gebhart/patrepeval huggingface dataset:
The Secreted Form of Invertase in Saccharomyces cerevisiae Is Synthesized from mRNA Encoding a Signal Sequence (1983)

The SUC2 gene of Saccharomyces cerevisiae encodes two differently regulated mRNAs (1.8 and 1.9 kilobases) that differ at their 5' ends. The larger RNA encodes a secreted, glycosylated form of invertase and the smaller RNA encodes an intracellular, nonglycosylated form. We have determined the nucleotide sequence of the amino-terminal coding region of the SUC2 gene and its upstream flanking region and have mapped the 5' ends of the SUC2 mRNAs relative to the DNA sequence. The 1.9-kilobase RNA contains a signal peptide coding sequence and presumably encodes a precursor to secreted invertase. The 1.8-kilobase RNA does not include the complete coding sequence for the signal peptide. The nucleotide sequence data prove that SUC2 is a structural gene for invertase, and translation of the coding information provides the complete amino acid sequence of an S. cerevisiae signal peptide.
A High Notch Pathway Activation Predicts Response to γ Secretase Inhibitors in Proneural Subtype of Glioma Tumor-Initiating Cells (2013)

Genomic, transcriptional, and proteomic analyses of brain tumors reveal subtypes that differ in pathway activity, progression, and response to therapy. However, a number of small molecule inhibitors under development vary in strength of subset and pathway-specificity, with molecularly targeted experimental agents tending toward stronger specificity. The Notch signaling pathway is an evolutionarily conserved pathway that plays an important role in multiple cellular and developmental processes. We investigated the effects of Notch pathway inhibition in glioma tumor-initiating cell (GIC, hereafter GIC) populations using γ secretase inhibitors. Drug cytotoxicity testing of 16 GICs showed differential growth responses to the inhibitors, stratifying GICs into responders and nonresponders. Responder GICs had an enriched proneural gene signature in comparison to nonresponders. Also gene set enrichment analysis revealed 17 genes set representing active Notch signaling components NOTCH1, NOTCH3, HES1, MAML1, DLL-3, JAG2, and so on, enriched in responder group. Analysis of The Cancer Genome Atlas expression dataset identified a group (43.9%) of tumors with proneural signature showing high Notch pathway activation suggesting γ secretase inhibitors might be of potential value to treat that particular group of proneural glioblastoma (GBM). Inhibition of Notch pathway by γ secretase inhibitor treatment attenuated proliferation and self-renewal of responder GICs and induces both neuronal and astrocytic differentiation. In vivo evaluation demonstrated prolongation of median survival in an intracranial mouse model. Our results suggest that proneural GBM characterized by high Notch pathway activation may exhibit greater sensitivity to γ secretase inhibitor treatment, holding a promise to improve the efficiency of current glioma therapy.
Alignment of fibroblasts on grooved surfaces described by a simple geometric transformation (1986)

The response of chick heart fibroblasts to grooved substrata was studied using microfabricated grooves and new measures of shape and alignment derived from the moments of cell shapes. Cell shape and alignment were measured on 23 different sets of regular, parallel grooves, which ranged in width from 1.65 to 8.96 micron, and in repeat spacing from 3.0 to 32.0 micron. The grooves were of constant depth, 0.69 micron. Digitized video images were analysed to extract the zero-, first- and second-order moments of the cell shapes, from which were calculated three measures of cell shape, and three measures of cell alignment. Regression analyses of the measures against parameters of the substratum such as groove width, repeat spacing and the ridge width between grooves show that ridge width is the main parameter affecting cell alignment (alignment being inversely proportional to ridge width), although groove width has a small additional effect. All the differences in cell shape between the different grooves can be summarized to a very good approximation as simple geometrical stretch transformations of the shapes of cells on planar surfaces. Our principal measure of cell alignment, paraxial elongation, is a measure of the necessary transformation. This finding has the interesting biological implication that the shape and orientation adopted by cells, in response to the grooves, are not governed by independent cellular mechanisms.
Further Studies on Proline Concentration in Grapes and Wines (1974)

Berry position in the cluster was found not to affect proline content. The relationship of sugar accumulation to proline accumulation in grape berries was demonstrated for four varieties. 9Cabernet Sauvignon9 accumulates proline at a faster rate and at lower total nitrogen levels than other varieties tested. The differences in varieties for proline concentration in wines were demonstrated by a large number of analyses of experimental and commercial wines. Fruit wines have much less proline (and total nitrogen) than grape wines. Proline concentration relates most directly to total nitrogen concentration of both grapes and wines. <i>Saccharomyces cerevisiae</i> will metabolize proline only under severe nitrogen starvation conditions. These conditions generally would not exist if proline were present in large amounts.
Hepatitis C virus: Historical perspective and current concept (1994)

Over the past 30 years, hepatitis C has emerged from shadowy enigma to important public health problem. The existence of the etiological agent of this disease was first appreciated two decades ago but significant progress in its understanding had to await its molecular characterization within the past 5 years. The virus is a member of the family Flaviviridae and is the cause of approximately 20% of clinical viral hepatitis in the United States. While the control of the transmission of hepatitis C virus in blood and blood products has been nothing less than spectacular, the control of community-acquired hepatitis C will be a major challenge to the scientific and medical communities.
Diagnosis and treatment of cutaneous melanoma: state of the art 2006* (2007)

Although the incidence of melanoma is still rising in Caucasian populations, the increase in mortality has leveled off. Improvements in early diagnosis, with more frequent diagnosis of low-risk patients (i.e. those with <1 mm of tumor thickness), is the main reason for these divergent developments. Primary prevention has not yet been successful and recent studies have demonstrated the lack of effectiveness of sunscreen in preventing nevi in children. Progress was made in early melanoma diagnosis when dermoscopy and digital dermoscopy were introduced, and computer algorithms have proved to be highly efficacious for automated melanoma diagnosis. Primary melanomas are now excised with narrower surgical margins of 1-2 cm. Sentinel-node biopsy is recommended as a nodal staging procedure in patients with tumor thickness of 1 mm and more, but the prognostic impact of this procedure has not yet been demonstrated. New imaging techniques, e.g. whole-body MRI and PET-CT, provide more accurate staging, particularly in patients with apparent metastasis, and facilitate decisions on surgical treatment strategies. Staging is now based on the 2001 TNM classification including tumor thickness and histopathologic ulceration in stages I and II and lymph node micro and macro-metastasis in stage III. A stage- and risk-adopted follow-up schedule is proposed for melanoma surveillance. Adjuvant therapy with interferon-alpha in high-risk patients offers a small benefit in terms of recurrence-free and overall survival; the optimal dosage and duration of this treatment are still to be defined. Almost no progress has been made in the medical treatment of disseminated metastasis of melanoma. Therapy with dacarbazine and a few other single agents remains the first-line treatment approach of choice. A number of new treatment modalities, including targeted molecules and immunologic approaches with monoclonal antibodies, are under development; hopefully, new treatment modalities will be available in the near future.
Congenital Transmission of Murine Leukemia Virus From Wild Mice Prone to the Development of Lymphoma and Paralysis<xref ref-type="fn" rid="FN1">2</xref><xref ref-type="fn" rid="FN2">3</xref> (1979)

Maternal congenital transmission of infectious murine leukemia virus, primarily via milk, was the major route of virus spread in Lake Casitas (LC) wild mice and in crosses of LC mice with uninfected wild and laboratory mice. An indirect extrachromosomal male transmission in utero of LC virus also readily occurred in matings of viremic LC males with C57L females but apparently not with other uninfected wild or NIH Swiss females. Both amphotropic and ecotropic classes of LC murine leukemia viruses were potentially transmissible by congenital and venereal epigenetic means and could induce the same two diseases, lymphoma and paralysis, that occurred naturally in LC wild mice. Lymphoma and paralysis both failed to occur in uninfected LC mice or their hybrid progeny that escaped congenital infection.
Presynaptic Dopaminergic Deficits in Lesch–Nyhan Disease (1996)

Patients with Lesch-Nyhan disease have abnormally few dopaminergic nerve terminals and cell bodies. The abnormality involves all dopaminergic pathways and is not restricted to the basal ganglia. These dopaminergic deficits are pervasive and appear to be developmental in origin, which suggests that they contribute to the characteristic neuropsychiatric manifestations of the disease.
A microphone array system with echo canceller (2006)

Abstract This paper proposes a microphone array unified with an echo canceller that resolves the problem of deteriorated echo suppression performance due to variations of the echo path when a microphone array and an echo canceller are connected. In a teleconferencing system, high‐quality sound acquisition with noise suppression is desirable in addition to acoustic echo suppression. However, in a configuration in which a microphone array to suppress the noise and an echo canceller to suppress the echo are simply connected, the adaptation for the echo canceller cannot follow the echo path variations due to directivity control of the microphone array, so that there is a problem of deteriorated echo suppression performance. In the microphone array with an echo canceller proposed in this paper, the training of the microphone array and that of the echo canceller are performed in a unified way. In this way, the problem of deteriorated echo suppression performance due to echo path variations can be resolved. An evaluation experiment shows that the proposed method can perform stable noise suppression and echo cancellation. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 89(10): 23–32, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/ecjc.20090
Multichannel Attention Network for Analyzing Visual Behavior in Public Speaking (2018)

We investigate the importance of human centered visual cues for predicting the popularity of a public lecture. We construct a large database of more than 1800 TED talk videos and leverage the corresponding (online) viewers' ratings from YouTube for a measure of popularity of the TED talks. Visual cues related to facial and physical appearance, facial expressions, and pose variations are learned using convolutional neural networks (CNN) connected to an attention-based long short-term memory (LSTM) network to predict the video popularity. The proposed overall network is end-to-end-trainable, and achieves state-of-the-art prediction accuracy indicating that the visual cues alone contain highly predictive information about the popularity of a talk. We also demonstrate qualitatively that the network learns a human-like attention mechanism, which is particularly useful for interpretability, i.e. how attention varies with time, and across different visual cues as a function of their relative importance.
ARTag, a Fiducial Marker System Using Digital Techniques (2005)

Fiducial marker systems consist of patterns that are mounted in the environment and automatically detected in digital camera images using an accompanying detection algorithm. They are useful for augmented reality (AR), robot navigation, and general applications where the relative pose between a camera and object is required. Important parameters for such marker systems is their false detection rate (false positive rate), their inter-marker confusion rate, minimal detection size (in pixels) and immunity to lighting variation. ARTag is a marker system that uses digital coding theory to get a very low false positive and inter-marker confusion rate with a small required marker size, employing an edge linking method to give robust lighting variation immunity. ARTag markers are bi-tonal planar patterns containing a unique ID number encoded with robust digital techniques of checksums and forward error correction (FEC). This proposed new system, ARTag has very low and numerically quantifiable error rates, does not require a grey scale threshold as does other marker systems, and can encode up to 2002 different unique ID's with no need to store patterns. Experimental results are shown validating this system.
On the fragmentation of monoclonal IgG1, IgG2a, and IgG2b from BALB/c mice. (1983)

Methods for the production and purification of F(ab')2 fragments from BALB/c monoclonal IgG1, IgG2a, and IgG2b with pepsin and other proteases were examined. The overall susceptibility to degradation is IgG2b greater than IgG2a greater than IgG1. Stable F(ab')2 can be produced in good yield from IgG1 with pepsin at pH 3.5 to 4.0 and can be made directly by pepsin treatment of ascites fluids or cell culture supernatants containing IgG1. IgG2a is cleaved in two steps by pepsin, first to F(ab')2 and then to Fab'. With carefully chosen conditions, F(ab')2 can be obtained in acceptable yield. The primary cleavage for the IgG2a heavy chain appears to be on the COOH terminal side of the interheavy chain disulfides, and secondary cleavage is on the NH2-terminal side. For IgG2b the reverse is true, and F(ab')2 has not been obtained in useful amounts; however, the primary cleavage of IgG2b appears to be assymetric with respect to the two heavy chains, and Fab/c fragments that have one Fab plus Fc can be made. Digestion with elastase resulted in the best yield of Fab/c. This finding may provide a method for retaining cytotoxicity in monoclonal antibodies against cell surface antigens while eliminating their capacity to modulate. The cleavage patterns of the three classes of IgG are rationalized in terms of the structure of their hinge regions.
Coordinated downregulation of the antigen presentation machinery and HLA class I/β2-microglobulin complex is responsible for HLA-ABC loss in bladder cancer (2004)

Downregulation of MHC class I expression is a widespread phenomenon used by tumor cells to escape antitumor T-cell-mediated immune responses. These alterations may play a role in the clinical course of the disease. The aim of our study was to investigate the molecular mechanism underlying the absence of HLA-class I molecule expression in bladder cancer cells. Microdissected tumor tissues were characterized by real-time quantitative PCR for the expression of HLA-ABC, beta2-microglobulin and the members of the antigen processing machinery (APM) of HLA class I molecules (LMP2, LMP7, TAP1, TAP2 and tapasin). Our results showed that irreversible HLA loss by mutations in the beta2-microglobulin gene was not the cause of low HLA class I expression in bladder cancers. In contrast, we observed a coordinated transcription downregulation of HLA-ABC and beta2-microglobulin and APM genes in microdissected tumor tissue derived from bladder carcinomas. This mechanism may represent a major factor for the downregulation of HLA class I expression and in the subsequent direct recognition of cancer cells by cytolytic T lymphocytes. Because this regulatory mechanism is frequently reversible by IFN-gamma treatment, we conclude that HLA class I expression should be a major consideration for immunotherapeutic purposes in patients with bladder cancer.
Tumor-Selective Delivery of Macromolecular Drugs via the EPR Effect: Background and Future Prospects (2010)

This paper briefly documents the history of the discovery of the EPR (enhanced permeability and retention) effect and elucidates an analogy between bacterial infection involving proteases that trigger kinin generation and cancer. The EPR effect of macromolecules in cancer tissues is defined, and the distinction between the EPR effect (with reference to clearance of macromolecules from the interstitial space of tumor tissues) and the simple passive targeting of drugs to tumors is described. Additional points of discussion include the uniqueness of tumor vessels, the influence of kinin and other vascular mediators such as nitric oxide (NO) and prostaglandins, and the heterogeneity of the EPR effect. Two different strategies to augment the EPR effect that were discovered are elevating blood pressure artificially via slow infusion of angiotensin II and applying nitroglycerin or other NO donors. Use of the nitroagent increased not only the blood flow of the tumor, but also the delivery of drug to the tumor and the drug's therapeutic effect. This finding shows an intriguing analogy to hypoxic cardiac infarct tissue, in that both are improved by NO. These two methods were applied to treatment of rodents and human cancers, in combination with other anticancer agents, with successful results achieved in rodents as well as humans. These data suggest very appealing prospects for utilization of the EPR effect in future development of cancer therapeutics.
Benzodiazepine peptidomimetic BZA-5B interrupts the MAP kinase activation pathway in H-Ras-transformed Rat-1 cells, but not in untransformed cells. (1994)

A benzodiazepine peptidomimetic, BZA-5B, inhibits farnesylation of H-Ras and normalizes the morphology of Rat-1 cells transformed with H-RasV12 at concentrations that do not affect the growth of untransformed Rat-1 cells. In the current experiments, we show that BZA-5B decreases the active forms of enzymes in the mitogen-activated protein (MAP) kinase signaling cascade, including Raf, MAP kinase kinase (MEK), and MAP kinase, in cells transformed with H-RasV12. BZA-5B had no effect on these enzymes in cells transformed with H-RasV12,L189, which is geranylgeranylated rather than farnesylated. In cells transformed with H-RasV12, BZA-5B reduced the activities of enzymes in the MAP kinase pathway at concentrations that only partially blocked farnesylation of H-RasV12, suggesting that nonfarnesylated H-RasV12 is a dominant inhibitor of the action of farnesylated H-RasV12 in the BZA-5B treated cells. In untransformed Rat-1 cells, BZA-5B did not inhibit MAP kinase activity nor did it prevent the acute activation triggered by epidermal growth factor, even though farnesylated endogenous H-Ras was no longer detectable. These data raise the possibility that untransformed cells contain a form of Ras (K-Ras or N-Ras) whose prenylation is not inhibited by BZA-5B, thus allowing them to resist the effects of BZA-5B.
Induction of islet cell neogenesis in the adult pancreas: the partial duct obstruction model (1998)

The proliferative capacity of adult pancreatic islet cells is limited, although the formation of new islets from cells associated with the ductal epithelium is achievable even in the adult gland. Understanding the mechanism whereby proliferation and subsequent differentiation of putative precursor cells leads the appearance of new islets, i.e., islet neogenesis, may be important as a modality for treatment of both Type I and type II diabetes, in which there is an absolute or relative deficiency of insulin. It appears that certain genes and their protein products are essential to the initiation of the initial step in the pathway. We have shown that partial obstruction of the hamster pancreas is able to reverse streptozotocin-induced diabetes more than 50% of the time. An extract, termed ilotropin, prepared from obstructed pancreata, also reverses the diabetes, whereas extracts of control non-obstructed pancreata do not. Ilotropin contains a protein that is heat and acid stable with MW around 20-45 kDa that is capable of stimulating the proliferation of isolated duct cells in culture. Using mRNA and a differential display technique, 20 genes were found to be expressed in the partially obstructed (regenerating), but not the non-obstructed (non-regenerating) pancreas. One of these islet neogenesis-associated proteins (INGAP) proved to be unique to the obstructed pancreas, and a peptide contained within the sequence was capable of stimulating the proliferation of ductal cells in culture. INGAP was found to be expressed early in the neogenic process before the onset of ductal cell proliferation, and was capable of stimulating tritiated thymidine uptake into protodifferentiated epithelial cells, compatible with the notion that it might be involved in initiating the process of islet neogenesis.
The Orphan Receptor CRF2-4 Is an Essential Subunit of the Interleukin 10 Receptor (1998)

The orphan receptor CRF2-4 is a member of the class II cytokine receptor family (CRF2), which includes the interferon receptors, the interleukin (IL) 10 receptor, and tissue factor. CRFB4, the gene encoding CRF2-4, is located within a gene cluster on human chromosome 21 that comprises three interferon receptor subunits. To elucidate the role of CRF2-4, we disrupted the CRFB4 gene in mice by means of homologous recombination. Mice lacking CRF2-4 show no overt abnormalities, grow normally, and are fertile. CRF2-4 deficient cells are normally responsive to type I and type II interferons, but lack responsiveness to IL-10. By approximately 12 wk of age, the majority of mutant mice raised in a conventional facility developed a chronic colitis and splenomegaly. Thus, CRFB4 mutant mice recapitulate the phenotype of IL-10-deficient mice. These findings suggest that CRF2-4 is essential for IL-10-mediated effects and is a subunit of the IL-10 receptor.
Double-strand-break repair recombination in Escherichia coli: physical evidence for a DNA replication mechanism in vivo (1999)

DNA double-strand-break repair (DSBR) is, in many organisms, accomplished by homologous recombination. In Escherichia coli DSBR was thought to result from breakage and reunion of parental DNA molecules, assisted by known endonucleases, the Holliday junction resolvases. Under special circumstances, for example, SOS induction, recombination forks were proposed to initiate replication. We provide physical evidence that this is a major alternative mechanism in which replication copies information from one chromosome to another generating recombinant chromosomes in normal cells in vivo. This alternative mechanism can occur independently of known Holliday junction cleaving proteins, requires DNA polymerase III, and produces recombined DNA molecules that carry newly replicated DNA. The replicational mechanism underlies about half the recombination of linear DNA in E. coli; the other half occurs by breakage and reunion, which we show requires resolvases, and is replication-independent. The data also indicate that accumulation of recombination intermediates promotes replication dramatically.