The rise of intelligent matter.

Artificial intelligence (AI) is accelerating the development of unconventional computing paradigms inspired by the abilities and energy efficiency of the brain. The human brain excels especially in computationally intensive cognitive tasks, such as pattern recognition and classification. A long-term goal is de-centralized neuromorphic computing, relying on a network of distributed cores to mimic the massive parallelism of the brain, thus rigorously following a nature-inspired approach for information processing. Through the gradual transformation of interconnected computing blocks into continuous computing tissue, the development of advanced forms of matter exhibiting basic features of intelligence can be envisioned, able to learn and process information in a delocalized manner. Such intelligent matter would interact with the environment by receiving and responding to external stimuli, while internally adapting its structure to enable the distribution and storage (as memory) of information. We review progress towards implementations of intelligent matter using molecular systems, soft materials or solid-state materials, with respect to applications in soft robotics, the development of adaptive artificial skins and distributed neuromorphic computing.

Effectiveness, safety and quality-of-life effects of guselkumab and ustekinumab in patients with psoriasis: Week 104 results from the non-interventional, prospective, German multicentre PERSIST study.

BACKGROUND: PERSIST was a prospective, non-interventional, real-world study of guselkumab and ustekinumab in adult patients with moderate-to-severe plaque psoriasis in Germany. OBJECTIVES: To examine effectiveness, safety and quality-of-life (QoL) outcomes to Week (W) 104 of treatment with guselkumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. METHODS: Patients (≥18 years of age) received guselkumab or ustekinumab as per routine clinical practice. Outcomes to W104 were examined separately in guselkumab and ustekinumab recipients. An ad hoc exploratory analysis of outcomes with guselkumab versus ustekinumab was also performed following propensity score matching. RESULTS: Overall, 302 and 313 patients received guselkumab and ustekinumab, respectively. Patients in both cohorts experienced improvements in disease activity and QoL that were maintained to W104, with 64.7% and 63.6% of guselkumab- and 54.6% and 64.4% of ustekinumab-treated patients achieving a Psoriasis Area and Severity Index (PASI) 90 response and a Dermatology Life Quality Index (DLQI) 0/1 score, respectively. Propensity score matching yielded well-balanced baseline characteristics except for prior biologic use, which was higher in guselkumab versus ustekinumab recipients (51.7% vs. 32.0%). Achievement of PASI ≤1 at W104 was more common in guselkumab versus ustekinumab recipients (58.7% vs. 49.7%). The W104 PASI90 response rate was 65.6% with guselkumab and 56.0% with ustekinumab; corresponding rates for PASI100 were 44.3% and 28.5%. In guselkumab recipients, response rates were higher in biologic-naïve versus biologic-experienced patients (PASI90, 77.1% vs. 53.4%; PASI100, 55.0% vs. 33.0%). A high level of response for QoL outcomes was observed for both treatments. CONCLUSIONS: Ustekinumab and guselkumab led to improvements in physician-assessed and patient-reported outcomes that were sustained for up to 2 years, with no new safety signals identified. Following propensity score matching, greater improvements in PASI outcomes were observed with guselkumab versus ustekinumab. Improvements with guselkumab were highest in biologic-naïve patients, highlighting the value of early treatment.

Early disease intervention with guselkumab in psoriasis leads to a higher rate of stable complete skin clearance ('clinical super response'): Week 28 results from the ongoing phase IIIb randomized, double-blind, parallel-group, GUIDE study.

BACKGROUND: Guselkumab is an interleukin (IL)-23 inhibitor with demonstrated efficacy in patients with psoriasis. OBJECTIVES: Evaluate the impact of early disease intervention on clinical responses following 28 weeks of guselkumab treatment in patients with moderate-to-severe plaque psoriasis. Correlate clinical response and disease duration data with serum biomarker data. METHODS: GUIDE is a phase IIIb randomized, double-blind, parallel-group, multicentre study of adults with moderate-to-severe plaque psoriasis. In study part 1, patients with a short disease duration (SDD [≤2 years]) or a long disease duration (LDD [>2 years]) received guselkumab 100 mg at Week (W) 0, 4, 12, and 20. Those achieving complete skin clearance at W20 and W28 were defined as a super responder (SRe). A multivariable logistic regression analysed the association between baseline factors and the likelihood of becoming an SRe. The relationship between clinical response, disease duration and serum biomarker data was assessed at W0 and 4. RESULTS: In total, 880 patients were enrolled (SDD/LDD = 40.6%/59.4% of patients). More SDD than LDD patients achieved absolute Psoriasis Area and Severity Index (PASI) = 0 at W28 (51.8% vs. 39.4%) and were SRes (43.7% vs. 28.1% [overall 34.4%]). SDD patients also achieved PASI = 0 quicker than LDD patients (median 141 vs. 200 days). Disease duration and prior biologic use had the greatest impact on becoming an SRe, with no strong association among these independent variables. At baseline, there were no significant differences in the serum biomarker levels of IL-17A, IL-17F, IL-22 and ß-defensin 2 between SDD and LDD patients, or between SRe and non-SRe patients. Guselkumab rapidly decreased these markers of systemic inflammation across all patient groups analysed at W4. Guselkumab was well tolerated. CONCLUSIONS: Guselkumab efficacy was consistent across subpopulations, on the skin and systemically. The proportion of SRes was higher in SDD than LDD patients, indicating early treatment intervention may improve clinical outcomes.

Real-world evidence from the non-interventional, prospective, German multicentre PERSIST study of patients with psoriasis after 1 year of treatment with guselkumab.

BACKGROUND: PERSIST was a prospective, non-interventional, long-term, German multicentre study of patients with moderate-to-severe psoriasis receiving guselkumab, an approved monoclonal antibody that binds to the p19 subunit of interleukin (IL)-23, in a real-world setting. OBJECTIVES: Evaluation of the efficacy and safety of guselkumab, and its effect on health-related quality of life (HRQoL), in patients with moderate-to-severe psoriasis who have received 52 weeks of treatment. METHODS: Patients (≥18 years old) were prescribed guselkumab as per routine clinical practice. End points assessed include Psoriasis Area and Severity Index (PASI), Physician's Global Assessment (PGA), target Nail Psoriasis Severity Index (NAPSI), and the Dermatology Life Quality Index (DLQI). RESULTS: Overall, 303 patients were enrolled and treated with guselkumab. Mean disease duration was 21.0 years, and 77.2% and 51.2% of patients had received ≥1 prior conventional systemic or ≥1 prior biologic therapy, respectively. Mean PASI score decreased from 16.4 at baseline to 3.0 by Week (W) 28, and further decreased to 2.4 by W52, while the proportion of patients achieving an absolute PASI score of ≤1 increased from 1.3% at baseline, to 50.8% at W28 and to 58.4% by W52. PASI90 and PASI100 responses also showed marked improvements between W28 and W52, regardless of biologic treatment history. Clearance of psoriatic skin was observed in difficult-to-treat areas, with the percentage of patients achieving a PGA score ≤1 increasing between W28 and W52. Guselkumab improved HRQoL; mean DLQI score decreased from 13.7 at baseline to 2.8 by W28, and further decreased to 2.4 by W52. At W52, 64.6% of patients achieved a DLQI score ≤1. The cumulative probability of drug survival was 92.4% at W52. CONCLUSIONS: Guselkumab is efficacious and well tolerated regardless of previous biologic therapies, comorbidities or psoriasis manifestation in difficult-to-treat areas. No new safety signals were observed.

Guselkumab is superior to fumaric acid esters in patients with moderate-to-severe plaque psoriasis who are naive to systemic treatment: results from a randomized, active-comparator-controlled phase IIIb trial (POLARIS).

BACKGROUND: Guselkumab, a fully human interleukin-23 antibody, is approved for systemic treatment of patients with moderate-to-severe plaque psoriasis. OBJECTIVES: To compare the efficacy and safety of guselkumab with those of fumaric acid esters (FAE) in patients with moderate-to-severe plaque psoriasis who are naive to systemic treatment. METHODS: Eligible patients were randomized to this multicentre, randomized, open-label, assessor-blinded, active-comparator-controlled phase IIIb study to receive guselkumab 100 mg by subcutaneous injection or oral FAE according to local label guidelines. RESULTS: Through week 24, 56 of 60 patients completed guselkumab treatment and 36 of 59 completed FAE treatment. The primary endpoint (proportion of patients with ≥ 90% improvement from their baseline Psoriasis Area and Severity Index; PASI 90 response) was achieved by significantly more patients receiving guselkumab than FAE at week 24 (82% vs. 14%, P < 0·001). Analysis of the major secondary endpoints confirmed a statistically significant difference between the treatments with regards to PASI 75 response (90% vs. 27%, P < 0·001) and Dermatology Life Quality Index score of 0 or 1 (no effect at all on the patient's quality of life; 62% vs. 17%, P < 0·001). More patients in the guselkumab group achieved completely clear skin (PASI 100 response) than in the FAE group (32% vs. 3%, P < 0·001). The incidence of adverse events was lower with guselkumab than with FAE (73% vs. 98%). Overall, 28% of patients on FAE discontinued due to an adverse event, compared with none receiving guselkumab. No new safety findings were observed for guselkumab. CONCLUSIONS: Guselkumab demonstrated superiority over FAE in systemic-treatment-naive patients with moderate-to-severe plaque psoriasis through 24 weeks.

Outflow and clogging of shape-anisotropic grains in hoppers with small apertures.

Outflow of granular material through a small orifice is a fundamental process in many industrial fields, for example in silo discharge, and in everyday's life. Most experimental studies of the dynamics have been performed so far with monodisperse disks in two-dimensional (2D) hoppers or spherical grains in 3D. We investigate this process for shape-anisotropic grains in 3D hoppers and discuss the role of size and shape parameters on avalanche statistics, clogging states, and mean flow velocities. It is shown that an increasing aspect ratio of the grains leads to lower flow rates and higher clogging probabilities compared to spherical grains. On the other hand, the number of grains forming the clog is larger for elongated grains of comparable volumes, and the long axis of these blocking grains is preferentially aligned towards the center of the orifice. We find a qualitative transition in the hopper discharge behavior for aspect ratios larger than ≈6. At still higher aspect ratios >8-12, the outflowing material leaves long vertical holes in the hopper that penetrate the complete granular bed. This changes the discharge characteristics qualitatively.

Combined use of EPR and 23Na MAS NMR spectroscopy for assessing the properties of the mixed cobalt-nickel-manganese layers of P3-NayCo1-2xNixMnxO2.

Knowledge on the formation of mixed transition metal layers on lithium and sodium transition metal oxides, Li/Na(Co,Ni,Mn,)O2, determines the ability to control their electrochemical properties as electrode materials in alkaline ion batteries. Taking this into account, herein we combine the EPR and 23Na MAS NMR spectroscopic techniques to gain insights into the structural peculiarities of the mixed cobalt-nickel-manganese layers of NayCo1-2xNixMnxO2 with a three-layer stacking (P3-type) structure. Two types of compositions are examined where diamagnetic Co3+ and paramagnetic Ni3+ and Mn4+ are stabilized: Na2/3Co1/3Ni1/3Mn1/3O2 and Na1/2Ni1/2Mn1/2O2. EPR spectroscopy operating in the X- and Q-band region is applied with an aim to improve the spectra resolution and, on the other hand, to provide straightforward information on the coordination of the transition metal ions inside the layers. The analysis of EPR spectra is based on the reference for the Mn4+ and Ni2+ ions occurring simultaneously in oxides with two layer stacking, P2-Na2/3Ni1/3Mn2/3O2. Complementary to EPR, 23Na MAS NMR spectroscopy at high spinning rates is undertaken to assess the local structure of the Na nucleus in the layered P3-NayCo1-2xNixMnxO2 oxides. All results are discussed taking into account the EPR and NMR data for the well-known lithium analogues O3-LiCo1/3Ni1/3Mn1/3O2 and O3-LiNi1/2Mn1/2O2. Finally, the structure peculiarities of the transition metal layers extracted from the EPR and NMR methods are demonstrated by electrochemical intercalation of Li+ ions into P3-NayCo1-2xNixMnxO2.

Minimizing the t1-noise when using an indirect 1H high-resolution detection of unlabeled samples.

The most utilized through-space correlation 1H-{X} methods with proton indirect detection use two consecutive transfers, 1H â†’ X and then X â†’ 1H, with the evolution time t1 in the middle. When the X isotope is not 100% naturally abundant (NA), only the signal of the protons close to these isotopes is modulated by the 1H-X dipolar interactions. This signal is theoretically disentangled with phase-cycling from the un-modulated one. However, this separation is never perfect and it may lead to t1-noise in case of isotopes with very small NA, such as 13C or even worse 15N. One way to reduce this t1-noise is to minimize, 'purge', during t1 the un-modulated 1H magnetization before trying to suppress it with phase-cycling. We analyze experimentally several sequences following the HORROR condition, which allow purging the 1H transverse magnetization. The comparison is made at three spinning speeds, including very fast ones for 1H resolution: 27.75, 55.5 and 111 kHz. We show (i) that the efficiency of this purging process increases with the spinning speed, and (ii) that the best recoupling sequences are the two simplest ones: XY and S1 = SR212. We then compare the S/N that can be achieved with the two most used 1H-{X} 2D methods, called D-HMQC and CP-CP. The only difference in between these two methods is that the transfers are done with either two π/2-pulses on X channel (D-HMQC), or two Cross-Polarization (CP) transfers (CP-CP). The first method, D-HMQC, is very robust and should be preferred when indirectly detecting nuclei with high NA. The second method, CP-CP, (i) requires experimental precautions to limit the t1-noise, and (ii) is difficult to use with quadrupolar nuclei because the two CP transfers are then not efficient nor robust. However, CP-CP is presently the best method to indirectly detect isotopes with small NA, such as 13C and 15N.

A highly specific competitive direct enzyme immunoassay for sterigmatocystin as a tool for rapid immunochemotaxonomic differentiation of mycotoxigenic Aspergillus species.

A simplified method to produce specific polyclonal rabbit antibodies against sterigmatocystin (STC) was established, using a STC-glycolic acid-ether derivative (STC-GE) conjugated to keyhole limpet haemocyanin (immunogen). The competitive direct enzyme immunoassay (EIA) established for STC had a detection limit (20% binding inhibition) of 130 pg ml-1 . The test was highly specific for STC, with minor cross-reactivity with O-methylsterigmatocystin (OMSTC, 0·87%) and negligible reactivity with aflatoxins (<0·02%). STC-EIA was used in combination with a previously developed specific EIA for aflatoxins (<0·1% cross-reactivity with STC and OMSTC), to study the STC/aflatoxin production profiles of reference strains of Aspergillus species. This immunochemotaxonomic procedure was found to be a convenient tool to identify STC- or aflatoxin-producing strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The carcinogenic mycotoxin sterigmatocystin (STC) is produced by several Aspergillus species, either alone or together with aflatoxins. Here, we report a very simple and straightforward procedure to obtain highly sensitive and specific anti-STC antibodies, and their use in the first ever real STC-specific competitive direct enzyme immunoassay (EIA). In combination with a previous EIA for aflatoxins, this study for the first time demonstrates the potential of a STC/aflatoxin EIA pair for what is branded as 'immunochemotaxonomic' identification of mycotoxigenic Aspergillus species. This new analytical tool enhances analytical possibilities for differential analysis of STC and aflatoxins.

High throughput transepithelial electrical resistance (TEER) measurements on perfused membrane-free epithelia.

Assessment of epithelial barrier function is critically important for studying healthy and diseased biological models. Here we introduce an instrument that measures transepithelial electrical resistance (TEER) of perfused epithelial tubes in the microfluidic OrganoPlate platform. The tubules are grown in microfluidic channels directly against an extracellular matrix, obviating the need for artificial filter membranes. We present TEER measurements on Caco-2 intestinal and renal proximal tubule epithelium. Forty tubules on one single plate were interrogated in less than a minute. We show that TEER measurement is significantly more sensitive than a fluorescent reporter leakage assay in response to staurosporine. We demonstrate a 40-channel time-lapse data acquisition over a 25 hour time period under flow conditions. We furthermore observed a 50% reduction in Caco-2 TEER values following exposure to a cocktail of inflammatory cytokines. To our best knowledge, this is the first instrument of its kind that allows routine TEER studies in perfused organ-on-a-chip systems without interference by artificial filter membranes. We believe the apparatus will contribute to accelerating routine adoption of perfused organ-on-a-chip systems in academic research and in industrial drug development.

Light controlled cell-to-cell adhesion and chemical communication in minimal synthetic cells.

Decorating GUVs, used as minimal synthetic cell models, with photoswitchable proteins allows controlling the adhesion between them and their assembly into multicellular structures with light. Thereby, the chemical communication between a sender and a receiver GUV, which strongly depends on their spatial proximity, can also be photoregulated.

Dynamic blue light-switchable protein patterns on giant unilamellar vesicles.

The blue light-dependent interaction between the proteins iLID and Nano allows recruiting and patterning proteins on GUV membranes, which thereby capture key features of patterns observed in nature. This photoswitchable protein interaction provides non-invasive, reversible and dynamic control over protein patterns of different sizes with high specificity and spatiotemporal resolution.

World-wide variation in HIV-1 phenotypic susceptibility in untreated individuals: biologically relevant values for resistance testing.

OBJECTIVES: To examine the natural phenotypic variability in drug susceptibility among recombinant HIV-1 isolates from a large number of untreated HIV-positive individuals from wide-ranging geographic locations, and to use this information to establish biologically relevant cut-off values for phenotypic antiretroviral susceptibility testing. METHODS: Phenotypic susceptibility to 14 antiretroviral agents was determined for HIV-1 samples from > 1000 treatment-naive individuals in seven clinical trials. Samples were from the USA (n = 351), Germany (n = 306), Canada (n = 265), and South Africa (n = 358). Geometric mean fold-resistance and confidence intervals were determined relative to a standard laboratory wild-type virus. RESULTS: Baseline fold-resistance was approximately log-normally distributed for all antiretroviral agents examined. There was no evidence of large geographical differences in average antiviral susceptibility. Geometric mean fold-resistance for each of 14 antiviral agents was similar (+/- 0.5-fold) for samples derived from the USA, Canada, Germany, or South Africa. The non-nucleoside reverse transcriptase inhibitors (NNRTI) exhibited the broadest distribution of susceptibility; approximately 97.5% of all isolates had < 2.5-4.0, < 3.0-4.5, and < 5-10 fold-decrease in susceptibility to five protease inhibitors, six nucleoside analogues, and three NNRTI, respectively. No consistent geographic pattern or clade effect (B versus C) in either the mean or the distribution of baseline antiretroviral susceptibility was observed. CONCLUSIONS: Phenotypic drug susceptibility of HIV-1 in untreated individuals varies markedly from drug to drug, with broadly similar patterns world-wide. These results have important implications in defining the 'normal range' of phenotypic susceptibility to antiretroviral agents and establish biologically relevant cut-off values for this phenotypic drug susceptibility test.

Prevalence of genotypic and phenotypic resistance to anti-retroviral drugs in a cohort of therapy-naïve HIV-1 infected US military personnel.

OBJECTIVE: While transmission of drug-resistant HIV-1 has been reported, estimates of prevalence of resistance in drug-naïve populations are incomplete. We investigated the prevalence of genotypic mutations and phenotypic antiretroviral resistance in a cohort of HIV-1 infected U.S. military personnel prior to the institution of antiretroviral therapy. DESIGN: Cross-sectional cohort study. METHODS: Plasma was obtained from 114 recently HIV-1 infected subjects enrolled in an epidemiological study. Genotypic resistance was determined by consensus sequencing of a PCR product from the HIV-1 pol gene. Sequences were interpreted by a phenotypic-genotypic correlative database. Resistance phenotypes were determined by a recombinant virus cell culture assay. RESULTS: Genotypic mutations and phenotypic resistance were found at a higher than expected frequency. Resistance to non-nucleoside reverse transcriptase inhibitors was most common, with a prevalence of 15% of 95 subjects by genotype and 26% of 91 subjects by phenotype. Genotypic and phenotypic resistance respectively were found in 4% and 8% of subjects for nucleoside reverse transcriptase inhibitors and in 10% and 1% for protease inhibitors. One subject harbored virus with resistance to all three drug classes. CONCLUSIONS: A substantial frequency of resistance to antiretroviral drugs was identified in a therapy-naïve U.S. cohort. In most cases, the genotypic and phenotypic assays yielded similar results, although the genotypic assay could detect some protease inhibitor resistance-associated mutations in the absence of phenotypic resistance. These data suggest the need for optimization of treatment guidelines based on current estimates of the prevalence of drug resistance in HIV-1 seroconverters.

Evaluation of segmentation algorithms for generation of patient models in radiofrequency hyperthermia.

Time-efficient and easy-to-use segmentation algorithms (contour generation) are a precondition for various applications in radiation oncology, especially for planning purposes in hyperthermia. We have developed the three following algorithms for contour generation and implemented them in an editor of the HyperPlan hyperthermia planning system. Firstly, a manual contour input with numerous correction and editing options. Secondly, a volume growing algorithm with adjustable threshold range and minimal region size. Thirdly, a watershed transformation in two and three dimensions. In addition, the region input function of the Helax commercial radiation therapy planning system was available for comparison. All four approaches were applied under routine conditions to two-dimensional computed tomographic slices of the superior thoracic aperture, mid-chest, upper abdomen, mid-abdomen, pelvis and thigh; they were also applied to a 3D CT sequence of 72 slices using the three-dimensional extension of the algorithms. Time to generate the contours and their quality with respect to a reference model were determined. Manual input for a complete patient model required approximately 5 to 6 h for 72 CT slices (4.5 min/slice). If slight irregularities at object boundaries are accepted, this time can be reduced to 3.5 min/slice using the volume growing algorithm. However, generating a tetrahedron mesh from such a contour sequence for hyperthermia planning (the basis for finite-element algorithms) requires a significant amount of postediting. With the watershed algorithm extended to three dimensions, processing time can be further reduced to 3 min/slice while achieving satisfactory contour quality. Therefore, this method is currently regarded as offering some potential for efficient automated model generation in hyperthermia. In summary, the 3D volume growing algorithm and watershed transformation are both suitable for segmentation of even low-contrast objects. However, they are not always superior to user-friendly manual programs for contour generation. When the volume growing algorithm is used, the contours have to be postprocessed with suitable filters. The watershed transformation has a large potential if appropriately developed to 3D sequences and 3D interaction features. After all, the practicality and feasibility of every segmentation method critically depend on various details of the user software as pointed out in this article.

Bonding to zirconia ceramic: adhesion methods and their durability.

OBJECTIVES: Resin bonding to yttrium-oxide--partially-stabilized zirconia ceramic (YPSZ) cannot be established by standard methods that are utilized for conventional silica-based dental ceramics. It was our hypothesis that adhesive bonding methods suitable for glass-infiltrated alumina ceramic can also be used to bond successfully to YPSZ. To prove this hypothesis, bonding methods suitable for alumina ceramic were used on YPSZ and the tensile bond strength and their durability evaluated in vitro. METHODS: Plexiglass tubes filled with resin composite were bonded to YPSZ discs following various adhesion protocols. Groups of 16 samples were bonded using seven different bonding methods. Subgroups of eight bonded samples were tested for tensile strength following storage in distilled water (37 degrees C) for either 3 or 150 days. In addition, the 150 day samples were thermal cycled 37,500 times as a method to stress the bond interface. The statistical analysis was made with the Kruskal-Wallis test followed by multiple pair-wise comparisons of the groups using the Wilcoxon rank sum test. RESULTS: Sandblasting alone, the additional use of a silane or acrylizing resulted in an initial bond of a conventional BisGMA resin composite to YPSZ which failed spontaneously over storage time. The use of the BisGMA resin composite after tribochemical silica coating of YPSZ and the use of a polyacid-modified resin composite after sandblasting of YPSZ resulted in an initial bond which decreased significantly over storage time (p = 0.05). A durable resin bond to YPSZ was achieved only after sandblasting the ceramic and using one of two resin composites containing a special phosphate monomer. SIGNIFICANCE: A durable bond to YPSZ was achieved only by using resin composites with a special adhesive monomer. Therefore, the hypothesis of the study was partially proved as a durable bond to alumina ceramic is achieved with the same resin composites. However, it was partially disproved as tribochemical silica coating of YPSZ did not result in a durable resin bond as it does on glass-infiltrated alumina ceramic.

Long-term resin bond strength to zirconia ceramic.

PURPOSE: The aim of this in vitro study was to evaluate the long-term bond strength of adhesive bonding systems to yttrium-oxide-partially-stabilized zirconia ceramic (YPSZ). MATERIALS AND METHODS: Plexiglas tubes filled with resin composite were bonded to industrially manufactured zirconia ceramic disks (96% ZrO2 stabilized by 4% Y2O3). After air abrading the ceramic and ultrasonic cleansing, groups of 16 samples were bonded in an alignment apparatus using 7 different bonding methods. Subgroups of 8 bonded samples were tested for tensile strength following storage in distilled water at 37 degrees C either for 3 days or 2 years. In addition, the 2-year samples were thermocycled 37,500 times. The statistical analyses were conducted with the Kruskal-Wallis test followed by multiple pair-wise comparison of the groups using the Wilcoxon rank sum test. RESULTS: A moderate to relatively high initial bond strength was achieved by air abrasion alone, the additional use of a silane, or acrylizing the YPSZ surface in combination with a conventional bis-GMA resin composite. However, these methods failed spontaneously over storage time. The use of the bis-GMA resin composite after tribochemical silica coating of YPSZ and the use of a polyacid-modified resin composite after air abrasion of YPSZ resulted in a high initial bond strength which decreased significantly over storage time. A durable resin bond strength to YPSZ was achieved only after air abrasion of YPSZ and using one of two resin composites containing a special phosphate monomer. CONCLUSION: A durable bond strength to YPSZ was achieved only by using resin composites containing a special adhesive monomer.