gebhart/patrepeval huggingface dataset:
Data from Improving the <i>In Vivo</i> Efficacy of an Anti-Tac (CD25) Immunotoxin by <i>Pseudomonas</i> Exotoxin A Domain II Engineering (2023)

&lt;div&gt;Abstract&lt;p&gt;Tac (CD25) is expressed on multiple hematologic malignancies and is a target for cancer therapies. LMB-2 is an extremely active anti-Tac recombinant immunotoxin composed of an Fv that binds to Tac and a 38-kDa fragment of &lt;i&gt;Pseudomonas&lt;/i&gt; exotoxin A (PE38). Although LMB-2 has shown high cytotoxicity toward Tac-expressing cancer cells in clinical trials, its efficacy was hampered by the formation of anti-drug antibodies against the immunogenic bacterial toxin and by dose-limiting off-target toxicity. To reduce toxin immunogenicity and nonspecific toxicity, we introduced six point mutations into domain III that were previously shown to reduce T-cell immunogenicity and deleted domain II from the toxin, leaving only the 11aa furin cleavage site, which is required for cytotoxic activity. Although this strategy has been successfully implemented for mesothelin and CD22-targeting immunotoxins, we found that removal of domain II significantly lowered the cytotoxic activity of anti-Tac immunotoxins. To restore cytotoxic activity in the absence of PE domain II, we implemented a combined rational design and screening approach to isolate highly active domain II–deleted toxin variants. The domain II–deleted variant with the highest activity contained an engineered disulfide-bridged furin cleavage site designed to mimic its native conformation within domain II. We found that this approach restored 5-fold of the cytotoxic activity and dramatically improved the MTD. Both of these improvements led to significantly increased antitumor efficacy &lt;i&gt;in vivo&lt;/i&gt;. We conclude that the next-generation anti-Tac immunotoxin is an improved candidate for targeting Tac-expressing malignancies. &lt;i&gt;Mol Cancer Ther; 17(7); 1486–93. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis (2021)

The ACE score, a deep learning model, can accurately discriminate ECGs from patients with and without cirrhosis. This novel relationship between AI-enabled ECG analysis and cirrhosis holds promise as the basis for future low-cost tools and applications in the care of patients with liver disease.
Virulence of a Phosphoribosylaminoimidazole Carboxylase-Deficient Candida albicans Strain in an Immunosuppressed Murine Model of Systemic Candidiasis (2001)

The relative pathogenicities of three Candida albicans strains differing in the function of ADE2 (the gene encoding phosphoribosylaminoimidazole carboxylase) were evaluated in a murine candidiasis model. C. albicans strain CAI7 (ade2/ade2), previously constructed by site-specific recombination, was avirulent in immunosuppressed mice compared to the parent strain, CAF2-1, and a heterozygous ADE2/ade2 strain obtained by transforming CAI7 with a wild-type allele. The reduced virulence of CAI7 was correlated with the inability to proliferate in either synthetic medium or serum without the exogenous addition of >10 microg of adenine/ml. The loss of virulence upon site-specific disruption of the ade2 locus, and the restoration of wild-type virulence with the repair of just one ade2 allele, confirmed that the ADE2 gene and de novo purine biosynthesis were required for Candida pathogenicity. The potential of the phosphoribosylaminoimidazole carboxylase enzyme as a novel target for antifungal drug discovery is discussed.
Tsunami Detection Using the PARIS Concept (2005)

On 26 December 2004 a tsunami generated by an earthquake with its epicentre in the Indian Ocean West of Indonesia caused a real human and material catastrophe in the region. After the event some proposals to establish a network of sensors for tsunami detection were put forward. This paper presents an alternative concept that can be applied from satellite, aircraft or from the coast, and which can complement such a network of sensors for fast tsunami detection. The concept makes use of GNSS signals reflected from the ocean’s surface to perform mesoscale ocean altimetry. The technique, designated PARIS (Passive Reflectometry and Interferometry System), aims at capturing fast topographic events happening on the ocean surface such as eddies and fronts. The paper includes details of some aircraft experiments whereby a PARIS altimeter was used to map a topographic signature with amplitude and wavelength similar to a tsunami in open ocean.
Electrical breakdown and ultrahigh electrical energy density in poly(vinylidene fluoride-hexafluoropropylene) copolymer (2009)

This paper investigates the electrical breakdown of a polar fluoropolymer, poly(vinylidene fluoride-hexafluoropropylene) which exhibits an exceptionally high discharged electrical energy density (&amp;gt;25 J/cm3). It is shown that above room temperature, the breakdown strength decreases with temperature. It is further shown that such a temperature dependence of breakdown strength is consistent with the electromechanical breakdown model by taking into consideration of the plastic deformation of semicrystalline polymers.
Applications, TN, STN Displays (1998)

The prelims comprise: Introduction Twisted Nematic Displays Addressing of Liquid Crystal Displays Supertwisted Nematic Displays Liquid Crystal Materials for Twisted Nematic and Supertwisted Nematic Display Devices
Endovascular Aortic Aneurysm Repair with the Zenith AAA Endovascular Graft: Does Gender Affect Procedural Success, Postoperative Morbidity, or Early Survival? (2005)

The purpose of this study was to analyze the effect of gender on deployment, early morbidity, and survival after endovascular aortic aneurysm repair (EVAR) using the Zenith Endovascular Graft. Data were obtained from the U.S. Multicenter Zenith Endograft trial and complemented with results from the Zenith female registry, including 40 women (10.9%) and 326 men (89.1%). Data analysis included preoperative medical risk factors, aneurysm morphology, deployment, and postoperative morbidity data, and 30-day and 1-year results. Preoperatively, women more often had experienced thromboembolic events (13% vs 4.3%; P = 0.04), but less angina pectoris (24% vs 49%; P = 0.002) or myocardial infarction (18% vs 38%; P = 0.01) compared with men. Women had more angulated aneurysm necks and narrower iliac arteries compared with men. Procedural success, cardiovascular, pulmonary, renal, bowel-related, neurologic, or other adverse events were comparable, as were 30-day and 1-year survival. Females experienced more wound dehiscences (5.0% vs 0.0%; P = 0.01) and open surgical conversions in the first year (5%) compared with men (0.31%) (P = 0.03). With more challenging aneurysm morphologies, women were found to be at a higher risk for conversion in the first year after EVAR using the Zenith endograft. This however does not translate into inferior survival or higher overall morbidity compared with men.
Supplementary Materials and Methods from E7386, a Selective Inhibitor of the Interaction between β-Catenin and CBP, Exerts Antitumor Activity in Tumor Models with Activated Canonical Wnt Signaling (2023)

&lt;p&gt;Supplementary Materials and Methods&lt;/p&gt;
Multiple Roles for TnpI Recombinase in Regulation of Tn 5401 Transposition in Bacillus thuringiensis (1999)

Tn5401 is a class II transposable element derived from the gram-positive bacterium Bacillus thuringiensis. The 4,837-bp transposon encodes a Tn3-like transposase (TnpA) and an integrase-like recombinase (TnpI) and is notable for its unusually long 53-bp terminal inverted repeats (TIRs). The tnpA and tnpI genes are transcribed from a common promoter, designated P(R), that is subject to negative regulation by TnpI. The TIRs of Tn5401 each contain a 38-bp sequence that can be aligned with the 38- to 40-bp TIR sequences of Tn3-like transposons and an adjacent 12-bp sequence that binds TnpI. This unique juxtaposition of TnpA and TnpI binding sites suggests that TnpI may regulate the binding or catalytic activity of TnpA. The results of the present study indicate that TnpI, in addition to functioning as a site-specific recombinase and as a transcriptional repressor, is required for TnpA binding to the TIRs of Tn5401.
Growth Dynamics for DNA-Guided Nanoparticle Crystallization (2013)

Spherical nucleic acid (SNA) nanostructures assemble into a large variety of well-defined crystalline superlattices via DNA-directed hybridization. Crystallities of SNA with various shapes emerge during the assembly process, which coalesce during coarsening, leading to polycrystalline materials. Here, we investigate the growth dynamics of SNAs into body-centered cubic superlattices and the coalescence of SNA aggregates using a colloidal model formulated from the competition of electrostatic core repulsions and localized DNA hybridization attractions. We find that the growth law of isolated SNA crystallities is well-described by the power law t(1/2), in agreement with experimental observations. At later times, coalescence slows the growth dynamics considerably and is dependent on the orientational mismatch (misorientation angle) of the coalescing crystallites. Molecular dynamics simulations show that the misorientation angle decreases continually during the coalescence, which is a signature of the grain rotation induced coalescence mechanism. This mechanism is followed by the coarsening of a "neck" that develops at the boundary between the coalescing crystallites. Remarkably, we find faster coalescence dynamics for larger SNAs compared to smaller SNAs due to their enhanced surface diffusion, which more effectively reduces curvature at the boundary of two superlattices. These findings provide fundamental insight into the relationship between nanoparticle surface chemistry and its crystallite growth and coalescence.
Localization of Nerve Cells in the Developing Rat Tooth (1997)

Earlier studies have shown that mammalian tooth formation can take place in the absence of peripheral nerve fibers. This has been taken to indicate that neurons are not needed for mammalian tooth development. However, our recent localization of peripherin, which is a neuronal cell marker, has suggested that neuronal cell bodies may be associated with developing teeth. In this study, we have analyzed in vivo and in vitro the presence of neuronal cells in developing rat tooth germs. When E14 and E16 rat first molars (thickening of presumptive dental epithelium and bud-stage tooth germ, respectively) were cultured in vitro, peripheral trigeminal axons degenerated. However, with antibodies against peripherin and L1 neural cell adhesion protein, we detected neuronal cell bodies and their axons in the explants. Next, the expression of neurofilament light-chain (NF-L) mRNAs was studied by in situ hybridization of embryonic E12 first branchial arches and tooth germs from initiation to completion of crown morphogenesis (E13, five-day post-natal teeth). NF-L transcripts were first seen at the bud stage (E15) next to the dental epithelium at the buccal side of the tooth germ. At the cap stage (E18), NF-L mRNAs were located under the oral epithelium at some distance from dental epithelium. These expression patterns correlate to the previous localization of peripherin-positive cells and suggest that NF-L expression also revealed neuronal cells. Taken together, these results demonstrate that, in addition to projections of peripheral neurons, neuronal cells are associated with the developing teeth. Hence, it is possible that neuronal cells may participate in the regulation of mammalian tooth formation.
Rotational Features Extraction for Ridge Detection (2011)

State-of-the-art approaches to detecting ridge-like structures in images rely on filters designed to respond to locally linear intensity features. While these approaches may be optimal for ridges whose appearance is close to being ideal, their performance degrades quickly in the presence of structured noise that corrupts the image signal, potentially to the point where it truly does not conform to the ideal model anymore. In this paper, we address this issue by introducing a learning framework that relies on rich, local, rotationally invariant image descriptors and demonstrate that we can outperform state-of-the-art ridge detectors in many different kinds of imagery. More specifically, our framework yields superior performance for the detection of blood vessel in retinal scans, dendrites in bright-field and confocal microscopy image-stacks, and streets in satellite imagery.
Demonstration of high waveguide bending efficiency (>90%) in a photonic-crystal slab at 1.5-μm wavelengths (2001)

Using a 2D photonic-crystal slab structure, we have demonstrated a strong 2D photonic band gap with the capability of fully controlling light in all three dimensions. Our demonstration confirms the predictions on the possibility of achieving 3D light control using 2D band gaps, with strong index guiding providing control in the third dimension, and raise the prospect of being able to realize novel photonic-crystal devices. Based on such slab structure with triangular lattice of holes, a 60 degree photonic-crystal waveguide bend is fabricated. The intrinsic bending efficiency is measured within the photonic band gap. As high as 90 percent bending efficiency is observed at some frequencies.
D22 Gender differences in insulin sensitivity and sympathetic responsiveness in young hypertensives (1997)

Nifbdipiac GITS (N-GITS) is a ence a day fcrmmdation of nitkdipinepmvidhg atabkplasmaconwnfmfiona overthcentirc24 heurdoaingirrtaval. To assesstbesndbypema ive efficacyofarrew 20mg fomtrrfation in anofficebased setting, M centreaacmssthc Countrv and lg7 Dstierrts were-ted. A&r a twe week lrlscebe S doubi-blind manner t04"&dra ofpidor N-GITStreatment 24 hour smbukry blcad prCS!OXt monitoring cccurreelin a subgroupof 66 pSti611tS at 5 of tbc cadres. A SIOIUUZUY of the "intentic+rt etreat" resultsis * below: A DBP (errnrHg) -5.4 -8.6@ A SBP(rmrrHg) .5.0 -9.3. 1 Rc3pondms'(%) 31,9 57,0 T/Pratio(DBP) 66.7% A V Ev d erw da 37,2Y. / 32.3. ( DBP < 90mrrWg IX> 10 rmnHgrtecreaae; p=o.ool; *p=o.oo63 Tksertaultsirr&atethet20mgofN-GITSis enefflcacioua dosein rk?messirrgBPwiflr alewineidenceof edveraemwrrta.
P063: Trial in Progress: Individualized Immunotherapy in Early-Stage Unfavorable Hodgkin Lymphoma - The Investigator-Initiated Phase II GHSG INDIE Trial (2022)

Figure 1: INDIE Trial Flowchart (Main Cohort age 18–60 years, N=100) Background: Immune-checkpoint blockade targeting the programmed cell death protein 1 (PD1) axis continue to reshape the therapeutic landscape of classical Hodgkin lymphoma (HL). The randomized phase II GHSG NIVAHL trial investigated nivolumab-based 1st-line treatment of early-stage unfavorable HL, either fully concomitant (4x nivo-AVD) or sequential (4x nivolumab, 2x nivo-AVD, 2x AVD) each followed by 30Gy involved-site radiotherapy (IS-RT; Bröckelmann PJ et al. JAMA Oncol 2020). The most recent update continued to show feasibility, a favorable safety profile and outstanding efficacy with 2-year progression-free (PFS) and overall survival (OS) of 99% and 100%, respectively (Bröckelmann PJ et al. ASH 2020). The upcoming GHSG phase II INDIE trial will investigate an individualized immunotherapy with the anti-PD1 antibody tislelizumab in this setting. Trial design: INDIE is an investigator-sponsored open-label phase II trial conducted at 35 GHSG trial sites in Germany. Patients with newly diagnosed early-stage unfavorable HL by GHSG criteria will receive two initial infusions of tislelizumab (200mg Q3W) followed by an FDG-PET/CT based restaging. Patients in complete metabolic remission will continue treatment with four additional tislelizumab infusions (300mg Q4W). Patients with residual metabolic activity will receive concomitant treatment with four cycles of AVD at standard dose and tislelizumab (300mg Q4W, tis-AVD). In the main cohort of N=100 patients aged 18–60 years, consolidative 30Gy IS-RT will only be applied in case of PET-positive residues (Figure 1). In an exploratory of N=20 patients >60 years of age, 30Gy IS-RT will be applied irrespective of remission status at end of systemic treatment. Primary endpoint is the 1-year PFS with 1- and 3-year OS, 3-year PFS, feasibility and safety, patient-reported outcomes and correlative studies being secondary endpoints. The trial is registered at clinicaltrials.gov (NCT04837859) and financially supported by BeiGene. Outlook: INDIE is the first trial to investigate an individualized immunotherapy in treatment naïve early-stage unfavorable HL, potentially omitting both chemo- and radiotherapy in optimally responding patients. Together with extensive correlative studies on longitudinal tumor biopsies, blood and stool samples, this trial will generate critical insights into response-adapted 1st-line HL immunotherapy.
Langerhans islets induce anti-tumor immunity at the expense of glycemic control and predict chemotherapy response in pancreatic cancer (2021)

ABSTRACT Induction of anti-tumor immunity in pancreatic ductal adenocarcinoma (PDA) is an unresolved challenge. Systematic investigation of the microenvironment of primary pancreatic tumors revealed a role of endocrine Langerhans islets in the coordination of immune activation. We found that intratumoral β-cells, regulated via STAT3, secrete C-C motif chemokine ligand 27 (CCL27) and thereby promote a T H 1 phenotype in the microenvironment resulting in an enhanced T cell infiltration and prolonged patient survival. The local effect can be abrogated in a patient-based human explant model by inhibition of the CCL27 receptor CCR10. This defense mechanism is paralleled by an impaired metabolic function of Langerhans islets with reduced insulin levels resulting in a dysregulation of glycemic control in patients. Based on these findings, screening of PDA cases (n= 2264) led to the identification of type 2 diabetes mellitus (T2DM) and extractable glycated haemoglobin (HbA1c) levels as response markers for neoadjuvant chemotherapy with fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX). Collectively these data provide insights into the interconnection of T2DM and PDA, and link declining glycemic control to therapeutic efficacy, which can be utilized as a tool for clinical decision-making and improve patient management.
Site-specific ubiquitination of MLKL targets it to endosomes and targets Listeria and Yersinia to the lysosomes (2022)

Phosphorylation of the pseudokinase mixed lineage kinase domain-like protein (MLKL) by the protein kinase RIPK3 targets MLKL to the cell membrane, where it triggers necroptotic cell death. We report that conjugation of K63-linked polyubiquitin chains to distinct lysine residues in the N-terminal HeLo domain of phosphorylated MLKL (facilitated by the ubiquitin ligase ITCH that binds MLKL via a WW domain) targets MLKL instead to endosomes. This results in the release of phosphorylated MLKL within extracellular vesicles. It also prompts enhanced endosomal trafficking of intracellular bacteria such as Listeria monocytogenes and Yersinia enterocolitica to the lysosomes, resulting in decreased bacterial yield. Thus, MLKL can be directed by specific covalent modifications to differing subcellular sites, whence it signals either for cell death or for non-deadly defense mechanisms.
Twiddler's Syndrome: A New Twist (1984)

Twiddler's syndrome, characterized by dislodgment of pacemaker leads due to twisting of pulse generators within the subcutaneous pocket with subsequent retraction of leads and loss of pacing function, has been well described in patients with permanent pacemakers implanted for bradyarrhythmias. The case presented here is the first report of a patient with an internal automatic cardioverter-defibrillator with lead dislodgment due to pulse generator rotation. This case exemplifies a new subset of patients prone to the Twiddler's syndrome.
Taking advantage of tumor cell adaptations to hypoxia for developing new tumor markers and treatment strategies (2009)

A series of efavirenz Mannich bases has been synthesized by reacting efavirenz, formaldehyde, and various aryl substituted piperazines using microwave irradiation (yield 35-88%). The synthesized compounds were evaluated for in-vitro anti-HIV and antimycobacterial activities. The in-vitro antiretroviral activities indicated that compound 7-(4-((6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2-oxo-2H-benzo[d] [1,3]oxazin-1 (4H)-yl)methyl)-3-methylpiperazin-l -yl)-1-cyclopropyl-6-fluoro-l,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid (4i) was equipotent to efavirenz with EC(50) of 2.4 nM. Compound 4i also inhibited M. tuberculosis with minimum inhibitory concentration of 0.2 microg/mL.
Simulating Snow Over Sea Ice In Climate Models (2002)

We have evaluated two methods of simulating the seasonal cycle of snow over sea ice in and around the Arctic: The NCAR global climate model CCM3, with its standard snow hydrology, and the snow pack model SNTHERM, forced with hourly atmospheric output from CCM3. A new dataset providing dates for the onset of snow melt over Arctic sea ice provides a means for assessing basin-wide how well the models simulate melt onset, but contains no information on how long it then takes for all the snow to melt. Use of data from the SHEBA site provides very detailed information on the behavior of the snow before and during the melt season, but only for a very limited area. Russian drift data provide climatological data on the seasonal cycle of snow water equivalent and snow density, over multi-year sea ice in the central Arctic basin. These datasets are used to compare the two modeling methods, and to see if use of the more physically-realistic SNTHERM provides any significant improvements. Conclusions obtained so far include: 1. Both CCM3 and CCM3/SNTHERM do a good job overall of matching the onset of snow melt dataset; although CCM3/SNTHERM consistently trends to underestimate the date and CCM3 to overestimate it. 2. SHEBA and ice drift data for the Arctic show that CCM3/ SNTHERM does a better job than CCM3 at simulating the total melt period. 3. Ice drift snow density and accumulation data suggest that while providing superior results, CCM3/SNTHERM may still suffer from overly vigorous melting. 4. Both the large-scale atmospheric forcing and snow pack physical processes are important in proper simulation of the snow seasonal cycle. Ongoing work includes further diagnosis of CCM3/SNTHERM, use of more observational datasets, especially from marginal seas in the pan-Arctic, and full coupling of SNTHERM into CCM3 (work to date has all been off-line simulations).
Broadband, Near Single-Cycle, Waveform-Stable Mid-Infrared Pulses Driven by a 2-μm Femtosecond Source (2019)

We present a novel source of ultrashort, watt-scale, 50-MHz repetition-rate, broadband (6-18 μm, or 555-1666 cm<sup>-1</sup>)pulses. Generation and electro-optic-sampling of the waveform-stable transients is driven with a femtosecond thulium-based fiber-amplifier.