Mechanistic models of how single cells respond to different perturbations can help integrate disparate big data sets or predict response to varied drug combinations. However, the construction and ...simulation of such models have proved challenging. Here, we developed a python-based model creation and simulation pipeline that converts a few structured text files into an SBML standard and is high-performance- and cloud-computing ready. We applied this pipeline to our large-scale, mechanistic pan-cancer signaling model (named SPARCED) and demonstrate it by adding an IFNγ pathway submodel. We then investigated whether a putative crosstalk mechanism could be consistent with experimental observations from the LINCS MCF10A Data Cube that IFNγ acts as an anti-proliferative factor. The analyses suggested this observation can be explained by IFNγ-induced SOCS1 sequestering activated EGF receptors. This work forms a foundational recipe for increased mechanistic model-based data integration on a single-cell level, an important building block for clinically-predictive mechanistic models.
Aims
To add a spore germination step in order to reduce decontamination temperature and time requirements compared to the current hot, humid air decontamination parameters, which are 75–80°C, ≥72 h, ...70–90% RH, down to ≤60°C and ≤24 h total decontamination time.
Methods and Results
Bacillus anthracis spore germination with l‐alanine+inosine+calcium dipicolinate (CaDPA) was quantified at 0–40°C, several time points and spore concentrations of 5–9 log10 per ml. Germination efficiency at 0–40°C was >99% at <8 log10 spores per ml. The temperature optimum was 20°C. Germination efficiency was significantly higher but slower at 0°C compared to ≥30°C at ≥8 log10 spores per ml. A single germinant application followed by 60°C, 1‐h treatment consistently inactivated >2 log10 (>99%) of spores. However, a repeat application of germinant was needed to achieve the objective of ≥6 log10 spore inactivation out of a 7 log10 challenge (≥99·9999%) for ≤24 h total decontamination time for nylon and aircraft performance coating.
Conclusions
l‐alanine+inosine+CaDPA stimulated germination across wide temperature and spore concentration ranges.
Significance and Impact of the Study
Germination expands the scope of spore decontamination to include materials from any industry sector that can be sprayed with an aqueous germinant solution.
Aim
To develop test methods and evaluate survival of Bacillus thuringiensis kurstaki cry− HD‐1 and B. thuringiensis Al Hakam spores after exposure to hot, humid air inside of a C‐130 aircraft.
...Methods and Results
Bacillus thuringiensis spores were either pre‐inoculated on 1 × 2 or 2 × 2 cm substrates or aerosolized inside the cargo hold of a C‐130 and allowed to dry. Dirty, complex surfaces (10 × 10 cm) swabbed after spore dispersal showed a deposition of 8–10 log10 m−2 through the entire cargo hold. After hot, humid air decontamination at 75–80°C, 70–90% relative humidity for 7 days, 87 of 98 test swabs covering 0·98 m2, showed complete spore inactivation. There was a total of 1·67 log10 live CFU detected in 11 of the test swabs. Spore inactivation in the 98 test swabs was measured at 7·06 log10 m−2.
Conclusions
Laboratory test methods for hot, humid air decontamination were scaled for a large‐scale aircraft field test. The C‐130 field test demonstrated that hot, humid air can be successfully used to decontaminate an aircraft.
Significance and Impact of the Study
Transition of a new technology from research and development to acquisition at a Technology Readiness Level 7 is unprecedented.
Motivation:
As the size of high-throughput DNA sequence datasets continues to grow, the cost of transferring and storing the datasets may prevent their processing in all but the largest data centers ...or commercial cloud providers. To lower this cost, it should be possible to process only a subset of the original data while still preserving the biological information of interest.
Results:
Using 4 high-throughput DNA sequence datasets of differing sequencing depth from 2 species as use cases, we demonstrate the effect of processing partial datasets on the number of detected RNA transcripts using an RNA-Seq workflow. We used transcript detection to decide on a cutoff point. We then physically transferred the minimal partial dataset and compared with the transfer of the full dataset, which showed a reduction of approximately 25% in the total transfer time. These results suggest that as sequencing datasets get larger, one way to speed up analysis is to simply transfer the minimal amount of data that still sufficiently detects biological signal.
Availability:
All results were generated using public datasets from NCBI and publicly available open source software.
Justification The most methods of extensive skin and soft tissue defects are aimed at accelerating wound healing and preventing infectious complications. To improve the effectiveness of such defects ...treatment, a method of dosed tissue distraction (MDTD) is used, consisting in the application of a continuously acting load to the area of healthy soft tissue in close proximity to the wound defect.
Purpose It performed the evaluation of the medico-social effectiveness of the introduction into clinical practice of developed methods and devices for implementing MDTD in the treatment of skin and soft tissue defects of the extremities.
Methods 407 patients were treated with wound defects of the extremities, which were divided into two groups: the main group – 198 patients in whose treatment MDTD was applied using original methods and devices; comparison group – 209 patients, in whose treatment standard treatment methods were applied. Comparison of the long-term results of treatment according to the frequency of repeated operations, complications, indicators of quality of life, frequency of disability.
Results The use of MDTD is characterized by better performance compared with the use of standard approaches. There is a decrease in the frequency of performing reconstructive plastic surgery after inpatient treatment (9-10 times), remote complications by 2.6 times, a reduced value of the Vancouver scale (by 28.8%), quality of life indicators higher levels. The use of the proposed approach is characterized by a shorter duration of treatment (by 26.0%), duration of disability (1.4 times), cases of disability (2.2 times).
Conclusion The use of MDTD is characterized by high medical and social efficiency, allows to reduce the cost of treating extensive skin and soft tissue defects by reducing the length of hospitalization, the frequency of repeated rehabilitation and reconstructive operations, accelerated recovery of patients, improving the quality of life and reducing the incidence of disability
Subscale testing of prompt agent defeat formulations
SHOCK COMPRESSION OF CONDENSED MATTER - 2015: Proceedings of the Conference of the American Physical Society Topical Group on Shock Compression of Condensed Matter,
01/2017
Conference Proceeding
To develop pathogenetically justified surgical treatment of diabetic neuroosteoarthropathy (DNOAP).
52 patients were operated and long-term results were studied in 36 of them. 2 groups were assessed ...depending on completeness of surgical treatment including changed synovial structures removal. Tarso-metatarsal arthrodesis was created after synovectomy in median foot to restore longitudinal arch. Cruro-calcaneal neoarthrosis was performed after elimination of posterior focus of DNOAP. Excision of large, deep plantar ulcer (or osteomyelitic fistula) was completed by tissues tension with needles for primary wound healing.
DNOAP patients are tolerant against surgical infection that is decreased in patients with neuropathic form of diabetic foot syndrome. Skin plasty is followed by rejection in DNOAP that was cured with prednisolone. Deep suppurations complicating foot skeleton fragmentation have subacute course and do not lead to sepsis. Infected wounds heal by primary intention in 98% after closure with primary suture. It was empirically found that synovectomy and osteochondral detritus removal discontinue DNOAP course. Reconstructive surgical stage is aimed to restoring the shape and function of the foot. Analysis of long-term outcomes showed absence of DNOAP signs in 76.2±9.2% of cases after radical surgery and positive results of treatment in 97.2±2.7% of patients.
Our data conceptually assume the possibility of autoimmune mechanism in DNOAP pathogenesis. On this basis pathogenetically reasonable surgical procedures are established to interrupt pathological process. These interventions differ by technological aspects only depending on middle or rear foot destruction.
to improve the results of advanced peritonitis management.
743 patients with advanced peritonitis were studied. Patients were divided into 2 groups depending on treatment strategy.
Programmed ...relaparotomy combined with removable draining musculoaponeurotic seams during laparotomy closure decreased mortality from 47.8±2.7% to 24.1±2.3% (p<0.001) and provided 4-fold reduction of postoperative suppuration incidence (p<0.001). Refusal from removable draining musculoaponeurotic seams and use of only cutaneous seams in persistent abdominal hypertension were associated with further decrease of mortality to 15.8±2.7% (p<0.05).
Programmed relaparotomy combined with removable draining musculoaponeurotic seams are advisable for advanced peritonitis management. Laparotomy closure with only cutaneous seams is indicated in case of persistent abdominal hypertension. Large eventration always requires abdominal wall repair. APACHE-III scale scores have significant prognostic value in patients with advanced peritonitis.
The known anterior prompts to the femoral neck are non-traumatic, but they exclude the possibility of myoplasty and are not large enough for intra-articular sequestrectomy.
Objective.
The aim of the ...study was to develop an anterior prompt to the hip joint for sequestrectomy with myoplasty.
Materials and research methods.
For surgery neck and head of the hip osteomyelitis we perform a semi-oval incision in the projection of the femoral head, from the anterior spines of the ilium we cut off the tendons of the sartorius and rectus head of the quadriceps femoris muscles. An operating field is formed, which allows sequestrectomy to be performed. Plasty of the osteomyelitis cavity is performed with the proximal parts of the two anterior ileofemoral muscles. The operating field, if necessary, can be increased by temporary transection of the lumbar-iliac muscle tendon.
Research results.
The key to the anterior surgical prompt to the hip joint is the sartorius and rectus head of the quadriceps. The length of the surgical wound reaches 17–22 cm, and the width is 16–18 cm. With the mobilized proximal part of the sartorius muscle, we fill the entire bone cavity in the neck and head of the femur. Of the 12 operated patients, 11 (91.7 ± 7.6 %) had a stable long-term remission.
Conclusion.
The proposed approach is less traumatic and allows you to operate at an angle of about 90°. It complements the advantages of the known anterior prompts and is devoid of their disadvantages.
To create a method of two-stage repair of high unformed conglomerate delimited debilitating jejunal fistulas via posterolateral laparotomy with low risk of surgical complications.
Methodology and ...treatment outcomes were analyzed in 37 patients with unformed conglomerate high debilitating delimited jejunal fistulas. Of these, 22 patients underwent one-stage treatment through 2 converging incisions and/or two-stage treatment through anterolateral access. They made up a control group. Fifteen patients in the main group underwent two-stage treatment via posterolateral left-sided laparotomy with unilateral disconnection of jejunum with fistula. In most patients of both groups, fistulas complicated surgery for acute adhesive intestinal obstruction. Topography of adhesions that caused acute intestinal obstruction in both groups was studied in 172 other patients. Identical jejunal fistulas and two different surgical approaches made it possible to consider our groups representative.
Two-stage treatment via posterolateral left-sided laparotomy reduced mortality from 63.6±10.2% to 20.0±10.3% (
=11.8;
<0.001). This approach simplified intraoperative diagnostics that became more informative. Posterolateral access increased the quality of anastomosis and safety of viscerolysis.
A new two-stage approach with posterolateral left-sided laparotomy allowed atraumatic imposing of inter-intestinal anastomosis with proximal disconnection of jejunal fistula. This exclusion turns the fistula into analogue of the definitive Meidl's jejunostomy, unloads the intestinal anastomosis and increases the quality of suture. New strategy reduced the risk of complications and mortality.
PDF
