gebhart/patrepeval huggingface dataset:
Expression of liver-specific member of the 3 beta-hydroxysteroid dehydrogenase family, an isoform possessing an almost exclusive 3-ketosteroid reductase activity. (1992)

We have recently characterized two types of rat 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) isoenzymes expressed in adrenals and gonads. In addition, we have cloned a third type of cDNA encoding a predicted type III 3 beta-HSD protein specifically expressed in the male rat liver which shares 80% similarity with the two other isoenzymes. Transient expression in human HeLa cells of the cDNAs reveals that the type III 3 beta-HSD protein does not display oxidative activity for the classical substrates of 3 beta-HSD, in contrast to the type I 3 beta-HSD isoenzyme. However, in the presence of NADH, type III isoenzyme, in common with the type I isoform, converts 5 alpha-androstane-3,17-dione (A-dione) and 5 alpha-dihydrotestosterone (DHT) to the corresponding 3 beta-hydroxysteroids. In fact, the type I and the type III isoenzymes have the same affinity for DHT with Km values of 5.05 and 6.16 microM, respectively. When NADPH is used as cofactor, the affinity for DHT of the type III isoform becomes higher than that of the type I isoform with Km values of 0.12 and 1.18 microM, respectively. The type III isoform is thus a 3-ketoreductase using NADPH as preferred cofactor which is responsible for the conversion of 3-keto-saturated steroids such as DHT and A-dione into less active steroids.
FUNCTIONAL OUTCOME OF THE ROBOT ASSISTED MINIMAL INVASIVE UNICOMPARTMENTAL KNEE ARTHROPLASTY AT 18 MONTHS (2008)

A Prospective, randomised controlled trial demonstrates superior outcomes using an active constraint robot compared with conventional surgical technique in unicompartmental knee arthroplasty (UKA). Computer assistance should extinguish outliers in arthroplasty, with robotic systems being able to execute the preoperative plan with millimetre precision. We used the Acrobot system to deliver tailor made surgery for each individual patient. A total of 27 patients (28 knees) awaiting unicompartmental knee arthroplasty were randomly assigned to have the operation performed either with the assistance of the Acrobot or conventionally. CT scans were obtained with coarse slices through hips and ankles and fine slices through the knee joint. Preoperative 3D plans were made and transferred to the Acrobot system in theatre, or printed out as a conventional surgical aid. Accurate co-registration was confirmed, prior to the surfaces of the femur and tibia being milled. The outcome parameters included measurements of the American Knee Society (AKS) score and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index. These measurements were performed pre-operatively and at six, 18 weeks, and 18 months post-operatively. After 18 months two UKA out of the conventional trial (n =15) had been revised into a total knee replacement (TKA), whereas there were no revisions in the Acrobot trial group (n = 13). Using an active constrained robot to assist the surgeon was significantly more accurate than the conventional surgical technique. This study has shown a direct correlation between accuracy and improvement in knee scores at 6, 18 weeks and 18 months after surgery. At 18 months there continues to be a significant improvement in the knee scores with again a marked correlation between radiological accuracy and clinical outcome with higher accuracy leading to better function based on the WOMAC and American Knee Society Score.
Proteomic Analysis of Temperature-Dependent Changes in Stored UHT Milk (2011)

Molecular changes in milk proteins during storage of UHT-treated milk have been investigated using two-dimensional electrophoresis (2-DE) coupled to MALDI-TOF mass spectrometry. UHT-treated samples were stored at three different temperatures, 4 °C, 28 °C, and 40 °C, for two months. Three main changes could be observed on 2-DE gels following storage. They were (1) the appearance of diffuse staining regions above the position of the monomeric caseins caused by nondisulfide cross-linking of α and β-caseins; (2) the appearance of additional acidic forms of proteins, predominantly of α(S1)-casein, caused by deamidation; and (3) the appearance of "stacked spots" caused by lactosylation of whey proteins. The extent of the changes increased with increased storage temperature. Mass spectrometric analysis of in-gel tryptic digests showed that the cross-linked proteins were dominated by α(S1)-casein, but a heterogeneous population of cross-linked forms with α(S2)-casein and β-casein was also observed. Tandem MS analysis was used to confirm deamidation of N(129) in α(S1)-casein. MS analysis of the stacked spots revealed lactosylation of 9/15 lysines in β-lactoglobulin and 8/12 lysines in α-lactalbumin. More extensive analysis will be required to confirm the nature of the cross-links and additional deamidation sites in α(S1)-casein as the highly phosphorylated nature of the caseins makes them challenging prospects for MS analysis.
Influence of Encapsulated Aroma Compounds on the Formation and Morphology of Gelatin Microparticles (2019)

In the present work aromatic essential oils obtained from orange (OO), basil (BO), cinnamon (CNO), and citronella (CO) were encapsulated in natural gelatin matrices through inverse suspension processes and the effects of oil encapsulation on the formation and morphology of the obtained gelatin microspheres were analyzed. Particularly, it is shown that each oil affected the course of the encapsulation process differently, leading to decrease of the viscosity of the dispersed phase of almost 70% during the reaction course, when compared with oil‐free gelatin solutions. Additionally, the interfacial tensions of the aqueous solutions containing essential oils were slightly higher than in absence of oils. Particle size distributions of the final particles were relatively broad, while the obtained beads presented spherical morphology and irregular surfaces. Finally, the thermal resistances of the oil‐containing microparticles were higher than observed in absence of oil, despite the relatively low oil contents of the final products.
Use of 3-Dimensional Volumetric Modeling of Adrenal Gland Size in Patients with Primary Pigmented Nodular Adrenocortical Disease (2016)

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare type of bilateral adrenal hyperplasia leading to hypercortisolemia. Adrenal nodularity is often appreciable with computed tomography (CT); however, accurate radiologic characterization of adrenal size in PPNAD has not been studied well. We used 3-dimensional (3D) volumetric analysis to characterize and compare adrenal size in PPNAD patients, with and without Cushing's syndrome (CS). Patients diagnosed with PPNAD and their family members with known mutations in PRKAR1A were screened. CT scans were used to create 3D models of each adrenal. Criteria for biochemical diagnosis of CS included loss of diurnal variation and/or elevated midnight cortisol levels, and paradoxical increase in urinary free cortisol and/or urinary 17-hydroxysteroids after dexamethasone administration. Forty-five patients with PPNAD (24 females, 27.8±17.6 years) and 8 controls (19±3 years) were evaluated. 3D volumetric modeling of adrenal glands was performed in all. Thirty-eight patients out of 45 (84.4%) had CS. Their mean adrenal volume was 8.1 cc±4.1, 7.2 cc±4.5 (p=0.643) for non-CS, and 8.0cc±1.6 for controls. Mean values were corrected for body surface area; 4.7 cc/kg/m(2)±2.2 for CS, and 3.9 cc/kg/m(2)±1.3 for non-CS (p=0.189). Adrenal volume and midnight cortisol in both groups was positively correlated, r=0.35, p=0.03. We conclude that adrenal volume measured by 3D CT in patients with PPNAD and CS was similar to those without CS, confirming empirical CT imaging-based observations. However, the association between adrenal volume and midnight cortisol levels may be used as a marker of who among patients with PPNAD may develop CS, something that routine CT cannot do.
Human correlates of a rat model of preeclampsia (2005)

Preeclampsia is a disorder which affects between 3 and 10% of all pregnancies. It is the second leading cause of fetal wastage and maternal morbidity and mortality. It is characterized by hypertension, proteinuria and, often, excessive edema as well as intrauterine growth restriction (IUGR). Progress in the understanding of the etiology (etiologies) of this disorder has been impeded by the lack of suitable animal models of the early events in its pathogenesis. We have developed a rat model of this syndrome by inducing excessive volume expansion utilizing the administration of desoxycorticosterone acetate (DOCA) and replacing the drinking water of pregnant animals with 0.9% saline. As reported elsewhere, these animals develop hypertension, proteinuria and IUGR. They do not develop glomerular endotheliosis, hematologic or hepatic sequelae, reduced glomerular filtration rate (GFR) or eclampsia. To determine if there is a group of preeclamptic patients who have the same phenotypic characteristics as our animals, we performed a retrospective search of 100 charts of patients discharged with a diagnosis of preeclampsia. Thirty-two of these patients had all of the data available to allow us to draw conclusions. We considered IUGR to be present if birth weight was below the 10th percentile for gestational age. We found 15 of these 32 patients who demonstrated hypertension (>140/80), proteinuria(> 300 mg /24 hours) and IUGR. Seven of these 15 patients had GFRs that were within the range expected for their gestational age. We conclude that there is a group of human patients whose characteristics mirror those of our animal model. Accordingly, there is a human counterpart of this rodent model of preeclampsia that is related to excessive expansion of the extracellular fluid volume.
Prodromal Spinocerebellar Ataxia Type 2 Subjects Have Quantifiable Gait and Postural Sway Deficits (2020)

This study demonstrates early alteration of gait and postural sway control in prodromal SCA2 using a wearable sensor-based system. This offers new pathophysiological hints into this early disease stage and provides novel potential biomarkers for future clinical trials. © 2020 International Parkinson and Movement Disorder Society.
Language Model Cascades (2022)

Prompted models have demonstrated impressive few-shot learning abilities. Repeated interactions at test-time with a single model, or the composition of multiple models together, further expands capabilities. These compositions are probabilistic models, and may be expressed in the language of graphical models with random variables whose values are complex data types such as strings. Cases with control flow and dynamic structure require techniques from probabilistic programming, which allow implementing disparate model structures and inference strategies in a unified language. We formalize several existing techniques from this perspective, including scratchpads / chain of thought, verifiers, STaR, selection-inference, and tool use. We refer to the resulting programs as language model cascades.
Directed Metabolic Pathway Evolution Enables Functional Pterin-Dependent Aromatic-Amino-Acid Hydroxylation in Escherichia coli (2020)

Tetrahydrobiopterin-dependent hydroxylation of aromatic amino acids is the first step in the biosynthesis of many neuroactive compounds in humans. A fundamental challenge in building these pathways in <i>Escherichia coli</i> is the provision of the non-native hydroxylase cofactor, tetrahydrobiopterin. To solve this, we designed a genetic selection that relies on the tyrosine synthesis activity of phenylalanine hydroxylase. Using adaptive laboratory evolution, we demonstrate the use of this selection to discover: (1) a minimum set of heterologous enzymes and a host <i>folE</i> (T198I) mutation for achieving this type of hydroxylation chemistry in whole cells, (2) functional complementation of tetrahydrobiopterin by indigenous cofactors, and (3) a tryptophan hydroxylase mutation for improving protein abundance. Thus, the goal of having functional aromatic-amino-acid hydroxylation in <i>E. coli</i> was achieved through directed metabolic pathway evolution.
Extended abstract: Theorem proving verification of privacy in WBSN for healthcare systems (2013)

This extended abstract presents a work in progress on improving the verification of the security requirements of Wireless Body Sensor Network (WBSN) in healthcare systems. Our investigation on this shows that most researchers are mainly using simulation to test healthcare systems. However, lack of simulation frameworks that support security, makes this method an improper technique to verify security in WBSN. Thus, a formal verification technique is proposed in this work for the verification of security aspects in healthcare systems. We adopt a firstorder theorem proving method (Event-B) to model WBSN and verify security requirements such as privacy at different levels of abstraction.
Temperature and pH Effects on the Coadsorption of Sodium Dodecyl Sulfate and Poly(ethylenimine) (2002)

The polar orientation and alkyl chain conformational ordering of sodium dodecyl sulfate (SDS) at the octadecanethiol/water hydrophobic interface have been investigated using sum frequency vibrational spectroscopy (SFS). The effects of different concentrations of the cationic polymer poly(ethylenimine), PEI, along with the solution pH and temperature have been determined. PEI was found to promote synergistic adsorption of ordered SDS at concentrations as low as 10 ppm at pH 6.0 through cooperative polymer/surfactant complex formation. At lower pH's and in the presence of the polymer stronger interfacial ordering of the surfactant was observed, attributed to increased protonation of PEI amino groups in acidic solutions and consequent decreases in the intersurfactant spacings of complexed SDS. SDS was found to be present at the hydrophobic surface at temperatures of up to 60 °C, although thermally induced motion of the surfactant chains resulted in a monotonic decrease in the degree of conformational order with rising temperature. In the presence of PEI the effect of temperature on the ordering of SDS, present predominantly in the form of a polymer/surfactant complex, was qualitatively similar.
RESURF p-n Diode With a Buried Layer, a Comprehensive Study (2013)

In this paper, important parameters of the p-buried layer of a high-voltage reduced surface field p-n diode are analyzed and discussed in terms of effects on device performance, including breakdown voltage and specific turn-on resistance, R <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">on,sp</sub> . Guidelines for optimizing the vertical position, lateral location, and doping concentration of the p-buried layer are suggested. The experimental results demonstrate that the p-n diode with the proposed p-buried layer optimization design can improve breakdown voltage by 30.7% but only increases 2.7% in specific on-resistance R <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">on,sp</sub> .
Design and implementation of a shielded underwater vector sensor for laboratory environments (2011)

Underwater acoustic vector sensors, for measuring acoustic intensity, are typically used in open water where electromagnetic interference (EMI) is generally not a contributor to overall background noise. However, vector sensors are also useful in a laboratory setting where EMI can be a limiting factor at low frequencies. An underwater vector sensor is designed and built with specific care for EMI immunity. The sensor, and associated signal processing, is shown to reduce background noise at EMI frequencies by 10-50 dB and 10-20 dB across the entire frequency bandwidth, as compared to an identical unshielded vector sensor.
Role of Cbfa1 in Ameloblastin Gene Transcription (2001)

Ameloblastin is a tooth-specific extracellular matrix protein that is thought to play a role in enamel crystal formation in the developing dentition. The murine ameloblastin promoter functions in a cell type-specific manner and contains cis-acting elements that function both to enhance and to suppress transcription. The objective of this study was to determine whether the transcription factor Cbfa1, known to be essential for transcription of other mineralized tissue genes, is also required for ameloblastin transcription. Site-directed mutagenesis of the Cbfa1-binding site (-248 base pairs) termed osteoblast-specific element 2 (OSE2) decreased ameloblastin promoter activity by greater than 50% in ameloblast-like cells. No differences in promoter activity were observed in two other oral tissue-derived cell lines transfected with similar constructs. Nuclear factor binding to the ameloblastin promoter was also shown to be cell type-specific and was altered by site-specific mutations in the OSE2 site. Cbfa1 was specifically shown to participate in the DNA-protein complexes between nuclear factors and the ameloblastin OSE2 site by supershift electrophoretic mobility shift assays. The findings that Cbfa1 interacts with functionally important regions of the ameloblastin promoter while promoter activity is diminished in constructs containing site-directed mutations in the Cbfa1 site indicate that Cbfa1 possesses an important function in transcription of the ameloblastin gene.
Whither Compatibility Testing? (1989)

Excipient compatibility studies are of limited value in the selection of ingredients which will provide a stable dosage form. These empirical tests are often substituted for estimates of potential instability based on known chemical interactions. They are inefficient, and their predictive value has not been rigorously established. It is more meaningful and economical to prepare initial formulations for stability screening than to test for excipient compatibilities in powder mixtures
N-terminal Transmembrane-Helix Epitope Tag for X-ray Crystallography and Electron Microscopy of Small Membrane Proteins (2021)

Structural studies of membrane proteins, especially small membrane proteins, are associated with well-known experimental challenges. Complexation with monoclonal antibody fragments is a common strategy to augment such proteins; however, generating antibody fragments that specifically bind a target protein is not trivial. Here we identify a helical epitope, from the membrane-proximal external region (MPER) of the gp41-transmembrane subunit of the HIV envelope protein, that is recognized by several well-characterized antibodies and that can be fused as a contiguous extension of the N-terminal transmembrane helix of a broad range of membrane proteins. To analyze whether this MPER-epitope tag might aid structural studies of small membrane proteins, we determined an X-ray crystal structure of a membrane protein target that does not crystallize without the aid of crystallization chaperones, the Fluc fluoride channel, fused to the MPER epitope and in complex with antibody. We also demonstrate the utility of this approach for single particle electron microscopy with Fluc and two additional small membrane proteins that represent different membrane protein folds, AdiC and GlpF. These studies show that the MPER epitope provides a structurally defined, rigid docking site for antibody fragments that is transferable among diverse membrane proteins and can be engineered without prior structural information. Antibodies that bind to the MPER epitope serve as effective crystallization chaperones and electron microscopy fiducial markers, enabling structural studies of challenging small membrane proteins.
Theoretical analysis of focus wedge mark for best-focus determination in photolithography (2014)

The focus wedge mark (FWM), a periodic array of wedge shaped marks, is a tool used to determine the best-focus position in photolithography. Here, we develop a one-dimensional physical model for the FWM and analyze the focus dependence of the wedge length under coherent imaging conditions. The amplification factor of the FWM, which describes the superiority of the FWM compared to measurements based on line and space marks, is determined by the geometrical magnification of the wedge. We show that around the exposure dose energy typically used in lithography the amplification factor is much higher than the geometrical magnification. Numerical lithography simulations confirm that the focus sensitivity of the FWM is much higher than that of a line and space pattern.
Structural/Chemical Characterization and Bond Strength of a New Self-Adhesive Bulk-fill Restorative. (2020)

While Su-O_LC bonded effectively and durably to FLAT dentin, Su-O_SC bonded more favorably than Su-O_LC in class-I cavities, which was probably related to shrinkage stress variously challenging the respective bond.
Self-Stabilizing Systems (2006)

This note was written upon reading Dijkstra’s classic paper “Self-stabilizing Systems in Spite of Distributed Control” that appeared in the November 1974 issue of CACM (see [58]). It generalizes one of the algorithms in Dijkstra’s paper from a line of processes to an arbitrary tree of processes. It also discusses the self-stabilizing properties of the bakery algorithm. I never tried to publish this note–probably because I regarded it as too small a piece of work to be worth a paper by itself. The note contains the intriguing sentence: “There is a complicated modified version of the bakery algorithm in which the values of all variables are bounded.” I never wrote down that version, and I’m not sure what I had in mind. But I think I was thinking of roughly the following modification. As a process waits to enter its critical section, it keeps reducing its number, not entering the critical section until its number equals one. A process p can reduce its number by at most one, and only when the next lower-numbered process’s number is at least two less than p’s number, and the next higher-numbered process is within one of p’s number. I think I intended to use the techniques of [25] to allow reading and writing of numbers to remain non-atomic while maintaining the order of waiting processes. (If eventually all processes stop changing their numbers, then all processes will eventually read the correct numbers, allowing some process to progress.) At one time, I convinced myself that this algorithm is correct. But I never wrote a rigorous proof, so I don’t know if it really works. Filling in the details and proving correctness should be a nice exercise.
Integration of Virtual and High Throughput Screening in Lead Discovery Settings (2011)

In the last decade mass screening strategies became the main source of leads in drug discovery settings. Although high throughput (HTS) and virtual screening (VS) realize the same concept the different nature of these lead discovery strategies (experimental vs theoretical) results that they are typically applied separately. The majority of drug leads are still identified by hit-to-lead optimization of screening hits. Structural information on the target as well as on bound ligands, however, make structure-based and ligand-based virtual screening available for the identification of alternative chemical starting points. Although, the two techniques have rarely been used together on the same target, here we review the existing prominent studies on their true integration. Various approaches have been shown to apply the combination of HTS and VS and to better use them in lead generation. Although several attempts on their integration have only been considered at a conceptual level, there are numerous applications underlining its relevance that early-stage pharmaceutical drug research could benefit from a combined approach.