gebhart/patrepeval huggingface dataset:
Unveiling the Transient Template in the Self-Assembly of a Molecular Oxide Nanowheel (2009)

Self-assembly has proven a powerful means of preparing structurally intricate nanomaterials, but the mechanism is often masked by the common one-pot mixing procedure. We employed a flow system to study the steps underlying assembly of a previously characterized molybdenum oxide wheel 3.6 nanometers in diameter. We observed crystallization of an intermediate structure in which a central {Mo36} cluster appears to template the assembly of the surrounding {Mo150} wheel. The transient nature of the template is demonstrated by its ejection after the wheel is reduced to its final electronic state. The template's role in the self-assembly mechanism is further confirmed by the deliberate addition of the template to the reaction mixture, which greatly accelerates the assembly time of the {Mo150} wheel and increases the yield.
Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles (2004)

Antisense oligonucleotide-mediated alternative splicing has great potential for treatment of Duchenne muscular dystrophy (DMD) caused by mutations within nonessential regions of the dystrophin gene. We have recently shown in the dystrophic mdx mouse that exon 23, bearing a nonsense mutation, can be skipped after intramuscular injection of a specific 2'-O-methyl phosphorothioate antisense oligoribonucleotide (2OMeAO). This skipping created a shortened, but in-frame, transcript that is translated to produce near-normal levels of dystrophin expression. This expression, in turn, led to improved muscle function. However, because DMD affects muscles body-wide, effective treatment requires dystrophin induction ideally in all muscles. Here, we show that systemic delivery of specific 2OMeAOs, together with the triblock copolymer F127, induced dystrophin expression in all skeletal muscles but not in cardiac muscle of the mdx dystrophic mice. The highest dystrophin expression was detected in diaphragm, gastrocnemius, and intercostal muscles. Large numbers of fibers with near-normal level of dystrophin were observed in focal areas. Three injections of 2OMeAOs at weekly intervals enhanced the levels of dystrophin. Dystrophin mRNA lacking the targeted exon 23 remained detectable 2 weeks after injection. No evidence of tissue damage was detected after 2OMeAO and F127 treatment either by serum analysis or histological examination of liver, kidney, lung, and muscles. The simplicity and safety of the antisense protocol provide a realistic prospect for treatment of the majority of DMD mutations. We conclude that a significant therapeutic effect may be achieved by further optimization in dose and regime of administration of antisense oligonucleotide.
Phase I study of twice-weekly dosing of the investigational oral proteasome inhibitor MLN9708 in patients (pts) with relapsed and/or refractory multiple myeloma (MM). (2012)

8017 Background: MLN9708 is the first oral proteasome inhibitor to enter clinical investigation in MM. This study (NCT00932698) assessed safety, MTD, and response rate with twice-weekly oral MLN9708 in pts with relapsed and/or refractory MM, and characterized plasma pharmacokinetics (PK) and blood pharmacodynamics. Methods: Pts aged ≥18 yrs with measurable MM received MLN9708 on d 1, 4, 8, and 11 of 21-d cycles. In the dose-escalation phase, pts required ≥2 prior therapies (including bortezomib, thalidomide/lenalidomide, and corticosteroids). At the MTD (2.0 mg/m 2 ), pts were enrolled to relapsed and refractory [RR], bortezomib-relapsed [VR], proteasome-inhibitor [PI] naïve, and carfilzomib [CZ] expansion cohorts. Results: 57 pts (53% M) were enrolled, 37 to the expansion cohorts (16 RR, 14 VR, 6 PI naïve, 1 CZ). Median age was 65 yrs (range 50-86). Median number of prior lines of therapy was 4 (range 1-28); 88%, 84%, 61%, and 5% had prior bortezomib, lenalidomide, thalidomide, and carfilzomib, respectively. Pts have received a median of 3 cycles (range 1-24) to date (data cut-off Dec 1, 2011); 7 (12%) have received ≥13 cycles. Drug-related AEs were seen in 89% of pts, including fatigue (46%), thrombocytopenia (40%), and nausea (30%); 63% had drug-related grade ≥3 AEs, including thrombocytopenia (33%), neutropenia (14%), fatigue (9%), and rash (7%). Only 6 (11%) pts had drug-related peripheral neuropathy (PN; no grade ≥3). 7 pts discontinued due to AEs. 2 pts died on study, due to PD and an unrelated cardiac disorder. Of 46 response-evaluable pts, 6 have achieved ≥PR, with 1 sCR (PI naïve cohort) and 5 PRs (2 in dose-escalation, 1 in RR, 2 in VR cohorts), and 1 VR pt has achieved MR, with duration of disease control of up to 18.6 mo. PK analyses showed MLN2238 (biologically active hydrolysis product) has linear plasma PK (0.8-2.23 mg/m 2 ), T max of 0.5-1.25 hr, and terminal half-life of 4-6 d. A dose-dependent increase in whole blood 20S proteasome inhibition was observed. Conclusions: Current data suggest MLN9708 has clinical activity in heavily pretreated MM pts, with durable responses/disease control, and is generally well tolerated with infrequent low-grade PN.
Recursive SVM feature selection and sample classification for mass-spectrometry and microarray data (2006)

The proposed R-SVM method is suitable for analyzing noisy high-throughput proteomics and microarray data and it outperforms SVM-RFE in the robustness to noise and in the ability to recover informative features. The multivariate SVM-based method outperforms the univariate method in the classification performance, but univariate methods can reveal more of the differentially expressed features especially when there are correlations between the features.
Neutrophils degrade subendothelial matrices in the presence of alpha-1-proteinase inhibitor. Cooperative use of lysosomal proteinases and oxygen metabolites. (1984)

Triggered neutrophils rapidly degraded labeled matrices secreted by cultured, venous endothelial cells via a process dependent on elastase but not oxygen metabolites. In the presence of high concentrations of alpha-1-proteinase inhibitor, the ability of the stimulated neutrophil to solubilize the matrix was impaired. However, at lower concentrations of alpha-1-proteinase inhibitor the neutrophil could enhance the degradative potential of its released elastase by a H2O2-dependent process. Coincident with this increase in matrix damage, the stimulated neutrophil destroyed the elastase inhibitory activity of the alpha-1-proteinase inhibitor via a catalase-inhibitable process. The ability of the triggered neutrophil to solubilize the matrix in the presence of alpha-1-proteinase inhibitor was unaffected by superoxide dismutase or hydroxyl radical scavengers but was markedly impaired by catalase, azide, or hypochlorous acid scavengers. We conclude that neutrophils can cooperatively use an oxidant with characteristics similar, if not identical, to hypochlorous acid and the lysosomal proteinase elastase to negate the protective effects of alpha-1-proteinase inhibitor in order to attack the subendothelial matrix.
Genome-Wide Platelet RNA Profiling in Clinical Samples (2009)

Human blood platelets are anucleate cells that contain minute amounts of translational active mRNA. Investigation of the gene expression profile by microarray analysis has become an excellent tool for better understanding of normal and pathological platelet function. Its use, however, is often limited by the low yield of megakaryocytic-derived mRNA, the possible contamination with leukocytes during platelet preparation and the small platelet volume in clinical settings, especially in pediatric patients. In this chapter, we present a protocol for the isolation of leukocyte-depleted platelet samples in clinical settings and an optimized procedure for transcript profiling, using the Agilent oligo microarray technology. In particular, we discuss the special aspects of platelet purification when working with blood sample volumes not exceeding 3-5 ml, which is typical in pediatric patients and we furthermore provide detailed information for transcript profiling of extremely small amounts of platelet RNA.
Regional network of magnetic resonance imaging gray matter volume in healthy aging (2006)

Healthy aging has been associated with brain volume reductions preferentially affecting the frontal cortex, but also involving other regions. We used a network model of regional covariance, the Scaled Subprofile Model, with magnetic resonance imaging voxel-based morphometry to identify the regional distribution of gray matter associated with aging in 26 healthy adults, 22-77 years old. Scaled Subprofile Model analysis identified a pattern that was highly correlated with age (R2=0.66, P<or=0.0001). Older age was associated with less gray matter in the bilateral frontal, temporal,thalamic, and right cerebellar regions. Gender differences suggested more advanced brain aging in the men. In this healthy adult sample, aging was associated with a regional pattern of gray matter atrophy most prominently involving the frontal and temporal cortices. Scaled Subprofile Model network analysis may aid in the detection and tracking of brain aging and in the evaluation of putative antiaging therapies.
A major cis activator of the IRBP gene contains CRX-binding and Ret-1/PCE-I elements. (1997)

These data suggest that a trans-acting complex binds a cis-element in the -70 to -45 sequence. This binding fully activates transcription but confers only partial tissue-specificity to IRBP gene expression.
DSP107 combines inhibition of CD47/SIRPα axis with activation of 4-1BB to trigger anticancer immunity (2022)

DSP107 effectively (re)activated innate and adaptive anticancer immune responses and may be of therapeutic use alone and in combination with rituximab for the treatment of DLBCL patients.
Antiemetic Effect of Delta-9-Tetrahydrocannabinol in Patients Receiving Cancer Chemotherapy (1975)

Anecdotal accounts suggested that smoking marihuana decreases the nausea and vomiting associated with cancer chemotherapeutic agents. Oral delta-9-tetrahydrocannabinol was compared with placebo in a controlled, randomized, "double-blind" experiment. All patients were receiving chemotherapeutic drugs known to cause nausea and vomiting of central origin. Each patient was to serve as his own control to determine whether tetrahydrocannabinol had an antiemetic effect. Twenty-two patients entered the study, 20 of whom were evaluable. For all patients an antiemetic effect was observed in 14 of 20 tetrahydrocannabinol courses and in none of 22 placebo courses. For patients completing the study, response occurred in 12 of 15 courses of tetrahydrocannabinol and in none of 14 courses of placebo (P less than 0.001). No patient vomited while experiencing a subjective "high". Oral tetrahydrocannabinol has antiemetic properties and is significantly better than a placebo in reducting vomiting caused by chemotherapeutic agents.
A Phase I Randomized, Placebo-Controlled, Dose-Exploration Study of Single-Dose Inhaled Montelukast in Patients with Chronic Asthma (2010)

Inhaled montelukast provided significant bronchodilation compared with placebo as early as 20 minutes after the administration that persisted for 24 hours and provided additive bronchodilation to albuterol.
DLL4-Notch Signaling Mediates Tumor Resistance to Anti-VEGF Therapy In Vivo (2011)

Resistance to VEGF inhibitors is emerging as a major clinical problem. Notch signaling has been implicated in tumor angiogenesis. Therefore, to investigate mechanisms of resistance to angiogenesis inhibitors, we transduced human glioblastoma cells with retroviruses encoding Notch delta-like ligand 4 (DLL4), grew them as tumor xenografts and then treated the murine hosts with the VEGF-A inhibitor bevacizumab. We found that DLL4-mediated tumor resistance to bevacizumab in vivo. The large vessels induced by DLL4-Notch signaling increased tumor blood supply and were insensitive to bevacizumab. However, blockade of Notch signaling by dibenzazepine, a γ-secretase inhibitor, disrupted the large vessels and abolished the tumor resistance. Multiple molecular mechanisms of resistance were shown, including decreased levels of hypoxia-induced VEGF and increased levels of the VEGF receptor VEGFR1 in the tumor stroma, decreased levels of VEGFR2 in large blood vessels, and reduced levels of VEGFR3 overall. DLL4-expressing tumors were also resistant to a VEGFR targeting multikinase inhibitor. We also observed activation of other pathways of tumor resistance driven by DLL4-Notch signaling, including the FGF2-FGFR and EphB4-EprinB2 pathways, the inhibition of which reversed tumor resistance partially. Taken together, our findings show the importance of classifying mechanisms involved in angiogenesis in tumors, and how combination therapy to block DLL4-Notch signaling may enhance the efficacy of VEGF inhibitors, particularly in DLL4-upregulated tumors, and thus provide a rational base for the development of novel strategies to overcome antiangiogenic resistance in the clinic.
Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer. (1992)

Moloney Murine Leukemia Virus (MoMuLV) causes T cell neoplasms in rodents but is not known to be a pathogen in primates. The core protein and enzyme genes of the MoMuLV genome together with an amphotropic envelope gene are utilized to engineer the cell lines that generate retroviral vectors for use in current human gene therapy applications. We developed a producer clone that generates a very high concentration of retroviral vector particles to optimize conditions for gene insertion into pluripotent hematopoietic stem cells. This producer cell line also generates a much lower concentration of replication-competent virus that arose through recombination. Stem cells from rhesus monkeys were purified by immunoselection with an anti-CD34 antibody, incubated in vitro for 80-86 h in the presence of retroviral vector particles with accompanying replication-competent virus and used to reconstitute recipients whose bone marrow had been ablated by total body irradiation. The retroviral vector genome was detected in circulating cells of five of eight transplant recipients of CD34+ cells and in the circulating cells of two recipients of infected, unfractionated bone marrow mononuclear cells. Three recipients of CD34+ cells had a productive infection with replication-competent virus. Six or seven mo after transplantation, each of these animals developed a rapidly progressive T cell neoplasm involving the thymus, lymph nodes, liver, spleen, and bone marrow. Lymphoma cells contained 10-50 copies of the replication-competent virus, but lacked the retroviral vector genome. We conclude that replication-competent viruses arising from producer cells making retroviral vectors can be pathogenic in primates, which underscores the importance of carefully screening retroviral producer clones used in human trials to exclude contamination with replication-competent virus.
Grafting of Cultured Allogeneic Epidermis on Second- and Third-degree Burn Wounds on 26 Patients (1986)

Twenty-six individuals with second- and third-degree burn wounds have been grafted with cultured allogeneic epidermal cells. These epidermal cell grafts were grown in culture from cadaver skin according to a technique which we have developed. After being grafted with cultured allogeneic epidermal cells, superficial wounds, e.g., donor sites, healed within 7 days, compared to 14 days for mirror image control sites. Deep second-degree burn wounds which were excised before grafting with cultured cells healed in a mean time of 10 days. Deep second-degree burn wounds which were not excised before grafting healed in a mean time of 14 days. The cultured cells produced rapid healing in 11 of the 12 patients with deep second-degree burn wounds. The deep second-degree wounds grafted with cultured allogeneic epidermal cells healed with results which were comparable to the deep second-degree wounds which were autografted. Grafts of cultured allogeneic epidermal cells placed on full-thickness, or third-degree burn, wounds did not grow well.
RESCUE-ESE identifies candidate exonic splicing enhancers in vertebrate exons (2004)

A typical gene contains two levels of information: a sequence that encodes a particular protein and a host of other signals that are necessary for the correct expression of the transcript. While much attention has been focused on the effects of sequence variation on the amino acid sequence, variations that disrupt gene processing signals can dramatically impact gene function. A variation that disrupts an exonic splicing enhancer (ESE), for example, could cause exon skipping which would result in the exclusion of an entire exon from the mRNA transcript. RESCUE-ESE, a computational approach used in conjunction with experimental validation, previously identified 238 candidate ESE hexamers in human genes. The RESCUE-ESE method has recently been implemented in three additional species: mouse, zebrafish and pufferfish. Here we describe an online ESE analysis tool (http://genes.mit.edu/burgelab/rescue-ese/) that annotates RESCUE-ESE hexamers in vertebrate exons and can be used to predict splicing phenotypes by identifying sequence changes that disrupt or alter predicted ESEs.
Design and fabrication of omnidirectional reflectors in the visible range (2005)

Abstract An omnidirectional reflector operating in the visible range with the centre wavelength around 532 nm is designed and fabricated. By the calculations of electrical field intensity distributions of the incident light along the propagation direction in the photonic crystal (PC) structure, a minimum period number for producing one-dimensional PCs with an omnidirectional photonic band gap (PBG) is determined. A 12-layer-pair stack of TiO2/SiO2 was grown by the electron-gun evaporation method. Transmission spectra measured with transverse-magnetic- and transverse-electric-polarized incident lights at various angles show that an omnidirectional PBG of 24 nm width is obtained, which is in agreement with theoretically simulated results. This kind of reflector may find applications in engineering measurements, laser beam security, optical filters, biosensors and so on. Acknowledgments We acknowledge support from Wuhan University for innovative programmes and the National Natural Science Foundation of China (grant 60278018).
Human melanoma antigen AH is an autoantigenic ganglioside related to GD2. (1982)

AH antigen, initially defined by an antibody present in a melanoma patient, is a cell surface antigen found on approximately 65% of melanoma cell lines. Absorption analysis indicates that AH is a differentiation antigen marking normal and malignant cells of neuroectodermal origin. The AH determinant has been found to be related to GD2 ganglioside.
An immunogenic region within residues Val1670-Glu1684 of the factor VIII light chain induces antibodies which inhibit binding of factor VIII to von Willebrand factor. (1988)

We have identified a monoclonal anti-factor VIII (FVIII) antibody, C4, which inhibits the binding of purified human FVIII to purified human von Willebrand factor (vWF). Both whole immunoglobulin C4 and its Fab fragment demonstrated dose-dependent inhibition of FVIII binding to vWF immobilized on the surface of polystyrene beads. Synthetic peptides based on the amino acid sequence of FVIII were tested for the ability to block the binding of C4 to FVIII in an enzyme-linked immunosorbent assay system. A single synthetic FVIII pentadecapeptide, consisting of residues Val1670-Glu1684, was able to inhibit C4 binding to FVIII. Under the conditions used, the Val1670-Glu1684 peptide demonstrated total inhibition of C4 binding at a concentration of 1 microM. Synthetic FVIII peptides flanking and overlapping the Val1670-Glu1684 peptide had no significant inhibitory activity on C4 binding in concentrations up to 100 microM. A polyclonal antibody made to the Val1670-Glu1684 peptide also demonstrated inhibition of FVIII binding to vWF. Polyclonal antibodies made to synthetic FVIII peptides flanking and partially overlapping the Val1670-Glu1684 sequence did not demonstrate such inhibition. Localization of the binding region of the monoclonal anti-FVIII antibody C4 to residues Val1670-Glu1684 suggests that this site is at, or near, a major vWF binding domain of FVIII.
Phase-encoded optical sampling for analog-to-digital converters (2000)

A high-speed optical sampling system for electrical signals has been developed using a gain-switched diode laser and a dual-output Mach-Zehnder interferometer. The optical phase shift between the branches of the interferometer is highly linear in the applied electrical signal. The phase shift is encoded in the two outputs of the interferometer and is recovered through digital signal processing. Analog-to-digital (A/D) conversion with 78-dB spur-free dynamic range is demonstrated. Our phase-encoded sampling technique allows high-resolution (12-bit) conversion with high linearity at practical laser power levels.
Isolation of a High Affinity Inhibitor of Urokinase-type Plasminogen Activator by Phage Display of Ecotin (1995)

Ecotin, a serine protease inhibitor found in the periplasm of Escherichia coli, is unique in its ability and mechanism of inhibiting serine proteases of a broad range of substrate specificity. However, although the catalytic domain of human urokinase-type plasminogen activator (uPA) has 40% identity to bovine trypsin and the substrate specificities of these two proteases are virtually identical, ecotin inhibits uPA almost 10,000-fold less efficiently than trypsin. Ecotin was expressed on the surface of filamentous bacteriophage (ecotin phage) to allow the isolation of more potent inhibitors of uPA from a library of ecotin variants. The 142-amino acid inhibitor was fused to the C-terminal domain of the M13 minor coat protein, pIII, through a Gly-Gly-Gly linker and assembled into phage particles. The ecotin phage were shown to react with anti-ecotin antibodies, revealing a stoichiometry of approximately one ecotin per bacteriophage. The ecotin displayed on the surface of phage inhibited trypsin with an equilibrium dissociation constant of 6.7 nM, in close approximation to that of free ecotin, indicating that phage-associated ecotin is correctly folded and functionally active. Reactive-site amino acids 84 and 85 of ecotin were then randomized and a library of 400 unique ecotin phage was created. Three hundred thousand members of the library were screened with immobilized uPA and subjected to three rounds of binding and in vitro selection. DNA sequence analysis of the selected ecotin phage showed that ecotin M84R/M85R predominated while ecotin M84R, M84K, and M84R/M85K were present at a lower frequency. The four ecotin variants were overexpressed and purified and their affinities toward uPA were determined. Each of the selected ecotin variants exhibited increased affinity for uPA when compared to wild-type ecotin with ecotin M84R/M85R showing a 2800-fold increase in binding affinity.