gebhart/patrepeval huggingface dataset:
Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile (2012)

We describe the development and clinical translation of a targeted polymeric nanoparticle (TNP) containing the chemotherapeutic docetaxel (DTXL) for the treatment of patients with solid tumors. DTXL-TNP is targeted to prostate-specific membrane antigen, a clinically validated tumor antigen expressed on prostate cancer cells and on the neovasculature of most nonprostate solid tumors. DTXL-TNP was developed from a combinatorial library of more than 100 TNP formulations varying with respect to particle size, targeting ligand density, surface hydrophilicity, drug loading, and drug release properties. Pharmacokinetic and tissue distribution studies in rats showed that the NPs had a blood circulation half-life of about 20 hours and minimal liver accumulation. In tumor-bearing mice, DTXL-TNP exhibited markedly enhanced tumor accumulation at 12 hours and prolonged tumor growth suppression compared to a solvent-based DTXL formulation (sb-DTXL). In tumor-bearing mice, rats, and nonhuman primates, DTXL-TNP displayed pharmacokinetic characteristics consistent with prolonged circulation of NPs in the vascular compartment and controlled release of DTXL, with total DTXL plasma concentrations remaining at least 100-fold higher than sb-DTXL for more than 24 hours. Finally, initial clinical data in patients with advanced solid tumors indicated that DTXL-TNP displays a pharmacological profile differentiated from sb-DTXL, including pharmacokinetics characteristics consistent with preclinical data and cases of tumor shrinkage at doses below the sb-DTXL dose typically used in the clinic.
Evaluation of ketamine HCl for anti-depressant activity. (1975)

Using several routine screening procedures to determine anti-depressant drug activity in experimental laboratory animals, ketamine HCl was found to possess significant activity over a wide-range of oral doses. The tests used were (a) reversal of tetrabenazine-induced ptosis in mice, (b) reversal of reserpine-induced hypothermia in rats, (c) enhancement of yohimbine toxicity in mice and (d) inhibition of oxotremorine-induced tremors in mice. In general, the anti-depressant potency of ketamine HCl was substantially less than that of imipramine HCl.
A Novel Mode of Gleevec Binding Is Revealed by the Structure of Spleen Tyrosine Kinase (2004)

Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase required for signaling from immunoreceptors in various hematopoietic cells. Phosphorylation of two tyrosine residues in the activation loop of the Syk kinase catalytic domain is necessary for signaling, a phenomenon typical of tyrosine kinase family members. Syk in vitro enzyme activity, however, does not depend on phosphorylation (activation loop tyrosine --> phenylalanine mutants retain catalytic activity). We have determined the x-ray structure of the unphosphorylated form of the kinase catalytic domain of Syk. The enzyme adopts a conformation of the activation loop typically seen only in activated, phosphorylated tyrosine kinases, explaining why Syk does not require phosphorylation for activation. We also demonstrate that Gleevec (STI-571, Imatinib) inhibits the isolated kinase domains of both unphosphorylated Syk and phosphorylated Abl with comparable potency. Gleevec binds Syk in a novel, compact cis-conformation that differs dramatically from the binding mode observed with unphosphorylated Abl, the more Gleevec-sensitive form of Abl. This finding suggests the existence of two distinct Gleevec binding modes: an extended, trans-conformation characteristic of tight binding to the inactive conformation of a protein kinase and a second compact, cis-conformation characteristic of weaker binding to the active conformation. Finally, the Syk-bound cis-conformation of Gleevec bears a striking resemblance to the rigid structure of the nonspecific, natural product kinase inhibitor staurosporine.
Increasing the Size of an Aromatic Helical Foldamer Cavity by Strand Intercalation (2014)

The postsynthetic modulation of capsules based on helical aromatic oligoamide foldamers would be a powerful approach for controlling their receptor properties without altering the initial monomer sequences. With the goal of developing a method to increase the size of a cavity within a helix, a single-helical foldamer capsule was synthesized with a wide-diameter central segment that was designed to intercalate with a second shorter helical strand. Despite the formation of stable double-helical homodimers (K(dim)>10(7) M(-1)) by the shorter strand, when it was mixed with the single-helical capsule sequence, a cross-hybridized double helix was formed with K(a)>10(5) M(-1). This strategy makes it possible to direct the formation of double-helical heterodimers. On the basis of solution- and solid-state structural data, this intercalation resulted in an increase in the central-cavity size to give a new interior volume of approximately 150 Å(3).
Stability of Surface-Immobilized Lubricant Interfaces under Flow (2015)

The stability and longevity of surface-stabilized lubricant layers is a critical question in their application as low- and nonfouling slippery surface treatments in both industry and medicine. Here, we investigate lubricant loss from surfaces under flow in water using both quantitative analysis and visualization, testing the effects of underlying surface type (nanostructured versus flat), as well as flow rate in the physiologically relevant range, lubricant type, and time. We find lubricant losses on the order of only ng/cm2 in a closed system, indicating that these interfaces are relatively stable under the flow conditions tested. No notable differences emerged between surface type, flow rate, lubricant type, or time. However, exposure of the lubricant layers to an air/water interface did significantly increase the amount of lubricant removed from the surface, leading to disruption of the layer. These results may help in the development and design of materials using surface-immobilized lubricant interfaces for repellency under flow conditions.
Descemet's Stripping With Endothelial Keratoplasty in 50 Eyes: A Refractive Neutral Corneal Transplant (2005)

Compared to standard penetrating keratoplasty, DSEK causes minimal refractive change and provides rapid visual recovery for patients with endothelial dysfunction. This technique maintains the structural integrity of the cornea by preserving the recipient's epithelium, Bowman's layer, and entire stromal thickness.
Phase Ib evaluation of MPDL3280A (anti-PDL1) in combination with bevacizumab (bev) in patients (pts) with metastatic renal cell carcinoma (mRCC). (2015)

410 Background: MPDL3280A, a human anti-PD-L1 IgG1 mAb engineered to remove Fc-effector function, prevents PD-L1 binding to the inhibitory receptors PD-1 and B7.1 on activated T cells. Single-agent MPDL3280A has demonstrated clinical activity in various cancers, including RCC. Bev was postulated to enhance the antitumor effects of MPDL3280A by blocking VEGF-related suppressive effects on immune function and lymphocyte traffic. Therefore, a multicenter Phase Ib study was conducted to determine the safety and activity of MPDL3280A + bev, including in a cohort of mRCC pts. Methods: mRCC pts with clear cell histology and available pre-treatment tumor specimens were enrolled. In addition to the safety and activity endpoints, an exploratory objective was to assess treatment effects on the tumor microenvironment and peripheral biomarkers. Bev 15 mg/kg was given alone on Cycle 1 Day 1 and concurrently with MPDL3280A 20 mg/kg q3w thereafter. On-treatment tumor biopsy was performed during Cycle 1 and 4-6 weeks after the start of Cycle 2. Objective responses were assessed by RECIST v1.1. The clinical data cutoff was July 7, 2014. Results: 12 pts were evaluable for safety. The median age was 64 y, 58% were male and 83% had no prior systemic therapy. The median duration of exposure was 232.5 days. Grade 3-4 AEs included postoperative wound infection, hypercalcemia, tumor pain, acute respiratory failure in a patient with influenza (1 pt each) and hypertension (3 pts). No Grade 3-4 AEs were assessed as related to MPDL3280A. Among first-line mRCC pts with ≥ 1 tumor assessment (n = 10), the ORR was 40% (3 of 4 responses confirmed at the time of the data cutoff). Minimum follow-up was 2.1 mo. Increases in tumor-infiltrating CD8+ T cells were observed on-treatment. Updated data, including biomarkers, will be presented. Conclusions: The combination of MPDL3280A + bev waswell tolerated in clear cell mRCC pts. Promising preliminary clinical activity and immune modulation of the tumor microenvironment were observed. A Phase II trial of MPLD3280A ± bevacizumab vs sunitinib in pts with previously untreated mRCC is currently ongoing. Clinical trial information: NCT01633970.
Comprehensive Inpatient Treatment of Refractory Chronic Daily Headache (2009)

Most patients (78%) improved following aggressive, comprehensive inpatient treatment. Maintenance of improvement is likely to depend on multiple post-discharge factors, including continuity of care, compliance, and home or work environment.
Subcutaneous co-administration of a potent bisphosphonate with recombinant human hyaluronidase (rHuPH20) inhibits injection site reactions with systemic bioavailability comparable to intravenous bisphosphonate administration in preclinical animal models (2008)

4033 Bisphosphonates (BPs) inhibit osteoclastic bone resorption and are used clinically to reduce elevated blood calcium levels and maintain skeletal bone mass. Typically administered by intravenous administration, bisphosphonates are indicated for the treatment of metastatic bone disease, multiple myeloma and hypercalcemia of malignancy. Subcutaneous (SC) injection of BP’s are associated with considerable cutaneous toxicity. The tolerability of SC BP with recombinant human hyaluronidase (rHuPH20), an enzyme that increases the absorption of locally injected drugs by degrading hyaluronan (HA) in the skin interstitium was therefore explored. Specifically, we investigated BP and rHuPH20 by local co-administration in both a rat interdermal (ID) model, as a high-throughput surrogate for human SC injection site reactions (ISRs); and in a porcine pharmacokinetic (PK) model, as a surrogate for human BP pharmacokinetics.  To evaluate whether rHuPH20 co-administration could alleviate ISRs associated with SC BP administration, rats were dosed ID with BP at 0.05 - 0.6 mg/ml, in admixture with rHuPH20. ID injections with BP resulted in reproducible ISRs that were quantified by adverse effect parameters including induration, erythema, and ulceration. All ISR parameters increased by BP dose in a concentration dependent manner. Co-administration of BP with 100 micrograms/mL rHuPH20 eliminated indurations and ulcerations in animals receiving doses
Has the mortality of septic shock changed with time? (1998)

The present review showed a slight reduction in mortality from septic shock over the years, although this result should be approached with caution. The heterogeneity of the articles and absence of a severity score for most of the studies limited our analysis. Furthermore, there was an increasing prevalence of Gram-positive causative organisms, and a change of the predominant origin of sepsis from the abdomen to the chest.
Role of hypoxia and extracellular matrix‐integrin binding in the modulation of angiogenic growth factors secretion by retinal pigmented epithelial cells (1999)

The retinal pigmented epithelium (RPE) is a monolayer of polarized cells located between retinal photoreceptors and blood vessels of the choroid. The basal surface of RPE cells rests on Bruch's membrane, a complex extracellular matrix structure which becomes abnormal in several disease processes, including age-related macular degeneration (AMD). Ruptures or abnormalities in Bruch's membrane are frequently accompanied by choroidal neovascularization. Disturbed interaction of RPE cells with their extracellular matrix (ECM) could play a role in this process. The present study was undertaken to examine the complex interactions between hypoxia, integrin, and ECM in the regulation of RPE functions. Antibody blocking experiments demonstrated that RPE cell adhesion to vitronectin is mediated primarily through alphavbeta5 and adhesion to fibronectin occurs through alpha5beta1. RPE adhesion to immobilized laminin demonstrated highest level of non-RGD-mediated adhesion as compared to that with collagen IV or the RGD matrices such as vitronectin (alphavalpha5) , fibronectin (alpha5beta1), or thrombospondin (alpha5beta1 + alphavbeta5). Addition of soluble vitronectin, or fibrinogen to RPE cell cultures resulted in a small to moderate increase in VEGF and FGF2 in the media, while each of these growth factors was dramatically increased after addition of thrombospondin 1 (TSP1). In contrast, soluble fibronectin resulted in differential upregulation of VEGF but not FGF2. Similarly, immobilized TSP1 resulted in differential greater upregulation in VEGF but not FGF2 release from RPE as compared to other ECMs under either normoxic or hypoxic conditions. Additionally, hypoxia resulted in a time-dependent increase in VEGF, but not FGF2 release in the media. RPE cells grown on TSP1-coated plates showed increased VEGF and FGF2 in their media compared to cells grown on plates coated with type IV collagen, laminin, vitronectin, or fibronectin. The TSP1-induced increase in secretion of growth factors was partially blocked by anti-alpha5beta1, anti-alphavbeta3, and anti-alphavbeta5 antibodies indicating that it may be mediated in part by TSP1 binding to those integrins. These data suggest that alterations in oxygen levels (hypoxia/ischemia) and ECM of RPE cells, a prominent feature of AMD, can cause increased secretion of angiogenic growth factors that might contribute to the development of choroidal neovascularization. These data also suggest the potential modulatory role of VEGF release from RPE by ECM and alphavbeta5 and alpha5beta1 integrins.
Inhibition of Bacterial Superantigens by Peptides and Antibodies (2001)

The pyrogenic exotoxins of group A streptococci and staphylococcal enterotoxins are a family of structurally related superantigens with similar biological activity. Two distinct areas have been identified which have a highly conserved amino acid homology in all of the toxin families. A number of peptides were constructed from these regions, some of which were concatenated and polymerized to enhance their immunogenicity in animals. Antibodies prepared against these polymerized peptides were used to serologically identify the majority of the superantigen toxins, block the biological activities of the superantigens, and protect an experimental animal model against shock. In addition certain peptides were able per se to block up to 90% of the proliferative responses induced by the toxins. The peptide also proved protective in a septic shock model in mice. Binding experiments indicate that the peptide binds tightly to the major histocompatibility complex class II molecule, thus preventing binding and hence activation of the superantigen. The selective and rapid binding of the peptide to the major histocompatibility complex class II molecule may lead to a novel therapeutic modality in treatment of superantigen-mediated diseases.
Prostanoic acid chemistry (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProstanoic acid chemistryJohn E. Pike, F. H. Lincoln, and William Paul SchneiderCite this: J. Org. Chem. 1969, 34, 11, 3552–3557Publication Date (Print):November 1, 1969Publication History Published online1 May 2002Published inissue 1 November 1969https://doi.org/10.1021/jo01263a071Request reuse permissions Article Views188Altmetric-Citations89LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (899 KB) Get e-Alertsclose Get e-Alerts
Double-Shelled Nanocapsules of V2O5-Based Composites as High-Performance Anode and Cathode Materials for Li Ion Batteries (2009)

Double-shelled nanocapsules of V(2)O(5)-SnO(2) composites were chemically assembled via a one-pot solution method. These hollow nanocapsules are composed of a double-shelled V(2)O(5) matrix that includes a low weight ratio of SnO(2) (e.g., 10 or 15%). In these double shells, open-structured V(2)O(5) acts as not only a supporting matrix but also an active electrode component. The gap between the two shells and the hollow cavity provide sufficient space for volume variation during conversion reactions and lithium alloying/dealloying processes. As a promising anode electrode, this nanocomposite shows a large, reversible capacity of 947 mA h g(-1) at a rate of 250 mA g(-1) and retains a high capacity of 673 mA h g(-1) after 50 cycles. Even at a high rate of 2500 mA g(-1), the current nanocomposite electrode can still deliver a reversible capacity of 505 mA h g(-1). As a cathode electrode, our nanocomposite shows not only a high reversible capacity of approximately 250 mA h g(-1) but also good cycling and rate capability.
Influence of Rheumatoid Arthritis on Employment, Function, and Productivity in a Nationally Representative Sample in the United States (2010)

In the most recent available national data for adults, RA was associated with reductions in employment, productivity, and function.
Increased Thermal Stability of Collagen in the Presence of Sugars and Polyols1 (1983)

The effects of sugars and polyols on the thermal denaturation temperature, Tm, of acid-soluble collagen from calf skin were studied at pH 4.0 under atmospheric pressure as well as high pressures up to 4,000 atm. Addition of these compounds invariably raised Tm with increases in their concentration over the whole range of pressure. The extent of stabilization by different sugars and polyols is discussed in terms of their different influences on the structure of water. The hydroxymethyl chain length of polyols and equatorial OH groups of the sugars were found to be decisive factors for their stabilizing effect on collagen structure. The similarity in their stabilizing effects on collagen and globular proteins suggests that our stabilization mechanism proposed for globular proteins can be essentially extended to fibrous proteins: such protein stabilization would be dominantly mediated through a preferential hydration of protein, originating in the water-structure-making character of sugars and polyols.
Association of post-cesarean delivery endometritis with colonization of the chorioamnion by (1995)

Colonization of the chorioamnion with U urealyticum in women with intact membranes being delivered by cesarean is a significant, independent predictor of subsequent endometritis.
MicroRNA Sequence Profiles of Human Kidney Allografts With or Without Tubulointerstitial Fibrosis (2012)

Differentially expressed miRNAs and their predicted targets identified by deep sequencing are candidates for further investigation to decipher the mechanism and management of kidney allograft fibrosis.
Noninvasive, Infrared Monitoring of Cerebral and Myocardial Oxygen Sufficiency and Circulatory Parameters (1977)

The relatively good transparency of biological materials in the near infrared region of the spectrum permits sufficient photon transmission through organs in situ for the monitoring of cellular events. Observations by infrared transillumination in the exposed heart and in the brain in cephalo without surgical intervention show that oxygen sufficiency for cytochrome a,a3, function, changes in tissue blood volume, and the average hemoglobin-oxyhemoglobin equilibrium can be recorded effectively and in continuous fashion for research and clinical purposes. The copper atom associated with heme a3 did not respond to anoxia and may be reduced under normoxic conditions, whereas the heme-a copper was at least partially reducible.
Molecular Targets for AIDS Therapy (1990)

The development of antiretroviral therapy against acquired immunodeficiency syndrome (AIDS) has been an intense research effort since the discovery of the causative agent, human immunodeficiency virus (HIV). A large array of drugs and biologic substances can inhibit HIV replication in vitro. Nucleoside analogs--particularly those belonging to the dideoxynucleoside family--can inhibit reverse transcriptase after anabolic phosphorylation. 3'-Azido-2',3'-dideoxythymidine (AZT) was the first such drug tested in individuals with AIDS, and considerable knowledge of structure-activity relations has emerged for this class of drugs. However, virtually every step in the replication of HIV could serve as a target for a new therapeutic intervention. In the future, non-nucleoside-type drugs will likely become more important in the experimental therapy of AIDS, and antiretroviral therapy will exert major effects against the morbidity and mortality caused by HIV.
A Self-Assembled Multivalent Pseudopolyrotaxane for Binding Galectin-1 (2004)

A self-assembled pseudopolyrotaxane consisting of lactoside-displaying cyclodextrin (CD) "beads" threaded onto a linear polyviologen "string" was investigated for its ability to inhibit galectin-1-mediated T-cell agglutination. The CDs of the pseudopolyrotaxane are able to spin around the axis of the polymer chain as well as to move back and forth along its backbone to alter the presentation of its ligand. This supramolecular superstructure incorporates all the advantages of polymeric structures, such as the ability to span large distances, along with a distinctively dynamic presentation of its lactoside ligands to afford a neoglycoconjugate that can adjust to the relative stereochemistries of the lectin's binding sites. The pseudopolyrotaxane exhibited a valency-corrected 10-fold enhancement over native lactose in the agglutination assay, which was greater than the enhancements observed for lactoside-bearing trivalent glycoclusters and a lactoside-bearing chitosan polymer tested using the same assay. The experimental results indicate that supramolecular architectures, such as the pseudopolyrotaxane, provide tools for investigating protein-carbohydrate interactions.
Surface‐Specific Zeolite‐Binding Proteins (2002)

Proteins that distinguish the crystallographic planes of zeolites have been identified. On EMT zeolite the proteins obscure only the (001) face and are able to immobilize an enzyme with negligible loss of activity (see dye‐exclusion assay, Figure). A general method for isolating proteins able to distinguish spatial orientations of atoms on non‐biological surfaces is described.