gebhart/patrepeval huggingface dataset:
CTNI-54. A SINGLE ARM PHASE II STUDY OF THE DUAL MTORC1/MTORC2 INHIBITOR VISTUSERTIB PROVIDED FOR SPORADIC PATIENTS WITH GRADE II-III MENINGIOMAS THAT RECUR OR PROGRESS AFTER SURGERY AND RADIATION (2021)

Abstract Grade II/III meningiomas have increased rates of recurrence with no approved medical therapies. The historical progression-free survival at 6 months (PFS-6) is 25% with rates &amp;gt;35% declared of interest for drug development. NF2 gene inactivation occurs in about half of meningiomas. Based on our studies showing mTORC1 and mTORC2/SGK1 pathway activation in NF2-deficient meningiomas and the paradoxical activation of the mTORC2/AKT pathway, we hypothesized that mTORC1/mTORC2 inhibitors would be active in meningiomas. We studied the effect of vistusertib in patients with progressive/recurrent grade II/III meningiomas (NCT03071874). Vistusertib was administered orally at 125mg twice daily on two consecutive days each week. MRIs were obtained every 56 days. Tumor size was defined as the largest cross-sectional area. Progression was defined as ≥ 25% increase in the sum of products of all measurable lesions over smallest sum observed. The primary endpoint was PFS-6. Secondary endpoints included toxicity, radiographic response, and correlative studies including immunohistochemistry for mTORC1/2 pathway activation and genetic biomarkers. Twenty-eight patients (13 female, median age 58 years, median KPS 80%) were enrolled. Median tumor size was 4.4cm; 71% were grade II and 50% harbored pathogenic NF2 variants. Four patients discontinued treatment voluntarily and 1 each withdrew for intercurrent illness and non-compliance. PFS-6 is 47% (CI, 26%-65%) and OS-12 is 72% (95%CI, 48%-86%). PFS but not OS was shorter for patients with grade 3 meningiomas; there was no difference in PFS/OS between genetic groups. Adverse events at least possibly related to vistusertib with frequency &amp;gt;10% include nausea, fatigue, hypophosphatemia, diarrhea, anorexia, dry mouth, hypertriglyceridemia, hypertension, vomiting, increased ALT, constipation, and weight loss. Vistusertib treatment was associated with a PFS-6 rate exceeding the target of 35% for recurrent high-grade meningioma. Adverse events were tolerable in this patient population. These data support the continued development of mTORC1/2 inhibitors in this setting.
Bayesian algorithmic mechanism design (2010)

The principal problem in algorithmic mechanism design is in merging the incentive constraints imposed by selfish behavior with the algorithmic constraints imposed by computational intractability. This field is motivated by the observation that the preeminent approach for designing incentive compatible mechanisms, namely that of Vickrey, Clarke, and Groves; and the central approach for circumventing computational obstacles, that of approximation algorithms, are fundamentally incompatible: natural applications of the VCG approach to an approximation algorithm fails to yield an incentive compatible mechanism. We consider relaxing the desideratum of (ex post) incentive compatibility (IC) to Bayesian incentive compatibility (BIC), where truthtelling is a Bayes-Nash equilibrium (the standard notion of incentive compatibility in economics). For welfare maximization in single-parameter agent settings, we give a general black-box reduction that turns any approximation algorithm into a Bayesian incentive compatible mechanism with essentially the same approximation factor.
Relationship between intestinal microbiota, diet and biological systems: an integrated view (2020)

The health-disease process can be influenced by the intestinal microbiota. As this plays a fundamental role in protecting the organism, the importance of studying the composition and diversity of this community becomes increasingly evident. Changes in the composition of the intestinal bacterial community may result in dysbiosis, and this process may contribute to triggering various diseases in all biological systems. This imbalance of intestinal microbiota homeostasis may alter commensal bacteria and the host metabolism, as well as immune function. Dysbiosis also causes an increase in intestinal permeability due to exposure to molecular patterns associated with the pathogen and lipopolysaccharides, leading to a chronic inflammatory process that can result in diseases for all biological systems. In this context, dietary intervention through the use of probiotics, prebiotics and antioxidant foods can be considered a contribution to the modulation of intestinal microbiota. Probiotics have been used to provide up to 10 billion colony forming units, and probiotic foods, Kefir and fermented natural yogurt are also used. Prebiotics, in turn, are found in supplemental formulations of processed foods and in functional foods that are also sources of phenolic compounds, such as flavonoids, antioxidant and anti-inflammatory substances, polyunsaturated fatty acids, vitamins, and minerals. In this review, we will discuss the relationship between an imbalance in the intestinal microbiota with the development of diseases, besides indicating the need for future studies that can establish bacterial parameters for the gastrointestinal tract by modulating the intestinal microbiota, associated with the adoption of healthy habits during all life cycles.
Terminal complement complex C5b-9 stimulates mitogenesis in 3T3 cells. (1993)

The membrane attack complex of complement (MAC) can induce reversible changes in cell membrane permeability resulting in significant but transient intracellular ionic changes in the absence of cell lysis. Because ion fluxes and cytosolic ionic changes are integral steps in the signaling cascade initiated when growth factors bind to their receptors, we hypothesized that the MAC-induced reversible changes in membrane permeability could stimulate cell proliferation. Using purified terminal complement components we have documented a mitogenic effect of the MAC for quiescent murine 3T3 cells. The MAC enhances the mitogenic effects of serum and PDGF, and also stimulates cell proliferation in the absence of other exogenous growth factors. MAC-induced mitogenesis represents a novel effect of the terminal complement complex that could contribute to focal tissue repair or pathological cell proliferation locally at sites of complement activation.
Cold Target Recoil Ion Momentum Spectroscopy (1996)

2. Kinematics of recoil ion production 101 2.1. Ion}atom collisions 102 2.2. Electron}atom collisions 107
Accelerated Co-evolutionary Algorithms (2002)

A new co-evolutionary algorithm, of which the convergence speed is accelerated by neural networks, is proposed and verified in this paper. To reduce computational load required for co-evolutionary optimization processes, the cost function and constraint information is stored in the neural networks, and the extra offspring group, whose cost is computed by the neural networks, is generated. It increases the offspring population size without overloading computational effort; therefore, the convergence speed is accelerated. The proposed algorithm is applied to attitude control design of flexible satellites, and it is verified by computer simulations and experiments using a torque-free air bearing system.
The Impact of Aging on Antiviral Pathways and Consequences for Immune Function (2021)

Abstract It is known that aging leads to increased morbidity and mortality, however, this has become more of a concern as the world population shifts to an increased percentage of older adults (&amp;gt;65) especially for COVID-19. These deaths may be from immunosenescence, a condition of chronic increased level of basal inflammation which can also result in diminished vaccine responses and immune system dysregulation, leading to COVID-19 complications. Current research shows a decrease in pro-inflammatory cytokines but the downstream signaling pathways in the context of aging have yet to be evaluated. Two critical pathway points in the production of type I IFN are the phosphorylation of pIRF7 in the TLR 7/8 pathway and of pTBK-1 in the RIG-I and cGAS-STING pathways. We show a decrease in pIRF7 and pTBK-1 in cDC1s, cDC2s, and CD14dimCD16+vascular patrolling monocytes from older adults (n=12) following stimulation with pathway specific agonists in comparison with healthy controls (n=12). This decrease correlates with decreased phagocytosis in the same cell subsets. These data support our previous reports of a delayed and decreased pro-inflammatory output following stimulation and demonstrate potential targets of antiviral pathways that can resolve dysfunctions of the aging immune system for an effective vaccination response. Therefore, we further hypothesize that cDC1, cDC2, and CD14dimCD16+ from older adults will have reduced antigen presentation and ability to cross-present viral peptides. We will utilize COVID-19 patient samples (n=110) to assess antigen-specificity of DCs and T cells in older COVID-19 pos. patients vs healthy controls (n=12).
ChemInform Abstract: Asymmetric [3 + 2] Annulation Approach to 3‐Pyrrolines: Concise Total Syntheses of (‐)‐Supinidine, (‐)‐Isoretronecanol, and (+)‐Elacomine. (2016)

Abstract The asymmetric [3 + 2] annulation reaction of Ellman imines with ester (I) yields enantiopure 3‐pyrroline products.
Does Ammonia Hydrogen Bond? (1987)

Spectroscopic characterizations of the stereochemistry of complexes of ammonia (NH(3)) have strongly confirmed some long-held ideas about the weak interactions of NH(3) while casting doubt on others. As expected, NH(3) is observed to be a nearly universal proton acceptor, accepting hydrogen bonds from even some of the weakest proton donors. Surprisingly, no evidence has been found to support the view that NH(3) acts as a proton donor through hydrogen bonding. A critical evaluation of the work that has been done to gather such evidence, as well as of earlier work involving condensed-phase observations, suggests that NH(3) might well be best described as a powerful hydrogen-bond acceptor with little propensity to donate hydrogen bonds.
Role of transcription factor RUNX1 in the maintenance of T helper cell epigenome and rapid recall response (2022)

Abstract Memory T cells exhibit an accelerated response after a second encounter with the same antigen. In our previous studies, we showed that the ability to produce effector molecules within minutes of the secondary exposure to antigen (“rapid recall response”) is associated with the epigenetic state of the rapid recall genes. This memory epigenome is established during the primary T cell encounter with its cognate antigen. To maintain a “rapid recall response” even when antigen is eliminated, resting memory T cells would have to maintain open chromatin signature for years despite episodic homeostatic T cell proliferation. However, the mechanisms underlying the long-term maintenance of this epigenetic pattern remains unclear. Here, we used 10X Multiome (scRNA-seq and scATAC-seq obtained from the same cells) analysis to show that the association between the chromatin state of memory cells and their cytokine expression upon activation is Th lineage specific. Bioinformatic analysis showed that open chromatin specific for memory but not naïve CD4 T cells is enriched with motifs of constitutively expressed transcription factors RUNX, SP1, and ETS. Our preliminary Cut&amp;Tag data in total human resting CD4 T cells demonstrates that RUNX1 binds DNA close to T helper cytokines genes (IL3, IL4, IL9, IL10, IL13, IFNG) at “memory-specific” ATAC-seq regions, suggesting the role of RUNX1 in maintaining this “rapid recall” epigenome. Together with the dynamic model of transcriptome and epigenome rearrangements this data could help us to understand how memory T cells establish a platform that enables and maintains their unique ability to respond more rapidly to subsequent encounters with antigen. Supported by R01AI153442-01A1 from NIAID, NIH
Serous papillary adenocarcinoma of the endometrium. Analysis of proto-oncogene amplification, flow cytometry, estrogen and progesterone receptors, and immunohistochemistry (1990)

Primary and metastatic tumor tissues of serous papillary adenocarcinoma of the endometrium were examined for the following: (1) amplification of int-2, c-erbB-2 and c-myc proto-oncogenes by Southern blot hybridization; (2) DNA ploidy by flow cytometric study; (3) and expression of specific proteins, such as estrogen and progesterone receptors, keratin, vimentin, and carcinoembryonic antigen (CEA) using immunohistochemical and biochemical techniques. Amplification of c-myc was observed in the specimens from the endometrium (ten-fold) and from omental metastasis (five-fold). Both int-2 and c-erbB-2 amplification were not observed. The tumor showed aneuploidy, with the specimens from the endometrium and omental metastasis exhibiting multiple populations of aneuploid tumor cells. Estrogen and progesterone receptors could not be detected biochemically; however, immunohistochemically, estrogen receptors were observed in tumor cells forming papillary structures but not in the tumor cells of the solid, more poorly differentiated areas. A similar distribution was observed for both low and high molecular weight keratin. The findings of c-myc amplification and aneuploidy in the serous papillary adenocarcinoma of the endometrium are consistent with its aggressive behavior observed clinically and emphasize the importance of distinguishing this lesion from other types of endometrial carcinoma.
Modeling and Simulation of an Operational Transformation Algorithm Using Finite State Machines (2018)

Although the principles of real-time collaborative editing have been explored since the eighties, team collaboration software facilitating the completion of tasks as a group continues to be a very hot research topic. A series of theoretical and practical results obtained by the research and industrial communities originated in the theory of distributed computing. They were devised for managing the concurrent nature of user actions and for maintaining the consistency of data as changes are introduced randomly, by multiple users and in real-time. As such, centralized collaborative editing servers were designed to allow users to work in parallel on a document from a typical web browser. In order to maintain the consistency of the content being modified at different sites in different orders, Operational Transformation (OT) mechanisms are at the core of collaboration servers enabling web-based co-editing. However, as expected of modern web application deployments, a centralized OT algorithm is required that must also exhibit properties such as scalability and reliability. In this paper, the processes involved in the client-server interactions of OT are modeled as real-time systems using Finite State Machine (FSM) theory. The consistency of the data is controlled by formal groups of FSMs. Hierarchical FSMs are used to define and simulate the real-time behavior of client and server components when processing and transforming changes initiated by users. The FSM-based OT implementation is tested using random inputs and the approach is shown to be helpful for organizing and managing the complex distributed aspects of such algorithms.
Estimation and Compensation for Near-Surface Wavefield Distortions Using Blind Channel Identification (2007)

E036 Estimation and Compensation for Near-Surface Wavefield Distortions Using Blind Channel Identification R. van Vossen* (Utrecht University) &amp; J. Trampert (Utrecht University) SUMMARY Near-surface wavefield perturbations can be very complex and completely mask target reflections. Despite this complexity conventional methods to compensate for these perturbations rely on simplified parameterizations and mainly focus on time shift corrections. We present a fully data-driven procedure which uses finite-impulse response filters to describe near-surface wavefield perturbations hence allowing time shifts to vary with frequency. These filters are obtained using blind channel identification. Subsequently the recorded data are compensated for the near-surface wavefield distortions using
Utility of Intravenous Alteplase Prior to Endovascular Stroke Treatment (2021)

We detected no differences in functional outcomes of IV thrombolysis-eligible patients with an acute LVO receiving dEVT compared to BT. Because uncertainty for most endpoints remains large and the available data are not able to exclude the possibility of overall benefit or harm, further RCTs are needed.
Metallic Artifacts From Internal Scaphoid Fracture Fixation Screws (2014)

Both MDCT and FPCT standard-dose acquisition showed comparatively less metal-induced artifacts and better overall image quality compared with FPCT low-dose and both CBCT acquisitions. Flat-panel CT may provide sufficient image quality to serve as a versatile CT alternative for postoperative imaging of internally fixated wrist fractures.
The theophylline–oxalic acid co-crystal system: solid phases, thermodynamics and crystallisation (2012)

The solid phases in the theophylline–oxalic acid co-crystal system have been investigated by thermal analysis techniques, X-ray diffraction analysis (XRD) and solubility measurements. The work includes the 2 : 1 co-crystal of theophylline and oxalic acid, polymorphs of theophylline, the theophylline monohydrate and solid oxalic acid. The DSC curve of the co-crystal presents two endothermic peaks, one at about 230 °C where the oxalic acid in the co-crystal decomposes and carbon dioxide is liberated, and another one at 279 °C where the remaining theophylline melts. At equilibrium with the solid co-crystal, the theophylline concentration is only 60% of the corresponding value for the pure solid theophylline. Using the solubility data, the standard Gibbs free energy of formation of the co-crystal from the pure solid phases is estimated to be approximately −6.0 kJ mole−1. In a chloroform/methanol mixture (4 : 1 v : v) the commercial form of pure theophylline (Form II) has been observed to transform into a more stable non-solvated form (Form I). The data suggest that the polymorphs are enantiotropically related with an approximate transition temperature of 70 °C. The 2 : 1 theophylline–oxalic acid co-crystal can be successfully produced by cooling crystallisation in chloroform/methanol mixture (4 : 1 v : v) and by slurry conversion crystallisation also in more benign solvents.
Optimized near-field antenna for UHF RFID smart shelf applications (2015)

This paper presents the design of UHF RFID read/write (R/W) antenna for the variety of smart shelf retail applications. Antenna operation is based on the EM coupling between the open-ended or shorted MS feed line and periodic planar metal strips of certain layout. The proposed antenna can be easily customized for the required volume of smart shelf RFID interrogation. Several antenna prototypes have been designed, produced and measured. The antenna performance has been evaluated in UHF RFID system for the simultaneous detection of arbitrary oriented tagged apparel items placed on the antenna surface. The proposed antenna demonstrates excellent ability to provide strong and uniform E-field distribution at the distances up to 50 cm form the antenna surface.
Supplementary Figure 1 from Onartuzumab (MetMAb): Using Nonclinical Pharmacokinetic and Concentration–Effect Data to Support Clinical Development (2023)

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Adjunctive Use of a Subgingival Controlled‐Release Chlorhexidine Chip Reduces Probing Depth and Improves Attachment Level Compared With Scaling and Root Planing Alone (1998)

The present studies evaluated the efficacy of a controlled-release biodegradable chlorhexidine (CHX) (2.5 mg) chip when used as an adjunct to scaling and root planing on reducing probing depth (PD) and improving clinical attachment level (CAL) in adult periodontitis. Two double-blind, randomized, placebo-controlled multi-center clinical trials (5 centers each) were conducted; pooled data are reported from all 10 centers (447 patients). At baseline, following 1 hour of scaling and root planing (SRP) in patients free of supragingival calculus, the chip was placed in target sites with PD 5 to 8 mm which bled on probing. Chip placement was repeated at 3 and/or 6 months if PD remained > or = 5 mm. Study sites in active chip subjects received either CHX chip plus SRP or SRP alone (to maintain study blind). Sites in placebo chip subjects received either placebo chip plus SRP or SRP alone. Examinations were performed at baseline; 7 days; 6 weeks; and 3, 6, and 9 months. At 9 months significant reductions from baseline favoring the chlorhexidine chip compared with both control treatments were observed with respect to PD (chlorhexidine chip plus SRP, 0.95 +/- 0.05 mm; SRP alone, 0.65 +/- 0.05 mm, P < 0.001; placebo chip plus SRP, 0.69 +/- 0.05 mm, P < 0.001) and CAL (chlorhexidine chip plus SRP, 0.75 +/- 0.06 mm; SRP alone, 0.58 +/- 0.06 mm, P < 0.05; placebo chip plus SRP, 0.55 +/- 0.06 mm, P < 0.05). The proportion of patients who evidenced a PD reduction from baseline of 2 mm or more at 9 months was significantly greater in the chlorhexidine chip group (19%) compared with SRP controls (8%) (P < 0.05). Adverse effects were minor and transient toothache, including pain, tenderness, aching, throbbing, soreness, discomfort, or sensitivity was the only adverse effect that was higher in the chlorhexidine group as compared to placebo (P = 0.042). These data demonstrate that the adjunctive use of the chlorhexidine chip results in a significant reduction of PD when compared with both SRP alone or the adjunctive use of a placebo chip. These multi-center randomized control trials suggest that the chlorhexidine chip is a safe and effective adjunctive chemotherapy for the treatment of adult periodontitis.
Activation of the Notch1/STAT3/Twist signaling axis promotes gastric cancer progression (2012)

Gastric carcinoma is one of the most common malignancies and a lethal cancer in the world. Notch signaling and transcription factors STAT3 (signal transducer and activator of transcription 3) and Twist regulate tumor development and are critical regulators of gastric cancer progression. Herein, the relationship among Notch, STAT3 and Twist pathways in the control of gastric cancer progression was studied. We found that Twist and phosphorylated STAT3 levels were promoted by the activated Notch1 receptor in human stomach adenocarcinoma SC-M1, embryonic kidney HEK293 and erythroleukemia K562 cells. Notch1 signaling dramatically induced Twist promoter activity through a C promoter binding factor-1-independent manner and STAT3 phosphorylation. Overexpression of Notch1 receptor intracellular domain (N1IC) enhanced the interaction between nuclear STAT3 and Twist promoter in cells. Gastric cancer progression of SC-M1 cells was promoted by N1IC through STAT3 phosphorylation and Twist expression including colony formation, migration and invasion. STAT3 regulated gastric cancer progression of SC-M1 cells via Twist. N1IC also elevated the progression of other gastric cancer cells such as AGS and KATO III cells through STAT3 and Twist. The N1IC-promoted tumor growth and lung metastasis of SC-M1 cells in mice were suppressed by the STAT3 inhibitor JSI-124 and Twist knockdown. Furthermore, Notch1 and Notch ligand Jagged1 expressions were significantly associated with phosphorylated STAT3 and Twist levels in gastric cancer tissues of patients. Taken together, these results suggest that Notch1/STAT3/Twist signaling axis is involved in progression of human gastric cancer and modulation of this cascade has potential for the targeted combination therapy.