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This paper is dedicated to the core challenge of sustainably integrating new and viable business models into logistics systems in the context of the digital transformation. On the one hand, enterprises are facing increased competitive pressure and growth gaps in their own product portfolio; on the other hand, new technology and system solutions are finding their way into enterprises. These new solutions lead to significant changes in the cost structure as well as in the process design. Especially in increasingly digitalised and automated economic sectors such as logistics, production or processing industries, the adaptation and development of the own business model requires a systematic approach that presupposes the use and integration of proven methods. In the context of designing Smart Logistics Zones the interaction of logistical objects, processes, systems and the physical and digital infrastructure is achieved in a goal-oriented manner, depending on the requirements and the situation. An interactive design of the future of human-technology organization takes places. The procedure of the Smart Logistics Zone should support entrepreneurial decision processes purposefully and on the core idea of an Industry 4.0 in preliminary way. In addition to the integrative research concept, this paper focuses on the application of the methodological approach to a reference scenario of the Smart Logistics Zone and an exemplary business model. [ABSTRACT FROM AUTHOR]

Background Cardiovascular disease has been associated with oxidative stress, which has been suggested to contribute to myocardial remodeling in human patients. Little is known about the relationship between myxomatous mitral valve disease ( MMVD) and oxidative stress in dogs. Objective To determine whether clinical stage of MMVD is associated with changes in the plasma concentrations of certain markers of oxidative stress in clinically healthy dogs and dogs with MMVD. Animals Seventy five privately owned dogs: 59 cavalier King Charles Spaniels ( CKCS) with different severities of MMVD and 16 dogs of different breeds with clinical signs of congestive heart failure ( CHF) caused by MMVD. Methods Markers of oxidative stress including malondialdehyde ( MDA), oxidized low-density lipoprotein (ox LDL), and vitamin E (α-tocopherol and γ-tocopherol) were measured in plasma and their association with clinical stage of MMVD was assessed by regression analyses. Results Plasma ox LDL concentration was significantly lower in female dogs compared with males ( P = .01). Significantly higher plasma γ-tocopherol concentrations were found in neutered ( P = .003) dogs. Vitamin E (α-tocopherol [ P = .0004] and γ-tocopherol [ P = .003]) was associated with body condition score ( BCS), but the association disappeared when cholesterol was included in the analyses. All markers of oxidative stress ( MDA, ox LDL, and vitamin E) were positively associated with serum cholesterol concentration ( P ≤ .04), but none were associated with clinical stage of MMVD. Conclusions In conclusion, markers of oxidative stress are associated with sex, BCS, neuter status, and cholesterol. The results cannot confirm a relationship between oxidative stress and clinical stage of the disease in dogs with MMVD. [ABSTRACT FROM AUTHOR]

Background Echocardiography is a cost-efficient method to screen cats for presence of heart disease. Current reference intervals for feline cardiac dimensions do not account for body weight ( BW). Objective To study the effect of BW on heart rate ( HR), aortic (Ao), left atrial ( LA) and ventricular ( LV) linear dimensions in cats, and to calculate 95% prediction intervals for these variables in normal adult pure-bred cats. Animals 19 866 pure-bred cats. Methods Clinical data from heart screens conducted between 1999 and 2014 were included. Associations between BW, HR, and cardiac dimensions were assessed using univariate linear models and allometric scaling, including all cats, and only those considered normal, respectively. Prediction intervals were created using 95% confidence intervals obtained from regression curves. Results Associations between BW and echocardiographic dimensions were best described by allometric scaling, and all dimensions increased with increasing BW (all P<0.001). Strongest associations were found between BW and Ao, LV end diastolic, LA dimensions, and thickness of LV free wall. Weak linear associations were found between BW and HR and left atrial to aortic ratio ( LA:Ao), for which HR decreased with increasing BW ( P<0.001), and LA:Ao increased with increasing BW ( P<0.001). Marginal differences were found for prediction formulas and prediction intervals when the dataset included all cats versus only those considered normal. Conclusions and Importance BW had a clinically relevant effect on echocardiographic dimensions in cats, and BW based 95% prediction intervals may help in screening cats for heart disease. [ABSTRACT FROM AUTHOR]

Background Endothelial dysfunction ( ED) has been suggested to be associated with myxomatous mitral valve disease ( MMVD) in dogs. Tetrahydrobiopterin ( BH4) is an important cofactor for production of the endothelium-derived vasodilator nitric oxide ( NO). Under conditions of oxidative stress, BH4 is oxidized to the biologically inactive form dihydrobiopterin ( BH2). Thus, plasma concentrations of BH2 and BH4 may reflect ED and oxidative stress. Objective To determine plasma concentrations of BH2 and BH4 in dogs with different degrees of MMVD. Animals Eighty-four privately owned dogs grouped according to ACVIM guidelines (37 healthy control dogs including 13 Beagles and 24 Cavalier King Charles Spaniels [ CKCSs], 33 CKCSs with MMVD of differing severity including 18 CKCSs [group B1] and 15 CKCSs [group B2], and 14 dogs of different breeds with clinical signs of congestive heart failure [ CHF] because of MMVD [group C]). Methods Dogs underwent clinical examination including echocardiography. Plasma concentrations of BH2 and BH4 were measured using high-performance liquid chromatography with fluorescence detection. Results Higher plasma BH4 and BH2 concentrations were found with dogs in CHF compared with all other groups (control, B1 and B2; P ≤ .001). Females had higher concentrations of BH4 and BH4/ BH2 ( P ≤ .0003). BH4/ BH2 was found to decrease with age ( P < .0001). Cardiovascular risk factors in humans such as passive smoking ( P ≤ .01) and increased body weight ( P ≤ .009) were associated with lower BH4 concentrations. Conclusions and Clinical Importance Age, sex, body weight, passive smoking, and cardiac status are associated with plasma biopterin concentration in dogs. Additional studies should clarify the clinical implications of the findings. [ABSTRACT FROM AUTHOR]

Background Syncope is a transient loss of consciousness occasionally occurring in dogs with advanced myxomatous mitral valve disease ( MMVD). Objective (1) To study ECG changes during syncopal episodes in dogs with advanced MMVD and (2) to compare the occurrence of arrhythmias and changes in heart rate variability ( HRV) between dogs with advanced MMVD with and without a history of syncope. Animals Forty-three privately owned dogs (<15 kg) with advanced MMVD: 21 with and 22 without a history of syncope. Methods Prospective study with dogs recruited for an evaluation including history, physical examination, echocardiography, and arrhythmia and HRV analysis performed on 24-hour Holter recordings. Results A syncopal episode was observed during Holter monitoring in 4 dogs: 3 dogs had sinus rhythm and 1 dog had sinus arrest followed by escape rhythm. An arrhythmia variable representing sinus arrhythmia was significantly lower in dogs with a history of syncope than in those without ( P = .008). Eight of 26 HRV variables were significantly different between dogs with and without a history of syncope. Conclusions and Clinical Importance Compared with dogs without a history of syncope, dogs with advanced MMVD and a history of syncope did not have a higher occurrence of arrhythmias, but had less sinus arrhythmia, and had changes in HRV variables representing decreased overall HRV, decreased parasympathetic, and increased sympathetic modulation of heart rate. [ABSTRACT FROM AUTHOR]

Background During the cardiac cycle, the ventricle undergoes a twisting motion because of the oblique orientation of the left ventricular ( LV) myofibers. This can be quantified by speckle-tracking echocardiography ( STE). In mitral regurgitation ( MR) in humans, the short axis deformation has been suggested as being pivotal to LV function. Decreased and delayed LV twist has been described in experimental MR, but has not been studied in myxomatous mitral valve disease ( MMVD). Hypotheses (1) Magnitude ( CSt) and rate ( CSRs) of systolic circumferential deformation decrease before the onset of congestive heart failure ( CHF); (2) magnitude and rate of LV twist decrease, and onset of untwist is delayed, with increasing MMVD severity. Animals A total of 97 privately owned small- to medium-sized dogs. Methods Severity of MMVD was assessed by echocardiography and presence of clinical signs of CHF. Magnitude and rate of LV twist and circumferential deformation were evaluated by STE. Results Dogs with CHF receiving treatment had increased CSt, CSRs, early diastolic untwisting rate, and delayed onset of untwist compared to dogs with minimal MMVD and increased systolic twist compared to dogs with mild MMVD (all P < .01). CSt and time to onset of untwist increased with echocardiographic variables of MR severity (all P < .002). CSRs and several LV twist variables decreased with increasing systolic LV internal diameter (all P < .01). Conclusions and Clinical Importance No STE-derived variable was decreased before onset of CHF. In dogs with CHF receiving treatment, the delayed onset of relaxation might indicate LV dysfunction and the hyperdynamic CSt and LV twist reflect compensatory mechanisms. [ABSTRACT FROM AUTHOR]

Background Few previous studies have investigated the association between biomarkers and cardiac disease findings in dogs with naturally occurring myxomatous mitral valve disease ( MMVD). Aim To investigate if histopathological changes at necropsy could be reflected by in vivo circulating concentrations of cTnI and aldosterone, and renin activity, in dogs with naturally occurring congestive heart failure because of MMVD. Animals Fifty privately owned dogs with MMVD and heart failure. Methods Longitudinal Study. Dogs were prospectively recruited and examined by clinical and echocardiographical examination twice yearly until time of death. Blood was stored for batched analysis of concentrations of cTnI and aldosterone, and renin activity. All dogs underwent a standardized necropsy protocol. Results cTnI were associated with echocardiographic left ventricular end-diastolic dimension ( P < .0001) and proximal isovolumetric surface area radius ( P < .004). Furthermore, in vivo cTnI concentrations reflected postmortem findings of global myocardial fibrosis ( P < .001), fibrosis in the papillary muscles ( P < .001), and degree of arterial luminal narrowing ( P < .001) Aldosterone or renin activity did not reflect any of the cardiac disease variables investigated. Conclusion and clinical importance Cardiac fibrosis and arteriosclerosis in dogs with MMVD are reflected by circulating cTnI concentration, but not by aldosterone concentration or renin activity. Cardiac troponin I could be a valuable biomarker for myocardial fibrosis in dogs with chronic cardiac diseases. [ABSTRACT FROM AUTHOR]

Background Assessment of left ventricular ( LV) function using conventional echocardiographic methods is difficult in mitral regurgitation ( MR) owing to altered hemodynamic loading conditions. Newer methods such as speckle-tracking echocardiography ( STE) provide assessment of LV strain ( St) and strain rates ( SR). Hypotheses Global St and SR are 1) decreased in dogs with clinical signs of congestive heart failure ( CHF) due to myxomatous mitral valve disease ( MMVD) compared with clinically healthy dogs, and are 2) associated with conventional echocardiographic indices of MMVD severity. Animals The study subjects were 93 privately owned dogs with different MMVD severities. Methods Prospectively recruited dogs were grouped according to MMVD severity based on echocardiographic evaluation of MR and presence of clinical signs. Global radial and longitudinal St, SR, and indices of LV dyssynchrony were assessed. Results On group-wise comparisons, dogs with CHF had increased global longitudinal St, global longitudinal and radial SR in systole ( SRs), and early diastole ( SRe) compared with dogs with no or minimal MR (all P < .04). On multiple regression analyses, these global STE variables increased with degree of MR, but associations with left atrial-to-aortic root ratio ( LA/ Ao) were best described by second-order polynomial equations. Thus, curvilinear relationships were found for LA/ Ao and longitudinal St, SRs, and SRe (all P < .002) and radial St and SRe (all P < .001). Conclusions and Clinical Importance Assessed by STE, LV function appeared to be augmented in moderate-to-severe disease. However, at CHF stages with greatly enlarged atria, a decrease to levels comparable to dogs with no or minimal MR was observed. [ABSTRACT FROM AUTHOR]

Background Autonomic modulation of heart rhythm is thought to influence the pathophysiology of myxomatous mitral valve disease ( MMVD). Hypotheses (1) Holter-derived variables reflecting autonomic modulation of heart rhythm change with MMVD severity in Cavalier King Charles Spaniels ( CKCS); (2) Holter-derived variables can identify MMVD severity in CKCS; and (3) Holter-derived variables in CKCS in congestive heart failure ( CHF) secondary to MMVD differ from those in dogs of other breeds in CHF. Animals Ninety privately owned dogs: 70 CKCS with variable MMVD severity and 20 non- CKCS in CHF secondary to MMVD. Methods Dogs were prospectively recruited and divided into 5 MMVD severity groups based on history, breed, and physical and echocardiographic examination findings. Holter-derived variables included heart rate variability ( HRV), heart rate ( HR), and arrhythmia evaluated from 24-hour Holter recordings. Results In CKCS, 18 of 26 HRV (all P < .0002) and 3 of 9 arrhythmia (all P < .0004) variables decreased with increasing MMVD, whereas minimum and mean HR (all P < .0001) increased with increasing MMVD severity. An arrhythmia variable representing sinus arrhythmia ('premature normals') ( P < .0001) and the HRV variable triangular index ( TI) ( P < .0001) could distinguish CKCS with moderate or severe mitral regurgitation from CKCS in CHF in specific intervals. Among dogs in CHF, Holter-derived variables did not differ among breeds. Conclusions and Clinical Importance In CKCS, Holter-derived variables changed with MMVD severity. 'Premature normals' and TI showed diagnostic potential. Breed differences were not seen among dogs in CHF secondary to MMVD. [ABSTRACT FROM AUTHOR]

Background Cardiovascular disease is associated with endothelial dysfunction in humans and studies of plasma biomarkers suggest that dogs with myxomatous mitral valve disease ( MMVD) might also have endothelial dysfunction. Hypothesis That progression of mitral regurgitation ( MR) is associated with development of endothelial dysfunction. Animals Forty-three Cavalier King Charles Spaniels ( CKCS) with MR of varying severity. Methods Privately owned CKCS were prospectively recruited and divided in 4 groups: (1) 12 CKCS with minimal MR; (2) 9 CKCS with mild MR; (3) 11 CKCS with moderate-severe MR; and (4) 11 CKCS with moderate-severe MR and clinical signs compatible with heart failure. Dogs underwent blood sampling, echocardiography, blood pressure ( BP) recordings, and flow-mediated vasodilation ( FMD) measurements. The effect of progressive MR on FMD was determined by multivariate analyses. Results Flow-mediated vasodilation decreased with progression of MR. Group 4 (4.79 ± 3.22%) had significantly lower FMD than groups 1 (10.40 ± 4.58%) and 2 (10.14 ± 3.67%) ( P < .005) and group 3 (6.79 ± 3.98%) had a significantly lower FMD than group 1 ( P = .03). Increasing left ventricular end-diastolic diameter ( P = .0004, R2 = 0.27) and the combination of age ( P = .01) and body weight ( P = .002) (R2 = 0.31) were significantly associated with reduced FMD. FMD did not correlate with sex, BP, or plasma markers. Conclusions and Clinical Importance Reduced FMD indicates that increased disease severity in CKCS with MMVD is associated with development of endothelial dysfunction which might be a future therapeutic and/or diagnostic target. [ABSTRACT FROM AUTHOR]

Background Multiple advanced resting ECG (A- ECG) techniques have improved the diagnostic or prognostic value of ECG in detecting human cardiac diseases even before onset of clinical signs or changes in conventional ECG. Objective To determine which A- ECG parameters, derived from 12-lead A- ECG recordings, change with severity of mitral regurgitation ( MR) caused by myxomatous mitral valve disease ( MMVD) in Cavalier King Charles Spaniels ( CKCSs) in sinus rhythm. Animals Seventy-six privately owned CKCSs. Methods Dogs were prospectively divided into 5 groups according to the degree of MR (estimated by color Doppler mapping as the percentage of the left atrial area affected by the MR jet) and presence of clinical signs. High fidelity approximately 5-minute 12-lead ECG recordings were evaluated using custom software to calculate multiple conventional and A- ECG parameters. Results Nineteen of 76 ECG parameters were significantly different ( P < .05) across the 5 dog groups. A 4-parameter model that incorporated results from 1 parameter of heart rate variability, 2 parameters of QT variability, and 1 parameter of QRS amplitude was identified that explained 82.4% of the variance with a correlation coefficient (R) of 0.60 ( P < .01). When age or murmur grade was included in the statistical model the prediction value further increased the R to 0.74 and 0.85 ( P < .01), respectively. Conclusion In CKCSs with sinus rhythm, 4 selected A- ECG parameters further improve prediction of MR jet severity beyond age and murmur grade, although the predictive increment in this study probably is not sufficient to warrant utilization in clinical veterinary practice. [ABSTRACT FROM AUTHOR]

Abstract: Dysfunction of basal ganglia circuits underlies a variety of movement disorders and neuropsychiatric conditions. Selective control of the electrical activity of striatal outflow pathways by manipulation of ion channel function presents a novel therapeutic approach. Toward this end, we have constructed and studied in vitro an adenoviral gene transfer vector that employs the promoter region of the dopamine-1 receptor to drive expression of the inward rectifier K+ channel Kir2.3. The use of this neuronal promoter confers cell-type specificity and a physiological level of trans-gene expression in rat primary striatal cultures. The electrophysiological properties were confirmed in transfected human embryonic kidney cells, in which an inwardly-rectifying, Cs+-sensitive current was measured by voltage clamp. Current clamp studies of transduced striatal neurons demonstrated an increase in the firing threshold, latency to first action potential and decrease in neuronal excitability. Neurotoxin-induced activation of c-Fos, a marker of neuronal activity, was blocked in transduced neurons indicating that the decrease in electrical excitability was physiologically significant. When used in vivo, this strategy may have the potential to positively impact movement disorders by selectively changing activity of neurons belonging to the direct striatal pathway, characterized by the expression of dopamine-1 receptors. [Copyright &y& Elsevier]

The present work reports on some chromatic characters and their change with size in two species of Tilapia ( T. zillii and T. guineensis) and their first generation hybrids. Successful reciprocal hybridizations between T. zillii and T. guineensis were performed in concrete tanks. The hybrids obtained were viable. The colour patterns of the hybrids and their parents were registered during a rearing cycle of 12 months. Between 2 and 13 cm standard length ( LS), the hybrids were found to be heterogeneous and three phenotypes were observed. The type (1) phenotype had a fully yellowish caudal fin without dots, the type (2) phenotype had a bicoloured caudal fin with the upper part clear yellowish and the lower part dark yellowish and without dots and the type (3) had a similar bicoloured caudal fin, but with dots. Above 13 cm LS, the hybrid population was homogenous and all specimens had a bicoloured caudal fin with dots. In T. zillii, all specimens >14 cm LS had a greyish caudal fin with dots while all T. guineensis >13 cm LS were characterized by a bicoloured caudal fin without dots. A multivariate analysis of the morphometric and meristic characters did not allow a clear separation of all groups. The study showed that the external morphology of the hybrids was intermediate to that of the parental species. [ABSTRACT FROM AUTHOR]

Rapid and reliable identification of tilapiine taxa and strains is essential for selective breeding purposes and the conservation of natural genetic resources. There is evidence that antisera-mediated erythrocyte agglutination assays can fit these requirements. We evaluated the applicability of agglutination tests by studying the capacity of species characteristic antisera to recognize erythrocytes from individuals of 10 natural Ghanaian populations of Oreochromis niloticus and Sarotherodon melanotheron. The vast majority of the 218 tested individuals could be identified based on antisera-mediated erythrocyte recognition. Controls indicated the specificity of these reactions. Still, erythrocytes from 16% of all tested specimens did not respond to any antiserum (zero responders), indicating the possible existence of blood group properties in tilapias. We discuss the specificity of the antisera, the relevance of zero responses and the applicability of these tests in aquaculture and field studies. [ABSTRACT FROM AUTHOR]

Morphometric, allozyme, globin chain and cytochrome b analyses were used for a revision of the subspecies complex of the black-chinned tilapia, Sarotherodon melanotheron Rüppell, 1852. Three out of four subspecies are recognized as valid: S. m. melanotheron (Ivory Coast to Benin), S. m. heudelotii (Senegal to Guinea) and S. m. leonensis (Sierra Leone to Liberia). The fourth subspecies, S. m. nigripinnis, is raised to the species level S. nigripinnis and is composed of the nominate subspecies S. n. nigripinnis known from Gabon and a newly introduced subspecies, S. n. dolloi, originally described as Tilapia dolloi and previously synonymized with S. m. nigripinnis. It is presently known from the mouth of the Congo to the Lower Kouilou. Phylogenetically, populations from the most eastern range, e.g. Gabon/Congo, are considered to represent the most ancient populations. From this area of origin, the western range of West Africa (Senegal to Benin) was colonized. Two independent colonization events are indicated by allozyme and mtDNA analyses. The initial invasion of the western range of West Africa could be dated back to about 2.5 million years ago. [ABSTRACT FROM AUTHOR]

The rapidly inactivating A-type K+ current (IA) is prominent in hippocampal neurons; and the speed of its inactivation may regulate electrical excitability. The auxiliary K+ channel subunit Kvβ1.1 confers fast inactivation to Shaker-related channels and is postulated to affect IA. Whole-cell patch clamp recordings of rat hippocampal pyramidal neurons in primary culture showed a developmental decrease in the time constant of inactivation (τin) of voltage-gated K+ currents: 17.9±1.5 ms in young neurons (5–7 days in vitro; n=53, mean±S.E.M.); 9.9±1.0 ms in mature neurons (12–15 days in vitro; n=72, mean±S.E.M., P<0.01). During the same developmental time, the level of Kvβ1.1 transcript increased more than two-fold in vitro and in vivo, determined by semi-quantitative reverse transcriptase-polymerase chain reaction for hippocampus. The hypothesis that up-regulation of Kvβ1.1 led to the changes in τin was tested in vitro, using antisense knockdown. Kvβ1.1-specific antisense DNA was introduced with a modified herpes virus co-expressing enhanced green fluorescent protein and knockdown of Kvβ1.1 was verified by immunocytochemistry. Following transduction with the antisense virus, mature neurons reverted to τin values characteristic of young neurons: 18.3±2.4 ms (n=20). The effect of antisense knockdown on electrical excitability was tested using current-clamp protocols to induce repetitive firing. Treatment with the antisense virus increased the interspike interval over a range of membrane depolarization (baseline membrane potential=−40 to +20 mV). This effect was most pronounced at −40 mV, where the ISI of the first pair of action potentials was nearly doubled.These data indicate that Kvβ1.1 contributes to the developmental control of IA in hippocampal neurons and that the magnitude of effect is sufficient to regulate electrical excitability. Viral-mediated antisense knockdown of Kvβ1.1 is capable of decreasing the electrical excitability of post-mitotic hippocampal neurons, suggesting this approach has applicability to gene therapy of neurological diseases associated with hyperexcitability. [Copyright &y& Elsevier]

Modification of K[sup +] currents by exogenous gene expression may lead to therapeutic interventions in skeletal muscle diseases characterized by alterations in electrical excitability. In order to study the specific effects of increasing outward K[sup +] currents, we expressed a modified voltage-dependent K[sup +] channel in primary cultured rat skeletal muscle cells. The rat Kv1.4 channel was expressed as an N-terminal fusion protein containing a bioluminescent marker (green fluorescent protein). Transgene expression was carried out using the helper-dependent herpes simplex 1 amplicon system. Transduced myoballs, identified using fluorescein optics and stud- ied electrophysiologically with single-cell patch clamp, exhibited a greater than two-fold increase in K[sup +] conductance by 20-30 h after infection. This increase in K[sup +] current led to a decrease in membrane resistance and a 10-fold increase in the current threshold for action potential generation. Electrical hyperexcitability induced by the Na[sup +] channel toxin anemone toxin II (1 µM) was effectively counteracted by overexpression of Kv1.4 at 30-32 h after transduction. Thus, virally induced overexpression of a voltage-gated K[sup +] channel in skeletal muscle has a powerful effect in reducing electrical excitability. [ABSTRACT FROM AUTHOR]

Based on morphometric and allozyme data of a large sample of black-chinned tilapia, Sarotherodon melanotheron, originating from over its entire geographical distribution range, the subspecific classification of this species has been revised. One subspecies, S. m. paludinosus, is synonymized with S. m. heudelotii. The validity of another subspecies, S. m. leonensis, is questioned. The remaining three subspecies, S. m. melanotheron, S. m. heudelotiiand S. m. nigripinnisare clearly distinguished as separate taxa. [ABSTRACT FROM AUTHOR]