gebhart/patrepeval huggingface dataset:
Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation (2003)

Heterochromatin protein 1 (HP1) is a key component of constitutive heterochromatin in Drosophila and is required for stable epigenetic gene silencing classically observed as position effect variegation. Less is known of the family of mammalian HP1 proteins, which may be euchromatic, targeted to expressed loci by repressor-corepressor complexes, and retained there by Lys 9-methylated histone H3 (H3-MeK9). To characterize the physical properties of euchromatic loci bound by HP1, we developed a strategy for regulated recruitment of HP1 to an expressed transgene in mammalian cells by using a synthetic, hormone-regulated KRAB repression domain. We show that its obligate corepressor, KAP1, can coordinate all the machinery required for stable gene silencing. In the presence of hormone, the transgene is rapidly silenced, spatially recruited to HP1-rich nuclear regions, assumes a compact chromatin structure, and is physically associated with KAP1, HP1, and the H3 Lys 9-specific methyltransferase, SETDB1, over a highly localized region centered around the promoter. Remarkably, silencing established by a short pulse of hormone is stably maintained for &gt;50 population doublings in the absence of hormone in clonal-cell populations, and the silent transgenes in these clones show promoter hypermethylation. Thus, like variegation in Drosophila , recruitment of mammalian HP1 to a euchromatic promoter can establish a silenced state that is epigenetically heritable.
Variants in the Wilms’ tumor gene are associated with focal segmental glomerulosclerosis in the African American population (2005)

Wilms' tumor gene (WT1) is important for nephrogenesis and gonadal growth. WT1 mutations cause Denys-Drash and Frasier syndromes, which are characterized by glomerular scarring. To test whether genetic variations in WT1 and WIT1 (gene immediately 5' to WT1) associate with focal segmental glomerulosclerosis (FSGS), patients with biopsy-proven idiopathic and HIV-1-associated FSGS were enrolled in a multicenter study. We genotyped SNP rs6508 located in WIT1 exon 1, three SNPs (rs2301250, rs2301252, rs2301254) in the promoter shared by WT1 and WIT1, rs2234590 in exon 6, rs2234591 in intron 6, rs16754 in exon 7, and rs1799937 in intron 9 of WT1. Cases (n = 218) and controls (n = 281) were compared in the African American population. Stratification by HIV-1 infection status showed that SNPs rs6508, rs2301254, and rs1799937 were significantly associated with FSGS [rs6508 odds ratio (OR) 1.82, P = 0.006; rs2301254 OR 1.65, P = 0.049; rs1799937 OR 1.91, P = 0.005] in the non-HIV-1 group and rs2234591 (OR 0.234, P = 0.011) in the HIV-1 group. Haplotype analyses in the population revealed that seven SNPs were associated with FSGS; five SNPs had the highest contingency score [-log10(P value) = 13.57] in the HIV-1 group. This association could not be explained by population substructure. We conclude that SNPs in WT1 and WIT1 genes are significantly associated with FSGS, suggesting that variants in these genes may mediate pathogenesis by altering WT1 function. Furthermore, HIV-1 infection status interacts with genetic variations in both genes to influence this phenotype. We speculate that nephropathy liability alleles in WT1 pathway genes cause podocyte dysfunction and glomerular scarring.
Dutch women with a low birth weight have an increased risk of myocardial infarction later in life: a case control study (2005)

BACKGROUND: To investigate whether low birth weight increases the risk of myocardial infarction later in life in women. METHODS: Nationwide population-based case-control study. Patients and controls: 152 patients with a first myocardial infarction before the age of 50 years in the Netherlands. 568 control women who had not had a myocardial infarction stratified for age, calendar year of the index event, and area of residence. RESULTS: Birth weight in the patient group was significantly lower than in control women (3214 vs. 3370 gram, mean difference -156.3 gram (95%CI -9.5 to -303.1). The odds ratio for myocardial infarction, associated with a birth weight lower than 3000 gram (20th percentile in controls) compared to higher than 3000 gram was 1.7 (95%CI 1.1-2.7), while the odds ratio for myocardial infarction for children with a low birth weight (< 2000 g) compared to a birth weight >/= 2000 g was 2.4 (95%CI 1.0 - 5.8). Both figures did not change after adjustment for putative confounders (age, education level, body mass index, waist-hip ratio, hypertension, diabetes, hypercholesterolemia, smoking, and family history of cardiovascular disease). CONCLUSIONS: Low birth weight is associated with an increased risk of myocardial infarction before age of 50 in Dutch women.
Effect of somatostatin analog on peptide release and tumor growth in the Zollinger-Ellison syndrome. (1990)

The clinical presentation of Zollinger-Ellison syndrome (ZES) is the result of gastrin hypersecretion and may be modified by secondary peptide hypersecretion. Treatment is medical (H2-blockers) or surgical (tumor excision and total gastrectomy). H2-blocker escape occurs up to 23 per cent and surgical mortality ranges to 15 per cent. Treatment of advanced disease has limited success. Sandostatin (SMS 201-995) has been shown to decrease basal gastrin and gastric acid secretion in ZES. We hypothesized that SMS would suppress basal and provoked gastrin and secondary peptide secretion in ZES. A patient with refractory, metastatic gastrinoma underwent provocative testing (test meal, calcium infusion, secretion bolus and tolbutamide bolus). Thirteen peptides were drawn at set intervals during these provocative tests. Testing was repeated during SMS therapy (100 micrograms subcutaneously three times per day). Gastrin, pancreatic polypeptide (PP) and glucagon levels were elevated at baseline. SMS suppressed all three peptides (mean 74 per cent) (p less than 0.05). Gastrin, PP and glucagon were provoked by all four tests (means above baseline, 19, 155 and 138 per cent, respectively). Gastrin-releasing peptide, gastric inhibitory peptide and insulin were provoked by calcium infusion (427, 306 and 162 per cent above baseline, respectively). SMS suppressed 14 of 15 of these peaked-provoked peptide levels (mean 72.5 per cent, p less than 0.05). Gastric analysis during calcium infusion showed SMS suppression of hourly gastric secretory volume by 77.5 per cent and of acid production (milliequivalents of acid) by 87.5 per cent. During a 20 month follow-up period, the patient was maintained on SMS, 200 micrograms subcutaneously three times per day. She has remained asymptomatic. Interval peptide profiles at two, eight and 18 months show normal gastrin, PP and glucagon levels. A computed tomographic scan at eight months shows a remarkable regression of primary and metastatic tumor. Regrowth, however, was noted at 19 months. SMS may be useful in ZES by suppressing basal and provoked gastrin and secondary peptide secretion and may occasionally give palliation by yielding temporary tumor registration.
Discordant Expression of Tissue Factor Antigen and Procoagulant Activity on Human Monocytes Activated with LPS and Low Dose Cycloheximide (1991)

The mechanisms underlying the superinduction of procoagulant activity by cycloheximide (CHX) on LPS-activated human monocytes have been investigated. Tissue factor (TF) activity of intact, viable cells was quantitated with a plasma recalcification assay and assays using chromogenic substrates specific for thrombin and factor Xa (FXa). TF antigen was measured simultaneously by immunocytochemical staining and immunoblotting with an anti-TF monoclonal antibody (MAb). Peripheral blood mononuclear cells (PBMC) activated with LPS in the presence of low dose CHX expressed more TF activity (approx. 100% increase) than cells activated with LPS alone. However, TF antigen levels were decreased approximately 70% by CHX. This discordant relationship was due primarily to differences in rates of activation of factor X (FX); LPS/CHX-treated PBMC activated nearly twice as much FX as LPS-treated cells (2.19 +/- 0.37 versus 1.10 +/- 0.21 ng FXa/10(6) PBMC/min, respectively). These studies indicate that TF cofactor activity on LPS/CHX-treated monocytes was approximately 7 times greater than that present on LPS-treated cells. Increased TF functional activity may be due to CHX-induced alterations in the type and content of phospholipids (PL) in the cell membrane. Results showed that exogenous mixed PL markedly increased TF activity on LPS-activated monocytes, but not on LPS/CHX-activated cells, without increasing TF antigen levels or altering cell viability. Membrane alterations may occur on monocytes in certain pathological or iatrogenic conditions resulting in a highly active form of TF in vivo.
Language to Logical Form with Neural Attention (2016)

Semantic parsing aims at mapping natural language to machine interpretable meaning representations. Traditional approaches rely on high-quality lexicons, manually-built templates, and linguistic features which are either domain- or representation-specific. In this paper we present a general method based on an attention-enhanced encoder-decoder model. We encode input utterances into vector representations, and generate their logical forms by conditioning the output sequences or trees on the encoding vectors. Experimental results on four datasets show that our approach performs competitively without using hand-engineered features and is easy to adapt across domains and meaning representations.
Specific antigen vaccination to treat autoimmune disease (2004)

Specific antigen vaccination by administration of the target antigen in aqueous solution has resulted in significant decreases of disease severity in animal models of experimental allergic encephalomyelitis, type I diabetes, and several forms of antigen-induced arthritis, even if administered after the initiation of symptoms. However, in experimental autoimmune encephalomyelitis (EAE) and type I diabetes in nonobese diabetic (NOD) mice, repeated administration of peptide fragments of target antigens in incomplete Freund's adjuvant has resulted in severe anaphylactic reactions. Although these methods of administration are known to potentiate CD4 T helper 2 (Th2) responses, which is the goal of specific antigen vaccination, the risk of anaphylaxis raises a red flag concerning use of this therapy for diseases such as type I diabetes, where the survival time after onset is quite long. It is clear that specific antigen vaccination is effective in preventing several animal models of autoimmune disease, and in treating these diseases once the symptoms are overt. However, the risks of this therapy require serious consideration of alternative methods for down-regulation of the autoimmune process.
Multi-frame infinitesimal motion model for the reconstruction of (dynamic) scenes with multiple linearly moving objects (2002)

We introduce new small-motion multi-frame equations applicable to the reconstruction of dynamic scenes in which points are allowed to move along straight-line paths with constant velocity. The motion equations apply to both static and dynamic points, thus prior segmentation is not necessary. We present a reconstruction algorithm of camera motion, scene structure, and point trajectories embedded into a multi-frame factorization principle which requires the minimum of 11 images and 7 points (out of which at feast 3 are dynamic).
Ultrastructure of the human spinal arachnoid mater and dura mater. (1996)

Human spinal dura and arachnoid, obtained during neurosurgical operations, were studied by transmission electron microscopy. The ultrastructure of spinal meninges largely conformed to the morphology of the cranial meninges, but some minor differences were detected. The dura was composed of an outermost loosely arranged fibroelastic layer, a middle basically fibrous portion and an innermost cellular layer (dural border cell layer). The dural border cell layer was characterised by multiple interdigitating cell processes, no extracellular collagen, significant extracellular spaces and few cell junctions. Paravascular vesiculated nerve profiles were encountered within the fibroadipose epidural tissue. The arachnoid was composed of an outermost portion (arachnoid barrier cell layer), presenting tightly packed cells, numerous tight junctions and no extracellular collagen. In view of its numerous tight junctions, the arachnoid barrier cell layer is considered to represent an effective morphological and physiological meningeal barrier between the cerebrospinal fluid in the subarachnoid space and the blood circulation in the dura. The arachnoid barrier layer was always characterised by a distinct continuous basal lamina on its inner surface towards the innermost collagenous portion of the arachnoid (arachnoid reticular cell layer). The interweaving arachnoid trabecular cells within this layer possessed numerous mitochondria and were anchored to the inner surface of the arachnoid barrier cell layer by desmosomes. An additional layer of flattened branching cells was demonstrated along the inner surface of the arachnoid reticular cell layer and assumed to be an "arachnoid border cell layer'. Morphological data suggest that the dura and arachnoid closely adhere at spinal levels in man without any naturally occurring "subdural space'. However, structurally, the dural border cell layer forms a weak cell layer at the dura-arachnoid continuum that is easily disrupted. The creation of an artifactual subdural space at spinal levels is discussed.
MEMS in space (2001)

The satellite industry could experience its biggest revolution since it joined the ranks of commerce, thanks to some of the smallest machines in existence. Researchers are performing experiments designed to convince the aerospace industry that microelectromechanical systems (MEMS) could open the door to low-cost, high-reliability, mass-produced satellites. MEMS combine conventional semiconductor electronics with beams, gears, levers, switches, accelerometers, diaphragms, microfluidic thrusters, and heat controllers, all of them microscopic in size. Some of the advantages of using MEMS-based satellites are low launch costs and high resistance to radiation and vibration. MEMS-based satellites also promise to be cheaper to develop and fabricate than conventional spacecraft.
Access in mesoporous materials: Advantages of a uniform pore structure in the design of a heavy metal ion adsorbent for environmental remediation (1997)

The access of guest species to the binding sites of adsorbent determines the metal‐binding capacity of materials, which is important for example in environmental remediation efforts. It is shown that MP‐HMS, the mercaptopropylsilane‐functionalized derivative of the molecualr sieve HMS, with its regular pore structure is a much better Hg 2⊕ absorbent than silica gels, in which functionalization leads to pore blocking (see Figure). magnified image
DNA‐Scaffolded Multivalent Ligands to Modulate Cell Function (2014)

We report a simple, versatile, multivalent ligand system that is capable of specifically and efficiently modulating cell-surface receptor clustering and function. The multivalent ligand is made of a polymeric DNA scaffold decorated with biorecognition ligands (i.e., antibodies) to interrogate and modulate cell receptor signaling and function. Using CD20 clustering-mediated apoptosis in B-cell cancer cells as a model system, we demonstrated that our multivalent ligand is significantly more effective at inducing apoptosis of target cancer cells than its monovalent counterpart. This multivalent DNA material approach represents a new chemical biology tool to interrogate cell receptor signaling and functions and to potentially manipulate such functions for the development of therapeutics.
Secure Multiparty AES (full paper). (2009)

We propose several variants of a secure multiparty computation protocol for AES encryption. The best variant requires 2200 + 400 255 expected elementary operations in expected 70 + 20 255 rounds to encrypt one 128-bit block with a 128-bit key. We implemented the variants using VIFF, a software framework for implementing secure multiparty computation (MPC). Tests with three players (passive security against at most one corrupted player) in a local network showed that one block can be encrypted in 2 seconds. We also argue that this result could be improved by an optimized implementation. The security requirements are the same as for the underlying MPC scheme.
Selective Solid State Photooxidant (2003)

Irradiation of biphenyl encapsulated in the cavities of a NaZSM-5 zeolite framework has been reported to result in the formation of an extremely long-lived radical cation. Here, we show that such zeolite encapsulated radical cations can act as irreversible one-electron oxidants for simple alkenes and dienes, in a solid-state analogue to solution-phase cosensitization. Compared to the well-known semiconductor photooxidizers, such as titanium dioxide, the NaZSM-5 zeolite-based solid photooxidants exhibit enhanced selectivity based on oxidation potential, molecular size and shape, and Lewis base character.
Evidence against a Stem Cell Origin of New Hepatocytes in a Common Mouse Model of Chronic Liver Injury (2014)

Hepatocytes provide most liver functions, but they can also proliferate and regenerate the liver after injury. However, under some liver injury conditions, particularly chronic liver injury where hepatocyte proliferation is impaired, liver stem cells (LSCs) are thought to replenish lost hepatocytes. Conflicting results have been reported about the identity of LSCs and their contribution to liver regeneration. To address this uncertainty, we followed candidate LSC populations by genetic fate tracing in adult mice with chronic liver injury due to a choline-deficient, ethionine-supplemented diet. In contrast to previous studies, we failed to detect hepatocytes derived from biliary epithelial cells or mesenchymal liver cells beyond a negligible frequency. In fact, we failed to detect hepatocytes that were not derived from pre-existing hepatocytes. In conclusion, our findings argue against LSCs, or other nonhepatocyte cell types, providing a backup system for hepatocyte regeneration in this common mouse model of chronic liver injury.
Glucagon‐like peptide 1 receptor stimulation as a means of neuroprotection (2010)

Glucagon-like peptide 1 (GLP-1) is a relatively recently discovered molecule originating in the so-called L-cells of the intestine. The peptide has insulinotrophic properties and it is this characteristic that has predominantly been investigated. This has led to the use of the GLP-1-like peptide exendin-4 (EX-4), which has a much longer plasma half-life than GLP-1 itself, being used in the treatment of type II diabetes. The mode of action of this effect appears to be a reduction in pancreatic apoptosis, an increase in beta cell proliferation or both. Thus, the effects of GLP-1 receptor stimulation are not based upon insulin replacement but an apparent repair of the pancreas. Similar data suggest that the same effects may occur in other peripheral tissues. More recently, the roles of GLP-1 and EX-4 have been studied in nervous tissue. As in the periphery, both peptides appear to promote cellular growth and reduce apoptosis. In models of Alzheimer's disease, Parkinson's disease and peripheral neuropathy, stimulation of the GLP-1 receptor has proved to be highly beneficial. In the case of Parkinson's disease this effect is evident after the neurotoxic lesion is established, suggesting real potential for therapeutic use. In the present review we examine the current status of the GLP-1 receptor and its potential as a therapeutic target.
Orbital Unsymmetrization Affects Facial Selectivities of Diels−Alder Dienophiles (1996)

We investigated the Diels-Alder reactions of maleic anhydrides embedded in a dibenzobicyclo[2.2.2]octatriene motif as a nonsterically biased dienophile. Substituents on a benzene ring in these dienophiles are far from the reaction center, providing a sterically equivalent pi-face. Instead substituents can unsymmetrize the dienophilic pi face through pi (anhydride)-pi (aromatic) orbital interactions. Electron-withdrawing substituents affect the facial bias and relative rates of these cycloadditions. The preference of the cycloadditions is opposite in direction to those observed in nucleophilic additions of 2-substituted-9,10-dihydro-9,10-ethanoanthracen-11-ones (dibenzobicyclo[2.2.2]octadienones) and in electrophilic additions of 2-substituted 9,10-dihydro-9,10-ethenoanthracenes (dibenzobicyclo[2.2.2]octatrienes), though all of them have related dibenzobicyclic systems.
From B Cell to Plasma Cell (2006)

B cell development culminates in the formation of plasma cells, potent secretors of the immunoglobulins (Ig), proteins crucial for the health of the organism. Two distinctive and crucial steps are required during B cell differentiation. First, variable gene segments encoding the antigen-binding region of Ig undergo directed rearrangement through a process known as V(D)J recombination. Second, alternative processing of the Ig heavy chain mRNA transcript enables plasma cells to secrete high levels of Ig protein. This review focuses on the molecular mechanisms that control V(D)J recombination in B cell progenitors and alternative RNA processing in plasma cells.
Inhibition of Human DHODH by 4‐Hydroxycoumarins, Fenamic Acids, and N‐(Alkylcarbonyl)anthranilic Acids Identified by Structure‐Guided Fragment Selection (2010)

A strategy that combines virtual screening and structure-guided selection of fragments was used to identify three unexplored classes of human DHODH inhibitor compounds: 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids. Structure-guided selection of fragments targeting the inner subsite of the DHODH ubiquinone binding site made these findings possible with screening of fewer than 300 fragments in a DHODH assay. Fragments from the three inhibitor classes identified were subsequently chemically expanded to target an additional subsite of hydrophobic character. All three classes were found to exhibit distinct structure-activity relationships upon expansion. The novel N-(alkylcarbonyl)anthranilic acid class shows the most promising potency against human DHODH, with IC(50) values in the low nanomolar range. The structure of human DHODH in complex with an inhibitor of this class is presented.
Interleukin-2 Administration Alters the CD4+FOXP3+ T-Cell Pool and Tumor Trafficking in Patients with Ovarian Carcinoma (2007)

Interleukin (IL)-2 is used in the immunotherapy of patients with certain cancer and HIV infection. IL-2 treatment reliably results in 16% to 20% objective clinical response rate in cancer patients, with significant durability of responses in selected patients. However, the mechanisms of therapeutic activity in responding versus nonresponding patients remain poorly understood. CD4(+)CD25(+)FOXP3(+) regulatory T (Treg) cells contribute to immunosuppressive networks in human tumors. We treated 31 ovarian cancer patients with IL-2. We show that administration of IL-2 induces the proliferation of existent Treg cells in patients with ovarian cancer. The potency of Treg cell proliferation is negatively determined by the initial prevalence of Treg cells, suggesting that Treg cells are a factor for self-controlling Treg cell proliferation. After IL-2 cessation, the number of Treg cells more efficiently dropped in clinical responders than nonresponders. Furthermore, IL-2 treatment stimulates chemokine receptor CXCR4 expression on Treg cells, enables Treg cell migration toward chemokine CXCL12 in the tumor microenvironment, and may enforce Treg cell tumor accumulation. Our findings support the concept that administration of IL-2 numerically and functionally affects the Treg cell compartment. These data provide an important insight in evaluating the clinical benefit and therapeutic prediction of IL-2 treatment in patients with cancer.