gebhart/patrepeval huggingface dataset:
Modeling and optimization of subscriber loop deployment strategy for Hanaro Telecom (2002)

The advance of technology has given many alternatives of subscriber loop. Having many choices is a blessing and a curse at the same time for a newly established organization. A group of experts from Hanaro Telecom and Sejong University was formed to investigate techno-economic aspects of the many alternatives. In the course of several discussions, both parties agreed on the urgency to form a techno-economic model which can precisely describe the underlying technical nature of the subscriber loop and its business aspects. This paper presents the modeling, solution processes and related topics.
Fas Ligand Expression in Hodgkin Lymphoma (2001)

Because previous investigations suggested involvement of the Fas ligand (FasL) in the selection process in the follicular dendritic cell (FDC)-associated cell cluster of the germinal center, we investigated the expression of FasL in Hodgkin lymphoma (HL) on protein and RNA level, while considering the Epstein-Barr virus status of the Hodgkin and Reed-Sternberg (HRS) cells. Tumor tissue from 47 patients with classic HL (32 nodular sclerosis [NS], 11 mixed cellularity [MC], and 4 lymphocyte-rich [LR]) was analyzed by immunohistochemistry for FasL, Fas, CD21, and CD23 and by Western blotting for FasL. FasL mRNA was detected by an exon 4-specific oligonucleotide and Epstein-Barr virus infection by in situ hybridization for Epstein-Barr virus early RNAs (EBER). Western blotting showed soluble and membrane-bound forms of FasL. Immunohistochemistry showed FasL expression in virtually all HRS of 94% of NS cases and 82% of MC cases. FasL expression did not correlate with the Epstein-Barr virus status of the HRS. Low FasL protein expression was found in some HRS of LR cases. FasL mRNA was detected in 39% of NS, 46% of MC, and 33% of LR cases. Seventy percent to 90% of the HRS cells expressed Fas. CD21 immunohistochemistry showed disrupted FDC networks in the tumor tissue with reduced and virtually absent expression of CD23 and FasL. These observations suggest that FasL expression in HRS cells and the absence of FasL in the FDC cluster represent a disturbed microenvironment that may be involved in the pathogenesis of HL.
Abstract IA10: Overcoming castration-resistant prostate cancer (2012)

Abstract Resistance to antiandrogen therapy is associated with increased expression of androgen receptor (AR) mRNA, AR gene amplification or AR mutation. Increased AR levels are necessary and sufficient to promote hormone-refractory growth in models and, paradoxically, alter the cellular response to classic AR antagonists such that they function as weak agonists. Therefore, second generation antiandrogens must overcome these resistance mechanisms. We searched for novel AR antagonists that might retain function in the context of increased AR expression through a cell-based screen. Using the high affinity AR agonist RU59063 as a starting point, we synthesized and screened over 200 compounds to construct a structure/activity profile that defines features of the scaffold essential for receptor binding and for maximal antagonism. We focused our further efforts on a novel compound MDV3100, which retains potent antiandrogen activity in cells expressing increased levels of AR, blocks AR function in mice and impairs the growth of LNCaP and LAPC-4 xenografts engineered to express high levels of AR, whereas bicalutamide had minimal activity. MDV3100 inhibits AR with 10-fold greater affinity than bicalutamide and functions through a novel mechanism of action that impairs nuclear translocation and DNA binding. MDV3100 produced sustained PSA responses (greater than 50% reduction) in about ∼55 percent of men with castrate-resistant prostate cancer in a 140 patient phase I-II clinical trial. In a phase III registration study of 1119 men with castration resistance, chemotherapy refractory prostate cancer, MDV3100 prolonged survival compared to best supportive care (18.4 months versus 13.6 months; hazard ratio 0.631). The heterogeneity of clinical response to anti-androgen therapy suggests additional molecular determinants of drug resistance. By conducting an integrated genomic analysis of 214 prostate cancers, we have defined a common set of molecular lesions and pathways that may define distinct subsets of prostate cancer as well as responder/non-responder populations to antiandrogen therapy. In preclinical models we found that tumors with PTEN loss are relatively insensitive to androgen ablation therapy due to reciprocal negative feedback between the AR and PI3K signaling pathways. PTEN-mediated resistance can be overcome with combined AR + PI3K pathway inhibition. Studies of these and other molecular abnormalities reveal unique features of prostate cancer progression with implications for downstream drug development. Citation Format: Charles L. Sawyers. Overcoming castration-resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA10.
Massive Gas Deposits (Clathrates) in the Gulf of Mexico (1991)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Common light chain chickens produce human antibodies of high affinity and broad epitope coverage for the engineering of bispecifics (2021)

Bispecific antibodies are an important and growing segment in antibody therapeutics, particularly in the immuno-oncology space. Manufacturing of a bispecific antibody with two different heavy chains is greatly simplified if the light chains can be the same for both arms of the antibody. Here, we introduce a strain of common light chain chickens, called OmniClic®, that produces antibody repertoires largely devoid of light chain diversity. The antibody repertoire in these chickens is composed of diverse human heavy chain variable regions capable of high-affinity antigen-specific binding and broad epitope diversity when paired with the germline human kappa light chain. OmniClic birds can be used in immunization campaigns for discovery of human heavy chains to different targets. Subsequent pairing of the heavy chain with a germline human kappa light chain serves to facilitate bispecific antibody production by increasing the efficiency of correct pairing. <b>Abbreviations</b>: AID: activation-induced cytidine deaminase; bsAb: bispecific antibody; CDR: complementarity-determining region; CL: light chain constant region; CmLC: common light chain; D: diversity region; ELISA: enzyme-linked immunosorbent assay; FACS: fluorescence-activated cell sorting; Fc: fragment crystallizable; FcRn: neonatal Fc receptor; FR: framework region; GEM: gel-encapsulated microenvironment; Ig: immunoglobulin; IMGT: the international ImMunoGeneTics information system®; J: joining region; KO: knockout; mAb: monoclonal antibody; NGS: next-generation sequencing; PBS: phosphate-buffered saline; PCR: polymerase chain reaction; PGC: primordial germ cell; PGRN: progranulin; TCR: T cell receptor; V: variable region; VK: kappa light chain variable region; VL: light chain variable region; VH: heavy chain variable region.
Supplementary Figure S2 from The Vigorous Immune Microenvironment of Microsatellite Instable Colon Cancer Is Balanced by Multiple Counter-Inhibitory Checkpoints (2023)

&lt;p&gt;Supplementary Figure S2. Absolute numbers of CD3 cells per gram of tumor and normal colon tissue collected from MSS and MSI human CRC patients.&lt;/p&gt;
Women in School Leadership in India and the United States (2023)

Women's representation in school leadership positions in India, and of Black women in the United States, remains unexplored. This chapter addresses the realities and complexities of women leaders in school education and develops a narrative based on current trends and anticipated challenges for the future. Existing research in educational leadership in schools, case studies, and interviews tend to focus on developing a coherent understanding of the topic. The representation of women in the school, from teachers to leaders, is an inverted pyramid. This chapter aims to provide an overview of how women school leaders from India and the USA manage crises, navigate politics, establish policies and budgets, and where the constraints lie at the school board and family level. Finally, using the grounded theory framework, the authors will present a pattern of women's leadership similarities, differences, and uniqueness in the context of both countries.
Integrated hybrid III&#x2013;V/Si laser and transmitter (2012)

This paper reports on recent advances on integrated hybrid InP/SOI lasers and transmitters. Based on a molecular wafer bonding technique, we develop hybrid III-V/Si lasers exhibiting new features: narrow III-V waveguide width of less than 3 μm, tapered III-V and silicon waveguides for mode transfer. These new features lead to good laser performances: a lasing threshold as low as 30mA and an output power of more than 10 mW at room temperature in continuous wave operation regime from a single facet. Continuous wave lasing up to 70°C is obtained. Moreover, hybrid III-V/Si lasers, integrating two intra-cavity ring resonators, are fabricated. Such lasers achieve a thermal tuning range of 45 nm, with a side mode suppression ratio higher than 40 dB. More recently we demonstrate a tunable transmitter, integrating a hybrid III-V/Si laser fabricated by wafer bonding and a silicon Mach-Zehnder modulator. The integrated transmitter exhibits 9 nm wavelength tunability by heating an intra-cavity ring resonator, high extinction ratio from 6 to 10 dB, and excellent bit-error-rate performance at 10 Gb/s.
Nothramicin, a New Anthracycline Antibiotic from Nocardia sp. MJ896-43F17. (1998)

A new antibiotic designated nothramicin was isolated from the culture broth of Nocardia sp. MJ896-43F17 which was closely related to Nocardia brasiliensis. It was isolated by the Diaion HP-20 column chromatography, butyl acetate extraction and purified by HPLC. It inhibited the growth of mycobacteria at the concentration of 1.56 approximately 25 microg/ml. Nothramicin was revealed to be a new member of anthracycline antibiotics by the various spectroscopies.
The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances inmyo‐Inositol Chemistry) (2015)

Cell signaling via inositol phosphates, in particular via the second messenger myo-inositol 1,4,5-trisphosphate, and phosphoinositides comprises a huge field of biology. Of the nine 1,2,3,4,5,6-cyclohexanehexol isomers, myo-inositol is pre-eminent, with "other" inositols (cis-, epi-, allo-, muco-, neo-, L-chiro-, D-chiro-, and scyllo-) and derivatives rarer or thought not to exist in nature. However, neo- and d-chiro-inositol hexakisphosphates were recently revealed in both terrestrial and aquatic ecosystems, thus highlighting the paucity of knowledge of the origins and potential biological functions of such stereoisomers, a prevalent group of environmental organic phosphates, and their parent inositols. Some "other" inositols are medically relevant, for example, scyllo-inositol (neurodegenerative diseases) and d-chiro-inositol (diabetes). It is timely to consider exploration of the roles and applications of the "other" isomers and their derivatives, likely by exploiting techniques now well developed for the myo series.
Abstract 3429: Beyond cereblon IMIDs - biophysics-based discovery of novel molecular glue chemotypes (2023)

Abstract Molecular glue degraders are compact, low molecular weight molecules that can efficiently induce specific and potent degradation of a target protein. This class of degraders function by inducing interactions between a target of interest and a ubiquitin-ligase, either by stabilization of weak pre-existing interactions, or by generation of entirely novel interactions. These molecules offer significant opportunity beyond heterobifunctional degraders such as PROTACs, not least in terms of improved molecular properties. However, beyond the IMID molecular glues, typified by thalidomide, pomalidomide and lenalidomide, novel molecular glue chemotypes remain scarce. To address this need, we have developed biophysics-based molecular glue screening platform, exploiting our internal, high quality fragment library and proximity-based screening platforms to rapidly identify promising new molecular glues for further optimization. A potential advantage of utilizing cell-free biophysical systems is the opportunity to select both the target and the desired ligase, opening up for development of degraders that capitalize upon differential expression of ligases in different tissues. As proof of concept, we have applied this platform to find new molecular glues to degrade CK1α. This Ser/Thr kinase has been found to be over-expressed in metastatic colorectal cancer, and this over-expression correlates with poor overall survival. The kinase has also been implicated as an oncogenic driver in tumors such as B-Cell lymphomas and non-Hodgkin lymphomas, suggesting a potential therapeutic application for novel CK1α molecular glues. Utilizing known IMID-derived molecular glues between CK1α and CRBN as benchmark controls, we identified several non-IMID derived chemotypes as tentative stabilizers of the CRBN/CK1α interaction. Further studies on these novel candidate degrader templates are now underway. Citation Format: Yujia Zhang, Jessica Bates, Benoit Gourdet, Louise Birch, Philip Addis, Roland Hjerpe, Allan M. Jordan. Beyond cereblon IMIDs - biophysics-based discovery of novel molecular glue chemotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3429.
Switched MEMS Antenna for Handheld Devices (2008)

Knowledge on insecticide resistance in target species is a basic requirement to guide insecticide use in malaria control programmes in local and global scales.
Evaluation of the 18F-labeled L-glutamate derivative 18F-FSPG (BAY 94-9392) in brain and head and neck cancer patients (2012)

274 Objectives (S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG alias BAY 94-9392) is a novel radiopharmaceutical developed by Bayer HealthCare for PET imaging (FDA eIND 108509). It is a glutamate analogue that shows promise for oncologic imaging. We present data on 5 brain and 5 head and neck cancer subjects. Methods Approximately 8 mCi (± 10%) of 18F-FSPG was given i.v. to 10 subjects (mean age: 59 ± 16 years) and 7 PET and 3 CT scans were acquired per patient over the next 2 hours. Vitals, EKGs and blood samples were obtained before and after imaging. Seven subjects also had a clinical 18F-FDG PET/CT scan within 1 month. SUV measurements (including unpaired T-tests) and visual comparison of the 18F-FSPG and 18F-FDG scans were done to assess relative efficacy and differences between these tracers. Results 18F-FSPG did not cause alterations in symptoms, vitals, EKGs, or lab values. There was similar distribution in all patients with primary clearance through the kidneys. Quantitatively, all malignant lesions were positive on 18F-FSPG but with a range of uptake (see table). Compared to the 18F-FDG scan, the 18F-FSPG scan showed lower absolute SUV values in the lesions, but higher tumor-to-background levels. This was confirmed visually in that 18F-FSPG showed higher uptake than 18F-FDG for brain lesions and similar uptake for head and neck lesions, but with less background brain uptake. However, these differences were not significantly different. Conclusions 18F-FSPG was well tolerated and showed increased uptake in both brain and head and neck cancer. Markedly lower background uptake than 18F-FDG, especially in the brain, appears to be beneficial. These results are promising and warrant further analysis in a larger cohort of subjects
Pharmacogenetics Meets Metabolomics: Discovery of Tryptophan as a New Endogenous OCT2 Substrate Related to Metformin Disposition (2012)

Genetic polymorphisms of the organic cation transporter 2 (OCT2), encoded by SLC22A2, have been investigated in association with metformin disposition. A functional decrease in transport function has been shown to be associated with the OCT2 variants. Using metabolomics, our study aims at a comprehensive monitoring of primary metabolite changes in order to understand biochemical alteration associated with OCT2 polymorphisms and discovery of potential endogenous metabolites related to the genetic variation of OCT2. Using GC-TOF MS based metabolite profiling, clear clustering of samples was observed in Partial Least Square Discriminant Analysis, showing that metabolic profiles were linked to the genetic variants of OCT2. Tryptophan and uridine presented the most significant alteration in SLC22A2-808TT homozygous and the SLC22A2-808G>T heterozygous variants relative to the reference. Particularly tryptophan showed gene-dose effects of transporter activity according to OCT2 genotypes and the greatest linear association with the pharmacokinetic parameters (Cl(renal), Cl(sec), Cl/F/kg, and Vd/F/kg) of metformin. An inhibition assay demonstrated the inhibitory effect of tryptophan on the uptake of 1-methyl-4-phenyl pyrinidium in a concentration dependent manner and subsequent uptake experiment revealed differential tryptophan-uptake rate in the oocytes expressing OCT2 reference and variant (808G>T). Our results collectively indicate tryptophan can serve as one of the endogenous substrate for the OCT2 as well as a biomarker candidate indicating the variability of the transport activity of OCT2.
Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome (2017)

Purpose Preliminary studies suggested that telotristat ethyl, a tryptophan hydroxylase inhibitor, reduces bowel movement (BM) frequency in patients with carcinoid syndrome. This placebo-controlled phase III study evaluated telotristat ethyl in this setting. Patients and Methods Patients (N = 135) experiencing four or more BMs per day despite stable-dose somatostatin analog therapy received (1:1:1) placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg three times per day orally during a 12-week double-blind treatment period. The primary end point was change from baseline in BM frequency. In an open-label extension, 115 patients subsequently received telotristat ethyl 500 mg. Results Estimated differences in BM frequency per day versus placebo averaged over 12 weeks were -0.81 for telotristat ethyl 250 mg ( P < .001) and ‒0.69 for telotristat ethyl 500 mg ( P < .001). At week 12, mean BM frequency reductions per day for placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg were -0.9, -1.7, and -2.1, respectively. Responses, predefined as a BM frequency reduction ≥ 30% from baseline for ≥ 50% of the double-blind treatment period, were observed in 20%, 44%, and 42% of patients given placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg, respectively. Both telotristat ethyl dosages significantly reduced mean urinary 5-hydroxyindole acetic acid versus placebo at week 12 ( P < .001). Mild nausea and asymptomatic increases in gamma-glutamyl transferase were observed in some patients receiving telotristat ethyl. Follow-up of patients during the open-label extension revealed no new safety signals and suggested sustained BM responses to treatment. Conclusion Among patients with carcinoid syndrome not adequately controlled by somatostatin analogs, treatment with telotristat ethyl was generally safe and well tolerated and resulted in significant reductions in BM frequency and urinary 5-hydroxyindole acetic acid.
Miniaturized Low-Voltage Power Converters With Fast Dynamic Response (2014)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2013.
Disaccharide‐Based Anionic Amphiphiles as Potent Inhibitors of Lipopolysaccharide‐Induced Inflammation (2018)

Despite significant advances made in the last decade in the understanding of molecular mechanisms of sepsis and in the development of clinically relevant therapies, sepsis remains the leading cause of mortality in intensive care units with increasing incidence worldwide. Toll-like receptor 4 (TLR4)-a transmembrane pattern-recognition receptor responsible for propagating the immediate immune response to Gram-negative bacterial infection-plays a central role in the pathogenesis of sepsis and chronic inflammation-related disorders. TLR4 is complexed with the lipopolysaccharide (LPS)-sensing protein myeloid differentiation-2 (MD-2) which represents a preferred target for establishing new anti-inflammatory treatment strategies. Herein we report the development, facile synthesis, and biological evaluation of novel disaccharide-based TLR4⋅MD-2 antagonists with potent anti-endotoxic activity at micromolar concentrations. A series of synthetic anionic glycolipids entailing amide-linked β-ketoacyl lipid residues was prepared in a straightforward manner by using a single orthogonally protected nonreducing diglucosamine scaffold. Suppression of the LPS-induced release of interleukin-6 and tumor necrosis factor was monitored and confirmed in human immune cells (MNC and THP1) and mouse macrophages. Structure-activity relationship studies and molecular dynamics simulations revealed the structural basis for the high-affinity interaction between anionic glycolipids and MD-2, and highlighted two compounds as leads for the development of potential anti-inflammatory therapeutics.
3D integration technologies for MEMS (2016)

This paper describes selected technologies for the 3D integration of MEMS devices. This comprises a Via Last approach for the formation of MEMS TSVs and a Cu based thermo-compression bonding method for the realization of small 3D-WLP devices. Moreover, the Aerosol Jet technique is discussed as method for the final assembly by means of printing conducting lines over 3D topography.
The Clinical Syndrome and the Biochemical Definition (2008)

This chapter contains sections titled: Definition of the Diabetic State The Clinical Syndrome The Biochemical Definition Significance of Blood Glucose in a Population
Tiapride in the Prevention of Relapse in Recently Detoxified Alcoholics (1994)

Tiapride merits serious consideration in the longer-term treatment of alcoholic patients.