gebhart/patrepeval huggingface dataset:
Abstract 3657: Upregulation of PD-1 and Tim-3 expression on tumor antigen-specific CD4+ T cells is associated with reversible T cell dysfunction in patients with advanced melanoma (2011)

Abstract The paradoxical coexistence of spontaneous tumor antigen-specific immune T cell responses with progressive disease in cancer patients furthers the need to dissect the molecular pathways involved in tumor-induced T cell dysfunction and exhaustion. We have previously observed in patients with advanced melanoma that the cancer-germline antigen NY-ESO-1 stimulates spontaneous NY-ESO-1-specific CD8+ T cells that upregulate PD-1 expression and that a fraction of PD-1+ NY-ESO-1-specific CD8+ T cells upregulates Tim-3 expression. We have found that Tim-3+PD-1+ NY-ESO-1-specific CD8+ T cells represent highly dysfunctional T cells in terms of cytokine production and proliferation. Importantly, Tim-3/Tim-3L blockade together with PD-1/PD-L1 blockade enhanced cytokine production and proliferation of NY-ESO-1-specific CD8+ T cells upon prolonged antigen stimulation. Whether the upregulation of PD-1 and Tim-3 is associated with tumor antigen-specific CD4+ T cell dysfunction/exhaustion in patients with advanced melanoma remains unknown. Here, our findings show that in contrast to EBV-specific, CMV-specific and total CD4+ T cells, PD-1 and Tim-3 expression is upregulated by NY-ESO-1-specific CD4+ T cells isolated from peripheral blood lymphocytes of patients with advanced melanoma. Interestingly, PD-1/PD-L1 blockade synergized with Tim-3/Tim-3L pathway blockade to restore the numbers of cytokine-producing and proliferating NY-ESO-1-specific CD4+ T cells. Collectively, our findings support the use of Tim-3/Tim-3L blockade in association with PD-1/PD-L1 blockade to reverse tumor-induced CD8+ and CD4+ T cell exhaustion/dysfunction in patients with advanced melanoma. Our findings have significant implication in terms of novel immunotherapeutic strategies aiming at promoting T cell-mediated tumor regression in patients with advanced cancers. This work was supported by NIH/NCI Grants CA90360 and CA112198 (HMZ) and Cancer Research Institute grant (HMZ). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3657. doi:10.1158/1538-7445.AM2011-3657
Years Continuous Anti-MAP Therapy for Crohnʼs -Observation of Side Effects (2008)

Purpose: The most effective accepted treatment for the management of Crohn's disease is courses of anti-TNF biologicals, however severe adverse drug reactions including death have incited the search for more benign therapies which can be taken long-term without compromising efficacy. Selby et al reported high remission rates using of a combination anti -mycobacterial (anti-MAP) treatment comprising rifabutin, clarithromycin, and clofazimine for the management of Crohn's disease with minimal side effects over a 2 year period. Here we report side-effects observed in Crohn's patients on 5 years continuous anti-MAP therapy. Methods: A retrospective review of 11 pts (7 M:4 F; 26–55 yrs) at the Centre for Digestive Diseases treated with a combination of rifabutin (≤600 mg/d), clofazimine (≤100 mg/d), clarithromycin (≤1 g/d) and in several with added ethambutol (≤800 mg/d) commenced as a ‘ramp-up’ dosing schedule then continuing for at least 5 years at a stable dose was conducted to document the long-term safety of anti-MAP therapy. Symptoms reported prior to therapy were excluded from analysis. Results: All pts developed a skin tan and orange colored urine known to be the result of rifabutin and clofazimine use, Overall, the most common side effects reported over the 5 year period were mild and included intermittent nausea (7/11 pts, 63%), arthralgia (4/11 pts, 36%), fevers (4/11 pts, 36%) and lethargy (3/11 pts, 27%) with the majority of these side effects reported in the first year of therapy and possibly related to active Crohn's disease. One patient developed a transient clarithromycin-related hepatitis and a second patient reported an incident of palpitation in the first 16 weeks of therapy. Both events resolved within a month and none terminated the therapy. Most pts had violet discoloration in the terminal ileum by the third year of therapy, a result of prolonged clofazimine use. Conclusion: 1. The side effects of prolonged anti-MAP therapy are benign and transient in nature. 2. In the early treatment stages all patients were on concomitant medications including immunosuppressants and 5ASA's which may have contributed to reported side effects. 3. Consistent with the Crohn's disease (Selby et al) trial results on tolerability, anti-MAP therapy provides a safe option for long-term management of Crohn's disease.
Kraft lignin depolymerisation by based catalysed degradation (BCD) - The effect of process parameters on conversion degree and structural features of BCD fractions (2014)

The objective of the study is the generation of oxy-aromatic compounds (monomer, oligomer) from Eucalyptus- Kraft-lignin via multi-stage processes. These processes (1st base catalysed degradation &amp; 2nd separation of the organic phase from reactor water) have to be feasible in bio refineries &amp; in new Pulp-mill bio refineries as a new technology module. The Eucalyptus-Kraft-lignin (Suzano Pulp &amp; Paper) was used for catalyzed conversion into oxy aromatics. Subsequently, the effect of process parameters: catalyst &amp; catalyst conc., mineral content, p: 250bars, 15min), T: 350°C)) was investigated. Liquid-liquid extraction of reactor water (pH=3) was&#13;\nperformed with MIBK for isolation of the monomer rich phase. The BCD fractions (oils) &amp; (tars) were characterized regarding their yields via carbon balance, &amp; their composition. A characterization of the monomer composition was done (GC-MS/FID &amp; EA (CHONS), 31P-NMR, 2D-NMR (HSQC), TGA). Types of monomers were summarized into groups (guaiacols (G), syringols (S), catechols (C )). Oligomer degradation products in the oil were characterized by Infusion MS Ion Trap &amp; the composition of the oligomer phase by PyGC-MS, SEC, EA, 31P-NMR, 2D-NMR (HSQC) &amp; TGA. On the one hand, depending on the botanical source &amp; the lignin recovery process (Organosolv, Kraft etc.), useful lignins differ in their structure (inter unit linkages) &amp; monomer composition, mineral &amp; sulphur content, MW, MN. These substrate factors effecting the degradation process&#13;\nduring the catalysed cleavage of aryl-aryl-ether &amp; aryl-methyl-ether bonds. On the other hand, process factors e. g.: p, catalyst conc. &amp; type of alkaline elements have a main effect on the cleavage processes, on the yield &amp; composition of the monomer rich phase (oil), on the molecular characteristic (Mw, Mn, OH-number (aliphatic &amp; phenolic -OH)) of the oligomer rich phase (tar) &amp; on the carbon balance. To get an overview about the main&#13;\n&amp; side effects in such complex situation, the study on the Kraft-lignin was done using DoE (Box-Behnken). A detailed evaluation regarding the main &amp; side effects of process factors on the yield of oil &amp; tar, on the&#13;\nconcentration of (G), (S) &amp; (C ) in the oil phase, on the carbon balance, on MW &amp; MN of the tars as well on functional groups (OH-number, differentiated into aliphatic &amp; phenolic), presence of inter unit linkages &amp;&#13;\nmethoxy groups will be given.
Reactions between Aromatic Hydrocarbons and Heterocycles: Covalent and Proton-Bound Dimer Cations of Benzene/Pyridine (2009)

Despite the fact that benzene (Bz) and pyridine (Py) are probably the most common and extensively studied organic molecules, the observation of a covalent adduct in the ionized benzene/pyridine system has never been reported. This Article reports the first experimental and theoretical evidence of a covalent (Bz x Py)(*+) adduct that results from the reaction of Bz(*+) with pyridine or Py(*+) with benzene. These reactions are studied using mass-selected ion mobility, chemical reactivity, collisional dissociation, and ab initio calculations. The (Bz x Py)(*+) adduct does not exchange ligands with Bz to form Bz(2)(*+) or with Py to form (Py)(2)H(+) despite the strong bonds in these homodimers. The thermochemistry then suggests that the (Bz x Py)(*+) heterodimer is bonded covalently with a bonding energy of >33 kcal/mol. Correspondingly, ab initio calculations identify covalently bonded propeller-shaped isomers of (Bz x Py)(*+) with bonding energies of 31-38 kcal/mol, containing a C-N bond. The mobility of the (Bz x Py)(*+) adduct in helium is consistent with these covalent dimers. As to noncovalent adducts, the computations identify novel distonic hydrogen-bonded complexes (C(5)H(5)NH(+) x C(6)H(5)(*)) where the charge resides on one component (PyH(+)), while the radical site resides on the other component (C(6)H(5)(*)). Collisional dissociation suggests that the covalent and distonic dimers may interconvert at high energies. The most stable distonic (C(5)H(5)NH(+) x C(6)H(5)(*)) complex contains a hydrogen bond to the phenyl radical carbon site with a calculated dissociation energy of 16.6 kcal/mol. This bond is somewhat stronger than the NH(+) x pi hydrogen bonds of PyH(+) to the pi system of the phenyl radical and of the benzene molecule. For this NH(+) x pi bond in the PyH(+) x Bz dimer, the measured binding energy is 13.4 kcal/mol, and ab initio calculations identify two T-shaped isomers with the NH(+) pointing to the center of the benzene ring or to the negatively charged C atoms of the ring. In contrast, the more stable proton-bound PyH(+) x Py dimer contains a linear NH(+)...N hydrogen bond. The formation of the (benzene/pyridine)(*+) adduct may represent a general class of addition reactions that can form complex heterocyclic species in ionizing environments.
Data from Intrinsic Breast Tumor Subtypes, Race, and Long-Term Survival in the Carolina Breast Cancer Study (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Previous research identified differences in breast cancer–specific mortality across 4 intrinsic tumor subtypes: luminal A, luminal B, basal-like, and human epidermal growth factor receptor 2 positive/estrogen receptor negative (HER2&lt;sup&gt;+&lt;/sup&gt;/ER&lt;sup&gt;−&lt;/sup&gt;).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; We used immunohistochemical markers to subtype 1,149 invasive breast cancer patients (518 African American, 631 white) in the Carolina Breast Cancer Study, a population-based study of women diagnosed with breast cancer. Vital status was determined through 2006 using the National Death Index, with median follow-up of 9 years.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Cancer subtypes luminal A, luminal B, basal-like, and HER2&lt;sup&gt;+&lt;/sup&gt;/ER&lt;sup&gt;−&lt;/sup&gt; were distributed as 64%, 11%, 11%, and 5% for whites, and 48%, 8%, 22%, and 7% for African Americans, respectively. Breast cancer mortality was higher for participants with HER2&lt;sup&gt;+&lt;/sup&gt;/ER&lt;sup&gt;−&lt;/sup&gt; and basal-like breast cancer compared with luminal A and B. African Americans had higher breast cancer–specific mortality than whites, but the effect of race was statistically significant only among women with luminal A breast cancer. However, when compared with the luminal A subtype within racial categories, mortality for participants with basal-like breast cancer was higher among whites (HR = 2.0, 95% CI: 1.2–3.4) than African Americans (HR = 1.5, 95% CI: 1.0–2.4), with the strongest effect seen in postmenopausal white women (HR = 3.9, 95% CI: 1.5–10.0).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our results confirm the association of basal-like breast cancer with poor prognosis and suggest that basal-like breast cancer is not an inherently more aggressive disease in African American women compared with whites. Additional analyses are needed in populations with known treatment profiles to understand the role of tumor subtypes and race in breast cancer mortality, and in particular our finding that among women with luminal A breast cancer, African Americans have higher mortality than whites. &lt;i&gt;Clin Cancer Res; 16(24); 6100–10. ©2010 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Modeling of tRNA‐assisted mechanism of Arg activation based on a structure of Arg‐tRNA synthetase, tRNA, and an ATP analog (ANP) (2009)

The ATP-pyrophosphate exchange reaction catalyzed by Arg-tRNA, Gln-tRNA and Glu-tRNA synthetases requires the assistance of the cognate tRNA. tRNA also assists Arg-tRNA synthetase in catalyzing the pyrophosphorolysis of synthetic Arg-AMP at low pH. The mechanism by which the 3'-end A76, and in particular its hydroxyl group, of the cognate tRNA is involved with the exchange reaction catalyzed by those enzymes has yet to be established. We determined a crystal structure of a complex of Arg-tRNA synthetase from Pyrococcus horikoshii, tRNA(Arg)(CCU) and an ATP analog with Rfactor = 0.213 (Rfree = 0.253) at 2.0 A resolution. On the basis of newly obtained structural information about the position of ATP bound on the enzyme, we constructed a structural model for a mechanism in which the formation of a hydrogen bond between the 2'-OH group of A76 of tRNA and the carboxyl group of Arg induces both formation of Arg-AMP (Arg + ATP --> Arg-AMP + pyrophosphate) and pyrophosphorolysis of Arg-AMP (Arg-AMP + pyrophosphate --> Arg + ATP) at low pH. Furthermore, we obtained a structural model of the molecular mechanism for the Arg-tRNA synthetase-catalyzed deacylation of Arg-tRNA (Arg-tRNA + AMP --> Arg-AMP + tRNA at high pH), in which the deacylation of aminoacyl-tRNA bound on Arg-tRNA synthetase and Glu-tRNA synthetase is catalyzed by a quite similar mechanism, whereby the proton-donating group (-NH-C+(NH2)2 or -COOH) of Arg and Glu assists the aminoacyl transfer from the 2'-OH group of tRNA to the phosphate group of AMP at high pH.
Continuous Reduced-Order Dynamic Model Based on Energy Balancing for Inductive Power Transfer Systems (2022)

Resonant circuits are commonly used in inductive power transfer (IPT) systems for the charging of electric vehicles because of the high power efficiency. Transient behaviors of the resonant circuits, which play a significant role in the design and analysis of IPT systems, are cumbersome to model analytically because of the high-order. This article develops a reduced-order continuous dynamic model based on the energy interactions among the resonant tanks. By applying the proposed energy balancing method (EBM), the order of the dynamic model is reduced to half of the number of the passive components in the resonant circuits. To show the accuracy of the EBM, the dynamics of a series–series (SS) compensated IPT system are modeled using Laplace phasor transformation (LPT) and EBM separately and the results are compared. The order of the EBM is found to be one-fourth of that of the LPT method. The sensitivity of the EBM to the switching frequency is discussed when the zero voltage switching turn- <sc xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">on</small> operation is attained. Besides, to prove the advantage of reducing the order of the dynamic model, model predictive controls (MPCs) based on EBM and LPT are developed. The transient performances of the MPC controllers are simulated and the control inputs are applied to an experimental setup. Finally, experiments are conducted to verify the accuracy of the proposed EBM under zero and nonzero conditions and the effectiveness of the developed MPC controller.
A Portable System With 0.1-ppm RMSE Resolution for 1–10 MHz Resonant MEMS Frequency Measurement (2020)

This article presents a portable and programmable frequency measurement system (PrO-FMS) with 0.1-ppm RMSE resolution over a measurement time interval of 33.2 s for bulk-acoustic resonator applications. PrO-FMS has a feature of choosing a frequency estimation method and accordingly the sampling frequency, which is programmable. Five frequency estimation methods, Candan, Djukanovic, Prony, M-Pisarenko, and zero crossing interpolation methods, are reviewed for high-resolution frequency measurement. PrO-FMS can also be reconfigured to select a particular resonance mode over a range of 1–10 MHz. Measurement results are provided for two different commercial quartz crystals and a microfabricated in-plane bulk acoustic resonator in two different modes of resonance. The results of these estimation methods are compared with a standard commercial tabletop frequency counter. Measurement results show that PrO-FMS can achieve a resolution of 0.1 ppm RMSE. For the same gate time, PrO-FMS provides better resolution than standard tabletop frequency counter. This article also provides a study on the behavior of the five different frequency estimation methods for short- and long-term measurements for quartz crystals and bulk acoustic resonator in two different modes.
Sequential sampling strategy for the modeling of parameterized microwave and RF components (2011)

Accurate modeling of parameterized microwave and RF components often requires a large number of full-wave electromagnetic simulations. In order to reduce the overall simulation cost, a sequential sampling algorithm is proposed that selects a sparse set of data samples which characterize the overall response of the system. The resulting data samples can be fed into existing modeling techniques. The effectiveness of the approach is illustrated by a parameterized H-shaped microwave antenna.
Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD (2017)

TRC101 safely and significantly increased the level of serum bicarbonate in patients with metabolic acidosis and CKD.
Transport Characteristics of Glycerol and Propylene Glycol in an Engineered Dermal Replacement (2002)

The ability to cryopreserve engineered tissues is important for the clinical application of therapies based on living cells. Cryopreservation facilitates the manufacture, transport and safety of cell-based therapies. The cryopreservation of cells and tissues had typically required the use of specialized solutions containing cryoprotective agents (CPAs). The addition of a CPA to the freezing solution may result in damage if it is not done properly. Tissues and intact organs can exhibit reduced cellular viability when exposed to sufficiently large step changes in external osmolarity resulting from introduction or removal of a cryopreservation solution (Pegg, 1972). Not only are large step changes in osmolarity potentially damaging, but also long-term exposure to even low concentrations of CPAs at room temperature can be lethal (Fahy et al., 1990). Exposure of cells to CPAs (in particular dimethyl sulfoxide, Me2SO) has been associated with a loss in viability with time of exposure. Subsequent studies have quantified specific cellular changes resulting from exposure to CPA, such as cytoskeletal reorganization, cross-linking of nuclear proteins, and alterations in membrane permeability (cf. ref (Fahy et al., 1990) for review) which may account for the loss in viability.
Reduced p38 mitogen-activated protein kinase in donor grafts accelerates acute intestinal graft-versus-host disease in mice (2005)

The gastrointestinal tract is a major target of graft-versus-host disease (GVHD), which constitutes a life-threatening complication of bone marrow transplantation. GVHD is mainly caused by the activation of donor-derived lymphocytes, in which cytokine cascades play essential roles. Since p38 MAPK (p38) has been identified as a regulator of cytokine reactions and proposed as a molecular target for anti-inflammatory therapy, we investigated the contribution of p38 to the severity of murine intestinal GVHD. Unexpectedly, p38alpha(+/-) donor graft induced more acute GVHD-related mortality and more severe gut injury. The survival of p38alpha(+/-) donor-derived intestinal intraepithelial lymphocytes (IEL) was prolonged in vitro and in vivo, and TNF-alpha expression in the p38alpha(+/-) donor-derived IEL was also increased compared with wild-type cells. In contrast, the p38alpha(+/-) grafted mice resulted in decreased expansion of donor lymphocytes in mesenteric lymph nodes, and the up-regulation of IL-12p40 and IL-18 was diminished. These findings suggest that p38 has dichotomous effects for inflammatory response in vivo; not only regulates inflammatory cytokine expression and lymphocyte expansion, but also has distinct regulatory functions for IEL in intestinal GVHD. In conclusion, the inhibition of p38 may not be a suitable anti-inflammatory strategy for GVHD due to the associated intestinal injury.
Design of a substrate-tailored peptiligase variant for the efficient synthesis of thymosin-α1 (2018)

The synthesis of thymosin-α<sub>1</sub>, an acetylated 28 amino acid long therapeutic peptide, via conventional chemical methods is exceptionally challenging. The enzymatic coupling of unprotected peptide segments in water offers great potential for a more efficient synthesis of peptides that are difficult to synthesize. Based on the design of a highly engineered peptide ligase, we developed a fully convergent chemo-enzymatic peptide synthesis (CEPS) process for the production of thymosin-α<sub>1</sub>via a 14-mer + 14-mer segment condensation strategy. Using structure-inspired enzyme engineering, the thiol-subtilisin variant peptiligase was tailored to recognize the respective 14-mer thymosin-α<sub>1</sub> segments in order to create a clearly improved biocatalyst, termed thymoligase. Thymoligase catalyzes peptide bond formation between both segments with a very high efficiency (>94% yield) and is expected to be well applicable to many other ligations in which residues with similar characteristics (e.g. Arg and Glu) are present in the respective positions P1 and P1'. The crystal structure of thymoligase was determined and shown to be in good agreement with the model used for the engineering studies. The combination of the solid phase peptide synthesis (SPPS) of the 14-mer segments and their thymoligase-catalyzed ligation on a gram scale resulted in a significantly increased, two-fold higher overall yield (55%) of thymosin-α<sub>1</sub> compared to those typical of existing industrial processes.
Supplementary Fig. S3 from Emergence of Enzalutamide Resistance in Prostate Cancer is Associated with BCL-2 and IKKB Dependencies (2023)

&lt;p&gt;Characterization of ENZ-resistant cell lines&lt;/p&gt;
Oral immunotherapy for the treatment of food allergy (2012)

Abstract In the absence of a curative treatment, patients with food allergy continue to live with the risk of accidental exposure to food allergens and the possibility of severe allergic reactions. Over the last 5 years, research in the area of immunotherapy for food allergy has intensified. Although this novel therapeutic option has not reached routine clinical practice, results from immunotherapy studies have yielded encouraging results. In this review article, we will discuss the immunological mechanisms involved in tolerance induction and the clinical efficacy and safety of oral and sublingual immunotherapy for food allergy.