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Over the last 20 years subsea processing and boosting (P&B) technologies have supported and pushed forward the offshore oil and gas production, maximizing field production and recovery factor. Although those technologies achieved remarkable success, P&B is still not a heavy-weight business, despite Operators considering it adds great value. Therefore, to enhance and maximize P&B applications, a task force was created to identify the main hurdles, showstoppers and barriers, as well as to establish a robust process, methods and procedures related, including O&G Operators and Suppliers point of views, internal standards and international codes analysis. Afterwards, a critical analysis was made, more than ten initiatives were prioritized, and a Program named Bosting to Boosting (B2B) was structured. This paper will present all initiatives have been carried out in B2B and the main results for subsea projects.

The alarming rise in superbugs that are resistant to drugs of last resort, including vancomycin-resistant enterococci and staphylococci, has become a significant global health hazard. Here, we report the click chemistry synthesis of an unprecedented class of shapeshifting vancomycin dimers (SVDs) that display potent activity against bacteria that are resistant to the parent drug, including the ESKAPE pathogens, vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), as well as vancomycin-resistant S. aureus (VRSA). The shapeshifting modality of the dimers is powered by a triazole-linked bullvalene core, exploiting the dynamic covalent rearrangements of the fluxional carbon cage and creating ligands with the capacity to inhibit bacterial cell wall biosynthesis. The new shapeshifting antibiotics are not disadvantaged by the common mechanism of vancomycin resistance resulting from the alteration of the C-terminal dipeptide with the corresponding d -Ala- d -Lac depsipeptide. Further, evidence suggests that the shapeshifting ligands destabilize the complex formed between the flippase MurJ and lipid II, implying the potential for a new mode of action for polyvalent glycopeptides. The SVDs show little propensity for acquired resistance by enterococci, suggesting that this new class of shapeshifting antibiotic will display durable antimicrobial activity not prone to rapidly acquired clinical resistance.

Supplementary Materials and Methods, Tables

Supplementary Figures S1-S9 show CD32b mRNA vs protein expression, preclinical activity of NVS32b1 vs NVS32b2, differential activation of human vs mouse FcgRs, CD32b expression on cell lines and healthy immune cells.

SuFEx click chemistry is a powerful method designed for the selective, rapid and modular synthesis of functional molecules. Classical SuFEx reactions form stable S-O linkages upon exchange of S-F bonds with aryl silyl-ether substrates, and while near-perfect in their outcome, are sometimes disadvantaged by relatively high catalyst loadings and prolonged reaction times. We herein report the development of 'Accelerated SuFEx Click Chemistry' (ASCC), an improved SuFEx method for the efficient and catalytic coupling of aryl and alkyl alcohols with a range of SuFExable hubs. We demonstrate Barton's hindered guanidine base (2- tert -butyl-1,1,3,3-tetramethylguanidine; BTMG) as a superb SuFEx catalyst that, when used in synergy with silicon additive hexamethyldisilazane (HMDS), yields stable S-O bond linkages in a single step; often within minutes. The powerful combination of BTMG and HMDS reagents allows for catalyst loadings as low as 1.0 mol% and, in congruence with click-principles, provides a scalable method that is safe, efficient, and practical for modular synthesis. ASSC expands the number of accessible SuFEx products and will find significant application in organic synthesis, medicinal chemistry, chemical biology, and materials science .

Background Antibody responses to virus reflect exposure and potential protection. Methods We developed a highly specific and sensitive approach to measuring antibodies against SARS-CoV-2 for population-scale immune surveillance. Antibody positivity was defined as a dual-positive response against both the receptor binding domain and nucleocapsid proteins of SARS-CoV-2. Antibodies were measured by immuno-precipitation assays in capillary blood from 15,771 children aged 1 to 18 years living in Bavaria, Germany, and participating in a public health type 1 diabetes screening program (Clinicaltrials.gov NCT04039945), in 1,916 dried blood spots from neonates in a Bavarian screening study (Clinicaltrials.gov NCT03316261), and in 75 SARS-CoV-2 positive individuals. Virus positive incidence was obtained from Bavarian health authority data. Findings. Dual-antibody positivity was detected in none of 3887 children in 2019 (100% specificity) and 73 of 75 SARS-CoV-2 positive individuals (97.3% sensitivity). Antibody surveillance in children during 2020 resulted in frequencies of 0.08% in January to March, 0.61% in April, 0.74% in May, 1.13% in June and 0.91% in July. Antibody prevalence from April 2020 was six-fold higher than the incidence of authority-reported cases (156 per 100,000 children), showed marked variation between the seven Bavarian regions (P, Graphical Abstract, Highlights • SARS-CoV-2 dual antibody strategy yielded 100% specificity and >95% sensitivity • Childhood surveillance finds 6-fold higher antibody prevalence than reported cases • Half of the antibody positive children were asymptomatic • No association found between SARS-Cov-2 antibodies and type 1 diabetes autoimmunity, Hippich et al developed a highly specific and sensitive dual antibody strategy for public health surveillance of SARS-CoV-2 antibody prevalence. In testing more than 11,000 children in Germany, they report an antibody prevalence that is six-fold higher than the health authority-reported SARS-CoV-2 incidence, including 50% of antibody-positive children without symptoms.

Over the last 20 years Brazil has been the stage where subsea processing and boosting (P&B) technology has supported and pushed the offshore oil and gas production to overcome its challenges and maximize field production and recovery factor. Subsea Oil-Water and Gas-Liquid Separation Systems, Multiphase Pumps, Electrical Submersible Pumps, Raw Water Injection Systems, and other innovative, enabler, optimizer or even disruptive technologies have been developing and applying in Brazil's fields to increase the NPV of projects and make feasible long tiebacks scenarios. This paper will present a retrospective of the most significant P&B systems developed and deployed in Brazil's fields, their operational experience, lessons learned, the next generation under development to surpass Pre-Salt and brown fields challenges and some initiatives to maximize these technologies applications.

Pelleted feeds (PF) are popular in horse nutrition because of high palatability and improved feeding hygiene, but ingestion is faster for PF than for cereals or muesli feed. The aim of the study was to evaluate whether variable amounts of two PFs produced with different physical properties from the same batch of feed can affect feed intake patterns in horses. Chewing patterns were measured in six warmblood mares (519 ± 36.3 kg) on two PFs (small-sized PF1: ø 5 mm, length 21.9 ± 4.97 mm, large-sized PF2: edge length 15.6 ± 0.14 × 15.6 ± 0.08 mm, length 54.4 ± 9.59 mm) in three different amounts (1.0, 1.5, 2.0 kg) once per day additional to hay. PF 2 was ingested faster than PF1 for the meal size 1.0 kg, but PF 1 was ingested more rapidly with a reduced chewing intensity if the offered meal size increased. The ingestion of PF 2 tendentially elevated the chewing intensity at higher meal sizes. An additional, but inverted meal size effect compared to 1.0 kg, was observed for 1.5 kg, where PF 1 was ingested at a higher speed combined with a lower chewing intensity compared to PF 2. Independent from the offered amount, PF 2 induced a markedly increased saliva production combined with a higher daily water intake. Larger-sized pellets seem to intensify the chewing process and decelerate the ingestion time if the meal size becomes larger.

Simple Summary Mineral deficiencies are very widespread among small ruminant herds throughout the world and play a big role in small ruminant herd health management. This paper describes the occurrence of a primary molybdenosis causing secondary copper deficiency, combined with ovine white liver disease (cobalt deficiency) and white muscle disease (selenium deficiency) in a group of pastured ram lambs in Northern Germany. To the authors’ knowledge, this is the first proven report of multiple trace element deficiencies in sheep in Germany for decades. Abstract To the author’s knowledge this paper describes the first proven report of a combined primary molybdenosis, secondary copper (Cu) deficiency, Ovine White Liver Disease—Cobalt (Co) deficiency, and selenium (Se) deficiency in a small pedigree herd of White Horned Heath sheep in Germany (8 ewes, 2 rams, 3 yearling ewes, 17 lambs) for decades. Clinical signs associated with these mineral deficiencies in a group of pastured ram lambs included emaciation, conjunctivitis, anaemia, growth retardation, discolouration of the wool and photodermatitis. Morbidities and mortalities arose in 4–6-month-old lambs despite intensive veterinary treatment in the summer of 2014 and 2015 (n = 13, 23% died). Se (3/5), Cu (4/7), and Co (3/3) deficiencies in combination with elevated values for Molybdenum (Mo, 2/2) were found. Hamburg is a large industrial city and an input of heavy metals from surrounding industries and coal-fired power stations in combination with a sandy, non-fertilised soil and monoculture grass species might offer a potential explanation for the severity of mineral deficiencies observed in this herd.

The sole inhibitory Fcγ receptor CD32b (FcγRIIb) is expressed throughout B and plasma cell development and on their malignant counterparts. CD32b expression on malignant B cells is known to provide a mechanism of resistance to rituximab that can be ameliorated with a CD32b-blocking antibody. CD32b, therefore, represents an attractive tumor antigen for targeting with a monoclonal antibody (mAb). To this end, two anti-CD32b mAbs, NVS32b1 and NVS32b2, were developed. Their complementarity-determining regions (CDR) bind the CD32b Fc binding domain with high specificity and affinity while the Fc region is afucosylated to enhance activation of FcγRIIIa on immune effector cells. The NVS32b mAbs selectively target CD32b+ malignant cells and healthy B cells but not myeloid cells. They mediate potent killing of opsonized CD32b+ cells via antibody-dependent cellular cytotoxicity and phagocytosis (ADCC and ADCP) as well as complement-dependent cytotoxicity (CDC). In addition, NVS32b CDRs block the CD32b Fc–binding domain, thereby minimizing CD32b-mediated resistance to therapeutic mAbs including rituximab, obinutuzumab, and daratumumab. NVS32b mAbs demonstrate robust antitumor activity against CD32b+ xenografts in vivo and immunomodulatory activity including recruitment of macrophages to the tumor and enhancement of dendritic cell maturation in response to immune complexes. Finally, the activity of NVS32b mAbs on CD32b+ primary malignant B and plasma cells was confirmed using samples from patients with B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma. The findings indicate the promising potential of NVS32b mAbs as a single agent or in combination with other mAb therapeutics for patients with CD32b+ malignant cells.