gebhart/patrepeval huggingface dataset:
The prevalence of colonic polyps in acromegaly: a colonoscopic and pathological study in 103 patients. (1995)

Patients with acromegaly are reported to be at risk of developing adenomatous colonic polyps, which are considered to be preneoplastic lesions. This assumption is, however, usually drawn from results obtained in rather small series of patients or without a control group. We, therefore, undertook a prospective colonoscopic and pathological study comprising 103 acromegalic patients and 138 nonacromegalic control subjects referred for irritable bowel syndrome. The prevalence of adenomatous colonic polyps was significantly increased in acromegalic patients compared to that in control subjects (22.3% vs. 8.0%; P = 0.0024). The significance was similarly present in male acromegalic patients (28.6% vs. 5.5% in male control subjects; P = 0.0026), but was absent in female acromegalic patients. The prevalence of colonic polyps was also significantly increased in the group of acromegalic patients under 55 yr of age (20.0% vs. 3.0% in the control group of the same age; P = 0.0026). Other characteristics of adenomatous colonic polyps in acromegaly were the multiplicity and the presence proximal to the splenic flexure. No difference in the duration of acromegaly was found between patients with or without adenomatous polyps. The prevalence of hyperplastic colonic polyps was also significantly increased to 24.3% in acromegalic patients vs 4.4% in control subjects (P < 0.001). In conclusion, in view of the increased incidence of adenomatous colonic polyps, colonoscopy should be part of the follow-up examination in acromegaly.
Using Single Protein/Ligand Binding Models to Predict Active Ligands for Unseen Proteins (2020)

Machine learning models that predict which small molecule ligands bind a single protein target report high levels of accuracy for held-out test data. An important challenge is to extrapolate and make accurate predictions for new protein targets. Improvements in drug-target interaction (DTI) models that address this challenge would have significant impact on drug discovery by eliminating the need for high-throughput screening experiments against new protein targets. Here we propose a data augmentation strategy that addresses this challenge to enable accurate prediction in cases where no experimental data is available. To proceed, we first build single protein-ligand binding models and use these models to predict whether additional ligands bind to each protein. We then use these predictions to augment the experimental data, train standard DTI models, and predict interactions between unseen test proteins and ligands. This approach achieves Area Under the Receiver Operator Characteristic (AUC) &gt; 0.9 consistently on test sets consisting exclusively of proteins and ligands for which the model is given no experimental data. We verify that performance improvements extend to held-out test proteins distant from the training set. Our data augmentation framework can be applied to any DTI model, and enhances performance on a range of simple models.
Abstract P764: Single versus Dual Dose of Intra-Arterial Stem Cell Therapy for Stroke (2021)

Introduction: Pre-clinical studies have shown great promise in the use of cell-based therapies for stroke. Intra-arterial (IA) delivery directs the cells to the injured brain, is minimally invasive and widely available, making it attractive for clinical translation. Our group and others have shown the safety and efficacy of IA Mesenchymal Stem Cell (MSC) treatment in a rodent stroke model at 24 hours post-reperfusion. The optimal timing of a single dose of IA MSC is unknown. Also, whether an additional dose will lead to greater benefit and the optimal timing of the second dose need to be determined for successful translation of IA MSC to clinic. The objective of this study is to determine if dual dose IA-MSC treatment is superior to single dose and find the optimal timing for the second dose. Methods: We used a reversible middle cerebral artery occlusion (rMCAO) model for stroke in rats. IA-MSCs were administered using a PE-10 catheter at 1, 2 and 4 day after stroke as single dose. Based on the results of the first experiment, dual doses were given at 1-4, 1-6 and 1-15 day. Behavioral analysis of rotarod, neurological deficit scoring and stroke volume were determined at 30 days after treatment. Results: Single dose IA-MSC at 1day was superior (p=0.02, 0.01, 0.04) to single dose given on day 2 and no benefit was seen when given on day 4. Among the dual dose groups, 1-6 day after stroke showed significant improvement in neurodeficit score and stroke volume (p=0.007, p=0.03). However, the percentage increase in improvement in 1-6day (dual) was much higher than that observed in 1day (single) group (Fig 1). Detailed results will be presented at the meeting. Conclusion: The results of our study indicate that 1day after stroke is optimal for single dose of IA-MSC. An additional dose at 6days after stroke enhances the effect of IA-MSC in aiding symptomatic recovery and stroke lesion reduction. In summary, our findings contribute to understanding of the benefit of dual dose of IA MSC for translation to the clinic.
ChemInform Abstract: New Synthesis of 2‐Aminobicyclo[2.1.1]hexane‐2,5‐dicarboxylic Acid‐I (ABHxD‐I), a Potent Metabotropic Receptor Agonist. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
HIGH PERFORMANCE LIQUID CHROMATOGRAPHY OF PEPTIDES USING SALT SOLUTIONS AS MOBILE PHASES (1981)

The purpose of this research was to develop new analytical techniques for the analysis of low molecular weight peptides in biological samples, using reversed phase high performance liquid chromatography. First, several neutral and ionic compounds were investigated as solutes to determine the effect of pH on the use of carboxylic acids as ion pairing reagents in RP-HPLC. It was found that the ion-pairing properties of carboxylic acids in mobile phases could be controlled by adjusting the pH of the solution. These results, coupled with the use of soft acid cation salts of carboxylic acids, provided a new system of static retention for peptides in HPLC which could be controlled by adjusting the pH of the eluent. It was found that increased retention of peptides was influenced by the soft acid character of the cation of the carboxylic acid salt used, and by the chain length of the acid. Longer chain length and softer acid character provided increased retention. Proton decoupled ('13)C-NMR spectroscopy was used to investigate the interaction of these salts with a series of model peptides. Silver(I) acetate was found to mainly interact with the amide carbonyls and terminal amino group on these peptides. An ammine type complexation was hypothesized for this interaction. The use of silver(I) valerate solutions for the analysis of peptide mixtures was attempted. By employing a split column technique and a pH and methanol gradient system, good separation of a series of model peptides, including Phe-(Gly)(,n), where n = 1-4, was obtained. Increased resolution of these peptides using this technique was obtained compared to isocratic elution. This is due to concentration of the sample at the head of the analytical column prior to elution, and the use of the gradient system. This concentration-elution system presents itself as an improved method of injection in HPLC. Preliminary results for the analysis of peptides in complex biological samples indicated that this technique suffers from poor resolution and low sensitivity for these samples. The use of other solvent or gradient systems, coupled with other methods of detection may increase the sensitivity and resolution of the present technique.
Comparison of fitting methods and b‐value sampling strategies for intravoxel incoherent motion in breast cancer (2014)

IVIM analysis may improve using optimized selection and "segmented" analysis, potentially enabling better differentiation of breast cancer subtypes and monitoring of treatment.
Temperature-Induced Variations in the Surface Topology of Cultured Lymphocytes Are Revealed by Scanning Electron Microscopy (1973)

Temperature-induced variations in the surface morphology of cultured lymphocytes were evaluated by scanning electron microscopy. At 25-37 degrees the cells' surfaces are largely obscured by numerous undulating microvilli of various lengths but uniform diameter. Temperature changes alter the number of microvilli, their lengths, diameters, distribution, branching, and fusing. Typically, chilling to 0-4 degrees markedly reduces the number of microvilli and increases the diameter of the survivors in a reversible process. In contrast, heating the cells to about 45 degrees rapidly and irreversibly transforms the ordinarily smooth membrane surface into one with a "cobblestone" morphology. At the same time most microvilli disappear and the few that remain clump into a cap. The data suggest that the low-temperature effects reflect a change in the physical state of membrane lipids, while the high-temperature alterations represent thermotropic protein transitions.
Electrostatic control of regioselectivity via ion pairing in a Au(i)-catalyzed rearrangement (2014)

Ion pairing controls regioselectivity in a Au(<sc>i</sc>)-catalyzed rearrangement by favoring the more polar product-determining transition state.
Ultrastructural changes in the Golgi apparatus and secretory granules of HL-60 cells treated with the imino sugar N-butyldeoxynojirimycin. (1997)

The imino sugar N-butyldeoxynojirimycin inhibits the N-linked oligosaccharide processing enzymes alpha-glucosidases I and II, and the ceramide specific glucosyltransferase which catalyses the first step in glucosphingolipid biosynthesis. We have studied the effects of this compound on the ultrastructure of HL-60 cells to identify novel activities of this compound. Treatment of HL-60 cells with this imino sugar results in several morphological changes within the cell, none of which result in cytotoxicity. The plasma membrane stains heavily with potassium ferrocyanide within 30 min following addition of the compound to the medium, and there is then a time dependent involvement of all other intracellular membranes. Secretory granules become enlarged and lose their dense core morphology and appear either empty and vacuolated or have low density contents. However, the most striking effect of NB-DNJ treatment is on the Golgi apparatus. The Golgi exhibits a time-dependent change from typical Golgi morphology to a structure almost completely devoid of cisternae and consisting predominantly of vesicles. All the observed changes are fully reversible on withdrawal of the compound.
Limits to silicon modulator bandwidth and power consumption (2009)

The limits to silicon modulator bandwidth and power consumption are explored. Traditional electrical interconnects provide insufficient bandwidth (~10Gb/s) and consume far too much power (~10pJ/bit) for future high performance computing applications. Microphotonic devices closely integrated with advanced CMOS electronics have the potential to dramatically lower intra- and inter-chip communication power consumption while greatly increasing available bandwidth. Our recent results confirm the significant advantages offered by microphotonic communication links. We have broken the 100fJ/bit barrier by demonstrating 4-micron diameter microdisk modulators achieving 10Gb/s data transmission with a bit-error-rate below 10<sup>-12</sup> and a measured power consumption of only 85fJ/bit. Through rigorous simulation and experimentation, we consider ultimate limits to silicon modulator bandwidth and power consumption.
Nanocapsules modify membrane interaction of polymyxin B to enable safe systemic therapy of Gram-negative sepsis (2021)

Systemic therapy of Gram-negative sepsis remains challenging. Polymyxin B (PMB) is well suited for sepsis therapy due to the endotoxin affinity and antibacterial activity. However, the dose-limiting toxicity has limited its systemic use in sepsis patients. For safe systemic use of PMB, we have developed a nanoparticulate system, called D-TZP, which selectively reduces the toxicity to mammalian cells but retains the therapeutic activities of PMB. D-TZP consists of an iron-complexed tannic acid nanocapsule containing a vitamin D core, coated with PMB and a chitosan derivative that controls the interaction of PMB with endotoxin, bacteria, and host cells. D-TZP attenuated the membrane toxicity associated with PMB but retained the ability of PMB to inactivate endotoxin and kill Gram-negative bacteria. Upon intravenous injection, D-TZP protected animals from pre-established endotoxemia and polymicrobial sepsis, showing no systemic toxicities inherent to PMB. These results support D-TZP as a safe and effective systemic intervention of sepsis.
Nanoparticle T cell engagers for the treatment of acute myeloid leukemia (2021)

Acute myeloid leukemia (AML) is the most common type of leukemia and has a 5-year survival rate of 25%. The standard-of-care for AML has not changed in the past few decades. Promising immunotherapy options are being developed for the treatment of AML; yet, these regimens require highly laborious and sophisticated techniques. We create nanoTCEs using liposomes conjugated to monoclonal antibodies to enable specific binding. We also recreate the bone marrow niche using our 3D culture system and use immunocompromised mice to enable use of human AML and T cells with nanoTCEs. We show that CD33 is ubiquitously present on AML cells. The CD33 nanoTCEs bind preferentially to AML cells compared to Isotype. We show that nanoTCEs effectively activate T cells and induce AML killing <i>in vitro</i> and <i>in vivo</i>. Our findings suggest that our nanoTCE technology is a novel and promising immuno-therapy for the treatment of AML and provides a basis for supplemental investigations for the validation of using nanoTCEs in larger animals and patients.
Functional Comparison of Posterior Cruciate Retained versus Cruciate-Sacrificed Total Knee Arthroplasty (1988)

Gait of 11 patients with bilateral paired posterior cruciate-retaining and cruciate-sacrificing total knee arthroplasties (TKA) was studied preoperatively and two years postoperatively on walking and stair climbing. Five-year clinical and roentgenographic examinations were included in the study. Differences between the two prostheses were noted both in level walking and in stair climbing. On level walking, cruciate-sacrificed TKA had more flexion in loading response and increased flexion and varus moments with increased muscle activity of quadriceps and biceps femoris. Abnormal gaits common to both types of knee were decreased flexion in stance and decreased single-limb stance. Both knees had a stiff-legged gait during stance. On stairs, the cruciate-sacrificed TKA substituted soleus muscle activity for knee stability. The single-limb stance and range of motion were similar for both knees. In clinical terms, the cruciate-sacrificed TKA is less efficient and has greater medial loading and higher joint reaction forces that may affect durability of the prosthesis. The five-year knee scores, patient satisfaction, and roentgenographic examinations were equal for both sets of knees.
Direct Imaging of The Lattice In Poly(Phthalocyaninato-Germoxane) Single Crystals (1985)

Abstract Poly(phthalocyaninatogermoxane, [Ge(Pc)O]>n, was prepared from single crystals of the monomer phthalocyaninato-germanium dihydroxide, Ge(Pc)(OH)2, by thermal condensation polymerization in solid state. Direct imaging of (100) lattice planes containing the extended molecular chains in the polymer single crystals was achieved using transmission electron microscopy. A mosaic block structure and many lattice imperfections were recorded.
X‐ray Diffraction Study of (±)‐5α‐ [2′‐Hydroxy‐l'‐Methoxycarbonyl‐2'‐(3″,4″,5″‐Trimethoxyphenyl) Ethyl)‐4α‐(3″‐4″‐Methylenedioxyphenyl)‐2α‐Phenyl‐1,3‐Dioxane (1984)

Abstract C 30 H 32 O 10 , monoclinic, P 2 1 / c , a = 12.932(5), b = 9.670(6), c = 23.276(13)Å, β = 103.87(4), ν = 2825.9(25)Å 3 , M r = 552.58, Z = 4, D x = 1.30 mg cm −3 . The structure was solved by direct methods (MULTAN 80) and refined (SHELX 76) to a final R value of 0.056 for 2344 observed reflections. The dioxane ring has a chair conformation. On this ring, two substituents, the phenyl and the methylenedioxyphenyl groups, are in equatorial positions while the substituted ethyl fragment is axial.
Modification of adverse inflammation is required to cure new-onset type 1 diabetic hosts (2007)

In nonobese diabetic (NOD) mice with overt new-onset type 1 diabetes mellitus (T1DM), short-term treatment with a "triple-therapy" regimen [rapamycin plus agonist IL-2-related and antagonist-type, mutant IL-15-related Ig fusion proteins (IL-2.Ig and mutIL-15.Ig)] halts autoimmune destruction of insulin-producing beta cells and restores both euglycemia and immune tolerance to beta cells. Increases in the mass of insulin-producing beta cells or circulating insulin levels were not linked to the restoration of euglycemia. Instead, the restoration of euglycemia was linked to relief from an inflammatory state that impaired the host's response to insulin. Both restoration of immune tolerance to beta cells and relief from the adverse metabolic effects of an inflammatory state in insulin-sensitive tissues appear essential for permanent restoration of normoglycemia in this T1DM model. Thus, this triple-therapy regimen, possessing both tolerance-inducing and select antiinflammatory properties, may represent a prototype for therapies able to restore euglycemia and self-tolerance in T1DM.
P693 Development and evaluation of i-TRACKER infliximab and i-TRACKER anti-Infliximab kits: fast and innovative chemiluminescent assays for the monitoring of patients treated with infliximab (2020)

Abstract Background Infliximab, a monoclonal antibody directed against TNFα, is a drug widely used for the treatment of inflammatory diseases (rheumatoid arthritis, Crohn’s disease, etc.). Therapeutic drug monitoring is currently proposed to provide useful information to clinicians to improve the efficacy of the treatment. Theradiag has just developed the innovative i-TRACKER Infliximab and i-TRACKER Anti-Infliximab kits: fast quantifications of Infliximab and Anti-Infliximab antibodies fully automated on the random access i-TRACK10 chemiluminescent analyser. Methods Analytical performances were assessed using two types of serum samples: human serum spiked with Infliximab or Anti-Infliximab antibodies, and samples from inflammatory bowel disease patients treated with Infliximab (n = 41). On one hand, Infliximab from serum sample was captured by TNFα coupled magnetic microparticles and Anti-Infliximab polyclonal antibodies conjugated to acridinium ester were used for the detection of Infliximab. On the other hand, Anti-Infliximab antibodies were captured according to Infliximab coupled magnetic microparticles and detected with the use of Infliximab conjugated to acridinium ester. Light emission was linked to the quantity of Infliximab, or anti-Infliximab antibodies, presents in the sample. Results Infliximab measurement showed high accuracy (recovery was comprised between 80% and 107%). High precisions were reached for both assays (intra-precision CV were below 8.1% and 2.7% for Infliximab and Anti-Infliximab assays; inter-precision CV were below 11.7% and 4.8% for Infliximab and Anti-Infliximab assays) and no interferences were seen with biologic agents (bilirubin, haemoglobin, lipids, biotin and rheumatoid factors). The dynamic ranges of the assays were 0.3–24 µg/ml for Infliximab quantification and 10–2000 ng/ml for Anti-Infliximab antibodies quantification. i-TRACKER Infliximab and i-TRACKER anti-Infliximab assays were compared with respective LISA-TRACKER assays and showed excellent correlation (R² = 0.94, Slope = 1.04 for Infliximab assay; Spearman’s coefficient correlation was 0.98 for Anti-Infliximab assay). Conclusion i-TRACKER kits are innovative assays which exhibit fast (time to results &amp;lt;40 min), accurate (standardised with NIBSC/WHO international standard Infliximab) and reproducible results for the quantification of princeps and biosimilar molecules (CT-P13, SB2). Excellent agreements were observed with respective LISA-TRACKER assays. i-TRACKER kits are valuable tools for the monitoring of patients treated with Infliximab.
Event-triggered Add-on Safety for Connected and Automated Vehicles Using\n Road-side Network Infrastructure (2019)

This paper proposes an event-triggered add-on safety mechanism to adjust the\ncontrol parameters for timely braking in a networked vehicular system while\nmaintaining maneuverability. Passenger vehicle maneuverability is significantly\naffected by the combined-slip friction effect, in which larger longitudinal\ntire slips result in considerable drop in lateral tire forces. This is of\nhigher importance when unexpected dangerous situations occur on the road and\nimmediate actions, such as braking, need to be taken to avoid collision. Harsh\nbraking can lead to high-slip and loss of maneuverability, hence, timely\nbraking is essential to reduce high-slip scenarios. In addition to the vehicles\nown active safety systems, the proposed event-triggered add-on safety is\nactivated upon being informed about dangers by the road-side infrastructure.\nThe aim is to incorporate the add-on safety feature to adjust the automatic\ncontrol parameters for smooth and timely braking such that a collision is\navoided while vehicle's maneuverability is maintained. We study two different\nwireless technologies for communication between the infrastructure and the\nvehicles, the Long-Term Evolution (LTE) and the fifth generation (5G) schemes.\nThe framework is validated through high-fidelity software simulations and the\nadvantages of including the add-on feature to augment the safety margins for\neach communication technology is evaluated.\n