gebhart/patrepeval huggingface dataset:
A ZINC‐DEFICIENCY DERMATITIS IN PATIENTS ON TOTAL PARENTERAL NUTRITION (1978)

Three patients on home total parenteral nutrition utilizing a synthetic amino acid solutions developed a dermatitis consistent with acrodermatitis enteropathica after 30, 43 and 62 days of therapy. The dermatitis resolved after changing to casein hydrolysate in 2 patients and after full oral alimentation in the third. Although measured serum zinc levels were repeatedly normal to elevated in all patients, sufficient retrospective data analysis combined with literature review on this subject, clearly implicates zinc deficiency as the etiology for their dermatitis. Adequate zinc supplementation of synthetic amino acid solutions is essential in order to avoid this complication.
Are Aqueous Biphasic Systems Composed of Deep Eutectic Solvents Ternary or Quaternary Systems? (2016)

Deep eutectic solvents (DES) have emerged in the past few years as a new class of solvents with promising applications in several fields. In the present work, the application of DES (formed by binary mixtures of cholinium chloride and carboxylic acids or urea) as phase-forming components of aqueous biphasic systems (ABS) is investigated. The mechanisms associated with the phases demixing of ABS composed of DES, as well as the DES stability in aqueous solutions, are investigated to address the critical question whether DES-based ABS are in fact ternary or quaternary mixtures. It is shown that the DES integrity is destroyed in ABS by the disruption of the hydrogen-bonding interactions of the complex (a result of the isolated components preferential solvation by water), and as confirmed by a nonstoichiometric partition of the DES components between the coexisting phases. As a result, there are no “real” DES-based ABS; instead, there is the formation of ABS composed of four components, where the carboxylic acid used as the hydrogen-bond donor species seems to act as an additive. Finally, it is shown that these ABS have an outstanding potential to be used in extraction processes, as it is here demonstrated with the complete separation of two dyes. However, the volatile nature of short chain carboxylic acids and the nonstoichiometric partition of the DES components in ABS make the development of recovery and recycling steps more difficult to accomplish.
A Concise Synthesis of Tetrahydroxy-LCB, α-Galactosyl Ceramide, and 1,4-Dideoxy-1,4-imino-l-ribitol via d-Allosamines as Key Building Blocks (2006)

The total syntheses of tetrahydroxy-LCB 1, alpha-galactosyl ceramide 2, and 1,4-dideoxy-1,4-imino-L-ribitol 3 via D-allosamine derivatives as common synthons are described here.
Human Breast Cancer Cells Harboring a Gatekeeper T798M Mutation in HER2 Overexpress EGFR Ligands and Are Sensitive to Dual Inhibition of EGFR and HER2 (2013)

Simultaneous blockade of HER2 and EGFR should be an effective treatment strategy against HER2 gene-amplified breast cancer cells harboring T798M mutant alleles.
Variability analysis of fetal heart rate signals as obtained from abdominal electrocardiographic recordings (1986)

The present paper introduces an original method of digital signal processing for an automatic analysis of non-invasive abdominal ECG recordings on pregnant women starting from the 25th week of gestation. The procedure has been implemented on a DEC-VAX 750 digital computer at the Department of Electrical Engineering, Polytechnic of Milano and the signals are recorded at the Department of Obstetrics and Gynecology "L. Mangiagalli", University of Milano, Italy. The experimental results presented in here are still preliminary as only few cases have been considered up to now (about 20) and the goal of the paper is mainly focused on the algorithmic aspects of the whole procedure implemented in the computer and on the approach of heart rate variability (HRV) signal analysis both in the mother and in the fetus. Abdominal ECG lead processing is illustrated starting from the step of maternal (M) and fetal (F) QRS recognitions through linear digital filtering (derivative and low-pass FIR filter, Weber-Cappellini window) and weighted averaging techniques synchronized with maternal QRS's. Figure 1 a shows the original abdominal lead; figure 1 b the filtered signal for MQRS recognitions; figure 2 a the template of maternal cardiac cycle as obtained after the averaging operation synchronized with the instants of MQRS occurrence. The subtraction of the template results in the abdominal lead shown in figure 1 c in which the contribution of MECG is practically entirely reduced even in the case of MQRS and FQRS overlapping.(ABSTRACT TRUNCATED AT 250 WORDS)
Design and Analysis of UHF Micropower CMOS DTMOST Rectifiers (2009)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> Design and analysis of ultrahigh-frequency (UHF) micropower rectifiers based on a diode-connected dynamic threshold MOSFET (DTMOST) is discussed. An analytical design model for DTMOST rectifiers is derived based on curve-fitted diode equation parameters. Several DTMOST six-stage charge-pump rectifiers were designed and fabricated using a CMOS 0.18-<formula formulatype="inline"><tex Notation="TeX">$\mu\hbox{m}$</tex></formula> process with deep n-well isolation. Measured results verified the design model with average accuracy of 10.85% for an input power level between <formula formulatype="inline"><tex Notation="TeX">$-$</tex></formula>4 and 0 dBm. At the same time, three other rectifiers based on various types of transistors were fabricated on the same chip. The measured results are compared with a Schottky diode solution. </para>
Measurements of Matching and High Count Rate Performance of Multichannel ASIC for Digital X-Ray Imaging Systems (2007)

We present the measurements of matching and high count rate performance of a 64 channel readout ASIC called DEDIX for high count rate position-sensitive measurements using semiconductor detectors. The ASIC is designed in 0.35 mum CMOS process and its total area is 3900 times 5000 mum2. The DEDIX has a binary readout architecture. Each channel is built of a charge sensitive amplifier (CSA) with a pole-zero cancellation circuit, a shaper, two independent discriminators and two independent 20-bit counters. The size of the input device in CSA has been optimized for a detector capacitance in the range of 1-3 pF per strip. An equivalent noise charge of 110 el rms has been achieved for a total detector capacitance of 1 pF at the shaper peaking time of 160 ns. Internal correction DAC implemented in each channel independently ensures a low spread of discriminator effective threshold, namely 0.4 mV at one sigma level. The mean gain in the multichannel ASIC is 54 muV/el, with a good uniformity from channel-to-channel (sd/mean ap 0.8%). Low noise performance and high rate capability have been demonstrated by the measurement up to and above 1 MHz average rate of input signals.
Hutchinson–Gilford progeria syndrome (2004)

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder that causes premature, rapid aging shortly after birth. Recently, de novo point mutations in the Lmna gene have been found in individuals with HGPS. Lmna encodes lamin A and C, the A-type lamins, which are an important structural component of the nuclear envelope. The most common HGPS mutation is located at codon 608 (G608G). This mutation creates a cryptic splice site within exon 11, which deletes a proteolytic cleavage site within the expressed mutant lamin A. Incomplete processing of prelamin A results in nuclear lamina abnormalities that can be observed in immunofluorescent studies of HGPS cells. Mouse models, such as Lmna knockout, Zmpste24 knockout, and Lmna L530P knockin will help the study of progeria. Lmna mutations have also recently been found in patients with atypical forms of progeria. The discovery of the HGPS mutations brings the total number of diseases caused by mutant Lmna to nine, underscoring the astonishing spectrum of laminopathies. Future research into HGPS could also provide important clues about the general process of aging and aging-related diseases.
FK 506-binding protein proline rotamase is a target for the immunosuppressive agent FK 506 in Saccharomyces cerevisiae. (1991)

FK 506 and cyclosporin A are potent immunosuppressive compounds that inhibit T-cell activation by interfering with signal transduction. In vitro, FK 506 binds and inhibits the activity of FK 506-binding protein (FKBP), a peptidylprolyl rotamase (cis-trans isomerase). Cyclosporin A acts similarly on a different proline rotamase, cyclophilin. Experiments described here demonstrate genetically that FKBP is a target for FK 506 in vivo. We have isolated the gene encoding the FKBP proline rotamase (FPR1) from Saccharomyces cerevisiae. The encoded yeast protein is highly homologous with bovine and human FKBP and shares no homology with cyclophilin. Disruption of FPR1 and CPR1 (encoding cyclophilin) individually or in combination is not lethal; thus, either enzymatic proline rotamerization is not essential for life or an unknown proline rotamase can substitute for the missing enzymes. Overexpression or disruption of FPR1 confers resistance to growth inhibition by FK 506, suggesting that FKBP is a target for FK 506 in yeast. However, FKBP is only one of at least two targets because strains lacking FKBP are only partially resistant to FK 506.
Electrical Stimulation to Promote Peripheral Nerve Regeneration (2015)

Peripheral nerve injury afflicts individuals from all walks of life. Despite the peripheral nervous system's intrinsic ability to regenerate, many patients experience incomplete functional recovery. Surgical repair aims to expedite this recovery process in the most thorough manner possible. However, full recovery is still rarely seen especially when nerve injury is compounded with polytrauma where surgical repair is delayed. Pharmaceutical strategies supplementary to nerve microsurgery have been investigated but surgery remains the only viable option. Brief low-frequency electrical stimulation of the proximal nerve stump after primary repair has been widely investigated. This article aims to review the currently known biological basis for the regenerative effects of acute brief low-frequency electrical stimulation on axonal regeneration and outline the recent clinical applications of the electrical stimulation protocol to demonstrate the significant translational potential of this modality for repairing peripheral nerve injuries. The review concludes with a discussion of emerging new advancements in this exciting area of research. The current literature indicates the imminent clinical applicability of acute brief low-frequency electrical stimulation after surgical repair to effectively promote axonal regeneration as the stimulation has yielded promising evidence to maximize functional recovery in diverse types of peripheral nerve injuries.
Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) (2010)

The original scales of the OAV were shown to be multidimensional constructs. Eleven new lower order scales were constructed and demonstrated to have desirable psychometric properties. The new lower order scales are most likely better suited to assess drug induced ASC.
N -Acetyl Cysteine Enhances the Response to Interferon-α in Chronic Hepatitis C: A Pilot Study (1993)

Hepatitis C virus (HCV) is an RNA virus that replicates in both the liver and lymphoid cells. Interferon-alpha (IFN-alpha) is a useful treatment of chronic hepatitis C (CHC) although resistance to this drug occurs frequently. The mechanisms underlying resistance to IFN remain unknown. In this work, we have measured the levels of glutathione in plasma and peripheral lymphoid cells from 15 healthy controls and 24 CHC patients, 10 of whom were without treatment and 14 showed high serum alanine aminotransferase (ALT) values despite therapy with lymphoblastoid IFN for more than 4 months. In all patients, glutathione levels in plasma and in mononuclear cells were depressed in comparison to controls. In IFN-unresponsive patients, the addition of 600 mg tid of oral N-acetyl cysteine (NAC), a glutathione precursor, resulted in a steady decrease of ALT values in all patients, with complete normalization in 41% of cases after 5-6 months of combined therapy. Administration of NAC alone for 1 month was without effect in the 10 patients that were not receiving IFN. Supplementation of IFN with NAC induced a near normalization of intralymphocytic glutathione, but plasma levels were only moderately increased. HCV replication was markedly inhibited in lymphocytes and viremia was cleared in one of the 8 patients tested. In conclusion, NAC enhances the response to IFN in CHC. Controlled studies are needed to ascertain whether antioxidant therapy might act in synergy with IFN in chronic viral hepatitis.
Accumulation of Maillard reaction products in skin collagen in diabetes and aging. (1993)

To investigate the contribution of glycation and oxidation reactions to the modification of insoluble collagen in aging and diabetes, Maillard reaction products were measured in skin collagen from 39 type 1 diabetic patients and 52 nondiabetic control subjects. Compounds studied included fructoselysine (FL), the initial glycation product, and the glycoxidation products, N epsilon-(carboxymethyl) lysine (CML) and pentosidine, formed during later Maillard reactions. Collagen-linked fluorescence was also studied. In nondiabetic subjects, glycation of collagen (FL content) increased only 33% between 20 and 85 yr of age. In contrast, CML, pentosidine and fluorescence increased five-fold, correlating strongly with age. In diabetic patients, collagen FL was increased threefold compared with nondiabetic subjects, correlating strongly with glycated hemoglobin but not with age. Collagen CML, pentosidine and fluorescence were increased up to twofold in diabetic compared with control patients: this could be explained by the increase in glycation alone, without invoking increased oxidative stress. There were strong correlations among CML, pentosidine and fluorescence in both groups, providing evidence for age-dependent chemical modification of collagen via the Maillard reaction, and acceleration of this process in diabetes. These results support the description of diabetes as a disease characterized by accelerated chemical aging of long-lived tissue proteins.
DDIS-08. THE SMALL MOLECULE IMIPRIDONE ONC201 IS ACTIVE IN GLIOBLASTOMA WITH DRD2 PATHWAY DYSREGULATION (2017)

ONC201, an imipridone that is a selective antagonist of the G protein-coupled receptors dopamine receptor D2 (DRD2) and D3 (DRD3), has exhibited tumor shrinkage and an exceptional safety profile in a phase II recurrent glioblastoma clinical trial (Arrillaga et al, 2017). In vitro and in vivo studies have previously demonstrated single agent ONC201 efficacy in glioblastoma models (Allen et al 2013). In vitro efficacy profiling of ONC201 in the Genomic of Drug Sensitivity in Cancer (GDSC) collection of cell lines confirmed broad anti-cancer efficacy with high sensitivity in human brain cancer cell lines. DRD2 is overexpressed in glioblastoma and DRD2 antagonism induces tumor cell apoptosis via the same signaling pathways that respond to ONC201. Investigation of The Cancer Genome Atlas (TCGA) revealed that DRD2 is highly expressed in glioblastoma relative to other dopamine receptor family members and that genetic aberrations were rare. High expression of DRD2 occurred in primary, rather than secondary, glioblastoma and was associated with a poor prognosis. Immunohistochemistry analyses of tissue microarrays revealed DRD2 overexpression in glioblastoma relative to normal brain. A linear correlation between DRD2 mRNA and ONC201 GI50 was observed among glioblastoma cell lines in the NCI60 panel. A significant induction of serum prolactin, a surrogate biomarker of target engagement, was detected in ONC201-treated glioblastoma patients. Interestingly, expression of DRD5, a D1-like dopamine receptor that counteracts DRD2 signaling, was significantly inversely correlated with ONC201 potency in the NCI60 and GDSC datasets (P <.05). Furthermore, a missense DRD5 mutation was identified in cancer cells with acquired resistance to ONC201. Resistance could be recapitulated with overexpression of the mutant DRD5 gene or, to a lesser extent, with the wild-type gene. In conclusion, the DRD2 pathway is a therapeutic target that is dysregulated in glioblastoma and contains biomarkers of tumor sensitivity to ONC201 that are under clinical evaluation.
Structural basis for recognition of the AGNN tetraloop RNA fold by the double-stranded RNA-binding domain of Rnt1p RNase III (2004)

Specific recognition of double-stranded RNA (dsRNA) by dsRNA-binding domains (dsRBDs) is involved in a large number of biological and regulatory processes. Although structures of dsRBDs in complex with dsRNA have revealed how they can bind to dsRNA in general, these do not explain how a dsRBD can recognize specific RNAs. Rnt1p, a member of the RNase III family of dsRNA endonucleases, is a key component of the Saccharomyces cerevisiae RNA-processing machinery. The Rnt1p dsRBD has been implicated in targeting this endonuclease to its RNA substrates, by recognizing hairpins closed by AGNN tetraloops. We report the solution structure of Rnt1p dsRBD complexed to the 5' terminal hairpin of one of its small nucleolar RNA substrates, the snR47 precursor. The conserved AGNN tetraloop fold is retained in the protein-RNA complex. The dsRBD contacts the RNA at successive minor, major, and tetraloop minor grooves on one face of the helix. Surprisingly, neither the universally conserved G nor the highly conserved A are recognized by specific hydrogen bonds to the bases. Rather, the N-terminal helix fits snugly into the minor groove of the RNA tetraloop and top of the stem, interacting in a non-sequence-specific manner with the sugar-phosphate backbone and the two nonconserved tetraloop bases. Mutational analysis of residues that contact the tetraloop region show that they are functionally important for RNA processing in the context of the entire protein in vivo. These results show how a single dsRBD can convey specificity for particular RNA targets, by structure specific recognition of a conserved tetraloop fold.
Dali server: conservation mapping in 3D (2010)

Our web site (http://ekhidna.biocenter.helsinki.fi/dali_server) runs the Dali program for protein structure comparison. The web site consists of three parts: (i) the Dali server compares newly solved structures against structures in the Protein Data Bank (PDB), (ii) the Dali database allows browsing precomputed structural neighbourhoods and (iii) the pairwise comparison generates suboptimal alignments for a pair of structures. Each part has its own query form and a common format for the results page. The inputs are either PDB identifiers or novel structures uploaded by the user. The results pages are hyperlinked to aid interactive analysis. The web interface is simple and easy to use. The key purpose of interactive analysis is to check whether conserved residues line up in multiple structural alignments and how conserved residues and ligands cluster together in multiple structure superimpositions. In favourable cases, protein structure comparison can lead to evolutionary discoveries not detected by sequence analysis.
Current trends in microsatellite genotyping (2011)

Microsatellites have been popular molecular markers ever since their advent in the late eighties. Despite growing competition from new genotyping and sequencing techniques, the use of these versatile and cost-effective markers continues to increase, boosted by successive technical advances. First, methods for multiplexing PCR have considerably improved over the last years, thereby decreasing genotyping costs and increasing throughput. Second, next-generation sequencing technologies allow the identification of large numbers of microsatellite loci at reduced cost in non-model species. As a consequence, more stringent selection of loci is possible, thereby further enhancing multiplex quality and efficiency. However, current practices are lagging behind. By surveying recently published population genetic studies relying on simple sequence repeats, we show that more than half of the studies lack appropriate quality controls and do not make use of multiplex PCR. To make the most of the latest technical developments, we outline the need for a well-established strategy including standardized high-throughput bench protocols and specific bioinformatic tools, from primer design to allele calling.
Simulation of the EUV Spectrum of Xe and Sn Plasmas (2004)

Complex spectra of Xe and Sn, and their feasibility for use in the lithographic extreme ultraviolet (EUV) source, are investigated. By combining calculations of atomic data using the HULLAC code and the Whiam collisional radiative model with a simple radiative transfer model, the EUV spectrum is shown to originate from a large number of fine structure transitions. Satellite lines of 4d-4f and 4d-5p transitions from near ten times ionized states are found to make a significant contribution to the emission from an optically thick plasma. The wavelengths and transition probabilities of emission lines, charge state distribution, and level population in the plasma, as well as radiation intensity from a laser-produced plasma source have been calculated. The effect of opacity is taken into account assuming a local thermodynamic equilibrium population in the plasma. The calculated result reproduces the observed spectra both for Xe and Sn, showing applicability of the present method to the spectroscopy of hot dense plasmas.
Isolation and characterization of Chinese hamster ovary cells defective in the intracellular metabolism of low density lipoprotein-derived cholesterol. (1992)

We have isolated clones of an established cell line which express defects in intracellular cholesterol metabolism. Chinese hamster ovary cells were mutagenized, and clones unable to mobilize low density lipoprotein (LDL)-derived cholesterol to the plasma membrane were selected. Biochemical analysis of two mutant clones revealed a phenotype characteristic of the lysosomal storage disease, Niemann-Pick type C. The mutant cell lines were found to be defective in the regulatory responses elicited by LDL-derived cholesterol. LDL-mediated stimulation of cholesterol esterification was grossly defective, and LDL suppression of 3-hydroxy-3-methylglutaryl-CoA reductase was impaired. However, the mutants modulated these activities normally in response to 25-hydroxycholesterol or mevalonate. The LDL-specific defects were predicated by the inability of these mutants to mobilize LDL-derived cholesterol from lysosomes. Cell fractionation studies showed that LDL-derived, unesterified cholesterol accumulated in the lysosomes of mutant cells to significantly higher levels than normal, commensurate with defective movement of cholesterol to other cellular membranes. Characterization of cell lines defective in intracellular cholesterol transport will facilitate identification of the gene(s) required for intracellular cholesterol movement and regulation.