gebhart/patrepeval huggingface dataset:
Large exons encoding multiple ectodomains are a characteristic feature of protocadherin genes (2000)

Recent studies revealed a striking difference in the genomic organization of classic cadherin genes and one family of "nonclassic cadherin" genes designated protocadherins. Specifically, the DNA sequences encoding the ectodomain repeats of classic cadherins are interrupted by multiple introns. By contrast, all of the encoded ectodomains of each member of the protocadherin gene clusters are present in one large exon. To determine whether large ectodomain exons are a general feature of protocadherin genes we have investigated the genomic organization of several additional human protocadherin genes by using DNA sequence information in GenBank. These genes include protocadherin 12 (Pcdh12), an ortholog of the mouse vascular endothelial cadherin-2 gene; hFmi1 and hFmi2, homologs of the Drosophila planar cell polarity gene, flamingo; hFat2, a homolog of the Drosophila tumor suppressor gene fat; and the Drosophila DN-cadherin and DE-cadherin genes. Each of these genes was found to be a member of the protocadherin subfamily, based on amino acid sequence comparisons of their ectodomains. Remarkably, all of these protocadherin genes share a common feature: most of the genomic DNA sequences encoding their ectodomains are not interrupted by an intron. We conclude that the presence of unusually large exons is a characteristic feature of protocadherin genes.
Specific Targeting of Pro-Death NMDA Receptor Signals with Differing Reliance on the NR2B PDZ Ligand (2008)

NMDA receptors (NMDARs) mediate ischemic brain damage, for which interactions between the C termini of NR2 subunits and PDZ domain proteins within the NMDAR signaling complex (NSC) are emerging therapeutic targets. However, expression of NMDARs in a non-neuronal context, lacking many NSC components, can still induce cell death. Moreover, it is unclear whether targeting the NSC will impair NMDAR-dependent prosurvival and plasticity signaling. We show that the NMDAR can promote death signaling independently of the NR2 PDZ ligand, when expressed in non-neuronal cells lacking PSD-95 and neuronal nitric oxide synthase (nNOS), key PDZ proteins that mediate neuronal NMDAR excitotoxicity. However, in a non-neuronal context, the NMDAR promotes cell death solely via c-Jun N-terminal protein kinase (JNK), whereas NMDAR-dependent cortical neuronal death is promoted by both JNK and p38. NMDAR-dependent pro-death signaling via p38 relies on neuronal context, although death signaling by JNK, triggered by mitochondrial reactive oxygen species production, does not. NMDAR-dependent p38 activation in neurons is triggered by submembranous Ca(2+), and is disrupted by NOS inhibitors and also a peptide mimicking the NR2B PDZ ligand (TAT-NR2B9c). TAT-NR2B9c reduced excitotoxic neuronal death and p38-mediated ischemic damage, without impairing an NMDAR-dependent plasticity model or prosurvival signaling to CREB or Akt. TAT-NR2B9c did not inhibit JNK activation, and synergized with JNK inhibitors to ameliorate severe excitotoxic neuronal loss in vitro and ischemic cortical damage in vivo. Thus, NMDAR-activated signals comprise pro-death pathways with differing requirements for PDZ protein interactions. These signals are amenable to selective inhibition, while sparing synaptic plasticity and prosurvival signaling.
Fractal extensions of near-field aperture shapes for enhanced transmission and resolution (2005)

Families of fractals are investigated as near-field aperture shapes. They are shown to have multiple transmission resonances associated with their multiple length scales. The higher iterations exhibit enhanced transmission, and spatial resolution exceeding the first order. Near-field enhancements of greater than 400 times the incident intensity and resolutions of better than ?/20 have been shown with apertures modeled after third iteration prefractals. Enhancements as large as 1011 have been shown, when compared with conventional square apertures that produce the same spot size. The effects of the complex permittivity values of the metal film are also addressed.
Cloning and Functional Characterization of a Mouse Intestinal Acyl-CoA:Monoacylglycerol Acyltransferase, MGAT2 (2003)

Acyl-CoA:monoacylglycerol transferase (MGAT) plays a predominant role in dietary fat absorption in the small intestine, where it catalyzes the first step of triacylglycerol resynthesis in enterocytes for chylomicron formation and secretion. Although the mouse small intestine exhibits the highest MGAT enzyme activity among all of the tissues studied, the gene encoding the enzyme has not been identified so far. In the present studies, we report the identification and characterization of a mouse intestinal MGAT, MGAT2. Transient expression of MGAT2 in AV-12, COS-7, and Caco-2 cells led to a more than 70-, 30-, and 35-fold increase in the synthesis of diacylglycerol, respectively. MGAT2 expressed in mammalian cells can catalyze the acylation of rac-1-, sn-2-, and sn-3-monoacylglycerols, and the enzyme prefers monoacylglycerols containing unsaturated fatty acyls as substrates. MGAT2 also demonstrates weak DGAT activity, which can be distinguished from its MGAT activity by detergent treatment that abolishes DGAT but not MGAT activity. We also analyzed the biochemical features of MGAT2 and demonstrated homogenate protein-, time-, and substrate concentration-dependent MGAT enzyme activity in transiently transfected COS-7 cells. Northern blot analysis indicates that the mouse MGAT2 is most abundantly expressed in the small intestine, suggesting that MGAT2 may play an important role in dietary fat absorption.
Time Series Clustering: Complex is Simpler! (2011)

Given a motion capture sequence, how to i-dentify the category of the motion? Classifying human motions is a critical task in motion editing and synthesizing, for which manual labeling is clearly inefficient for large databases. Here we study the general problem of time series clustering. We propose a novel method of clustering time series that can (a) learn joint temporal dynamics in the data; (b) handle time lags; and (c) produce interpretable features. We achieve this by developing complex-valued linear dynamical systems (CLDS), which include real-valued Kalman filters as a special case; our advantage is that the transition matrix is simpler (just diagonal), and the transmission one easier to interpret. We then present Complex-Fit, a novel EM algorithm to learn the parameters for the general model and its special case for clustering. Our approach produces significant improvement in clustering quality, 1.5 to 5 times better than well-known competitors on real motion capture sequences. 1.
Inhibition of Indoleamine 2,3-Dioxygenase in Dendritic Cells by Stereoisomers of 1-Methyl-Tryptophan Correlates with Antitumor Responses (2007)

Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that contributes to tolerance in a number of biological settings. In cancer, IDO activity may help promote acquired tolerance to tumor antigens. The IDO inhibitor 1-methyl-tryptophan is being developed for clinical trials. However, 1-methyl-tryptophan exists in two stereoisomers with potentially different biological properties, and it has been unclear which isomer might be preferable for initial development. In this study, we provide evidence that the D and L stereoisomers exhibit important cell type-specific variations in activity. The L isomer was the more potent inhibitor of IDO activity using the purified enzyme and in HeLa cell-based assays. However, the D isomer was significantly more effective in reversing the suppression of T cells created by IDO-expressing dendritic cells, using both human monocyte-derived dendritic cells and murine dendritic cells isolated directly from tumor-draining lymph nodes. In vivo, the d isomer was more efficacious as an anticancer agent in chemo-immunotherapy regimens using cyclophosphamide, paclitaxel, or gemcitabine, when tested in mouse models of transplantable melanoma and transplantable and autochthonous breast cancer. The D isomer of 1-methyl-tryptophan specifically targeted the IDO gene because the antitumor effect of D-1-methyl-tryptophan was completely lost in mice with a disruption of the IDO gene (IDO-knockout mice). Taken together, our findings support the suitability of D-1-methyl-tryptophan for human trials aiming to assess the utility of IDO inhibition to block host-mediated immunosuppression and enhance antitumor immunity in the setting of combined chemo-immunotherapy regimens.
Effects of 3 Months of Continuous Subcutaneous Administration of Glucagon-Like Peptide 1 in Elderly Patients With Type 2 Diabetes (2003)

A GLP-1 compound is a promising therapeutic option for elderly diabetic patients.
Lack of Impact of the Loss of Constitutive Folate Receptor α Expression, Achieved by RNA Interference, on the Activity of the New Generation Antifolate Pemetrexed in HeLa Cells (2004)

Pemetrexed [PMX (Alimta)] is a new generation antifolate with activity in a variety of solid tumors. It is an excellent substrate for most folate transporters, notably the reduced folate carrier (RFC) and folate receptor (FR)-alpha. The role of FR-alpha in PMX pharmacological activity is uncertain. Whereas high-level expression may enhance the activity of this agent, it is not clear what role constitutive levels of this transporter contribute to PMX activity. In this study, constitutive levels of FR-alpha expression were abolished by small interfering RNA-induced silencing in HeLa cells and RFC-null HeLa R5 cells as confirmed by Northern blotting, immunohistochemistry, and cell surface binding. PMX growth inhibition was unchanged in HeLa and R5 cells in the absence of FR-alpha expression. Loss of FR-alpha expression did not decrease net accumulation of PMX in either wild-type or RFC-null HeLa cells. Likewise, folate pools in wild-type HeLa cells were not decreased by FR-alpha gene silencing and were negligibly affected in the RFC-null R5 subline grown with 5-formyltetrahydrofolate. FR-alpha surface binding in HeLa cells was shown to be greater than that in a variety of other human solid tumor cell lines. Hence, constitutively expressed FR-alpha in HeLa cells does not contribute to PMX activity in the presence or absence of RFC function. This is likely the case in many human solid tumor cell lines.
Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia (2005)

Mitochondrial permeability transition (PT) is a phenomenon induced by high levels of matrix calcium and is characterized by the opening of the PT pore (PTP). Activation of the PTP results in loss of mitochondrial membrane potential, expansion of the matrix, and rupture of the mitochondrial outer membrane. Consequently, PT has been implicated in both apoptotic and necrotic cell death. Cyclophilin D (CypD) appears to be a critical component of the PTP. To investigate the role of CypD in cell death, we created a CypD-deficient mouse. In vitro, CypD-deficient mitochondria showed an increased capacity to retain calcium and were no longer susceptible to PT induced by the addition of calcium. CypD-deficient primary mouse embryonic fibroblasts (MEFs) were as susceptible to classical apoptotic stimuli as the WT, suggesting that CypD is not a central component of cell death in response to these specific death stimuli. However, CypD-deficient MEFs were significantly less susceptible than their WT counterparts to cell death induced by hydrogen peroxide, implicating CypD in oxidative stress-induced cell death. Importantly, CypD-deficient mice displayed a dramatic reduction in brain infarct size after acute middle cerebral artery occlusion and reperfusion, strongly supporting an essential role for CypD in an ischemic injury model in which calcium overload and oxidative stress have been implicated.
Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects (2009)

The CSF biomarker signature of AD defined by A beta(1-42) and t-tau in the autopsy-confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD.
Study on the Immunomodulatory Effects of Functional Milk in Mice (2013)

The immunomodulatory effects of Functional Milk including FOS(Fructo oligosaccharide),inulin,Selenium enriched yeast in mice were explored.Two hundred and fifty mice,weight in the range of 17 and 23 gram,were divided into five treatment groups and fed at five dose.The dose groups were normal control group,milk control group,low dose group(0.4 mL/kg.bw),middle dose group(0.8 mL/kg.bw) and high dose group(2.5 mL/kg.bw) respectively.Cellular immunity,humoral immunity,monocyte-macrophage cell function and activity of natural-killer(NK) cells were investigated to verify immune function of functional milk.The results showed that no significant effect was observed on weight gain.Compared with the normal and milk control group,the phagocytic capacity of macrophage in medium dose group was significantly different.The activity of lymphocyte transformation,delayed type hypersensitivity(DTH),antibody formation cell and haemolysis value,clearance capacity of carbon and phagocytic capacity of macrophages,activity of NK cells in high dose group were highly significantly different.According to '2003 checking and appraising a technical code on health-care food' decides,functional milk can enhance the immune function in mice.
Increased expression of metadherin protein predicts worse disease‐free and overall survival in laryngeal squamous cell carcinoma (2013)

Metadherin (MTDH) is involved in tumourigenesis and cancer progression in multiple human malignancies. However, the MTDH protein has rarely been reported in laryngeal squamous cell carcinoma (LSCC). The expression pattern of the MTDH protein in 176 primary archival LSCC and 27 corresponding adjacent noncarcinoma specimens was detected by immunohistochemistry and further correlated with clinicopathological parameters. The results demonstrated that 161 (91.48%) primary LSCC samples stained positive for MTDH; however, staining was barely detectable in all adjacent noncarcinoma samples. Moreover, the expression of the MTDH protein was significantly associated with the primary tumour site (p = 0.021), T classification (p = 0.002), clinical stage (I + II/III + IV; p < 0.001), lymph node metastasis (p < 0.001) and postoperational recurrence (p < 0.001). Kaplan-Meier analysis revealed that MTDH expression was significantly associated with worse disease-free survival (DFS) and overall survival (OS) rates in patients with LSCC (both p < 0.001). When lymph node metastasis and MTDH expression were considered together, patients with lymph node metastasis and high MTDH expression had both poorer DFS and OS rates than others (both p < 0.001). Finally, multivariate analysis demonstrated that MTDH expression was an independent prognostic factor for both DFS and OS rates in patients with LSCC. Strong MTDH expression was negatively correlated with a canonical epithelial-mesenchymal transition molecule E-cadherin (p < 0.001) and positively associated with proangiogenic protein vascular endothelial growth factor (p < 0.001). MTDH overexpression was tightly associated with more aggressive tumour behaviour and a poor prognosis, indicating that MTDH is a valuable molecular biomarker for LSCC progression.
Does Calcium Supplementation Prevent Postmenopausal Bone Loss? (1987)

During a two-year study, we examined the effect of calcium supplementation on postmenopausal bone loss in 43 women in the early postmenopausal period who were assigned to one of three treatment groups: percutaneous 17 beta-estradiol (combined with progesterone during the second year), oral calcium (2000 mg daily), and placebo. All participants were examined every three months. Bone mineral content in the forearm (measured by single-photon absorptiometry) and in the entire body and spine (measured by dual-photon absorptiometry) remained constant in the estrogen-treated group but decreased significantly in the groups receiving calcium and placebo. In the calcium-treated group, we observed a tendency toward a slowed loss of compact bone (in the proximal forearm and total skeleton) as compared with the placebo group, while the rate of loss of trabecular bone (the distal forearm and spine) was the same as in the placebo group. Our preliminary data suggest that calcium supplementation in the dosage we used is not as effective as estrogen therapy for the prevention of early postmenopausal bone loss. Calcium supplementation may have had a minor effect on the loss of cortical bone, but it had no effect on the trabecular bone.
A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast. (1995)

We have used a lipophilic styryl dye, N-(3-triethylammoniumpropyl)-4- (p-diethylaminophenyl-hexatrienyl) pyridinium dibromide (FM 4-64), as a vital stain to follow bulk membrane-internalization and transport to the vacuole in yeast. After treatment for 60 min at 30 degrees C, FM 4-64 stained the vacuole membrane (ring staining pattern). FM 4-64 did not appear to reach the vacuole by passive diffusion because at 0 degree C it exclusively stained the plasma membrane (PM). The PM staining decreased after warming cells to 25 degrees C and small punctate structures became apparent in the cytoplasm within 5-10 min. After an additional 20-40 min, the PM and cytoplasmic punctate staining disappeared concomitant with staining of the vacuolar membrane. Under steady state conditions, FM 4-64 staining was specific for vacuolar membranes; other membrane structures were not stained. The dye served as a sensitive reporter of vacuolar dynamics, detecting such events as segregation structure formation during mitosis, vacuole fission/fusion events, and vacuolar morphology in different classes of vacuolar protein sorting (vps) mutants. A particularly striking pattern was observed in class E mutants (e.g., vps27) where 500-700 nm organelles (presumptive prevacuolar compartments) were intensely stained with FM 4-64 while the vacuole membrane was weakly fluorescent. Internalization of FM 4-64 at 15 degrees C delayed vacuolar labeling and trapped FM 4-64 in cytoplasmic intermediates between the PM and the vacuole. The intermediate structures in the cytoplasm are likely to be endosomes as their staining was temperature, time, and energy dependent. Interestingly, unlike Lucifer yellow uptake, vacuolar labeling by FM 4-64 was not blocked in sec18, sec14, end3, and end4 mutants, but was blocked in sec1 mutant cells. Finally, using permeabilized yeast spheroplasts to reconstitute FM 4-64 transport, we found that delivery of FM 4-64 from the endosome-like intermediate compartment (labeled at 15 degrees C) to the vacuole was ATP and cytosol dependent. Thus, we show that FM 4-64 is a new vital stain for the vacuolar membrane, a marker for endocytic intermediates, and a fluor for detecting endosome to vacuole membrane transport in vitro.
Isolation and characterization of a cloned growth factor dependent macrophage cell line, BAC1.2F5 (1987)

The SV40 transformed murine macrophage cell line, BAC1, proliferates in response to the colony stimulating factor, CSF-1 (Schwarzbaum et al., J. Immunol., 132:1158, 1984). In order to obtain a cell line suitable for biochemical and genetic studies of CSF-1 signal transduction, clones of BAC1 were established. Clones ranged from being completely autonomous to being completely dependent on CSF-1 for growth. Cells of one clone (2F5), which proliferated in response to either CSF-1 or granulocyte-macrophage CSF (GM-CSF) were characterized in detail. The kinetics of receptor-mediated internalization and intracellular destruction of CSF-1 were comparable to the kinetics observed with peritoneal exudate macrophages. CSF-1 was shown to regulate cell spreading, cell survival, protein degradation, and the duration of the G1 and S phases of the cell cycle. The 2F5 clone therefore exhibits a number of CSF-1 stimulated responses and is being used for genetic and biochemical studies of CSF-1 action.
Intramuscular Interferon Beta-1A Therapy Initiated during a First Demyelinating Event in Multiple Sclerosis (2000)

Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value.
5-Hydroxytryptophan (5-HTP) and a MAOI (Nialamide) in theTreatment of Depressions (1976)

Through a controlled double-blind study in 30 hospitalized patients affected with endogenous depression, the antidepressant action of the combination of nialamide+l-5-HTP has been evaluated and compared with a control group which only received nialamide (+ placebo). The patients treated with nialamide + l-5-HTP achieved a fuller recovery than those who were treated with nialamide alone. The treatment with nialamide + l-5-HTP proved to have a shorter delay of onset. Side effects showed no marked differences except for the orthostatic hypotension which was less apparent in those patients treated with nialamide + l-5-HTP.
Standardized Agricultural Land Use Classification Scheme at Various Spatial Resolution of Satellite Images (2004)

This study is to present a standardized agricultural land use classification scheme at various spatial resolution (from 1 m to 30 m) of satellite images including Landsat TM, KOMPSAT-1 EOC, ASTER VNIR and IKONOS panchromatic (PAN) and multi-spectral (MS) images. The satellite images were interpreted especially for identifying agricultural land use, crop types, agricultural facilities and structures of 18 items. It was found that there is a threshold spatial resolution between 4 m and 6.6 m to identify the full items. Thus it is suggested that IKONOS fusion image (MS enhanced by PAN) is required to produce land use map for agricultural purpose.
Silencing suppressors: viral weapons for countering host cell defenses (2011)

RNA silencing is a conserved eukaryotic pathway involved in the suppression of gene expression via sequence-specific interactions that are mediated by 21-23 nt RNA molecules. During infection, RNAi can act as an innate immune system to defend against viruses. As a counter-defensive strategy, silencing suppressors are encoded by viruses to inhibit various stages of the silencing process. These suppressors are diverse in sequence and structure and act via different mechanisms. In this review, we discuss whether RNAi is a defensive strategy in mammalian host cells and whether silencing suppressors can be encoded by mammalian viruses. We also review the modes of action proposed for some silencing suppressors.
Mechanism of Action of T-705 against Influenza Virus (2005)

T-705, a substituted pyrazine compound, has been found to exhibit potent anti-influenza virus activity in vitro and in vivo. In a time-of-addition study, it was indicated that T-705 targeted an early to middle stage of the viral replication cycle but had no effect on the adsorption or release stage. The anti-influenza virus activity of T-705 was attenuated by addition of purines and purine nucleosides, including adenosine, guanosine, inosine, and hypoxanthine, whereas pyrimidines did not affect its activity. T-705-4-ribofuranosyl-5'-triphosphate (T-705RTP) and T-705-4-ribofuranosyl-5'-monophosphate (T-705RMP) were detected in MDCK cells treated with T-705. T-705RTP inhibited influenza virus RNA polymerase activity in a dose-dependent and a GTP-competitive manner. Unlike ribavirin, T-705 did not have an influence on cellular DNA or RNA synthesis. Inhibition of cellular IMP dehydrogenase by T-705RMP was about 150-fold weaker than that by ribavirin monophosphate, indicating the specificity of the anti-influenza virus activity and lower level of cytotoxicity of T-705. These results suggest that T-705RTP, which is generated in infected cells, may function as a specific inhibitor of influenza virus RNA polymerase and contributes to the selective anti-influenza virus activity of T-705.