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This paper proposes an extended Petri net formalism as a suitable language for composing optimal scheduling problems of industrial production processes with real and binary decision variables. The proposed approach is modular and scalable, as the overall process dynamics and constraints can be collected by parsing of all atomic elements of the net graph. To conclude, we demonstrate the use of this framework for modeling the moulding sand preparation process of a real foundry plant.
HOXA9 and MEIS1 are frequently upregulated in acute myeloid leukemia (AML), including those with MLL‐rearrangement. Because of their pivotal role in hemostasis, HOXA9 and MEIS1 appear non‐druggable. We, thus, interrogated gene expression data of pre‐leukemic (overexpressing Hoxa9) and leukemogenic (overexpressing Hoxa9 and Meis1; H9M) murine cell lines to identify cancer vulnerabilities. Through gene expression analysis and gene set enrichment analyses, we compiled a list of 15 candidates for functional validation. Using a novel lentiviral multiplexing approach, we selected and tested highly active sgRNAs to knockout candidate genes by CRISPR/Cas9, and subsequently identified a H9M cell growth dependency on the cytosolic phospholipase A2 (PLA2G4A). Similar results were obtained by shRNA‐mediated suppression of Pla2g4a. Remarkably, pharmacologic inhibition of PLA2G4A with arachidonyl trifluoromethyl ketone (AACOCF3) accelerated the loss of H9M cells in bulk cultures. Additionally, AACOCF3 treatment of H9M cells reduced colony numbers and colony sizes in methylcellulose. Moreover, AACOCF3 was highly active in human AML with MLL rearrangement, in which PLA2G4A was significantly higher expressed than in AML patients without MLL rearrangement, and is sufficient as an independent prognostic marker. Our work, thus, identifies PLA2G4A as a prognostic marker and potential therapeutic target for H9M‐dependent AML with MLL‐rearrangement.
A novel method has been implemented to prepare metal oxide nanopowders covered with known quantities of adsorbed water; we subsequently studied the γ-radiolysis of ZrO2 nanopowders covered with H2O layers. H2 yields from the adsorbed water radiolysis are of importance in multiple industrial contexts – the nuclear industry being a prime example. Measured H2 yields at water coverages of just below and above one monolayer are around 350 times greater than for neat water, but these yields decrease rapidly with increasing water loading of the ZrO2 nanoparticles, approaching the yield of bulk water at coverages of tens of water layers. The observed plateau of the yields at 0.5 to 2.0 monolayers coverage can be explained by the ease with which electronic excitations in the ZrO2 can be transferred across the interface to the first one or two adsorbed water layers. However, with increasing water loading, energy transfer to water layers further away from the interface becomes less efficient, and above ~30 water layers, most of the water is not affected by any exciton formation in the ZrO2.
Nitric oxide adsorption on a Au(100) single crystal has been investigated to identify the type of adsorption, the adsorption site, and the orientation and alignment of the adsorbed NO relative to the surface. This was done using a combination of 3D-surface velocity map imaging, near-ambient pressure X-ray photoelectron spectroscopy, and density functional theory. NO was observed to be molecularly adsorbed on gold at ~200 K. Very narrow angular distributions and cold rotational distributions of photodesorbed NO indicate that NO adsorbs on high-symmetry sites on the Au crystal, with the N–O bond axis close to the surface normal. Our density functional theory calculations show that NO preferentially adsorbs on the symmetric bridge (2f) site, which ensures efficient overlap of the NO π* orbital with the orbitals on the two neighbouring Au atoms, and with the N–O bond axis aligned along the surface normal, in agreement with our conclusions from the rotational state distributions. The combination of XPS, which reveals the orientation of NO on gold, with 3D-surface velocity map imaging and density functional theory thus allowed us to determine the adsorption site, orientation and alignment of nitric oxide adsorbed on Au(100).
Fenster versorgen die Innenräume mit Tageslicht, dienen der Lufterneuerung in den Räumen und schützen vor Umwelteinflüssen wie Kälte, Wärme, Lärm, Wind und Niederschlägen. Entsprechend weitgefächert ist das Spektrum deer planungsrelevanten Aspekte. Sowohl licht-, lüftungs-, wärme-, schall und wohntechnische als auch hygienische, psychologische und nicht zuletzt wirtschaftliche Gesichtspunkte sind bei edr täglichen Arbeit zu beachten.
Die Umsetzung der an sich seit längerem bekannten Logistikkonzepte stößt in vielen Unternehmen auf Schwierigkeiten. Oft fehlen durchgängige, prozessorientierte Gesamtlösungen. Zum Teil liegt dies daran, dass die üblichen PPS-Systeme im Feinplanungs- und Steuerungsbereich die gestiegenen logistischen Anforderungen nicht erfüllen können.
Logistische Funktionsketten mit der Integration von Information, Arbeits- und Materialflüssen für einen durchgängigen Auftragsabwicklungsprozeß müssen auch Qualitätssicherungsfunktionen mit beinhalten. Dies ist nur über eine entsprechende QS-Systemarchitektur zu realisieren, die an jeder Stelle im dispositiven und operativen Ablauf im Sinne der Fehlervermeidung dafür sorgt, daß die angestrebten Qualitätsziele erreicht werden.
The antimicrobial activity of a phagemixture and a lactic acid bacteriumagainst Staphylococcus aureus isolates from bovine origin was investigated in vitro with regard to possible applications in the therapy of udder inflammation (mastitis) caused by bacterial infections. The S. aureus isolates used for inoculation derived from quarter foremilk samples of mastitis cases. For the examination of the antimicrobial activity, the reduction of the S. aureus germ density was determined [log10 cfu/mL]. The phage mixture consisted of the three obligatory lytic and S. aureus-specific phages STA1.ST29, EB1.ST11 and EB1.ST27 (1:1:1). The selected Lactobacillus plantarum strain with proven antimicrobial properties and the phage mixture were tested against S. aureus in milk, both alone and in combination. The application of the lactic acid bacterium showed only a low reduction ability for a 24 h incubation period. The bacteriophage mixture as well as its combination with the lactic acid bacterium showed high antimicrobial activity against S. aureus for a 24 h incubation period at 37 C, with only the phage mixture showing significance.
The objective of this study was to investigate the occurrence of bacteremia in dairy cows with severe mastitis. Milk samples were collected from affected udder quarters, and corresponding blood samples were collected from dairy cows with severe mastitis at the time of diagnosis before any therapeutic measures were undertaken. The cultural detection of pathogens in blood classified a bacteremia. Further diagnostic tests were performed to provide evidence of bacteremia. This was realized by PCR with regard to S. aureus, E. coli and S. uberis and the Limulus test. Detection of culturable pathogens in the blood of cows with severe clinical mastitis was rare and occurred in only one of 70 (1.4%) cases. Overall, bacterial growth was detected in 53 of 70 (75.7%) milk samples. S. uberis (22/70), E. coli (12/70) and S. aureus (4/70) were the most frequently isolated pathogens from milk of cows with severe mastitis. PCR was performed in 38 of 70 (54.3%) blood samples. PCR was positive in eight of 38 cases. S. uberis was found most frequently in six blood samples (8.6%). E. coli was found on PCR in one blood sample (1.4%). S. aureus was identified in one blood sample (1.4%). When Coliforms were detected in the quarter milk sample, a Limulus test was performed in the corresponding blood sample. In three of 15 cases, the Limulus test was positive (4.3% of samples). Further studies are needed to investigate the occurrence of bacteremia in cows with severe mastitis in a higher population size.
The objective of this study was to investigate the association between teat skin colonization and intramammary infection (IMI) with Staphylococcus aureus or Streptococcus agalactiae at the quarter level in herds with automatic milking systems. Milk and teat skin samples from 1,142 quarters were collected from 300 cows with somatic cell count >200,000 cells/mL from 8 herds positive for Strep. agalactiae. All milk and teat skin samples were cultured on calf blood agar and selective media. A subset of samples from 287 quarters was further analyzed using a PCR assay (Mastit4 PCR; DNA Diagnostic A/S, Risskov, Denmark). Bacterial culture detected Staph. aureus in 93 (8.1%) of the milk samples and 75 (6.6%) of the teat skin samples. Of these, 15 (1.3%) quarters were positive in both the teat skin and milk samples. Streptococcus agalactiae was cultured in 84 (7.4%) of the milk samples and 4 (0.35%) of the teat skin samples. Of these, 3 (0.26%) quarters were positive in both the teat skin and milk samples. The PCR detected Staph. aureus in 29 (10%) of the milk samples and 45 (16%) of the teat skin samples. Of these, 2 (0.7%) quarters were positive in both the teat skin and milk samples. Streptococcus agalactiae was detected in 40 (14%) of the milk samples and 51 (18%) of the teat skin samples. Of these, 16 (5.6%) quarters were positive in both the teat skin and milk samples. Logistic regression was used to investigate the association between teat skin colonization and IMI at the quarter level. Based on bacterial culture results, teat skin colonization with Staph. aureus resulted in 7.8 (95% confidence interval: 2.9; 20.6) times higher odds of Staph. aureus IMI, whereas herd was observed as a major confounder. However, results from the PCR analyses did not support this association. Streptococcus agalactiae was isolated from the teat skin with both PCR and bacterial culture, but the number of positive teat skin samples detected by culture was too low to proceed with further analysis. Based on the PCR results, Strep. agalactiae on teat skin resulted in 3.8 (1.4; 10.1) times higher odds of Strep. agalactiae IMI. Our results suggest that Staph. aureus and Strep. agalactiae on teat skin may be a risk factor for IMI with the same pathogens. Focus on proper teat skin hygiene is therefore recommended also in AMS.
Obwohl durchgängige CIM- und Logistik-Konzepte zur Erfüllung der permanent steigenden Kundenforderungen hinsichtlich spezifischer Produktausführungen bei qualitätsgerechter und termintreuer Auslieferung in den meisten Unternehmen noch nicht realisiert sind, beginnt bereits die Diskussion um eine neue Unternehmensstrategie: die "Lean Production". Das Ziel heißt diesmal, in allen Bereichen Ressourcen zu minimieren, um mit Hilfe einer schlanken Fertigung bei den Kosten Weltstandard zu erreichen.
The aim of this cross-sectional study was to investigate the occurrence of bacteremia in severe mastitis cases of dairy cows. Milk and corresponding blood samples of 77 cases of severe mastitis were bacteriologically examined. All samples (milk and blood) were incubated aerobically and anaerobically to also investigate the role of obligate anaerobic microorganisms in addition to aerobic microorganisms in severe mastitis. Bacteremia occurred if identical bacterial strains were isolated from milk and blood samples of the same case. In addition, pathogen shedding was examined, and the data of animals and weather were collected to determine associated factors for the occurrence of bacteremia in severe mastitis. If Gram-negative bacteria were detected in milk samples, a Limulus test (detection of endotoxins) was also performed for corresponding blood samples without the growth of Gram-negative bacteria. In 74 cases (96.1%), microbial growth was detected in aerobically incubated milk samples. The most-frequently isolated bacteria in milk samples were Escherichia (E.) coli (48.9%), Streptococcus (S.) spp. (18.1%), and Klebsiella (K.) spp. (16%). Obligatory anaerobic microorganisms were not isolated. In 72 cases (93.5%) of the aerobically examined blood samples, microbial growth was detected. The most-frequently isolated pathogens in blood samples were non-aureus Staphylococci (NaS) (40.6%) and Bacillus spp. (12.3%). The Limulus test was positive for 60.5% of cases, which means a detection of endotoxins in most blood samples without the growth of Gram-negative bacteria. Bacteremia was confirmed in 12 cases (15.5%) for K. pneumoniae (5/12), E. coli (4/12), S. dysgalactiae (2/12), and S. uberis (1/12). The mortality rate (deceased or culled) was 66.6% for cases with bacteremia and 34.1% for cases without bacteremia. High pathogen shedding and high humidity were associated with the occurrence of bacteremia in severe mastitis.
In order to reduce antimicrobial treatment and prevent environmental mastitis, the aim of the present study was to investigate associations between herd level factors and microbial load on teat ends with environmental mastitis pathogens. Quarterly farm visits of 31 dairy farms over a one-year period were used for statistical analysis. During each farm visit, teat-skin swabs, bedding and air samples were taken and management practices and herd parameters were documented. Total mesophilic bacteria, esculin-positive streptococci and coliform bacteria were examined in the laboratory procedures from teat skin and environmental samples. Esculin-positive streptococci and coliform bacteria on teat ends increased with high temperature–humidity indices (THI) in the barn during the spring and summer. Significantly more coliform bacteria on teat ends were found in herds with an increased percentage of normal or slightly rough teat ends. Cleaning cubicles more frequently, pre-cleaning teats before milking as well as post-dipping them after milking had a decreasing effect of teat-skin load with total mesophilic and coliform bacteria at the herd level. To conclude, teat-skin bacterial load with environmental pathogens is subject to fluctuations and can be influenced by aspects of farm hygiene.
Die Anpassungsfähigkeit eines Unternehmens an rasch wechselnde Wettbewerbssituationen bei kundenwunschorientierter Produktion mit veränderlichen Losgrößen und unterschiedlichen Terminrestriktoren kann nur über ausgefeilte Strategien und durch DV-Einsatz erzeugt werden. Anforderungsgerechte CIM- und Logistik-Konzepte sind eine wesentliche Vorraussetzung, damit die geforderte Flexibilität erreicht wird. Den unabdingbaren Informationsfluss schafft hierbei die Betriebsdatenerfassung.
Wegen der Vielzahl unterschiedlicher Teile in variierenden Losgrößen ist es in der spanenden Fetigung besonders wichtig, Hardware und Software für logistische Aufgaben anforderungsgerecht auszuwählen. Ausgehend von den logistischen Grundfunktionen im Betrieb sind die Grunddatenbereitstellung, die Prozessstruktur, die Produktgestaltung, das Beschaffen und das Lagern auf die rechnergestützte Logistik auszurichten.
Für die Produktion von drei Sorten stichfestem Joghurt (Natur, mit unterlegter Frucht und Mix) werden die Kosten nach einer speziellen Form der Teilkostenrechnung in Abhängigkeit von der Kapazitätsauslastung bestimmt. Es werden drei Modelle mit unterschiedlicher Kapazitätsgröße dargestellt: 6500, 13.000 und 26.000 Becher/h. Durch Variationen der Produktmenge, Produktionstage und Produktanteile ergeben sich Kosten zwischen 12,6 und 9,3 Pf/Becher Joghurt Natur bzw. 18,7 und 15,5 Pf/Becher Joghurt mit unterlegter Frucht bzw. 17,0 und 14,0 Pf/Becher Joghurt Mix. Je nach Produktionsbedingungen können Stückkostendifferenzen von über 20 Pfennig je kg Produkt auftreten.
In dieser Arbeit werden die Grundlagen zur Bestimmung des Kostenverlaufs einzelner ausgewählter Molkereibetriebsabteilungen bei unterschiedlichen Kapazitätsgrößen und -auslastungen bestimmt. Den Produkten (Abteilungen) werden die mengenproportionalen Produkteinzelkosten zugerechnet sowie die Gemeinkosten der Abteilung, die sich aus jahresfixen, tagesfixen und chargenfixen Kosten zusammensetzen. Für Energie werden lediglich mengenproportionale Kosten in Ansatz gebracht. Die sonstigen Kosten der Hilfskostenstellen werden grundsätzlich nicht auf die Produkte bzw. Abteilungen umgelegt; sie werden im letzten Teil dieser Veröffentlichungsreihe behandelt. Die objektive Vergleichbarkeit der Kosten kann so gewährleistet werden. Ein wichtiger Bestandteil dieser Arbeit war die Entwicklung eines für alle Abteilungen brauchbaren Simulationsmodells, das für den Einsatz in der EDV konzipiert wurde. Neben der Berechnung der anfallenden Kosten bei unterschiedlichen Anlagengrößen sind bei dem Computermodell beliebige Variationen der folgenden Faktoren möglich. Dadurch können die Auswirkungen eines veränderten Beschäftigungsgrades bzw. einer anderen Kapazitätsauslastung auf die Stückkosten der einzelnen Produkte ermittelt werden. Es ist vorgesehen, die Daten über Jahre hinaus auf dem neuesten Stand zu halten und zu veröffentlichen.
In der vorliegenden Arbeit werden die Kosten der Sprühtrocknung bei drei verschiedenen Kapazitätsgrößen mit jeweils variierender Kapazitätsauslastung nach einer speziellen Form der Teilkostenrechnung bestimmt. Die Kapazitätsgrößen betragen 10800, 21600 und 32400 kg Magermilch pro Stunde. Die verarbeiteten Milchmengen liegen
zwischen 12,8 Mio. und 256,6 Mio. kg im Jahr; dabei variieen die Stückkosten zwischen 4,80 und 1,78 Pf/kg Mm. Es hat sich dabei gezeigt, daß die Kostendegression bedeutend stärker durch den Grad der Kapazitätsauslastung als durch die Kapazitätsgröße beeinflußt wird.