gebhart/patrepeval huggingface dataset:
(R)-(-)-10-Methyl-11-hydroxyaporphine: a highly selective serotonergic agonist (1988)

Prior work in these laboratories identified (+/-)-5-hydroxy-6-methyl-2- (di-n-propylamino)tetralin as a dopaminergic agonist prodrug. The ortho methyl hydroxy aromatic substitution pattern in this molecule has now been incorporated into the aporphine ring system to give a congener of the dopaminergic agonist apomorphine in which the position 10 OH group has been replaced by methyl. Preparation of the target compound involved acid-catalyzed rearrangement of the 3-(1-phenyltetrazolyl) ether of morphine and subsequent molecular modification of the product, the 10-(1-phenyltetrazolyl) ether of (R)-(-)-apomorphine. Surprisingly, the target compound elicited no responses in any assays for effects at dopamine receptors, but rather it displayed pharmacological properties consistent with its being a serotonergic agonist with a high degree of selectivity for 5-HT1A receptors similar to the serotonergic agonist 8-hydroxy-2-(di-n-propylamino)tetralin.
An image-directed robotic system for precise orthopaedic surgery (1994)

The authors have developed an image-directed robotic system to augment the performance of human surgeons in precise bone machining procedures in orthopaedic surgery, initially targeted at cementless total hip replacement surgery. The total system consists of an interactive CT-based presurgical planning component and a surgical system consisting of a robot, redundant motion monitoring, and man-machine interface components. In vitro experiments conducted with this system have demonstrated an order-of-magnitude improvement in implant fit and placement accuracy, compared to standard manual preparation techniques. The first generation system described in this paper was used in a successful veterinary clinical trial on 26 dogs needing hip replacement surgery. It was the basis for subsequent development of a second-generation system that is now in human clinical trials.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Dynamic characterization of elastico-mechanoluminescence towards structural health monitoring (2017)

Light emission from zinc sulfide phosphors during elastic loading (elastico-mechanoluminescence, or EML) is characterized for application in structural health monitoring. Micron-sized EML particles are dispersed in an elastomeric matrix for characterization experiments. Numerical models and experimental investigations are combined to arrive at a correlation between EML emission intensity and average stress acting on phosphor particles. A maximum luminance of 25 cd/m 2 is observed from composites with a 6.25:3 phosphor–matrix weight ratio. This intensely bright EML emission is visible under indoor lighting and is attributed to efficient interfacial stress transfer between the matrix and particles facilitated by a moisture-resistant coating. EML emission is captured over 2.5 million actuation cycles and a correlation between the structural health of the elastomer and the measured EML intensity is made. A significant drop in EML emission is observed right before the onset of structural failure which enables real-time prediction and prevention.
Emerging Concepts in the Immunopathogenesis of AIDS (2008)

There is an intense interplay between HIV and the immune system, and the literature is replete with studies describing various immunological phenomena associated with HIV infection. Many of these phenomena seem too broad in scope to be attributable either to HIV-infected cells or to the HIV-specific immune response. Recently, a more fundamental understanding of how HIV affects various T cells and T cell compartments has emerged. This review covers the role of immune activation in HIV immunopathogenesis, how that activation could be mediated directly by HIV replicating within and damaging the gut mucosal barrier, how HIV affects multiple T cell functions and phenotypes, and how chronic HIV replication induces immune modulatory pathways to negatively regulate certain functions in HIV-specific T cells.
A Novel Mode of Intervention with Serine Protease Activity (2008)

Serine proteases are secreted from cells as single-chain zymogens, typically having activities orders of magnitude lower than those of the mature two-chain enzymes. Activation occurs by a conformational change initiated by cleavage of a specific peptide bond. We have derived a monoclonal antibody (mAb-112) which binds with subnanomolar affinity to pro-uPA, the zymogen form of urokinase-type plasminogen activator (uPA). We mapped the epitope of the antibody to the autolysis loop, one of the structural elements known to change conformation during zymogen activation. A mechanistic evaluation with biophysical methods elucidated a novel bifunctional inhibitory mechanism whereby mAb-112 not only delays the proteolytic conversion of single-chain pro-uPA into the two-chain form but also subsequently averts the conformational transition to a mature protease by sequestering the two-chain form in a zymogen-like, noncatalytic state. Functional studies employing two variants of human HT-1080 cells, exhibiting high and low levels of dissemination in a chorioallantoic membrane assay, demonstrate that mAb-112 is an effective inhibitor of tumor cell intravasation. These findings show that pharmacological interference with zymogen activation is a plausible and robust means to regulate uPA activity and the downstream effects of plasminogen activation in the spread of cancer and other processes of pathological tissue remodeling. A strategy that targets regions related to pro-enzyme activation likely provide a unique inhibitor-protease interaction surface and is, thus, expected to enhance the chances of engineering high inhibitor specificity. Our results provide new information about the structural flexibility underlying the equilibrium between active and inactive forms of serine proteases.
Effect of Adenovirus-Mediated Expression of Sonic Hedgehog Gene on Hair Regrowth in Mice With Chemotherapy-Induced Alopecia (2001)

Localized, transient, enhanced expression of Shh gene in skin, mediated by an adenovirus vector, might be a future strategy to accelerate hair follicle regrowth after chemotherapy-induced alopecia.
Reconstruction of a thyroid gland equivalent from cells and matrix materials (1984)

Abstract A living thyroid gland equivalent has been fabricated with a cultivated strain of rat thyroid cells (FRTL), dermal or thyroid fibroblasts, and matrix materials. The mixture becomes tissuelike in vitro by virtue of interactions between fibroblasts and collagen. Initially in vitro the thyroid cells are uniformly distributed as single cells and a small number of clusters containing less than 10 cells. When implanted into thyrodectomized hosts the thyroid cells in the tissue lattice become organized into follicles containing a colloidlike material. The follicles were found in clusters in sizes up to 0.3 mm. The clusters are vascularized. It is thought that they arise within clones rather than by an aggregation process. Using an antithyroglobulin antibody it was shown that both thyroid cells and the colloidlike material within follicles reacted positively. Development of follicles was strictly dependent on whether hosts were thyroidectomized. In nonthyroidectomized hosts no follicles were observed. We conclude that an organotypic structure can develop in vivo from a “gland‐equivalent” fabricated with adult cells and matrix materials combined in vitro, and that cells cultivated for years in vitro retain the capacity to express differentiated functions in a reconstituted organ equivalent in vivo.
Repetitive mild traumatic brain injury induces ventriculomegaly and cortical thinning in juvenile rats (2015)

Traumatic brain injury (TBI) most frequently occurs in pediatric patients and remains a leading cause of childhood death and disability. Mild TBI (mTBI) accounts for nearly 75% of all TBI cases, yet its neuropathophysiology is still poorly understood. While even a single mTBI injury can lead to persistent deficits, repeat injuries increase the severity and duration of both acute symptoms and long-term deficits. In this study, to model pediatric repetitive mTBI (rmTBI) we subjected unrestrained juvenile animals (postnatal day 20) to repeat weight-drop impacts. Animals were anesthetized and subjected to sham injury or rmTBI once per day for 5 days. Magnetic resonance imaging (MRI) performed 14 days after injury revealed marked cortical atrophy and ventriculomegaly in rmTBI animals. Specifically, beneath the impact zone the thickness of the cortex was reduced by up to 46% and the area of the ventricles increased by up to 970%. Immunostaining with the neuron-specific marker NeuN revealed an overall loss of neurons within the motor cortex but no change in neuronal density. Examination of intrinsic and synaptic properties of layer II/III pyramidal neurons revealed no significant difference between sham-injured and rmTBI animals at rest or under convulsant challenge with the potassium channel blocker 4-aminopyridine. Overall, our findings indicate that the neuropathological changes reported after pediatric rmTBI can be effectively modeled by repeat weight drop in juvenile animals. Developing a better understanding of how rmTBI alters the pediatric brain may help improve patient care and direct "return to game" decision making in adolescents.
Rock albedo and monitoring of thermal conditions in respect of weathering: some expected and some unexpected results (2005)

Abstract Broadly speaking, there is, at least within geomorphic circles, a general acceptance that rocks with low albedos will warm both faster and to higher temperatures than rocks with high albedos, reflectivity influencing radiative warming. Upon this foundation are built notions of weathering in respect of the resulting thermal differences, both at the grain scale and at the scale of rock masses. Here, a series of paving bricks painted in 20 per cent reflectivity intervals from black through to white were used to monitor albedo‐influenced temperatures at a site in northern Canada in an attempt to test this premise. Temperatures were collected, for five months, for the rock surface and the base of the rock, the blocks being set within a mass of local sediment. Resulting thermal data did indeed show that the dark bricks were warmer than the white but only when their temperatures were equal to or cooler than the air temperature. As brick temperature exceeded that of the air, so the dark and light bricks moved to parity; indeed, the white bricks frequently became warmer than the dark. It is argued that this ‘negating’ of the albedo influence on heating is a result of the necessity of the bricks, both white and black, to convect heat away to the surrounding cooler air; the darker brick, being hotter, initially convects faster than the white as a product of the temperature difference between the two media. Thus, where the bricks become significantly hotter than the air, they lose energy to that air and so their respective temperatures become closer, the albedo influence being superceded by the requirement to equilibrate with the surrounding air. It is argued that this finding will have importance to our understanding of weathering in general and to our perceptions of weathering differences between different lithologies. Copyright © 2005 John Wiley &amp; Sons, Ltd.
Photochemie elektronenreicher 1,3‐Distyrylbenzole (1988)

Abstract Die 1,3‐Distyrylbenzole 3 mit bis zu sieben Alkoxygruppen werden der oxidativen Photocyclisierung unterworfen. Bei der Bildung der Produkte 6, 7 und 8 können als Konkurrenz‐ bzw. Folgeprozesse die Abspaltung von Methanol ( 3bb → 7bb , 3bf → 7bf ) und die Chinonoxidation ( 3cf → 8 ) auftreten. Die eigensensiblisierte Erzeugung von Singulettsauerstoff kann bei 6bf zur Endoperoxidbildung führen ( 6bf → 11 ).
Buffalopox: an emerging and re-emerging zoonosis (2007)

Outbreaks of buffalopox or pox-like infections affecting buffaloes, cows and humans have been recorded in many parts of the world. Since the first outbreak in India, a large number of epidemics have occurred. Unlike in the previous years, generalized forms of the disease are now rare; however, there are severe local forms of the disease affecting the udder and teats, leading to mastitis thereby undermining the productivity of milk animals. The causative agent buffalopox virus (BPXV) is a member of the Orthopoxvirus, and is closely related to Vaccinia virus (VACV), the type-species of the genus. Earlier studies with restriction fragment length polymorphism and recent investigations involving sequencing of the genes that are essential in viral pathogenesis have shown that BPXV is phylogenetically very closely related to VACV and may be considered as a clade of the latter. The review discusses the epidemiology, novel diagnostic methods for the disease, and molecular biology of the virus, and infers genetic relationships of BPXV with other members of the genus.
Flow cytometric monitoring of anthracycline accumulation after anti-neoplastic ether phospholipid treatment (1994)

Ether phospholipids are new anti-neoplastic drugs that have been found active against a variety of tumor cell lines, including drug-resistant sublines. We have characterized the antiproliferative activity of three ether phospholipids, i.e. ET-18-OCH3 (Edelfosine), BM 41.440 (limofosine) and a new aza-derivative (BN 52205), on three leukemic cell lines, i.e. K562 (chronic myeloid leukemia, blast crisis), HL60 (promyelocytic acute leukemia) and CEM (T cell leukemia), and their respective drug-resistant sublines, i.e. K562-ADR (adryamicin resistant), HL60-DNR [daunorubicin (DNR) resistant] and CEM-VLB (vinblastin resistant). These resistant sublines have been found to express the multidrug-resistant phenotype, revealed by the presence of the P-glycoprotein (PgP) using different monoclonal antibodies. Increased cellular accumulation of the fluorescent anthracycline has been found in both sensitive and resistant cell lines after different ether phospholipid treatment times. In resistant cells, the ether phospholipid effect on DNR accumulation has also been found after blocking the PgP function by verapamil and cyclosporin A. These results confirm that the ether phospholipid action is closely linked with the membrane biochemical composition and that these new anti-tumor drugs are able to change the dynamic structural organization of the tumor cell membrane.
LNCaP Atlas: Gene expression associated with in vivoprogression to castration-recurrent prostate cancer (2010)

The in vivo gene expression atlas for LNCaP was sequenced and support a role for the androgen receptor in CRPC.
Dynamic simulations help improve generator protection (2007)

This paper describes a digital simulation study of a set of two 160 MW generating units operating in the Juan de Dios Batiz Paredes thermal power station, in Topolobampo, Sinaloa, Mexico. This plant belongs to Comision Federal de Electricidad, the national Mexican utility. We first discuss the factors that limit the active and reactive power delivered by a generating unit, such as thermal and voltage limits, power-system imposed limits, and the minimum excitation limiter. We then describe generator protection functions related to the capability curve. Later, we propose a P-Q plane-based scheme that provides generator loss-of-field protection and capability-curve violation alarming. Finally, we present the simulation results of loss-of-field and loss-of-synchronism conditions of one of the two generating units for several cases, including different initial load conditions, different loss-of-field modes, and different numbers of units on line.
Nucleotide sequence and expression of human chromosome 21-encoded superoxide dismutase mRNA. (1983)

Cytoplasmic superoxide dismutase (SOD-1; EC 1.15.1.1) is encoded by human chromosome 21. The SOD-1 gene locus is located at chromosomal region 21q22, which is involved in Down syndrome. cDNA clones containing sequences of human SOD-1 were previously isolated. In the present study the nucleotide sequence of one clone, designated pS61-10, was determined. It contains 459 nucleotides representing the entire coding region and 95 nucleotides of the 3' untranslated region. In human cells two poly(A)-containing SOD-1 RNAs of 0.7 and 0.5 kilobases were detected. These two species are also present in monkey cells, whereas mouse cells contain only a 0.5-kilobase RNA. In a mouse/human hybrid line that contains chromosome 21 as the only human chromosome, the two human SOD-1 RNAs were detected, indicating that both are encoded by this chromosome. These RNAs were found in poly(A)-containing polysomal RNA and were translated in vitro to SOD-1 polypeptide; they are therefore functional mRNAs. In normal human fibroblasts 0.002-0.006% of the poly(A)-containing RNA was SOD-1 RNA. The level in monosomic 21 cells was 70% of this value and the level in fibroblasts from Down syndrome patients was about 2 times higher than normal.
Vulvovaginal candidiasis from non-albicans species: retrospective study of recurrence rate after fluconazole therapy. (2006)

The recurrence rate of symptomatic vulvovaginal candidiasis colonized by non-albicans species after fluconazole therapy was 50.4% at 6 months and 54.2% at 12 months. Nulliparity and age <35 or > 65 years and fastidious vulvar cleaning were positively associated with symptomatic recurrent episodes.
Gaussian process data fusion for heterogeneous HRTF datasets (2013)

Head-Related Transfer Function (HRTF) measurement and extraction are important tasks for personalized-spatial audio. Many laboratories have their own apparatuses for data-collection but few studies have compared their results to a common subject or have modeled inter-dataset variances. We present a Bayesian fusion method based on Gaussian process (GP) modeling of joint spatial-frequency HRTFs over different spherical-measurement grids. Neumann KU-100 dummy HRTFs from 7 labs in the “Club Fritz” study are compared and fused to each other based on learning a set of transformations from the GP data-likelihood and covariance assumptions; parameter and hyperparameter training is automatic. Experimental results show that fused models for horizontal and median-plane HRTFs generalize the datasets better than pre-transformed ones.
APC promoter methylation and protein expression in hepatocellular carcinoma (2007)

Promoter methylation of the APC gene seems to be of significance in hepatocarcinogenesis and results in reduced protein expression in HCC. Interestingly, APC promoter methylation is also present in the vast majority of non-cancerous liver tissue whose (patho)physiological function remains unresolved.
Experiences with the new genetic variant of Chlamydia trachomatis in Örebro county, Sweden – proportion, characteristics and effective diagnostic solution in an emergent situation (2007)

A Chlamydia trachomatis variant that contains a 377 bp deletion in the cryptic plasmid was recently reported in Sweden. This deletion includes the targets for Cobas Amplicor, Cobas TaqMan48, and Abbott m2000. We examined the proportion and characteristics of this variant in Orebro county, Sweden and developed an effective diagnostic solution. In total, 2,401 consecutive C. trachomatis culture samples and 536 PCR samples from symptomatic and asymptomatic patients and screened females were included. Culture, Cobas Amplicor, and LightMix 480HT were used for diagnosis. A mutant-specific PCR, plasmid sequencing, omp1 sequencing and multilocus sequence typing (MLST) were used to identify and characterise mutants. In total, 162 (6.7%) of the cultured samples were positive for C. trachomatis. However, 61 (38%) of those were negative when using Cobas Amplicor, and 60 of these were subsequently confirmed as the new variant. 13 of these mutant isolates were further characterised genetically, and all were of identical genotype E and the unique MLST sequence type: 21, 19, 1, 2, 1. Of all culture-positive samples, 161 of 162 were positive in the LightMix 480HT assay. The single negative sample was only weakly positive in culture, and negative in all PCRs. Of the 536 PCR samples, 37 were positive in both Cobas Amplicor and LightMix 480HT, 13 were only positive in LightMix 480HT (mutants), and two were only positive in Cobas Amplicor. Mutated C. trachomatis were prevalent in Orebro county in the period from October 2006 to February 2007, and it appeared to be a single clone. LightMix 480HT seemed sensitive, specific, and enabled high throughput diagnostics. However, rare low positive samples may be false-negative. Frequent surveillance and evaluations of diagnostic methods worldwide are crucial.
Microfabricated immunoisolating biocapsules (1998)

A microfabricated silicon-based biocapsule for the immunoisolation of cell transplants is presented. The biocapsule-forming process employs bulk micromachining to define cell-containing chambers within single crystalline silicon wafers. These chambers interface with the surrounding biological environment through polycrystalline silicon filter membranes. The membranes are surface micromachined to present a high density of uniform pores, thus affording sufficient permeability to oxygen, glucose, and insulin. The pore dimensions, as small as 20 nm, are designed to impede the passage of immune molecules and graft-borne viruses. The underlying filter-membrane nanotechnology has been successfully applied in controlled cell culture systems (Ferrari et al., 1995), and is under study for viral elimination in plasma fractionation protocols. Here we report the encouraging results of in vitro experiments investigating the biocompatibility of the microfabricated biocapsule, and demonstrate that encapsulated rat neonatal pancreatic islets significantly outlive and outperform controls in terms of insulin-secretion capability over periods of several weeks. These results appear to warrant further investigations on the potential of cell xenografts encapsulated within microfabricated, immunoisolating environments for the treatment of insulin-dependent diabetes.
The Cytokine Network in the Critically Ill (1992)

There is increasing experimental and clinical evidence that a number of cytokines play a major role in the response to injury and infection and in the development of organ damage in critically ill patients. Tumour necrosis factor (TNF) is now proposed to be a key mediator of organ injury during sepsis. It is elevated early in the course of septic shock and high levels correlate with unfavourable outcome. In animals it can produce the effects of endotoxin. The prophylactic administration of anti-TNF antisera protects mice and rabbits from lethal effects of lipopolysaccharide. Interleukin-1 (IL-1) is an endogenous pyrogen which induces leukocytosis and muscle catabolism. It causes hypotension and tachycardia by reducing smooth muscle contractility. IL-1 receptor blockers have been shown to diminish mortality in experimental endotoxic shock. Interleukin-6 (IL-6) is a pyrogen and lymphocyte activator. It is the major stimulus to acute phase protein production by the liver. A recently described neutrophil-activating peptide (Interleukin-8; IL-8) may be involved in the pathogenesis of ARDS. High blood levels of IL-8 have been found in patients with septic shock. Platelet-derived growth factor (PDGF) has been shown to stimulate TNF production, leukocyte chemotaxis and pulmonary vasoconstriction in response to endotoxin. Other cytokines and growth factors have not yet been studied in critical illness. The cytokine network can be either protective or damaging. Its activation during critical illness triggers complex and still poorly understood interactions. A better comprehension of its role in protection from infection and in the pathogenesis of multiple organ failure may allow therapeutic manipulations aimed at minimising adverse effects while retaining immunological protection.