gebhart/patrepeval huggingface dataset:
Stain Specific Standardization of Whole-Slide Histopathological Images (2015)

Variations in the color and intensity of hematoxylin and eosin (H&E) stained histological slides can potentially hamper the effectiveness of quantitative image analysis. This paper presents a fully automated algorithm for standardization of whole-slide histopathological images to reduce the effect of these variations. The proposed algorithm, called whole-slide image color standardizer (WSICS), utilizes color and spatial information to classify the image pixels into different stain components. The chromatic and density distributions for each of the stain components in the hue-saturation-density color model are aligned to match the corresponding distributions from a template whole-slide image (WSI). The performance of the WSICS algorithm was evaluated on two datasets. The first originated from 125 H&E stained WSIs of lymph nodes, sampled from 3 patients, and stained in 5 different laboratories on different days of the week. The second comprised 30 H&E stained WSIs of rat liver sections. The result of qualitative and quantitative evaluations using the first dataset demonstrate that the WSICS algorithm outperforms competing methods in terms of achieving color constancy. The WSICS algorithm consistently yields the smallest standard deviation and coefficient of variation of the normalized median intensity measure. Using the second dataset, we evaluated the impact of our algorithm on the performance of an already published necrosis quantification system. The performance of this system was significantly improved by utilizing the WSICS algorithm. The results of the empirical evaluations collectively demonstrate the potential contribution of the proposed standardization algorithm to improved diagnostic accuracy and consistency in computer-aided diagnosis for histopathology data.
?‐MANNOSIDASE DEFICIENCY IN ANGLO NUBIAN GOATS (1981)

SUMMARY Two newly‐born Anglo Nubian kids with clinical evidence of a severe neurological condition were examined. Pathological examination revealed extensive cytoplasmic vacuolation in neural tissue and in localised areas in the kidney, pancreas and lymphoid tissue. Biochemical investigations demonstrated a deficiency of ?T‐mannosidase in tissues and blood serum.
Genetic risk factors in infertile men with severe oligozoospermia and azoospermia (2002)

A genetic abnormality was identified in 36/150 (24%) men with extreme oligozoospermia and azoospermia. Application of ICSI in these couples can result in offspring with an enhanced risk of unbalanced chromosome complement, male infertility due to the transmission of a Y-chromosomal microdeletion, and cystic fibrosis if both partners are CFTR gene mutation carriers. Genetic testing and counselling is clearly indicated for these couples before ICSI is considered.
Binding of the Factor IX γ-Carboxyglutamic Acid Domain to the Vitamin K-dependent γ-Glutamyl Carboxylase Active Site Induces an Allosteric Effect That May Ensure Processive Carboxylation and Regulate the Release of Carboxylated Product (2004)

Propeptides of the vitamin K-dependent proteins bind to an exosite on gamma-glutamyl carboxylase; while they are bound, multiple glutamic acids in the gamma-carboxyglutamic acid (Gla) domain are carboxylated. The role of the propeptides has been studied extensively; however, the role of the Gla domain in substrate binding is less well understood. We used kinetic and fluorescence techniques to investigate the interactions of the carboxylase with a substrate containing the propeptide and Gla domain of factor IX (FIXproGla41). In addition, we characterized the effect of the Gla domain and carboxylation on propeptide and substrate binding. For the propeptide of factor IX (proFIX18), FIXproGla41, and carboxylated FIXproGla41, the Kd values were 50, 2.5, and 19.7 nM and the koff values were 273 x 10(-5), 9 x 10(-5), and 37 x 10(-5) s(-1), respectively. The koff of proFIX18 is reduced 3-fold by FLEEL and 9-fold by the Gla domain (residues 1-46) of FIX. The pre-steady state rate constants for carboxylation of FIXproGla41 was 0.02 s(-1) in enzyme excess and 0.016 s(-1) in substrate excess. The steady state rate in substrate excess is 4.5 x 10(-4) s(-1). These results demonstrate the following. 1) The pre-steady state carboxylation rate constant of FIXproGla41 is significantly slower than that of FLEEL. 2) The Gla domain plays an allosteric role in substrate-enzyme interactions. 3) Carboxylation reduces the allosteric effect. 4) The similarity between the steady state carboxylation rate constant and product dissociation rate constant suggests that product release is rate-limiting. 5) The increased dissociation rate after carboxylation contributes to the release of product.
Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of β1-integrins (2006)

Dynamic turnover of integrin cell adhesion molecules to and from the cell surface is central to cell migration. We report for the first time an association between integrins and Rab proteins, which are small GTPases involved in the traffic of endocytotic vesicles. Rab21 (and Rab5) associate with the cytoplasmic domains of alpha-integrin chains, and their expression influences the endo/exocytic traffic of integrins. This function of Rab21 is dependent on its GTP/GDP cycle and proper membrane targeting. Knock down of Rab21 impairs integrin-mediated cell adhesion and motility, whereas its overexpression stimulates cell migration and cancer cell adhesion to collagen and human bone. Finally, overexpression of Rab21 fails to induce cell adhesion via an integrin point mutant deficient in Rab21 association. These data provide mechanistic insight into how integrins are targeted to intracellular compartments and how their traffic regulates cell adhesion.
Inhibition of Tumor Growth with Antiangiogenic Cancer Vaccine Using Epitope Peptides Derived from Human Vascular Endothelial Growth Factor Receptor 1 (2006)

These results strongly suggest that VEGFR1 is a promising target for antiangiogenic cancer vaccine and warrants further clinical development of this strategy.
A randomized study of out-of-hospital continuous positive airway pressure for acute cardiogenic pulmonary oedema: physiological and clinical effects (2007)

When compared to usual medical care, immediate application of CPAP alone in out-of-hospital treatment of ACPO is significantly better improving physiological variables and symptoms and significantly reduces tracheal intubation incidence and in-hospital mortality.
Lyme disease: a growing threat to urban populations. (1994)

Lyme disease or Lyme borreliosis, which is caused by three groups of the spirochete Borrelia burgdorferi, is transmitted in North America, Europe, and Asia by ticks of the Ixodes ricinus complex. The primary areas around the world that are now affected by Lyme disease are near the terminal moraine of the glaciers 15,000 years ago. The emergence of Lyme disease in the United States in this century is thought to have occurred because of ecological conditions favorable for deer. From 1982 through 1991, 40,195 cases occurring in 47 states were reported to the Centers for Disease Control, but enzootic cycles of B. burgdorferi have been identified in only 19 states. During the last several decades, the disease has spread to new areas and has caused focal outbreaks, including locations near Boston, New York, and Philadelphia. Lyme disease is like syphilis in its multisystem involvement, occurrence in stages, and mimicry of other diseases. Diagnosis of late neurologic abnormalities of the disorder has created the most difficulty. A recent phenomenon is that a number of poorly understood conditions, such as chronic fatigue syndrome or fibromyalgia, are misdiagnosed as "chronic Lyme disease." Part of the reason for misdiagnosis is due to problems associated with diagnostic tests. The various manifestations of Lyme disease can usually be treated successfully with oral doxycycline or amoxicillin, except for objective neurologic manifestations, which seem to require intravenous therapy. Vector control of thick-borne diseases has been difficult and, therefore, reduction of the risk of infection has been limited primarily to personal protection measures.
A Parathyroid Hormone-Related Protein Implicated in Malignant Hypercalcemia: Cloning and Expression (1987)

Humoral hypercalcemia of malignancy is a common complication of lung and certain other cancers. The hypercalcemia results from the actions of tumor factors on bone and kidney. We report here the isolation of full-length complementary DNA clones of a putative hypercalcemia factor, and the expression from the cloned DNA of the active protein in mammalian cells. The clones encode a prepro peptide of 36 amino acids and a mature protein of 141 amino acids that has significant homology with parathyroid hormone in the amino-terminal region. This previously unrecognized hormone may be important in normal as well as abnormal calcium metabolism.
Role of the Aryl Hydrocarbon Receptor in Carcinogenesis and Potential as a Drug Target (2013)

The aryl hydrocarbon receptor (AHR) is highly expressed in multiple organs and tissues, and there is increasing evidence that the AHR plays an important role in cellular homeostasis and disease. The AHR is expressed in multiple tumor types, in cancer cell lines, and in tumors from animal models, and the function of the AHR has been determined by RNA interference, overexpression, and inhibition studies. With few exceptions, knockdown of the AHR resulted in decreased proliferation and/or invasion and migration of cancer cell lines, and in vivo studies in mice overexpressing the constitutively active AHR exhibited enhanced stomach and liver cancers, suggesting a pro-oncogenic role for the AHR. In contrast, loss of the AHR in transgenic mice that spontaneously develop colonic tumors and in carcinogen-induced liver tumors resulted in increased carcinogenesis, suggesting that the receptor may exhibit antitumorigenic activity prior to tumor formation. AHR ligands also either enhanced or inhibited tumorigenesis, and these effects were highly tumor specific, demonstrating that selective AHR modulators that exhibit agonist or antagonist activities represent an important new class of anticancer agents that can be directed against multiple tumors.
Mutations Affecting Amino Sugar Metabolism in Escherichia coli K-12 (1972)

The genetic loci determining N-acetylglucosamine-6-phosphate deacetylase and glucosamine-6-phosphate deaminase have been located at min 16 on the Escherichia coli K-12 genetic map.
MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1 (2008)

Adhesion molecules expressed by activated endothelial cells play a key role in regulating leukocyte trafficking to sites of inflammation. Resting endothelial cells normally do not express adhesion molecules, but cytokines activate endothelial cells to express adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1), which mediate leukocyte adherence to endothelial cells. We now show that endothelial cells express microRNA 126 (miR-126), which inhibits VCAM-1 expression. Transfection of endothelial cells with an oligonucleotide that decreases miR-126 permits an increase in TNF-alpha-stimulated VCAM-1 expression. Conversely, overexpression of the precursor to miR-126 increases miR-126 levels and decreases VCAM-1 expression. Additionally, decreasing endogenous miR-126 levels increases leukocyte adherence to endothelial cells. These data suggest that microRNA can regulate adhesion molecule expression and may provide additional control of vascular inflammation.
High-throughput assay and engineering of self-cleaving ribozymes by sequencing (2015)

Self-cleaving ribozymes are found in all domains of life and are believed to play important roles in biology. Additionally, self-cleaving ribozymes have been the subject of extensive engineering efforts for applications in synthetic biology. These studies often involve laborious assays of multiple individual variants that are either designed rationally or discovered through selection or screening. However, these assays provide only a limited view of the large sequence space relevant to the ribozyme function. Here, we report a strategy that allows quantitative characterization of greater than 1000 ribozyme variants in a single experiment. We generated a library of predefined ribozyme variants that were converted to DNA and analyzed by high-throughput sequencing. By counting the number of cleaved and uncleaved reads of every variant in the library, we obtained a complete activity profile of the ribozyme pool which was used to both analyze and engineer allosteric ribozymes.
Cleavage of Ethers (1983)

The scope and limitations of reagents for the cleavage of ethers are discussed. The reagents are conveniently classified in the five main headings. Selectivity patterns of some of the reagents are discussed in cases where sufficient data has been given in the literature. 1. Introduction 2. Acidic Reagents 2.1. Brönsted Acids 2.2. Lewis Acids 3. Basic Reagents 3.1. Alkali Hydroxides 3.2. Alkali Alkoxides 3.3. Alkali Amides 3.4. Alkali Metals 3.5. Organo-Alkali Metal Compounds 3.6. Sodium Cyanide/Dimethyl Sulfoxide 3.7. Sodium Ethanethiolate 3.8. Sodium Thiocresolate 3.9. Lithium Iodide 3.10. Sodium Benzeneselenolate 4. Miscellaneous Reagents 4.1. Iodotrimethylsilane 4.2. Iodotrichlorosilane 4.3. Dichloroiodomethylsilane 4.4. Bromotrimethylsilane 4.5. Alkylthiotrimethylsilanes 4.6. Ethanethiol or Ethanedithiol/Boron Trifluoride Etherate 4.7. Aluminium Halide/Thiol Systems 4.8. Acetyl Iodide and Pivaloyl Iodide 4.9. Diiodomethyl Ether/Hydrogen Iodide 5. Reductive Cleavage of Ethers 5.1. Lithium Tris[t-butoxy]aluminium Hydride/Triethylborane Complex 5.2. Hydrogenolysis 6. Oxidative Cleavage of Ethers 6.1. Ceric Ammonium Nitrate 6.2. Silver Oxide 6.3. Dichlorodicyanoquinone 6.4. Tris[p-bromophenyl]ammonium Hexachloroantimonate 7. Photochemical Cleavage of Ethers 8. Selectivity in Ether Cleavage 8.1. Stereoelectronic Characteristics of the Ether-Cleaving Agent 8.2. Structural Features of the Groups Cleaved 8.3. Molecular Environment of the C-O Bond not Undergoing Cleavage 9. Addendum
Splenic Cytokine Responses in Indian Kala‐Azar before and after Treatment (1998)

Cytokine mRNA levels were measured in serial splenic aspirates from 27 patients with visceral leishmaniasis during monotherapy with interferon-gamma (IFN-gamma; n = 9), sodium antimony gluconate (SAG; n = 8), or amphotericin B lipid complex (ABLC; n = 10). At baseline, mRNA for IFN-gamma was detected in 18 (86%) of 21 patients, and mRNA for interleukin (IL)-10 and IL-4 was detected in 21 (100%) and 10 (48%) of 21 patients, respectively. With IFN-gamma treatment alone, levels of IFN-gamma mRNA decreased by day 10 and then returned to baseline levels; IL-10 mRNA levels were high throughout treatment. In the SAG and ABLC groups, levels of IFN-gamma and IL-10 mRNA decreased significantly. Polarized Th2 cell type responses do not appear to develop in Indian kala-azar; instead, there is an initial mixed Th1-Th2 cell picture. With successful treatment and resolution of infection, both components of the immune response appear to involute.
Proparathyroid Hormone-related Protein Is Associated with the Chaperone Protein BiP and Undergoes Proteasome-mediated Degradation (1998)

Parathyroid hormone-related peptide (PTHrP) is an important causal factor for hypercalcemia associated with malignancy. In addition to the endocrine functions attributed to secretory forms of the peptide, PTHrP also plays a local role as a mediator of cellular growth and differentiation presumably at least in part through intracellular pathways. In studying the post-translational regulation of PTHrP, we observed that PTHrP was conjugated to multiple ubiquitin moieties. We report here that the proteasome is responsible for the degradation of the endoplasmic reticulum-associated precursor, pro-PTHrP. Cells expressing prepro-PTHrP and exposed to lactacystin accumulate pro-PTHrP assessed by anti-pro specific antibodies. Brefeldin A-treated cells also accumulate pro-PTHrP suggesting that degradation does not occur in the endoplasmic reticulum (ER) lumen. Subcellular fractionation of both lactacystin and brefeldin A-treated cells indicated that accumulated pro-PTHrP resides in microsomal fractions with a portion of the protein exposed to the cytosolic side of the ER membrane as assessed by protease protection experiments. Immunoprecipitation and Western blot analysis identified pro-PTHrP in association with the ER molecular chaperone protein BiP. We conclude that pro-PTHrP from the ER can gain access to the cytoplasmic side of the ER membrane where it can undergo ubiquitination and degradation by the proteasome.
Genetic deletion of BACE1 in mice affects remyelination of sciatic nerves (2008)

BACE1 is a promising therapeutic and preventive target for Alzheimer's disease because it is essential for amyloid deposition. However, the recent demonstration of BACE1 in modulating developmental myelination in both peripheral and central nervous systems raises a concern of its effect on myelin maintenance or remyelination, and inhibition of these processes will potentially be detrimental to the BACE1 inhibitor users who are susceptible to myelination diseases such as adult peripheral nerve injury or multiple sclerosis. In this report, we investigated the role of BACE1 during peripheral nerve remyelination in wild-type (WT) and BACE1-null mice. We show here that genetic deletion of BACE1 affects sciatic nerve remyelination. The impaired remyelination appears to stem from the loss of neuregulin-1 cleavage by BACE1. To demonstrate a direct cleavage of neuregulin-1 by BACE1, we have identified a BACE1 cleavage site that turns out be highly conserved among neuregulin-1 paralogues. Moreover, we show that neuregulin-1 family member neuregulin-3 is also cleavable by BACE1. We hypothesize that the BACE1-cleaved extracellular domain of axonal neuregulin-1, perhaps neuregulin-3 as well, binds to Schwann cell ErbB receptors, which in turn regulate remyelination. Pharmacological inhibition of BACE1 should be carefully monitored to avoid alteration of signaling pathway that regulates remyelination.
A gene expression study on strains of Nostoc (Cyanobacteria) revealing antimicrobial activity under mixotrophic conditions (2012)

Cyanobacteria are well known for their production of a multitude of highly allelopathic compounds. These products have features such as incorporation of non-proteinogenic amino acids which are characteristics of peptides biosynthesized by non-ribosomal peptide synthetases (NRPSs). Some of these peptides have acetate-derived moieties, suggesting that their biosynthesis also involves polyketide synthases (PKSs). Among the photosynthetic microorganisms, cyanobacteria belonging to the genus Nostoc are regarded as good candidates for producing biologically active secondary metabolites. Aiming at the maximization in the production of natural product, we compared autotrophic, and mixotrophic growth at high light intensity of two Nostoc species in relation to the production of bioactive compounds with the antimicrobial activity at different source of sugar. Glucose was shown to be the best substrate for the production of high natural product when compared with sucrose. Also, the rate of biomass production and antimicrobial activity was reaching ~2.0 to 2.5 and ~1.5 times greater than that of the autotrophic and sucrose grown cultures, respectively. Also, we conduct a combined NRPSs and PKSs polymerase chain reaction (PCR). The sequences presented in this study was deposited in GenBank and had accession numbers JF795278 and JF795279 (NRPS A domains) and JF795280 and JF795281 (PKS KS domains). Computer modeling and phylogenetic analysis was conducted to predict the putative amino acid recognized by the unknown adenylation domain in the NRPS sequences. This study highlights the importance of environmental and nutrimental factors in maximization of antibiotic production of two Nostoc species. Keywords: Peptide synthetase gene, polyketide synthase gene, Nostoc , secondary metabolites, mixotrophic conditions
Affinity Purification of Human Plasma Vitamin-D-Binding Protein (1995)

During the course of our studies to probe the vitamin D ligand-binding domains of vitamin D-binding protein and vitamin D receptor, we developed a synthetic procedure to modify the 3 beta-hydroxyl group of vitamin D3 and its 25-hydroxy- and 1,25-dihydroxy metabolites with a 3'-aminopropylether group. In the present study we have coupled 25-hydroxyvitamin D3-3 beta-3'-aminopropylether to an activated Sepharose matrix. Using this stable and reusable affinity matrix we have purified human vitamin D-binding protein from human plasma to homogeneity.
Spherical solid dispersion containing amorphous tolbutamide embedded in enteric coating polymers or colloidal silica prepared by spray-drying technique. (1987)

Spherical solid dispersion particles of tolbutamide were prepared by spray-drying a diluted ammonia solution of the drug with additives. Enteric coating polymers (Eudragit ® L100-55, hydroxypropyl methylcellulose phthalate) and colloidal silica (Aerosil ®) were useful as additives for the solid dispersions. Most of the tolbutamide was dispersed in the amorphous state in the solid dispersion particles when the drug and the additive were formulated in the ratio of 1 : 1. It was a characteristic of the spray-dried solid dispersions that the additive content was smaller than that of dispersions prepared by conventional solvent evaporation or by a grinding method. The drug dissolution in vitro was investigated using the disintegration solution No. 2 (pH 6.8) specified in JP X. The dissolution rate from the solid dispersions was markedly improved compared with that from the original or spray-dried drug powder. The rapid dissolution rate from the solid dispersion with enteric coating polymers was attributed to improved wettability and rapid dissolution of the polymer, while that from the dispersion with colloidal silica was found to have a close relationship with the drug crystallinity as well as the wettability.
Long-term Recurrent Convolutional Networks for Visual Recognition and Description (2014)

Models based on deep convolutional networks have dominated recent image interpretation tasks; we investigate whether models which are also recurrent are effective for tasks involving sequences, visual and otherwise.We describe a class of recurrent convolutional architectures which is end-to-end trainable and suitable for large-scale visual understanding tasks, and demonstrate the value of these models for activity recognition, image captioning, and video description.In contrast to previous models which assume a fixed visual representation or perform simple temporal averaging for sequential processing, recurrent convolutional models are "doubly deep" in that they learn compositional representations in space and time.Learning long-term dependencies is possible when nonlinearities are incorporated into the network state updates.Differentiable recurrent models are appealing in that they can directly map variable-length inputs (e.g., videos) to variable-length outputs (e.g., natural language text) and can model complex temporal dynamics; yet they can be optimized with backpropagation.Our recurrent sequence models are directly connected to modern visual convolutional network models and can be jointly trained to learn temporal dynamics and convolutional perceptual representations.Our results show that such models have distinct advantages over state-of-the-art models for recognition or generation which are separately defined or optimized.