•Separation of proteins enabled via computer-assisted modeling.•Chaotropic agents minimizes conformational changes of biomolecules.•Liner and polynomial regression retention models delivered optimal ...chromatographic conditions.•Excellent correlation between experimental and modeled retention times for proteins (12–670 kDa)
Recent advances in biomedical and pharmaceutical processes has enabled a notable increase of protein- and peptide-based drug therapies and vaccines that often contain a higher-order structure critical to their efficacy. Hyphenation of chromatographic and spectrometric techniques is at the center of all facets of biopharmaceutical analysis, purification and chemical characterization. Although computer-assisted chromatographic modeling of small molecules has reached a mature stage across the pharmaceutical industry, software-based method optimization approaches for large molecules has yet to see the same revitalization. Conformational changes of biomolecules under chromatographic conditions have been identified as the major culprit in terms of sub-optimal modeling outcomes. In order to circumvent these challenges, we herein investigate the outcomes generated via computer-assisted modeling from using different chaotropic and denaturing mobile phases (trifluoroacetic acid, sodium perchlorate and guanidine hydrochloride in acetonitrile/water-based eluents). Linear and polynomial regression retention models using ACD/Labs software were built as a function of gradient slope, column temperature and mobile phase buffer for eight different model proteins ranging from 12 to 670 kDa (holo-transferrin, cytochrome C, apomyoglobin, ribonuclease A, ribonuclease A type I-A, albumin, y-globulin and thyroglobulin bovine). Correlation between experimental and modeled outputs was substantially improved by using strong chaotropic and denaturing modifiers in the mobile phase, even when using linear regression modeling as typically observed for small molecules. On the contrary, the use of conventional TFA buffer concentrations at low column temperatures required the used of polynomial regression modeling indicating potential conformational structure changes of proteins upon chromatographic conditions. In addition, we illustrate the power of modern computer-assisted chromatography modeling combined with chaotropic agents in the developing of new RPLC assays for protein-based therapeutics and vaccines.
Abstract
Background
Drain insertion following chronic subdural hematoma (CSDH) evacuation improves patient outcomes.
Objective
To examine whether this is influenced by variation in drain location, ...positioning or duration of placement.
Methods
We performed a subgroup analysis of a previously reported multicenter, prospective cohort study of CSDH patients performed between May 2013 and January 2014. Data were analyzed relating drain location (subdural or subgaleal), position (through a frontal or parietal burr hole), and duration of insertion, to outcomes in patients aged >16 yr undergoing burr-hole drainage of primary CSDH. Primary outcomes comprised modified Rankin scale (mRS) at discharge and symptomatic recurrence requiring redrainage within 60 d.
Results
A total of 577 patients were analyzed. The recurrence rate of 6.7% (12/160) in the frontal subdural drain group was comparable to 8.8% (30/343) in the parietal subdural drain group. Only 44/577 (7.6%) patients underwent subgaleal drain insertion. Recurrence rates were comparable between subdural (7.7%; 41/533) and subgaleal (9.1%; 4/44) groups (P = .95). We found no significant differences in discharge mRS between these groups. Recurrence rates were comparable between patients with postoperative drainage for 1 or 2 d, 6.4% and 8.4%, respectively (P = .44). There was no significant difference in mRS scores between these 2 groups (P = .56).
CONCLUSION
Drain insertion after CSDH drainage is important, but position (subgaleal or subdural) and duration did not appear to influence recurrence rate or clinical outcomes. Similarly, drain location did not influence recurrence rate nor outcomes where both parietal and frontal burr holes were made. Further prospective cohort studies or randomized controlled trials could provide further clarification.
By the end of October 2022, the US HL-LHC Accelerator Upgrade Project (AUP) had completed fabrication of ten MQXFA magnets and tested eight of them. The MQXFA magnets are the low-beta quadrupole ...magnets to be used in the Q1 and Q3 Inner Triplet elements of the High Luminosity LHC. This AUP effort is shared by BNL, Fermilab, and LBNL, with strand verification tests at NHMFL. An important step of the AUP QA plan is the testing of MQXFA magnets in a vertical cryostat at BNL. The acceptance criteria that could be tested at BNL were all met by the first four production magnets (MQXFA03-MQXFA06). Subsequently, two magnets (MQXFA07 and MQXFA08) did not meet some of the criteria and were disassembled. Lessons learned during the disassembly of MQXFA07 caused a revision to the assembly specifications that were used for MQXFA10 and subsequent magnets. In this article, we present a summary of: 1) the fabrication and test data for all the MQXFA magnets; 2) the analysis of MQXFA07/A08 test results with characterization of the limiting mechanism; 3) the outcome of the investigation, including the lessons learned during MQXFA07 disassembly; and 4) the finite element analysis correlating observations with test performance.
Recent work suggests that closely related cerambycid species often share pheromone components, or even produce pheromone blends of identical composition. However, little is known of the pheromones of ...species in the subfamily Prioninae. During field bioassays in California, males of three species in the prionine genus
Tragosoma
were attracted to 2,3-hexanediols, common components of male-produced aggregation pheromones of beetles in the subfamily Cerambycinae. We report here that the female-produced sex pheromone of
Tragosoma depsarium
“sp. nov. Laplante” is (2
R
,3
R
)-2,3-hexanediol, and provide evidence from field bioassays and electroantennography that the female-produced pheromone of both
Tragosoma pilosicorne
Casey and
T. depsarium
“
harrisi
” LeConte may be (2
S
,3
R
)-2,3-hexanediol. Sexual dimorphism in the sculpting of the prothorax suggests that the pheromone glands are located in the prothorax of females. This is the second sex attractant pheromone structure identified from the subfamily Prioninae, and our results provide further evidence of pheromonal parsimony within the Cerambycidae, in this case extending across both subfamily and gender lines.
The SARS-CoV-2 Alpha variant was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between Alpha ...variant infection and increased hospitalisation and 28-day mortality. However, none have addressed the impact on maximum severity of illness in the general population classified by the level of respiratory support required, or death. We aimed to do this.
In this retrospective multi-centre clinical cohort sub-study of the COG-UK consortium, 1475 samples from Scottish hospitalised and community cases collected between 1st November 2020 and 30th January 2021 were sequenced. We matched sequence data to clinical outcomes as the Alpha variant became dominant in Scotland and modelled the association between Alpha variant infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no respiratory support, 2. supplemental oxygen, 3. ventilation and 4. death.
Our cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (Alpha variant versus pre-Alpha variants).
The Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
37.
This Week in Science Vinson, Valda; Ash, Caroline; Alderton, Gemma ...
Science (American Association for the Advancement of Science),
03/2021, Letnik:
371, Številka:
6536
Journal Article
Garrett et al review the state of the art in the physical chemistry and chemical physics of electron-initiated processes in aqueous systems and raise critical research issues and fundamental ...questions that remain unanswered. Because of the complexity inherent in treating electron-driven processes in water, important questions regarding the primary chemical events remain after decades of inquiry.
This Week in Science Scanlon, Seth Thomas; Ash, Caroline; Zahn, Laura M. ...
Science (American Association for the Advancement of Science),
05/2019, Letnik:
364, Številka:
6442
Journal Article
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