gebhart/patrepeval huggingface dataset:
Topical and light-based treatments for actinic keratoses (2003)

Actinic keratosis is currently believed to be an early stage in the evolution of squamous cell carcinoma. Active and intensive treatment of actinic keratosis may prevent the formation of invasive squamous cell carcinoma and potential metastases. While destructive methods of treatment of actinic keratosis remain the gold standard for the eradication of visible and palpable actinic keratoses, new medical therapies may accomplish this goal more comfortably and reliably for the patient. Newer topical medications, light therapy and photodynamic therapy are generating promising results that presage more widespread use in the future. These novel therapies for the early treatment of actinic keratosis may be administered in combination or serially, with the locus of treatment at any given time possibly restricted to a region of affected skin. Treatment of incipient or subclinical lesions may mitigate the risk of future squamous cell carcinomas lesions. Widespread actinic keratosis constitutes a persistent medical problem that requires long-term management. The role of traditional and novel treatments in the routine treatment of actinic keratosis will be determined by the efficacy, limitations and the practicality of each of these methods in individual patients. As the first stage of squamous cell carcinoma, actinic keratosis is worthy of prompt evaluation and active treatment.
Genital Herpes Simplex Virus Infections: Clinical Manifestations, Course, and Complications (1983)

The clinical course and complications of 268 patients with first episodes and 362 with recurrent episodes of genital herpes infection were reviewed. Symptoms of genital herpes were more severe in women than in men. Primary first-episode genital herpes was accompanied by systemic symptoms (67%), local pain and itching (98%), dysuria (63%), and tender adenopathy (80%). Patients presented with several bilaterally distributed postular ulcerative lesions that lasted a mean of 19.0 days. Herpes simplex virus was isolated from the urethra, cervix, and pharynx of 82%, 88%, and 13% of women with first-episode primary genital herpes, and the urethra and pharynx of 28% and 7% of men. Complications included aseptic meningitis (8%), sacral autonomic nervous system dysfunction (2%), development of extragenital lesions (20%), and secondary yeast infections (11%). Recurrent episodes were characterized by small vesicular or ulcerative unilaterally distributed lesions that lasted a mean of 10.1 days. Systemic symptoms were uncommon and 25% of recurrent episodes were asymptomatic. The major concerns of patients were the frequency of recurrences and fear of transmitting infection to partners or infants.
Modulation of p75NTR‐dependent motor neuron death by a small non‐peptidyl mimetic of the neurotrophin loop 1 domain (2006)

The p75 neurotrophin receptor (p75NTR) is expressed by degenerating spinal motor neurons in amyotrophic lateral sclerosis (ALS). The mature and pro-form of nerve growth factor (NGF) activate p75NTR to trigger motor neuron apoptosis. However, attempts to modulate p75NTR-mediated neuronal death in ALS models by downregulating or antagonizing p75NTR with synthetic peptides have led to only modest results. Recently, a novel ligand of p75NTR, compound LM11A-24, has been identified. It is a non-peptidyl mimetic of the neurotrophin loop 1 domain that promotes hippocampal neuron survival through p75NTR and exerts protection against p75NTR-mediated apoptosis of oligodendrocytes induced by proNGF. Thus, LM11A-24 appears to activate p75NTR-linked survival but not death mechanisms, and may interfere with the ability of neurotrophins to induce apoptosis. Given these findings, we hypothesized that LM11A-24 might be a particularly potent inhibitor of motor neuron degeneration. We examined the effects of LM11A-24 on apoptosis of cultured rat embryonic motor neurons. Interestingly, in contrast to the effects observed in hippocampal cultures, LM11A-24 was unable to prevent motor neuron apoptosis induced by trophic factor deprivation. However, picomolar concentrations of LM11A-24 prevented p75NTR-dependent motor neuron death induced by either exogenous addition of NGF or spinal cord extracts from symptomatic superoxide dismutase-1G93A mice, in the presence of low steady-state concentrations of nitric oxide. LM11A-24 also inhibited motor neuron death induced by NGF-producing reactive astrocytes in co-culture conditions. These studies suggest that modulation of p75NTR by small molecule ligands targeting this receptor might constitute a novel strategy for preventing motor neuron degeneration.
Glucose Starvation in Cardiomyocytes Enhances Exosome Secretion and Promotes Angiogenesis in Endothelial Cells (2015)

Cardiomyocytes (CMs) and endothelial cells (ECs) have an intimate anatomical relationship that is essential for maintaining normal development and function in the heart. Little is known about the mechanisms that regulate cardiac and endothelial crosstalk, particularly in situations of acute stress when local active processes are required to regulate endothelial function. We examined whether CM-derived exosomes could modulate endothelial function. Under conditions of glucose deprivation, immortalized H9C2 cardiomyocytes increase their secretion of exosomes. CM-derived exosomes are loaded with a broad repertoire of miRNA and proteins in a glucose availability-dependent manner. Gene Ontology (GO) analysis of exosome cargo molecules identified an enrichment of biological process that could alter EC activity. We observed that addition of CM-derived exosomes to ECs induced changes in transcriptional activity of pro-angiogenic genes. Finally, we demonstrated that incubation of H9C2-derived exosomes with ECs induced proliferation and angiogenesis in the latter. Thus, exosome-mediated communication between CM and EC establishes a functional relationship that could have potential implications for the induction of local neovascularization during acute situations such as cardiac injury.
Precise point positioning for the efficient and robust analysis of GPS data from large networks (1997)

Networks of dozens to hundreds of permanently operating precision Global Positioning System (GPS) receivers are emerging at spatial scales that range from 10 0 to 10 3 km. To keep the computational burden associated with the analysis of such data economically feasible, one approach is to first determine precise GPS satellite positions and clock corrections from a globally distributed network of GPS receivers. Then, data from the local network are analyzed by estimating receiver‐specific parameters with receiver‐specific data; satellite parameters are held fixed at their values determined in the global solution. This “precise point positioning” allows analysis of data from hundreds to thousands of sites every day with 40‐Mflop computers, with results comparable in quality to the simultaneous analysis of all data. The reference frames for the global and network solutions can be free of distortion imposed by erroneous fiducial constraints on any sites.
Nearest matched filter classification of spatiotemporal patterns (1987)

Recent advances in massively parallel optical and electronic neural network processing technology have made it plausible to consider the use of matched filter banks containing large numbers of individual filters as pattern classifiers for complex spatiotemporal pattern environments such as speech, sonar, radar, and advanced communications. This paper begins with an overview of how neural networks can be used to approximately implement such multidimensional matched filter banks. The nearest matched filter classifier is then formally defined. This definition is then reformulated to show that the classifier is equivalent to a nearest neighbor classifier in a separable infinite-dimensional metric space that specifies the local-in-time behavior of spatiotemporal patterns. The result of Cover and Hart is then applied to show that, given a statistically comprehensive set of filter templates, the nearest matched filter classifier will have near-Bayesian performance for spatiotemporal patterns. The combination of near-Bayesian classifier performance with the excellent performance of matched filtering in noise yields a powerful new classification technique. This result adds additional interest to Grossberg's hypothesis that the mammalian cerebral cortex carries out local-in-time nearest matched filter classification of both auditory and visual sensory inputs as an initial step in sensory pattern recognition-which may help explain the almost instantaneous pattern recognition capabilities of animals.
The ras-related gene rhoB is an immediate-early gene inducible by v-Fps, epidermal growth factor, and platelet-derived growth factor in rat fibroblasts. (1991)

A set of genes is rapidly inducible when quiescent fibroblasts are stimulated by growth factors or by the activation of temperature-sensitive retroviral protein-tyrosine kinases. Most of these so-called immediate-early genes were cloned by differential cDNA hybridization. DNA sequence analysis identified many of them as putative members of the growth factor or of the transcription factor gene family, suggesting a role in signal transmission during the G0-to-G1 transition. In this study, we identified one of the genes that are rapidly inducible by the retroviral protein-tyrosine kinases v-Src and v-Fps of Rous sarcoma virus and Fujinami sarcoma virus, respectively, as the rhoB gene, a member of the ras gene superfamily whose products are GTP-binding proteins, rhoB is transiently activated at the transcriptional level by v-Fps and by epidermal growth factor. Its labile RNA is inducible in the presence of cycloheximide but not of actinomycin D. rhoB is strongly induced by epidermal growth factor and by platelet-derived growth factor both in subconfluent, serum-starved and in density-arrested Rat-2 fibroblasts. Fetal calf serum is a poor inducer, particularly in density-arrested cells, and phorbol esters do not increase rhoB expression at all. These data suggest that rhoB is inducible by protein-tyrosine kinases through a pathway not involving the activation of protein kinase C. Neither the closely related rhoC and rhoA genes nor the distantly related c-H-ras gene is rapidly inducible by mitogens. Thus, rhoB is the first known member of the small GTP-binding proteins among the immediate-early genes.
Environmental testing of an all-reflective spatial heterodyne spectrometer for wide input angle measurements of H Ly-alpha at high spectral resolving power (2012)

Scattered solar and collisionally stimulated H Ly-α emission is a proven diagnostic for the study of the Sun, comets, the interplanetary medium, planet atmospheres, and corona. Here we discuss the construction and testing of a narrow bandpass instrument designed to observe H Ly-α emission at a resolving power of R~100,000 from targets with an angular extent of ≤½ degree. The instrument is an all-reflective form of the spatial heterodyne spectrometer (SHS), a self-scanning Fourier Transform Spectrometer. It will be incorporated into the focal plane of a suborbital telescope that is scheduled for a March 2013 launch. Initial alignment and vibrational testing was performed with the instrument aligned to a visible analog line. The results showed alignment stability under vibration, but revealed several unacceptable resonances that have been corrected in the mechanical design.
Gastroparesis: Clinical Update. CME (2006)

Gastroparesis refers to chronically abnormal gastric motility characterized by symptoms suggestive of mechanical obstruction and delayed gastric emptying in the absence of mechanical obstruction. It may be idiopathic or attributable to neuropathic or myopathic abnormalities, such as diabetes mellitus, postvagotomy, postviral infection, and scleroderma. Dietary and behavioral modification, prokinetic drugs, and surgical interventions have been used in managing patients with gastroparesis. Although mild gastroparesis is usually well managed with these treatment options, severe gastroparesis may be very difficult to control and may require referral to a specialist center if symptoms are intractable despite pharmacological therapy and dietetic support. New advances in drug therapy, botulinum toxin injection, and gastric electrical stimulation techniques have been introduced and might provide new hope to patients with refractory gastroparesis. This article critically reviews the advances in the field from the perspective of the clinician.
Neutralisation of TGF-β1 and TGF-β2 or exogenous addition of TGF-β3 to cutaneous rat wounds reduces scarring (1995)

Exogenous addition of neutralising antibody to transforming growth factor-beta 1,2 to cutaneous wounds in adult rodents reduces scarring. Three isoforms of transforming growth factor-beta (1, 2 and 3) have been identified in mammals. We investigated the isoform/isoforms of TGF-beta responsible for cutaneous scarring by: (i) reducing specific endogenous TGF-beta isoforms by exogenous injection of isoform specific neutralising antibodies; and (ii) increasing the level of specific TGF-beta isoforms by exogenous infiltration into the wound margins. Exogenous addition of neutralising antibody to TGF-beta 1 plus neutralising antibody to TGF-beta 2 reduced the monocyte and macrophage profile, neovascularisation, fibronectin, collagen III and collagen I deposition in the early stages of wound healing compared to control wounds. Treatment with neutralising antibodies to TGF-betas 1 and 2 markedly improved the architecture of the neodermis to resemble that of normal dermis and reduced scarring while the control wounds healed with scar formation. Exogenous addition of neutralising antibody to TGF-beta 1 alone also reduced the monocyte and macrophage profile, fibronectin, collagen III and collagen I deposition compared to control wounds. However, treatment with neutralising antibody to TGF-beta 1 alone only marginally reduced scarring. By contrast, wounds treated with neutralising antibody to TGF-beta 2 alone did not differ from control wounds. Interestingly, exogenous addition of the TGF-beta 3 peptide also reduced the monocyte and macrophage profile, fibronectin, collagen I and collagen III deposition in the early stages of wound healing and markedly improved the architecture of the neodermis and reduced scarring. By contrast, wounds treated with either TGF-beta 1 or with TGF-beta 2 had more extracellular matrix deposition in the early stages of wound healing but did not differ from control wounds in the final quality of scarring. This study clearly demonstrates isoform specific differences in the role of TGF-betas in wound healing and cutaneous scarring. TGF-beta 1 and TGF-beta 2 are implicated in cutaneous scarring. This study also suggests a novel therapeutic use of exogenous recombinant, TGF-beta 3 as an anti-scarring agent.
Pyrazole Ligands:  Structure−Affinity/Activity Relationships and Estrogen Receptor-α-Selective Agonists (2000)

We have found that certain tetrasubstituted pyrazoles are high-affinity ligands for the estrogen receptor (ER) (Fink et al. Chem. Biol. 1999, 6, 205-219) and that one pyrazole is considerably more potent as an agonist on the ERalpha than on the ERbeta subtype (Sun et al. Endocrinology 1999, 140, 800-804). To investigate what substituent pattern provides optimal ER binding affinity and the greatest enhancement of potency as an ERalpha-selective agonist, we prepared a number of tetrasubstituted pyrazole analogues with defined variations at certain substituent positions. Analysis of their binding affinity pattern shows that a C(4)-propyl substituent is optimal and that a p-hydroxyl group on the N(1)-phenyl group also enhances affinity and selectivity for ERalpha. The best compound in this series, a propylpyrazole triol (PPT, compound 4g), binds to ERalpha with high affinity (ca. 50% that of estradiol), and it has a 410-fold binding affinity preference for ERalpha. It also activates gene transcription only through ERalpha. Thus, this compound represents the first ERalpha-specific agonist. We investigated the molecular basis for the exceptional ERalpha binding affinity and potency selectivity of pyrazole 4g by a further study of structure-affinity relationships in this series and by molecular modeling. These investigations suggest that the pyrazole triols prefer to bind to ERalpha with their C(3)-phenol in the estradiol A-ring binding pocket and that binding selectivity results from differences in the interaction of the pyrazole core and C(4)-propyl group with portions of the receptor where ERalpha has a smaller residue than ERbeta. These ER subtype-specific interactions and the ER subtype-selective ligands that can be derived from them should prove useful in defining those biological activities in estrogen target cells that can be selectively activated through ERalpha.
Amelioration of Experimental Autoimmune Encephalomyelitis with Anti-OX40 Ligand Monoclonal Antibody: A Critical Role for OX40 Ligand in Migration, But Not Development, of Pathogenic T Cells (2001)

OX40 (CD134) and its ligand (OX40L) have been implicated in T cell activation and migration. In this study, we examined the contribution of these molecules to the pathogenesis of experimental autoimmune encephalomyelitis (EAE) by administering a neutralizing mAb against murine OX40L (RM134L) to proteolipid protein (139-151) peptide-induced EAE in SJL mice. Administration of RM134L effectively ameliorated the disease in both actively induced and adoptively transferred EAE models. Histological examination showed that the RM134L treatment greatly reduced mononuclear cell infiltration into the spinal cord. The RM134L treatment did not inhibit the development of pathogenic T cells, given that proliferative response and IFN-gamma production by draining lymph node cells were not reduced or rather enhanced upon restimulation with proteolipid protein (139-151) in vitro, and these cells effectively transferred EAE to naive SJL mice. Flow cytometric analyses showed that the RM134L treatment inhibited the accumulation of OX40-expressing CD4(+) T cells and the migration of adoptively transferred CD4(+) T cells in the spinal cord. Immunohistochemical staining showed that OX40L was most prominently expressed on endothelial cells in the inflamed spinal cord. These results suggest that the OX40/OX40L interaction plays a critical role for the migration of pathogenic T cells into the CNS in the pathogenesis of EAE.
Power browser (2000)

We have designed and implemented new Web browsing facilities to support effective navigation on Personal Digital Assistants (PDAs) with limited capabilities: low bandwidth, small display, and slow CPU. The implementation supports wireless browsing from 3Com's Palm Pilot. An HTTP proxy fetches web pages on the client's behalf and dynamically generates summary views to be transmitted to the client. These summaries represent both the link structure and contents of a set of web pages, using information about link importance. We discuss the architecture, user interface facilities, and the results of comparative performance evaluations. We measured a 45% gain in browsing speed, and a 42% reduction in required pen movements.
The Fibronectin Domain ED-A Is Crucial for Myofibroblastic Phenotype Induction by Transforming Growth Factor-β1 (1998)

Transforming growth factor-beta1 (TGFbeta1), a major promoter of myofibroblast differentiation, induces alpha-smooth muscle (sn) actin, modulates the expression of adhesive receptors, and enhances the synthesis of extracellular matrix (ECM) molecules including ED-A fibronectin (FN), an isoform de novo expressed during wound healing and fibrotic changes. We report here that ED-A FN deposition precedes alpha-SM actin expression by fibroblasts during granulation tissue evolution in vivo and after TGFbeta1 stimulation in vitro. Moreover, there is a correlation between in vitro expression of alpha-SM actin and ED-A FN in different fibroblastic populations. Seeding fibroblasts on ED-A FN does not elicit per se alpha-SM actin expression; however, incubation of fibroblasts with the anti-ED-A monoclonal antibody IST-9 specifically blocks the TGFbeta1-triggered enhancement of alpha-SM actin and collagen type I, but not that of plasminogen activator inhibitor-1 mRNA. Interestingly, the same inhibiting action is exerted by the soluble recombinant domain ED-A, but neither of these inhibitory agents alter FN matrix assembly. Our findings indicate that ED-A-containing polymerized FN is necessary for the induction of the myofibroblastic phenotype by TGFbeta1 and identify a hitherto unknown mechanism of cytokine-determined gene stimulation based on the generation of an ECM-derived permissive outside in signaling, under the control of the cytokine itself.
Exposure to a stressor produces a long lasting enhancement of fear learning in rats (2008)

In contextual fear conditioning, footshock is given in a context, and re-exposure to this context elicits the conditional defensive response of freezing, a reliable behavioral index of conditional fear. Normally, the amount of contextual freezing is directly proportional to the number of shocks an animal receives in the context. However, pre-exposure to a stressor can produce an enhancement in conditional freezing. Pre-exposure to repeated footshock in one context produces an enhancement of conditional freezing to cues associated with a single shock in a second distinct context. This model of stress-enhanced fear learning (SEFL) can be utilized to study how stress affects learning of future aversive events. The experiments in this paper characterize the magnitude and longevity of SEFL. In the first experiment, the number of footshocks given during the pre-exposure session was varied and conditional fear to the single shock was assessed. Pre-exposure to 1 shock did not produce an enhancement in fear learning in the second context, but pre-exposure to 4 or 15 shocks did. The time-course of the enhancement was examined in the next two experiments. These experiments show that SEFL persists for at least 3 months.
Scalably synthesized environmentally benign, aqueous-based binary nanoparticle inks for Cu2ZnSn(S,Se)4 photovoltaic cells achieving over 9% efficiency (2017)

We report a scalable method for producing efficient Cu<sub>2</sub>ZnSn(S,Se)<sub>4</sub> photovoltaic cells by combining binary metal sulfide nanoparticles synthesized in aqueous solutions.