gebhart/patrepeval huggingface dataset:
Immunodetection and quantitation of the two forms of transforming growth factor‐beta (TGF‐β1 and TGF‐β2) secreted by cells in culture (1989)

Transforming growth factor beta (TGF-beta), a potent modulator of cell growth, differentiation, and the expression of extracellular matrix components in a variety of cell types, exists as two distinct homodimers (TGF-beta 1 and TGF-beta 2), sharing 71% sequence homology. Radioreceptor and previously described radioimmunological assays using rabbit antibodies have not been able to distinguish between these two forms. We have developed antisera in turkeys against native TGF-beta 1 and TGF-beta 2, each of which specifically blocks both the receptor binding and biological activity of each of these peptides. With these immunological reagents we describe sensitive and specific immunological assays for TGF-beta 1 and TGF-beta 2 in complex biological fluids. Using these assays we show that both TGF-beta 1 and TGF-beta 2 are secreted by a variety of cultured cells, but that some cells secrete predominantly either TGF-beta 1 or TGF-beta 2 while others secrete both peptides in nearly equal amounts. Our results demonstrate that the expression of each of the two forms of TGF-beta is independently regulated.
Most mRNAs in the nematode Ascaris lumbricoides are trans-spliced: a role for spliced leader addition in translational efficiency. (1995)

Some pre-mRNAs in nematodes are processed by trans-splicing. In this reaction, a 22-nt 5' terminal exon (the spliced leader, SL) and its associated 2,2,7-trimethylguanosine cap are acquired from a specialized Sm snRNP, the SL RNP. Although it has been evident for many years that not all nematode mRNAs contain the SL sequence, the prevalence of trans-spliced mRNAs has, with the exception of Caenorhabditis elegans, not been determined. To address this question in an organism amenable to biochemical analysis, we have prepared a message-dependent protein synthesis system from developing embryos of the parasitic nematode, Ascaris lumbricoides. Using this system, we have used both hybrid-arrest and hybrid-selection approaches to show that the vast majority (80-90%) of A. lumbricoides mRNAs contain the SL sequence and therefore are processed by trans-splicing. Furthermore, to examine the effect of SL addition on translation, we have measured levels of protein synthesis in extracts programmed with a variety of synthetic mRNAs. We find that the SL sequence itself and its associated hypermethylated cap functionally collaborate to enhance translational efficiency, presumably at the level of initiation of protein synthesis. These results indicate that trans-splicing plays a larger role in nematode gene expression than previously suspected.
GROWTH FAILURE WITH NORMAL SERUM RIA-GH AND LOW SOMATOMEDIN ACTIVITY: SOMATOMEDIN RESTORATION AND GROWTH ACCELERATION AFTER EXOGENOUS GH (1978)

Two three-year-old boys with dwarfism (height ages 1-4/2 and 1-11/12 years) and delayed bone ages (1-4/12 and 1-9/12 years) had normal growth hormone (GH) responses after stimulation and low levels of somatomedin. Unlike patients with Laron syndrome, the two patients generated normal levels of somatomedin after administration of exogenous hGH. Treatment with hGH (2 IU every other day) brought about a significant increase in the growth rate of both patients. The growth rate of the first patient increased from 2 cm/year before treatment to 12 cm/year on therapy. The growth rate of the second patient was 4.5 cm/year before treatment, and 8.3 cm/year while on treatment. The two cases represent a new syndrome of dwarfism which may be caused by secretion of a biologically inactive but immunoreactive GH.
Erythropoietin-induced tyrosine phosphorylations in a high erythropoietin receptor-expressing lymphoid cell line (1992)

Retroviral gene transfer of the murine erythropoietin receptor (EpR) cDNA into the pro-B-cell line, Ba/F3, was used to generate cells expressing high EpR levels. One of the resulting clones, Ba/F3 clone C5, contained 5 integrated copies of the gene and expressed, at the cell surface, a single affinity class of EpRs at 10 to 15 times the level present on spleen cells from phenylhydrazine-treated mice. Cross- linking studies with clone C5, using 125I-Ep, yielded the same two 105- and 88-Kd major species as that seen with typical erythroid cells. This was distinct from that obtained with EpR-transfected COS cells or L cells, which gave species of 88 and 65 Kd. This suggests that the biologically active EpR complex generated in this Ba/F3 cell line may closely resemble that present in native Ep-responsive erythroid progenitor cells. Tyrosine phosphorylation experiments showed that several proteins in clone C5 cells were rapidly phosphorylated on tyrosine residues in response to Ep, one being the EpR itself. The proportion of cell surface EpRs tyrosine phosphorylated in response to Ep was substantial, reaching a maximum of approximately 10% within 30 minutes of incubation at 37 degrees C. A comparison of Ep- and murine interleukin-3 (mIL-3)-induced tyrosine phosphorylation patterns in clone C5 cells showed that both growth factors stimulated the tyrosine phosphorylation of proteins with molecular weights of 135, 93, 70, and 55 Kd. This could suggest that the Ep and mIL-3 receptors are capable of using the same tyrosine kinase in these cells.
A system for machine recognition of music patterns (2002)

We introduce a system for machine recognition of music patterns. The problem is put into a pattern recognition framework in the sense that an error between a target pattern and scanned pattern is minimized. The error takes into account pitch and rhythm information. The pitch error measure consists of an absolute (objective) error and a perceptual error. The latter depends on an algorithm for establishing the tonal context which is based on Krumhansl's (1990) key-finding algorithm. The sequence of maximum correlations that it outputs is smoothed with a cubic spline and is used to determine weights for perceptual and absolute pitch errors. Maximum correlations are used to create the assigned key sequence, which is then filtered by a recursive median filter to improve the structure of the output of the key finding algorithm. A procedure for choosing weights given to pitch and rhythm errors is discussed.
Stimulation of angiogenesis by substance P and interleukin‐1 in the rat and its inhibition by NK1or interleukin‐1 receptor antagonists (1993)

1. Daily administration of 1 nmol substance P or 3 pmol recombinant human interleukin-1 alpha (IL-1 alpha) caused intense neovascularization in a rat sponge model of angiogenesis. Lower doses of substance P (10 pmol) or IL-1 alpha (0.3 pmol) were ineffective when given alone. When combined at these low doses, substances P and IL-1 alpha interacted to produce an enhanced neovascular response. 2. By use of selective tachykinin NK1, NK2 and NK3 receptor agonists, ([Sar9,Met(O2)11]substance P, [beta-Ala8]neurokinin A(4-10), Succ-[Asp6,MePhe8]substance P(6-11) (senktide), respectively), it was established that the activation of NK1 receptors is most likely to mediate the angiogenic response to substance P in this model. 3. The angiogenic activity of substance P and IL-1 alpha (10 pmol and 0.3 pmol day-1, respectively) was abolished by co-administration of (i) the selective peptide NK1 receptor antagonist, L-668,169 (1 nmol day-1), (ii) the selective non-peptide NK1 receptor antagonists, RP 67580 and (+/-)-CP-96,345 (both at 1 nmol day-1) or (iii) the IL-1 receptor antagonist, IL-1ra, (50 micrograms day-1). In contrast, the selective NK2 receptor antagonist, L-659,874 (1 nmol day-1) was ineffective. 4. The angiogenic action of substance P and IL-1 alpha was resistant to modification by mepyramine (1 nmol day-1) and/or cimetidine (10 nmol day-1), indomethacin (7 nmol day-1) or the platelet-activating factor (PAF) antagonist, WEB-2086 (22 nmol day-1), indicating that histamine, prostaglandins and PAF are not likely to be involved in this neovascular response. 5. The inhibition of the substance P/IL-1 angiogenic response by selective NK1 receptor antagonists or by an IL-1 receptor antagonist demonstrates that angiosuppression can be achieved by blocking the activity of angiogenic factors at the receptor level.
Geldanamycin Induces Heat Shock Protein 70 and Protects against MPTP-induced Dopaminergic Neurotoxicity in Mice (2005)

As key molecular chaperone proteins, heat shock proteins (HSPs) represent an important cellular protective mechanism against neuronal cell death in various models of neurological disorders. In this study, we investigated the effect as well as the molecular mechanism of geldanamycin (GA), an inhibitor of Hsp90, on 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity, a mouse model of Parkinson disease. Neurochemical analysis showed that pretreatment with GA (via intracerebral ventricular injection 24 h prior to MPTP treatment) increased residual dopamine content and tyrosine hydroxylase immunoreactivity in the striatum 24 h after MPTP treatment. To dissect out the molecular mechanism underlying this neuroprotection, we showed that the GA-mediated protection against MPTP was associated with a reduction of cytosolic Hsp90 and an increase in Hsp70, with no significant changes in Hsp40 and Hsp25 levels. Furthermore, in parallel with the induction of Hsp70, striatal nuclear HSF1 levels and HSF1 binding to heat shock element sites in the Hsp70 promoter were significantly enhanced by the GA pretreatment. Together these results suggested that the molecular cascade leading to the induction of Hsp70 is critical to the neuroprotection afforded by GA against MPTP-induced neurotoxicity in the brain and that pharmacological inhibition of Hsp90 may represent a potential therapeutic strategy for Parkinson disease.
Biomaterials Fabrication and Processing Handbook (2008)

Focusing on a lucrative and increasingly important area of biomedicine, the Biomaterials Fabrication and Processing Handbook brings together various biomaterials production and processing aspects, including tissue engineering scaffold materials, drug delivery systems, nanobiomaterials, and biosensors. With contributions from renowned interna
Neutrophil CD64 Expression in Inflammatory Autoimmune Diseases: Its Value in Distinguishing Infection from Disease Flare (2010)

The purpose of this research was to clarify the significance of neutrophil CD64 expression in discrimination between infection and disease flare in patients with inflammatory autoimmune diseases. The study included 63 subjects, 20 healthy controls and 43 patients with inflammatory autoimmune diseases (24 with rheumatoid arthritis & 19 with systemic lupus erythematosus). The FC gamma receptor I (CD64 expression) on neutrophils was measured using flow cytometry. The intensity of CD64 expression on neutrophils was significantly elevated in patients with infections; 49.0 (13-205), and active autoimmune disease; 36.15 (12-133) compared to healthy controls; 5.35 (2.6-14) or patients with inactive disease; 7.5 (3.3-18). In the infectious disease group, expression of CD64 was significantly higher than in the active inflammatory disease group, while there was no significant difference between the group of patients with inactive inflammatory disease and healthy controls (P > 0.05). The sensitivity of CD64 bearing neutrophil intensity for detection of infection (using a cut off value of ≥43.5) was 94.4% and specificity was 88.9%. Neutrophil CD64 expression has a good sensitivity and specificity in differentiating infection from disease flare in patients with inflammatory autoimmune diseases. This assay could facilitate early and accurate diagnosis and greatly aid timely institution of appropriate treatment.
Clinical and Microbiological Characteristics of SevereStreptococcus pyogenesDisease in Europe (2009)

In an attempt to compare the epidemiology of severe Streptococcus pyogenes infection within Europe, prospective data were collected through the Strep-EURO program. Surveillance for severe cases of S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe by using a standardized case definition and questionnaire. Patient data as well as bacterial isolates were collected and characterized by T and M/emm typing, and selected strains were analyzed for the presence of superantigen genes. Data were analyzed to compare the clinical and microbiological patterns of the infections across the participating countries. A total of 4,353 isolates were collected from 5,521 cases with severe S. pyogenes infections who were identified. A wide diversity of M/emm types (n = 104) was found among the S. pyogenes clinical isolates, but the M/emm type distribution varied broadly between participating countries. The 10 most predominant M/emm types were M/emm type 1 (M/emm1), M/emm28, M/emm3, M/emm89, M/emm87, M/emm12, M/emm4, M/emm83, M/emm81, and M/emm5, in descending order. A correlation was found between some specific disease manifestations, the age of the patients, and the emm types. Although streptococcal toxic shock syndrome and necrotizing fasciitis were caused by a large number of types, they were particularly associated with M/emm1 and M/emm3. The emm types included in the 26-valent vaccine under development were generally well represented in the present material; 16 of the vaccine types accounted for 69% of isolates. The Strep-EURO collaborative program has contributed to enhancement of the knowledge of the spread of invasive disease caused by S. pyogenes within Europe and encourages future surveillance by the notification of cases and the characterization of strains, which are important for vaccination strategies and other health care issues.
Non-invasive transcranial ultrasound therapy based on a 3D CT scan: protocol validation andin vitroresults (2009)

A non-invasive protocol for transcranial brain tissue ablation with ultrasound is studied and validated in vitro. The skull induces strong aberrations both in phase and in amplitude, resulting in a severe degradation of the beam shape. Adaptive corrections of the distortions induced by the skull bone are performed using a previous 3D computational tomography scan acquisition (CT) of the skull bone structure. These CT scan data are used as entry parameters in a FDTD (finite differences time domain) simulation of the full wave propagation equation. A numerical computation is used to deduce the impulse response relating the targeted location and the ultrasound therapeutic array, thus providing a virtual time-reversal mirror. This impulse response is then time-reversed and transmitted experimentally by a therapeutic array positioned exactly in the same referential frame as the one used during CT scan acquisitions. In vitro experiments are conducted on monkey and human skull specimens using an array of 300 transmit elements working at a central frequency of 1 MHz. These experiments show a precise refocusing of the ultrasonic beam at the targeted location with a positioning error lower than 0.7 mm. The complete validation of this transcranial adaptive focusing procedure paves the way to in vivo animal and human transcranial HIFU investigations.
Interleukin-1 receptor antagonist alters the response to vessel wall injury in a porcine coronary artery model (2005)

IL-1ra was associated with a sustained, significant reduction in neointima after vessel wall injury as long as it is given for the duration of the stimulation of the IL-1 system, in this case at least 28 days. This suggests that therapies based on the antagonism of IL-1 may modulate the coronary artery response to injury.
Force Modeling for Needle Insertion Into Soft Tissue (2004)

The modeling of forces during needle insertion into soft tissue is important for accurate surgical simulation, preoperative planning, and intelligent robotic assistance for percutaneous therapies. We present a force model for needle insertion and experimental procedures for acquiring data from ex vivo tissue to populate that model. Data were collected from bovine livers using a one-degree-of-freedom robot equipped with a load cell and needle attachment. computed tomography imaging was used to segment the needle insertion process into phases identifying different relative velocities between the needle and tissue. The data were measured and modeled in three parts: 1) capsule stiffness, a nonlinear spring model; 2) friction, a modified Karnopp model; and 3) cutting, a constant for a given tissue. In addition, we characterized the effects of needle diameter and tip type on insertion force using a silicone rubber phantom. In comparison to triangular and diamond tips, a bevel tip causes more needle bending and is more easily affected by tissue density variations. Forces for larger diameter needles are higher due to increased cutting and friction forces.
Regulation of alternative splicing of the receptor for advanced glycation endproducts (RAGE) through G-rich cis-elements and heterogenous nuclear ribonucleoprotein H (2009)

Receptor for advanced glycation endproducts (RAGE) is a cell-surface receptor. The binding of ligands to membrane-bound RAGE (mRAGE) evokes cellular responses involved in various pathological processes. Previously, we identified a novel soluble form, endogenous secretory RAGE (esRAGE) generated by alternative 5' splice site selection in intron 9 that leads to extension of exon 9 (exon 9B). Because esRAGE works as an antagonistic decoy receptor, the elucidation of regulatory mechanism of the alternative splicing is important to understand RAGE-related pathological processes. Here, we identified G-rich cis-elements within exon 9B for regulation of the alternative splicing using a RAGE minigene. Mutagenesis of the G-rich cis-elements caused a drastic increase in the esRAGE/mRAGE ratio in the minigene-transfected cells and in loss of binding of the RNA motif to heterogenous nuclear ribonucleoprotein (hnRNP) H. On the other hand, the artificial introduction of a G-stretch in exon 9B caused a drastic decrease in the esRAGE/mRAGE ratio accompanied by the binding of hnRNP H to the RNA motif. Thus, the G-stretches within exon 9B regulate RAGE alternative splicing via interaction with hnRNP H. The findings should provide a molecular basis for the development of medicines for RAGE-related disorders that could modulate esRAGE/mRAGE ratio.
Synthesis of 2′- and 3′-Amino-Substituted Uridine, Thymidine and Adenosine, and Their Inhibitions of HIV Replication (1990)

Reactions of primary and secondary amines with appropriately protected 2′- O-mesyl-3′-deoxynucleosides 1, 5, and 18 gave 2′,3′-dideoxy-2′-alkylaminonucleosides 2a-d, 6a-c and 19a-d, f, n-q (35–40%) as well as a small amount of 2′,3′-glyceropentofuranosyl nucleoside 3, 7 or 11 (∼15%). Displacement of the 3′- O-mesyl group in 9b with amines gave mainly the elimination product 11, except in the reaction with morpholine and benzylamine which gave 3′-amino-substituted products 10c and 10d at a yield of 52% and 24%, respectively. The ring-opening reactions of appropriately protected 2′, 3′,- O-lyxoanhydro-adenosine 13 by a variety of primary and secondary amines gave isomeric mixtures of 2′-alkylamino nucleosides 15a-k (∼20%) and 3′-alkylamino nucleosides 14a-m (∼60%). These alkylamino nucleosides have been subsequently deprotected under acidic conditions to give the parent nucleosides in good yields; their biological activities as inhibitors of human immunodeficiency virus (HIV) replication have been also evaluated. The 2′,3′-dideoxy-2′-substituted and 2′,3′-dideoxy-3′-substituted nucleosides described herein are not available through any other known routes.
UBIQUITIN-IMMUNOREACTIVE INTRANEURONAL INCLUSIONS IN AMYOTROPHIC LATERAL SCLEROSIS (1991)

Antibodies to ubiquitin have been used to search for evidence of abnormal protein degradation in amyotrophic lateral sclerosis--motor neuron disease (ALS). Anterior horn cell ubiquitin-immunoreactive (IR) inclusions were present in all of 31 ALS cases but in none of 23 neurologically normal and in only 1 of 22 neurologically abnormal controls. These inclusions, which were present in familial and sporadic ALS cases, and in cases with dementia, took the form of dense rounded or irregular ubiquitin-IR cytoplasmic inclusions (dense bodies), or loosely arranged bundles ('skeins') of filamentous-appearing material. The presence of ubiquitin-IR inclusions corresponded to the pattern of selective neuronal vulnerability in ALS, although inclusions in pyramidal neurons of the motor cortex were infrequent and were noted in only a minority of cases. Ubiquitin-IR inclusions were more prevalent than Bunina bodies. The latter were present in 67% of ALS cases but were seldom labelled by antibodies to ubiquitin. Intraneuronal inclusions resembling Lewy bodies were present in 23% of ALS cases and were often identified by antibodies to ubiquitin. We conclude that the presence of ubiquitin-IR inclusions in lower motor neurons represents a characteristic pathological feature of ALS in its various clinical forms. Ubiquitin-IR inclusions in ALS differ from ubiquitinated inclusions in other neuronal degenerations in that they are not readily identified by antibodies to cytoskeletal proteins. They may represent accumulations of altered or abnormal neuronal proteins resistant to degradation via the ubiquitin proteolytic pathway.
A Generic Intron Increases Gene Expression in Transgenic Mice (1991)

To investigate the role of splicing in the regulation of gene expression, we have generated transgenic mice carrying the human histone H4 promoter linked to the bacterial gene for chloramphenicol acetyltransferase (CAT), with or without a heterologous intron in the transcription unit. We found that CAT activity is 5- to 300-fold higher when the transgene incorporates a hybrid intron than with an analogous transgene precisely deleted for the intervening sequences. This hybrid intron, consisting of an adenovirus splice donor and an immunoglobulin G splice acceptor, stimulated expression in a broad range of tissues in the animal. Although the presence of the hybrid intron increased the frequency of transgenics with significant CAT activity, it did not affect the integration site-dependent variation commonly seen in transgene expression. To determine whether the enhancement is a general outcome of splicing or is dependent on the particular intron, we also produced equivalent transgenics carrying the widely used simian virus 40 small-t intron. We found that the hybrid intron is significantly more effective in elevating transgene expression. Our results suggest that inclusion of the generic intron in cDNA constructs may be valuable in achieving high levels of expression in transgenic mice.
Learning Hierarchical Features for Scene Labeling (2012)

Scene labeling consists of labeling each pixel in an image with the category of the object it belongs to. We propose a method that uses a multiscale convolutional network trained from raw pixels to extract dense feature vectors that encode regions of multiple sizes centered on each pixel. The method alleviates the need for engineered features, and produces a powerful representation that captures texture, shape, and contextual information. We report results using multiple postprocessing methods to produce the final labeling. Among those, we propose a technique to automatically retrieve, from a pool of segmentation components, an optimal set of components that best explain the scene; these components are arbitrary, for example, they can be taken from a segmentation tree or from any family of oversegmentations. The system yields record accuracies on the SIFT Flow dataset (33 classes) and the Barcelona dataset (170 classes) and near-record accuracy on Stanford background dataset (eight classes), while being an order of magnitude faster than competing approaches, producing a $(320\times 240)$ image labeling in less than a second, including feature extraction.