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PubMed2006

Experimental evidence of dynamic trapping in the scattering of H2 from Pd(110).

We have performed H2(D2) diffraction experiments on a Pd(110) surface using two different high-sensitivity set-ups. We have found that, although the total reflectivity of Pd(110) is comparable to that observed in other reactive systems, the corresponding H2(D2) diffraction patterns are quite different: no diffraction peak, including the specular one, is observed on Pd(110). This unexpected result is the consequence of dynamic trapping. Such interpretation is supported by classical dynamics calculations based on accurate ab initio potential energy surfaces.

Journal Article↗

PubMed2006

Growth and structure of Pd films on ZnO(0001).

The growth and structure of Pd films on ZnO(0001) were investigated using high resolution electron energy loss spectroscopy, x-ray photoelectron spectroscopy, and low energy electron diffraction. Vapor deposited Pd films at 300 K were found to follow a two-dimensional (2D) island growth mode, in which 2D metal islands are formed up to a critical coverage at which point growth occurs primarily in a layer-by-layer fashion on top of the islands. Heating to only 350 K was found to be sufficient to induce partial agglomeration of Pd films into three-dimensional particles. In addition to causing further agglomeration into particles, heating to 700 K resulted in partial reduction of the ZnO surface and the formation of a PdZn alloy.

Journal Article↗

PubMed2004

OH-Pd(0) interaction as a stabilizing factor in palladium-catalyzed allylic alkylations.

In palladium-catalyzed alkylations of allylic acetates with malonate as nucleophile, catalysts with oxazoline ligands bearing hydroxymethyl substituents in 4-position have been shown by density functional theory computations to undergo a conformational change on nucleophilic attack, which is accompanied by reduction of Pd(II) to Pd(0). The conformations of the Pd(0) complexes were shown to be governed by the presence of a hydrogen bond with the metal center acting as a hydrogen bond acceptor. The conformational change, which is absent in catalysts with O-alkylated analogs, largely affects the enantioselectivity of the catalytic process. This process is a previously uninvestigated example of where this type of weak hydrogen bond has been shown to influence the stereochemistry of a chemical reaction.

Journal Article↗

PubMed2026

DESTINY-Lung06: trastuzumab deruxtecan and pembrolizumab as first-line treatment for HER2-overexpressing, PD-L1 TPS <50% NSCLC.

Non-small cell lung cancer (NSCLC) that overexpresses human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis, and no HER2-targeting therapies for HER2-overexpressing NSCLC are currently approved in the first-line setting. Pembrolizumab plus pemetrexed and platinum-based chemotherapy is a recommended first-line treatment option for nonsquamous NSCLC with no actionable genomic alterations. However, improved outcomes with pembrolizumab-based therapies correlate with higher programmed death-ligand 1 (PD-L1) levels, underscoring the need for more targeted treatment options for patients with lower PD-L1 tumor proportion scores (TPS; <50%). DESTINY-Lung06 is a multicenter, open-label, randomized, phase III trial evaluating the efficacy and safety of trastuzumab deruxtecan (T-DXd) in combination with pembrolizumab in the first-line setting in patients with HER2-overexpressing (≥25% moderate/strong membrane staining), PD-L1 TPS <50% NSCLC. Planned enrollment will be approximately 686 patients randomly assigned to either T-DXd 5.4 mg/kg with pembrolizumab 200 mg intravenously every 3 weeks (Q3W) or pembrolizumab 200 mg plus pemetrexed 500 mg/m2 with platinum-based chemotherapy (cisplatin 75 mg/m2 or carboplatin under the concentration-time curve 5 mg min/mL) intravenously Q3W. Progression-free survival by blinded independent central review and overall survival are the primary and key secondary endpoints of the study, respectively.Clinical trial registration: www.ClinicalTrials.gov identifier is NCT06899126; EudraCT identifier is 2024-515658-26-00.

First-line↗

PubMed2026

Conserved miRNA regulators of PD-1/PD-L1 in glioblastoma and colorectal cancer.

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have transformed cancer therapy, but their efficacy remains limited in glioblastoma (GBM) and heterogeneous in colorectal cancer (CRC). MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, including immune checkpoint molecules, yet conserved regulatory miRNA networks across distinct cancers remain poorly defined. Five conserved miRNAs (miR-106a-5p, miR-106b-5p, miR-20a-5p, miR-20b-5p, miR-138-5p) fulfilled the selection criteria and were consistently dysregulated in GBM and CRC. MiR-106a-5p and miR-106b-5p were upregulated in both cancers and showed favourable prognostic associations, with higher expression correlating with improved survival. miR-20a-5p and miR-20b-5p were preferentially expressed in microsatellite-stable (MSS) CRC and correlated with favourable outcomes in both cancers, whereas miR-138-5p was downregulated in both tumours compared to normal tissue, but showed opposite survival associations, with higher levels linked to worse prognosis. Correlation analysis revealed significant inverse associations between several miRNAs and checkpoint gene expression, including moderate inverse correlations for CD274-miR-106a-5p in GBM, CD274-miR-20a-5p in CRC and PDCD1LG2-miR-20a-5p in both cancers. Pan-cancer profiling demonstrated broad and heterogeneous dysregulation, with expression absent in ovarian cancer for four of the five miRNAs. Pathway enrichment implicated the TGF-β, Hippo, FoxO, and cell cycle pathways, consistent with their known roles in tumour immune evasion. We identified a conserved set of miRNAs that are dysregulated in both GBM and CRC, correlate with survival, and display inverse relationships with PD-1/PD-L1/PD-L2 expression. These miRNAs represent candidate regulators of the PD-1/PD-L1/PD-L2 axis and potential biomarkers of tumour biology that may influence immune checkpoint signalling.

Humans↗

PubMed1994

In-vitro activity of clinafloxacin (CI-960) and PD 131628-2 against anaerobic bacteria.

The antimicrobial activities of two new quinolones, CI-960 and PD 131628-2 were determined against 339 strains of anaerobic bacteria and compared to cefoxitin, imipenem and metronidazole. The NCCLS-approved Wadsworth agar dilution technique with Brucella-lysed blood agar was used throughout the study. Breakpoints of the new quinolones are 2 mg/L, and breakpoints for cefoxitin, imipenem and metronidazole are 32, 8 and 16 mg/L, respectively. CI-960 displayed excellent activity, inhibiting all strains tested at 1 mg/L. PD 131628-2 inhibited 94% of Bacteroides fragilis, 75% of other B. fragilis group isolates, 87% of Prevotella spp, 79% of the Fusobacterium mortiferum-varium group, 74% of non-sporing gram-positive bacilli, and 89-100% of Clostridium spp other than Clostridium difficile at 2 mg/L. None of the eight strains of C. difficile was inhibited at 2 mg/L although they were inhibited at 4 mg/L. PD 131628-2 inhibited all strains of other Bacteroides spp, Porphyromonas spp, and Fusobacterium nucleatum at < or = 1 mg/L.

Anti-Infective Agents↗

PubMed1998

Study of the interaction of DNA with cisplatin and other Pd(II) and Pt(II) complexes by atomic force microscopy.

Modifications in the structure of a 260 bp DNA (hlyM) fragment from Escherichia coli caused by interaction with Pd(II) and Pt(II) complexes were studied. Cisplatin and transplatin [cis- and trans-PtCl2(NH3)2 respectively], Pt2Cl2(Spym)4 (Spym = 2-mercaptopyrimidine anion), Pd-famotidine and Pt-famotidine were incubated with DNA for 24 h at 37 degrees C and then observed with an atomic force microscope. Atomic force microscopy (AFM) provides the opportunity for nanometer resolution in research on the interaction between nucleic acids and metal complexes. The complexes induced noticeable changes in DNA topography according to their different characteristics and structure. In the case of cisplatin a shortening in DNA strands was observed. Transplatin and Pt2Cl2(Spym)4 caused shortening and compaction, whilst an aggregation of two strands was observed for the Pt-famotidine compound but not for the Pd-famotidine compound or the metal-free famotidine.

Antineoplastic Agents↗

PubMed2025

Structural investigation of an RNA device that regulates PD-1 expression in mammalian cells.

Synthetic RNA devices are engineered to control gene expression and offer great potential in both biotechnology and clinical applications. Here, we present multidisciplinary structural and biochemical data for a tetracycline (Tc)-responsive RNA device (D43) in both ligand-free and bound states, providing a structure-dynamical basis for signal transmission. Activation of self-cleavage is achieved via ligand-induced conformational and dynamical changes that stabilize the elongated bridging helix harboring the communication module, which drives proper coordination of the catalytic residues. We then show the utility of CRISPR-integrated D43 in EL4 lymphocytes to regulate programmed cell death protein 1 (PD-1), a key receptor of immune checkpoints. Treatment of these cells with Tc showed a dose-dependent reduction in PD-1 by immunostaining and a decrease in messenger RNA levels by quantitative PCR as compared with wild type. PD-1 expression was recoverable upon removal of Tc. These results provide mechanistic insight into RNA devices with potential for cancer immunotherapy or other applications.

Programmed Cell Death 1 Receptor↗

PubMed1997

One-dose cefuroxime i.v. and i.p. reduces microbial growth in PD patients after catheter insertion.

BACKGROUND: When a peritoneal dialysis catheter is inserted intra-abdominally in a patient starting peritoneal dialysis (PD) there is always a risk for postoperative wound infection and peritonitis. At our centre, PD is started immediately after the dialysis catheter is inserted. This may increase the postoperative risk for peritonitis and wound infection. The aim of this prospective, randomized, study was to evaluate whether the incidence of microbial growth postoperatively (within 10 days) after catheter insertion could be reduced by prophylactic antibiotic therapy. SUBJECTS AND METHODS: During a period of 27 months, 38 patients, who consecutively entered the PD programme, (11 women and 27 men, mean age 57 years) were included in the study. Eighteen patients were given cefuroxime 1.5 g i.v. preoperatively and 250 mg i.p. in the first dialysis bag (containing 1 litre fluid) as prophylaxis. Twenty patients were not given prophylactic antibiotics (control group). All catheter insertions were performed in an operating theatre by the same surgeons using the same technique. RESULTS: In the test group, none of the patients showed microbial growth in the dialysis fluid during the post-operative period, while in the control group six of 20 patients (30%) suffered from such growth (P = 0.021). CONCLUSION: Prophylactic treatment by cefuroxime i.v. pre- and i.p. perioperatively may reduce the risk for microbial growth and peritonitis after insertion of a Tenckhoff catheter.

Adult↗

PubMed2006

Streptococcal PD peritonitis--a 10-year review of one centre's experience.

BACKGROUND: Detailed descriptive studies focusing on streptococcal peritonitis in patients on peritoneal dialysis are lacking. Most of the current information is available through isolated case reports. METHODS: We conducted a retrospective analysis of our peritoneal dialysis (PD) peritonitis database over the last decade to study the clinical profile and treatment outcomes of streptococcal peritonitis. RESULTS: A total of 68 patients (age: 57.12 +/- 16.6 years; male: 58.7%) with 104 episodes of streptococcal peritonitis (11.7% of total peritonitis) were identified. Of the patients, 18 (26.4%) were considered immunocompromised [failed renal transplant, systemic lupus erythematosus (SLE)] and 28 (41.1%) had diabetes. Streptococcus viridans accounted for the majority (94 episodes: 90.3%) of the streptococcal peritonitis. One patient developed S. viridans peritonitis after dental cleaning without antibiotic prophylaxis. Two (1.9%) infections with S. agalactiae and S. bovis each and seven (6.7%) with non-haemolytic Streptococcus were noted. Three patients had hospital-acquired infection. Twenty-six (25%) episodes needed 8 +/- 5.9 days of hospitalization. Concurrent infection with two organisms accounted for 17 (16.3%) episodes. Cefazolin (71) and vancomycin (29) were the primary antibiotics used for the treatment. Five episodes needed two antibiotics and one patient required antifungal treatment. A third of the patients (33.3%) had peritonitis that resolved slowly, although the majority of those (94%) did ultimately resolve with antibiotics alone. Five (4.8%) episodes required removal of the PD catheter. Three of them were associated with dual infections (one each with yeast, Stenotrophomonas and Enterococcus). Relapse occurred in eight (7.6%) episodes, and 11 (10.5%) recurred over the period from 4 weeks to 6 months after treatment. CONCLUSIONS: Streptococci remain a significant cause of PD peritonitis. Viridans strep is the primary subtype responsible. Isolated infections with these organisms are associated with slower response, good outcome and higher rates of recurrence.

Female↗

PubMed2001

'Chemical condoms' for the prevention of HIV infection: evaluation of novel agents against SHIV(89.6PD) in vitro and in vivo.

BACKGROUND: Vaginal agents which are antiviral and/or inhibit the entry of HIV into the cell could prevent heterosexual transmission of HIV, and protect women who cannot negotiate condom use. METHODS: Four agents have been investigated for activity in vitro and in vivo against SHIV(89.6PD): two anionic polymers, dextrin-2-sulphate (D2S) and PRO 2000 (P2K), and two virucidal agents; a non-ionic detergent, nonoxynol-9 (N9) and a cyclic peptide ionophore, gramicidin-D (GD). All four agents were investigated in rhesus macaques, using an intra-vaginal challenge of two inoculations of 1 x 104 50% tissue culture infectious doses (TCID)50 of SHIV(89.6PD). RESULTS: D2S, P2K, GD and N9 all inhibited SHIV(89.6PD) in vitro. In vivo, three out of four control macaques were infected as judged by viral culture, seroconversion, DNA and RNA PCR; infection was confirmed in four out of eight macaques pre-treated with P2K, two out of four pre-treated with D2S, one out of four pre-treated with N9, two out of four pre-treated with GD and four out of four pre-treated with D2S + GD, a combination additive in vitro. INTERPRETATION: D2S and PRO-2000, novel inhibitors of HIV entry, showed evidence of protection in vivo, comparable to that seen with the virucide, N9. These data, together with the results of phase I and phase II studies in healthy women which have shown minimal toxicity, support plans for a phase III efficacy trial of chemically simple inhibitors of HIV entry with low toxicity, for the prevention of HIV infection in women.

Administration, Intravaginal↗

PubMedDate not supplied

Signal, contrast, and resolution in optimized PD- and T2-weighted turbo SE images of the knee.

OBJECTIVE: Signal and contrast behavior, delineation of anatomical details, and flow artifacts were compared in dual echo SE and turbo SE (TSE) sequences. Results were correlated with theoretical aspects of the TSE technique. MATERIALS AND METHODS: A TSE sequence (TR = 3,500 ms, TEeff = 19, 93 ms, ETL = 3) and a conventional SE sequence (TR = 2,500 ms, TE = 20, 70 ms) were applied to 64 patients with knee injuries. Signal intensities of anatomical structures were measured in regions of interest. Contrast and edge sharpness of menisci and posterior cruciate ligament were evaluated by three independent observers. RESULTS: The TSE sequence yielded similar signal and contrast behavior compared with SE. Visual evaluation revealed nearly equivalent contrast and edge sharpness of menisci and posterior cruciate ligament in proton-density (PD)-weighted TSE images. Contrast and edge sharpness of menisci were significantly lower in T2-weighted TSE images. Reduced flow artifacts were found in PD- and especially in T2-weighted TSE images. Differences between both techniques are interpreted, taking into account influence of TEeff, ETL, k-space trajectory, magnetization transfer effects, and J-coupling. CONCLUSION: The TSE sequence yielded good image quality in PD-weighted, but slightly inferior quality in T2-weighted, images, reducing the time of acquisition by 50%.

Adult↗

PubMed1993

Comparative studies with the endothelin receptor antagonists BQ-123 and PD 142893 indicate at least three endothelin receptors.

Endothelin-1 (ET-1), endothelin-3 (ET-3), sarafotoxin 6b (SX6b), and sarafotoxin 6C (SX6c) were used as agonists, and BQ-123 (ETA-selective) and PD 142893 (ET receptor-nonselective) were used as antagonists to characterize the receptors mediating the effects of the ET/SX peptides on a variety of isolated smooth-muscle preparations. Contractions of the rat thoracic aorta, rat isolated perfused mesentery, and guinea pig ileum and potentiation of twitch of the rat vas deferens were mediated by ETA receptors in that they showed the order of potency ET-1 = SX6b > ET-3 >> SX6C. These effects were antagonized by BQ-123 or PD 142893. Contractions of the rabbit pulmonary artery and rat stomach strip, inhibition of twitches in the guinea pig ileum, and vasodilatations of the rat isolated perfused mesentery showed the order of potency ET-1 = SX6b = ET-3 = SX6c and were unaffected by BQ-123, suggesting involvement of ETB receptors. However, in these tissues, PD 142893 antagonized only dilatations of the rat mesentery to ET-1 but not any of the other effects of ET-1. Thus, we suggest that there are three types of endothelin receptors: ETA and two subtypes of ETB.

Amino Acid Sequence↗

PubMed2000

Bridging the pressure and materials gaps: high pressure sum frequency generation study on supported Pd nanoparticles

Infrared-visible sum frequency generation vibrational spectroscopy is applied for the first time to monitor CO stretching vibrations on alumina supported Pd nanoparticles in a pressure range from 10(-7) to 200 mbar. The adsorption behavior of Pd aggregates with 3 and 6 nm mean size is dominated by surface defects and two different adsorption sites (twofold bridging and on-top) were identified. The CO adsorption site occupancy on Pd nanocrystals is mainly governed by the gas phase pressure while the structure of the particles and their temperature have a smaller influence.

Journal Article↗

PubMed2001

COI oxidation on a single Pd atom supported on magnesia.

The oxidation of CO on single Pd atoms anchored to MgO(100) surface oxygen vacancies is studied with temperature-programmed-reaction mass spectrometry and infrared spectroscopy. In one-heating-cycle experiments, CO(2), formed from O(2) and CO preadsorbed at 90 K, is detected at 260 and 500 K. Ab-initio simulations suggest two reaction routes, with Pd(CO)(2)O(2) and PdCO(3)CO found as precursors for the low and high temperature channels, respectively. Both reactions result in annealing of the vacancy and induce migration and coalescence of the remaining Pd-CO to form larger clusters.

Journal Article↗

PubMed2001

Formation of a stable decagonal quasicrystalline Al-Pd-Mn surface layer.

We report the in situ formation of an ordered equilibrium decagonal Al-Pd-Mn quasicrystal overlayer on the fivefold symmetric surface of an icosahedral Al-Pd-Mn monograin. The decagonal structure of the epilayer is evidenced by x-ray photoelectron diffraction, low-energy electron diffraction, and electron backscatter diffraction. This overlayer is also characterized by a reduced density of states near the Fermi edge as expected for quasicrystals. This is the first time that a millimeter-size surface of the stable decagonal Al-Pd-Mn is obtained, studied, and compared to its icosahedral counterpart.

Journal Article↗

PubMed2002

Non-nearest-neighbor jumps in 2D diffusion: Pd on W(110).

A variety of jumps has in the past been identified in diffusion of atoms on 1D channeled surfaces. To establish the jump processes important in diffusion on a 2D surface, the movement of individual Pd atoms has been examined on W(110). From the distribution of displacements of Pd at high temperatures, double jumps are found along the close-packed <111>. For the first time, sizable differences are also observed between the mean-square displacements along x and y, which demonstrate unexpected contributions from jumps along <110>, but not along <001>. These jumps proceed over activation barriers higher than for single jumps, under conditions predicted from previous work with Pd on the channeled W(211).

Journal Article↗

PubMed2003

Influence of a heterogeneous Al2O3 surface on the electronic properties of single Pd atoms.

Electronic properties of single Pd atoms, deposited on Al(2)O(3)/NiAl(110), have been characterized by scanning tunneling spectroscopy at 12 K. The spectra reveal distinct conductivity resonances, assigned to discrete electronic levels in the atom. The energy position of the resonances reflects adsorption properties of Pd atoms on different sites of the oxide support. Mapping the spatial extent of conductivity channels in the Pd atoms yields the symmetry of the underlying electronic states. The results demonstrate the effect of a heterogeneous oxide surface on the electronic structure of adsorbed metal atoms.

Journal Article↗