gebhart/patrepeval huggingface dataset:
Simultaneous monitoring of monoclonal antibody variants by strong cation-exchange chromatography hyphenated to mass spectrometry to assess biosimilar-ity of rituximab-based biotherapeutics (2021)

The increasing importance of biosimilars in the biopharmaceutical market leads to high demands for enhanced protein characterization methods. Different manufacturing processes can lead to a significant variability of biotherapeutics arising from chemical and enzymatic post translational modifications (PTMs), resulting in the co-existence of a plethora of proteoforms with different physicochemical properties. Thus, biosimilarity to the originator product must be proven rigorously. Among these PTMs, N-terminal pyroglutamate formation, C-terminal lysine clipping, glycosylation, glycation, and deamidation lead to differences in the net charge of the protein, resulting in charge variants (CV). To unravel the heterogeneity of these proteoforms, Strong Cat-ion eXchange (SCX) High-Performance Liquid Chromatography (HPLC) is routinely used. However, the use of non-volatile salts makes the technique incompatible for hyphenation to mass spectrometry (MS). Recently, an approach employing volatile salts and a pH gradient was applied for CV analysis, opening the era of SCX-HPLC-MS approaches. Here, we apply an already established SCX-HPLC-MS approach by Füssl et al. to characterize two Rituximab-based biotherapeutics, the originator MabThera® and its Indian copy product Reditux™. The study assessed molecular differences between the two drug products and constitutes the basis for biosimilarity characterization using a fast SCX-HPLC-MS approach.
Isotope Labeling Studies of the Oxidation of Silicon at 1000° and 1300°C (1984)

Oxygen‐18 profiles in thermal oxides grown on silicon at 1000° and 1300°C in sequential oxidation steps in the parabolic oxidation regime indicate a change in the dominant oxygen transport process. At 1000°C, oxygen‐18 pile‐up at the surface and at the oxide/silicon interface is consistent with a large flux of oxygen via molecular oxygen permeation and very slow diffusion of lattice oxygen ions . At 1300°C, the oxygen‐18 concentration is uniformly high across the oxide, which suggests a much larger lattice oxygen diffusivity and a total flux due to lattice oxygen diffusion which contributes significantly to the supply of oxygen to the growth interface.
An Equivalent Circuit Model for CMOS Multi-level Spiral Inductors (2005)

This paper presents a simple structure wide-band equivalent circuit model for multi-level spiral inductor on silicon substrates.In our proposed model,skin effect and proximity effect are well modeled by additional RL branch and mutual inductance.Verification with measurement data from a series of novel spiral inductors in 2P4M Si process demonstrates accurate performance over wide band frequency range.
Orotidylate decarboxylase: insights into the catalytic mechanism from substrate specificity studies (1992)

Pyrimidine nucleotides were tested as substrates for pure yeast orotidylate decarboxylase in an attempt to gain insight into the nature of the catalytic mechanism of the enzyme. Substitutions of the 5-position in the pyrimidine ring of the orotidylate substrate resulted in compounds that are either excellent inhibitors or substrates of the enzyme. The 5-bromo- and 5-chloroorotidylates are potent inhibitors while the 5-fluoro derivative is a good substrate with a turnover number 30 times that observed with orotidylate. When carbon 5 of the pyrimidine ring is replaced by nitrogen in 5-azaorotidylate, the resulting compound is unstable in solution with a half-life of 25 min at pH 6. However, studies with freshly generated 5-azaorotidylate show that an enzyme-dependent reaction occurs, presumably decarboxylation. This enzyme reaction follows simple Michaelis-Menten kinetics. Because the 5-aza group is not electrophilic, an enzyme mechanism utilizing a nucleophilic addition of the enzyme at the 5-position is ruled out. We also present studies that are not compatible with a mechanism requiring the formation of a Schiff's base prior to decarboxylation. The enzyme is tolerant of modest substitution at the 4-position, for the 4-keto group can be replaced with a thioketone. However, no catalysis is observed when the same substitution is made at the 2-position. Similarities in the substrate specificity of orotate phosphoribosyltransferase and orotidylate decarboxylase led us to compare the amino acid sequences of the two enzymes; significant (20%) sequence homology was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Total Synthesis and Stereochemical Revision of the Chlorinated Sesquiterpene (±)‐Gomerone C (2012)

Revised: the total synthesis of gomerone C results in revision of the stereochemical assignment at C3. The synthetic strategy relies on a late-stage Conia-ene reaction, which efficiently forms the bicyclo[3.2.1]octane containing the bridgehead chloride and generates an exocyclic olefin, which can be used as a flexible handle for further elaboration. The two contiguous quaternary centers are installed by means of a Diels-Alder reaction.
X-ray diffraction studies of the arrangement of collagenous fibres in human fetal intervertebral disc. (1980)

X-ray diffraction shows that the arrangement of collagenous fibres in the annulus fibrosus of the fetal intervertebral disc is essentially the same as in the adult tissue. Collagen fibrils, when first forming, are apparently laid down with the same orientation as in the adult. Mechanical stress is suggested as a possible morphogenic factor. Mean values for the fibre tilt and its angular spread are calculated for anterior, posterior and lateral regions of the annulus.
Hepatic fatty acid synthase gene transcription is induced by a dietary copper deficiency (1997)

A dietary copper (Cu) deficiency is associated with a twofold increase in hepatic fatty acid biosynthesis. We hypothesized that the induction of hepatic lipogenesis associated with a dietary Cu deficiency reflected an enhanced expression of genes encoding lipogenic enzymes, i.e., fatty acid synthase (FAS). Male weanling rats were pair-meal fed for 42 days a high-sucrose diet that was Cu deficient (CuD; 0.7 microgram Cu/g) or Cu adequate (CuA; 5.0 micrograms Cu/g). The CuD diet increased FAS enzymatic activity twofold (P < 0.05). This rise in enzymatic activity was accompanied by a threefold increase in FAS mRNA and a 2.5-fold increase in FAS gene transcription (P < 0.05). Neither the mRNA abundance nor the rate of gene transcription for phosphoenolpyruvate carboxykinase or beta-actin was affected by the CuD diet. The induction of FAS gene transcription was associated with a 65-85% increase in hepatic reduced glutathione (GSH; P < 0.05). When hepatic GSH synthesis was suppressed by treating CuD rats with L-buthionine sulfoximine, the induction of FAS expression was completely prevented. Similarly, feeding N-acetylcysteine to CuA rats increased hepatic GSH levels 2.5-fold, and this was accompanied by a significant induction in FAS expression. These data indicate that the increase in hepatic lipogenesis associated with a Cu deficiency reflects an induction in hepatic lipogenic gene transcription (i.e., FAS) and that the rate of gene transcription may be dependent on hepatic thiol redox.
Structural basis for the inactivation of the P54 mutant of .beta.-lactamase from Staphylococcus aureus PC1 (1991)

The crystal structure of a mutant protein of a class A beta-lactamase from Staphylococcus aureus PC1, in which Asp179 is replaced by an asparagine (P54), has been determined and refined at 2.3-A resolution (1 A = 0.1 nm). The resulting crystallographic R factor [formula: see text] are the observed and calculated structure factor amplitudes) is 0.181 for 12289 reflections with I greater than or equal to sigma (I) within the 6.0-2.3-A resolution range. The mutated residue is located at the C-terminus of an extensive loop (the omega-loop), remote from the active site, and results in a drastically reduced activity. Examination of the native and P54 structures reveals that the overall fold is similar, except that there is substantial disorder of the omega-loop of P54. This is a consequence of the elimination of a salt bridge between Asp179 and Arg164 that links the two ends of the omega-loop in native beta-lactamase. It is associated with a difference in side-chain conformation between Asn179 in P54 and Asp179 in the native structure. An alternate interaction occurs in P54 between Asn179 and Ala69, adjacent to the catalytic Ser70. This disorder affects catalysis since some of the disordered residues, in particular Glu166, form part of the active site.(ABSTRACT TRUNCATED AT 250 WORDS)
Lipid Mediators in Critically Ill Patients: A Step Towards Precision Medicine (2020)

A dysregulated response to systemic inflammation is a common pathophysiological feature of most conditions encountered in the intensive care unit (ICU). Recent evidence indicates that a dysregulated inflammatory response is involved in the pathogenesis of various ICU-related disorders associated with high mortality, including sepsis, acute respiratory distress syndrome, cerebral and myocardial ischemia, and acute kidney injury. Moreover, persistent or non-resolving inflammation may lead to the syndrome of persistent critical illness, characterized by acquired immunosuppression, catabolism and poor long-term functional outcomes. Despite decades of research, management of many disorders in the ICU is mostly supportive, and current therapeutic strategies often do not take into account the heterogeneity of the patient population, underlying chronic conditions, nor the individual state of the immune response. Fatty acid-derived lipid mediators are recognized as key players in the generation and resolution of inflammation, and their signature provides specific information on patients' inflammatory status and immune response. Lipidomics is increasingly recognized as a powerful tool to assess lipid metabolism and the interaction between metabolic changes and the immune system <i>via</i> profiling lipid mediators in clinical studies. Within the concept of precision medicine, understanding and characterizing the individual immune response may allow for better stratification of critically ill patients as well as identification of diagnostic and prognostic biomarkers. In this review, we provide an overview of the role of fatty acid-derived lipid mediators as endogenous regulators of the inflammatory, anti-inflammatory and pro-resolving response and future directions for use of clinical lipidomics to identify lipid mediators as diagnostic and prognostic markers in critical illness.
Effect of annealing on photocatalytic activities of hydrothermally grown ZnO nanorods (2013)

We investigated the effect of postfabrication annealing on optical and photocatalytic properties of hydrothermally grown zinc oxide nanorods. Three annealing conditions (oxygen flow, forming gas flow, and zinc ambient) were performed at 250 °C and 350 °C. Optical properties (photoluminescence spectra) and photocatalytic activities of the rods were examined. Effects of annealing on the optical properties and photocatalytic activities of hydrothermally grown ZnO nanorods were discussed in detail.
During canine viscero-cutaneous leishmaniasis the anti-Hsp70 antibodies are specifically elicited by the parasite protein (1996)

A Leishmania infantum cDNA library was screened with sera from dogs with viscero-cutaneous leishmaniasis. Sequence analysis of a positive clone isolated from the library revealed that it coded for the carboxyl-terminal region of a member of the 70-kDa heat-shock protein family. The full-length sequence of the L. infantum hsp70 gene was determined after isolation of genomic clones. This protein shows a high degree of sequence conservation with the homologous protein from other organisms. To test its antigenicity a recombinant Hsp70 protein fused to the maltose-binding protein was produced in Escherichia coli using the expression vector pMAL-cRI. By FAST-ELISA assays it was observed that while the complete recombinant protein was recognized by 100% of the sera, the 20 carboxyl-terminal amino acids of the protein were only recognized by 30% of those sera. Thus, although a B-cell epitope must be present within the carboxyl terminal end of the protein other antigenic determinant(s) must reside out of this region. The analysis of the cross-reactivity with mouse Hsp70 by Western blotting strongly suggests that the anti-Hsp70 antibodies generated by infection with L. infantum are directed at specific determinants of the L. infantum Hsp70. Thus, our results indicate that anti-Hsp70 autoantibodies are not induced during Leishmania infection.
A Method of Remote Fault Diagnosis Based on Analytical Hierarchy Process (2008)

This paper presents a method for neural network ensemble. In the method, five subsystems of classifier used four kinds of neural networks, such as SOM,PNN,LVQ,RBF. Those neural networks compute parallel which have been trained solely The recognition result of subsystems, the expectation and variance between input pattern and goal pattern have been integrated by analytical hierarchy process. In experiments, the proposed methods have been successfully evaluated using thirteen different datasets, it is more effective than the relative majority voting scheme. The integration method consumes little computing resource and the result of calculation accords with the actual conditions, which indicates that AHP is an efficient ensemble method.
An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and IGRA negative persons with M. tuberculosis specific antibodies in Cape Town, South Africa (2020)

Immune reconstituted HIV+ persons can be persistently non-immunoreactive to TST and interferon-γ T-cell responses to Mtb, yet develop species-specific antibody responses. Exposure is evidenced by Mtb-specific antibody titres. Our identification of HIV+ individuals displaying a persisting lack of response to TST and IGRA T-cell immune conversion paves the way for future studies to investigate this phenotype in the context of HIV-infection that so far have received only scant attention.
In vitro growth factor-induced bio engineering of mature articular cartilage (2012)

Articular cartilage maturation is the postnatal development process that adapts joint surfaces to their site-specific biomechanical demands. Maturation involves gross morphological changes that occur through a process of synchronised growth and resorption of cartilage and generally ends at sexual maturity. The inability to induce maturation in biomaterial constructs designed for cartilage repair has been cited as a major cause for their failure in producing persistent cell-based repair of joint lesions. The combination of growth factors FGF2 and TGFβ1 induces accelerated articular cartilage maturation in vitro such that many molecular and morphological characteristics of tissue maturation are observable. We hypothesised that experimental growth factor-induced maturation of immature cartilage would result in a biophysical and biochemical composition consistent with a mature phenotype. Using native immature and mature cartilage as reference, we observed that growth factor-treated immature cartilages displayed increased nano-compressive stiffness, decreased surface adhesion, decreased water content, increased collagen content and smoother surfaces, correlating with a convergence to the mature cartilage phenotype. Furthermore, increased gene expression of surface structural protein collagen type I in growth factor-treated explants compared to reference cartilages demonstrates that they are still in the dynamic phase of the postnatal developmental transition. These data provide a basis for understanding the regulation of postnatal maturation of articular cartilage and the application of growth factor-induced maturation in vitro and in vivo in order to repair and regenerate cartilage defects.
Genetic Diversity at 15 Fluorescent-Labeled Short Tandem Repeat Loci in the Patel and Other Communities of Gujarat, India (2004)

Thirteen tetranucleotide and 2 pentanucleotide repeat units were analyzed in 120 unrelated individuals of Patel and other communities of Gujarat, India. Allele frequency data obtained from the analysis of 15 short tandem repeat markers of the population were found to be satisfying Hardy-Weinberg equilibrium, with marginal deviations. Departures from Hardy-Weinberg equilibrium were observed in Patel communities at locus vWA and for that of the other communities at locus D7S820 and at locus TPOX. The power of discrimination values on an average fall within the range of 0.718 and 0.870, with deviations at locus D3S1358 showing a value of 0.400 for Patels. The value ranged between 0.709 and 0.869, with slight variations among the studied alleles in the other group. Thus, the 15 markers selected for this study were found to be highly suitable in human identification and for providing information on genetic polymorphism of the population of Gujarat.
A new phenothiazine derivate is active against Clostridioides difficile and shows low cytotoxicity (2021)

The rapid evolution of antibiotic resistance in Clostridioides difficile and the consequent effects on prevention and treatment of C. difficile infections (CDIs) are matters of concern for public health. Thioridazine, a compound belonging to the phenothiazine group, has previous shown antimicrobial activity against C. difficile. The purpose of this present study was to investigate the potential of a novel phenothiazine derivative, JBC 1847, as an oral antimicrobial for treatment of intestinal pathogens and CDIs. The minimal inhibition concentration and the minimum bactericidal concentration of JBC 1847 against C. difficile ATCC 43255 were determined 4 μg/mL and high tolerance after oral administration in mice was observed (up to 100 mg/kg bodyweight). Pharmacokinetic modeling was conducted in silico using GastroPlusTM, predicting low (< 10%) systemic uptake after oral exposure and corresponding low Cmax in plasma. Impact on the intestinal bacterial composition after four days of treatment was determined by 16s rRNA MiSeq sequencing and revealed only minor impact on the microbiota in non-clinically affected mice, and there was no difference between colony-forming unit (CFU)/gram fecal material between JBC 1847 and placebo treated mice. The cytotoxicity of the compound was assessed in Caco-2 cell-line assays, in which indication of toxicity was not observed in concentrations up to seven times the minimal bactericidal concentration. In conclusion, the novel phenothiazine derivative demonstrated high antimicrobial activity against C. difficile, had low predicted gastrointestinal absorption, low intestinal (in vitro) cytotoxicity, and only induced minor changes of the healthy microbiota, altogether supporting that JBC 1847 could represent a novel antimicrobial candidate. The clinical importance hereof calls for future experimental studies in CDI models.
Robotic arm control through mimicking of miniature robotic arm (2017)

In the recent technology advancements, employing robots for handling precise operations were seen in abundance like industrial, medical and rescue operations etc. Introducing human interaction with the robotic arm in the real-time scenario opens new doors in innovations and applications of the robotic arms. This paper reports the making and testing of a miniature prototype robotic controller arm using Bluetooth wireless technology which can be used to manually control an actual robotic arm that has 3 degrees of freedom. The main objective is to design and employ a miniature version of robotic arm which can make the main robotic arm imitate as it does when the miniature arm is operated by a human operator. This can be achieved with the help of simple potentiometers at the joints of the miniature arm. The data is exchanged by the miniature robotic arm and the main robotic arm with the help of Bluetooth wireless interface.
Sublime vision and self-derision: the aesthetics of death in Tolstoy (2010)

Death features prominently in Tolstoy's artistic and intellectual universe. Tolstoy's very first work, Childhood, a semi-fictional account of scenes inspired by his childhood, relates the 10-year-old protagonist's first confrontation with death when his mother unexpectedly succumbs to an illness. Tolstoy was about 2 years old when his mother died, and 9 when his father followed her. This initial painful realization of human mortality clearly exerted a profound impact, prompting him to recreate the image of his mother in Childhood and to return again and again to the theme of death in his subsequent works. Both War and Peace and Anna Karenina contain celebrated death scenes unparalleled in world literature, but shorter works have been just as powerful, in particular “Three Deaths,” The Death of Ivan Ilych, and The Kreutzer Sonata. Notable death scenes are also scattered in many, if not most, of his other pieces, including the Sevastopol sketches, The Cossacks, and Hadji Murat. The prominence of death in Tolstoy's oeuvre can hardly be overstated, and so it is no surprise that Philippe Ariès discusses Tolstoy's treatment of death at length in his seminal The Hour of Death, a survey of the history of dying in Western civilization.
Influence of the type of ceramic moulding materials on the top layer of titanium precision castings (2007)

The article presents the results of the research which was executed to describe the conditions specific of the formation of surface of certain micro-geometry and of the upper layers on precision titanium castings for medical industry. On the ready precision castings some tests were carried out to obtain the surface micro-geometry satisfying the requirements of implants to be used in human organism. The surfaces with specific spherical macro-unevenness were formed as well as plane surfaces of 2 ÷ 6μm roughness. With the help of the light and electron microscopy, the possibility of formation of upper layers directly through an interaction of liquid titanium or Ti6Al4V alloy with the first layer of ceramic mould made from the ceramic mixtures based on Ekosil binder and molochite or zirconia has been confirmed.
Cytokine therapy for craniosynostosis (2004)

The birth prevalence of craniosynostosis (premature suture fusion) is 300-500 per 1,000,000 live births. Surgical management involves the release of the synostosed suture. In many cases, however, the suturectomy site rapidly reossifies, further restricts the growing brain and alters craniofacial growth. This resynostosis requires additional surgery, which increases patient morbidity and mortality. New findings in bone biology and molecular pathways involved with suture fusion, combined with novel tissue engineering techniques, may allow the design of targeted and complementary therapies to decrease complications inherent in high-risk surgical procedures. This paper selectively reviews recent advances in i) identifying genetic mutations and the aetiopathogenesis of a number of craniosynostotic conditions; ii) cranial suture biology and molecular biochemical pathways involved in suture fusion; and iii) the design, development and application of various vehicles and tissue engineered constructs to deliver cytokines and genes to cranial sutures. Such biologically based therapies may be used as surgical adjuncts to rescue fusing sutures or help manage postoperative resynostosis.