gebhart/patrepeval huggingface dataset:
Acute myocardial infarct imaging with indium-111-labeled monoclonal antimyosin Fab. (1987)

Indium-111 monoclonal antimyosin Fab scintigraphy was used to detect myocardial necrosis in 52 of 54 patients (96.3%) with acute myocardial infarction. Infarcts were visualized when coronary arteries were persistently occluded (n = 10), became patent after thrombolysis (n = 33), or became patent after spontaneous reperfusion (n = 7). Posteroinferolateral visualizations were obtained in two patients with clinical and enzymatic evidence of infarction but normal electrocardiograms. Of the two patients in whom no infarcts were visualized, one had an anterior myocardial infarct. This patient underwent successful thrombolytic therapy, with attendant minimization of creatine kinase release. The other patient had a small, nonreperfused inferior myocardial infarct. Five patients with a history of remote infarction and acute necrosis showed antimyosin uptake only in regions concordant with the acute episodes of infarction, and radiolabeled antimyosin Fab localized in neither old infarcts nor normal, noninfarcted myocardium. Antimyosin Fab scintigraphy, thus, appears to be a highly specific means of delineating necrotic myocardium, at least in this limited and selected group of patients.
Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma (2012)

Natural killer T (iNKT) cells can help mediate immune surveillance against tumors in mice. Prior studies targeting human iNKT cells were limited to therapy of advanced cancer and led to only modest activation of innate immunity. Clinical myeloma is preceded by an asymptomatic precursor phase. Lenalidomide was shown to mediate antigen-specific costimulation of human iNKT cells. We treated 6 patients with asymptomatic myeloma with 3 cycles of combination of α-galactosylceramide-loaded monocyte-derived dendritic cells and low-dose lenalidomide. Therapy was well tolerated and led to reduction in tumor-associated monoclonal immunoglobulin in 3 of 4 patients with measurable disease. Combination therapy led to activation-induced decline in measurable iNKT cells and activation of NK cells with an increase in NKG2D and CD56 expression. Treatment also led to activation of monocytes with an increase in CD16 expression. Each cycle of therapy was associated with induction of eosinophilia as well as an increase in serum soluble IL2 receptor. Clinical responses correlated with pre-existing or treatment-induced antitumor T-cell immunity. These data demonstrate synergistic activation of several innate immune cells by this combination and the capacity to mediate tumor regression. Combination therapies targeting iNKT cells may be of benefit toward prevention of cancer in humans.
Durable Remissions with Ivosidenib in IDH1 -Mutated Relapsed or Refractory AML (2018)

In patients with advanced IDH1-mutated relapsed or refractory AML, ivosidenib at a dose of 500 mg daily was associated with a low frequency of grade 3 or higher treatment-related adverse events and with transfusion independence, durable remissions, and molecular remissions in some patients with complete remission. (Funded by Agios Pharmaceuticals; ClinicalTrials.gov number, NCT02074839 .).
Unified Extraction of Health Condition Descriptions (2012)

This paper discusses a method for identifying diabetes symptoms and conditions in free text electronic health records in Bulgarian. The main challenge is to automatically recognise phrases and paraphrases for which no canonical forms exist in any dictionary. The focus is on extracting blood sugar level and body weight change which are some of the dominant factors when diagnosing diabetes. A combined machine-learning and rule-based approach is applied. The experiment is performed on 2031 sentences of diabetes case history. The F-measure varies between 60 and 96% in the separate processing phases.
Measurement and Compartmental Modeling of the Effect of CYP3A5 Gene Variation on Systemic and Intrarenal Tacrolimus Disposition (2012)

We evaluated the hypothesis that cytochrome P450 3A5 (CYP3A5) expression can affect intrarenal tacrolimus accumulation. Tacrolimus was administered orally to 24 healthy volunteers who were selected on the basis of their CYP3A5 genotype. As compared with CYP3A5 nonexpressors, expressors had a 1.6-fold higher oral tacrolimus clearance and 2.0- to 2.7-fold higher metabolite/parent area under the curve (AUC) ratios for 31-desmethyl tacrolimus (31-DMT), 12-hydroxy tacrolimus, and 13-desmethyl tacrolimus (13-DMT). In addition, the apparent urinary tacrolimus clearance was 36% lower in CYP3A5 expressors as compared with nonexpressors. To explore the mechanism behind this observation, we developed a semiphysiological model of renal tacrolimus disposition and predicted that tacrolimus exposure in the renal epithelium of CYP3A5 expressors is 53% of that for CYP3A5 nonexpressors, when normalized to blood AUC. These data suggest that, at steady state, intrarenal accumulation of tacrolimus and its primary metabolites will depend on the CYP3A5 genotype of the liver and kidneys. This may contribute to interpatient differences in the risk of tacrolimus-induced nephrotoxicity.
NO is more important than PGI2 in maintaining low vascular tone in feto-placental vessels (1993)

The endothelial cells of the human umbilical artery and vein release the vasodilators prostacyclin [prostaglandin (PG) I2] and nitric oxide (NO). However, the role of these two substances in the maintenance of vasodilator tone in the feto-placental circulation is not known. Studies were therefore undertaken to compare the relative release of PGI2 and NO from perfused segments (10 cm) of endothelium-intact human umbilical artery (HUA) and vein (HUV) utilizing the cascade bioassay. The endothelium-denuded bovine pulmonary arterial strip was used as the detector tissue because this tissue relaxes equally to various concentrations of PGI2 and S-nitroso-N-acetylpenicillimine (SNAP), which acts by releasing NO. The basal release of NO from the HUA was approximately five times greater than that of PGI2. After stimulation with A-23187, the release of NO from HUV was five to six times greater, and from the HUA, the release was three times greater compared with the PGI2. SNAP was significantly more potent compared with PGI2 in relaxing endothelium-denuded rings of human umbilical and chorionic plate arteries in vitro. These studies suggest that NO is more important than PGI2 for maintenance of low vascular tone in feto-placental vessels, because there is a greater release of NO from the HUA and HUV, and NO is more potent in relaxing endothelium-denuded feto-placental vessels in vitro relative to PGI2.
(+)-14β-Hydroxylabda-8(17),12-dieno-16,15-lactone [(+)-Isocoronarin-D]: a New Diterpene From Hedychium coronarium (Zingiberaceae) (1991)

An investigation of the rhizome of Hedychium coronarium ( Zingiberaceae ), collected in the Kathmandu Valley, Nepal, has yielded coronarin -D, coronarin -D ethyl ether, coronarin -E, and a new diterpene identified as (+)-14ß-hydroxylabda-8(17),12-dieno-16,15-lactone, assigned the trivial name of isocoronarin-D. The structure of isocoronarin-D (3) was determined by spectroscopic and X-ray crystallographic studies.
Networks on silicon: blessing or nightmare? (2003)

Continuing VLSI technology scaling raises several deep submicron (DSM) problems like relatively slow interconnect, power dissipation and distribution, and signal integrity. Those problems are encountered particularly on long wires for global interconnect. As clock frequencies increase, scaled wires become relatively slower and on-chip communication will be the limiting performance factor of future chips. We explain why efficiently sharing of the wires for long distance communication is the solution to this problem. We introduce networks on silicon (NoS), that route packets over shared (semi)-global wires. NoS performance is expected to be high, but comes at a cost. Balancing the performance and cost of a NoS is a major challenge, and we believe busses still have a role to play.
A Nonlinear Observation Model for Removing Noise from Corrupted Speech Log Mel-Spectral Energies (2002)

In this paper we present a new statistical model, which describes the corruption to speech recognition Mel-frequency spectral features caused by additive noise. This model explicitly represents the effect of unknown phase together with the unobserved clean speech and noise as three hidden variables. We use this model to produce noise robust features for automatic speech recognition. The model is constructed in the log Mel-frequency feature domain. In addition to being linearly related to MFCC recognition parameters, we gain the advantage of low dimensionality and independence of the corruption across feature dimensions. We illustrate the surprising result that, even when the true noise Mel-frequency spectral feature is known, the traditional spectral subtraction formula is flawed. We show the new model can be used to derive a spectral subtraction formula which produces superior error rate results, and is less sensitive to tuning parameters. Finally, we present results demonstrating that the new model is more general than spectral subtraction, and can take advantage of a prior noise estimate to produce robust features, rather than relying on point estimates of noise.
Comparative studies of multiwalled carbon nanotube sheets before and after shrinking (2007)

The multiwalled carbon nanotube (MWCNT) yarns converted from superaligned MWCNT arrays are self-assembled sheetlike structure in which MWCNTs are aligned along the stretching direction and will shrink into a tight fiber after passing through volatile solvents. In this paper, we report the comparative studies on the physical properties of the MWCNT sheets and shrunk yarns. The major differences between them lie in the surface area and intertube interactions, which result in different mechanical and electrical properties. Their surface areas were measured according to the energy conservation law and Stefan-Boltzmann law, manifesting that the surface area of the sheet is around 30 times larger than that of the shrunk yarn. With the measured surface area, the thermionic emission from them was further studied. There is no difference in their work function, emission efficiency, as well as Richardson's emission constant which is approximately equal to the theoretical value of $120.4\phantom{\rule{0.3em}{0ex}}\mathrm{A}\phantom{\rule{0.2em}{0ex}}{\mathrm{cm}}^{\ensuremath{-}2}\phantom{\rule{0.2em}{0ex}}{\mathrm{K}}^{\ensuremath{-}2}$. The electronic transport properties were studied in low temperature ranging from $3\phantom{\rule{0.3em}{0ex}}\text{to}\phantom{\rule{0.3em}{0ex}}390\phantom{\rule{0.3em}{0ex}}\mathrm{K}$ and high temperature around $1100--2300\phantom{\rule{0.3em}{0ex}}\mathrm{K}$. In all the temperature range, there exists a resistance reduction from the MWCNT sheet to the shrunk yarn which was attributed to the increase of intertube crosstalk points between neighboring MWCNTs. It is also found that $R$ decreases with increasing temperature until $1800\phantom{\rule{0.3em}{0ex}}\mathrm{K}$ above which $R$ increases due to the electron-phonon scattering at high $T$.
Determining glioma response to radiation therapy using recombinant peptides (2008)

Presently, cancer response is measured by imaging assessment of tumor volumes or by repeated biopsy to analyze pharmacodynamics. These methods of monitoring cancer response are inefficient because volume changes typically require therapy for prolonged time intervals and neoplasms within the brain are less amenable to sequential biopsies. Peptide ligands selected from phage-displayed peptide libraries can rapidly differentiate responding from resistant gliomas. These peptides, in turn, can be labeled with internal emitters to provide a means of noninvasive assessment of glioma susceptibility to radiotherapy within 24 h of therapy. This is platform technology and could allow for ineffective therapy to be modified or switched so that patients are not subjected to a delayed reassessment (2 months) of response to therapy.
Cannabinoids for Medical Use (2015)

There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.
Intramolecular Fluorescence-Quenched Substrate Libraries (2003)

As described in Chapter 6 , the most versatile fluorescence-quenched pair with respect to both ease of synthesis and efficiency of energy transfer is the Abz/Tyr (3-NO2) pair (2-aminobenzoyl/3-nitrotyrosme). The synthesis of the surtably protected building blocks that can be used in a flexrble way in multrple-column peptide synthesis (MCPS) mvolves the preparation of Fmoc-Tyr(NO2-OH (fluorene-9-ylmethyloxycarbonyl-Tyr(NO2)-OH) and Fmoc-Lys(Boc-Abz)-OPfp (Fmoc-Lys(tert-butyloxycarbonyl-Abz)-O-pentafluorophenyl ester) as described (in Subheadings 2.2.1.–2.2.4.). The Fmoc-Tyr(NO2-OH can be activated in situ since protection of the acidtc phenol is drffrcult and any acylation of the nitrotyrosme side-chain during syntheses 1s completely reverted in the subsequent treatment with prperrdme. The MCPS is particularly useful for portion mixing since all that IS needed is to add a mixing chamber above the open columns of the synthesizer. A detailed procedure for the synthesis of a fluorescence-quenched substrate library is described below and demonstrated for the serme protease subtiltsm Carlsberg substrate with the structure H-Y(NO2)X1X2PX3X4X5K(Abz)-(PEGA) where X can be any of the 20 naturally encoded amino acids. Prolme has been inserted to direct the cleavage since prolme is only accepted in S2; however, it is not a requrrement to dnect the cleavage and subsequent substrate libraries have been randomized in all positions
The clinical significance of MAGEA3 expression in pancreatic cancer (2005)

The MAGEA gene family that encodes cancer testis antigens is differentially expressed in many cancers. Though MAGEA3 expression has been detected in gastrointestinal malignancies, its role in pancreatic ductal adenocarcinoma (PDAC) has not been well established. We assessed 57 patients who underwent intent-to-cure surgery for PDAC. Total RNA from paraffin-embedded pancreatic tumors was extracted and assessed for MAGEA3 gene expression by an optimized probe-based quantitative real-time RT-PCR (qRT) assay. MAGEA3 gene expression was detected by qRT in 25 (44%) patients. For the entire cohort, detection of MAGEA3 expression was associated with significantly decreased overall survival (median, 16 vs 33 months; log-rank, p = 0.032). When clinicopathologic factors, including age, gender, stage, tumor extent, lymph node metastasis, tumor grade, perineural invasion and lymphovascular invasion were assessed by univariate analysis, MAGEA3 gene expression and tumor grade were significant prognostic factors for poor survival (HR 2.1, 95% CI: 1.0-4.4, p = 0.041; and HR 3.7, 95% CI: 1.8-7.6, p = 0.0004, respectively). Immunohistochemistry (IHC) was performed and confirmed MAGEA3 protein in PDAC specimens. In conclusion, MAGEA3 is differentially expressed in patients with PDAC; its expression correlates with significantly worse survival. Molecular assessment for MAGEA3 should be considered to improve prognostic evaluation and to identify eligible patients for potential immune-based therapy.
The pathogenesis of discogenic low back pain (2005)

Discogenic low back pain is a common cause of disability, but its pathogenesis is poorly understood. We collected 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, 12 from physiologically ageing discs and ten from normal control discs. We investigated the histological features and assessed the immunoreactive activity of neurofilament (NF200) and neuropeptides such as substance P (SP) and vasoactive-intestinal peptide (VIP) in the nerve fibres. The distinct histological characteristic of the painful disc was the formation of a zone of vascularised granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus along the edges of the fissures. SP-, NF- and VIP-immunoreactive nerve fibres in the painful discs were more extensive than in the control discs. Growth of nerves deep into the annulus fibrosus and nucleus pulposus was observed mainly along the zone of granulation tissue in the painful discs. This suggests that the zone of granulation tissue with extensive innervation along the tears in the posterior part of the painful disc may be responsible for causing the pain of discography and of discogenic low back pain.
Characterization of the synthesis of N,N‐dimethyltryptamine by reductive amination using gas chromatography ion trap mass spectrometry (2010)

The present study established an impurity profile of a synthetic route to the hallucinogenic N,N-dimethyltryptamine (DMT). The synthesis was carried out under reductive amination conditions between tryptamine and aqueous formaldehyde in the presence of acetic acid followed by reduction with sodium cyanoborohydride. Analytical characterization of this synthetic route was carried out by gas chromatography ion trap mass spectrometry using electron- and chemical-ionization modes. Methanol was employed as a liquid CI reagent and the impact of stoichiometric modifications on side-products formation was also investigated. Tryptamine 1, DMT 2, 2-methyltetrahydro-β-carboline (2-Me-THBC, 3), N-methyl-N-cyanomethyltryptamine (MCMT, 4), N-methyltryptamine (NMT, 5), 2-cyanomethyl-tetrahydro-β-carboline (2-CM-THBC, 6) and tetrahydro-β-carboline (THBC, 7) have been detected under a variety of conditions. Replacement of formaldehyde solution with paraformaldehyde resulted in incomplete conversion of the starting material whereas a similar replacement of sodium cyanoborohydride with sodium borohydride almost exclusively produced THBC instead of the expected DMT. Compounds 1 to 7 were quantified and the limits of detection were 28.4, 87.7, 21.5, 23.4, 41.1, 36.6, and 34.9 ng mL(-1), respectively. The limits of quantification for compounds 1 to 7 were 32.4, 88.3, 25.4, 24.6, 41.4, 39.9, and 37.0 µg mL(-1), respectively. Linearity was observed in the range of 20.8-980 µg mL(-1) with correlation coefficients > 0.99. The application holds great promise in the area of forensic chemistry where development of reliable analytical methods for the detection, identification, and quantification of DMT are crucial and also in pharmaceutical analysis where DMT might be prepared for use in human clinical studies.
Evidence of T-cell recognition in mice of a purified lipophosphoglycan from Leishmania major (1989)

We have previously reported that a Leishmania major lipophosphoglycan (LPG), given with killed Corynebacterium parvum as an adjuvant, can vaccinate mice against cutaneous leishmaniasis. In order to analyze whether T cells are able to recognize this important parasite antigen, we have studied both humoral and cellular immune responses to L. major LPG that had been isolated from promastigotes by sequential solvent extraction and hydrophobic chromatography. The data show that immunization of mice with highly purified LPG induced an increase in frequency of L. major-reactive T cells and the production of immunoglobulin G antibodies to LPG. Furthermore, genetically resistant mice infected with L. major were able to develop a specific delayed-type hypersensitivity response in the ear to L. major LPG. These findings strongly suggest that T cells can recognize and respond to glycolipid antigens, in this case a host-protective Leishmania LPG, even though such antigens appear not to be potent T-cell stimulators in mice.
The blood-brain and blood-tumor barriers: A review of strategies forincreasing drug delivery (2000)

Drug delivery to brain tumors has been a controversial subject. Some believe the blood-brain barrier is not important, while others believe it is the major obstacle in treatment and have devised innovative approaches to circumvent it. These approaches can be divided into two categories: those that attempt to increase drug delivery of intravascularly administered drugs by manipulating either the drugs or capillary permeability, and those that attempt to increase drug delivery by local administration. Several strategies have been developed to increase the fraction of intravascular drug reaching the tumor, including intra-arterial administration, barrier disruption, new ways of packaging drugs, and, most recently, inhibiting drug efflux from tumor. When given intravascularly, all drugs have a common drawback: the body acts as a sink, and, even in the best situations, only a small fraction of administered drug actually reaches the tumor. A consequence is that systemic toxicity is usually the dose-limiting factor. When given locally, such as into the cerebrospinal fluid or directly into the tumor, 100% of an administered dose is delivered to the target site. However, local delivery is associated with variable and unpredictable spatial distribution and variation in drug concentration. The major dose-limiting factor of most local delivery methods will be neurotoxicity. The relative advantages and disadvantages of the different methods of circumventing the blood-brain barrier are presented in this review, and special attention is given to convection-enhanced delivery, which has particular promise for the local delivery of large therapeutic agents such as monoclonal antibodies, antisense oligonucleotides, or viral vectors.
Rat liver iodothyronine monodeiodinase. Evaluation of the iodothyronine ligand-binding site. (1986)

Ligand binding characteristics of rat liver microsomal type I iodothyronine deiodinase were evaluated by measuring dose-response inhibition and apparent Michaelis-Menten or inhibitor constants of iodothyronine analogues to compete as substrates or inhibitors for the natural substrate L-thyroxine. These data show strong correlations with the binding requirements of hormone analogues to serum thyroxine-binding prealbumin since iodothyronine analogues with a negatively charged side chain, a negative charge or hydrogen bonding function in the 4'-position, tetraiodo ring substitution, and a skewed hormone conformation are structural features shared in common which markedly affect enzyme activity and protein binding affinity. 3,3',5'-Triiodo-L-thyronine is the most potent natural substrate (IC50 = 0.3 microM) and tetraiodothyroacetic acid is the most potent inhibitor (IC50 = 0.2 microM). Both thyroxine (T4)-5'- and T4-5-deiodination pathways are inhibited by these potent analogues, providing further evidence for a single enzyme catalyzing the rat liver microsomal deiodination reactions. These data also show that L-hormone analogues are preferentially deiodinated via the T4-5'-deiodination pathway, whereas D-analogues produce products via the T4-5-deiodination pathway. The thyroxine-binding prealbumin complex was used to model the interaction of thyroid hormones with the deiodinase active site. Computer graphic modeling of the prealbumin complex showed that only those analogues which are potent deiodinase inhibitors or substrates can be accommodated in the hormone binding site. This model suggests the design of functionally specific ligands which can modulate peripheral thyroid hormone metabolism and act as antithyroidal drugs.