gebhart/patrepeval huggingface dataset:
Simulation of brain tumor resection in image-guided neurosurgery (2011)

Preoperative magnetic resonance images are typically used for neuronavigation in image-guided neurosurgery. However, intraoperative brain deformation (e.g., as a result of gravitation, loss of cerebrospinal fluid, retraction, resection, etc.) significantly degrades the accuracy in image guidance, and must be compensated for in order to maintain sufficient accuracy for navigation. Biomechanical finite element models are effective techniques that assimilate intraoperative data and compute whole-brain deformation from which to generate model-updated MR images (uMR) to improve accuracy in intraoperative guidance. To date, most studies have focused on early surgical stages (i.e., after craniotomy and durotomy), whereas simulation of more complex events at later surgical stages has remained to be a challenge using biomechanical models. We have developed a method to simulate partial or complete tumor resection that incorporates intraoperative volumetric ultrasound (US) and stereovision (SV), and the resulting whole-brain deformation was used to generate uMR. The 3D ultrasound and stereovision systems are complimentary to each other because they capture features deeper in the brain beneath the craniotomy and at the exposed cortical surface, respectively. In this paper, we illustrate the application of the proposed method to simulate brain tumor resection at three temporally distinct surgical stages throughout a clinical surgery case using sparse displacement data obtained from both the US and SV systems. We demonstrate that our technique is feasible to produce uMR that agrees well with intraoperative US and SV images after dural opening, after partial tumor resection, and after complete tumor resection. Currently, the computational cost to simulate tumor resection can be up to 30 min because of the need for re-meshing and the trial-and-error approach to refine the amount of tissue resection. However, this approach introduces minimal interruption to the surgical workflow, which suggests the potential for its clinical application with further improvement in computational efficiency.
Rho‐kinase/ROCK: A key regulator of the cytoskeleton and cell polarity (2010)

Rho-associated kinase (Rho-kinase/ROCK/ROK) is an effector of the small GTPase Rho and belongs to the AGC family of kinases. Rho-kinase has pleiotropic functions including the regulation of cellular contraction, motility, morphology, polarity, cell division, and gene expression. Pharmacological analyses have revealed that Rho-kinase is involved in a wide range of diseases such as vasospasm, pulmonary hypertension, nerve injury, and glaucoma, and is therefore considered to be a potential therapeutic target. This review focuses on the structure, function, and modes of activation and action of Rho-kinase.
Fibromyalgia and menopause (1986)

Women predominate at all ages among patients diagnosed as having primary fibromyalgia. Of 100 patients reviewed, the average age at onset of fibromyalgia was 46. Of 65 patients in whom menopause occurred before diagnosis of fibromyalgia, the average age at menopause was 42, and most of these women had menopause related to surgery and insufficient estrogen therapy. Estrogen deficit is, thus, a prominent promoting factor in the majority of fibromyalgia patients and is likely to have an effect on sleep, mood, and anxiety state. These emotional responses may subsequently be somatized as pain. Therefore, estrogen therapy should be added to the treatment armamentarium for fibromyalgia in selected patients.
[The mangrove and others vegetation associations in de Gandoca lagoon, Limón, Costa Rica]. (2001)

Six plant associations were identified at Gandoca Lagoon by photointerpretation and field verification: a) mangroves, b) palm trees swamp, and palm trees with Acrostichum aureum and A. danaefolium, c) mixed palm trees, d) very humid tropical rain forest, and e) tropical beach vegetation. The mangroves cover 12.5 ha surrounding the lagoon and extend 2 km up the Gandoca River. Rhizophora mangle (red mangrove) was the dominant species, with Avicennia germinans (black mangrove), Laguncularia racemosa (white mangrove) and Conocarpus erectus (buttonwood) also present. Moving inland the mangroves grade into a tropical rain forest. Gandoca, the largest and best preserved mangrove of Caribbean Costa Rica, tripled its area from 1976 to 2000. Possible causes include sedimentation and the Limón earthquake, which may have subside the lagoon area.
The presence of cysteine in the cytoplasmic domain of the vesicular stomatitis virus glycoprotein is required for palmitate addition. (1984)

The transmembrane glycoprotein (G protein) of vesicular stomatitis virus (VSV) is known to contain 1-2 mol of covalently linked fatty acid (palmitate) per mol of protein. G protein is oriented in cellular membranes such that the carboxyl-terminal 29 amino acids protrude into the cytoplasm. We have obtained expression in eukaryotic cells of mutagenized cDNA clones that encode VSV G proteins lacking portions of this cytoplasmic domain. Labeling of these truncated proteins with [3H]palmitate indicated that the palmitate might be linked to an amino acid residue within the first 14 residues on the carboxyl-terminal side of the transmembrane domain. Using oligonucleotide directed mutagenesis, we changed the single codon specifying cysteine in this domain to a codon specifying serine. Expression of this mutant gene results in synthesis of a G protein lacking palmitate. We suggest that linkage of palmitate to G protein is through the cysteine in the cytoplasmic domain and that such a linkage may occur in many viral and cellular glycoproteins. The G protein lacking palmitate is glycosylated and is transported normally to the cell surface.
Zac1 (Lot1), a Potential Tumor Suppressor Gene, and the Gene for ɛ-Sarcoglycan Are Maternally Imprinted Genes: Identification by a Subtractive Screen of Novel Uniparental Fibroblast Lines (2000)

Imprinted genes are expressed from one allele according to their parent of origin, and many are essential to mammalian embryogenesis. Here we show that the epsilon-sarcoglycan gene (Sgce) and Zac1 (Lot1) are both paternally expressed imprinted genes. They were identified in a subtractive screen for imprinted genes using a cDNA library made from novel parthenogenetic and wild-type fibroblast lines. Sgce is a component of the dystrophin-sarcoglycan complex, Zac1 is a nuclear protein inducing growth arrest and/or apoptosis, and Zac1 is a potential tumor suppressor gene. Sgce and Zac1 are expressed predominantly from their paternal alleles in all adult mouse tissues, except that Zac1 is biallelic in the liver and Sgce is weakly expressed from the maternal allele in the brain. Sgce and Zac1 are broadly expressed in embryos, with Zac1 being highly expressed in the liver primordium, the umbilical region, and the neural tube. Sgce, however, is strongly expressed in the allantoic region on day 9.5 but becomes more widely expressed throughout the embryo by day 11.5. Sgce is located at the proximal end of mouse chromosome 6 and is a candidate gene for embryonic lethality associated with uniparental maternal inheritance of this region. Zac1 maps to the proximal region of chromosome 10, identifying a new imprinted locus in the mouse, homologous with human chromosome 6q24-q25. In humans, unipaternal disomy for this region is associated with fetal growth retardation and transient neonatal diabetes mellitus. In addition, loss of expression of ZAC has been described for a number of breast and ovarian carcinomas, suggesting that ZAC is a potential tumor suppressor gene.
Checkpointing and Rollback-Recovery for Distributed Systems (1987)

We consider the problem of bringing a distributed system to a consistent state after transient failures. We address the two components of this problem by describing a distributed algorithm to create consistent checkpoints, as well as a rollback-recovery algorithm to recover the system to a consistent state. In contrast to previous algorithms, they tolerate failures that occur during their executions. Furthermore, when a process takes a checkpoint, a minimal number of additional processes are forced to take checkpoints. Similarly, when a process rolls back and restarts after a failure, a minimal number of additional processes are forced to roll back with it. Our algorithms require each process to store at most two checkpoints in stable storage. This storage requirement is shown to be minimal under general assumptions.
Expanding the scope of crystal form evaluation in pharmaceutical science. (2006)

The commentary seeks to provide a brief history and perspective on the importance of crystal forms of pharmaceuticals as a means of achieving performance criteria. The expanding scope of crystal form selection, emergence of crystal engineering in pharmaceutical science and pharmaceutical co-crystals are topics of this brief review.
A Universal Strategy for Adoptive Immunotherapy of Cancer through Use of a Novel T-cell Antigen Receptor (2012)

Adoptive immunotherapies composed of T cells engineered to express a chimeric antigen receptor (CAR) offer an attractive strategy for treatment of human cancer. However, CARs have a fixed antigen specificity such that only one tumor-associated antigen (TAA) can be targeted, limiting the efficacy that can be achieved because of heterogeneous TAA expression. For this reason, a more generalized and effective application of CAR therapy would benefit from the capability to produce large panels of CARs against many known TAAs. In this study, we show a novel strategy to extend the recognition specificity potential of a bioengineered lymphocyte population, allowing flexible approaches to redirect T cells against various TAAs. Our strategy employs a biotin-binding immune receptor (BBIR) composed of an extracellular-modified avidin linked to an intracellular T-cell signaling domain. BBIR T cells recognized and bound exclusively to cancer cells pretargeted with specific biotinylated molecules. The versatility afforded by BBIRs permitted sequential or simultaneous targeting of a combination of distinct antigens. Together, our findings show that a platform of universal T-cell specificity can significantly extend conventional CAR approaches, permitting the tailored generation of T cells of unlimited antigen specificity for improving the effectiveness of adoptive T-cell immunotherapies for cancer.
Discovery, Synthesis, and Structure–Activity Relationship Development of a Series of N-4-(2,5-Dioxopyrrolidin-1-yl)phenylpicolinamides (VU0400195, ML182): Characterization of a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu4) with Oral Efficacy in an Antiparkinsonian Animal Model (2011)

There is an increasing amount of literature data showing the positive effects on preclinical antiparkinsonian rodent models with selective positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)). However, most of the data generated utilize compounds that have not been optimized for druglike properties, and as a consequence, they exhibit poor pharmacokinetic properties and thus do not cross the blood-brain barrier. Herein, we report on a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides with improved PK properties with excellent potency and selectivity as well as improved brain exposure in rodents. Finally, ML182 was shown to be orally active in the haloperidol induced catalepsy model, a well-established antiparkinsonian model.
Fusion of PDGFRB to MPRIP, CPSF6, and GOLGB1 in three patients with eosinophilia‐associated myeloproliferative neoplasms (2015)

In eosinophilia-associated myeloproliferative neoplasms (MPN-eo), constitutive activation of protein tyrosine kinases (TK) as consequence of translocations, inversions, or insertions and creation of TK fusion genes is recurrently observed. The most commonly involved TK and their potential TK inhibitors include PDGFRA at 4q12 or PDGFRB at 5q33 (imatinib), FGFR1 at 8p11 (ponatinib), and JAK2 at 9p24 (ruxolitinib). We here report the identification of three new PDGFRB fusion genes in three male MPN-eo patients: MPRIP-PDGFRB in a case with t(5;17)(q33;p11), CPSF6-PDGFRB in a case with t(5;12)(q33;q15), and GOLGB1-PDGFRB in a case with t(3;5)(q13;q33). The fusion proteins identified by 5'-rapid amplification of cDNA ends polymerase chain reaction (PCR) or DNA-based long distance inverse PCR are predicted to contain the TK domain of PDGFRB. The partner genes contain domains like coiled-coil structures, which are likely to cause dimerization and activation of the TK. In all patients, imatinib induced rapid and durable complete remissions.
Purification and Characterization of a Polysome-associated Endoribonuclease That Degrades c-myc mRNA in Vitro (1998)

The regulation of mRNA half-lives is determined by multiple factors, including the activity of the messenger RNases (mRNases) responsible for destroying mRNA molecules. Previously, we used cell-free mRNA decay assays to identify a polysome-associated endonuclease that cleaves c-myc mRNA within the coding region. A similar activity has been solubilized and partially purified from a high salt extract of adult rat liver polysomes. Based on a correlation between protein and enzyme activity, the endonuclease is tentatively identified as a approximately 39-kDa protein. It cleaves the coding region stability determinant of c-myc mRNA with considerable specificity. Cleavages occur predominantly in an A-rich segment of the RNA. The endonuclease is resistant to RNase A inhibitors, sensitive to vanadyl ribonucleoside complex, and dependent on magnesium. In these and other respects, the soluble enzyme we have purified resembles the polysome-associated c-myc mRNase.
Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers (2017)

We successfully modeled the inhalation of nebulized esketamine in healthy volunteers. Nebulized esketamine is inhaled with a substantial reduction in bioavailability. Although the reduction in dose-independent bioavailability is best explained by retention of drug and particle exhalation, the reduction in dose-dependent bioavailability is probably due to sedation-related loss of drug into the air.
Identification of a Major Susceptibility Locus on Chromosome 6p and Evidence for Further Disease Loci Revealed by a Two Stage Genome-Wide Search in Psoriasis (1997)

Psoriasis is a common chronic inflammatory disorder of the skin. To further understand the pathogenesis of psoriasis we have chosen to investigate the molecular genetic basis of the disorder. We have used a two-stage approach to search the human genome for the location of genes conferring susceptibility to psoriasis, using a total of 106 affected sibling pairs identified from 68 independent families. As over a third of the extended kindreds included affected relatives besides siblings, in addition to an analysis of allele sharing between affected sibling pairs, a novel linkage strategy was applied that extracts full non-parametric information. Four principal regions of possible linkage were identified on chromosomes 2, 8, 20 (p <0.005) and markers from the MHC region at 6p21 (p <0.0000006) for which significant evidence of linkage disequilibrium was also observed (p <0.00002). Whilst data from limited case control associations exist to implicate the MHC, the results of this genome wide analysis demonstrate that, at least in the population studied, a gene or genes located within the MHC and close to the class 1 HLA loci, represent the major determinant of the genetic basis of psoriasis.
Influence of TCF7L2 gene variants on the therapeutic response to the dipeptidylpeptidase-4 inhibitor linagliptin (2014)

Linagliptin significantly improved hyperglycaemia in patients with type 2 diabetes both with and without the TCF7L2 gene diabetes risk alleles. However, differences in treatment response were observed, indicating that diabetes susceptibility genes may be an important contributor to the inter-individual variability of treatment response.
Mapping of quantitative trait loci for blood pressure and cardiac mass in the rat by genome scanning of recombinant inbred strains. (1995)

In the HXB and BXH recombinant inbred strains derived from the spontaneously hypertensive rat and the normotensive Brown Norway rat, we determined the strain distribution patterns of 500 genetic markers to scan the rodent genome for quantitative trait loci regulating cardiac mass and blood pressure. The markers spanned approximately 1,139 cM of the genome and were tested for correlations with left ventricular mass adjusted for body weight, and with systolic, diastolic, and mean arterial pressures. The marker for the dopamine 1A receptor (Drd1a) on chromosome 17 showed the strongest correlation with left ventricular heart weight (P = .00038, r = -0.59) and the relationship to heart weight was independent of blood pressure. The markers showing the strongest correlations with systolic, diastolic, and mean arterial pressure were D19Mit7 on chromosome 19 (P = .0012, r = .55), D2N35 on chromosome 2 (P = .0008, r = .56), and Il6 on chromosome 4 (P = .0018, r = .53), respectively. These studies demonstrate that the HXB and BXH strains can be effectively used for genome scanning studies of complex traits and have revealed several chromosome regions that may be involved in the genetic control of blood pressure and cardiac mass in the rat.
Inhaled calcium salts reduce expression of inflammatory mediators associated with tobacco smoke exposure to reduce airway inflammation (2012)

PUR118, an inhaled calcium based dry powder (DP) formulation exhibits preclinical anti-inflammatory and anti-infective activity. PUR118 may provide a novel approach for acute exacerbation control in patients with COPD and CF where the combination of underlying inflammation and pathogen infection result in reduced lung function and quality of life. The goal of this study was to evaluate the impact of PUR118 on gene expression in lung samples from a tobacco smoke (TS) exposure model. Mice were exposed to TS for 4d and treated with PUR118 or DP control 1h prior to TS. Mice were euthanized 4h after the last TS exposure and BAL and lung RNA were collected for cell counts, protein levels and QPCR analyses. Expression of 336 genes was evaluated using targeted QPCR arrays. TS exposure increased BAL cell counts that were reduced with PUR118 (79% reduction in neutrophils; p<0.001) to similar levels as a p38 MAPK inhibitor. TS exposure upregulated 21 genes more than 2-fold compared to control mice not exposed to TS and PUR118 treatment inhibited the expression of 11 of these 21 genes. Ten out of the 11 downregulated genes were validated using independent QPCR with 5 significantly inhibited by PUR118 (p<0.05). Among genes found downregulated with PUR118 treatment, many were associated with neutrophilic inflammation including: KC, MIP2, ENA78, IL-6, and MCP-1. BAL protein levels of several of these were similarly reduced by PUR118 compared to controls. Thus, PUR118 diminishes the inflammatory signals induced by TS exposure including many key drivers of neutrophilic inflammation at both the gene and protein level as a mechanism to reduce airway inflammation.
Efficacy of Topical Calcineurin Inhibitors in Psoriasis (2014)

The evidence (double-blind and open studies) is strong that topical tacrolimus and, to a lesser extent, pimecrolimus have efficacy in the treatment of psoriasis. Since these agents do not cause cutaneous atrophy, they likely have a special role in facial, genital, and intertriginous psoriasis. Further studies would help define their roles in psoriasis.
Overcrowded alkene-based molecular motors: from single molecule to multimotor systems (2013)

Het onderzoek richt zich op het beter begrijpen van de rotatie van de zogeheten tweede generatie licht-aangedreven moleculaire rotatiemotoren, met als uiteindelijk doel deze te gebruiken in de nanotechnologie. In het eerste experimentele hoofdstuk wordt de conformatieverandering tijdens de thermische stap bestudeerd met behulp van kwantummechanische berekeningen en spectroscopie. Hieruit bleek hoe deze stap precies verloopt. Vervolgens wordt gekeken naar de conformatieverandering tijdens de fotochemische stap op de sub-picoseconde tijdschaal. Om volledig op te helderen hoe deze stap verloopt zijn nog meer experimenten nodig. Het tweede deel van het proefschrift richt zich meer op manieren waarop de rotatie mogelijk kan worden toegepast. Ten eerste is een manier ontwikkeld waarmee de rotatie kan worden aangedreven met zichtbaar licht in plaats van UV licht. Dit zou een eerste stap kunnen zijn naar het gebruik van deze moleculaire motoren in biologische systemen. Ten tweede zijn geordende monolagen van de moleculaire motoren op grafiet gemaakt. Door de moleculen te ordenen kan mogelijk gebruik worden gemaakt van de cooperatieve beweging van een groot aantal motoren om werk te verrichten; rotatie van de moleculen in de monolaag kon echter niet worden aangetoond. Tenslotte zijn de moleculaire motoren ingebouwd in polymeren. De rotatie van de motoren werkt nog steeds als het polymeer in oplossing is. Bovendien werd gevonden dat de motoren de conformatie van de polymeerketens beinvloeden.
Similar substrate recognition motifs for mammalian AMP‐activated protein kinase, higher plant HMG‐CoA reductase kinase‐A, yeast SNF1, and mammalian calmodulin‐dependent protein kinase I (1995)

We have analysed phosphorylation of the synthetic peptide AMARAASAAALARRR, and 23 variants by mammalian, higher plant and yeast members of the SNF1 protein kinase subfamily (AMP-activated protein kinase (AMPK), HMG-CoA reductase kinase (HRK-A), and SNF1 itself), and by mammalian calmodulin-dependent protein kinase I (CaMKI). These four kinases recognize motifs which are very similar, although distinguishable. Our studies define the following recognition motifs: AMPK: phi (X beta)XXS/TXXX phi; HRK-A: phi (X,beta)XXSXXX phi; Snf1: phi XRXXSXXX phi; CaMKI: phi XRXXS/TXXX phi; where phi is a hydrophobic residue (M, V, L, I or F) and beta is a basic residue (R, K or H).
Early Diagnosis and Treatment of Pancreatic Dysplasia in Patients with a Family History of Pancreatic Cancer (1999)

Thorough screening of patients with a family history of pancreatic cancer is feasible. Clinical data combined with imaging studies (endoscopic ultrasonography and ERCP) can be used to identify high-risk patients who have dysplasia. The role of molecular genetic testing is uncertain at this time.
Homozygous Deletion in KVLQT1 Associated With Jervell and Lange-Nielsen Syndrome (1999)

A novel homozygous KVLQT1 mutation causes JLNS in an Amish family with deafness that is inherited as an autosomal recessive trait.