trial (http:clinicaltrials.gov “NCT00764907”). Stratification into 3 RGs was based on early treatment response (evaluated in PB on day 8 and in BM on days 15 and 33), age, initial WBC, and presence/absence of BCR/ABL or MLL/AF4. Standard Risk (SR) criteria were: < 1,000 blasts/μL in PB day 8 after 7 days of oral prednisone with 1 intrathecal methotrexate (IT-MTX) and age ≥ 1 yr and < 6 yr and initial WBC < 20,000/μL and M1 or M2 marrow on day 15 and M1 marrow on day 33 (all criteria must be fulfilled). Intermediate Risk (IR) criteria were: < 1,000 blasts/μL in PB day 8 and age < 1 yr or ≥ 6 yr and/or WBC ≥ 20,000/μL and M1 or M2 marrow on day 15 and M1 marrow on day 33 (or SR criteria but M3 marrow on day 15 and M1 marrow on day 33). High Risk (HR) criteria were: IR and M3 marrow on day 15, PB on day 8 ≥ 1,000 blasts/μL, M2 or M3 marrow on day 33, translocation t(9;22) BCR/ABL or t(4;11) MLL/AF4 (at least one criterion must be fulfilled). The majority of infants < 1 yr were treated in studies Interfant 99 and Interfant 06. Treatment consisted of protocol I‘/I, SR/IR consolidation with 6-MP and MD MTX 2g/m2 × 4 (with additional IT-MTX in maintenance) for BCP-ALL, 6-MP and HD MTX 5g/m2 × 4 for T-ALL, HR consolidation with 3 HR polychemotherapy blocks. A randomized question was asked in late intensification: SR: would 2 shorter elements (protocol III × 2) be more effective than 1 longer (protocol II × 1) even though the cumulative dose of most drugs is not increased? IR: could the risk of failure be reduced by a third reintensification element (protocol III × 3)? HR: could the use of 3 reintensification elements (protocol III × 3) achieve the same or better results than the HR approach applied in BFM (3 HR blocks + protocol II × 1) or AIEOP (protocol II × 2)? Chemotherapy was concluded by maintenance therapy (6-MP/MTX), making up a total of 2 yrs overall treatment. Prophylactic CNS radiotherapy 12 Gy was applied in T-ALL and HR pts.
With median follow-up 4.9 yr, the 5-yr EFS was 74 ± 1% and 5-yr OS 82 ± 1% for the whole group of 5060 pts. The CR rate was 97%, 255 (5%) children died in remission. The 5-yr EFS/OS was 81 ± 1%/90 ± 1% in 1564 SR pts (30.9% of all pts), 75 ± 1%/83 ± 1% in 2650 IR pts (52.4%) and 55 ± 2%/62 ± 2% in 846 HR pts (16.7%). Randomization rate was 79% of those patients who survived for at least 20 weeks (planned timepoint of randomization). None of the experimental arms achieved significantly better EFS compared to standard treatment.
CI of relapses at 5 yr was 18 ± 1% overall, CI for isolated BM relapse was 12 ± 1%, isolated and combined CNS relapse 4 ± 0.3%, isolated and combined testicular relapse 2 ± 0.2%. Secondary malignancy was diagnosed so far in 26 patients (5-yr CI 0.6 ± 0.1%). Significantly better EFS was achieved in BCP-ALL(75 ± 1%) in comparison with T-ALL (69 ± 1%), girls vs. boys (76 ± 1% vs 72 ± 1%), children aged < 10 yr vs ≥ 10 yr (77 ± 1% vs 65 ± 1%), M1/M2 BM D15 vs. M3(76 ± 1% vs 50 ± 3%). 140 pts with Ph+ALL achieved a EFS of 47 ± 4% Allogeneic HSCT in CR1 was done in 139 pts with 5 -yr DFS of 64 ± 4%.
Although the experimental arm was no better than the traditional one across individual RGs, the majority of participating countries, many of them were new-comers to this intensive therapy, improved their treatment results against previous national studies. The trial confirmed the validity and feasibility of a simple risk stratification of ALL applied in a complex and heterogeneous multinational environment. Despite the great differences between individual countries, the trial set a firm stage for willing national leukemia groups to run collaborative clinical trials in ALL under the umbrella of I-BFM-SG.
Supported by MSM0021620813 and MZ0FNM2005.
No relevant conflicts of interest to declare.
The paper deals with the results of a six-year investigation on the influence of small rodents in the process of recovery (sanation process) and renovation of pedunculate oak forest stands (Genista ...elatae-Quercetum roboris caricetosum brizoides H t. 1938.) by narrow-leaved ash seedling plants (Fraxinus angustifolia Vahl). In the spring of 1996, damage by small rodents in the form of bites of various intensity on a sample of 2580 two-year old narrow-leaved ash seedling plants was recorded in the lower parts of the stalk of 2197 seedling plants (85.16%). According to the intensity of the damage, the plants were divided into three categories. In December 2000, the increment of 31 trees was analysed. Having analysed the variance of diameter (F = 117.14, df = 2, p less than 0.0001) and height (F = 128.41, df = 2, p less than 0.0001) of trees, significant difference between damage categories was established. Scheffes post-hoc test showed statistically significant difference between damage categories, annual radial growth and their interaction.
Background and Purpose: One of the most productive and economically important tree species in the USA is Douglas fir (Pseudotsuga menziesii (Mirb.)). Because of its broad natural range, in the ...horizontal as well as in the vertical sense (from California to British Columbia and from sea level up to an altitude of 1500 m), a variety of its provenances has been differentiated. European foresters, thanks to their insight into Douglas fir productivity
and usage in its native country, initiated at the beginning of the
19th century the establishment of provenance tests and research on the success of individual provenances outside their natural distribution. In the framework of the IUFRO programme, numerous European countries, among them Croatia, started provenance tests with the aim of researching the adaptability of this valuable species. In several bioclimatic localities in Croatia (Istria, North-West, Central and Eastern Croatia) different provenances have shown good success. The importance of Douglas fir is becoming
increasingly evident in conditions of a changing climate and when the possible application of Douglas fir in the establishment of forest cultures is taken into consideration. Douglas fir can be established on uncovered forest and non-forest areas for wood supply or as a potential renewable energy source. The exploitation of wood and biomass from forest cultures enables the conservation
of biodiversity and the survival of our natural forest ecosystems.
Material and Methods: This paper is based on research conducted on a Douglas fir provenance trial in the locality of »Kontija« in Istria. The trial, in which ten Douglas fir provenances were included, started in 1969. On the trial plots, dendrometric parameters such as DBH and tree heights were measured on the basis of which wood volume was calculated. Descriptive statistics were made for all analysed variables (DBH, h, V). The differences between the provenances for the investigated variables were tested with an analysis of variance (ANOVA). Provenances which differ between themselves
were determined using the Tukey post hoc test. According to data on
the survival rate for all provenances, the average survival rate inside the trial was estimated and tested with a test of proportion to determine which provenances differ statistically from the average survival rate. Using a non-hierarchical (κ-means) cluster analysis, provenances were grouped according to standardised variables (N, DBH, h, V). In the same way, the species’ health condition was determined, as was the resistance of provenances to forest pests.
Results and Conclusion: The average survival rate of all provenances in the trial amounts to 64.8% (ranging from 52% for the provenance PE ALL to 77% for the provenance ELMA). The best height growth was identified in the provenance SHELTON which originates from lower altitudes in Washington while the provenance SHADE COVE from higher areas of Oregon shows lowest growth. High volume is
evidenced in the provenance PE ALL. The results of the analysis of variance (ANOVA) show that there is a statistically significant difference for all analysed variables for the investigated provenances. A κ-means cluster analysis grouped ten Douglas fir provenances in four clusters. In cluster 1, only the provenance SHADY COVE is included with a high number of trees with lower heights and smaller DBH and volume. Provenances from cluster 3 (PE ALL and YELM) have, in a small number of trees, higher DBH and volume. The rest of the provenances are grouped in two clusters (cluster 2 and cluster 4) with similar values but with the difference
that the provenances SHELTON, CORVALIS, ELMA and HVIDILDE (cluster 2) have higher values than average for the analysed parameters, while the provenances IPKA, BUZET and CASTLE ROCK (cluster 4) have lower than average values. In general, all the provenances in the trial are vital and show a good health condition without any determined pests.
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