gebhart/patrepeval huggingface dataset:
Immunological approach to inhibit formation of anti‐antibodies to allo‐ and xenogeneic anti‐T cell immunoglobulin (1994)

Inhibitory anti-antibodies induced in patients by xenogeneic or even by humanized anti-T cell antibodies remain an unresolved problem. Mice also produce anti-antibodies following injection of xeno- or allogeneic anti-T cell antibodies. Here we report a principle based on sequentially applied anti-T cell antibodies generated in different species, which results in suppressed anti-antibody formation and prolonged immunosuppression. Thus, a single priming injection in mice of mouse (MmT1 or MmT5 differing by idiotype only) or of rat (RmT1) anti-mouse Thy-1 monoclonal antibodies (mAb) or of rat anti-mouse L3T4 + Ly-2 (RmCD4 + CD8) mAb suppressed anti-antibody formation against subsequent booster injections of one of the above antibodies, provided that they differed in species origin from the priming antibody. Correspondingly, a sixfold and longer prolongation of 50% survival of fully mismatched skin grafts was observed. Less or no anti-antibody suppression and little prolongation of graft survival was obtained if the 'first' and the 'second' (and following) antibody injections were of the same species, differing by iso- or idiotype only. Finally, the suppressive principle did not manifest itself at all if the initial antibody injection included both the first and second antibody. These findings are discussed with reference to earlier studies on hapten/carrier effects as well as on immunosuppression attributed to 'non-depleting' rat anti-CD4/CD8 T cell antibodies.
Supplementary Methods and Figure Legend from Proteomic Profiling Identifies Dysregulated Pathways in Small Cell Lung Cancer and Novel Therapeutic Targets Including PARP1 (2023)

&lt;p&gt;PDF file, 142K.&lt;/p&gt;
A phase 3 trial comparing fianlimab (anti–LAG-3) plus cemiplimab (anti–PD-1) to pembrolizumab in patients with completely resected high-risk melanoma. (2023)

TPS9598 Background: Melanoma (Mel) accounts for the majority of skin cancer-related deaths. Most patients (pts) with a newly diagnosed Mel have resectable disease and are potentially cured by surgery. However, regional nodal and/or distant relapses can occur after curative-intent resection. Postoperative adjuvant therapy with immune checkpoint inhibitors improves relapse-free survival (RFS) and distant metastasis-free survival (DMFS) of pts at high risk of Mel. Fianlimab (anti-LAG-3) and cemiplimab (anti-PD-1) are both high-affinity, fully human, IgG4 monoclonal antibodies (MAbs) that combined have shown high clinical activity in pts with advanced Mel in a phase 1 study. Additionally, combination of relatlimab (anti-LAG-3) and nivolumab (anti-PD-1) have shown superiority over nivolumab for PFS in advanced Mel. These observations provide a rationale for use of fianlimab and cemiplimab combination in high-risk adjuvant Mel. Methods: Our study (NCT05608291) is a three-way, double-blind, phase 3 trial to compare fianlimab + cemiplimab to pembrolizumab in the adjuvant therapy (Rx) of high-risk, resected Mel. The primary objective is RFS, and the secondary objectives are overall survival, safety, pharmacology, and immunogenicity. This international trial will be conducted at 200 sites. Pt eligibilities: (1) ≥12 years of age; (2) Stage IIc, III or IV (all M-stages) and histologically confirmed Mel, completely resected ≤12 weeks prior to randomization; (3) no prior systemic anti-cancer Rx or radiation Rx for Mel in the previous 5 years; (4) no evidence of metastatic disease on staging investigations; and (5) an Eastern Cooperative Oncology Group performance status (PS) of 0 or 1 (for adult pts), Karnofsky PS &gt;70 (pts &gt;16 years) or Lansky PS &gt;70 (pts &lt;16 years). Study arms (all Rx every 3 weeks intravenously for one year): A. fianlimab (1600 mg) + cemiplimab (350 mg); B. fianlimab (400 mg) + cemiplimab (350 mg); C. pembrolizumab (200 mg) + saline/dextrose placebo. The placebo controlled trial will enroll about 1530 pts, randomized 1:1:1 to Arms A:B:C, treated for up to 1 year. The trial will stratify by disease stage (stage IIIA vs IIC-IIIB-IIIC vs IIID-IV [M1a/b] vs IV [M1c/d]), and geography (North America vs Europe vs Rest of World). The primary endpoint is investigator-assessed RFS. The secondary endpoints include efficacy (overall survival, DMFS, melanoma-specific survival), safety [treatment-emergent adverse events (TEAEs), interruption or discontinuation of drugs due to TEAEs], pharmacokinetic (concentrations of fianlimab and cemiplimab in serum over time), immunogenicity (anti-drug Abs and neutralizing Abs in serum against fianlimab or cemiplimab), and patient reported outcomes. The first analysis will be performed when 242 RFS events have been observed. Clinical trial information: NCT05608291 .
Extensive Pleural and Pericardial Effusion In 4 CML Patients Treated with Dasatinib at 100 Mg or 50 Mg Once Daily. (2010)

Abstract Abstract 4496 The multikinase BCR/ABL inhibitor dasatinib exerts major growth-inhibitory effects in imatinib-resistant patients with chronic myeloid leukemia (CML). Although previously reported to be a well-tolerated drug, several side effects such as pleural and pericardial effusion have been reported at a dose of 140 mg daily. Therefore, the approved standard dose of dasatinib was reduced to 100 mg daily. More recent data suggest that freshly diagnosed patients with CML treated with dasatinib at 100 mg once daily may still develop pleural effusions, but the frequency of this side effect was reported to be lower compared to patients receiving 140 mg daily dasatinib. Moreover, effusion formation was reported to be less severe, with almost no grade 3/4 events, in patients receiving 100 mg daily dasatinib. We examined a cohort of CML patients (n=13) treated with dasatinib at 100 mg or 50 mg daily, for development of severe non-hematologic side effects. Patients received dasatinib for at least 3 months (range: 3–38 months; observation period: March 2005 to June 2010). Of these 13 patients, 4 had previously received 140 mg dasatinib daily. In all 4 patients, the dose of dasatinib was reduced to 100 mg or 50 mg daily because of effusion formation. In the other 9 patients, the initial dose of dasatinib was 100 mg daily. Of these 9 patients, 2 patients in chronic phase (CP) received dasatinib as frontline therapy. Four of our 13 patients developed severe effusions (grade 3/4) while on dasatinib at 100 mg or 50 mg daily, including one CP patient receiving dasatinib as frontline therapy. In two patients, massive pleural effusions were recorded, and two developed pericardial effusion together with pleural effusions. In two patients, effusion formation required paracentesis and surgical intervention. No pre-existing cardiac or pulmonary diseases were known in these 4 patients. In 3 patients, dasatinib had to be discontinued despite treatment with low dose glucocorticosteroids and diuretics. After switching to an alternative BCR/ABL inhibitor, no further effusion formation occurred. In summary, dasatinib-treated patients are at risk for the development of pleural and pericardial effusions even when the drug is administered at a dose of 100 mg or 50 mg daily. Therefore, all patients should be examined carefully for pre-existing relevant comorbidities and cardiovascular risk factors before dasatinib is started, and all patients should have repeated chest × ray controls during long-term treatment with dasatinib. Disclosures: Valent: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding.
Performance limitation by finite gbw in continuous-time quadrature bandpass sigma-delta modulators (2009)

Continuous-time quadrature bandpass sigma-delta modulators seriously suffer from finite gain bandwidth of the amplifiers they contain. In this paper, the performance limitation of the continuous-time quadrature bandpass sigma-delta modulator caused by finite gain bandwidth is presented. Finite gain bandwidth results in an unstable behavior of the complex integrators and a deviation from the center frequency. In order to improve stability of the complex integrator by finite GBW, it is desirable to employ a lossy integrator. The deviation from the center freqency affects the in-band noise power of the modulator. A compensation solution for reducing the deviation from the center frequency is proposed by means of transconductors at the amplifier inputs.
Detecting Trojaned DNNs Using Counterfactual Attributions (2023)

We target the problem of detecting Trojans or backdoors in DNNs. Such models behave normally with typical inputs but produce targeted mispredictions for inputs poisoned with a Trojan trigger. Our approach is based on a novel intuition that the trigger behavior is dependent on a few ghost neurons that are activated for both input classes and trigger pattern. We use counterfactual explanations, implemented as neuron attributions, to measure significance of each neuron in switching predictions to a counter-class. We then incrementally excite these neurons and observe that the model’s accuracy drops sharply for Trojaned models as compared to benign models. We support this observation through a theoretical result that shows the attributions for a Trojaned model are concentrated in a small number of features. We encode the accuracy patterns by using a deep temporal set encoder for trojan detection that enables invariance to model architecture and a number of classes. We evaluate our approach on four US IARPA/NIST-TrojAI benchmarks with high diversity in model architectures and trigger patterns. We show consistent gains over state-of-the-art adversarial attack based model diagnosis (+5.8%absolute) and trigger reconstruction based methods (+23.5%), which often require strong assumptions on the nature of the attack.
Optimal Subspace Techniques for DOA Estimation in the Presence of Noise and Model Errors (2006)

Signal parameter estimation and specically direction of arrival (DOA) es-timation for sensor array data is encountered in a number of applications ranging from electronic surveillance to wireless communications. Subspace based methods have shown to provide computationally as well as statis-tically ecient algorithms for DOA estimation. Estimator performance is ultimately limited by model disturbances such as measurement noise and model errors. Herein, we review a recently proposed framework that allows the derivation of optimal subspace methods taking both nite sample eects (noise) and model perturbations into account. We show how this general estimator reduces to well known techniques for cases when one disturbance dominates completely over the other. 1.1
Dopaminergic mechanisms underlying bladder hyperactivity in rats with a unilateral 6‐hydroxydopamine (6‐OHDA) lesion of the nigrostriatal pathway (2003)

1. This study was undertaken to elucidate dopaminergic mechanisms underlying bladder hyperactivity in a rat model of Parkinson's disease (PD) induced by a unilateral 6-OHDA injection into the substantia nigra pars compacta. 2. In 6-OHDA-lesioned rats, voided volume per micturition (0.41+/-0.04 ml, mean+/-s.e.m.) measured during 24 h in a metabolic cage was significantly smaller than in sham-operated rats (0.67+/-0.07 ml). 3. Cystrometrograms (CMG) in conscious animals revealed significantly smaller bladder capacity (BC) (0.46+/-0.03 ml) in 6-OHDA-lesioned rats than in sham rats (0.72+/-0.06 ml). 4. SKF38393 (D1/D5 receptor agonist, i.v.) significantly increased BC in 6-OHDA rats without apparent effects in sham rats. SKF38393 applied intracerebroventricularly (i.c.v.) under urethane anesthesia also increased BC in 6-OHDA-lesioned rats and by a smaller increment in sham rats. 5. In contrast, quinpirole (D2/D3/D4 receptor agonist, i.v.) significantly reduced BC in sham and 6-OHDA-lesioned rats. Intrathecal injection of quinpirole similarly reduced BC in sham and 6-OHDA-lesioned rats. 6. PD128907 (D(3)-receptor agonist) did not have significant effects on BC in 6-OHDA-lesioned rats. 7. These results indicate that a rat model of PD exhibited bladder hyperactivity as observed in patients with PD, and that stimulation of D1/D5 dopamine receptors at a supraspinal site can suppress bladder hyperactivity in PD, whereas stimulation of D2/D4, but not D3, dopamine receptors had the opposite effect to reduce bladder capacity. Thus, D1/D5 dopamine receptor agonists might be effective in treating neurogenic bladder hyperactivity in PD.
Anionic N-Fries Rearrangement Induced by I-Mg Exchange (2008)

This article presents an expedient one-pot process for the easy preparation of oxo-anilides, via an iodine-magnesium exchange, regiospecific anionic ortho-N-Fries rearrangement and in situ trapping of the aniline anion. The oxo-anilides can subsequently be subjected to McMurry cyclization reactions, thus offering a convenient access to 1,2,3-trisubstituted indoles with tertiary carbon substituents at the C3 position.
Low detection limit sensor based on subwavelength grating racetrack resonator (2017)

Subwavelength grating (SWG) ring resonators have demonstrated better sensitivity compared to the conventional silicon strip ring resonators due to the enhanced photon-analyte interaction. As the sensors are usually used in absorptive ambient environment, it is extreme challenging to further improve the sensitivity of the SWG ring resonator without deteriorating the quality factor because the coupling strength between the bus waveguide and the circular ring resonator is not sufficient to compensate the loss. To explore the full potential of the SWG ring resonator, we experimentally demonstrate a silicon-based high quality factor and low detection limit transverse magnetic (TM) mode SWG racetrack resonator around 1550 nm. A quality factor of 9800 is achieved in aqueous environment when the coupling length and gap are equal to 6.5 &mu;m and 140 nm, respectively. The bulk sensitivity (S) is ~429.7 nm/RIU (refractive index per unit), and the intrinsic detection limit (iDL) is 3.71&times;10<sup>-4</sup> RIU reduced by 32.5% compared to the best value reported for SWG microring sensors.
Secondary structural complementarity between DNA and proteins. (1977)

A model for the complex between double-stranded DNA and a beta-ribbon (a two-stranded antiparallel beta-sheet) of proteins is proposed as one of the possible modes of structural recognition between DNA and proteins. In this model, the contact occurs on the narrow groove of DNA, and the symmetry elements as well as the repeat distances of DNA and the beta-ribbon coincide, thus providing favorable complementary contacts.
S-Figure-4 from Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma (2023)

&lt;p&gt;In vitro combination treatment of Lkb1-null cell lines with AZD7762 plus the indicated other drug&lt;/p&gt;
Routine 3D magnetic resonance imaging of joints (2011)

Due to its high spatial resolution and excellent tissue contrast, magnetic resonance imaging (MRI) has become the most commonly used imaging method to evaluate joints. Most musculoskeletal MRI is performed using 2D fast spin-echo sequences. However, 3D sequences have also been used for joint imaging and have the advantage of acquiring thin continuous slices through joints, which reduces the effects of partial volume averaging. With recent advances in MR technology, 3D sequences with isotropic resolution have been developed. These sequences allow high-quality multiplanar reformat images to be obtained following a single acquisition, thereby eliminating the need to repeat sequences with identical tissue contrast in different planes. Preliminary results on the diagnostic performance of 3D isotropic resolution sequences are encouraging. However, additional studies are needed to determine whether these sequences can replace currently used 2D fast spin-echo sequences for providing comprehensive joint assessment in clinical practice.
Voltage holding considerations for direct-collection units (1973)

Results have been obtained from initial experiments designed to study high-voltage breakdown under conditions of importance to the design of direct- collection units. A coaxial configuration was used to mock-up critical fields near grid wires. With appropriate heat conditioning, fields as high as 9.6 x 10/ sup 5/ V/cm were maintained at the surface of a 7-mil-diam tungsten wire. This represents an enhanced field of ~10/sup 8/V/cm at whisker'' sites. Breakdown criteria are proposed for three regimes; initial, field-emission, and ultimate, which differ by the amount of prior conditioning applied to the wire. Additional considerations of importance to direct collectors such as the effect of thermionic emission and ion bombardment are discussed. (auth)
Combined Computational-Experimental Analyses ofCFTRExon Strength Uncover Predictability of Exon-Skipping Level (2013)

With the increased number of identified nucleotide sequence variations in genes, the current challenge is to classify them as disease causing or neutral. These variants of unknown clinical significance can alter multiple processes, from gene transcription to RNA splicing or protein function. Using an approach combining several in silico tools, we identified some exons presenting weaker splicing motifs than other exons in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. These exons exhibit higher rates of basal skipping than exons harboring no identifiable weak splicing signals using minigene assays. We then screened 19 described mutations in three different exons, and identified exon-skipping substitutions. These substitutions induced higher skipping levels in exons having one or more weak splicing motifs. Indeed, this level remained under 2% for exons with strong splicing motifs and could reach 40% for exons having at least one weak motif. Further analysis revealed a functional exon splicing enhancer within exon 3 that was associated with the SR protein SF2/ASF and whose disruption induced exon skipping. Exon skipping was confirmed in vivo in two nasal epithelial cell brushing samples. Our approach, which point out exons with some splicing signals weaknesses, will help spot splicing mutations of clinical relevance.
Reciprocity calibration of Distributed Massive MIMO Access Points for Coherent Operation (2021)

Novel network architectures for 6G distributed massive MIMO systems rely on coherent signaling by distributed antenna panels which are coordinated by a central controller. This type of network architecture is based on reciprocity operation where antenna panels rely on uplink channel estimates for coherent downlink precoding. This paper proposes a calibration method for distributed massive MIMO systems, which overcomes hardware non-reciprocities in order to enable reciprocity-based operation. Measurements for system calibration are collected via a beam-sweep between all pairs of antenna panels. We lay out the system model for this new setup, and propose a maximum likelihood-based procedure to compute calibration coefficients based on the collected measurement set. The procedure is computationally efficient and stable, since 1) each iteration has a closed-form, and 2) the procedure is guaranteed to converge to at least a local optimum (or saddle point). Simulations indicate significant calibration improvements compared to re-using state of the art calibration schemes for the problem at hand.
Isolation and characterization of copper methylene (CuCH2) via FTIR matrix isolation spectroscopy (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIsolation and characterization of copper methylene (CuCH2) via FTIR matrix isolation spectroscopySou Chan Chang, Zakya H. Kafafi, Robert H. Hauge, W. Edward Billups, and John L. MargraveCite this: J. Am. Chem. Soc. 1987, 109, 15, 4508–4513Publication Date (Print):July 1, 1987Publication History Published online1 May 2002Published inissue 1 July 1987https://pubs.acs.org/doi/10.1021/ja00249a013https://doi.org/10.1021/ja00249a013research-articleACS PublicationsRequest reuse permissionsArticle Views220Altmetric-Citations28LEARN 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-Alertsclose Get e-Alerts
A Distributed Stubs Technique to Mitigate Flicker Noise Upconversion in a mm-Wave Rotary Traveling-Wave Oscillator (2021)

A rotary traveling-wave oscillator (RTWO) has an ability to generate multiple phases at millimeter-wave (mmW) frequencies while achieving low phase noise (PN). Unfortunately, due to the practically unavoidable transmission line (TL) dispersion, which causes the higher-order harmonics to travel faster than the fundamental, RTWOs suffer from flicker noise upconversion. In this article, we propose a “distributed stubs” technique to mitigate this mechanism in which tuning capacitors placed on the TL stubs away from the maintaining amplifiers will slow down the travel speed of higher-order harmonics relative to the fundamental, thus lowering the phase shifts due to the TL dispersion. We further provide a comprehensive analysis of the flicker noise upconversion mechanism due to the TL dispersion. The proposed 26.2-30-GHz RTWO is implemented in 22-nm fully depleted silicon-on-insulator (FD-SOI) CMOS with eight differential phases. At 30 GHz, it achieves PN of -107.6 and -128.9 dBc/Hz at 1- and 10-MHz offsets, respectively. This translates into figures-of-merit (FoMs) of 184.2 and 185.4 dB, respectively, for a single phase. The proposed architecture consumes 20 mW from 0.8-V supply. It achieves a flicker PN corner of 180 kHz, which is an order-of-magnitude better than currently achievable by state-of-the-art mmW RTWOs.
Testing incremental adaptation (1994)

A robot system operating in an environment in which there is uncertainty and change needs to combine the ability to react with the ability to plan ahead. In a previous paper we proposed a solution to the problems of integrating planning and reaction: cast planning as adaptation of a reactive system. In this paper, we present our first experimental results from the planner-reactor architecture, and compare the approach with other work in the planning and learning literatures.
Sequence‐Defined Oligomers from Hydroxyproline Building Blocks for Parallel Synthesis Applications (2016)

The functionality of natural biopolymers has inspired significant effort to develop sequence-defined synthetic polymers for applications including molecular recognition, self-assembly, and catalysis. Conjugation of synthetic materials to biomacromolecules has played an increasingly important role in drug delivery and biomaterials. We developed a controlled synthesis of novel oligomers from hydroxyproline-based building blocks and conjugated these materials to siRNA. Hydroxyproline-based monomers enable the incorporation of broad structural diversity into defined polymer chains. Using a perfluorocarbon purification handle, we were able to purify diverse oligomers through a single solid-phase extraction method. The efficiency of synthesis was demonstrated by building 14 unique trimers and 4 hexamers from 6 diverse building blocks. We then adapted this method to the parallel synthesis of hundreds of materials in 96-well plates. This strategy provides a platform for the screening of libraries of modified biomolecules.