gebhart/patrepeval huggingface dataset:
Preparation of an oakmoss absolute with reduced allergenic potential (1992)

Synopsis Oakmoss absolute, an extract of the lichen Evernia prunastri, is known to cause allergenic skin reactions due to the presence of certain aromatic aldehydes such as atranorin, chloratranorin, ethyl hematommate and ethyl chlorohematommate. In this paper it is shown that treatment of Oakmoss absolute with amino acids such as lysine and/or leucine, lowers considerably the content of these allergenic constituents including atranol and chloratranol. The resulting Oakmoss absolute, which exhibits an excellent olfactive quality, was tested extensively in comparative studies on guinea pigs and on man. The results of the Guinea Pig Maximization Test (GPMT) and Human Repeated Insult Patch Test (HRIPT) indicate that, in comparison with the commercial test sample, the allergenicity of this new quality of Oakmoss absolute was considerably reduced, and consequently better skin tolerance of this fragrance for man was achieved.
Monomeric destetrapeptide human insulin from a precursor expressed inSaccharomyces cerevisiae (2001)

Destetrapeptide insulin (DTI, human insulin with B27-30 removed) was obtained from a monomeric precursor (MIP) expressed in Saccharomyces cerevisiae through tryptic transpeptidation in the presence of synthetic tetrapeptide Gly-Phe-Phe-Tyr. The in vivo biological activity of DTI, determined by mouse convulsion assay, is 22 IU/mg. Its binding activity with insulin receptor on human placental membrane is 80% and its in vitro biological activity, determined by free fat cell assay, is 77%. Compared with native insulin, DTI molecules do not associate in solution but exist in the monomeric form, thus leading to its rapid utilization in vivo.
REVIEW Human Sulfotransferases and Their Role in Chemical Metabolism (2006)

Sulfonation is an important reaction in the metabolism of numerous xenobiotics, drugs, and endogenous compounds. A supergene family of enzymes called sulfotransferases (SULTs) catalyze this reaction. In most cases, the addition of a sulfonate moiety to a compound increases its water solubility and decreases its biological activity. However, many of these enzymes are also capable of bioactivating procarcinogens to reactive electrophiles. In humans three SULT families, SULT1, SULT2, and SULT4, have been identified that contain at least thirteen distinct members. SULTs have a wide tissue distribution and act as a major de-toxification enzyme system in adult and the developing human fetus. Nine crystal structures of human cytosolic SULTs have now been determined, and together with site-directed mutagenesis experiments and molecular modeling, we are now beginning to understand the factors that govern distinct but overlapping sub-strate specificities. These studies have also provided insight into the enzyme kinetics and inhibition characteristics of these enzymes. The regulation of human SULTs remains as one of the least explored areas of research in the field, though there have been some recent advances on the molecular transcription mechanism con-trolling the individual SULT promoters. Interindividual variation in sulfonation capacity may be important in determining an individual’s response to xenobiotics, and recent studies have begun to suggest roles for SULT polymorphism in disease susceptibility. This review aims to provide a summary of our present un-derstanding of the function of human cytosolic sulfotransferases. Key Words: human sulfotransferases; SULT1A1 regulation; SULT crystal structures; bioactivation.
Optical Evidence for a Nonmolecular Phase of Nitrogen above 150 GPa (2000)

Optical spectroscopy techniques, including visible and near infrared (IR) Raman and synchrotron IR methods have been applied to study solid nitrogen at megabar pressures. We find that nitrogen becomes totally opaque above 150 GPa, accompanied by the disappearance of Raman and IR vibrational excitations, while new broad IR and Raman bands become visible. Optical absorption measurements reveal that the semiconducting absorption edge responsible for the change of color is characterized by the presence of a wide Urbach-like tail and a high-energy (Tauc) region. These data are consistent with the dissociation of molecular nitrogen into a nonmolecular (possibly amorphous) phase.
An Update on the Pathogenesis of COVID-19 and the Reportedly Rare Thrombotic Events Following Vaccination (2021)

Today the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global health problem. After more than a year with the pandemic, although our knowledge has progressed on COVID-19, there are still many unknowns in virological, pathophysiological and immunological aspects. It is obvious that the most efficient solution to end this pandemic are safe and efficient vaccines. This manuscript summarizes the pathophysiological and thrombotic features of COVID-19 and the safety and efficacy of currently approved COVID-19 vaccines with an aim to clarify the recent concerns of thromboembolic events after COVID-19 vaccination. The influx of newer information is rapid, requiring periodic updates and objective assessment of the data on the pathogenesis of COVID-19 variants and the safety and efficacy of currently available vaccines.
Femtosecond laser fragmentation from water-dispersed microcolloids: toward fast controllable growth of ultrapure Si-based nanomaterials for biological applications (2013)

An ultrashort laser-assisted method for fast production of concentrated aqueous solutions of ultrapure Si-based colloidal nanoparticles is reported. The method profits from the 3D geometry of femtosecond laser ablation of water-dispersed microscale colloids, prepared preliminarily by the mechanical milling of a Si wafer, in order to avoid strong concentration gradients in the ablated material and provide similar conditions of nanocluster growth within a relatively large laser caustics volume. We demonstrate the possibility for the fast synthesis of non-aggregated, low-size-dispersed, crystalline Si-based nanoparticles, whose size and surface oxidation can be controlled by changing the initial microcolloid concentration and the amount of dissolved oxygen in the water. Due to their much superior purity compared to the chemically synthesized counterparts and their photoluminescence response, the nanoparticles present the possibility for biological in vivo applications such as drug vectoring, imaging, and therapeutics.
Similarity in Programs (2006)

Abstract. An overview of the concept of program similarity is presented. It divides similarity into two types—syntactic and semantic— and provides a review of eight categories of methods that may be used to measure program similarity. A summary of some applications of these methods is included. The paper is intended to be a starting point for a more comprehensive analysis of the subject of similarity in programs, which is critical to understand if progress is to be made in fields such as clone detection.
An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes. (1988)

We have identified a protein present only in erythroid cells that binds to two adjacent sites within an enhancer region of the chicken beta-globin locus. Mutation of the sites, so that binding by the factor can no longer be detected in vitro, leads to a loss of enhancing ability, assayed by transient expression in primary erythrocytes. Binding sites for the erythroid-specific factor (Eryf1) are found within regulatory regions for all chicken globin genes. A strong Eryf1 binding site is also present within the enhancer of at least one human globin gene, and proteins from human erythroid cells (but not HeLa cells) bind to both the chicken and the human sites.
Origin and Function of Circulating Plasmablasts during Acute Viral Infections (2012)

Activated B cells proliferate and differentiate into antibody-producing cells, long-lived plasma cells, and memory B cells after immunization or infection. Repeated encounter of the same antigen triggers the rapid re-activation of pre-existing specific memory B cells, which then potentially enter new germinal center reactions and differentiate into short-lived plasmablasts or remain in the system as memory B cells. Short-lived class-switched IgG and IgA plasmablasts appear in the circulation transiently and the frequency of these cells can be remarkably high. The specificities and affinities of single plasmablasts in humans have been reported for several viral infections, so far most extensively for influenza and HIV. In general, the immunoglobulin variable regions of plasmablasts are highly mutated and diverse, suggesting that plasmablasts are derived from memory B cells, yet it is unclear which memory B cell subsets are activated and whether activated memory B cells adapt or mature before differentiation. This review summarizes what is known about the phenotype and the origin of human plasmablasts in the context of viral infections and whether these cells can be predictors of long-lived immunity.
A Hybrid Electric Vehicle Thermal Management System - Nonlinear Controller Design (2015)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;The components in a hybrid electric vehicle (HEV) powertrain include the battery pack, an internal combustion engine, and the electric machines such as motors and possibly a generator. These components generate a considerable amount of heat during driving cycles. A robust thermal management system with advanced controller, designed for temperature tracking, is required for vehicle safety and energy efficiency. In this study, a hybridized mid-size truck for military application is investigated. The paper examines the integration of advanced control algorithms to the cooling system featuring an electric-mechanical compressor, coolant pump and radiator fans. Mathematical models are developed to numerically describe the thermal behavior of these powertrain elements. A series of controllers are designed to effectively manage the battery pack, electric motors, and the internal combustion engine temperatures. These controllers regulate the refrigerant compressor, coolant pump, and cooling fans to minimize the temperature fluctuations while reducing the overall cooling system power consumption. Simulation results for assault and convoy escort driving cycles are presented to show that the controllers meet the powertrain heat removal requirements. The battery core temperature can be tracked to within 0.8 °C of the target value, the internal (stator) temperature of electric motors can be maintained within 1.1 °C of the desired value. The coolant temperature at engine's outlet exhibited a 0.4 °C error range from the prescribed target value of 90 °C. The overall auxiliary power consumption of the cooling system is reduced by 45% when compared to a conventional cooling control method.&lt;/div&gt;&lt;/div&gt;
Allotransplanted DRG neurons or Schwann cells affect functional recovery in a rodent model of sciatic nerve injury (2014)

These results suggest that in complete peripheral nerve transections, surgical repair using nerve guide conduits with allotransplanted DRG and Schwann cells may improve recovery, especially DRG neurons, which elicit less of an immune response.
PH<sup>2</sup> - A dermoscopic image database for research and benchmarking (2013)

The increasing incidence of melanoma has recently promoted the development of computer-aided diagnosis systems for the classification of dermoscopic images. Unfortunately, the performance of such systems cannot be compared since they are evaluated in different sets of images by their authors and there are no public databases available to perform a fair evaluation of multiple systems. In this paper, a dermoscopic image database, called PH², is presented. The PH² database includes the manual segmentation, the clinical diagnosis, and the identification of several dermoscopic structures, performed by expert dermatologists, in a set of 200 dermoscopic images. The PH² database will be made freely available for research and benchmarking purposes.
SMAD4 loss in colorectal cancer: Correlation with recurrence, chemoresistance, and immune infiltrate. (2017)

587 Background: Few markers reliably identify colorectal cancer (CRC) patients at risk of recurrence and death. SMAD4 loss occurs in 10-20% of cases and has shown promise in identifying high-risk stage II/III patients. We examined SMAD4 status and association with clinical/pathologic features in 446 stage I-IV CRC patients at Memorial Sloan Kettering (MSK). Methods: Patients undergoing curative resection were included (1981-2010). Familial polyposis syndrome patients and those with inadequate tissue were excluded. Tissue microarrays were constructed (n=364). Immunohistochemistry for SMAD4 and mismatch repair (MMR) proteins was completed. SMAD4 nuclear stain intensity was scored (scale=0-3; 0=loss). On whole sections, MMR proteins (present or absent), tumor-infiltrating lymphocytes (TILs) and peritumoral lymphocyte aggregates (PLAs) were scored (scale=0-3). Associations between clinical/pathologic features and SMAD4 loss vs. retention were analyzed. Kaplan-Meier estimates and log-rank test were used for recurrence-free and overall survival analyses (RFS and OS). Results: SMAD4 loss was noted in 13%. Median age at diagnosis was 53 years, and 51% were male. The cohort consisted of 61% hindgut tumors and 62% stage II/III patients. With up to 33 years of follow-up, the mean was 6 years. SMAD4 loss correlated with higher tumor and nodal stage, adjuvant therapy use, and lower TIL and PLA scores (p&lt;0.04 for all). Unlike prior studies, no significant differences in OS based on SMAD4 status across the entire cohort were noted; however, older patients (&gt;median) were noted to have worse OS with SMAD4 loss (p&lt;0.01). SMAD4 loss did correlate with worse RFS (p=0.02), persisting even when excluding MMR-deficient patients. Additionally, SMAD4 loss was associated with worse RFS in both the adjuvant chemotherapy group (median RFS=3.8 vs. 13 years; p=0.06) and the resection-only group (median RFS=4.2 years vs. not yet reached; p&lt; 0.01). Conclusions: SMAD4 loss correlates with worse RFS and resistance to adjuvant therapy. SMAD4 loss also correlates with lower TIL and PLA scores. Future work will address chemoresistance mechanisms, relevance to adjuvant therapy use, and loss of immune infiltrate in SMAD4-null tumors.
Abstract 1501: Tumor cells engineered to codisplay on their surface 4-1BBL and LIGHT costimulatory proteins as a novel vaccine approach for cancer immunotherapy (2010)

Abstract Therapeutic vaccines based on whole tumor cells genetically modified to express various immunomodulatory molecules represent an important modality for the treatment of cancer. However, generation of genetically modified tumor cells as vaccine is not only cost, labor, and time intensive, but also has safety repercussions. As an alternative, we have recently developed the ProtEx™ technology that involves modification of the cell membrane with biotin and engineering of biotinylated cells with proteins of interest chimeric with core streptavidin. We herein tested if tumor cells can be engineered efficiently to simultaneously display on their surface two SA-chimeric costimulatory ligands, SA-4-1BBL and SA-LIGHT, and if vaccination with such engineered cells has better therapeutic efficacy than cells displaying single molecule in the TC-1 cervical cancer mouse model. The choice of 4-1BBL is due to pleiotropic immune activity of 4-1BBL to stimulate innate, adaptive immune responses as well as overcome various immune evasion mechanisms. The choice of LIGHT is due to its stimulatory effects on tumor stroma, which pose a physical barrier to the entry of effector immune cells to tumor site. Biotinylated TC-1 tumor cells codisplayed both chimeric costimulatory ligands on their surface with equal efficiency after incubation with equal molar of SA-4-1BBL and SA-LIGHT proteins. Vaccination with irradiated TC-1 tumor cells codisplaying both chimeric costimulatory ligands resulted in the generation of antigen specific T cell proliferative and killing responses, resulting in 100% efficacy in prophylactic and &amp;gt; 57% efficacy in therapeutic settings. In marked contrast, vaccination with TC-1 tumor cells displaying on their surface either of these molecules singly only delayed the tumor growth in the prophylactic setting. Vaccine efficacy was associated with effective generation of primary and memory T cell and Ab responses, enhanced CD8+ T cell infiltration into the tumor, IFN-γ production, and tumor-specific killing. In conclusion, engineering tumor cells in a rapid and effective manner to simultaneously display on their surface a collection of immunostimulatory molecules with distinct immune functions presents a novel approach with considerable potential for cancer immunotherapy. Funded in parts by NIH 2R44 AI071618-02, R43 AI074176, R41 CA121665, KLCP, the W.M. Keck Foundation, and the Commonwealth of Kentucky Research Challenge Trust Fund. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1501.
Tuning the Surface Chemistry of Second-Harmonic-Active Lithium Niobate Nanoprobes Using a Silanol–Alcohol Condensation Reaction (2021)

The surface functionalization of nanoparticles (NPs) is of great interest for improving the use of NPs in, for example, therapeutic and diagnostic applications. The conjugation of specific molecules with NPs through the formation of covalent linkages is often sought to provide a high degree of colloidal stability and biocompatibility, as well as to provide functional groups for further surface modification. NPs of lithium niobate (LiNbO<sub>3</sub>) have been explored for use in second-harmonic-generation (SHG)-based bioimaging, expanding the applications of SHG-based microscopy techniques. The efficient use of SHG-active LiNbO<sub>3</sub> NPs as probes will, however, require the functionalization of their surfaces with molecular reagents such as polyethylene glycol and fluorescent molecules to enhance their colloidal and chemical stability and to enable a correlative imaging platform. Herein, we demonstrate the surface functionalization of LiNbO<sub>3</sub> NPs through the covalent attachment of alcohol-based reagents through a silanol-alcohol condensation reaction. Alcohol-based reagents are widely available and can have a range of terminal functional groups such as carboxylic acids, amines, and aldehydes. Attaching these molecules to NPs through the silanol-alcohol condensation reaction could diversify the reagents available to modify NPs, but this reaction pathway must first be established as a viable route to modifying NPs. This study focuses on the attachment of a linear alcohol functionalized with carboxylic acid and its use as a reactive group to further tune the surface chemistry of LiNbO<sub>3</sub> NPs. These carboxylic acid groups were reacted to covalently attach other molecules to the NPs using copper-free click chemistry. This derivatization of the NPs provided a means to covalently attach polyethylene glycols and fluorescent probes to the NPs, reducing NP aggregation and enabling multimodal tracking of SHG nanoprobes, respectively. This extension of the silanol-alcohol condensation reaction to functionalize the surfaces of LiNbO<sub>3</sub> NPs can be extended to other types of nanoprobes for use in bioimaging, biosensing, and photodynamic therapies.
Construction and characterization of new piggyBac vectors for constitutive or inducible expression of heterologous gene pairs and the identification of a previously unrecognized activator sequence in piggyBac (2007)

This study is significant because (a) it demonstrates the utility of a strategy for the construction of piggyBac vectors that can provide constitutive or inducible heterologous gene pair expression and (b) it reveals the presence of a previously unrecognized transcriptional activator in piggyBac, which is an important and increasingly utilized transposable element.
A von Willebrand factor fragment containing the D′D3 domains is sufficient to stabilize coagulation factor VIII in mice (2014)

Plasma factor VIII (FVIII) and von Willebrand factor (VWF) circulate together as a complex. We identify VWF fragments sufficient for FVIII stabilization in vivo and show that hepatic expression of the VWF D'D3 domains (S764-P1247), either as a monomer or a dimer, is sufficient to raise FVIII levels in Vwf(-/-) mice from a baseline of ∼5% to 10%, to ∼50% to 100%. These results demonstrate that a fragment containing only ∼20% of the VWF sequence is sufficient to support FVIII stability in vivo. Expression of the VWF D'D3 fragment fused at its C terminus to the Fc segment of immunoglobulin G1 results in markedly enhanced survival in the circulation (t1/2 > 7 days), concomitant with elevated plasma FVIII levels (>25% at 7 days) in Vwf(-/-) mice. Although the VWF D'D3-Fc chimera also exhibits markedly prolonged survival when transfused into FVIII-deficient mice, the cotransfused FVIII is rapidly cleared. Kinetic binding studies show that VWF propeptide processing of VWF D'D3 fragments is required for optimal FVIII affinity. The reduced affinity of VWF D'D3 and VWF D'D3-Fc for FVIII suggests that the shortened FVIII survival in FVIII-deficient mice transfused with FVIII and VWF D'D3/D'D3-Fc is due to ineffective competition of these fragments with endogenous VWF for FVIII binding.
Formulation optimization of long-acting depot injection of aripiprazole by using D-optimal mixture design. (2009)

Non-adherence to medication specifications is a major cause for poor outcomes in the therapy of schizophrenia. In situ implantable preparation of aripiprazole, an atypical antipsychotic drug, was intended with the aim to improve the patient compliance and to offer an effective antipsychotic drug therapy. D-optimal mixture design was employed to design and optimize long-acting depot injection of aripiprazole using polylactide-co-glycolide (PLGA) 50:50, 75:25, 85:15, and cholesterol as release rate-retarding material. Desirability technique was used for the optimization of formulation. Predicted optimized formulation was experimentally validated, and it was found that the developed formulation releases the drug for a 14-day time period. The optimized formulation showed that the cholesterol-containing formulation exhibits a better drug release profile. The pharmacokinetic studies confirmed that the developed cholesterol-based depot formulation was capable of releasing the drug for a time period of more than 14 days. The implant formulation was sterilized by gamma radiation and ethylene oxide sterilization method. The D-optimal mixture design was proved to be an efficient technique for the formulation optimization.
Retrieval of leukocyte antigens in paraffin-embedded rat tissues. (1996)

We compared the immunohistochemical reactivity of various rat leukocyte antigens in frozen and paraffin-embedded thymus, spleen, abdominal lymph node, liver, and brain tissues of healthy Sprague-Dawley rats, fixed in various fixatives. Immune reactivity after fixation in Methacarn was superior to that of 4% neutral buffered formalin, a mercury-based fixative (B-5), or Carnoy. Microwave (MW) antigen retrieval (AR) enhanced antigen reactivity. Ten of the 11 leukocyte antigens studied could be retrieved in Methacarn-fixed, paraffin-embedded sections with a reactivity comparable to that obtained on frozen sections.