gebhart/patrepeval huggingface dataset:
Targeting the X Chromosome during Spermatogenesis Induces Y Chromosome Transmission Ratio Distortion and Early Dominant Embryo Lethality in Anopheles gambiae (2008)

We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes induced a strong bias toward Y chromosome-carrying spermatozoa. Notably, these male mosquitoes also induced complete early dominant embryo lethality in crosses with wild-type females. Morphological and molecular data indicated that all spermatozoa, irrespectively of the inheritance of the transgene, carried a substantial amount of I-PpoI protein that could attack the maternally inherited chromosome X of the embryo. Besides the obvious implications for implementing vector control measures, our data demonstrated the feasibility of generating synthetic sex distorters and revealed the intriguing possibility of manipulating maternally inherited genes using wild-type sperm cells carrying engineered endonucleases.
Disruption of PF4/H multimolecular complex formation with a minimally anticoagulant heparin (ODSH) (2012)

Recent studies have shown that ultra-large complexes (ULCs) of platelet factor 4 (PF4) and heparin (H) play an essential role in the pathogenesis of heparin-induced thrombocytopenia (HIT), an immune-mediated disorder caused by PF4/H antibodies. Because antigenic PF4/H ULCs assemble through non-specific electrostatic interactions, we reasoned that disruption of charge-based interactions can modulate the immune response to antigen. We tested a minimally anticoagulant compound (2-O, 3-O desulfated heparin, ODSH) with preserved charge to disrupt PF4/H complex formation and immunogenicity. We show that ODSH disrupts complexes when added to pre-formed PF4/H ULCs and prevents ULC formation when incubated simultaneously with PF4 and UFH. In other studies, we show that excess ODSH reduces HIT antibody (Ab) binding in immunoassays and that PF4/ODSH complexes do not cross-react with HIT Abs. When ODSH and unfractionated heparin (UFH) are mixed at equimolar concentrations, we show that there is a negligible effect on amount of protamine required for heparin neutralisation and reduced immunogenicity of PF4/UFH in the presence of ODSH. Taken together, these studies suggest that ODSH can be used concurrently with UFH to disrupt PF4/H charge interactions and provides a novel strategy to reduce antibody mediated complications in HIT.
Fibronectin, laminin, and collagen types I, III, IV and V in the healing rat colon anastomosis. (1990)

The purpose of this work was to study normal anastomotic healing in the rat colon. The unprepared sigmoid colon was divided and a colo-colostomy performed using a one-layer inverting technique. Frozen sections were taken and studied immunohistologically with specific antibodies to fibronectin, laminin and collagen types I, III, IV and V. From day one onwards a strong fibronectin reaction was observed in the anastomosis, reaching maximum staining intensity on postoperative day five. Type III collagen and pericellular type V collagen were at first detected in the anastomosis on day two. From day three onwards all collagens studied and laminin were present in the repair tissue (laminin and type IV and V collagen in the regenerating capillary walls). Maximum immunofluorescence was observed on day seven and it remained on a high level throughout the study, except for fibronectin, which weakened gradually after the fifth postoperative day. The results indicate that healing of the colon anastomosis occurs by rapid accumulation of connective tissue components between the inverted leaves of the colonic wall, as also new capillaries consisting of the basement membrane components, type IV and V collagen as well as laminin, are formed.
Human 5-HT1A receptor C(−1019)G polymorphism and psychopathology (2004)

Dysfunction of the serotonin (5-HT1A) receptor (5-HTR1A) has been implicated in mood disorders, anxiety disorders, psychosis and the action of antidepressants. A common C(-1018)G [C(-1019)G] functional polymorphism in the promoter region of the human 5-HT1A receptor gene has been reported, which may be useful in identifying psychopathology associated with altered function of the human 5-HT1A receptor. We studied the relationship of this polymorphism to psychopathology and 5-HT1A binding in prefrontal cortex. The 5-HT1A receptor genotype for the C(-1019)G polymorphism was typed in 696 unrelated psychiatric subjects, 107 unrelated healthy volunteers, and in post-mortem brain samples from 241 cases. 5-HT1A receptor binding was assayed in post-mortem prefrontal cortex using [3H]8-OH-DPAT, and specific binding determined by 1 microM 5-HT. An association of genotype distribution and allele frequency of the 5-HTR1A C(-1019)G locus was observed in schizophrenia (chi2=9.51, d.f.=2, p=0.009; chi2=9.52, d.f.=1, p=0.002; Armitage's trend test: chi2=9.07, d.f.=1, p=0.003), in substance use disorder (chi2=8.41, d.f.=2, p=0.015; chi2=8.35, d.f.=1, p=0.004; Armitage's trend test: chi2=6.27, d.f.=1, p=0.0012), and in panic attack (chi2=6.31, d.f.=2, p=0.043; chi2=6.14, d.f.=1, p=0.013; Armitage's trend test: chi2=6.27, d.f.=1, p=0.012). An association of the 5-HTR1A C(-1019)G locus with schizophrenia, substance use disorder, and panic attack was suggested by our results. In post-mortem brain samples, 5-HT1A receptor binding in prefrontal cortex and suicide were not associated with genotype. The relationship does not appear to be explained by binding differences, although we cannot rule out altered receptor affinity and transduction.
Automated acoustic intensity measurements and the effect of gear tooth profile on noise (1987)

Acoustic intensity measurements were made at NASA Lewis Research Center on a spur gear test apparatus. The measurements were obtained with the Robotic Acoustic Intensity Measurement System developed by Cleveland State University. This system provided dense spatial positioning, and was calibrated against a high quality acoustic intensity system. The measured gear noise compared gearsets having two different tooth profiles. The tests evaluated the sound field of the different gears for two speeds and three loads. The experimental results showed that gear tooth profile had a major effect on measured noise. Load and speed were found to have an effect on noise also.
Flexible Analog Search with Kernel PCA Embedded Molecule Vectors (2017)

Studying analog series to find structural transformations that enhance the activity and ADME properties of lead compounds is an important part of drug development. Matched molecular pair (MMP) search is a powerful tool for analog analysis that imitates researchers' ability to select pairs of compounds that differ only by small well-defined transformations. Abstraction is a challenge for existing MMP search algorithms, which can result in the omission of relevant, inexact MMPs, and inclusion of irrelevant, contextually dissimilar MMPs. In this work, we present a new method for MMP search that returns approximate results and enables flexible control over abstraction of contextual information. We illustrate the concepts and mechanics of our method with a series of exemplar MMP queries, and then benchmark search accuracy using MMPs found by fragment indexing. We show that we can search for MMPs in a context dependent manner, and accurately approximate context independent fragment index based MMP search over a range of fingerprint and dataset conditions. Our method can be used to search for pairwise correspondences among analog sets and bolster MMP datasets where data is missing or incomplete.
Penetration state transition analysis: A rule-based intrusion detection approach (2003)

A new approach to representing computer penetrations is introduced called penetration state transition analysis. This approach models penetrations as a series of state transitions described in terms of signature actions and state descriptions. State transition diagrams are written to correspond to the states of an actual computer system, and these diagrams form the basis of a rule-based expert system for detecting penetrations, referred to as STAT.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Endorphin-Mediated Increases in Pain Threshold During Pregnancy (1980)

Maternal pain thresholds in rats were determined during various stages of pregnancy and parturition by measuring the intensity of electric shock that elicited reflexive jumping. There was a gradual rise in the pain threshold between 16 and 4 days prior to parturition and a more abrupt rise 1 to 2 days before that event. This increase was abolished by long-term administration of the narcotic antagonist naltrexone. The endorphin system is thus an important component of intrinsic mechanisms that modulate responsiveness to aversive stimuli. The data also demonstrate the activation during pregnancy of an endorphin system that is apparently quiescent in nonpregnant female rats treated the same way.
Chemical Studies ofAloe VeraJuice II: Inorganic Ingredients (1969)

(1969). Chemical Studies of Aloe Vera Juice II: Inorganic Ingredients. Quarterly Journal of Crude Drug Research: Vol. 9, No. 4, pp. 1445-1453.
The Stumbling Block in Lung Repair of Emphysema: Elastic Fiber Assembly (2006)

The mechanical properties of the lung are largely determined by the connective tissue networks laid down during development. The macromolecules most important for lung mechanics and structural integrity are collagen, elastin, and proteoglycans. Members of the fibrillar collagen gene family provide the structural framework of the various lung compartments and elastic fibers provide elastic recoil. Elastin is also an important architectural component that influences lung development, predominantly during the alveolar stage. Previous studies have conclusively shown that elastin degradation is a key step in the pathogenesis of chronic obstructive pulmonary disease. Exacerbating the disease process is the inability of lung cells to repair damaged elastic fibers, which leads to permanently compromised lung function and ongoing degenerative disease. Elastic fibers are among the most difficult matrix structures to repair because of their size, molecular complexity, and the requirement for numerous helper proteins to facilitate fiber assembly. Recent studies of elastin assembly combined with new insight into the functional role of elastic fiber proteins obtained from gene inactivation studies and linkage of human disease to elastin mutations provide new insight into the molecular and cellular complexities of elastin homeostasis.
Anxiolyticlike Effects of Atrial Natriuretic Peptide on Cholecystokinin Tetrapeptide–Induced Panic Attacks (2001)

The present study indicates that ANP exerts anxiolyticlike effects on CCK-4-stimulated anxiety attacks in patients with panic disorder. In addition, ANP produced an inhibition of the hypothalamopituitary-adrenocortical system and sympatholytic effects.
Rapid analysis of controlled substances using desorption electrospray ionization mass spectrometry (2005)

The recently developed technique of desorption electrospray ionization (DESI) has been applied to the rapid analysis of controlled substances. Experiments have been performed using a commercial ThermoFinnigan LCQ Advantage MAX ion-trap mass spectrometer with limited modifications. Results from the ambient sampling of licit and illicit tablets demonstrate the ability of the DESI technique to detect the main active ingredient(s) or controlled substance(s), even in the presence of other higher-concentration components. Full-scan mass spectrometry data provide preliminary identification by molecular weight determination, while rapid analysis using the tandem mass spectrometry (MS/MS) mode provides fragmentation data which, when compared to the laboratory-generated ESI-MS/MS spectral library, provide structural information and final identification of the active ingredient(s). The consecutive analysis of tablets containing different active components indicates there is no cross-contamination or interference from tablet to tablet, demonstrating the reliability of the DESI technique for rapid sampling (one tablet/min or better). Active ingredients have been detected for tablets in which the active component represents less than 1% of the total tablet weight, demonstrating the sensitivity of the technique. The real-time sampling of cannabis plant material is also presented.
Multiple-dose pharmacokinetics of rectally administered acetaminophen in term infants (1999)

In term neonates, multiple rectal doses of acetaminophen, 20 mg/kg body weight, led to widely varying serum concentrations but did not result in therapeutic concentrations in all infants. Boys had higher peak concentrations. Because accumulation was not found, a dose of 30 mg/kg followed by doses of 20 mg/kg at 6- to 8-hour administration intervals are appropriate to reach therapeutic concentrations. A concentration-effect relationship could not be determined.
Prognostic Value of Histologic Grade and Proliferative Activity in Axillary Node–Positive Breast Cancer: Results From the Eastern Cooperative Oncology Group Companion Study, EST 4189 (2000)

A subset of axillary lymph node-positive patients with improved prognosis may be identified using a lower (< 3 mitoses/10 HPF) mitotic count than is usually performed.
Conjugated linoleic acid—snake oil or wonder fat? (1999)

Conjugated linoleic acid is a mixture of positional and geometric isomers of linoleic acid with conjugated double bonds located at positions 7,9, 8,10, 9,11, 10,12 or 11,13 on the carbon chain. Substantial amounts of CLA are found in products of ruminant origin due to the presence of anaerobic bacteria in the rumen that are responsible for the synthesis of CLA or precursors. Over the past decade there has been increasing interest in this group of fatty acids, particularly because of the potent antioxidative and anticarcinogenic properties attributed to one or more of these isomers. In addition, under some circumstances, dietary conjugated linoleic acid has been shown to decrease fat accretion in rodents. In this review we have compiled some very recent data on the effects of CLA on lipid metabolism in large domestic animals, specifically pigs and dairy cows. There is growing evidence that at least one isomer of CLA is a potent inhibitor of fat accretion and milk fat secretion. While the broad ranging effects of CLA that are discussed may appear reminiscent of some previous much touted snake oils it is hoped that this review may persuade the reader to rank CLA more as a wonder fat.
A field study of the software design process for large systems (1988)

The problems of designing large software systems were studied through interviewing personnel from 17 large projects. A layered behavioral model is used to analyze how three of these problems—the thin spread of application domain knowledge, fluctuating and conflicting requirements, and communication bottlenecks and breakdowns—affected software productivity and quality through their impact on cognitive, social, and organizational processes.
Transfusion and acute lung injury in the critically ill (2006)

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN (Gajic) Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA (Toy)
Membrane‐anchored growth factors, the epidermal growth factor family: Beyond receptor ligands (2008)

The epidermal growth factor (EGF) family and the EGF receptor (EGFR, ErbB) tyrosine kinase family have been spearheading the studies of signal transduction events that determine cell fate and behavior in vitro and in vivo. The EGFR family and their signaling pathways are giving us tremendous advantages in developing fascinating molecular target strategies for cancer therapy. Currently, two important types of EGFR inhibitors are in clinical use: neutralizing antibodies of EGFR or ErbB2, and synthetic small compounds of tyrosine kinase inhibitors designed for receptors. On the other hand, basic research of the EGF family ligands presents new challenges as membrane-anchored growth factors. All members of the EGF family have important roles in development and diseases and are shed from the plasma membrane by metalloproteases. The ectodomain shedding of the ligands has emerged as a critical component in the functional transactivation of EGFRs in interreceptor cross-talk in response to various shedding stimulants such as G-protein coupled receptor agonists, growth factors, cytokines, and various physicochemical stresses. Among the EGFR-ligands, heparin-binding EGF-like growth factor (HB-EGF) is a prominent ligand in our understanding of the pathophysiological roles of ectodomain shedding in cancer, wound healing, cardiac diseases, etc. Here we focus on ectodomain shedding of the EGF family ligands, especially HB-EGF by disintegrin and metalloproteases, which are not only key events of receptor cross talk, but also novel intercellular signaling by their carboxy-terminal fragments to regulate gene expression directly.
How does surface wettability influence nucleate boiling? (2009)

Although the boiling process has been a major subject of research for several decades, its physics still remain unclear and require further investigation. This study aims at highlighting the effects of surface wettability on pool boiling heat transfer. Nanocoating techniques were used to vary the water contact angle from 20° to 110° by modifying nanoscale surface topography and chemistry. The experimental results obtained disagree with the predictions of the classical models. A new approach of nucleation mechanism is established to clarify the nexus between the surface wettability and the nucleate boiling heat transfer. In this approach, we introduce the concept of macro- and micro-contact angles to explain the observed phenomenon.
Oxprenolol absorption in man after single bolus dosing into two segments of the colon compared with that after oral dosing. (1985)

The systemic availability of oxprenolol after colonic and oral administration has been compared in a crossover study involving six healthy male volunteers. Drug administration into two regions of the colon (caecum and left flexure) was achieved by means of a colonoscopic technique. There were no obvious differences in plasma concentrations after drug administration to the caecum and left flexure, although in one subject it was necessary to repeat colonic administration because of unexpectedly high plasma drug levels on the first occasion. The possible reasons for this abnormal response are discussed. The mean systemic availability of oxprenolol was 82% after colonic compared with oral dosing, although marked differences were observed in individual plasma levels following drug administration by the two routes. The results of this study support the concept of extending the duration of oxprenolol release from a rate‐controlled dosage form to permit once‐ daily administration with this short elimination half‐life drug.
Cell-Specific Gene Expression In Plants (1990)

We have made rapid progress in recent years in identifying the genetic causes of many human diseases. However, despite this recent progress, our mechanistic understanding of these diseases is often incomplete. This is a problem because it limits our ...Read More
Electrical stimulation of the sciatic nerve alters neuropeptide content and lymphocyte migration in the subcutaneous tissue of the rat hind paw (1995)

To study the possible mechanism by which peripheral nerves mediate immune responses in target tissues, electrical stimulation of the sciatic nerve was combined with subcutaneous microdialysis of the hind paw. Following unilateral stimulation of the sciatic nerve, an ipsilateral rise in substance P and a bilateral rise in VIP levels were observed in dialysate samples from experimental vs control animals. Electrical stimulation of the sciatic nerve induced a marked hyperemia and swelling of the ipsilateral paw. Quantitative immunocytochemical analysis of paraffin-embedded sections of the hind foot pads demonstrated T lymphocyte migration ipsilateral to the stimulated nerve. These findings suggest that peripheral nerves can directly modulate local immune and inflammatory responses.
Integrin-mediated localization of Bordetella pertussis within macrophages: role in pulmonary colonization. (1991)

The adherence of Bordetella pertussis to human respiratory cilia is critical to the pathogenesis of whooping cough but the significance of bacterial attachment to macrophages has not been determined. Adherence to cilia and macrophages is mediated by two large, nonfimbrial bacterial proteins, filamentous hemagglutinin (FHA), and pertussis toxin (PT). PT and FHA both recognize carbohydrates on cilia and macrophages; FHA also contains an Arg-Gly-Asp (RGD) sequence which promotes bacterial association with the macrophage integrin complement receptor 3 (CR3). We determined that virulent B. pertussis enter and survive in mammalian macrophages in vitro and that CR3 is important for this uptake process. We then determined the relative contribution of CR3 versus carbohydrate-dependent interactions to in vivo pulmonary colonization using a rabbit model. B. pertussis colonized the lung as two approximately equal populations, one extracellular population attached to ciliary and macrophage surface glycoconjugates and another population within pulmonary macrophages. Loss of the CR3 interaction, either by mutation of FHA or treatment with antibody to CR3, disrupted accumulation of viable intracellular bacteria but did not prevent lung pathology. In contrast, elimination of carbohydrate-bound bacteria, either by a competitive receptor analogue or an anti-receptor antibody, was sufficient to prevent pulmonary edema. We propose that CR3-dependent localization of B. pertussis within macrophages promotes persistence of bacteria in the lung without pulmonary injury. On the other hand, the presence of extracellular bacteria adherent to cilia and macrophages in carbohydrate-dependent interactions is associated with pulmonary pathology.