gebhart/patrepeval huggingface dataset:
Reciprocal modulation of ammonia and melanin production has implications for cryptococcal virulence (2023)

The fungus Cryptococcus neoformans is the causative agent of cryptococcosis, a disease that is uniformly lethal unless treated with antifungal drugs, yet current regimens are hindered by host toxicity and pathogen resistance. An attractive alternative approach to combat this deadly disease is the direct targeting of pathogen-derived virulence mechanisms. C. neoformans expresses multiple virulence factors that have been studied previously as isolated entities. Among these, are urease, which increases phagosomal pH and promotes brain invasion, and melanization, which protects against immune cells and antifungal treatments. Here we report a reciprocal interdependency between these two virulence factors. Cells hydrolyzing urea release ammonia gas which acts at a distance to raise pH and increase melanization rates for nearby cells, which in turn reduces secretion of urease-carrying extracellular vesicles. This reciprocal relationship manifests as an emergent property that may explain why targeting isolated virulence mechanisms for drug development has been difficult and argues for a more holistic approach that considers the virulence composite.
Reverse-Phase Phosphoproteome Analysis of Signaling Pathways Induced by Rift Valley Fever Virus in Human Small Airway Epithelial Cells (2010)

Rift valley fever virus (RVFV) infection is an emerging zoonotic disease endemic in many countries of sub-Saharan Africa and in Egypt. In this study we show that human small airway epithelial cells are highly susceptible to RVFV virulent strain ZH-501 and the attenuated strain MP-12. We used the reverse-phase protein arrays technology to identify phosphoprotein signaling pathways modulated during infection of cultured airway epithelium. ZH-501 infection induced activation of MAP kinases (p38, JNK and ERK) and downstream transcriptional factors [STAT1 (Y701), ATF2 (T69/71), MSK1 (S360) and CREB (S133)]. NF-κB phosphorylation was also increased. Activation of p53 (S15, S46) correlated with the increased levels of cleaved effector caspase-3, -6 and -7, indicating activation of the extrinsic apoptotic pathway. RVFV infection downregulated phosphorylation of a major anti-apoptotic regulator of survival pathways, AKT (S473), along with phosphorylation of FOX 01/03 (T24/31) which controls cell cycle arrest downstream from AKT. Consistent with this, the level of apoptosis inhibitor XIAP was decreased. However, the intrinsic apoptotic pathway marker, caspase-9, demonstrated only a marginal activation accompanied by an increased level of the inhibitor of apoptosome formation, HSP27. Concentration of the autophagy marker, LC3B, which often accompanies the pro-survival signaling, was decreased. Cumulatively, our analysis of RVFV infection in lung epithelium indicated a viral strategy directed toward the control of cell apoptosis through a number of transcriptional factors. Analyses of MP-12 titers in challenged cells in the presence of MAPK inhibitors indicated that activation of p38 represents a protective cell response while ERK activation controls viral replication.
A contracted bromine basis set for use in calculation of molecular energies (1991)

Abstract A contracted [9s6p2d] basis set derived from Dunning's (14s11p5d) primitive Gaussian set for bromine has been used in ab initio molecular orbital calculations of the dissociation energies of HBr, CH 3 Br, and Br 2 , the ionization potentials of Br and HBr, and the electron affinity of Br. The calculated energies are within 0.1 eV of the experimental values. This is similar to the accuracy obtained in a previous study, also using a contracted [9s6p2d] basis set, of the dissociation and ionization energies of the GeH n , AsH n , and SeH n hydrides.
Fungizide gegen Kartoffelfäule und Falschen Mehltau – die nächste Generation (2007)

Abstract Zunehmende Resistenzen, auslaufender Patentschutz und Umweltdiskussionen bei Re‐Registrierungen, die vor allem auf älteren Präparaten lasten, stimulieren die Suche nach Fungiziden mit neuen Wirkmechanismen weiter. Gegen Algenpilze – sie lösen verheerende Pflanzenkrankheiten in Acker‐ und Weinbau aus – sind mittlerweile effiziente Wirkstoffe auf dem Markt, die eine neue Phase der Schädlingsbekämpfung einläuten.
Effect of Adalimumab Dose Escalation on Hospitalization Risk in Patients With Moderately to Severely Active Ulcerative Colitis (2015)

Introduction: We assessed the effect of adalimumab dose escalation on risk of hospitalization in patients with moderately to severely active UC who did not respond or lost response after adalimumab induction therapy. Methods: Data were pooled from two randomized, double-blind, placebo-controlled phase 3 trials of adalimumab in patients with moderately to severely active UC (ULTRA 1 and 2: NCT00385736; NCT00408629). Patients randomized to adalimumab 160/80 mg induction therapy at weeks 0/2 followed by adalimumab 40 mg EOW who later dose escalated to 40 mg every week owing to non-response or loss of response were included in the analysis. Kaplan-Meier time-to-event analysis was used to estimate observed risks of all-cause and UC-related hospitalization within 90 days after dose escalation. Cox proportional hazards models were used to establish the relationship between hospitalization (both all-cause and UC-related) and partial Mayo scores after dose escalation, controlling for age, sex, prior anti-tumor necrosis factor (anti-TNF) status (naive or experienced), and partial Mayo score before dose escalation. This model's coefficients were then used to predict the 90-day all-cause and UC-related hospitalization risks had no dose escalation occurred, by assuming no changes in patients' partial Mayo scores in the period after dose escalation vs before dose escalation. Results: Of 122 patients who escalated to weekly adalimumab dosing, the majority were male (68%) and naive to anti-TNF agents (74%); mean age was 39.5 years and mean UC duration was 8.3 years. Mean partial Mayo score decreased from 6.8 before dose escalation to an average of 5.17 after dose escalation. For patients who dose escalated, the observed (Kaplan Meier) 90-day all-cause and UC-related hospitalization risks were 8.7% and 6.7%, respectively. The predicted 90-day all-cause and UC-related hospitalization risks, had patients continued on EOW therapy, were 13.0% and 10.3%, respectively. The relative risk of both all-cause and UC-related hospitalization in patients who dose escalated was lowered by 33.2% and 35.5%, respectively, compared with the predicted risk without dose escalation, reflecting the benefits of dose adjustment. Conclusion: Dose escalation of adalimumab in patients with moderately to severely active UC who did not respond or lost response after induction therapy reduced the 90-day risk of hospitalization and reflected a benefit of adalimumab dose escalation for treating these UC patients.
Reverse Shoulder Arthroplasty in Patients With Amputation or Paralysis of the Contralateral Upper Extremity (One‐Arm Patients) (2017)

IV.
Modeling and Conventional/Adaptive PI Control of a Lathe Cutting Process (1988)

A mathematical model for predicting dynamics between the feedrate and cutting force in the lathe cutting process is presented. The model comes from combinations of a parameter identification technique and geometrical consideration for chip thickness time variation. The model prediction of transient responses is in good agreement with the experimental results. The model is used for tuning a PI controller for regulating the cutting force as well as to show performance limitations of the conventional PI controller. A simple adaptive control scheme that makes use of the model structure is proposed. Experimental results from laboratory evaluation of the proposed controllers are presented.
The Reliability of Computed Tomography and Magnetic Resonance Imaging Grading of Lumbar Facet Arthropathy in Total Disc Replacement Patients (2009)

The current grading system for facet arthropathy has only fair agreement. CT is slightly more reliable for grading. Intrarater reliability was only fair for MRI and moderate for CT. Only limited agreement existed between surgeons as to the extent of facet disease that would pose as a contraindication for TDR.
The fork restart factor PHF6 interacts with RRM2 and binds to H3K56ac marked nascent DNA (2023)

Abstract The PHF6 protein is a presumed chromatin reader implicated in disease through germline loss-of-function mutations causing cognitive disability syndromes and somatic mutations are predominantly observed in acute T-cell leukemia. Previous reports support a role for PHF6 in DNA damage repair, replication fork restart as well as hematopoietic precursor cell self-renewal capacity and lineage commitment. To explore better how PHF6 mediates these functions, we mapped the PHF6 interactome and identified RRM2 as a consistent binding partner across different normal and malignant cell types. Next, PHF6 knockdown imposed increased replicative stress/DNA damage and suggested possible binding of PHF6 to H3K56ac, a marker for nascent DNA at sites of DNA damage repair. Genome-wide mapping of PHF6 chromatin binding indeed revealed overlap with sites of active DNA damage, binding sites of replication fork proteins and functional crosstalk with the neuroblastoma transcription core regulatory circuitry. Altogether, we show a canonical PHF6-RRM2 interaction enabling active transport of RRM2 to genomic sites of PHF6 mediated fork restart and PHF6 localization to H3K56ac at highly transcribed genes facilitating fork restart following replication-transcription conflicts.
Modeling real life LED spectra from data sheet information only (2021)

LEDs not only have widely varying spectral (and electrical) properties at the fixed temperature and current "grouping conditions" used to characterize them after production, to group them into "bins". LED spectrum and voltage also change with temperature and current in operation. For an actual product, it is nontrivial to predict spectra and voltages from limited information in data sheets for real life driving conditions. We show how spectra and voltages can indeed be predicted from data sheet values, and which generic a priori information about LEDs is required in addition, demonstrating our open source, public domain Matlab implementation.
AlGaN/GaN HFETs on Si Substrates for WiMAX Applications (2006)

AlGaN/GaN HFETs on Si substrates are tested under OFDM modulations and show excellent performance from 3.3GHz to 3.8GHz. Performance on an 8mm device (NPT35010) in power small outline package (PSOP2) shows 1.5W output power, 11.2dB gain, 28.6% drain efficiency and 2% EVM at 3.5GHz. Large periphery 36mm devices were mounted in ceramic packages (NPT35050) and showed greater than 7W output power, > 11dB gain, 27.2% drain efficiency and 2% EVM at 3.5 GHz. Additionally data was taken across process from 23 devices and 5 process lots to demonstrate repeatability. Finally the same RF data was collected over flange temperature from -40degC to +85degC and demonstrated stable performance over temperature. These results demonstrate the potential for GaN-on-Si HEMTs for use in WiMAX applications
ANALYSIS OF THE MUELLER ANTEROLATERAL FEMOROTIBIAL LIGAMENT (ALFTL) RECONSTRUCTION USING A COMPUTERIZED KNEE MODEL (1984)

Gibson, Mike*,†; Mikoz, Rich; Reider, Bruce M.D.†; Andriacchi, Thomas Ph.D. Author Information
Figure S2 from AZD4320, A Dual Inhibitor of Bcl-2 and Bcl-x<sub>L</sub>, Induces Tumor Regression in Hematologic Cancer Models without Dose-limiting Thrombocytopenia (2023)

&lt;p&gt;Figure S2&lt;/p&gt;
P2–411: Amelioration of calcium dyshomeostasis by immunotherapy with BIIB037 in Tg2576 mice (2013)

Immunotherapy remains a promising approach for the treatment of Alzheimer's disease (AD), and anti-Abeta monoclonal antibodies with different binding, pharmacological, and safety profiles are in clinical development. We have previously demonstrated the ability to monitor individual senile plaques and alterations in calcium homeostasis in the brains of living APP mice using multiphoton imaging. Since resting calcium levels are elevated in some neurons in aged APP mice, amelioration of this calcium overload could serve as a functional indicator of treatment efficacy. To this end, we evaluated the effects of BIIB037, a fully human antibody that preferentially binds parenchymal fibrillar Abeta, on plaque clearance and calcium homeostasis in Tg2576 mice. Using longitudinal imaging with multiphoton microscopy, we measured the acute effect of topical application of BIIB037 on existing senile plaques in 22 month-old Tg2576 mice. We also monitored intracellular calcium using the genetically encoded calcium sensor YC3.6 along with methoxy-XO4 labeled amyloid pathology during a chronic dosing study initiated in 18 month-old Tg2576 mice. BIIB037 was administered at 10 mg/kg for 6 months via weekly IP injections. Acute topical application of BIIB037 resulted in clearance of existing amyloid plaques within 3 weeks but did not prevent formation of new plaques. Brain penetration and colocalization with amyloid plaques was observed following IP injections of fluorescently labeled BIIB037. Chronic systemic administration of the antibody in 18 month-old animals did not lead to clearance of existing plaques detected with monthly imaging over the 6 month s treatment period. However, calcium overload was progressively reduced over this time course. Non-specific antibody treatment resulted in neither plaque clearance nor reductions in calcium overload. Treatment with BIIB037, a fully human anti-amyloid antibody, led to the reversal of a functional outcome measure in Tg2576 mice without significantly reducing the amyloid load. This suggests that this antibody may have beneficial effects on neuronal network function that likely underlies cognitive deficits, and that functional endpoint could be considered in addition to amyloid burden to monitor immunotherapy efficacy.
Micelles-Assisted Oxidation of Isoleucine: A Kinetic Study (2011)

Abstract The title reaction has been studied spectrophotometrically as a function of [], [isoleucine], [H2SO4], and temperature in absence and presence of cationic micelles of cetyltrimethylammonium bromide (CTAB). Under pseudo-first order conditions, the reaction follows first order kinetics with respect [isoleucine]. At lower values of [CTAB] (≤40.0 × 10−4 mol dm−3), the catalytic effect of cationic micelles of CTAB may be due to the incorporation/solubilization of isoleucine and into the interfacial region of Stern- and palisade layer.In contrast, at higher values of [CTAB] (≥40.0 × 10−4 mol dm−3), the inhibitory effect was observed due to the dilution.Thermodynamic parameters were computed by studying the reactions at different temperatures (303–333 K). Plausible mechanisms are suggested. Keywords: CTABisoleucinemicellar catalysispermanganate
Combining Designer Cells and Click Chemistry for a One‐Pot Four‐Step Preparation of Enantiopure β‐Hydroxytriazoles (2010)

Abstract The multistep catalytic process using designer cells, either added as freshly prepared suspensions or as stable lyophilized powder, and click reaction can be performed in one pot. The sequence of four reactions allows the production of both enantiomers of β‐hydroxytriazoles with high enantiomeric excess.
PEBBLES study protocol: a randomised controlled trial to prevent atopic dermatitis, food allergy and sensitisation in infants with a family history of allergic disease using a skin barrier improvement strategy (2019)

ACTRN12617001380381 and NCT03667651.
Experimental design of bandstop filters based on unconventional defected ground structures (2016)

ABSTRACT A modified design of band stop filters using unconventional defected ground structures (DGS) is presented. The new proposed structures have conventional dumbbell DGS and spiral DGS integrated with U‐slots. These microstrip structures provide high selectivity and Q‐factor. By integrating the U‐slot to the conventional structures, the overall capacitance and inductance increase which results in shift of resonance frequency from3.434 GHz to2.323 GHz for modified dumbbell and from 1.818 GHz to 1.702 GHz for modified spiral structure. Sharp transition is achieved from pass band to stop band and reduced ripples in the pass band for the new proposed DGS while the DGS sizes remain the same. The proposed designs were fabricated and tested on a dielectric substrate with dielectric permittivity of 10. © 2016 Wiley Periodicals, Inc. Microwave Opt Technol Lett 58:2969–2973, 2016
SETD2 non genomic loss of function in advanced systemic mastocytosis is mediated by an Aurora kinase A/MDM2 axis and can be therapeutically targeted (2022)

Abstract Background : The SETD2 tumor suppressor gene encodes a histone methyltransferase that safeguards transcription fidelity and genomic integrity via trimethylation of histone H3 lysine 36 (H3K36Me3). SETD2 loss of function has been observed in solid and hematologic malignancies. We have recently reported that most patients with advanced systemic mastocytosis (AdvSM) and some with indolent or smoldering SM display H3K36Me3 deficiency as a result of a reversible loss of SETD2 due to reduced protein stability. Methods: Experiments were conducted in SETD2-proficient (ROSA KIT D816V ) and -deficient (HMC-1) cell lines and in primary cells from patients with various SM subtypes. A short interfering RNA approach was used to silence SETD2 (in ROSA KIT D816V cells), MDM2 and AURKA (in HMC-1 cells). Protein expression and post-translational modifications was assessed by Western Blotting and Immunoblotting. Proteins interactions were tested by using co-immunoprecipitation. Apoptotic cell death was evaluated by flow cytometry after annexin V and propidium iodide staining, respectively. Drug cytotoxicity in in vitro experiments was evaluated by clonogenic assays. Results: Here, we show that the proteasome inhibitors carfilzomib and ixazomib suppress cell growth and induce apoptosis in neoplastic mast cells by promoting SETD2/H3K36Me3 re-expression. Moreover, we found that Aurora kinase A and MDM2 are implicated in SETD2 loss of function in AdvSM. In line with this observation, direct or indirect targeting of Aurora kinase A with alisertib or volasertib induced reduction of clonogenic potential and apoptosis in human mast cell lines and primary neoplastic cells from patients with AdvSM. Efficacy of Aurora A or proteasome inhibitors was comparable to that of avapritinib. Conclusions: Our mechanistic insights into SETD2 non-genomic loss of function in AdvSM highlight the potential value of novel therapeutic targets and agents for the treatment of patients who fail or do not tolerate midostaurin or avapritinib.
Superhydrophobic, infrared transmissive moth eye-like substrates for use in wet conditions (2017)

Infrared (IR) transmissive moth eye-like substrates, including randomly patterned fused silica and various periodically patterned germanium substrates, were surface modified using a simple process. Goniometric analysis showed that the surface modification altered the surface wettability of each substrate, rendering them superhydrophobic. Following the surface modification, it was determined that the desirable IR transmission and antireflective properties of each substrate type were maintained. Furthermore, the hydrophobicity, IR transmission and antireflective capabilities of the substrates were shown to be significantly enhanced in comparison to native, non-patterned fused silica and germanium substrates that underwent the same processes. The results of this work provide an opportunity for the development of enhanced utility for infrared transmissive optics in wet or humid conditions.
ChemInform Abstract: PALLADIUM HYDRIDES IN ORGANIC SYNTHESIS. REDUCTION OF ARYL HALIDES BY SODIUM METHOXIDE CATALYZED BY TETRAKIS(TRIPHENYLPHOSPHINE)PALLADIUM (1978)

Abstract Bei der Behandlung mit Natriummethylat (II) erhält man aus den Arylhalogeniden (I) in Gegenwart des Pd‐Katalysators (III) glatt die Kohlenwasserstoffe (IV).
Long‐Term Follow‐Up of Idiopathic Ventricular Fibrillation in a Pediatric Population: Clinical Characteristics, Management, and Complications (2019)

Background The natural history and long-term outcome in pediatric patients with idiopathic ventricular fibrillation ( IVF ) are poorly characterized. We sought to define the clinical characteristics and long-term outcomes of a pediatric cohort with an initial diagnosis of IVF . Methods and Results Patients were included from an International Registry of IVF (consisting of 496 patients). Inclusion criteria were: (1) VF with no identifiable cause following comprehensive analysis for ischemic, electrical or structural heart disease and (2) age ≤16 years. These included 54 pediatric IVF cases (age 12.7±3.7 years, 59% male) among whom 28 (52%) had a previous history of syncope (median 2 syncopal episodes [interquartile range 1]). Thirty-six (67%) had VF in situations associated with high adrenergic tone. During a median 109±12 months of follow-up, 31 patients (57%) had recurrence of ventricular arrhythmias, mainly VF . Two patients developed phenotypic expression of an inherited arrhythmia syndrome during follow-up (hypertrophic cardiomyopathy and long QT syndrome, respectively). A total of 15 patients had positive genetic testing for inherited arrhythmia syndromes. Ten patients (18%) experienced device-related complications. Three patients (6%) died, 2 due to VF storm. Conclusions In pediatric patients with IVF , a minority develop a definite clinical phenotype during long-term follow-up. Recurrent VF is common in this patient group.
Oral fecal microbiota transplant for recurrent Clostridium difficile in pediatric autoimmune enteropathy (2019)

Singh, Harveen; Ross, Lindsey; Smith, Harriet; Borody, Thomas J.; Lemberg, Daniel A. Author Information
Appendix B: The FALCON Project (2012)

This appendix contains sections titled: Introduction Overview The Diagnostic Philosophy Underlying the FALCON System Target Process System The FALCON System Derivation of the FALCON Diagnostic Knowledge Base The Ideal FALCON System Use of the Knowledge-Based System Paradigm in Problem Solving References
Supplementary Figure 1 from <i>JAK3</i> Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients (2023)

&lt;p&gt;Patient cohorts analyzed in this project.&lt;/p&gt;