Chemical design of non-ionic polymer brushes as biointerfaces : poly(2-oxazine)s outperform both poly(2-oxazoline)s and PEG

The era of poly(ethylene glycol) (PEG) brushes as a universal panacea for preventing non-specific protein adsorption and providing lubrication to surfaces is coming to an end. In the functionalization of medical devices and implants, in addition to preventing non-specific protein adsorption and cell adhesion, polymer-brush formulations are often required to generate highly lubricious films. Poly(2-alkyl-2-oxazoline) (PAOXA) brushes meet these requirements, and depending on their side-group composition, they can form films that match, and in some cases surpass, the bioinert and lubricious properties of PEG analogues. Poly(2-methyl-2-oxazine) (PMOZI) provides an additional enhancement of brush hydration and main-chain flexibility, leading to complete bioinertness and a further reduction in friction. These data redefine the combination of structural parameters necessary to design polymer-brush-based biointerfaces, identifying a novel, superior polymer formulation

Design of a Novel Multifunction Decision Support Display for Anesthesia Care: AlertWatch® OR

Abstract Background This paper describes the design of a multifunction alerting display for intraoperative anesthetic care. The design was inspired by the multifunction primary flight display used in modern aviation. Results The display retrieves live data from multiple sources; the physiologic monitors, the anesthesia information management system, the laboratory values and comorbidities from patient’s problem summary list, medical history or history & physical. This information is integrated into a display composed of readily identifiable icons of organ systems, which are color coded to signify normal range, marginal range, abnormal range (by green, yellow, red respectively) and orange outlines for comorbidities/risk factors. There are dozens of text alerts, which can be presented as black text (informational), red text (important information) and red scrolling text (highest importance information). The alerts are derived from current standards in the literature and some involve complex calculations being conducted in the background. Conclusions The goal of such a system is to improve the quality and safety of anesthetic care by providing enhanced situational awareness in a fashion analogous to the “glass cockpit” and its primary flight display which has improved aviation safety.https://deepblue.lib.umich.edu/bitstream/2027.42/142347/1/12871_2018_Article_478.pd

Design of a novel multifunction decision support/alerting system for in-patient acute care, ICU and floor (AlertWatch AC)

Abstract Background Multifunction surveillance alerting systems have been found to be beneficial for the operating room and labor and delivery. This paper describes a similar system developed for in-hospital acute care environments, AlertWatch Acute Care (AWAC). Results A decision support surveillance system has been developed which extracts comprehensive electronic health record (EHR) data including live data from physiologic monitors and ventilators and incorporates them into an integrated organ icon-based patient display. Live data retrieved from the hospitals network are processed by presenting scrolling median values to reduce artifacts. A total of 48 possible alerts are generated covering a broad range of critical patient care concerns. Notification is achieved by paging or texting the appropriated member of the critical care team. Alerts range from simple out of range values to more complex programing of impending Ventilator Associated Events, SOFA, qSOFA, SIRS scores and process of care reminders for the management of glucose and sepsis. As with similar systems developed for the operating room and labor and delivery, there are green, yellow, and red configurable ranges for all parameters. A census view allows surveillance of an entire unit with flashing or text to voice alerting and enables detailed information by windowing into an individual patient view including live physiologic waveforms. The system runs via web interface on desktop as well as mobile devices, with iOS native app available, for ease of communication from any location. The goal is to improve safety and adherence to standard management protocols. Conclusions AWAC is designed to provide a high level surveillance view for multi-bed hospital units with varying acuity from standard floor patients to complex ICU care. Alerts are generated by algorithms running in the background and automatically notify the selected member of the patients care team. Its value has been demonstrated for low acuity patients, further study is required to determine its effectiveness in high acuity patients.http://deepblue.lib.umich.edu/bitstream/2027.42/173425/1/12871_2021_Article_1411.pd

Metabolic engineering of β-oxidation in Penicillium chrysogenum for improved semi-synthetic cephalosporin biosynthesis

Industrial production of semi-synthetic cephalosporins by Penicillium chrysogenum requires supplementation of the growth media with the side-chain precursor adipic acid. In glucose-limited chemostat cultures of P. chrysogenum, up to 88% of the consumed adipic acid was not recovered in cephalosporin-related products, but used as an additional carbon and energy source for growth. This low efficiency of side-chain precursor incorporation provides an economic incentive for studying and engineering the metabolism of adipic acid in P. chrysogenum. Chemostat-based transcriptome analysis in the presence and absence of adipic acid confirmed that adipic acid metabolism in this fungus occurs via β-oxidation. A set of 52 adipate-responsive genes included six putative genes for acyl-CoA oxidases and dehydrogenases, enzymes responsible for the first step of β-oxidation. Subcellular localization of the differentially expressed acyl-CoA oxidases and dehydrogenases revealed that the oxidases were exclusively targeted to peroxisomes, while the dehydrogenases were found either in peroxisomes or in mitochondria. Deletion of the genes encoding the peroxisomal acyl-CoA oxidase Pc20g01800 and the mitochondrial acyl-CoA dehydrogenase Pc20g07920 resulted in a 1.6- and 3.7-fold increase in the production of the semi-synthetic cephalosporin intermediate adipoyl-6-APA, respectively. The deletion strains also showed reduced adipate consumption compared to the reference strain, indicating that engineering of the first step of β-oxidation successfully redirected a larger fraction of adipic acid towards cephalosporin biosynthesis.

Challenges in the design of concentrator photovoltaic (CPV) modules to achieve highest efficiencies

Concentrator photovoltaics (CPV) is a special high efficiency system technology in the world of PV-technologies. The idea of CPV is to use optical light concentrators to increase the incident power on solar cells. The solar cell area is comparatively tiny, thus saving expensive semiconductor materials and allowing the use of more sophisticated and more costly multi-junction solar cells. The highest CPV module efficiency achieved is 38.9%. This CPV module uses four-junction III-Vbased solar cells. Moreover, mini-modules have already achieved an efficiency of 43.4%. The interaction between optics, cells, and layout of the module and tracker determines the overall field performance. Today, some utility scale CPV plants are installed. The CPV technology allows for many technical solutions for system designs and for optimizing performance while maintaining the economics. This paper will review the achievements and discuss the challenges for the CPV module technology and its components. We discuss the different components and the most important effects regarding the module design. Furthermore, we present the module designs that have shown the highest efficiencies

Genomics and drug profiling of fatal TCF3-HLF\ue2 'positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options

TCF3-HLF 12positive acute lymphoblastic leukemia (ALL) is currently incurable. Using an integrated approach, we uncovered distinct mutation, gene expression and drug response profiles in TCF3-HLF 12positive and treatment-responsive TCF3-PBX1 12positive ALL. We identified recurrent intragenic deletions of PAX5 or VPREB1 in constellation with the fusion of TCF3 and HLF. Moreover somatic mutations in the non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF ALL suggest cooperation within a restricted genetic context. The enrichment for stem cell and myeloid features in the TCF3-HLF signature may reflect reprogramming by TCF3-HLF of a lymphoid-committed cell of origin toward a hybrid, drug-resistant hematopoietic state. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics but sensitivity to glucocorticoids, anthracyclines and agents in clinical development. Striking on-target sensitivity was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This integrated approach thus provides alternative treatment options for this deadly disease

Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options

TCF3-HLF-fusion positive acute lymphoblastic leukemia (ALL) is currently incurable. Employing an integrated approach, we uncovered distinct mutation, gene expression, and drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL. Recurrent intragenic deletions of PAX5 or VPREB1 were identified in constellation with TCF3-HLF. Moreover somatic mutations in the non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF ALL suggest cooperation within a restricted genetic context. The enrichment for stem cell and myeloid features in the TCF3-HLF signature may reflect reprogramming by TCF3-HLF of a lymphoid-committed cell of origin towards a hybrid, drug-resistant hematopoietic state. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics, but sensitivity towards glucocorticoids, anthracyclines and agents in clinical development. Striking on-target sensitivity was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This integrated approach thus provides alternative treatment options for this deadly disease