gebhart/patrepeval huggingface dataset:
Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies (2023)

Abstract Background The prognosis for patients with relapsed and/or refractory (R/R) non-Hodgkin’s lymphoma (NHL) or acute lymphoblastic leukaemia (ALL) remains poor, with existing treatments having significant side effects. Developed for the treatment of these cancers, AFM11 is a tetravalent, bispecific humanised recombinant antibody construct (TandAb®) designed to bind to human CD19 and CD3 and lead to the activation of T cells inducing apoptosis and killing of malignant B cells. Methods Two open-label, multicentre, dose-escalation phase 1 studies evaluated the safety, pharmacokinetics and activity of AFM11 in patients with R/R CD19-positive B cell NHL (AFM11-101) and in patients with CD19 + B-precursor Philadelphia-chromosome negative ALL (AFM11-102). Adverse events (AEs) were assessed and recorded; imaging (NHL) or bone marrow assessment (ALL) were used to evaluate response. Additional pharmacodynamic assays undertaken included cytokine release analysis and B-cell and T-cell depletion. Results In AFM11-101, 16 patients with R/R NHL received AFM11 in five different dose cohorts. Of which, 14 experienced drug-related treatment-emergent AEs (TEAEs) [including five serious AEs (SAEs)], five patients experienced dose-limiting toxicity (DLT) and ten patients discontinued the study. The high number of neurological events led to a decrease in infusion frequency during the study. No objective response to treatment was observed. In AFM11-102, 17 patients with R/R ALL received AFM11 in six different dose cohorts. Thirteen patients experienced drug-related TEAEs (including four SAEs), DLTs occurred in two patients and five patients discontinued the study. An objective response was recorded in three patients. The maximum tolerated dose could not be determined in either study due to early termination. Conclusions AFM11 treatment was associated with frequent neurological adverse reactions that were severe in some patients. In ALL, some signs of activity, albeit short-lived, were observed whereas no activity was observed in patients with NHL; therefore, further clinical development was terminated. Trial registration NCT02106091 . Safety Study to Assess AFM11 in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL. Registered April 2014. NCT02848911 . Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL. Registered July 2016.
Can we screen high-risk individuals to detect early pancreatic carcinoma? (2000)

An estimated 10% of individuals with pancreatic cancer have an inherited predisposition to the disease. Germline mutations in BRCA2, p16, STK11, and the cationic trypsinogen gene contribute to inherited forms of pancreatic cancer, but the gene(s) responsible for much of the familial pancreatic cancer burden remains to be identified. The high lifetime risk of pancreatic cancer that exists among at-risk members of families with multiple pancreatic cancers highlights the pressing need for pancreatic cancer early detection strategies. Since curative pancreatic resection is still the only curative treatment for most patients with pancreatic cancer, the early detection of symptomless pancreatic cancer using endoscopic ultrasound or molecular markers may provide the best chance of cure for individuals at high risk of this disease. J. Surg. Oncol. 2000:74:243–248. © 2000 Wiley-Liss, Inc.
122 In-vivo Biomechanical Comparison of the Effects of Rear Tip Extenders on Penile Implants (2018)

A biomechanical study of the AMS CX, AMS LGX, and Coloplast Titan inflatable penile prosthesis (IPP) was conducted where the effect of rear tip extenders was compared in a three cadaver in vivo study. Certified and recognized surgeons inserted the IPPs and recognized scientists and engineers conducted biomechanical testing using approaches that were correlated to standard test methods. Longitudinal compression, modified cantilever deflection, and flexural 3-point bending were used to compare the three IPPs where each were surgically inserted with 1cm, 1.5cm, or 2cm rear tips in three cadavers and inflated to 10psi and 20psi conditions. Furthermore for a corporal length IPP of 20cm made by using an 18cm + 2cm rear tip, a 20cm IPP with no rear tip was tested for comparison. Compression, modified cantilever, and bend data were acquired for the in vivo IPPs. Analysis was assessed based on kink formation in compression, max loading in cantilever testing and 3-point bend testing. Rigidity was also used to assess rear tip effects. Testing order, sequence, and pressure level were other parameters for the assessment.
Co-continuous Metal−Ceramic Nanocomposites (2005)

A room temperature technique was developed to produce continuous metal nanowires embedded in random nanoporous ceramic skeletons. The synthesis involves preparation of uniform, nanoporous ceramic pre-forms and subsequent electrochemical metal infiltration at room temperature, so to avoid material incompatibilities frequently encountered in traditional high-temperature liquid metal infiltration. Structure and preliminary evaluations of mechanical and electronic properties of copper/alumina nanocomposites are reported.
Cavity solitons and patterns in an optically pumped semiconductor amplifier with coherent injection (2005)

We show the spontaneous formation of cavity solitons in a 120 microns diameter, specially designed and very uniform optically pumped semiconductor microcavity as well as patterns with local hexagonal symmetry.
Corneal Collagen Ordering After In Vivo Rose Bengal and Riboflavin Cross-Linking (2020)

Increased OC corresponded with increased collagen fiber organization in CXL corneas. Changes in collagen organization parallel reported temporal changes in cornea stiffness after CXL and also, surprisingly, are detected deeper in the stroma than the regions stiffened by collagen cross-links.
Imaging enzyme activity with polarization‐sensitive confocal fluorescence microscopy (2004)

We describe a technique for imaging enzyme activity through steady-state fluorescence anisotropy measurements on a per-pixel basis with a confocal microscope. With this method, enzyme activity is reported by changes in the fluorescence anisotropy of a fluorescently labelled substrate. Enzymatic cleavage of the substrate yields smaller labelled fragments that tumble more readily than the intact substrate and therefore yield a lower anisotropy. Anisotropy is recovered to an accuracy of 7% or better on and off the optical axis to depths of 210 microm using objective numerical apertures as high as 0.75. Enzyme imaging experiments were performed with Bodipy-FL-labelled bovine serum albumin (BSA) attached to sepharose beads as a substrate for trypsin and proteinase K. Anisotropy images acquired up to 1 h after enzyme addition revealed more rapid digestion of BSA with proteinase K than with trypsin, but in both cases anisotropy decreased by at least five-fold. Fluorescence lifetime and time-resolved anisotropy decay measurements were made on the construct in fluid solution to reveal the effects of enzyme activity. The Bodipy-FL lifetime increased from 1.34 ns for the construct without enzyme to 5.98 ns after 1 h in the presence of proteinase K. Anisotropy decays yielded average rotational correlation times of 1.13 ns before enzymatic action and 0.27 ns after enzymatic action, consistent with the presence of smaller Bodipy-containing protein fragments. These results suggest wide applicability of the technique in biological systems when used in conjunction with appropriately designed constructs.
Model to Hardware Matching; For nano-meter Scale Technologies (2006)

Our ability to reliably predict the outcome of a semiconductor manufacturing process has been steadily deteriorating. This is happening because of two important factors. First, the overall CMOS technology slowdown has led to rapidly increasing complexity in the process and in its interaction with design. This has in turn caused an increase in the number and magnitude of systematic sources of mismatch between simulation models (both at the technology-CAD and at the circuit simulation levels) and hardware measurements. Second, manufacturing variability resulting from random as well as systematic phenomena -long a source of concern only for analog design- is becoming important for digital design as well and thus its prediction is now a first order priority. Process complexity and the challenges of accurately modeling variability have conspired to increase the error in performance predictions, leading to a gap in model to hardware matching. In this paper, we will review these issues and show examples of potential solutions to this problem some of which are currently being developed in IBM, and some which are longer term and would benefit greatly from the attention of the academic community
Chronic Allopregnanolone Treatment Accelerates Alzheimer's Disease Development in AβPPSwePSEN1ΔE9 Mice (2012)

The endogenous neurosteroid allopregnanolone alters neuronal excitability via modulation of the GABAA receptor and causes decreased neurotransmission. In Alzheimer's disease (AD), neurotransmission seems to alter the levels of toxic intracellular amyloid-β (Aβ) oligomers, which are implicated in AD pathogenesis and cause cognitive decline. Inhibition of synaptic activity has been shown to increase levels of intracellular Aβ. Allopregnanolone at endogenous stress levels inhibits synaptic activity and could have similar effects. By using a transgenic AβPP(Swe)PSEN1(ΔE9) mouse model for AD, we observed that chronic allopregnanolone treatment for three months with stress levels of allopregnanolone impaired learning in the Morris water maze. The learning impairment was seen one month after the end of treatment. Chronic allopregnanolone treatment also led to increased levels of soluble Aβ in the brain, which could be a sign of advanced pathogenesis. Since the learning and memory of wild-type mice was not affected by the treatment, we propose that chronic allopregnanolone treatment accelerates the pathogenesis of AD. However, further studies are required in order to determine the underlying mechanism.
Development of a core outcome set for clinical trials in inflammatory bowel disease: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey (2017)

Given that over 30 novel therapeutic compounds are in development for IBD treatment, the design of robust clinical trials measuring relevant and standardised outcomes is crucial. Standardising outcomes through a COS will reduce heterogeneity in trial reporting, facilitate valid comparisons of new therapies and improve clinical trial quality.
ChemInform Abstract: Enantioselective Synthesis of Altohyrtin C (Spongistatin 2): Fragment Assembly and Revision of the Spongistatin 2 Stereochemical Assignment. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Repression of Cyclin D1: a Novel Function of MYC (1994)

Constitutive expression of human MYC represses mRNA levels of cyclin D1 in proliferating BALB/c-3T3 fibroblasts. We expressed a series of mutant alleles of MYC and found that downregulation of cyclin D1 is distinct from previously described properties of MYC. In particular, we found that association with Max is not required for repression of cyclin D1 by MYC in vivo. Conversely, the integrity of a small amino-terminal region (amino acids 92 to 106) of MYC is critical for repression of cyclin D1 but dispensable for transformation of established RAT1A cells. Runoff transcription assays showed that repression occurs at the level of transcription initiation. We cloned the promoter of the gene for human cyclin D1 and found that it lacks a canonical TATA element. Transcription starts at an initiator element similar to that of the adenovirus major late promoter; this element can be directly bound by USF in vitro. Expression of MYC represses the cyclin D1 promoter via core promoter elements and antagonizes USF-mediated transactivation. Taken together, our data define a new pathway for gene regulation by MYC and show that the cyclin D1 gene is a target gene for repression by MYC.
ChemInform Abstract: A New Family of Modular Chiral Ligands for the Catalytic Enantioselective Reduction of Prochiral Ketones. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Pili of Neisseria meningitidis. Analysis of structure and investigation of structural and antigenic relationships to gonococcal pili. (1985)

To provide information useful for the design of a pilus vaccine effective for the prevention of both meningococcal and gonococcal disease, the electron microscopic morphology of meningococcal pili and the structural and antigenic relationships of meningococcal pili to gonococcal pili were investigated. Meningococcal pili were 4-6 nm in width, extended 500-6,000 nm from the organism surface, and occurred singly or in bundles composed of 8-10 pili per bundle. Meningococcal pilin varied between 17,250 and 20,600 daltons. Pilin was present in outer membrane preparations of some meningococcal isolates that were nonpiliated by electron microscopic examination. Antibodies to gonococcal pili, cyanogen bromide cleavage fragments of gonococcal pilin, or synthetic peptide analogues corresponding to regions of the gonococcal pilin sequence, were used to detect common meningococcal and gonococcal antigenic determinants that might indicate the existence of a conserved sequence beyond residue 29. Antibody to intact gonococcal pili or to the variable CNBR-3 region of gonococcal pilin detected little shared antigenicity with meningococcal pilin. However, pilin from all tested meningococcal isolates reacted with antibody to the CNBR-2 fragment of gonococcal pilin, a region highly conserved among gonococcal strains. Meningococcal pilins were also broadly crossreactive with antibody to a synthetic peptide corresponding to residues 69-84 of the gonococcal sequence, a part of the CNBR-2 region that appears to be critical for gonococcal receptor-binding function. If a sequence similar to 69-84 is also important for receptor-binding function in meningococcal pili, a peptide corresponding to this region may elicit antibodies that block the adherence function of pili elaborated by both Neisseria gonorrhoeae and N. meningitidis.
Pulsewidth-stretchable femtosecond erbium fiber lasers using an intracavity short-pass edge filter (2011)

We demonstrate pulsewidth-stretchable Er3+-doped femtosecond mode-locked fiber lasers by incorporating a tunable short-pass edge filter into the ring cavity. Pulsewidth stretch ratio of 3.53 (882/250) can be efficiently achieved under a temperature variation of 4°C.
Optoelectronic oscillator using push-pull Mach-Zehnder modulator biased at null point for optical two-tone signal generation (2005)

We propose a novel optoelectronic oscillator (OHO) made of a push-pull Mach-Zehnder modulator biased at null point, oscillating at half the frequency of feedback signal. Optical two-tone signal with 10.5-GHz frequency difference is experimentally generated.
Femtojoule high speed planar GaAs E-JFET logic (1978)

An integrated inverter stage operating in the gigabit range at a static power dissipation of 100 µW was built for future use in LSI logic circuits. Planar gallium arsenide technology was employed using selective ion-implanted enhancement mode junction field-effect transistors (E-JFET) having 3-µm gate lengths. A nine-stage ring oscillator served as a test vehicle to assess the speed-power product for digital applications. A theoretical analysis shows the transistor operates during the switching transient in the saturation regime, notwithstanding steady-state operation in the linear regime. When the transistor is switched off, the transient response is governed by the load resistance and the input capacitance of the subsequent stage. Means of reducing the switching time by increasing the supply voltage, nonlinear load devices, an output buffer stage, and reduction of gate length and width are described. Directly coupled E-JFET logic does not require level shifting, and, therefore, offers advantages over depletion-mode gallium arsenide MESFET logic by reducing the number of circuit elements per gate. Projected gallium arsenide E-JFET LSI logic circuits will surpass silicon-based bipolar logic with respect to both speed and power, and n-channel silicon MOS logic with respect to speed.
Discovery of N-[2-[5-[Amino(imino)methyl]-2-hydroxyphenoxy]-3,5-difluoro- 6-[3-(4,5-dihydro-1-methyl-1H-imidazol-2-yl)phenoxy]pyridin-4-yl]-N-methylglycine (ZK-807834):  A Potent, Selective, and Orally Active Inhibitor of the Blood Coagulation Enzyme Factor Xa (1998)

ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTDiscovery of N-[2-[5-[Amino(imino)methyl]-2-hydroxyphenoxy]-3,5-difluoro- 6-[3-(4,5-dihydro-1-methyl-1H-imidazol-2-yl)phenoxy]pyridin-4-yl]-N-methylglycine (ZK-807834): A Potent, Selective, and Orally Active Inhibitor of the Blood Coagulation Enzyme Factor Xa 1Gary B. Phillips, Brad O. Buckman, David D. Davey, Keith A. Eagen, William J. Guilford, Josephine Hinchman, Elena Ho, Sunil Koovakkat, Amy Liang, David R. Light, Raju Mohan, Howard P. Ng, Joseph M. Post, Kenneth J. Shaw, Dave Smith, Babu Subramanyam, Mark E. Sullivan, Lan Trinh, Ron Vergona, Janette Walters, Kathy White, Marc Whitlow, Shung Wu, Wei Xu, and Michael M. MorrisseyView Author Information Discovery Research, Berlex Biosciences, 15049 San Pablo Avenue, P.O. Box 4099, Richmond, California 94804-0099 Cite this: J. Med. Chem. 1998, 41, 19, 3557–3562Publication Date (Web):August 15, 1998Publication History Received4 May 1998Published online15 August 1998Published inissue 1 September 1998https://pubs.acs.org/doi/10.1021/jm980280hhttps://doi.org/10.1021/jm980280hrapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views658Altmetric-Citations61LEARN 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 InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Conformation,Inhibition,Inhibitors,Peptides and proteins,Phenyls Get e-Alerts
Supplementary Table 3 from Intraprostatic Androgens and Androgen-Regulated Gene Expression Persist after Testosterone Suppression: Therapeutic Implications for Castration-Resistant Prostate Cancer (2023)

Supplementary Table 3 from Intraprostatic Androgens and Androgen-Regulated Gene Expression Persist after Testosterone Suppression: Therapeutic Implications for Castration-Resistant Prostate Cancer
Estimation of Direct and Indirect Causal Effects in Longitudinal Studies (2004)

The causal effect of a treatment on an outcome is generally mediated by several intermediate variables. Estimation of the component of the causal effect of a treatment that is mediated by a given intermediate variable (the indirect effect of the treatment), and the component that is not mediated by that intermediate variable (the direct effect of the treatment) is often relevant to mechanistic understanding and to the design of clinical and public health interventions. Under the assumption of no-unmeasured confounders, Robins &amp; Greenland (1992) and Pearl (2000), develop two identifiability results for direct and indirect causal effects. They define an individual direct effect as the counterfactual effect of a treatment on an outcome when the intermediate variable is set at the value it would have had if the individual had not been treated, and the population direct effect as the mean of these individual counterfactual direct effects. The identifiability result developed by Robins &amp; Greenland (1992) relies on an additional ``No-Interaction Assumption'', while the identifiability result developed by Pearl (2000) relies on a particular assumption about conditional independence in the population being sampled. Both assumptions are considered very restrictive. As a result, estimation of direct and indirect effects has been considered infeasible in many settings. We show that the identifiability result of Pearl (2000), also holds under a new conditional independence assumption which states that, within strata of baseline covariates, the individual direct effect at a fixed level of the intermediate variable is independent of the no-treatment counterfactual intermediate variable. We argue that our assumption is typically less restrictive than both the assumption of Pearl (2000), and the ``No-interaction Assumption'' of Robins &amp; Greenland (1992). We also generalize the current definition of the direct (and indirect) effect of a treatment as the population mean of individual counterfactual direct (and indirect) effects to 1) a general parameter of the population distribution of individual counterfactual direct (and indirect) effects, and 2) change of a general parameter of the population distribution of the appropriate counterfactual treatment-specific outcome. Subsequently, we generalize our identifiability result for the mean to identifiability results for these generally defined direct effects. We also discuss methods for modelling, testing, and estimation, and we illustrate our results throughout using an example drawn from the treatment of HIV infection.
Molecular analysis of the interaction between cardosin A and phospholipase Dα (2005)

Here we report the identification of phospholipase Dalpha as a cardosin A-binding protein. The interaction was confirmed by coimmunoprecipitation studies and pull-down assays. To investigate the structural and molecular determinants involved in the interaction, pull-down assays with cardosin A and various glutathione S-transferase-fused phospholipase Dalpha constructs were performed. Results revealed that the C2 domain of phospholipase Dalpha contains the cardosin A-binding activity. Further assays with mutated recombinant forms of cardosin A showed that the RGD motif as well as the unprecedented KGE motif, which is structurally and charge-wise very similar to RGD, are indispensable for the interaction. Taken together our results indicate that the C2 domain of plant phospholipase Dalpha can act as a cardosin A-binding domain and suggest that plant C2 domains may have an additional role as RGD/KGE-recognition domains.