gebhart/patrepeval huggingface dataset:
Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study (2012)

The combination of lenalidomide-dexamethasone is active in multiple myeloma (MM). Preclinical data showed that the Akt inhibitor, perifosine, sensitized MM cells to lenalidomide and dexamethasone, providing the rationale for this Phase I, multicentre, single-arm study to assess the safety and determine the maximum-tolerated dose (MTD) of perifosine-lenalidomide-dexamethasone in relapsed and relapsed/refractory MM. Patients received escalating doses of perifosine 50-100 mg daily and lenalidomide 15-25 mg once daily on days 1-21 of each 28-d cycle, plus dexamethasone 20-40 mg weekly thereafter, as indicated. Thirty-two patients were enrolled across four dose cohorts. MTD was not reached, with 31 patients evaluable for safety/tolerability. The most common all-causality grade 1-2 adverse events were fatigue (48%) and diarrhoea (45%), and grade 3-4 neutropenia (26%), hypophosphataemia (23%), thrombocytopenia (16%), and leucopenia (13%). Among 30 evaluable patients, 73% (95% confidence interval, 57·5-89·2%) achieved a minimal response or better, including 50% with a partial response or better. Median progression-free survival was 10·8 months and median overall survival 30·6 months. Response was associated with phospho-Akt in pharmacodynamic studies. Perifosine-lenalidomide-dexamethasone was well tolerated and demonstrated encouraging clinical activity in relapsed and relapsed/refractory MM.
Inhomogeneous liver fibrosis distribution revealed by macromolecular proton fraction quantification based on spin-lock MRI (2022)

Yurui Qian, Vincent Wai-Sun Wong, Jian Hou, Baiyan Jiang, Winnie Chiu-Wing Chu, Weitian Chen
The Utility of Virtual Biopsies for Dataset Augmentation as Applied to AI-Based Detection of Tumor Infiltration in Non-Enhancing Brain Lesion (2023)

Delineation of invasive tumor from peritumoral edematous tissue remains a major obstacle to glioma treatment. To address this problem, a neural network was trained to distinguish between these regions using biopsies paired with colocalized MRI inputs. In addition to histologically confirmed biopsies, virtual biopsies sampled from non-contrast enhancing, FLAIR enhancing regions of non-invasive tumors (meningioma, metastasis) were used with an assumed classification of &amp;ldquo;non-tumor&amp;rdquo;. The current work is a preliminary assessment of this assumption and it's impact on model performance.
Direct Interaction of SOS1 Ras Exchange Protein with the SH3 Domain of Phospholipase C-γ1 (2000)

A recent report that microinjection of the SH3 domain of PLC-gamma1 could induce DNA synthesis raised the functional importance of the SH3 domain of PLC-gamma1 in mitogenic signaling. In this report, we provide evidence that SOS1, a p21Ras-specific guanine nucleotide exchange factor, directly binds to the SH3 domain of PLC-gamma1, and that the SH3 domain of PLC-gamma1 is involved in SOS1-mediated p21Ras activation. SOS1 was coprecipitated with the GST-fused SH3 domain of PLC-gamma1 in vitro. The interaction between SOS1 and the PLC-gamma1 SH3 domain is mediated by direct physical interaction. The carboxyl-terminal proline-rich domain of SOS1 is involved in the interaction with the PLC-gamma1 SH3 domain. Moreover, PLC-gamma1 could be co-immunoprecipitated with SOS1 antibody in cell lysates. From transient expression studies, we could demonstrate that the SH3 domain of PLC-gamma1 is necessary for the association with SOS1 in vivo. Intriguingly, overexpression of the SH3 domain of PLC-gamma1, lipase-inactive PLC-gamma1, or wild-type PLC-gamma1 elevated p21Ras activity and ERK activity when compared with vector transfected cells. The PLC-gamma1 mutant lacking the SH3 domain could not activate p21Ras. p21Ras activities in cell lines overexpressing either PLC-gamma1 or the SH2-SH2-SH3 domain of PLC-gamma1 were elevated about 2-fold compared to vector transfected cells. This study is the first to demonstrate that the PLC-gamma1 SH3 domain enhances p21Ras activity, and that the SH3 domain of PLC-gamma1 may be involved in the SOS1-mediated signaling pathway.
Space for the Cures: Science Launches a New Journal Dedicated to Translational Research in Biomedicine (2009)

Science Translational Medicine seeks to serve as the medium for the evolving transformation of biomedical research.
Capacity of large-scale CSMA wireless networks (2009)

In the literature, asymptotic studies of multi-hop wireless network capacity often consider only centralized and deterministic TDMA (time-division multi-access) coordination schemes. There have been fewer studies of the asymptotic capacity of large-scale wireless networks based on CSMA (carrier-sensing multi-access), which schedules transmissions in a distributed and random manner. With the rapid and widespread adoption of CSMA technology, a critical question is that whether CSMA networks can be as scalable as TDMA networks. To answer this question and explore the capacity of CSMA networks, we first formulate the models of CSMA protocols to take into account the unique CSMA characteristics, not captured by existing interference models in the literature. These CSMA models determine the feasible states, and consequently the capacity of CSMA networks. %and are functions of various CSMA parameters. We then study the throughput efficiency of CSMA scheduling as compared to TDMA. Finally, we tune the CSMA parameters so as to maximize the throughput to the optimal order. As a result, we show that CSMA can achieve throughput as Ω(1/√n), the same order as optimal centralized TDMA, on uniform random networks. Our CSMA scheme makes use of an efficient backbone-peripheral routing scheme and a careful design of dual carrier-sensing and dual channel scheme. We also address practical implementation issues of our capacity-optimal CSMA scheme.
PO-516 E6/E7 RNA(LIP): a novel liposomal RNA vaccine for treatment of patients with HPV16-positive malignancies (2018)

Introduction Human papillomavirus (HPV) has emerged as a major risk factor for Head Neck squamous cell carcinoma (HNSCC) and the incidence of HPV-positive HNSCC continues to rise. Standard treatment of HNSCC given with curative intent causes substantial and long-term physical and functional impairments, but nonetheless, approx. 50% of patients die of their disease. Alternative treatments are urgently needed to improve survival but also to reduce treatment-associated morbidity. Both CD8+ and CD4+ T cells are important for viral clearance and regression of HPV-positive premalignant lesions; density of tumor-infiltrating lymphocytes (TILs) is a strong predictor of the outcome of HPV-positive oropharyngeal cancers. Consequently, therapeutic cancer vaccines hold great promise to achieve long-term disease control in HPV-positive malignancies if they generate tumour antigen-specific and durable anti-cancer immunity that can recognise viral antigen at the tumour site. Material and methods Recent advances in the systemic delivery of antigen-encoding lipid-complexed RNA (RNA(LIP)) allow efficient targeting and RNA delivery to secondary lymphoid organs body-wide with early data supporting substantial immunological and clinical effects. With E6/E7 RNA(LIP), BioNTech has developed a promising immunotherapeutic approach to address a high unmet medical need. Results and discussions E6/E7 RNA(LIP) is the first systemically administrable therapeutic cancer vaccine based on two lipid-complexed RNA drug products targeting the well-characterised HPV16-derived viral antigens E6 and E7. Preclinical studies in two independent syngeneic mouse tumour models demonstrated that vaccine treatment significantly increased the frequency of TILs, leading to strong tumour microenvironment polarisation and consistent regression of large established tumours. Conclusion Based on the encouraging preclinical proof-of-concept data, E6/E7 RNA(LIP) is currently evaluated in a multi-centre, first-in-human phase I/II trial in patients with HPV16-positive HNSCC and other HPV16-positive cancers (Sponsor: University Hospital of Southampton NHS Foundation Trust; Eudra CT No.: 2014-002061-30). Objectives of the trial are to study safety, tolerability, and immunogenicity of the novel immunotherapeutic approach. Where measurable tumour is present clinical response rate and expansion of HPV-specific TILs will be evaluated. Here we present the preclinical proof-of-concept data as well as preliminary data from the ongoing clinical trial.
Design of an Efficient Security Protocol Analyzer (2007)

In this paper, we present a efficient security protocol analyzer to verify cryptographic security protocols. Our analyzer verifies security protocols based on notions of provable security. The analyzer only checks whether the core properties of security protocols satisfy the notions, making it faster than previous tools. The analyzer automatically checks whether authentication and key distribution protocols satisfy definitions such as Secure Mutual Authentication, Semantic Security, and Forward Secrecy. A user can design and evaluate security protocols by using our analyzer, according to the condition that the protocol will be used. Furthermore, our analyzer has a sophisticated GUI to set security protocols to be evaluated. Thus, the analyzer is useful for constructing and checking security protocols for many services. Key words:
Full Duplex for IEEE 802.11 Wireless LANs (2022)

&lt;p&gt;With the development of wireless LANs, they are expected to have wide applications not only in traditional home but also in industrial applications. Therefore, the next generation of IEEE 802.11 wireless LAN standard demands higher throughput and lower latency. Full duplex (FD) technology, which allows a device to simultaneously transmit and receive signals on the same channel by cancelling self-interference, is one of the promising solutions to meet those requirements. Feasibility studies for applying FD technology to wireless LAN systems started in IEEE 802.11 standardization. In this article, we provide an overview of the FD mechanism and the technical problems for the realization. Furthermore, we provide the direction of the FD system for wireless LANs in IEEE 802.11 standardization. In addition, we discuss the expected low latency effect of the FD mechanism on the wireless LAN systems based on the direction in IEEE 802.11 standardization.&lt;/p&gt;
Lack of Essential Role of NF-κB p50, RelA, and cRel Subunits in Virus-Induced Type 1 IFN Expression (2007)

Type 1 IFNs (IFN-alphabeta) play pivotal roles in the host antiviral response and in TLR-induced signaling. IFN regulatory factor (IRF) and NF-kappaB transcription factors are thought to be crucial for virus-induced mRNA expression of IFN-beta. Although recent studies have demonstrated essential roles for IRF3 and IRF7, the definitive role of NF-kappaB factors in IFN-beta (or IFN-alpha) expression remains unknown. Using mice deficient in distinct members of the NF-kappaB family, we investigated NF-kappaB function in regulating type 1 IFN expression in response to Sendai virus and Newcastle disease virus infection. Surprisingly, IFN-beta and IFN-alpha expression was strongly induced following virus infection of mouse embryonic fibroblasts (MEFs) from p50(-/-), RelA/p65(-/-), cRel(-/-), p50(-/-)cRel(-/-), and p50(-/-)RelA(-/-) mice. Compared with wild-type MEFs, only RelA(-/-) and p50(-/-)RelA(-/-) MEFs showed a modest reduction in IFN-beta expression. To overcome functional redundancy between different NF-kappaB subunits, we expressed a dominant-negative IkappaBalpha protein in p50(-/-)RelA(-/-) MEFs to inhibit activation of remaining NF-kappaB subunits. Although viral infection of these cells failed to induce detectable NF-kappaB activity, both Sendai virus and Newcastle disease virus infection led to robust IFN-beta expression. Virus infection of dendritic cells or TLR9-ligand CpG-D19 treatment of plasmacytoid dendritic cells from RelA(-/-) or p50(-/-)cRel(-/-) mice also induced robust type 1 IFN expression. Our findings therefore indicate that NF-kappaB subunits p50, RelA, and cRel play a relatively minor role in virus-induced type 1 IFN expression.
The distribution of CD10 (NEP 24.11, CALLA) in humans and mice is similar in non‐lymphoid organs but differs within the hematopoietic system: absence on murine T and B lymphoid progenitors (1995)

Prior studies in the human have implied an important function for CD10 (CALLA, neutral endopeptidase 24.11) in early lymphoid development. To examine the role of this ectoenzyme in an experimental system, a rat mAb specific for mouse CD10, termed R103, was generated. Immunohistological and flow cytometric analyses indicate that the distribution of CD10 in non-lymphoid anatomical compartments is virtually identical in human and mouse. However, CD10 expression within the hematopoietic system is strikingly different. In contrast to human spleen, lymph node and thymus, the corresponding mouse organs contain no detectable CD10+ cells. Mouse granulocytes, unlike human granulocytes, also lack CD10 expression. Five-color flow cytometric studies of adult bone marrow (BM) from C57BL/6 and BALB/c mice with mAb specific for CD43, B220, HSA, BP-1 and immunoglobulin M fail to detect any significant number of CD10+ cells at pro-B, pre-B or B cell stages. In addition, lymphoid cells in both (rIL-7) independent and rIL-7-dependent in vitro pro-B cell cultures lack CD10 expression. Consistent with this result, CD10 mRNA is not detected. Unlike the AA4.1+ population from day 13 and 14 fetal liver, the CD10+ subset is unable to reconstitute T and B lymphoid compartments in RAG-2-/- mice. Nevertheless, mouse CD10 is readily found on BM stromal elements known to support early B lineage lymphoid development. Given the common expression of CD10 on human and mouse BM stromal elements, this enzyme may have an important function in the stromal cell-dependent phase of hematopoiesis.
Development of Potent Fluorescent Polyamine Toxins and Application in Labeling of Ionotropic Glutamate Receptors in Hippocampal Neurons (2013)

The natural product argiotoxin-636 (ArgTX-636) found in the venom of the Argiope lobata spider is a potent open-channel blocker of ionotropic glutamate (iGlu) receptors, and recently, two analogues, ArgTX-75 and ArgTX-48, were identified with increased potency and selectivity for iGlu receptor subtypes. Here, we have exploited these analogues as templates in the development of fluorescent iGlu receptor ligands to be employed as unique tools for dynamic studies. Eighteen fluorescent analogues were designed and synthesized, and subsequently pharmacologically evaluated at three iGlu receptor subtypes, which resulted in the discovery of highly potent fluorescent iGlu receptor antagonists with IC50 values as low as 11 nM. The most promising ligands were further characterized showing retention of their mechanism of action, as open-channel blockers of iGlu receptors, as well as preservation of the photophysical properties of the incorporated fluorophores. Finally, we demonstrate the applicability of the developed probes for imaging of iGlu receptors in hippocampal neurons.
The diamidine DB75 targets the nucleus of Plasmodium falciparum (2019)

Abstract Background DB289, [2,5-bis(4-amidinophenyl)furan bis-O-methylamidoxime], is a broad spectrum anti-parasitic compound which has been shown to be effective against malaria in recent clinical trials. DB75, [2,5-bis(4-amidinophenyl)furan], is the active metabolite of this drug. The objective of this study was to determine the mechanism of action of DB75 in Plasmodium falciparum. Methods Live parasites were observed by confocal microscopy after treatment with organelle specific dyes and DB75, an inherently fluorescent compound. Parasites were exposed to DB75 and assessed for growth and morphological changes over time using blood smears and light microscopy. Also, to determine if DB75 affects gene transcription, real time PCR was used to monitor transcript levels over time for six developmentally expressed genes, including trophozoite antigen R45-like (PFD1175w), lactate dehydrogenase (PF13_0141), DNA primase (PFI0530c), isocitrate dehydrogenase (PF13_0242), merozoite surface protein-1 (PFI1475w), and merozoite surface protein-7 (PF13_0197). Results The results show that DB75 localizes in the parasite nucleus but not in other organelles. Once rings are exposed, parasites mature to the trophozoite stage and stall. No stage-dependent or gene-specific inhibition of transcription was seen. However, DB75 delayed peak transcription of trophozoite-stage genes. Conclusion Taken together, DB75 appears to concentrate in the nucleus and delay parasite maturation.
Transvalencin A, a Thiazolidine Zinc Complex Antibiotic Produced by a Clinical Isolate of Nocardia transvalensis: I.Taxonomy, Fermentation, Isolation and Biological Activities (2004)

A new thiazolidine-type antibiotic with zinc in its structure, designated transvalencin A, was isolated from Nocardia sp. IFM 10065, a clinical isolate from a patient with actinomycotic mycetoma. The strain was identified as Nocardia transvalensis based on its morphological, phenotypic and phylogenetic characteristics. Transvalencin A showed antimicrobial activity against fungi such as Trichophyton mentagrophytes and Cryptococcus neoformans. The antibiotic is also active against Gram-positive bacteria such as Micrococcus luteus. We observed higher activity for fungi in an acidic medium than in a neutral medium.
Designing Far Memory Data Structures (2019)

Technologies like RDMA and Gen-Z, which give access to memory outside the box, are gaining in popularity. These technologies provide the abstraction of far memory, where memory is attached to the network and can be accessed by remote processors without mediation by a local processor. Unfortunately, far memory is hard to use because existing data structures are mismatched to it. We argue that we need new data structures for far memory, borrowing techniques from concurrent data structures and distributed systems. We examine the requirements of these data structures and show how to realize them using simple hardware extensions.
A preclinical study to evaluate the combination of azeliragon, an inhibitor of the receptor for advanced glycation endproducts (RAGE), with radiation therapy as a potential treatment of glioblastoma. (2023)

e14056 Background: Systemic lymphopenia, which is independently associated with poor overall survival, is observed in approximately 30-50% of patients with glioblastoma (GBM) after chemoradiotherapy. We recently found that cranial irradiation of GBM tumors increases circulating myeloid-derived suppressor cells (MDSC) contributing to systemic lymphopenia. Additionally, we found that cranial radiation increases circulating levels of the RAGE ligands S100A8/9 and HMGB1, which have been reported to increase MDSC and their immunosuppressive effects through binding RAGE. We, therefore, hypothesized that targeting RAGE receptors on MDSC could prevent immunosuppression and improve survival in preclinical GBM models. Methods: We orthotopically implanted GBM cells (GL261 and CT2A) into immunocompetent C57BL6 mice. The GBM tumor-bearing mice were treated with five doses of fractionated radiation therapy (RT, 2 Gy/day for 5 consecutive days) to the whole head in combination with RAGE inhibitor azeliragon (0.1mg/mice/day i.p starting one day before RT for up to 10 days). We evaluated the immune cells in the tumor microenvironment (TME) and spleen at 14 days post-tumor implantation. We also evaluated the circulating immune cells and RAGE ligands (HMGB1 and S100A8/A9) in the plasma at 7, 14, and 21 days post-tumor implantation and monitored the mice for survival up to 60 days. Results: GBM tumor-bearing mice (GL261 &amp; CT2A) treated with RT plus azeliragon had significantly improved survival when compared to RT alone or azeliragon alone. RT plus azeliragon significantly reduced the accumulation of granulocytic-MDSC (G-MDSC), monocytic-MDSC (M-MDSC), tumor-associated macrophages (TAM), and regulatory T cells (T reg ), while increasing infiltrating CD8 T cells in the TME as compared to RT alone. RT alone significantly increased the accumulation of G-MDSC and M-MDSC in the spleen, which was significantly reduced with concurrent azeliragon. Concurrent administration of azeliragon with RT did not significantly affect the radiation-induced increase of circulating M-MDSC as well as plasma HMGB1 and S100A8/A9 concentration, though there was a modest reduction of circulating G-MDSC. Conclusions: Our study indicates that azeliragon, by blocking RAGE interaction with its ligands, helps to overcome the MDSC-mediated immunosuppression that occurs after RT. The combination of azeliragon with RT enhances survival in preclinical models. Clinical trials evaluating the safety and efficacy of azeliragon in combination with RT for newly diagnosed GBM are currently under development.
Joint localization and transmit-ambiguity resolution for ultra-low energy wireless sensors (2016)

Technological advances in the miniaturization of millimeter-sized sensor motes facilitate new application cases where the motes' inherent energy constraints enforce radical changes with respect to the sensors' communication procedures. An upcoming application scenario is the surveying and exploration of hardly permeable and hardly accessible underground environments such as those of oil-sand mining areas. This scenario requires ten-thousands of millimeter-sized sensor motes (outer diameter less than 5mm) to examine the resource wealth. Within this scope, a correspondingly large amount of extremely resource constrained sensors motes need to have the possibility to sense their environment and interact with each other. In order to enable such application cases, significant energy savings are necessary. An interesting and promising approach is to shorten the sensors' DS-CDMA code sequences and, thereby, reduce the communication related energy costs. In this work, we investigate the resulting downsides of this approach on the range-based localization. As the code shortening leads to the problem of nonunique transmitter identification and consequently non-relatable pairwise distance measurements, the localization of the sensors by typical means is prevented in the first place. This is because multiple sensor motes will concurrently use the same transmit-codes. In this regard, we propose an approach which enables the joint localization and ambiguity resolution and reduces the complexity compared to sequential approaches where at fist the transmit-ambiguities are resolved and a localization with typical methods is performed subsequently.
Interior Noise Predictions in the Preliminary Design of the Large Civil Tiltrotor (LCTR2) (2013)

A prediction scheme was established to compute sound pressure levels in the interior of a simplified cabin model of the second generation Large Civil Tiltrotor (LCTR2) during cruise conditions, while being excited by turbulent boundary layer flow over the fuselage, or by tiltrotor blade loading and thickness noise. Finite element models of the cabin structure, interior acoustic space, and acoustically absorbent (poro-elastic) materials in the fuselage were generated and combined into a coupled structural-acoustic model. Fluctuating power spectral densities were computed according to the Efimtsov turbulent boundary layer excitation model. Noise associated with the tiltrotor blades was predicted in the time domain as fluctuating surface pressures and converted to power spectral densities at the fuselage skin finite element nodes. A hybrid finite element (FE) approach was used to compute the low frequency acoustic cabin response over the frequency range 6-141 Hz with a 1 Hz bandwidth, and the Statistical Energy Analysis (SEA) approach was used to predict the interior noise for the 125-8000 Hz one-third octave bands.