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"Andersen, Hanne"
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Empirical philosophy of science : introducing qualitative methods into philosophy of science
The book examines the emerging approach of using qualitative methods, such as interviews and field observations, in the philosophy of science. Qualitative methods are gaining popularity among philosophers of science as more and more scholars are resorting to empirical work in their study of scientific practices. At the same time, the results produced through empirical work are quite different from those gained through the kind of introspective conceptual analysis more typical of philosophy. This volume explores the benefits and challenges of an empirical philosophy of science and addresses questions such as: What do philosophers gain from empirical work? How can empirical research help to develop philosophical concepts? How do we integrate philosophical frameworks and empirical research? What constraints do we accept when choosing an empirical approach? What constraints does a pronounced theoretical focus impose on empirical work? Nine experts discuss their thoughts and empirical results in the chapters of this book with the aim of providing readers with an answer to these questions.
Book
Silicon-Carbon composite anodes from industrial battery grade silicon
In this work, silicon/carbon composites for anode electrodes of Li-ion batteries are prepared from Elkem’s Silgrain® line. Gentle ball milling is used to reduce particle size of Silgrain, and the resulting Si powder consists of micrometic Si with some impurities. Silicon/carbon composite with CMC/SBR as a dual binder can achieve more than 1200 cycles with a capacity of 1000 mAh g
−1
of Si. This excellent electrochemical performance can be attributed to the use of a buffer as a solvent to control the pH of the electrode slurry, and hence the bonding properties of the binder to the silicon particles. In addition, the use of FEC as an electrolyte additive is greatly contributing to a stabilized cycling by creating a more robust SEI layer. This work clearly demonstrates the potential of industrial battery grade silicon from Elkem.
Journal Article
Correlates of protection against SARS-CoV-2 in rhesus macaques
Recent studies have reported the protective efficacy of both natural
1
and vaccine-induced
2
–
7
immunity against challenge with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in rhesus macaques. However, the importance of humoral and cellular immunity for protection against infection with SARS-CoV-2 remains to be determined. Here we show that the adoptive transfer of purified IgG from convalescent rhesus macaques (
Macaca mulatta
) protects naive recipient macaques against challenge with SARS-CoV-2 in a dose-dependent fashion. Depletion of CD8
+
T cells in convalescent macaques partially abrogated the protective efficacy of natural immunity against rechallenge with SARS-CoV-2, which suggests a role for cellular immunity in the context of waning or subprotective antibody titres. These data demonstrate that relatively low antibody titres are sufficient for protection against SARS-CoV-2 in rhesus macaques, and that cellular immune responses may contribute to protection if antibody responses are suboptimal. We also show that higher antibody titres are required for treatment of SARS-CoV-2 infection in macaques. These findings have implications for the development of SARS-CoV-2 vaccines and immune-based therapeutic agents.
Adoptive transfer of purified IgG from convalescent macaques protects naive macaques against SARS-CoV-2 infection, and cellular immune responses contribute to protection against rechallenge with SARS-CoV-2.
Journal Article
The Cognitive Structure of Scientific Revolutions
Thomas Kuhn's Structure of Scientific Revolutions became the most widely read book about science in the twentieth century. His terms 'paradigm' and 'scientific revolution' entered everyday speech, but they remain controversial. In the second half of the twentieth century, the new field of cognitive science combined empirical psychology, computer science, and neuroscience. In this book, the theories of concepts developed by cognitive scientists are used to evaluate and extend Kuhn's most influential ideas. Based on case studies of the Copernican revolution, the discovery of nuclear fission, and an elaboration of Kuhn's famous 'ducks and geese' example of concept learning, this volume, first published in 2006, offers accounts of the nature of normal and revolutionary science, the function of anomalies, and the nature of incommensurability.
eBook
Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection
Barney Graham and colleagues have developed a hemagglutinin stem–based nanoparticle as a vaccine that confers protection against different influenza strains in mice and ferrets.
The antibody response to influenza is primarily focused on the head region of the hemagglutinin (HA) glycoprotein, which in turn undergoes antigenic drift, thus necessitating annual updates of influenza vaccines. In contrast, the immunogenically subdominant stem region of HA is highly conserved and recognized by antibodies capable of binding multiple HA subtypes
1
,
2
,
3
,
4
,
5
,
6
. Here we report the structure-based development of an H1 HA stem–only immunogen that confers heterosubtypic protection in mice and ferrets. Six iterative cycles of structure-based design (Gen1–Gen6) yielded successive H1 HA stabilized-stem (HA–SS) immunogens that lack the immunodominant head domain. Antigenic characterization, determination of two HA–SS crystal structures in complex with stem-specific monoclonal antibodies and cryo-electron microscopy analysis of HA–SS on ferritin nanoparticles (H1–SS–np) confirmed the preservation of key structural elements. Vaccination of mice and ferrets with H1–SS–np elicited broadly cross-reactive antibodies that completely protected mice and partially protected ferrets against lethal heterosubtypic H5N1 influenza virus challenge despite the absence of detectable H5N1 neutralizing activity
in vitro
. Passive transfer of immunoglobulin from H1–SS–np–immunized mice to naive mice conferred protection against H5N1 challenge, indicating that vaccine-elicited HA stem–specific antibodies can protect against diverse group 1 influenza strains.
Journal Article
Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans
1
. CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12 μg lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (
n
= 6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates.
CV2CoV, a second-generation mRNA COVID-19 vaccine with non-modified nucleosides but optimized non-coding regions, is demonstrated to be effective against SARS-CoV-2 challenge when tested in non-human primates.
Journal Article
Sarcopenia and osteoporosis in older people: a systematic review and meta-analysis
Background
Age-related loss of muscle and bone (sarcopenia and osteoporosis), increases the risk of falls and fractures and consequently leads to a substantial economic burden for the society. The combined condition, osteosarcopenia, may identify patients at a higher risk of those outcomes and could be relevant for assessment and treatment in clinical practice.
Aim
To evaluate the current knowledge of the prevalence of osteosarcopenia and the fracture risk in older people.
Method
A systematic literature review was conducted until 10th March 2018. A total of 1105 papers were detected, whereof 1049 and 29 were excluded by title/abstracts and full-text assessment, respectively. Twenty-seven original papers were included in the systematic review, whereof 17 were suitable for meta-analysis.
Results
The prevalence of osteosarcopenia varied (5–37%) depending on the classification of sarcopenia and whether participants were classified initially according to sarcopenia or osteoporosis. In patients with low-energy osteoporotic fractures, sarcopenia was present in 7.8–58% and 1.3–96.3% of the cases, women and men, respectively. The meta-analysis of prevalence of sarcopenia in patients with low-energy fracture (
n
= 9) was 46% (95% CI 44, 48;
p
< 0.001). The relative risk of fracture (sarcopenic versus non-sarcopenic) in meta-analysis of four studies was 1.37 (95% CI 1.18, 1.59;
p
< 0.001). Mean bone mineral density (
n
= 5) and T-score (
n
= 3) of femoral neck was significantly lower in sarcopenic participants [− 0.07 g/cm
2
(95% CI 0.08, 0.06) and − 0.34 (95% CI − 0.46, − 0.23), respectively].
Conclusion
Osteosarcopenia is frequent and the relative risk of fracture is higher among sarcopenic patients. A standard and strict classification of sarcopenia is needed to assess its true relationship and consequences.
Journal Article
SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution
SARS-CoV-2 variants of interest and concern will continue to emerge for the duration of the COVID-19 pandemic. To map mutations in the receptor-binding domain (RBD) of the spike protein that affect binding to angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, we applied in vitro evolution to affinity-mature the RBD. Multiple rounds of random mutagenic libraries of the RBD were sorted against decreasing concentrations of ACE2, resulting in the selection of higher affinity RBD binders. We found that mutations present in more transmissible viruses (S477N, E484K and N501Y) were preferentially selected in our high-throughput screen. Evolved RBD mutants include prominently the amino acid substitutions found in the RBDs of B.1.620, B.1.1.7 (Alpha), B1.351 (Beta) and P.1 (Gamma) variants. Moreover, the incidence of RBD mutations in the population as presented in the GISAID database (April 2021) is positively correlated with increased binding affinity to ACE2. Further in vitro evolution increased binding by 1,000-fold and identified mutations that may be more infectious if they evolve in the circulating viral population, for example, Q498R is epistatic to N501Y. We show that our high-affinity variant RBD-62 can be used as a drug to inhibit infection with SARS-CoV-2 and variants Alpha, Beta and Gamma in vitro. In a model of SARS-CoV-2 challenge in hamster, RBD-62 significantly reduced clinical disease when administered before or after infection. A 2.9 Å cryo-electron microscopy structure of the high-affinity complex of RBD-62 and ACE2, including all rapidly spreading mutations, provides a structural basis for future drug and vaccine development and for in silico evaluation of known antibodies.
Evolution of the SARS-CoV-2 spike protein receptor-binding domain in vitro recapitulates SARS-CoV-2 variant emergence and produces an effective antiviral spike receptor-binding domain variant.
Journal Article
Substoichiometric Silicon Nitride – An Anode Material for Li-ion Batteries Promising High Stability and High Capacity
Silicon is often regarded as a likely candidate to replace graphite as the main active anode material in next-generation lithium ion batteries; however, a number of problems impacting its cycle stability have limited its commercial relevance. One approach to solving these issues involves the use of convertible silicon sub-oxides. In this work we have investigated amorphous silicon sub-nitride as an alternative convertible silicon compound by comparing the electrochemical performance of a-SiN
x
thin films with compositions ranging from pure Si to SiN
0.89
. We have found that increasing the nitrogen content gradually reduces the reversible capacity of the material, but also drastically increases its cycling stability, e.g. 40 nm a-SiN
0.79
thin films exhibited a stable capacity of more than 1,500 mAh/g for 2,000 cycles. Consequently, by controlling the nitrogen content, this material has the exceptional ability to be tuned to satisfy a large range of different requirements for capacity and stability.
Journal Article