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Our recent work on linear and affine dynamical systems has laid out a general framework for inferring the parameters of a differential equation model from a discrete set of data points collected from a system being modeled. It introduced a new class of inverse problems where qualitative information about the parameters and the associated dynamics of the system is determined for regions of the data space, rather than just for isolated experiments. Rigorous mathematical results have justified this approach and have identified common features that arise for certain classes of integrable models. In this work we present a thorough numerical investigation that shows that several of these core features extend to a paradigmatic linear-in-parameters model, the Lotka–Volterra (LV) system, which we consider in the conservative case as well as under the addition of terms that perturb the system away from this regime. A central construct for this analysis is a concise representation of parameter and dynamical features in the data space that we call the P n -diagram, which is particularly useful for visualization of the qualitative dependence of the system dynamics on data for low-dimensional (small n) systems. Our work also exposes some new properties related to non-uniqueness that arise for these LV systems, with non-uniqueness manifesting as a multi-layered structure in the associated P 2-diagrams.

Summary Staphylococcus aureus is one of the most common causes of infection in people and is increasingly recognized in dogs. The increasing prevalence of methicillin resistant S. aureus (MRSA) is complicating the treatment of these infections. Panton Valentine leukocidin (PVL), a toxin involved in the pathogenesis of necrotic syndromes in people may be partially responsible for the rise of MRSA. Canine and human S. aureus from the same geographic area are genetically similar, indicating a common population and likely transmission. The implications of increasing antimicrobial resistance complicated by interspecies transmission, necessitates including both dogs and humans in S. aureus resistance surveillance studies. A collection of 126 S. aureus isolates from people (n = 99) and dogs (n = 27) were included, minimum inhibitor concentrations to a panel of 33 antimicrobials used in human and veterinary medicine were determined. No resistance to vancomycin, linezolid, daptomycin, quinupristin/dalfopristin or nitrofurantoin was found. A wide range of antibiograms were found; including resistance to 0–12 drugs (0–6 drug classes). Outstanding antibiograms included a canine MRSA resistant to rifampin and a human MRSA resistant to chloramphenicol. Inducible clindamycin resistance was found among 78% and 4% of canine and human MRSA and 17% and 25% of canine colonizing and human methicillin susceptible S. aureus (MSSA), respectively. Resistance to mupirocin was only found among human isolates including 20% of MRSA and 4% of MSSA. While no canine isolates were PVL positive, 39% of human MRSA and 2% of MSSA carried the gene. The bidirectional transmission of S. aureus between people and dogs necessitates the inclusion of isolates from both species in future studies.

The relationship between obesity and cancer has become of particular interest due to the rapidly growing prevalence of overweight individuals. Obesity predisposes individuals to the development of hepatic steatosis and is an independent risk factor for several neoplasms. Toll-like receptor 4 (TLR4) is the innate receptor for endotoxin, and steatotic livers are known to be sensitive to endotoxin. TLR4 signaling has been shown to have proneoplastic effects in vitro due to its effect on immune surveillance. Thus far, studies have predominantly focused on the effect of tumor-cell-derived TLR4 without regard to host TLR4 signaling. In the present study we show that steatotic livers have increased expression of TLR4. Obese animals developed higher metastatic tumor burden in the liver than lean controls regardless of the presence or absence of intact host TLR4. After silencing TLR4 expression using RNAi in the mouse colon cancer cell line MC38, there was a significant decrease in metastatic tumor burden within the liver of obese animals. These findings demonstrate that steatotic livers have increased susceptibility to metastatic tumor growth and that silencing tumor cell TLR4 reduces metastatic tumor burden in steatotic liver.

Staphylococcus aureus is one of the most common causes of infection in people and is increasingly recognized in dogs. The increasing prevalence of methicillin resistant S. aureus (MRSA) is complicating the treatment of these infections. Panton Valentine leukocidin (PVL), a toxin involved in the pathogenesis of necrotic syndromes in people may be partially responsible for the rise of MRSA. Canine and human S. aureus from the same geographic area are genetically similar, indicating a common population and likely transmission. The implications of increasing antimicrobial resistance complicated by interspecies transmission, necessitates including both dogs and humans in S. aureus resistance surveillance studies. A collection of 126 S. aureus isolates from people (n = 99) and dogs (n = 27) were included, minimum inhibitor concentrations to a panel of 33 antimicrobials used in human and veterinary medicine were determined. No resistance to vancomycin, linezolid, daptomycin, quinupristin/dalfopristin or nitrofurantoin was found. A wide range of antibiograms were found; including resistance to 0-12 drugs (0-6 drug classes). Outstanding antibiograms included a canine MRSA resistant to rifampin and a human MRSA resistant to chloramphenicol. Inducible clindamycin resistance was found among 78% and 4% of canine and human MRSA and 17% and 25% of canine colonizing and human methicillin susceptible S. aureus (MSSA), respectively. Resistance to mupirocin was only found among human isolates including 20% of MRSA and 4% of MSSA. While no canine isolates were PVL positive, 39% of human MRSA and 2% of MSSA carried the gene. The bidirectional transmission of S. aureus between people and dogs necessitates the inclusion of isolates from both species in future studies.

Recent experimental evidence suggests that synaptic plasticity depends on the precise timing of pre- and post-synaptic activity. In this paper, an iterative model for a multiplicative form of this spike-timing-dependent plasticity (mSTDP) is introduced. This model is incorporated into a neural network with many input cells coupled via excitation to a single output cell. Analysis of this network yields a criterion for the output cell to fire on every iteration, as well as general formulae for the steady-state output firing rate and the steady-state value to which all synaptic weights are driven by mSTDP. These characterize the basic state of network operation generated by mSTDP.

The human beta-globin locus control region (LCR) contains chromatin opening and transcriptional enhancement activities that are important to include in beta-globin gene therapy vectors. We previously used single-copy transgenic mice to map chromatin opening activity to the 5'HS3 LCR element. Here, we test novel hybrid globin genes to identify beta-globin gene sequences that functionally interact with 5'HS3. First, we show that an 850-base pair (bp) 5'HS3 element activates high-level beta-globin gene expression in fetal livers of 17 of 17 transgenic mice, including 3 single-copy animals, but fails to reproducibly activate Agamma-globin transgenes. To identify the beta-globin gene sequences required for LCR activity by 5'HS3, we linked the 815-bp beta-globin promoter to Agamma-globin coding sequences (BGT34), together with either the beta-globin intron 2 (BGT35), the beta-globin 3' enhancer (BGT54), or both intron 2 and the 3' enhancer (BGT50). Of these transgenes, only BGT50 reproducibly expresses Agamma-globin RNA (including 7 of 7 single-copy animals, averaging 71% per copy). Modifications to BGT50 show that LCR activity is detected after replacing the beta-globin promoter with the 700-bp Agamma-globin promoter, but is abrogated when an AT-rich region is deleted from beta-globin intron 2. We conclude that LCR activity by 5'HS3 on globin promoters requires the simultaneous presence of beta-globin intron 2 sequences and the 260-bp 3' beta-globin enhancer. The BGT50 construct extends the utility of the 5'HS3 element to include erythroid expression of nonadult beta-globin coding sequences in transgenic animals and its ability to express antisickling gamma-globin coding sequences at single copy are ideal characteristics for a gene therapy cassette.

Fifteen continuous ambulatory peritoneal dialysis (CAPD) patients from our dialysis unit were studied while using two different types of exchange systems: a snap-disconnect Y-set system and the Baxter UltraBag system. The incidence of peritonitis in the snap-disconnect Y-system was found to be 32 cases in 187 months, or a rate of 1 case of peritonitis every 5.8 months. When these patients switched to the Baxter UltraBag system, the incidence of peritonitis dropped to 4 cases in 175 months, or 1 case every 43.8 months, a highly significant difference. We conclude, therefore, that the UltraBag system is highly effective in reducing the incidence of peritonitis in CAPD patients.

Silicon levels in plasma and urine have been studied in normal subjects, in chronic renal failure patients, and in regular hemodialysis patients. Plasma levels were elevated in chronic renal failure, and in hemodialysis patients they were three times the control values. Urine silicon excretion is significantly related to creatinine clearance, and to urinary omolality, magnesium and calcium levels. A small amount of residual silicon is found in the hollow fiber artificial kidneys made by some manufacturers. High concentrations of silicon are found in commercial dialysate and pass down a chemical concentration gradient into the blood compartment. It is concluded that silicon is sequestered rapidly in the body during hemodialysis, and that this amounts to 58 g of silicic acid per annum from hemodialysis alone.