gebhart/patrepeval huggingface dataset:
Neurohumoral interactions in conscious dehydrated rabbit (1988)

The purpose of this study was to examine the role of angiotensin II (ANG II), arginine vasopressin (AVP), and neurogenic mechanisms in maintaining arterial pressure (MAP) in conscious water-deprived rabbits. Water deprivation produced marked increases in plasma renin activity and the concentration of AVP; however, plasma catecholamine concentrations were unchanged. Arterial baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) was similar in water-replete and dehydrated animals. Administration of an ANG II receptor antagonist (ANG IIX) to water-deprived animals produced a small decrease in MAP but no significant changes in HR or mesenteric and hindquarters vascular resistances. Similarly, there was no significant effect on MAP, HR, or regional hemodynamics when dehydrated animals received an AVP-V1 antagonist (AVPX). RSNA increased by maximums of 61 and 43% in response to ANG IIX and AVPX, respectively. Combined administration of ANG IIX and AVPX produced significant decreases in MAP (-9 mmHg) and hindquarters resistance (-24%) and 117% and 23 beat/min increases in RSNA and HR, respectively. The effect on mesenteric resistance was variable; however, the response was generally a decrease. We conclude that ANG II and AVP pressor mechanisms are activated to sustain MAP in the dehydrated state. In contrast, the basal level and baroreflex control of sympathetic nervous system activity are unchanged from the water-replete state. However, activation of sympathetic nerve activity may become important in maintaining peripheral resistance when ANG II and AVP receptors are blocked in water-deprived animals.
Understanding the Effects of Ionicity in Salts, Solvates, Co-Crystals, Ionic Co-Crystals, and Ionic Liquids, Rather than Nomenclature, Is Critical to Understanding Their Behavior (2013)

The incorporation of active pharmaceutical ingredients (APIs) into multicomponent solid forms (such as salts and co-crystals) or liquid forms (such as ionic liquids (ILs) or deep eutectic mixtures) is important in optimizing the efficacy and delivery of APIs. However, there is a current debate regarding the classification of these multicomponent systems based on their ionicity which could interfere with their consideration in important applications. Multicomponent systems of intermediate ionicity can show a combination of properties, leading to behavior that is neither strictly typical of either purely ionic or purely neutral compounds, nor easily described as intermediate between the two. In this perspective, we attempt to illustrate the problems in classifying multicomponent APIs based on one of two categories by discussing selected literature regarding solid and liquid multicomponent APIs and presenting the crystal structures of some relevant systems as case studies. It is clear that a focus on restrictive nomenclature carries with it the risk that a thorough examination of the physicochemical properties of the compounds will be overlooked.
Texture analysis and classification with tree-structured wavelet transform (1993)

A multiresolution approach based on a modified wavelet transform called the tree-structured wavelet transform or wavelet packets is proposed. The development of this transform is motivated by the observation that a large class of natural textures can be modeled as quasi-periodic signals whose dominant frequencies are located in the middle frequency channels. With the transform, it is possible to zoom into any desired frequency channels for further decomposition. In contrast, the conventional pyramid-structured wavelet transform performs further decomposition in low-frequency channels. A progressive texture classification algorithm which is not only computationally attractive but also has excellent performance is developed. The performance of the present method is compared with that of several other methods.
The structural basis of translational control by eIF2 phosphorylation (2019)

Protein synthesis in eukaryotes is controlled by signals and stresses via a common pathway, called the integrated stress response (ISR). Phosphorylation of the translation initiation factor eIF2 alpha at a conserved serine residue mediates translational control at the ISR core. To provide insight into the mechanism of translational control we have determined the structures of eIF2 both in phosphorylated and unphosphorylated forms bound with its nucleotide exchange factor eIF2B by electron cryomicroscopy. The structures reveal that eIF2 undergoes large rearrangements to promote binding of eIF2α to the regulatory core of eIF2B comprised of the eIF2B alpha, beta and delta subunits. Only minor differences are observed between eIF2 and eIF2αP binding to eIF2B, suggesting that the higher affinity of eIF2αP for eIF2B drives translational control. We present a model for controlled nucleotide exchange and initiator tRNA binding to the eIF2/eIF2B complex.
Immune escape by human immunodeficiency virus type 1 from neutralizing antibodies: evidence for multiple pathways (1993)

Sera from many HIV-1-infected individuals contain broadly reactive, specific neutralizing antibodies. Despite their broad reactivity, variant viruses, resistant to neutralization, can be selected in vitro in the presence of such antisera. We have previously shown that neutralization resistance of an escape mutant with an amino acid substitution in the transmembrane protein (A582T) occurs because of alteration of a conformational epitope that is recognized by neutralizing antibodies directed against the CD4 binding site. In this report we demonstrate that immune escape via a single-amino-acid substitution (A281V) within a conserved region of the envelope glycoprotein gp120 confers neutralization resistance against a broadly reactive neutralizing antiserum from a seropositive individual. We show this alteration affects V3 and additional regions unrelated to V3 or the CD4 binding site. Together with previous studies on escape mutants selected in vitro, our findings suggest that immune-selective pressure can arise by multiple pathways.
Targeting histone deacetylase activity in rheumatoid arthritis and asthma as prototypes of inflammatory disease: should we keep our HATs on? (2008)

Cellular activation, proliferation and survival in chronic inflammatory diseases is regulated not only by engagement of signal trans-duction pathways that modulate transcription factors required for these processes, but also by epigenetic regulation of transcription factor access to gene promoter regions. Histone acetyl transferases coordinate the recruitment and activation of transcription factors with conformational changes in histones that allow gene promoter exposure. Histone deacetylases (HDACs) counteract histone acetyl transferase activity through the targeting of both histones as well as nonhistone signal transduction proteins important in inflammation. Numerous studies have indicated that depressed HDAC activity in patients with inflammatory airway diseases may contribute to local proinflammatory cytokine production and diminish patient responses to corticosteroid treatment. Recent observations that HDAC activity is depressed in rheumatoid arthritis patient synovial tissue have predicted that strategies restoring HDAC function may be therapeutic in this disease as well. Pharmacological inhibitors of HDAC activity, however, have demonstrated potent therapeutic effects in animal models of arthritis and other chronic inflammatory diseases. In the present review we assess and reconcile these outwardly paradoxical study results to provide a working model for how alterations in HDAC activity may contribute to pathology in rheumatoid arthritis, and highlight key questions to be answered in the preclinical evaluation of compounds modulating these enzymes.
Research methodology: cancer cachexia syndrome (2004)

Cachexia is a syndrome and therefore does not have a specific definition. Patients are characterized by the presence of anorexia, early satiety, weight loss, weakness, anaemia and oedema. These features occur to a variable extent in different patients and may change in severity during the course of a patient's illness. The multifactorial origin of cachexia precludes a uniform pathophysiological definition. Taken together these factors have hindered clinical studies both at a fundamental level and in terms of the introduction of effective therapy. The advent of novel therapeutic targets (e.g., ubiquitin-proteasome pathway) and biological response modifiers has opened possibilities for new clinical trials in cachexia. Regulatory authorities feel it is important not only to demonstrate efficacy in terms of patients' nutritional status (e.g., lean body mass) but also functional status (e.g., performance status). This article reviews current methods to assess the latter. Methods focused on measuring physical activity level (e.g., doubly labelled water technique or physical activity meters) promise objective data which can be readily interpreted in terms of clinically meaningful benefit.
A Ring Enlargement from Seven‐ to Ten‐Membered‐Ring sulfonamide derivatives (1996)

Abstract The reaction of 3‐(dimethylamino)‐2,2‐dimethyl‐2 H ‐azirine ( 1a ) with 4,5‐dihydro‐7,8‐dimethoxy‐1,2‐benzothiazepin‐3‐one 1,1‐dioxide ( 4 ) in dioxane at room temperature gave the correspondingly substituted 4 H ‐1,2,5‐benzothiadiazecin‐6‐one 1,1‐dioxide 5a in 64% yield ( Scheme 2 ). The structure of this novel ten‐membered ring‐enlargement product was established by X‐ray crystallography ( Fig. ). Under more vigorous conditions (refluxing dichloroethane), 5a was formed together with the isomeric 6a , both in low yield. The 3‐(dimethylamino)‐2 H ‐azirines 1b and 1c reacted sluggishly to give the two isomeric ring‐enlargement products of type 5 and 6 in yields of 24–29% and 2–4%, respectively ( Table 1 ). Even less reactive is 2,2‐dimethyl‐3‐( N ‐methyl‐ N ‐phenylamino)‐2 H ‐azirine ( 1d ), which reacted with 4 in MeCN only at 65°. Under these conditions, besides numerous decomposition products, only traces of 5d and 6d were formed. No ring enlargement was observed with the sterically crowded 1e , which bears an isopropyl group at C(2).
Activation of human eosinophils and epidermal keratinocytes by Th2 cytokine IL-31: implication for the immunopathogenesis of atopic dermatitis (2010)

IL-31 is a novel T(h) type 2 cytokine that can induce pruritus and dermatitis in mice resembling human atopic dermatitis (AD). Eosinophil infiltration in skin lesions is a predominant pathological feature of AD. In the present study, we investigated the effects of IL-31 on the activation of human eosinophils and epidermal keratinocytes. Eosinophils and keratinocytes were cultured either together or separately in the presence or absence of IL-31 stimulation. IL-31 could significantly induce the release of pro-inflammatory cytokines IL-1beta, IL-6 and AD-related chemokines CXCL1, CXCL8, CCL2 and CCL18 from eosinophils, via functional cell surface IL-31 receptor. Such induction was further enhanced upon the co-culture of eosinophils and keratinocytes, in which eosinophils were the main source for releasing pro-inflammatory cytokines and chemokines. The presence of transwell inserts in co-culture system demonstrated that the direct interaction between eosinophils and keratinocytes was required for IL-31-induced cytokine and chemokine release. Cell surface expression of adhesion molecule CD18 on eosinophils and intercellular adhesion molecule-1 on keratinocytes was up-regulated in the co-culture, and levels were further enhanced upon IL-31 stimulation. The interaction between eosinophils and keratinocytes under IL-31 stimulation was differentially mediated through intracellular mitogen-activated protein kinases, nuclear factor-kappaB and phosphatidylinositol 3-kinase-Akt pathways. The above findings suggest a crucial immunopathological role of IL-31 in AD through activation of eosinophils-keratinocytes system.
Enigma Interacts with Adaptor Protein with PH and SH2 Domains to Control Insulin-Induced Actin Cytoskeleton Remodeling and Glucose Transporter 4 Translocation (2006)

APS (adaptor protein with PH and SH2 domains) initiates a phosphatidylinositol 3-kinase-independent pathway involved in insulin-stimulated glucose transport. We recently identified Enigma, a PDZ and LIM domain-containing protein, as a partner of APS and showed that APS-Enigma complex plays a critical role in actin cytoskeleton organization in fibroblastic cells. Because actin rearrangement is important for insulin-induced glucose transporter 4 (Glut 4) translocation, we studied the potential involvement of Enigma in insulin-induced glucose transport in 3T3-L1 adipocytes. Enigma mRNA was expressed in differentiated adipocytes and APS and Enigma were colocalized with cortical actin. Expression of an APS mutant unable to bind Enigma increased the insulin-induced Glut 4 translocation to the plasma membrane. By contrast, overexpression of Enigma inhibited insulin-stimulated glucose transport and Glut 4 translocation without alterations in proximal insulin signaling. This inhibitory effect was prevented with the deletion of the LIM domains of Enigma. Using time-lapse fluorescent microscopy of green fluorescent protein-actin, we demonstrated that the overexpression of Enigma altered insulin-induced actin rearrangements, whereas the expression of Enigma without its LIM domains was without effect. A physiological link between increased expression of Enigma and an alteration in insulin-induced glucose uptake was suggested by the increase in Enigma mRNA expression in adipose tissue of diabetic obese patients. Taken together, these data strongly suggest that the interaction between APS and Enigma is involved in insulin-induced Glut 4 translocation by regulating cortical actin remodeling and raise the possibility that modification of APS/Enigma ratio could participate in the alteration of insulin-induced glucose uptake in adipose tissue.
X-ray-induced P-selectin localization to the lumen of tumor blood vessels. (1998)

P-selectin is a cell adhesion molecule that is sequestered in Weibel-Palade storage reservoirs within the vascular endothelium and alpha granules in platelets. P-selectin is rapidly translocated to the vascular lumen after tissue injury to initiate the adhesion and activation of platelets and leukocytes. We studied the histological pattern of P-selectin expression in irradiated tumor blood vessels. We observed that P-selectin was localized within the endothelium of tumor vessels prior to treatment. At 1-6 h following irradiation, P-selectin was mobilized to the lumen of blood vessels. To determine whether radiation-induced vascular lumen localization of P-selectin was tumor type specific or species specific, we studied tumors in rats, C3H mice, C57BL6 mice, and nude mice. P-selectin localization to the vascular lumen was present in all tumors and all species studied. Irradiated intracranial gliomas showed P-selectin localization to the vascular lumen within 1 h, whereas blood vessels in normal brain showed no P-selectin staining in the endothelium and no localization to the irradiated vascular lumen. Radiation-induced P-selectin localization to the vascular lumen increased in time-dependent manner, until 24 h after irradiation. P-selectin in platelets may account for the time-dependent increase in staining within the vascular lumen after irradiation. We therefore used immunohistochemistry for platelet antigen GP-IIIa to differentiate between endothelial and platelet localization of P-selectin. We found that GP-IIIa staining was not present at 1 h after irradiation, but it increased at 6 and 24 h. P-selectin localization to the vascular lumen at 6-24 h was, in part, associated with platelet aggregation. These findings indicate that radiation-induced P-selectin staining in the vascular lumen of neoplasms is associated with aggregation of platelets. Radiation-induced localization of P-selectin to the vascular lumen is specific to the microvasculature of malignant gliomas and is not present in the blood vessels of the irradiated normal brain.
Automatic selection of application-specific reconfigurable processor extensions (2008)

This paper presents a new method for automatic selection of application-specific processor extensions and shows how applications are scheduled on these new reconfigurable architectures. The extensions are implemented as specialized sequential or parallel instructions. They correspond to identified most frequently occuring computational patterns or other interesting patterns and are finally selected during mapping and scheduling. Our methods can handle both time-constrained and resource-constrained scheduling. Experimental results show that the presented method provides high coverage of application graphs with small number of patterns and ensures high application execution speed-up both for sequential and parallel application execution with processor extensions implementing selected patterns.
Expression Pattern and Neurotrophic Role of the c-fmsProto-Oncogene M-CSF Receptor in Rodent Purkinje Cells (1998)

To investigate whether the c-fms proto-oncogene plays a role in the CNS, we examined its expression in mouse brain. We found that c-fms-positive Purkinje cells first appeared in caudal cerebellum at postnatal day 0 (P0) arranged in a parasagittal manner, and most Purkinje cells gradually became positive by P6. This differential expression was not seen from P7 to adulthood, and the parasagittal pattern until P5 was different from those of L7, zebrins, and the integrin beta1 subunit. No neuronal expression of c-fms was found in the other brain regions examined. In both reeler and weaver mutant mice in the adult stage, all Purkinje cells were positive for c-fms as in the wild-type controls; however, the parasagittal bands of c-fms-positive Purkinje cells were observed even in the adult staggerer mutant. To check the neurotrophic effect of macrophage colony-stimulating factor (M-CSF), we immunostained cerebella derived from osteopetrotic mutant mice, that is, those devoid of active M-CSF. We found that the number of calbindin-positive Purkinje cells in a given cerebellum began to decrease substantially during the initial 4-5 weeks of the postnatal period. In addition, cultured Purkinje cells were dependent on M-CSF for their survival. These data suggest that expression of the c-fms gene is intrinsically programmed in the Purkinje cells and never affected by the afferent synaptic input and that neuronal survival of Purkinje cells is dependent on M-CSF after weaning. Therefore, c-fms is considered to be a new developmental marker for Purkinje cells.
Hyper-high-sensitivity wash-free magnetoreduction assay on biomolecules using high-Tc superconducting quantum interference devices (2008)

In this work, we develop a platform for assaying biomolecules involving the measurement of alternating current (ac) magnetoreduction of magnetic reagent mixed with a detected sample. The magnetic reagent contains magnetic nanoparticles coated with a given kind of antibody, which associates with conjugated biomolecules. Then, the biomolecules can be quantitatively detected by measuring the ac magnetoreduction of magnetic reagent. To achieve hyper-high-sensitivity assay, a system utilizing a high-transition-temperature rf superconducting quantum interference device (SQUID) as a sensor to probe the magnetoreduction of reagent due to the association between biomolecules and magnetic nanoparticles. Examples to assay multiactive epitope, single-active epitope, and small molecules are given to demonstrate the validity of the assay platform, as well as the hyper-high sensitivity.
The British Army's African Recruitment Policy, 1790-1807 (2024)

The article is drawn from a presentation to the Five College Black Studies Seminar Series, University of Massachusetts Amherst, 25 February 1982. It argues that delays in the British abolition of the slave trade was related to military policies and imperial interests.
The Effect of Nasal Polyp Epithelial Cells on Eosinophil Activation (2003)

The results suggest that eosinophils in nasal secretions are activated by GM-CSF, which is produced by nasal epithelial cells.
Component‐Specific Analysis of Plasma Protein Corona Formation on Gold Nanoparticles Using Multiplexed Surface Plasmon Resonance (2015)

At the nano-bio interface, human plasma differentially interacts with engineered nanomaterials through the creation of protein coronas, which in turn become primary determinants of both the pharmacokinetics and pharmacodynamics of circulating nanoparticles. Here, for the first time, the specific binding kinetics of the four major corona forming proteins (human serum albumin, fibrinogen, ApoA1, and polyclonal IgG) are determined for gold nanoparticles (AuNPs). Using a multiplexed surface plasmonic assay, highly reproducible measurements of on rate (k(on)), off rate (k(off)), and disassociation constant (K(D)), in addition to relative amounts of protein binding, are obtained. Dramatic differences in k(on) for individual components are shown as primary determinants of protein affinities, with k(on) ranging over nearly two orders of magnitude for the proteins studied, while k(off) remains within a factor of two for the set. The effect of polyethylene glycol (PEG) modification on plasma component binding is also studied and the effect of PEG length on human serum interaction is characterized through systematic screening of PEG molecular weight (2-30k). The effect of nanoparticle modification on particle targeting is also characterized through study of a hybrid AuNP system.
Nonuniform Heating During Radiofrequency Catheter Ablation With Long Electrodes (1997)

Maximum heating from radiofrequency energy occurs at the electrode edges, particularly with long electrodes. The safety of temperature-feedback atrial ablation with these electrodes is significantly improved by monitoring temperatures at the edges.
Mutational Landscape of Aggressive Cutaneous Squamous Cell Carcinoma (2014)

The mutational spectrum of cSCC is similar to that of head and neck squamous cell carcinoma and dominated by tumor-suppressor genes. These results improve the foundation for understanding this disease and should aid in identifying and treating aggressive cSCC.
Evaluation of peptide vaccine immunogenicity in draining lymph nodes and peripheral blood of melanoma patients (2001)

Many peptide epitopes for cytotoxic T lymphocytes (CTLs) have been identified from melanocytic differentiation proteins. Vaccine trials with these peptides have been limited mostly to those associated with HLA-A2, and immune responses have been detected inconsistently. Cases of clinical regression have been observed after peptide vaccination in some trials, but melanoma regressions have not correlated well with T-cell responses measured in peripheral blood lymphocytes (PBLs). We vaccinated stage IV melanoma patients with a mixture of gp100 and tyrosinase peptides restricted by HLA-A1 (DAEKSDICTDEY), HLA-A2 (YLEPGPVTA and YMDGTMSQV) and HLA-A3 (ALLAVGATK) in an emulsion with GM-CSF and Montanide ISA-51 adjuvant. CTL responses were assessed in PBLs and in a lymph node draining a vaccine site (sentinel immunized node, SIN). We found CTL responses to vaccinating peptides in the SIN in 5/5 patients (100%). Equivalent assays detected peptide-reactive CTLs in PBLs of 2 of these 5 patients (40%). CTLs expanded from the SIN lysed melanoma cells naturally expressing tyrosinase or gp100. We demonstrated immunogenicity for peptides restricted by HLA-A1 and -A3 and for 1 HLA-A2 restricted peptide, YMDGTMSQV. Immune monitoring of clinical trials by evaluation of PBLs alone may under-estimate immunogenicity; evaluation of SIN provides a new and sensitive approach for defining responses to tumor vaccines and correlating these responses with clinical outcomes. This combination of an immunogenic vaccine strategy with a sensitive analysis of CTL responses demonstrates the potential for inducing and detecting anti-tumor immune responses in the majority of melanoma patients.