gebhart/patrepeval huggingface dataset:
Idiopathic generalized epilepsy of adolescence (1995)

Juvenile myoclonic epilepsy, juvenile absence epilepsy, and epilepsy with generalized tonic-clonic seizures (GTCS) on awakening are the three syndromes of idiopathic generalized epilepsy of adolescent onset currently included in the classification of epilepsy syndromes of the International League Against Epilepsy (ILAE). Although they differ in their predominant seizure types, the syndromes share several clinical features, thus giving rise to questions of phenotypic overlap and purity. We studied the clinical features of 101 patients with idiopathic generalized epilepsy beginning in adolescence. A standardized interview was used to elucidate seizure phenomenology, precipitants, frequency, and response to treatment. Groups defined by seizure type were compared and their similarities examined. The group with myoclonic but not absence seizures (21 patients) corresponded to the ILAE syndrome of juvenile myoclonic epilepsy, whereas those with absences but not myoclonus (37 patients) resembled juvenile absence epilepsy. Twenty-six patients shared the features of juvenile myoclonic epilepsy and juvenile absence epilepsy. Epilepsy with GTCS on awakening was not a specific syndromic entity; 10 patients had this seizure type alone. Seven patients were without a syndromic diagnosis. In these patients only GTCS occurred, but neither on awakening nor in the evening period of relaxation. We conclude that whilst syndromes of idiopathic generalized epilepsy of adolescence can be recognized, the current classification does not include all patients. In addition, the boundaries between the syndromes are indistinct, suggesting underlying neurobiological, possibly genetic, relationships.
New modality of radiation therapy under increased tumor oxygen tension with angiotensin II: a pilot study. (1993)

Elevation of the mean arterial blood pressure to approximately 150 mmHg by infusion of angiotensin II (AT II) resulted in a selective increase of blood flow in tumor tissue. A concomitant increase in tumor oxygen tension was also observed, suggesting the possibility of hyperbaric oxygenation radiation therapy. By controlling the infusion rate of AT II, mean blood pressure was increased up to 1.5-fold of normotension, and radiation was given (AT II-RT). Forty-one patients with recurrent tumors after intensive radiation therapy or with locally far advanced tumors were treated. Using an uneven dose fractionation scheme, total dose ranged from 5,100 to 7,800 cGy. The radiation response to the tumor was quite good. Including three complete responders, more than 50% tumor regression was obtained in 24 patients (58.5%), less than 50% in 13 (31.7%) and no effect in four (9.7%). On the other hand, damage to normal tissue was minimal, and no serious morbidity was experienced. For example, comparing the results in the two groups of lung cancer patients treated with or without AT II, superiority of AT II-RT was indicated. The curative ability of AT II-RT will be investigated further.
Sequence specificity of inter‐ and intramolecular G‐quadruplex formation by human telomeric DNA (2007)

Human telomeric DNA consists of tandem repeats of the sequence 5'-d(TTAGGG)-3'. Guanine-rich DNA, such as that seen at telomeres, forms G-quadruplex secondary structures. Alternative forms of G-quadruplex structures can have differential effects on activities involved in telomere maintenance. With this in mind, we analyzed the effect of sequence and length of human telomeric DNA on G-quadruplex structures by native polyacrylamide gel electrophoresis and circular dichroism. Telomeric oligonucleotides shorter than four, 5'-d(TTAGGG)-3' repeats formed intermolecular G-quadruplexes. However, longer telomeric repeats formed intramolecular structures. Altering the 5'-d(TTAGGG)-3' to 5'-d(TTAGAG)-3' in any one of the repeats of 5'-d(TTAGGG)(4)-3' converted an intramolecular structure to intermolecular G-quadruplexes with varying degrees of parallel or anti-parallel-stranded character, depending on the length of incubation time and DNA sequence. These structures were most abundant in K(+)-containing buffers. Higher-order structures that exhibited ladders on polyacrylamide gels were observed only for oligonucleotides with the first telomeric repeat altered. Altering the sequence of 5'-d(TTAGGG)(8)-3' did not result in the substantial formation of intermolecular structures even when the oligonucleotide lacked four consecutive telomeric repeats. However, many of these intramolecular structures shared common features with intermolecular structures formed by the shorter oligonucleotides. The wide variability in structure formed by human telomeric sequence suggests that telomeric DNA structure can be easily modulated by proteins, oxidative damage, or point mutations resulting in conversion from one form of G-quadruplex to another.
Transfection into mouse L cells of genes encoding two serologically and functionally distinct bovine class I MHC molecules from a MHC-homozygous animal: evidence for a second class I locus in cattle. (1990)

w10 and KN104 are distinct class I major histocompatibility complex (MHC) serological specificities present in Boran (Bos indicus) cattle. Although these specificities are commonly expressed together, they may also be expressed independently. To establish whether w10 and KN104, when expressed together, are on the same or different molecules, and whether a second class I MHC locus exists in cattle, genomic DNA from an animal homozygous for a haplotype encoding the w10 and KN104 specificities was transfected into thymidine kinase-deficient mouse L cells (Ltk- cells), and the transfected cells were screened with monoclonal antibodies (mAb) specific for the w10 or KN104 allospecificities. Two different populations of transfectants were identified: the cells of one population reacted only with w10-specific mAb, whereas those of the other population were recognized only by the KN104-specific mAb. Alloreactive cytotoxic T lymphocytes (CTL) also distinguished between the two populations. Two CTL clones, shown to be restricted by the KN104 specificity, killed only those L cells expressing molecules recognized by the KN104-reactive mAb. Of eight CTL clones which recognized class I molecules associated with the w10 specificity, four killed the L cells expressing the w10 specificity. The remaining four clones did not kill either population of transfectants. Finally, immunoprecipitation studies revealed that both populations express full-length bovine class I MHC molecules. These results demonstrate that the w10 and KN104 specificities are on distinct class I molecules. As the genes encoding these molecules were derived from a MHC-homozygous animal, the findings also provide strong evidence that there are at least two classical class I loci in cattle.
2‘-O-{2-[N,N-(Dialkyl)aminooxy]ethyl}- Modified Antisense Oligonucleotides (2000)

[structure] Oligonucleotides with two novel modifications, 2'-O-¿2-[N, N-(dimethyl)aminooxy]ethyl¿ (2'-O-DMAOE) and 2'-O-¿2-[N, N-(diethyl)aminooxy]ethyl¿ (2'-O-DEAOE), have been synthesized. These modifications exhibit high binding affinity to target RNA (and not to DNA) and enhance the nuclease stability of oligonucleotides considerably with t(1/2) > 24 h as a phosphodiester.
Pathology of lumbar nerve root compression Part 1: Intraradicular inflammatory changes induced by mechanical compression (2003)

Inflammatory reaction, such as Wallerian degeneration, breakdown of blood-nerve barrier and appearance of macrophage, may be deeply involved in radiculitis arising from mechanical compression, and these factors seem to be important in the manifestation of radiculopathy.
The Nature and Significance of Memory Disturbance in Posttraumatic Stress Disorder (2011)

Disturbances in aspects of memory described in current learning and cognitive theories are much more strongly associated with the presence of psychiatric disorder than with mere exposure to traumatic events. In posttraumatic stress disorder (PTSD), there are numerous associated changes that involve memory capacity, the content of memories for trauma, and a variety of memory processes. Whereas some changes appear to reflect the effects of the disorder, other evidence supports a predictive or causal role for memory disturbance. The following aspects of memory are likely to play a causal role in the development or maintenance of PTSD: verbal memory deficits, negative conceptual knowledge concerning the self, overgeneral memory, avoidance or suppression of memories, and negative interpretation of memory symptoms. Other aspects of memory likely to play a causal role that are in addition specific to PTSD are the integration of the trauma with identity, impairment in retrieval of voluntary trauma memories, and increased incidence of sensation-based memories or flashbacks.
Metabolic Delivery of Ketone Groups to Sialic Acid Residues (1998)

The development of chemical strategies for decorating cells with defined carbohydrate epitopes would greatly facilitate studies of carbohydrate-mediated cell surface interactions. This report describes a general strategy for engineering the display of chemically defined oligosaccharides on cell surfaces that combines the concepts of metabolic engineering and selective chemical reactivity. Using a recently described method (Mahal, L. K., Yarema, K. J., and Bertozzi, C. R. (1997) Science 276, 1125-1128), we delivered a uniquely reactive ketone group to endogenous cell surface sialic acid residues by treating cells with the ketone-bearing metabolic precursor N-levulinoylmannosamine (ManLev). The ketone undergoes highly selective condensation reactions with complementary nucleophiles such as aminooxy and hydrazide groups. The detailed quantitative parameters of ManLev metabolism in human and nonhuman-derived cell lines were determined to establish a foundation for the modification of cell surfaces with novel epitopes at defined cell-surface densities. Ketones within the glycoconjugates on ManLev-treated cells were then reacted with synthetic aminooxy and hydrazide-functionalized carbohydrates. The remodeled cells were endowed with novel lectin binding profiles as determined by flow cytometry analysis. The simplicity and generality of this method make it well suited for use in the study of carbohydrate-mediated cell surface interactions.
Polynomial functions can be realized by finite size multilayer feedforward neural networks (1991)

The authors present an analytic method to construct polynomial functions by multilayer feedforward neural networks. Because the polynomials consist of multiplication operations and linear weighted summations, if the multiplier can be constructed by a neural network, any polynomial function can be represented by a neural network (a single unit already has the function of weighted summation). The authors try to construct a neural network module with one hidden layer that works as a multiplier (it is referred to as a neural multiplier module). It is shown, in principle, that the multiplier can be approximated by a neural network with four hidden units, with arbitrary accuracy on a bounded closed set.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
High consumptions of grain, fish, dairy products and combinations of these are associated with a low prevalence of metabolic syndrome (2007)

A high consumption of dairy products, fish, or cereal grains is associated with a lower probability of IRS. The probability decreases when intakes of all three types of food were high.
Ebselen in Acute Ischemic Stroke (1998)

Early treatment with ebselen improved the outcome of acute ischemic stroke. Ebselen may be a promising neuroprotective agent.
Dairy Consumption, Obesity, and the Insulin Resistance Syndrome in Young Adults (2002)

Dietary patterns characterized by increased dairy consumption have a strong inverse association with IRS among overweight adults and may reduce risk of type 2 diabetes and cardiovascular disease.
Retention time optimization for eDRAM in 22nm tri-gate CMOS technology (2013)

A high performance eDRAM technology has been developed on a high-performance and low-power 22nm tri-gate CMOS SoC technology. By applying noise reduction circuit techniques and extensive device and design co-optimization on eDRAM bitcell and critical circuits, over 100μs retention time at 95°C has been achieved for a Gbit eDRAM with robust manufacturing yield.
A human monoclonal antibody directed to blood group i antigen: heterohybridoma between human lymphocytes from regional lymph nodes of a lung cancer patient and mouse myeloma. (1986)

A fusion of human lymphocytes released from regional lymph nodes of papillary adenocarcinoma of lung cancer with mouse myeloma P3-X63-Ag8-U1 cells resulted in a stable hybridoma-secreting human IgM antibody (NCC-1004) that reacts with a large proportion of squamous cell carcinomas of lung and esophagus as well as carcinoma of thyroid glands. However, the antibody also reacts with normal red blood cells, B lymphocytes, and a few other limited loci in normal tissues such as the basal cells of bronchial epithelium and the basal cell layer of stratified squamous epithelium, as well as endothelium and alveolar lining epithelium. The antigen defined by NCC-1004 has been characterized as blood group i antigen on the basis of the following results. The antibody preferentially agglutinates cord erythrocytes in contrast to adult erythrocytes. The agglutination was obvious at 4 degrees C, but diminished greatly at 37 degrees C, and was enhanced after sialidase treatment. The antibody specifically reacts with lacto-norhexaosylceramide (nLc6) and sialosyllacto-norhexaosylceramide (IV3NeuAcnLc6), but does not react with lacto-neotetraosylceramide (nLc4), sialosyllacto-neotetraosylceramide (IV3NeuAcnLc4), lacto-isooctaosylceramide (IV6Gal beta 1----4GlcNAcnLc6; I antigen), and other standard glycolipids so far tested. The properties of the antibody and its antigen are identical to those previously described for the i blood group system. Inasmuch as the hybridoma was established by hybridization of lymphocytes derived from regional lymph nodes of lung cancer, and the antigen was found in the patient's lung cancer tissue, the i antigen in lung cancer is probably recognized as a tumor-associated antigen by the host's immune cell system.
A novel approach to preventing the hemolysis of paroxysmal nocturnal hemoglobinuria: both complement-mediated cytolysis and C3 deposition are blocked by a monoclonal antibody specific for the alternative pathway of complement (2010)

The clinical hallmark of paroxysmal nocturnal hemoglobinuria (PNH) is chronic intravascular hemolysis that is a consequence of unregulated activation of the alternative pathway of complement (APC). Intravascular hemolysis can be inhibited in patients by treatment with eculizumab, a monoclonal antibody that binds complement C5 thereby preventing formation of the cytolytic membrane attack complex of complement. However, in essentially all patients treated with eculizumab, persistent anemia, reticulocytosis, and biochemical evidence of hemolysis are observed; and in a significant proportion, their PNH erythrocytes become opsonized with complement C3. These observations suggest that PNH patients treated with eculizumab are left with clinically significant immune-mediated hemolytic anemia because the antibody does not block APC activation. With a goal of improving PNH therapy, we characterized the activity of anti-C3b/iC3b monoclonal antibody 3E7 in an in vitro model of APC-mediated hemolysis. We show that 3E7 and its chimeric-deimmunized derivative H17 block both hemolysis and C3 deposition on PNH erythrocytes. The antibody is specific for the APC C3/C5 convertase because classical pathway-mediated hemolysis is unaffected by 3E7/H17. These findings suggest an approach to PNH treatment in which both intravascular and extravascular hemolysis can be inhibited while preserving important immune functions of the classical pathway of complement.
Emerging Anabolic Treatments in Osteoporosis (2011)

Anabolic treatment that remodels bone tissue and restores bone biomechanical competence is essential in the treatment of osteoporosis. In addition, long term antiresorptive therapy may have limitations because of the reduced renewal of bone tissue. The only pure anabolic drugs available at present are intact PTH (1-84) (Preotact®) and the truncated PTH (1-34) (Teriparatide, Forteo®) while strontium ranelate may possess antiresorptive as well as anabolic properties. The marketed antiresorptive and anabolic antiosteoporotic drugs have limitations in their use due to adverse effects or to the occurrence of rare but severe late complications. Furthermore, indications may be restricted by co-existing diseases or treatment duration may be limited. However, new anabolic drugs are being developed mimicking the effect of PTH, or targeting the calcium sensing receptor (CaSR) or the Wnt/β-catenin signalling pathway. The PTH mimetics are truncated or altered PTH fragments, parathyroid hormone related peptide (PTHrP) and calcilytics stimulating endogenous PTH secretion. Calcimimetics (e.g. strontium) and calcilytics (e.g. lithium) may also affect bone cells directly through the CaSR. The Wnt pathway that stimulates osteoblastic proliferation, differentiation and function may be activated by neutralizing antibodies to secreted inhibitors of Wnt signalling (e.g. Sclerostin or Dickkopf) or by small molecules (e.g. lithium) that inhibits the glycogen synthase kinase 3β mediated degradation of β-catenin. Finally, blocking of activin A by soluble receptor fusion proteins has been shown to increase bone mass by a dual anabolic-antiresorptive action. The present paper summarises the physiological background and the present evidence for these effects.
The peptide transporter PepT2 is expressed in rat brain and mediates the accumulation of the fluorescent dipeptide derivative ?-Ala-Lys-N?-AMCA in astrocytes (1999)

We describe the synthesis of a fluorescent dipeptide derivative, beta-Ala-Lys-Nepsilon-AMCA, which could be used as an excellent reporter molecule for studying the oligopeptide transport system in brain cell cultures. Fluorescence microscopic and immunocytochemical studies revealed that the reporter peptide specifically accumulated in astrocytes (type I and II) and O-2A progenitor cells but not in neurons or differentiated oligodendrocytes. In astroglia-rich cell culture the dipeptide derivative is taken up in unmetabolized form by an energy dependent, saturable process with apparent kinetic constants of KM = 28 microM and Vmax = 6 nmol x h(-1) x mg protein(-1) at pH 7.2. Competition studies revealed that the accumulation of beta-Ala-Lys-Nepsilon-AMCA is strongly inhibited by dipeptides and pseudopeptides such as bestatin, arphamenine A and B. The biochemical data indicated that the properties of this high-affinity oligopeptide carrier closely resemble those of the renal peptide transport system PepT2 and Northern blot analysis demonstrated that PepT2 mRNAis expressed in glial but not in neuronal cell cultures. In situ hybridization histochemistry also revealed a non-neuronal localization of PepT2 transcripts and a diffuse, widespread distribution of PepT2 signals throughout the entire rat brain. The selective accumulation of the fluorescent reporter molecule by brain cells under viable conditions may provide a useful tool for studying peptide uptake systems and other aspects of astroglial physiology.
Experiences of virus, retrovirus and retrovirus-like particles in Chinese hamster ovary (CHO) and hybridoma cells used for production of protein therapeutics. (1998)

Garnick and coworkers indicated that they experienced two independent MVM outbreaks in a period where approximately 2000 fermentations were performed, hypothesizing that such events were rare but inevitable consequences of very large scale operations. In GIs experience over the last 12 years we have seen no incidence of MVM (or any other virus) in close to 3000 fermentations, albeit at lower volumes than produced at Genentech; GI has used 250-2500L bioreactors for manufacturing whereas Genentech have reported using 100-10,000L bioreactors. Nonetheless, volumes of complex media in the same range as used at Genentech have been used at GI with no observations of viral contamination events. The reason for this is not clear. However, GI's experience in combination with experience from sub-contract testing agencies who service the majority of the biotechnology industry may call the inevitability of an MVM outbreak into question. It would appear that very few adventitious viral contaminations of cell cultures have occurred in industry in the last decade. Interestingly, the frequency of contamination events appear to be lower in CHO cells than in hybridoma cells. It should be noted, however, that these conclusions are not statistically based and the scope of the above survey was somewhat limited. RVLPs are present in both CHO and hybridoma cells. The characteristics of both are compared in Table 4. C-type particles from hybridoma cells are more abundant as a rule than those from CHO cells. Although the majority of C-type particles produced by hybridoma cells appear to be non-infective (in S+L- assays), approximately one in a million particles are competent to replicate in S+L- cells. The evidence that C-type particles can replicate in human cells has proved difficult to reproduce consistently. It is likely that replication of xenotropic hybridoma C-type particles in human cells is inefficient or restricted to only a small number of specific cell lines. C-type RVLPs from CHO cells are produced less abundantly than those from hybridoma cells and are not competent to replicate due to a defective endonuclease gene. However, over the last two decades the use of hybridoma cells and products derived from these cells has not provided any evidence of transmission of these viruses to humans; in addition they can be readily removed or inactivated. Thus, neither agent would appear to constitute a significant risk to pharmaceutical products made from their respective host cells. Nonetheless, given the difference in relative safety profiles between RVLPs from CHO and hybridoma cells it is not unreasonable to propose that safety factors (clearance factors in removal/inactivation studies in excess of the reduction of virus loads to zero) required should be less for a CHO process than for a hybridoma process.
Genome-Wide Analysis of DNA Methylation and Gene Expression Changes in Two Arabidopsis Ecotypes and Their Reciprocal Hybrids (2012)

Heterosis is a fundamental biological phenomenon characterized by the superior performance of a hybrid over its parents in many traits, but the underlying molecular basis remains elusive. To investigate whether DNA methylation plays a role in heterosis, we compared at single-base-pair resolution the DNA methylomes of Arabidopsis thaliana Landsberg erecta and C24 parental lines and their reciprocal F1 hybrids that exhibited heterosis. Both hybrids displayed increased DNA methylation across their entire genomes, especially in transposable elements. Interestingly, increased methylation of the hybrid genomes predominantly occurred in regions that were differentially methylated in the two parents and covered by small RNAs, implying that the RNA-directed DNA methylation (RdDM) pathway may direct DNA methylation in hybrids. In addition, we found that 77 genes sensitive to methylome remodeling were transcriptionally repressed in both reciprocal hybrids, including genes involved in flavonoid biosynthesis and two circadian oscillator genes circadian clock associated1 and late elongated hypocotyl. Moreover, growth vigor of F1 hybrids was compromised by treatment with an agent that demethylates DNA and by abolishing production of functional small RNAs due to mutations in Arabidopsis RNA methyltransferase HUA enhancer1. Together, our data suggest that genome-wide remodeling of DNA methylation directed by the RdDM pathway may play a role in heterosis.