In vitro Efficacy of a Novel Guanosine-Analog Phosphonate

Actinic keratosis, a frequent carcinoma in situ of non-melanoma skin cancer (NMSC), can transform into life-threatening cutaneous squamous cell carcinoma. Current treatment is limited due to low complete clearance rates and asks for novel therapeutic concepts; the novel purine nucleotide analogue OxBu may be an option. In order to enhance skin penetration, solid lipid nanoparticles (SLN, 136-156 nm) were produced with an OxBu entrapment efficiency of 96.5 ± 0.1%. For improved preclinical evaluation, we combined tissue engineering with clinically used keratin-18 quantification. Three doses of 10-3 mol/l OxBu, dissolved in phosphate-buffered saline as well as loaded to SLN, were effective on reconstructed NMSC. Tumour response and apoptosis induction were evaluated by an increase in caspase-cleaved fragment of keratin-18, caspase-7 activation as well as by reduced expression of matrix metallopeptidase-2 and Ki-67. OxBu efficacy was superior to equimolar 5-fluorouracil solution, and thus the drug should be subjected to the next step in preclinical evaluation

Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients

Complete chloroplast genome sequence of Holoparasite Cistanche Deserticola (Orobanchaceae) reveals gene loss and horizontal gene transfer from Its host Haloxylon Ammodendron (Chenopodiaceae)

The central function of chloroplasts is to carry out photosynthesis, and its gene content and structure are highly conserved across land plants. Parasitic plants, which have reduced photosynthetic ability, suffer gene losses from the chloroplast (cp) genome accompanied by the relaxation of selective constraints. Compared with the rapid rise in the number of cp genome sequences of photosynthetic organisms, there are limited data sets from parasitic plants. The authors report the complete sequence of the cp genome of Cistanche deserticola, a holoparasitic desert species belonging to the family Orobanchaceae

A Dual Fluorescence–Spin Label Probe for Visualization and Quantification of Target Molecules in Tissue by Multiplexed FLIM–EPR Spectroscopy

Simultaneous visualization and concentration quantification of molecules in biological tissue is an important though challenging goal. The advantages of fluorescence lifetime imaging microscopy (FLIM) for visualization, and electron paramagnetic resonance (EPR) spectroscopy for quantification are complementary. Their combination in a multiplexed approach promises a successful but ambitious strategy because of spin label-mediated fluorescence quenching. Here, we solved this problem and present the molecular design of a dual label (DL) compound comprising a highly fluorescent dye together with an EPR spin probe, which also renders the fluorescence lifetime to be concentration sensitive. The DL can easily be coupled to the biomolecule of choice, enabling in vivo and in vitro applications. This novel approach paves the way for elegant studies ranging from fundamental biological investigations to preclinical drug research, as shown in proof-of-principle penetration experiments in human skin ex vivo

The evolution of the plastid chromosome in land plants: gene content, gene order, gene function

This review bridges functional and evolutionary aspects of plastid chromosome architecture in land plants and their putative ancestors. We provide an overview on the structure and composition of the plastid genome of land plants as well as the functions of its genes in an explicit phylogenetic and evolutionary context. We will discuss the architecture of land plant plastid chromosomes, including gene content and synteny across land plants. Moreover, we will explore the functions and roles of plastid encoded genes in metabolism and their evolutionary importance regarding gene retention and conservation. We suggest that the slow mode at which the plastome typically evolves is likely to be influenced by a combination of different molecular mechanisms. These include the organization of plastid genes in operons, the usually uniparental mode of plastid inheritance, the activity of highly effective repair mechanisms as well as the rarity of plastid fusion. Nevertheless, structurally rearranged plastomes can be found in several unrelated lineages (e.g. ferns, Pinaceae, multiple angiosperm families). Rearrangements and gene losses seem to correlate with an unusual mode of plastid transmission, abundance of repeats, or a heterotrophic lifestyle (parasites or myco-heterotrophs). While only a few functional gene gains and more frequent gene losses have been inferred for land plants, the plastid Ndh complex is one example of multiple independent gene losses and will be discussed in detail. Patterns of ndh-gene loss and functional analyses indicate that these losses are usually found in plant groups with a certain degree of heterotrophy, might rendering plastid encoded Ndh1 subunits dispensable

Hydroponic technologies

This open access book, written by world experts in aquaponics and related technologies, provides the authoritative and comprehensive overview of the key aquaculture and hydroponic and other integrated systems, socio-economic and environmental aspects. Aquaponic systems, which combine aquaculture and vegetable food production offer alternative technology solutions for a world that is increasingly under stress through population growth, urbanisation, water shortages, land and soil degradation, environmental pollution, world hunger and climate change.Hydroponics is a method to grow crops without soil, and as such, these systems are added to aquaculture components to create aquaponics systems. Thus, together with the recirculating aquaculture system (RAS), hydroponic production forms a key part of the aqua-agricultural system of aquaponics. Many different existing hydroponic technologies can be applied when designing aquaponics systems. This depends on the environmental and financial circumstances, the type of crop that is cultivated and the available space. This chapter provides an overview of different hydroponic types, including substrates, nutrients and nutrient solutions, and disinfection methods of the recirculating nutrient solutions

Stress-compensating MEMS sensor assembly

In this work, a system assembly technology will be presented that allows an effective mechanical decoupling of the MEMS element from the environment while maintaining minimal package footprint and cost. It utilizes a Si interposer with planar spring structures for an independent suspension of all interconnects to the MEMS element. The design of the planar springs was optimized for maximum stability and effectiveness using finite element analysis. The MEMS die is arranged below the interposer for mechanical protection during assembly and operation. The required clearance to the substrate is provided only by industry standard solder balls. The interposer is manufactured on a temporary carrier wafer by deep reactiveion etching, the interconnect to the MEMS die is realized by thermo-compression bonding. The effectiveness of this approach is demonstrated through the example of a high accuracy pressure sensor, although beyond that it has the potential to provide a functional package platform for MEMS sensors in a multitude of applications

LiTaO3 capping technology for wafer level chip size packaging of SAW filters

In this paper we present a novel low-cost wafer level packaging technology for surface acoustic wave (SAW) filter devices which provides quasi-hermetic device sealing and full compatibility to surface mount assembly technology. The wafer level packaging concept is based on sealing each sensitive SAW structure with a LiTaO3 cap while keeping the peripheral IO pads of the devices accessible. To enable such a process scheme LiTaO3 posts with adhesive bonding frames were pre-processed from LiTaO3 wafers and subsequently bonded to the SAW device wafers using thermo-compression type wafer-to-wafer bonding processes. Subsequently, the wafers with the pre-processed post structures were back-ground to separate the bonded cap structures on the device wafers. A subsequent balling of the peripheral pads with pre-formed SAC305 solder balls finalized the wafer level processing. The process was developed using 403 MHz SAW devices for MICS (Medical Implant Communication Service) band application. Process flow for fabrication and assembly of the SAW filter CSPs with final dimensions of 1.7 × 1.5 × 0.45 mm3 as well as the measured electrical performance will be discussed in the paper. Additionally, options for process modifications regarding size and cost reduction will be presented

Evaluation of micro structured glass layers as dielectric-and passivation material for wafer level integrated thin film capacitors and resistors

This work describes the integration of thin micro-structured glass layers into copper / benzocyclobutene (Cu/BCB) thin film multi layer. The glass, which is deposited by a low temperature PVD-PIAD process (physical vapor deposition with plasma ion assisted deposition) using special synthesized targets, was evaluated to act as local dielectric and passivation material for integrated capacitors and resistors. Metal-insulator-metal (MIM) capacitors and micro strip resonators were realized to determine the breakdown voltage as well as the dielectric constant of the material. Furthermore the glass material was used as passivation for integrated nickel-chromium (NiCr) resistors, which were evaluated regarding their maximum applicable current density, temperature coefficient of resistance as well as long-term stability. The first chapters of this paper describe the glass deposition and structuring as well as the integration of these processes into the Cu/BCB redistribution process of Fraunhofer IZM. Afterwards the fabrication of the test structures and the results from their characterization are discussed in detail