Background: Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance. Patients and methods: Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 3

Most land-living organisms regularly experience dehydration. In nature, one commonly applied strategy to protect against this osmotic stress is to introduce small polar molecules with low vapor pressure, commonly called osmolytes. Two examples of naturally occurring small polar compounds are urea and trimethylamine N-oxide (TMAO), which are known to have counteracting effects on protein stability.

The outer layer of the skin, stratum corneum (SC) is an efficient transport barrier and it tolerates mechanical deformation. At physiological conditions, the majority of SC lipids are solid, while the presence of a small amount of fluid lipids is considered crucial for SC barrier and material properties. Here we use solid-state and diffusion nuclear magnetic resonance to characterize the compositi

An international panel of experts representing 17 European countries and Israel convened to discuss current needs and future developments in BRCA testing and counselling and to issue consensus recommendations. The experts agreed that, with the increasing availability of high-throughput testing platforms and the registration of poly-ADP-ribose-polymerase inhibitors, the need for genetic counselling

When including relativistic effects in quantum chemical calculations, basis sets optimized for relativistic Hamiltonians such as the atomic natural orbital-relativistic core-correlated (ANO-RCC) basis set have to be used to avoid large errors that appear upon contraction of the basis set. While the large size of the ANO-RCC basis set in terms of primitive basis functions allows for highly accurate

BACKGROUND: The role of vitamin D in obesity and diabetes is debated. Obese and/or diabetic patients have elevated levels of free fatty acids, increased susceptibility to gastrointestinal symptoms and are suggested to have altered vitamin D balance. The enteric nervous system is pivotal in regulating gastrointestinal activity and high fat diet (HFD) has been shown to cause loss of enteric neurons

Allemansrätten påverkar bostadsbyggandet genom dess betydelse för detaljplaner, bygglov och fastighetsbildning. Det blir lätt snårig juridik när olika myndigheter och intressen möts och det gäller att hålla isär begrepp som strandskydd, fastighet, tomt och hemfridszon för att bena ut vad som egentligen gäller.

In this presentation we review the evolution of radio access networks and introduce 5G, based on the current plans and expectations, as reported in the recent series of the Ericsson Mobility Reports. Standardization is an on-going effort, and much industry research is devoted to finding a good match of requirements - balancing system performance, flexibility and implementation imphcations. We pres

Botulinum neurotoxins are highly toxic substances and are all encoded together with one of two alternative gene clusters, the HA or the OrfX gene cluster. Very little is known about the function and structure of the proteins encoded in the OrfX gene cluster, which in addition to the toxin contains five proteins (OrfX1, OrfX2, OrfX3, P47, and NTNH). We here present the structures of OrfX2 and P47,

Fragment-based lead discovery has emerged as a leading drug development strategy for novel therapeutic targets. Although fragment-based drug discovery benefits immensely from access to atomic-resolution information, structure-based virtual screening has rarely been used to drive fragment discovery and optimization. Here, molecular docking of 0.3 million fragments to a crystal structure of cancer t

Here we present a two-step diastereoselective methodology building on a multicomponent aza-Diels-Alder reaction. Using previously unexplored cyclic ketones, heterocyclic amines and cyclopentadiene derivatives, we obtained novel spiro-heterocyclic frameworks at the interphase between "drug-like" molecules and natural products.

Botulinum neurotoxins are known to have seven serotypes (BoNT/A-G). Here we report a new BoNT serotype, tentatively named BoNT/X, which has the lowest sequence identity with other BoNTs and is not recognized by antisera against known BoNTs. Similar to BoNT/B/D/F/G, BoNT/X cleaves vesicle-associated membrane proteins (VAMP) 1, 2 and 3, but at a novel site (Arg66-Ala67 in VAMP2). Remarkably, BoNT/X

Botulinum neurotoxin B is a Food and Drug Administration-approved therapeutic toxin. However, it has lower binding affinity toward the human version of its major receptor, synaptotagmin II (h-Syt II), compared to mouse Syt II, because of a residue difference. Increasing the binding affinity to h-Syt II may improve botulinum neurotoxin B's therapeutic efficacy and reduce adverse effects. Here we ut

The tetanus neurotoxin (TeNT) is a highly potent toxin produced by Clostridium tetani that inhibits neurotransmission of inhibitory interneurons, causing spastic paralysis in the tetanus disease. TeNT differs from the other clostridial neurotoxins by its unique ability to target the central nervous system by retrograde axonal transport. The crystal structure of the tetanus toxin reveals a "closed"

In this article, we review the evolution of radio access networks and introduce fifth generation (5G), based on the current plans and expectations, as reported in the 2017 Ericsson Mobility Reports. Standardization is an ongoing effort, and much industry research is devoted to finding a good match of requirements, including balancing system performance, flexibility, and implementation implications

The use of a wake-up receiver (WUR) is an attractive means to reduce power consumption. However, when the wake-up signal (WUS) is sent in-band, the use of a WUR may potentially reduce the spectrum efficiency of the system. In this paper, we propose to multiplex the WUS, based on ON-OFF keying, with the user data using FDMA or OFDMA to allow for spectrum efficient use of WURs. The proposed WUR arch