gebhart/patrepeval huggingface dataset:
Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1 (2005)

Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder caused by a CTG repeat expansion in the DMPK gene. Aberrant splicing of several genes has been reported to contribute to some symptoms of DM1, but the cause of muscle weakness in DM1 and elevated Ca2+ concentrations in cultured DM muscle cells is unknown. Here, we investigated the alternative splicing of mRNAs of two major proteins of the sarcoplasmic reticulum, the ryanodine receptor 1 (RyR1) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) 1 or 2. The fetal variants, ASI(-) of RyR1 which lacks residue 3481-3485, and SERCA1b which differs at the C-terminal were significantly increased in skeletal muscles from DM1 patients and the transgenic mouse model of DM1 (HSALR). In addition, a novel variant of SERCA2 was significantly decreased in DM1 patients. The total amount of mRNA for RyR1, SERCA1 and SERCA2 in DM1 and the expression levels of their proteins in HSALR mice were not significantly different. However, heterologous expression of ASI(-) in cultured cells showed decreased affinity for [3H]ryanodine but similar Ca2+ dependency, and decreased channel activity in single-channel recording when compared with wild-type (WT) RyR1. In support of this, RyR1-knockout myotubes expressing ASI(-) exhibited a decreased incidence of Ca2+ oscillations during caffeine exposure compared with that observed for myotubes expressing WT-RyR1. We suggest that aberrant splicing of RyR1 and SERCA1 mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle.
Immune responses of mice to orally administered asialo GM1-specific rabbit IgG in the presence or absence of cholera toxin. (1992)

Cholera toxin (CT) has been shown to be a most potent mucosal immunogen and an adjuvant to orally administered unrelated antigens. We investigated the effect of the oral administration of substances with the ability to bind to intestinal epithelial cells on the immune responses against themselves in the presence or absence of CT. Mice were fed non-specific rabbit IgG (RGG) or rabbit IgG (a-GA1) specific to asialo GM1 glycolipid, a major component of the apical membrane of mouse small intestinal epithelial cells, with or without CT. Oral administration of a-GA1 evoked stronger antibody responses than that of RGG in both the serum and intestinal fluid in the presence of CT. However, when the antigens were administered singly without CT, no significant antibody response was detected. In this case, oral administration of RGG induced severe suppression of the systemic antibody response to a subsequent intraperitoneal injection of RGG. In contrast, a-GA1 could not induce oral tolerance. Together these findings suggest that substances with the ability to bind to intestinal epithelial cells are strong immunogens in the presence of CT and weak tolerogens in the absence of CT.
Copolymerization of propene‐nonconjugated dienes: Derivatization through hydroboration and epoxydation (1993)

Abstract Copolymerization of propylene and nonconjugated dienes such as 1–9 decadiene (α–ω symmetric) and 7‐methyl‐1,6 octadiene (asymmetric) is carried out in the presence of highly active isospecific catalysts for propene polymerization. The incorporation of the diene is random and does not affect the isospecificity of the catalytic system. For a low amount of diene, whatever its structure, an activation effect is observed. For the symmetric diene, the reactivity of the second double bond gives rise to crosslinking. Derivatization through hydroboration or epoxydation is carried out in suspension, using a toluenetetrahydrofuran solvent mixture that is able to swell the polypropylene and dissolve the reactants. After hydroboration the copolymer is transformed into hydroxylated polymer through oxidation in a phase transfer condition. The epoxydized copolymer shows excellent adhesive properties on anodized stainless steel.
Use of a DNA toolbox for the characterization of mutation scanning methods. I: Construction of the toolbox and evaluation of heteroduplex analysis (1999)

A systematic characterization of the effects of important physical parameters on the sensitivity and specificity of methods in searching for unknown base changes (mutations or single nucleotide polymorphisms) over a relatively long DNA segment has not been previously reported. To this end, we have constructed a set of molecules of varying G+C content (40, 50, and 60% GC) having all possible base changes at a particular location — the “DNA toolbox”. Exhaustive confirmatory sequencing demonstrated that there were no other base changes in any of the clones. Using this set of clones as polymerase chain reaction (PCR) templates, amplicons of various lengths with the same base mutated to all other bases were generated. The behavior of these constructs in manual and automated heteroduplex analysis was analyzed as a function of the size and overall base content of the fragment, the nature and location of the base change. Our results show that in heteroduplex analysis, the nature of the mismatched base pair is the overriding determinant for the ability to detect the mutation, regardless of fragment length, GC content, or the location of the mutation.
A PCR-based method for site-specific domain replacement that does not require restriction recognition sequences. (1993)

We describe a PCR-based method for domain replacement that does not require restriction site sequences. We illustrate the technique in which the first epidermal growth factor (EGF1)-like domain of factor IX (FIX) is replaced by the EGF1-like domain of protein C. The method employs four oligonucleotide primers. Two are external primers (forward primer A and inverse primer B) and contain sequences flanking the FIX cDNA nucleotides. The other two primers (forward primer C and inverse primer D) direct the PCR amplification of the EGF1-like domain of protein C, and they are hybrid primers that contain sequences of protein C gene at the 3' end and of FIX gene at the 5' end. Thus the amplified fragment of EGF1-like domain of protein C (PCEGF1 fragment) is flanked by FIX gene sequences on both ends. When this fragment is mixed with FIX cDNA and subjected to one cycle of PCR, two products are obtained: one containing PCEGF1 fragment linked to FIX cDNA sequence upstream and the other containing PCEGF1 fragment linked to FIX cDNA sequence downstream of its EGF1-like domain. The first product is amplified using primers A and D, and the second product is amplified using primers B and C. Both products contain overlapping sequences, which allow annealing upon mixing. The annealed product is amplified by PCR using primers A and B. The final product contains FIX cDNA in which its EGF1 sequence has been replaced by the PCEGF1 sequence.
Using light to tell the time of day: sensory coding in the mammalian circadian visual network (2016)

Circadian clocks are a near-ubiquitous feature of biology, allowing organisms to optimise their physiology to make the most efficient use of resources and adjust behaviour to maximise survival over the solar day. To fulfil this role, circadian clocks require information about time in the external world. This is most reliably obtained by measuring the pronounced changes in illumination associated with the earth's rotation. In mammals, these changes are exclusively detected in the retina and are relayed by direct and indirect neural pathways to the master circadian clock in the hypothalamic suprachiasmatic nuclei. Recent work reveals a surprising level of complexity in this sensory control of the circadian system, including the participation of multiple photoreceptive pathways conveying distinct aspects of visual and/or time-of-day information. In this Review, I summarise these important recent advances, present hypotheses as to the functions and neural origins of these sensory signals, highlight key challenges for future research and discuss the implications of our current knowledge for animals and humans in the modern world.
Operator strength reduction (2001)

Operator strength reduction is a technique that improves compiler-generated code by reformulating certain costly computations in terms of less expensive ones. A common case arises in array addressing expressions used in loops. The compiler can replace the sequence of multiplies generated by a direct translation of the address expression with an equivalent sequence of additions. When combined with linear function test replacement, strength reduction can speed up the execution of loops containing array references. The improvement comes from two sources: a reduction in the number of operations needed to implement the loop and the use of less costly operations.This paper presents a new algorithm for operator strength reduction, called OSR. OSR improves upon an earlier algorithm of Allen, Cocke, and Kennedy [Allen et al. 1981]. OSR operates on the static single assignment (SSA) form of a procedure [Cytron et al. 1991]. By taking advantage of the properties of SSA form, we have derived an algorithm that is simple to understand, quick to implement, and, in practice, fast to run. Its asymptotic complexity is, in the worst case, the same as the Allen, Cocke,and Kennedy algorithm (ACK). OSR achieves optimization results that are equivalent to those obtained with the ACK algorithm. OSR has been implemented in several research and production compilers.
Prevention of Lethal Acute Hepatic Failure by Antimacrophage Migration Inhibitory Factor Antibody in Mice Treated With Bacille Calmette–Guerin and Lipopolysaccharide (1999)

During the past few years, the biological functions of macrophage migration inhibitory factor (MIF) have been extensively re-evaluated. This has been found to be protein involved in broad-spectrum pathophysiological states as an inflammatory cytokine, pituitary-derived hormone, and glucocorticoid-induced immunomodulator. In this study, we investigated the involvement of this cytokine in the pathogenesis of lethal liver injury. Injecting a small dose of lipopolysaccharide (LPS) into bacille Calmette-Guerin (BCG)-primed Jcl:ICR mice caused a lethal hepatic injury mimicking fulminant hepatitis, in which 8 of 11 mice died within 48 hours (27% survival rate). Massive necrosis of parenchymal hepatocytes with marked mononuclear cell infiltration was observed by histological examination. Immunohistochemical analysis showed that most of the infiltrating mononuclear cells were Kupffer cells, macrophages, and, to a lesser extent, T cells. In parallel, serum aminotransferase and tumor necrosis factor-alpha (TNF-alpha) levels were increased. When an anti-MIF polyclonal antibody (0.3 mg IgG fraction/mouse) was intraperitoneally injected into mice primed with BCG, it protected them from acute hepatic failure (90% survival rate) with concomitant improvement of histological features. Injection of the antibody also suppressed the up-regulation of TNF-alpha and T-cell infiltration induced by LPS. Taken together, these results suggested that treatment with the anti-MIF antibody suppresses the endotoxin-induced fatal hepatic failure by regulating production of inflammatory cytokines and T-cell infiltration.
1987 Volvo Award in Clinical Sciences: A New Clinical Model for the Treatment of Low-Back Pain (1987)

Because there is increasing concern about low-back disability and its current medical management, this analysis attempts to construct a new theoretic framework for treatment. Observations of natural history and epidemiology suggest that low-back pain should be a benign, self-limiting condition, that low back-disability as opposed to pain is a relatively recent Western epidemic, and that the role of medicine in that epidemic must be critically examined. The traditional medical model of disease is contrasted with a biopsychosocial model of illness to analyze success and failure in low-back disorders. Studies of the mathematical relationship between the elements of illness in chronic low-back pain suggest that the biopsychosocial concept can be used as an operational model that explains many clinical observations. This model is used to compare rest and active rehabilitation for low-back pain. Rest is the commonest treatment prescribed after analgesics but is based on a doubtful rationale, and there is little evidence of any lasting benefit. There is, however, little doubt about the harmful effects--especially of prolonged bed rest. Conversely, there is no evidence that activity is harmful and, contrary to common belief, it does not necessarily make the pain worse. Experimental studies clearly show that controlled exercises not only restore function, reduce distress and illness behavior, and promote return to work, but actually reduce pain. Clinical studies confirm the value of active rehabilitation in practice. To achieve the goal of treating patients rather than spines, we must approach low-back disability as an illness rather than low-back pain as a purely physical disease. We must distinguish pain as a purely the symptoms and signs of distress and illness behavior from those of physical disease, and nominal from substantive diagnoses. Management must change from a negative philosophy of rest for pain to more active restoration of function. Only a new model and understanding of illness by physicians and patients alike makes real change possible.
Dissecting the Human Identity (2011)

Biometrics has emerged as the key technology for personal identification, with India leading the way in full-scale deployment of a biometric-based universal ID system.
Aspirin for the Primary Prevention of Cardiovascular Events: Recommendation and Rationale (2002)

This statement summarizes the recommendation of the third U.S. Preventive Services Task Force (USPSTF) for aspirin for the primary prevention of cardiovascular events, as well as the supporting scientific evidence. The complete information on which this statement is based, including evidence tables and references, can be found in a companion article in this issue. Copies of this document, the summary of the evidence, and the systematic evidence review can be obtained through the USPSTF Web site (http://www.ahrq.gov/clinic/uspstfix.htm) and in print through the Agency for Healthcare Research and Quality Publications Clearinghouse (800-358-9295).
The rise, fall and reinvention of combinatorial chemistry (2011)

Combinatorial chemistry provides a powerful tool for the rapid creation of large numbers of synthetic compounds. Ideally, these libraries should be a rich source of bioactive molecules, but there is the general feeling that the initial promise of combinatorial chemistry has not yet been realized. In particular, enthusiasm for conducting unbiased (non-structure-guided) screens of large libraries for protein or RNA ligands has waned. A central challenge in this area is to devise methods for the synthesis of chemically diverse, high-quality libraries of molecules with many of the desirable features of natural products. These include diverse functionality, a significant representation of chiral sp(3) centers that provide conformational bias to the molecule, significant skeletal diversity, and good pharmacokinetic properties. However, these libraries must be easy to make from cheap, readily available building blocks, ideally those that would support convenient hit optimization/structure reactivity relationship studies. Meeting these challenges will not be easy. Here I review some recent advances in this area and provide some thoughts on likely important developments in the next few years.
High‐Strength and Multifunctional Macroscopic Fabric of Single‐Walled Carbon Nanotubes (2007)

More than a sixfold increase in tensile strength and modulus of the macroscopic SWNT membranes is demonstrated (see figure) using electron-beam irradiation to effectively form intertube crosslinks. The strength increase is a quadratic function of irradiation dose.
Impact of clinic interventions on the rate of influenza vaccination in pregnant women. (2007)

Interventions to improve influenza vaccination rates among pregnant women, particularly standing orders, are effective. These interventions should be implemented nationally in all prenatal care clinics.
Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions. (1996)

Mutations in the human Cu,Zn superoxide dismutase gene (SOD1) are found in 20% of kindreds with familial amyotrophic lateral sclerosis. Transgenic mice (line G1H) expressing a human SOD1 containing a mutation of Gly-93 --> Ala (G93A) develop a motor neuron disease similar to familial amyotrophic lateral sclerosis, but transgenic mice (line N1029) expressing a wild-type human SOD1 transgene do not. Because neurofilament (NF)-rich inclusions in spinal motor neurons are characteristic of amyotrophic lateral sclerosis, we asked whether mutant G1H and/or N1029 mice develop similar NF lesions. NF inclusions (i.e., spheroids, Lewy body-like inclusions) were first detected in spinal cord motor neurons of the G1H mice at 82 days of age about the time these mice first showed clinical evidence of disease. Other neuronal intermediate filament proteins (alpha-internexin, peripherin) also accumulated in these spheroids. The onset of accumulations of ubiquitin immunoreactivity in the G1H mice paralleled the emergence of vacuoles and NF-rich spheroids in neurons, but they did not colocalize exclusively with spheroids. In contrast, NF inclusions were not seen in the N1029 mice until they were 132 days old, and ubiquitin immunoreactivity was not increased in the N1029 mice even at 199 days of age. Astrocytosis in spinal cord was associated with a marked increase in glial fibrillary acidic protein immunoreactivity in the G1H mice, but not in the N1029 mice. Finally, comparative studies revealed a striking similarity between the cytoskeletal pathology in the G1H transgenic mice and in patients with amyotrophic lateral sclerosis. These findings link a specific SOD1 mutation with alterations in the neuronal cytoskeleton of patients with amyotrophic lateral sclerosis. Thus, neuronal cytoskeletal abnormalities may be implicated in the pathogenesis of human familial amyotrophic lateral sclerosis.
Herpes Simplex Virus 1 Infection Promotes the Growth of a Subpopulation of Tumor Cells in Three-Dimensional Uveal Melanoma Cultures (2018)

Herpes simplex virus 1 (HSV-1)-mediated oncolytic therapy is an emerging cancer treatment modality with potential effectiveness against a variety of malignancies. To better understand the interaction of HSV-1 with neoplastic cells, we inoculated three-dimensional (3D) cultures of human uveal melanoma cells with HSV-1. 3D melanoma cultures were established by placing tumor cells on the surface of a Matrigel matrix, which was followed by the growth of tumor cells on the matrix surface and invasion of the Matrigel matrix by some tumor cells to form multicellular tumor spheroids within the matrix. When established 3D melanoma cultures were inoculated with HSV-1 by placing virus on the surface of cultures, virus infection caused extensive death of melanoma cells growing on the surface of the 3D matrix and significantly decreased the number of tumor cell spheroids within the matrix. However, HSV-1 infection did not lead to a complete destruction of tumor cells in the 3D cultures during a 17-day observation period and, surprisingly, HSV-1 infection promoted the growth of some melanoma cells within the matrix as determined by the significantly increased size of residual viable multicellular tumor spheroids in virus-inoculated 3D cultures at 17 days after virus inoculation. Acyclovir treatment inhibited HSV-1-induced tumor cell killing but did not block the virus infection-induced increase in spheroid size. These findings suggest that although HSV-1 oncolytic virotherapy may cause extensive tumor cell killing, it may also be associated with the unintended promotion of the growth of some tumor cells.<b>IMPORTANCE</b> Cancer cells are exposed to HSV-1 during oncolytic virotherapy with the intention of killing tumor cells. Our observations reported here suggest that potential dangers of HSV-1 oncolytic therapy include promotion of growth of some tumor cells. Furthermore, our findings raise the possibility that HSV-1 infection of neoplastic cells during natural infections or vaccinations may promote the growth of tumors. Our study indicates that HSV-1 infection of 3D tumor cell cultures provides an experimental platform in which mechanisms of HSV-1-mediated promotion of tumor cell growth can be effectively studied.
Immune interferon activates multiple class II major histocompatibility complex genes and the associated invariant chain gene in human endothelial cells and dermal fibroblasts. (1984)

Immune interferon (IFN-gamma) increases the surface expression of HLA-A,B antigens and induces the surface expression of HLA-DR antigens on vascular endothelial cells and dermal fibroblasts. Here we report that IFN-gamma induces parallel expression of two other class II major histocompatibility complex (MHC) antigens, SB and DC. Maximal surface expression of all three antigens is reached in 4-6 days, and HLA-DR and -SB are induced to a higher level of expression than HLA-DC. For all three class II antigens, induction is marked by the de novo appearance of detectable transcripts of class II heavy and light chains and of the non-MHC-encoded invariant chain, suggestive of the transcription of multiple previously silent genes. Class I message levels and antigen expression are also increased by IFN-gamma at similar rates but from initial levels that are 50% of maximal. After removal of IFN-gamma, class II antigen expression persists for at least 4 days, while mRNA levels decrease rapidly. The parallel induction and persistence of the several class II MHC antigens may be important in conferring immune accessory function on vascular and stromal cells.
Enhanced coding of high-frequency tonal components in MPEG-D USAC through joint application of ESBR and sinusoidal modeling (2011)

The new eSBR tool of MPEG-D Universal Speech and Audio Coding offers a great advantage in compression of high frequency content, however it produces audible artifacts for sounds whose pitch frequencies are strongly variable or exceeding the split frequency of eSBR. We propose an extension of the forthcoming standard by adding a high frequency sinusoidal tool. This tool introduces additional parametric information to the data bitstream in order to encode the challenging tonal components which are excluded from eSBR processing. Listening tests demonstrate benefits of the proposed approach for test items of strongly tonal character.