gebhart/patrepeval huggingface dataset:
Dysfunctions of innate and adaptive immune tumor microenvironment in Waldenström macroglobulinemia (2022)

Waldenström macroglobulinemia (WM) is a rare subtype of non-Hodgkin lymphoma characterized by malignant lymphoplasmacytic cells in the bone marrow (BM). To dissect the pathophysiology of WM, we evaluated clonal cells by mapping of B cell lymphomagenesis with adaptive and innate immune tumor microenvironment (TME) in the BM of WM patients using mass cytometry (CyTOF). In-depth immunophenotypic profiling of WM cells exhibited profound expansion of clonal cells in both unswitched and switched memory B cells and also plasma cells with aberrant expression variations. WM B lymphomagenesis was associated with reduction of most B cell precursors assessed with the same clonally restricted light chain and phenotypic changes. The immune TME was infiltrated by mature monocytes, neutrophils and adaptive T cells, preferentially subsets of effector T helper, effector CTL and effector memory CTL cells that were associated with superior overall survival (OS), in contrast to progenitors of T cells and myeloid/monocytic lineage subsets that were suppressed in WM cohort. Moreover, decrease in immature B and NKT cells was related to worse OS in WM patients. Innate and adaptive immune subsets of WM TME were modulated by immune checkpoints, including PD-1/PD-L1&PD-L2, TIGIT/PVR, CD137/CD137-L, CTLA-4, BTLA and KIR expression. The response of ibrutinib treatment to the reduction of clonal memory B cell was associated with high levels of immature B cells and effector memory CTL cells. Our study demonstrates that CyTOF technology is a powerful approach for characterizing the pathophysiology of WM at various stages, predicting patient risk and monitoring the effectiveness of treatment strategies.
Abstract 2114: Tumor cell-targeted STING-agonist antibody-drug conjugates achieve potent anti-tumor activity by delivering STING agonist specifically to tumor cells andFcγRI-expressing subset of myeloid cells (2022)

Abstract STING pathway agonism has emerged as a potential therapeutic strategy to stimulate anti-tumor immune responses. We have previously shown that tumor cell-targeted antibody-drug conjugates (ADCs) carrying a novel STING agonist induce anti-tumor activity without causing substantial elevations in systemic cytokine levels, thus suggesting a therapeutic advantage of STING agonist ADCs relative to unconjugated agonists. ADCs constitute a proven therapeutic modality that is ideally suited to enable systemic administration and delivery of the conjugated drug to desired cell types within the tumor microenvironment. In addition to delivering STING agonist into the antigen-expressing tumor cells, antigen-bound ADCs deliver STING agonist to tumor-resident myeloid cells through Fcγ receptor (FcγR)-mediated internalization. In this study we investigated the mechanism of FcγR-mediated internalization of the tumor cell-targeted STING-agonist ADCs into myeloid cells and the nature of the subsequent STING pathway activation. We developed flow cytometry-based assays to determine the changes in FcγRI, FcγRII, and FcγRIII cell surface detection levels in the presence of ADCs specifically designed to be either proficient or deficient in FcγR-binding. Combined with functional assays based on co-culture of cancer cells and FcγRI knock out myeloid cells, we identified FcγRI as the major Fcγ receptor that mediates target-bound ADC internalization into myeloid cells in vitro. Even though FcγRI is expressed only by a subset of CD11b+ myeloid cells, tumor cell-targeted ADCs induce greater production of interferons and other cytokines and more potent cancer cell killing than CD11b-targeted-ADCs, which deliver STING agonist into FcγRI- (non-productive) as well as FcγRI+ (productive) myeloid cells. Finally, we demonstrate that myeloid cells within dissociated primary human tumors from multiple donors express FcγRI and are capable of tumor cell killing in response to tumor cell-targeted STING agonist ADCs in vitro. In summary, our data indicate that the ADC-mediated delivery of a STING agonist specifically into FcγRI-expressing myeloid cells efficiently activates innate immune responses in the most relevant immune cell types within the tumor microenvironment. Citation Format: Naniye Malli Cetinbas, Kalli C. Catcott, Travis Monnell, Jahna Soomer-James, Keith Bentley, Susan Clardy, Bingfan Du, Eoin Kelleher, Marina Protopopova, Cheri Stevenson, Joshua D. Thomas, Alex Uttard, Dorin Toader, Jeremy Duvall, Raghida Bukhalid, Marc Damelin, Timothy B. Lowinger. Tumor cell-targeted STING-agonist antibody-drug conjugates achieve potent anti-tumor activity by delivering STING agonist specifically to tumor cells andFcγRI-expressing subset of myeloid cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2114.
A framework for clustering massive graph streams (2010)

Abstract In this paper, we examine the problem of clustering massive graph streams. Graph clustering poses significant challenges because of the complex structures which may be present in the underlying data. The massive size of the underlying graph makes explicit structural enumeration very difficult. Consequently, most techniques for clustering multidimensional data are difficult to generalize to the case of massive graphs. Recently, methods have been proposed for clustering graph data, though these methods are designed for static data, and are not applicable to the case of graph streams. Furthermore, these techniques are especially not effective for the case of massive graphs, since a huge number of distinct edges may need to be tracked simultaneously. This results in storage and computational challenges during the clustering process. In order to deal with the natural problems arising from the use of massive disk‐resident graphs, we propose a technique for creating hash‐compressed microclusters from graph streams. The compressed microclusters are designed by using a hash‐based compression of the edges onto a smaller domain space. We provide theoretical results which show that the hash‐based compression continues to maintain bounded accuracy in terms of distance computations. Since clustering is a data summarization technique, it can also be naturally extended to the problem of evolution analysis. We provide experimental results which illustrate the accuracy and efficiency of the underlying method. Copyright © 2010 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 3: 399‐416, 2010
Abstract 4389: Post-translational modifications of histone demethylase JMJD1A in prostate cancer cells (2019)

Castration-resistant prostate cancer (CRPC) is the major cause of death for prostate cancer (PCa) patients. Re-activation of androgen receptor (AR) activity during androgen-deprivation therapy is believed to underlie CRPC development. We have found that histone demethylase JMJD1A primarily regulates AR and c-Myc activity and thus plays a key role in promoting PCa cell proliferation or survival. Unfortunately, specific JMJD1A inhibitors are not yet available. Here, we identified several post-translational modifications of JMJD1A by performing the JMJD1A immunoprecipitation and mass spectrometry analysis. These modifications include the canonical ubiquitination that targets JMJD1A for proteasome-dependent degradation, non-canonical ubiquitination that enhances the recruitment of co-activators, as well as those that can regulate these ubiquitination events. We also found that these modifications could be manipulated by commercially available inhibitors, to reduce the JMJD1A protein level and prostate cancer cell growth. Thus, targeting the JMJD1A modifications may serve as an alternative means to inhibit JMJD1A activity for the anti-PCa therapy.Note: This abstract was not presented at the meeting.Citation Format: Songhui Xu, Lingling Fan, Xiaolu Cui, Fengbo Zhang, Arif Hussain, Ladan Fazli, Martin Gleave, Jianfei Qi. Post-translational modifications of histone demethylase JMJD1A in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4389.
Site-Occupation-Tuned Superionic LixScCl3+xHalide Solid Electrolytes for All-Solid-State Batteries (2020)

The enabling of high energy density of all-solid-state lithium batteries (ASSLBs) requires the development of highly Li+-conductive solid-state electrolytes (SSEs) with good chemical and electrochemical stability. Recently, halide SSEs based on different material design principles have opened new opportunities for ASSLBs. Here, we discovered a series of LixScCl3+x SSEs (x = 2.5, 3, 3.5, and 4) based on the cubic close-packed anion sublattice with room-temperature ionic conductivities up to 3 × 10–3 S cm–1. Owing to the low eutectic temperature between LiCl and ScCl3, LixScCl3+x SSEs can be synthesized by a simple co-melting strategy. Preferred orientation is observed for all the samples. The influence of the value of x in LixScCl3+x on the structure and Li+ diffusivity were systematically explored. With increasing x value, higher Li+, lower vacancy concentration, and less blocking effects from Sc ions are achieved, enabling the ability to tune the Li+ migration. The electrochemical performance shows that Li3ScCl6 possesses a wide electrochemical window of 0.9–4.3 V vs Li+/Li, stable electrochemical plating/stripping of Li for over 2500 h, as well as good compatibility with LiCoO2. LiCoO2/Li3ScCl6/In ASSLB exhibits a reversible capacity of 104.5 mAh g–1 with good cycle life retention for 160 cycles. The observed changes in the ionic conductivity and tuning of the site occupations provide an additional approach toward the design of better SSEs.
Diminished pheromone‐induced sexual behavior in neurokinin‐1 receptor deficient (TACR1−/−) mice (2012)

Studies in mice with targeted deletions of tachykinin genes suggest that tachykinins and their receptors influence emotional behaviors such as aggression, depression and anxiety. Here, we investigated whether TAC1- and TAC4-encoded peptides (substance P and hemokinin-1, respectively) and the neurokinin-1 receptor (NK-1R) are involved in the modulation of sexual behaviors. Male mice deficient for the NK-1R (TACR1 (-/-)) exhibited decreased exploration of female urine in contrast to C57BL/6 control mice and mice deficient for NK-1R ligands such as TAC1 (-/-), TAC4 (-/-) and the newly generated TAC1 (-/-) /TAC4 (-/-) mice. In comparison to C57BL/6 mice, mounting frequency and duration were decreased in male TACR1 (-/-) mice, while mounting latency was increased. Decreased preference for sexual pheromones was also seen in female TACR1 (-/-) mice. Furthermore, administration of the NK-1R-antagonist L-703,606 decreased investigation of female urine by male C57BL/6 mice, suggesting an involvement of NK-1R in urine sniffing behavior. Our results provide evidence for the NK-1R in facilitating sexual approach behavior, as male TACR1 (-/-) mice exhibited blunted approach behavior toward females following the initial interaction compared with C57BL/6 mice. NK-1R signaling may therefore play an important role in pheromone-induced sexual behavior.
Video Coding Using a Simplified Block Structure and Advanced Coding Techniques (2010)

This paper describes a new video coding scheme based on a simplified block structure that significantly outperforms the coding efficiency of the ISO/IEC 14496-10 ITU-T H.264 advanced video coding (AVC) standard. Its conceptual design is similar to a typical block-based hybrid coder applying prediction and subsequent prediction error coding. The basic coding unit is an 8 × 8 block for inter, and an 8 × 8 or a 16 × 16 block for intra, instead of the usual 16 × 16 macroblock. No larger block sizes are considered for prediction and transform. Based on this simplified block structure, the coding scheme uses simple and fundamental coding tools with optimized encoding algorithms. In particular, the motion representation is based on a minimum partitioning with blocks sharing motion borders. In addition, compared to AVC, the new and improved coding techniques include: block-based intensity compensation, motion vector competition, adaptive motion vector resolution, adaptive interpolation filters, edge-based intra prediction and enhanced chrominance prediction, intra template matching, larger trans forms and adaptive switchable transforms selection for intra and inter blocks, and nonlinear and frame-adaptive de-noising loop filters. Finally, the entropy coder uses a generic flexible zero tree representation applied to both motion and texture data. Attention has also been given to algorithm designs that facilitate parallelization. Compared to AVC, the new coding scheme offers clear benefits in terms of subjective video quality at the same bit rate. Objective quality improvements are equally significant. At the same quality, an average bit-rate reduction of 31% compared to AVC is reported.
Traffic Engineering Extensions to OSPF for GMPLS Control of Evolving G.709 Optical Transport Networks (2014)

This document describes Open Shortest Path First - Traffic Engineering
(OSPF-TE) routing protocol extensions to support GMPLS control of
Optical Transport Networks (OTNs) specified in ITU-T Recommendation
G.709 as published in 2012. It extends mechanisms defined in RFC 4203.
Production of melanin pigment fromPseudomonas stutzeriisolated from red seaweedHypnea musciformis (2013)

This investigation reports a marine Pseudomonas stutzeri strain HMGM-7 [MTCC 11712] that produces significant quantities of melanin (6·7 g l(-1) ) in sea-water medium without the supplementation of L-tyrosine. The confirmation of the produced melanin was carried out by various chemical and physical characterization studies. The isolated melanin may find potential application for use in cosmetic and/or pharmaceutical industries.
A recovery algorithm for a distributed database system (1983)

We describe a reliability algorithm being considered for DDM, a distributed database system under development at Computer Corporation of America. The algorithm is designed to tolerate clean site failures in which sites simply stop running. The algorithm allows the system to reconfigure itself to run correctly as sites fail and recover. The algorithm solves the subproblems of atomic commit and replicated data handling in an integrated manner.
Efficient Synthesis and Anti-Tubercular Activity of a Series of Spirocycles: An Exercise in Open Science (2014)

Tuberculosis afflicts an estimated 2 billion people worldwide and causes 1.3 million deaths annually. Chemotherapeutic solutions rely on drugs developed many years ago, with only one new therapeutic having been approved in the last 40 years. Given the rise of drug-resistant strains, there is an urgent need for the development of a more robust drug development pipeline. GlaxoSmithKline recently placed the structures and activities of 177 novel anti-tubercular leads in the public domain, as well as the results of ongoing optimisation of some of the series. Since many of the compounds arose from screening campaigns, their provenance was unclear and synthetic routes were in many cases not reported. Here we present the efficient synthesis of several novel analogues of one family of the GSK compounds-termed "Spiros"-using an oxa-Pictet-Spengler reaction. The new compounds are attractive from a medicinal chemistry standpoint and some were potent against the virulent strain, suggesting this class is worthy of further study. The research was carried out using open source methodology, providing the community with full access to all raw experimental data in real time.
Supplementary Legends for Figure 1 and Tables 1-5 from Distinct Patterns of Dysregulated Expression of Enzymes Involved in Androgen Synthesis and Metabolism in Metastatic Prostate Cancer Tumors (2023)

&lt;p&gt;PDF file - 68K&lt;/p&gt;
Contralateral Interhemispheric Approach to Deep-Seated Cavernous Malformations (2014)

The contralateral interhemispheric approach is a safe, clinically well tolerated, and surgically efficacious approach to deep-seated cavernomas.
The detailed characterisation of a 400 kb cosmid walk in the BRCA1 region: identification and localisation of 10 genes including a dual-specificity phosphatase (1994)

We have produced a detailed physical and transcriptional map of a 400 kb region within the narrowest flanking markers known to contain the hereditary breast and ovarian susceptibility gene, BRCA1. The approach described here has avoided the problems of chimaerism, instability and rearrangements commonly observed in yeast artificial chromosomes by converting the YAC clones into ordered chromosome 17-specific cosmid contigs and joining these contigs by cosmid end-walking. A detailed long-range restriction map provided a framework for the cosmid contig assembly and further refines existing physical mapping data. We have used a combined approach towards the isolation of the genes housed within these cosmids. This has resulted in the isolation and precise localisation of eight novel genes, including a novel G protein and an endogenous retrovirus related to the HERV-K family, and the previously described dual-specificity VHR phosphatase and MOX1 homeobox genes.
SDN use cases for service provider networks: part 1 [Guest Editorial] (2016)

Software defined networking (SDN) is being heralded as a major breakthrough for provisioning new services, commoditizing network hardware and reducing service provider capital and operational expenditures. Decoupling the control plane from the data plane has inherent advantages in terms of offering flexibility and presenting new service capabilities, but also presents operational and functional challenges. Such decoupling would create a new set of use cases, equipment, and network best practices that providers would have to imbibe in the near future. The key scope of this Feature Topic (FT) was to understand, from an implementation perspective, how SDNs can be implemented in very large networks using commodity gear or white boxes through use cases.
Joint Routing and Resource Allocation for Millimeter Wave Picocellular Backhaul (2019)

Picocellular architectures are essential for providing the spatial reuse required to satisfy the ever-increasing demand for mobile data. A key deployment challenge is to provide backhaul connections with sufficiently high data rate. Providing wired support (e.g., using optical fiber) to pico base stations deployed opportunistically on lampposts and rooftops is impractical, hence wireless backhaul becomes an attractive approach. A multihop mesh network comprised of directional millimeter (mm) wave links is considered here for this purpose. Such networks are well suited for scaling backhaul data rates due to the abundance of spectrum in the mm wave bands, and the ability to form highly directional, electronically steerable beams. The backhaul design problem is formulated as one of joint routing and resource allocation, accounting for mutual interference across simultaneously active links. A computationally tractable formulation is developed by leveraging the localized nature of interference and the provable existence of a sparse optimal allocation. Numerical results are provided for topologies modeling urban and suburban settings.
Design-performance trade-offs in CMOS-domino logic (1986)

The authors present a study of the charge-sharing problem and its effect on the performance of CMOS-domino logic. Several solutions to the charge-sharing problem are examined, and the results are verified by simulation. Thus, the charge-sharing problem in CMOS-domino logic was identified and alternate approaches were evaluated.
Icariside II, a Prenyl-Flavonol, Alleviates Inflammatory and Neuropathic Pain by Inhibiting T-Type Calcium Channels and USP5-Cav3.2 Interactions (2023)

Cav3.2 channels play an important role in the afferent nociceptive pathway, which is responsible for both physiological and pathological pain transmission. Cav3.2 channels are upregulated during neuropathic pain or peripheral inflammation in part due to an increased association with the deubiquitinase USP5. In this study, we investigated nine naturally occurring flavonoid derivatives which we tested for their abilities to inhibit transiently expressed Cav3.2 channels and their interactions with USP5. Icariside II (ICA-II), one of the flavonols studied, inhibited the biochemical interactions between USP5 and Cav3.2 and concomitantly and effectively blocked Cav3.2 channels. Molecular docking analysis predicts that ICA-II binds to the cUBP domain and the Cav3.2 interaction region. In addition, ICA-II was predicted to interact with residues in close proximity to the Cav3.2 channel's fenestrations, thus accounting for the observed blocking activity. In mice with inflammatory and neuropathic pain, ICA-II inhibited both phases of the formalin-induced nocifensive responses and abolished thermal hyperalgesia induced by injection of complete Freund's adjuvant (CFA) into the hind paw. Furthermore, ICA-II produced significant and long-lasting thermal anti-hyperalgesia in female mice, whereas Cav3.2 null mice were resistant to the action of ICA-II. Altogether, our data show that ICA-II has analgesic activity via an action on Cav3.2 channels.
STRide probes: Single-labeled short tandem repeat identification probes (2021)

The demand for forensic DNA profiling at the crime scene or at police stations is increasing. DNA profiling is currently performed in specialized laboratories by PCR amplification of Short Tandem Repeats (STR) followed by amplicon sizing using capillary electrophoresis. The need for bulky equipment to identify alleles after PCR presents a challenge for shifting to a decentralized workflow. We devised a novel hybridization-based STR-genotyping method, using Short Tandem Repeat Identification (STRide) probes, which could help tackle this issue. STRide probes are fluorescently labeled oligonucleotides that rely on the quenching properties of guanine on fluorescein derivatives. Mismatches between STRide probes and amplicons can be detected by melting curve analysis after asymmetric PCR. The functionality of the STRide probes was demonstrated by analyzing synthetic DNA samples for the D16S539 locus. Next, STRide probes were developed for five different CODIS core loci (D16S539, TH01, TPOX, FGA, and D7S820). These probes were validated by analyzing 13 human DNA samples. Successful genotyping was obtained using inputs as low as 31 pg of DNA, demonstrating high sensitivity. The STRide probes are ideally suited to be implemented in a microarray and present an important step towards a portable device for fast on-site forensic DNA fingerprinting.
Poly(ester anhydride)s prepared by the insertion of ricinoleic acid into poly(sebacic acid) (2003)

Abstract New degradable poly(ester anhydride)s were prepared by the melt polycondensation of diacid oligomers of poly(sebacic acid) (PSA) transesterified with ricinoleic acid. The transesterification of PSA with ricinoleic acid to form oligomers was conducted via a melt bulk reaction between a high molecular weight PSA and ricinoleic acid. A systematic study on the synthesis, characterization, degradation in vitro , drug release, and stability of these polymers was performed. Polymers with weight‐average molecular weights of 2000–60,000 and melting temperatures of 24–77 °C were obtained for PSA containing 20–90% (w/w) ricinoleic acid. NMR and IR analyses indicated the formation of ester bonds along the polyanhydride backbone. These new degradable copolymers have potential use as drug carriers. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1059–1069, 2003