Intrinsically Polar Elastic Metamaterials

In many applications, one needs to combine materials with varying properties to achieve certain functionalities. For example, the inner layer of a helmet should be soft for cushioning while the outer shell should be rigid to provide protection. Over time, these combined materials either separate or wear and tear, risking the exposure of an undesired material property. This work presents a design principle for a material that gains unique properties from its 3D microstructure, consisting of repeating basic building blocks, rather than its material composition. The 3D printed specimens show, at two of its opposing faces along the same axis, different stiffness (i.e., soft on one face and hard on the other). The realized material is protected by design (i.e., topology) against cuts and tears: No matter how material is removed, either layer by layer, or in arbitrary cuts through the repeating building blocks, two opposing faces remain largely different in their mechanical response

In vitro functional assays to assess the reciprocal interplay between tumor cells and macrophages.

Tumor-associated macrophages (TAMs) are integral components of the tumor microenvironment. They are involved in various aspects of tumor cell biology, driving pathological processes such as tumor cell proliferation, metastasis, immunosuppression, and resistance to therapy. TAMs exert their tumorigenic effects by secreting growth factors, cytokines/chemokines, metabolites, and other soluble bioactive molecules. These mediators directly promote tumor cell proliferation and modulate interactions with immune and stromal cells, facilitating further tumor growth. As research into therapies targeting TAMs intensifies, there is a growing need for reliable methods to comprehend the impact of TAMs on cancer progression and to validate novel therapeutics directed at TAMs. The traditional "M1-M2" macrophage classification based on transcriptional profiles of TAMs is not only too simplistic to describe their physiological roles, it also does not explain differences observed between mouse and human macrophages. In this context, methods that assess how TAMs influence tumor or immune cells, either through direct contact or the release of soluble factors, offer a more promising approach. We describe here comprehensive protocols for in vitro functional assays to study TAMs, specifically regarding their impact on the growth of lung cancer cells. We have applied these methods to both mouse and human macrophages, achieving similar outcomes in promoting the proliferation of cancer cells. This methodology can serve as a standardized approach for testing novel therapeutic approaches, targeting TAMs with novel immunotherapeutic compounds, or utilizing gene-editing techniques. Taken together, the described methodology may contribute to our understanding of complex macrophage-tumor interactions and support the development of innovative therapeutic strategies

Observation of a phononic quadrupole topological insulator

The modern theory of charge polarization in solids is based on a generalization of Berry’s phase. The possibility of the quantization of this phase arising from parallel transport in momentum space is essential to our understanding of systems with topological band structures. Although based on the concept of charge polarization, this same theory can also be used to characterize the Bloch bands of neutral bosonic systems such as photonic or phononic crystals. The theory of this quantized polarization has recently been extended from the dipole moment to higher multipole moments. In particular, a two-dimensional quantized quadrupole insulator is predicted to have gapped yet topological one-dimensional edge modes, which stabilize zero-dimensional in-gap corner states. However, such a state of matter has not previously been observed experimentally. Here we report measurements of a phononic quadrupole topological insulator. We experimentally characterize the bulk, edge and corner physics of a mechanical metamaterial (a material with tailored mechanical properties) and find the predicted gapped edge and in-gap corner states. We corroborate our findings by comparing the mechanical properties of a topologically non-trivial system to samples in other phases that are predicted by the quadrupole theory. These topological corner states are an important stepping stone to the experimental realization of topologically protected wave guides in higher dimensions, and thereby open up a new path for the design of metamaterials

Observation of a phononic quadrupole topological insulator

The modern theory of charge polarization in solids is based on a generalization of Berry’s phase. The possibility of the quantization of this phase arising from parallel transport in momentum space is essential to our understanding of systems with topological band structures. Although based on the concept of charge polarization, this same theory can also be used to characterize the Bloch bands of neutral bosonic systems such as photonic or phononic crystals. The theory of this quantized polarization has recently been extended from the dipole moment to higher multipole moments. In particular, a two-dimensional quantized quadrupole insulator is predicted to have gapped yet topological one-dimensional edge modes, which stabilize zero-dimensional in-gap corner states. However, such a state of matter has not previously been observed experimentally. Here we report measurements of a phononic quadrupole topological insulator. We experimentally characterize the bulk, edge and corner physics of a mechanical metamaterial (a material with tailored mechanical properties) and find the predicted gapped edge and in-gap corner states. We corroborate our findings by comparing the mechanical properties of a topologically non-trivial system to samples in other phases that are predicted by the quadrupole theory. These topological corner states are an important stepping stone to the experimental realization of topologically protected wave guides in higher dimensions, and thereby open up a new path for the design of metamaterials

A Novel, “Double-Clamp” Binding Mode for Human Heme Oxygenase-1 Inhibition

The development of heme oxygenase (HO) inhibitors is critical in dissecting and understanding the HO system and for potential therapeutic applications. We have established a program to design and optimize HO inhibitors using structure-activity relationships in conjunction with X-ray crystallographic analyses. One of our previous complex crystal structures revealed a putative secondary hydrophobic binding pocket which could be exploited for a new design strategy by introducing a functional group that would fit into this potential site. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have synthesized and characterized 1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone (QC-308). Using a carbon monoxide (CO) formation assay on rat spleen microsomes, the compound was found to be ∼15 times more potent (IC50 = 0.27±0.07 µM) than its monophenyl analogue, which is already a potent compound in its own right (QC-65; IC50 = 4.0±1.8 µM). The crystal structure of hHO-1 with QC-308 revealed that the second phenyl group in the western region of the compound is indeed accommodated by a definitive secondary proximal hydrophobic pocket. Thus, the two phenyl moieties are each stabilized by distinct hydrophobic pockets. This “double-clamp” binding offers additional inhibitor stabilization and provides a new route for improvement of human heme oxygenase inhibitors

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

A Bio-Catalytic Approach to Aliphatic Ketones

Depleting oil reserves and growing environmental concerns have necessitated the development of sustainable processes to fuels and chemicals. Here we have developed a general metabolic platform in E. coli to biosynthesize carboxylic acids. By engineering selectivity of 2-ketoacid decarboxylases and screening for promiscuous aldehyde dehydrogenases, synthetic pathways were constructed to produce both C5 and C6 acids. In particular, the production of isovaleric acid reached 32 g/L (0.22 g/g glucose yield), which is 58% of the theoretical yield. Furthermore, we have developed solid base catalysts to efficiently ketonize the bio-derived carboxylic acids such as isovaleric acid and isocaproic acid into high volume industrial ketones: methyl isobutyl ketone (MIBK, yield 84%), diisobutyl ketone (DIBK, yield 66%) and methyl isoamyl ketone (MIAK, yield 81%). This hybrid “Bio-Catalytic conversion” approach provides a general strategy to manufacture aliphatic ketones, and represents an alternate route to expanding the repertoire of renewable chemicals

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age