gebhart/patrepeval huggingface dataset:
Data from Chimeric Antigen Receptor T Cells with Dissociated Signaling Domains Exhibit Focused Antitumor Activity with Reduced Potential for Toxicity &lt;i&gt;In Vivo&lt;/i&gt; (2023)

&lt;div&gt;Abstract&lt;p&gt;Adoptive immunotherapy using T lymphocytes genetically modified to express a chimeric antigen receptor (CAR-T) holds considerable promise for the treatment of cancer. However, CAR-based therapies may involve on-target toxicity against normal tissues expressing low amounts of the targeted tumor-associated antigen (TAA). To specify T cells for robust effector function that is selective for tumor but not normal tissue, we developed a trans-signaling CAR strategy, whereby T-cell activation signal 1 (CD3ζ) is physically dissociated from costimulatory signal 2 (CD28) in two CARs of differing antigen specificity: mesothelin and a-folate receptor (FRa). Human T cells were genetically modified to coexpress signal 1 (anti-Meso scFv-CD3ζ) and signal 2 (anti-FRa scFv-CD28) CARs in trans. Trans-signaling CAR-T cells showed weak cytokine secretion against target cells expressing only one TAA &lt;i&gt;in vitro&lt;/i&gt;, similar to first-generation CAR-T cells bearing CD3ζ only, but showed enhanced cytokine secretion upon encountering natural or engineered tumor cells coexpressing both antigens, equivalent to that of second-generation CAR-T cells with dual signaling in cis. CAR-T cells with dual specificity also showed potent anticancer activity and persistence &lt;i&gt;in vivo&lt;/i&gt;, which was superior to first-generation CAR-T cells and equivalent to second-generation CARs. Importantly, second-generation CAR-T cells exhibited potent activity against cells expressing mesothelin alone, recapitulating normal tissue, whereas trans-signaling CAR-T cells did not. Thus, a dual specificity, trans-signaling CAR approach can potentiate the therapeutic efficacy of CAR-T cells against cancer while minimizing parallel reactivity against normal tissues bearing single antigen. &lt;i&gt;Cancer Immunol Res; 1(1); 43–53. ©2013 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Measurement and Analysis of the Swarm Social Network With Tens of Millions of Nodes (2018)

Social graphs have been widely used for representing the relationship among users in online social networks (OSNs). As crawling an entire OSN is resource- and time-consuming, most of the existing works only pick a sampled subgraph for study. However, this may introduce serious inaccuracy into the analytic results, not to mention that some important metrics cannot even be calculated. In this paper, we crawl the entire social network of Swarm, a leading mobile social app with more than 60 million users, using a distributed approach. Based on the crawled massive user data, we conduct a data-driven study to get a comprehensive picture of the whole Swarm social network. This paper provides a deep analysis of social interactions between Swarm users, and reveals the relationship between social connectivity and check-in activities.
Automated Quantitative Analysis of Capnogram Shape for COPD–Normal and COPD–CHF Classification (2014)

We develop an approach to quantitative analysis of carbon dioxide concentration in exhaled breath, recorded as a function of time by capnography. The generated waveform--or capnogram--is currently used in clinical practice to establish the presence of respiration as well as determine respiratory rate and end-tidal CO 2 concentration. The capnogram shape also has diagnostic value, but is presently assessed qualitatively, by visual inspection. Prior approaches to quantitatively characterizing the capnogram shape have explored the correlation of various geometric parameters with pulmonary function tests. These studies attempted to characterize the capnogram in normal subjects and patients with cardiopulmonary disease, but no consistent progress was made, and no translation into clinical practice was achieved. We apply automated quantitative analysis to discriminate between chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF), and between COPD and normal. Capnograms were collected from 30 normal subjects, 56 COPD patients, and 53 CHF patients. We computationally extract four physiologically based capnogram features. Classification on a hold-out test set was performed by an ensemble of classifiers employing quadratic discriminant analysis, designed through cross validation on a labeled training set. Using 80 exhalations of each capnogram record in the test set, performance analysis with bootstrapping yields areas under the receiver operating characteristic (ROC) curve of 0.89 (95% CI: 0.72-0.96) for COPD/CHF classification, and 0.98 (95% CI: 0.82-1.0) for COPD/normal classification. This classification performance is obtained with a run time sufficiently fast for real-time monitoring.
Adsorption of Sodium Dodecyl Sulfate and 2-Naphthol Adsolubilization on Titanium Dioxide with Quaternary Ammonium Groups (1998)

The adsorption behavior of sodium dodecyl sulfate (SDS) was investigated on titanium dioxide with quaternary ammonium groups (XNm, m is the carbon number of the alkyl chain, 4−16) by measuring amount adsorbed, ζ potential, and dispersion stability. The amount of SDS adsorbed increased sharply at low SDS concentration, reached a constant level on XN4, XN8, and XN12, and gradually increased on XN16. However, the amount of SDS adsorbed on untreated titanium dioxide was significantly low compared with that on XNm. The suspensions of XNm created by adsorption of SDS showed a dispersion−flocculation−redispersion sequence, accompanying a change in the ζ potential from positive to negative for all XNm. The flocs formed could be transferred to a toluene phase by adding toluene to the XNm suspensions, indicating that the flocs of all XNm are hydrophobic regardless of different alkyl chain lengths. The order parameter of methyl 12-doxylstearate located in the SDS adsorbed layer estimated by electron spin resonance shows that the mobilities of the probe are not restricted in the SDS adsorbed layer for all XNm. Adsolubilization behavior of 2-naphthol in the SDS adsorbed layer on XNm was peculiar; the amount of 2-naphthol adsolubilized was insensitive to the SDS concentration and was almost the same as the amount of 2-naphthol adsorbed on XNm in the absence of SDS, where the amount of 2-naphthol adsorbed increased with increasing alkyl chain length of XNm. In the case of untreated titanium dioxide, the amount of 2-naphthol adsolubilized increased with the SDS concentration, reached a maximum, and then decreased. Thus, the adsolubilization behavior of 2-naphthol for XNm was significantly different from that for untreated titanium dioxide.
Direct Chemical Vapor Deposition Synthesis of Phase-Pure Iron Pyrite (FeS<sub>2</sub>) Thin Films (2015)

Resurgent interest in iron pyrite (FeS2) as an earth-abundant, nontoxic semiconductor for solar applications has resulted in many attempts to grow phase-pure thin films via chemical vapor deposition (CVD). However, all thin films grown via CVD or sulfidation to date have contained marcasite phase or other iron sulfide impurities. Here, we report the use of metallic cobalt pyrite (cattierite, CoS2) thin films as an ideal substrate leading to the first direct growth of phase-pure iron pyrite thin films via atmospheric pressure CVD. This synthesis was achieved by reacting FeCl3 and ditert butyl disulfide (TBDS) at 400–450 °C. The products were confirmed as phase-pure iron pyrite using X-ray diffraction (XRD), Raman spectroscopy, and energy dispersive X-ray spectroscopy (EDS). In addition to phase-purity, the synthesis produced crystal domains >1 μm and a conformal coating 3–5 μm thick, which are attributed to the <2% lattice mismatch of the isostructural cattierite substrate. The surface was characterized by ultraviolet and X-ray photoelectron spectroscopy (UPS & XPS) and the electrical properties by electrochemical impedance spectroscopy (EIS) and Mott–Schottky analysis. The direct growth of a phase-pure iron pyrite film on a conductive substrate provides the most convenient configuration so far for potential solar cells.
Noninferiority of Preservative-free Versus BAK-preserved Latanoprost-timolol Fixed Combination Eye Drops in Patients With Open-angle Glaucoma or Ocular Hypertension (2019)

Preservative-free latanoprost-timolol fixed combination T2347 showed noninferior efficacy compared with the preserved comparator and was well tolerated.
Joy in Work for Clinicians and Staff: Identifying Remedial Predictors of Burnout from the Mini Z Survey (2020)

The Mini Z-derived T/T score could be useful for quick assessment of the degree of burnout and identifying burnout drivers related to effective organizational structure and supportive teamwork in <i>practice personnel</i>.
Effects of Vasodilatory Antihypertensive Agents on Endothelial Dysfunction in Rats with Ischemic Acute Renal Failure. (2000)

Ischemic acute renal failure is associated with vascular endothelial dysfunction. We examined whether vasodilatory antihypertensive agents would improve endothelial function in rats with ischemia/reperfusion renal injury. Rat kidneys were isolated and perfused after clipping of the bilateral renal arteries for 45 min and reperfusion for 24 h, and renal perfusion pressure and nitric oxide concentration in the venous effluent (chemiluminescence assay) were monitored. Preischemic administration of celiprolol (a beta-blocker; 100 mg/kg p.o.), benidipine (a calcium channel blocker; 1 mg/kg p.o.), or imidapril (an angiotensin converting-enzyme inhibitor; 3 mg/kg p.o.) restored endothelial function in rats subjected to acute renal ischemia (deltarenal perfusion pressure [10(-8) M acetylcholine]: sham -42+/-3%, ischemia -31+/-1%, ischemia +celiprolol -39+/-1%*, ischemia+benidipine -38+/-2%*, ischemia+imidapril -42+/-2%*; *p<0.05 vs. ischemia). Serum urea nitrogen and creatinine levels were also lower in the treated groups. Furthermore, ischemia-induced decreases in the response to acetylcholine and renal excretory function were smaller in SHR than in deoxycorticosterone-salt hypertensive rats, in which endothelial damage was marked. These results suggest that preischemic endothelial function may influence the degree of ischemic renal injury. Calcium channel blockers, converting-enzyme inhibitors, and endothelial NO synthase-activating beta-blockers had beneficial effects on renovascular endothelial dysfunction due to ischemia.
Silver staining two types of meiotic nodules (1992)

We have developed a reliable method for silver staining nodules on synaptonemal complexes (SCs) of tomato (Lycopersicon esculentum). This technique involves hypotonically bursting primary microsporocytes, fixing SC spreads with paraformaldehyde, and incubating the spreads at 40 degrees C in a 33% aqueous silver nitrate solution covered with nylon mesh. When tomato SCs were stained by this method, nodules were observed with the same distribution and frequency as nodules stained with uranyl acetate and lead citrate. Incubation in silver nitrate at higher temperatures caused the loss of some or all nodules. The pattern of loss suggests that two types of nodules coexist during late zygonema and early pachynema and that one type becomes the late nodules of mid-pachynema through early diplonema.
Novel insights into the mitochondrial permeability transition (2014)

Alavian and colleagues recently provided further evidence in support of the notion that the c subunit of the mitochondrial F1FO ATP synthase constitutes the long-sought pore-forming unit of the supramolecular complex responsible for the so-called 'mitochondrial permeability transition' (MPT). Besides shedding new light on the molecular mechanisms that underlie the MPT, these findings corroborate the notion that several components of the cell death machinery, including cytochrome c and the F1FO ATP synthase, mediate critical metabolic activities.
Living Related Liver Transplantation in Adults (1998)

Our LRLT program for adult patients has produced good results. LRLT in adults can be indicated for selected donor-recipient combinations.
DOP080 Low viral richness at baseline in ulcerative ulcerative colitis associated with faecal microbiota transplantation success (2017)

Background: Faecal microbiota transplantation (FMT) has been seen as a promising tool in inflammatory bowel disease (IBD), but its use remains controversial. Bacteriome dysbiosis in IBD is well established, however the role of viruses is still understudied. Recently, an increased viral richness together with decreased bacterial diversity has been associated with IBD. We accessed the viral longitudinal dynamics in nine ulcerative colitis (UC) patients that underwent FMT (Figure). Of these, two patients (1 and 3, figure) presented endoscopic and long-term (>2-years) remission after FMT. However, the first FMT for patient 3 was followed by pneumonia and a course of antibiotics, and only sample related to the second FMT, of which no follow-up samples were available, were analysed. Figure 1. Overview of the sample collection analysed for the virome dynamics. Methods: Viral particles were purified from faeces using protocol NetoVIR and subsequently shotgun sequenced on an Illumina platform. Sequences were trimmed, de novo assembled, translated and compared to a protein database for taxonomic annotation. Richness and diversity were calculated using the vegan package in R. Results: A higher viral richness at baseline was observed (p=0.023) in patients (n=9) when compared to their donors (n=8). When comparing all longitudinal samples from FMT responders (n=7) and non-responders (n=43), a lower richness (p=0.0005) was found for the responders. Comparing samples collected before FMT (baseline) from patients based on their outcome showed that responders (n=2) already presented a trend towards a lower richness (p=0.056) compared to non-responders (n=7). Finally, no significant differences could be observed (p=0.286) in viral richness of donors and outcome of patients. Transferred phylotypes were defined as viral genera present in the donor sample and increased in the patient samples post-transplantation. We observed that in the responder with longitudinal data available, 8 viral genera were transferred, while the 6 non-responders, presented on average 32 transferred species. Since no samples post-transplantation were available for patient 3 we could not further verify this observation. Conclusions: Our data confirms that diseased individuals present a higher viral richness and our study suggests that lower viral richness at baseline is associated with a good FMT outcome. Interestingly, the responder presented less transferred viral genera, in line with previous findings that a lower viral diversity is beneficial, suggesting that pre-screening of patients could lead to an increased success of FMT.
The Dynamics of Naturally Acquired Immune Responses to Plasmodium falciparum Sexual Stage Antigens Pfs230 &amp; Pfs48/45 in a Low Endemic Area in Tanzania (2010)

In a longitudinal study, anti-Pfs230 and Pfs48/45 antibodies developed rapidly after exposure to gametocytes and were strongly associated with transmission-reducing activity. Our data indicate that the extent of antigen exposure is important in eliciting functional transmission-reducing immune responses.
Information-Theoretic Lower Bounds on the Storage Cost of Shared Memory\n Emulation (2016)

The focus of this paper is to understand storage costs of emulating an atomic\nshared memory over an asynchronous, distributed message passing system.\nPrevious literature has developed several shared memory emulation algorithms\nbased on replication and erasure coding techniques. In this paper, we present\ninformation-theoretic lower bounds on the storage costs incurred by shared\nmemory emulation algorithms. Our storage cost lower bounds are universally\napplicable, that is, we make no assumption on the structure of the algorithm or\nthe method of encoding the data.\n We consider an arbitrary algorithm $A$ that implements an atomic multi-writer\nsingle-reader (MWSR) shared memory variable whose values come from a finite set\n$\\mathcal{V}$ over a system of $N$ servers connected by point-to-point\nasynchronous links. We require that in every fair execution of algorithm $A$\nwhere the number of server failures is smaller than a parameter $f$, every\noperation invoked at a non-failing client terminates. We define the storage\ncost of a server in algorithm $A$ as the logarithm (to base 2) of number of\nstates it can take on; the total-storage cost of algorithm $A$ is the sum of\nthe storage cost of all servers.\n Our results are as follows. (i) We show that if algorithm $A$ does not use\nserver gossip, then the total storage cost is lower bounded by $2\n\\frac{N}{N-f+1}\\log_2|\\mathcal{V}|-o(\\log_2|\\mathcal{V}|)$. (ii) The total\nstorage cost is at least $2 \\frac{N}{N-f+2}\n\\log_{2}|\\mathcal{V}|-o(\\log_{2}|\\mathcal{V}|)$ even if the algorithm uses\nserver gossip. (iii) We consider algorithms where the write protocol sends\ninformation about the value in at most one phase. We show that the total\nstorage cost is at least $\\nu^* \\frac{N}{N-f+\\nu^*-1} \\log_2( |\\mathcal{V}|)-\no(\\log_2(|\\mathcal{V}|),$ where $\\nu^*$ is the minimum of $f+1$ and the number\nof active write operations of an execution.\n
Transcranial magnetic stimulation: a historical evaluation and future prognosis of therapeutically relevant ethical concerns (2010)

Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique increasingly used in clinical and research practices around the world. Historically, the ethical considerations guiding the therapeutic practice of TMS were largely concerned with aspects of subject safety in clinical trials. While safety remains of paramount importance, the recent US Food and Drug Administration approval of the Neuronetics NeuroStar TMS device for the treatment of specific medication-resistant depression has raised a number of additional ethical concerns, including marketing, off-label use and technician certification. This article provides an overview of the history of TMS and highlights the ethical questions that are likely arise as the therapeutic use of TMS continues to expand.
Mediator Kinase Phosphorylation of STAT1 S727 Promotes Growth of Neoplasms With JAK-STAT Activation (2017)

Constitutive JAK-STAT signaling drives the proliferation of most myeloproliferative neoplasms (MPN) and a subset of acute myeloid leukemia (AML), but persistence emerges with chronic exposure to JAK inhibitors. MPN and post-MPN AML are dependent on tyrosine phosphorylation of STATs, but the role of serine STAT1 phosphorylation remains unclear. We previously demonstrated that Mediator kinase inhibitor cortistatin A (CA) reduced proliferation of JAK2-mutant AML in vitro and in vivo and also suppressed CDK8-dependent phosphorylation of STAT1 at serine 727. Here we report that phosphorylation of STAT1 S727 promotes the proliferation of AML cells with JAK-STAT pathway activation. Inhibition of serine phosphorylation by CA promotes growth arrest and differentiation, inhibits colony formation in MPN patient samples and reduces allele burden in MPN mouse models. These results reveal that STAT1 pS727 regulates growth and differentiation in JAK-STAT activated neoplasms and suggest that Mediator kinase inhibition represents a therapeutic strategy to regulate JAK-STAT signaling.
Antihypertensive Action and Blockade of α 1 -Adrenoceptors by DL-017, a Quinazoline Derivative (2001)

3-[[4-(2-Methoxyphenyl)piperazin-1-yl]methyl]-5-(methylthio)-2,3-dihydroimidazo[1,2-c]quinazoline (DL-017), a quinazoline derivative, exhibits alpha 1 -adrenoceptor antagonistic and type I antiarrhythmic effects on mammalian cardiac tissues. In the current study, the effects of DL-017 on the hemodynamic profile in anesthetized, spontaneously hypertensive rats were evaluated. Intravenous administration of DL-017 induced dose-dependent reductions of heart rate and blood pressure, which persisted over 2 h. DL-017 exerted a maximal antihypertensive effect at 0.1 mg/kg, which was similar to that of 0.1 mg/kg of prazosin. DL-017 was able to block the pressor response to phenylephrine but not to angiotensin II. Regional cerebral blood flow of the right parietal cortex decreased by 14 +/- 4% 10 min after bolus injection and then rapidly returned to control levels while the arterial pressure was still low. These results indicate that blockade of the alpha 1 -adrenoceptor by DL-017 contributes to reduction of arterial pressure. The antihypertensive effect without reflex tachycardia and loss of autoregulation of cerebral blood flow makes DL-017 suitable for chronic long-term treatment of hypertension.
DEVELOPMENT OF RAT MODELS FOR CHOROIDAL NEOVASCULARISATION (CNV) A Comparison between Laser and Recombinant Adenovirus Induced CNV (1999)

SUMMARY This project aimed to investigate whether the overexpression of vascular endothe­ lial growth factor (VEGF) in the retinal pigment epithelium (RPE), induced by recombinant adenovirus mediated delivery of VEGF164, is sufficient to initiate the development of leaky choroidal blood vessels in a rat model. Eyes of pigmented rats were subjected to krypton laser photocoagulation or subretinal injection with recombinant adenovirus constructs Ad.RSV.VEGF or Ad.CMV.VEGE Initially the animals were examined with fundus photography followed by fluorescein angiography. Retinal photographs demonstrated that the krypton laser produced moderate burns and that the subretinal injection resulted in the formation of a bleb in the subretinal space. Injection of control recombinant adenovirus Ad.RSV.pgal resulted in the expres­ sion of pgal reporter gene in the RPE layer. Of the 141 laser spots delivered into a total of 17 rat eyes, 52.4% developed fluorescein leakage that was detectable by angiogra­ phy. Of seven eyes injected with Ad.RSV.VEGF, 5 developed leakage at 2 weeks post injection, and of 8 eyes which were injected with Ad.CMV.VEGF, 5 developed leakage at 1 week post injection. However, the development of leaky blood vessels was
An instance-based learning approach for evaluating the perception of ride-hailing waiting time variability (2023)

Understanding user's perception of service variability is essential to discern their overall perception of any type of (transport) service. We study the perception of waiting time variability for ride-hailing services. We carried out a stated preference survey in August 2021, yielding 936 valid responses. The respondents were faced with static pre-trip information on the expected waiting time, followed by the actually experienced waiting time for their selected alternative. We analyse this data by means of an instance-based learning (IBL) approach to evaluate how individuals respond to service performance variation and how this impacts their future decisions. Different novel specifications of memory fading, captured by the IBL approach, are tested to uncover which describes the user behaviour best. Additionally, existing and new specification of inertia (habit) are tested. Our model outcomes reveal that the perception of unexpected waiting time is within the expected range of 2-3 times the value-of-time. Travellers seem to place a higher reward on an early departure compared to a penalty for a late departure of equal magnitude. A cancelled service, after having made a booking, results in significant disutility for the passenger and a strong motivation to shift to a different provider. Considering memory decay, our results show that the most recent experience is by far the most relevant for the next decision, with memories fading quickly in importance. The role of inertia seems to gain importance with each additional consecutive choice for the same option, but then resetting back to zero following a shift in behaviour.