Mode of action and characterization of a novel biological response modifier isolated from fractionated caprine serum

Immune Cell Potentiating Factor (ICPF) represents a class of biological response modifiers initially only found within active caprine serum fractions. Controlled studies have since demonstrated active ICPF derived from several non-caprine mammalian sources; including equine and human. ICPF is able to increase survivability in murine gram negative induced sepsis (60%) as well as secondary infection and subsequent sepsis in canines infected within canine parvo virus 2 (36%) despite showing no innate antiviral properties. ICPF is able to initiate systemic proteomic changes within several organ systems; including serum, liver, brain, lung, and spleen. ICPF initiated an early acute phase response, specifically through the increased expression of serum amyloid A, with systemic serum levels increasing from 1.5 μg/mL to 403.0 μg/mL within 24 hours and increased to 3,400 μg/mL within 48 hours following ICPF administration. Evaluation of cytokine expression following ICPF treatment revealed the up-regulation of IL-6, INF-γ, and the chemokine CXCL1\KC in vivo as well as the expression of IL-6 and IFN-γ in vitro within 3 hours of treatment. Development of an in vitro bioassay through the expression of IL-6 and IFN-γ within whole blood and peripheral blood mononuclear cells will allow for further elucidation and testing of ICPF outside of an animal host. The early expression of proinflammatory cytokines and chemokines, an acute phase response including serum amyloid A, and ICPF’s inability to alleviate mortality in a lipopolysaccharide animal mortality model strongly indicates an active role for ICPF as an immune regulatory peptide capable of promoting an early inflammatory response to Salmonella enterica serovar Typhimurium thereby reducing the risk and mortality associated with sepsis

Neurotrophic Factor Genetics of Cognitive Progression and Neuropsychiatric Symptom Presentation in Alzheimer\u27s Disease and Related Disorders

The Cache County Study on Memory in Aging (CCSMA) and subsequent Dementia Progression Study (DPS) were two research studies that took place in Cache County, Utah. These studies followed 5092 participants aged 65 or older for approximately 12 years and looked at risk and protective factors for dementia, including Alzheimer’s disease. One of the factors investigated was genes that are known to influence brain health, such as brain-derived neurotrophic factor (BDNF), a protein found in the brain that helps with the survival of brain cells. BDNF genes have been shown to be associated with Alzheimer’s disease and related dementia (ADRD) risk, but little is known about the influence these genes have after dementia is diagnosed. The current study looked at how BDNF related genes were associated with learning and memory abilities (i.e. cognitive ability) and problematic behaviors (e.g. delusions, agitation/aggression, anxiety) in individuals from the CCSMA and DPS who were diagnosed with ADRD. This research is important to help understand what may contribute to often-seen differences in dementia progression and help inform possible treatment decisions. The results of the current project showed that BDNF genes influenced both progression of cognitive difficulties and problematic behaviors in individuals with ADRD. Additionally, it was shown that many of these effects depended on the sex of the individual, such that men and women progressed at different rates and were influenced by different BDNF related genotypes. These results provide evidence of the influence of BDNF genes after dementia diagnosis and highlights the need to investigate contributing factors related to the sex of the individual. Targeted medication or behavioral treatment of dementia that both improves BDNF function in the brain, as well as mitigates any sex-related effects, may also be another avenue for future research

High Resolution Triple Axis X-Ray Diffraction Analysis of II-VI Semiconductor Crystals

The objective of this research program is to develop methods of structural analysis based on high resolution triple axis X-ray diffractometry (HRTXD) and to carry out detailed studies of defect distributions in crystals grown in both microgravity and ground-based environments. HRTXD represents a modification of the widely used double axis X-ray rocking curve method for the characterization of grown-in defects in nearly perfect crystals. In a double axis rocking curve experiment, the sample is illuminated by a monochromatic X-ray beam and the diffracted intensity is recorded by a fixed, wide-open detector. The intensity diffracted by the sample is then monitored as the sample is rotated through the Bragg reflection condition. The breadth of the peak, which is often reported as the full angular width at half the maximum intensity (FWHM), is used as an indicator of the amount of defects in the sample. This work has shown that high resolution triple axis X-ray diffraction is an effective tool for characterizing the defect structure in semiconductor crystals, particularly at high defect densities. Additionally, the technique is complimentary to X-ray topography for defect characterization in crystals

Comparison of Multiple Antibiotic Resistant Staphylococcus Aureus Genomes and the Genome Structure of Elizabethkingia Meningoseptica

i. The aim of this study was to determine if methicillin-resistant Staphylococcus aureus (MRSA) strains could be identified in the milk of dairy cattle in a Paso Del Norte region dairy. Using physiological and PCR-based identification schemes, 40 S. aureus strains were isolated from 133 milk samples analyzed. This investigation also included the production of draft genome sequences of a MRSA and a methicillin-susceptible isolate. Genomic analysis of these strains demonstrate that strains H29 and PB32 represent novel clones of sequenced human and/or bovine-related strains of S. aureus.ii. The draft genomes of a heterogeneous vancomycin-intermediate resistant Staphylococcus aureus (VISA) strain MM66 and strain MM66RVI-4 expressing reduced vancomycin-intermediate resistance harbored the same mutation in graS of a two-component regulatory system. MM66RVI-4 has also lost staphylococcal cassette chromosome, SCCmec, corroborating methicillin-resistance in this strain and harbored mutations present in vraG, encoding an ATP-binding cassette transporter. The observed genetic alterations in both strains have been shown to affect vancomycin resistance levels in VISA. iii. Elizabethkingia species are environmental isolates that exhibit a multidrug-resistance phenotype and are a cause of life-threatening infections in immunocompromised individuals. To date, most studies have focused on the clinical aspects of this organism, and little is known regarding its antimicrobial resistance mechanisms. In addition, the phylogenetics and speciation of this genus is still highly controversial and has yet to be thoroughly defined. In an effort to clear up confusion surrounding the speciation of this genus as well as identifying possible antimicrobial resistance mechanisms, we report the draft genome sequence of the E. meningoseptica type strain ATCC 13253T.Biochemistry & Molecular Biolog

Application of Digital Twin technology in the development of logistics process

A digital twin is a living model that drives a business outcome” (Colin J. Parris, GE). Digital twin technology is appearing more and more fields, including logistics, which nowadays generates new research opportunities for the logistics professionals. However multiple key technologies had already been developed. The aim of this article is to present the technology, development and types of digital twins, as well as to provide an overview of the possibilities of their application in logistics. Furthermore, the purpose of the publication is to present the research guidelines of the field

Does the nonlinear Schroedinger equation correctly describe beam propagation?

The parabolic equation (nonlinear Schrödinger equation) that appears in problems of stationary nonlinear beam propagation (self-focusing) is reconsidered. It is shown that an additional term, which involves changes of the propagation constant along the propagation direction, should be taken into account. The physical consequences of this departure from the standard approximation, which uses the parabolic equation, are discussed. A numerical simulation showing the difference between the new approach and the standard nonlinear Schrödinger equation is given as an example. © 1993 Optical Society of AmericaPeer Reviewe

Specific Cognitive/Behavioral Domains Predict Neuropsychiatric Symptoms in Severe Dementia

Background: Neuropsychiatric symptoms (NPS) have high prevalence in Alzheimer’s disease and related disorders (ADRD), with nearly 100% of individuals experiencing some type of symptom over the course of dementia (Tschanz et al, 2011). The occurrence of NPS is highly variable and fluctuates in severity (Tschanz et al., 2016). Their occurrence differs by type of dementia and increases over time (Kazui et al., 2016). Although risk factors for NPS in ADRD have been studied (e.g., Steinberg et al., 2014; Treiber et al, 2008), greater understanding of the nature of NPS and their triggers is needed to inform care management strategies (Gauthier et al., 2010). While much research has examined NPS in mild-to-moderate dementia, fewer studies have examined NPS in severe dementia. We investigated the cognitive correlates of NPS in patients with severe dementia in a community-based sample, examining whether impairments in specific cognitive or behavioral domains were more predictive of specific NPS. We hypothesized that poorer cognitive abilities would be associated with more severe NPS (e.g., agitation) and higher cognitive scores with affective symptoms in severe dementia. Methods: Eighty-nine (27%) out of 328 total participants of a longitudinal study of dementia progression (the Cache County Dementia Progression Study) met criteria for severe dementia: Mini-Mental State Exam (MMSE) score of ≤10 or Clinical Dementia Rating of 3 (severe). Forty-eight (54%) of these individuals completed the Severe Cognitive Impairment Profile (SCIP), which assessed the following domains: Comportment, Attention, Language, Memory, Motor, Conceptualization, Arithmetic, and Visuospatial abilities. NPS were assessed by caregiver report using the Neuropsychiatric Inventory (NPI). The NPI assesses delusions, hallucinations, depression, anxiety, irritability, apathy, agitation/aggression, judgement, aberrant motor behaviors, euphoria, sleep and appetite. Demographic information, overall health, place of residence (private home, assisted living facility and nursing home), and dementia duration were also assessed. NPI severity scores (intensity x frequency) were summed across domains to yield a total NPI score (Total NPI-12) and domain clusters of psychotic symptoms (hallucinations and delusions), affective symptoms (depression, anxiety, and irritability), apathy, and agitation/aggression were examined. Bivariate correlations between SCIP domain scores and Total NPI-12 and the domain clusters were examined. SCIP domain scores that were significantly correlated with NPI scores in bivariate analyses were entered into multiple regression models. Covariates tested included the age at which severe dementia criteria was met, the duration of dementia from age of onset, gender, place of residence, overall health and years of education. Results: Mean (SD) age and education were 86.23 (6.12) and 13.13 (3.13), respectively. Total NPI-12 scores showed significant correlations with the SCIP sub scores of comportment ( r = -0.36, p = 0.017) and memory (r = - 0.31, p = 0.047). Apathy significantly correlated with comportment (r = -0.38, p = 0.010) while agitation/aggression correlated with conceptualization (r = -0.41, p = 0.007), language (r = -0.36, p = 0.017), memory (r = -0.48, p = 0.001), and visuospatial ability (r = -0.31, p = 0.045). In multiple regression models (with inclusion of significant covariates), total NPI-12 scores were significantly associated with comportment (β = -1.32, SE = 0.56, p = 0.02); apathy was significantly associated with comportment (β = -0.01, SE = 0.02, p = 0.003); and agitation/aggression was significantly associated with memory (β = -0.43, SE = 0.12, p = 0.001). NPI affective and psychotic scores were not associated with any SCIP domains. Conclusion: In this sample of individuals with severe dementia, we found several cognitive or behavioral domains were associated with NPS. Poorer abilities in Comportment, which consisted of responses to social questions (e.g., greetings) were associated with more severe apathy, and poorer abilities in conceptualization, language, memory and visuospatial skills were associated with more severe agitation/aggression. With the latter, multiple regression models found only memory scores to independently predict agitation/aggression, reflecting moderate correlation between cognitive domains. Our results suggest that poor cognitive abilities may increase vulnerability to NPS, possibly as a result of impaired comprehension of activities and events in the environment. Cognitive testing may be useful to identify those at greatest risk for NPS. Furthermore, environmental manipulations that aim to decrease the complexity and therefore degree of stimulation for persons with dementia to a level more appropriate to their level of cognitive function may help reduce the occurrence of NPS in severe dementia

Triple‐crystal x‐ray diffraction analysis of reactive ion etched gallium arsenide

This is the published version. Copyright 1994 American Institute of PhysicsThe effect of BCl3 reactive ion etching on the structural perfection of GaAs has been studied with diffuse x‐ray scattering measurementsconducted by high‐resolution triple‐crystal x‐ray diffraction. While using a symmetric 004 diffraction geometry revealed no discernible differences between etched and unetched samples, using the more surface‐sensitive and highly asymmetric 113 reflection revealed that the reactive ion etched samples etched displayed less diffusely scattered intensity than unetched samples, indicating a higher level of structural perfection. Increasing the reaction ion etch bias voltage was found to result in decreased diffuse scattering initially, until an apparent threshold voltage was reached, after which no further structural improvement was observed. Furthermore, we have shown that this reduction in process‐induced surfacestructural damage is not due merely to the removal of residual chemical‐mechanical polishing damage