gebhart/patrepeval huggingface dataset:
Mutations in the LMNA gene encoding lamin A/C (2000)

Very recently, mutations within the LMNA gene on chromosome 1q21.2 were shown to result in forms of muscular dystrophy, conduction-system disease, cardiomyopathy, and partial lipodystrophy. The LMNA gene encodes for the nucleophilic A-type lamins, lamin A and lamin C. These isoforms are generated by different splicing within exon 10 of LMNA. Thus lamin A/C is, besides emerin, the first known nucleophilic protein which plays a role in human disease. To date, 41 different mutations, predominantly missense, in the LMNA gene are known causing variable phenotypes. Twenty-three different mutations of LMNA have so far been shown to cause autosomal-dominant Emery-Dreifuss muscular dystrophy (EDMD2), three mutations were reported to cause limb-girdle muscular dystrophy (LGMD1B), eight mutations are known to result in dilated cardiomyopathy (CMD1A), and seven mutations were reported to cause familial partial lipodystrophy (FPL). The reports of lamin mutations including the corresponding phenotype are of great interest in order to gain insights into the function of lamin A/C. Here we summarize the mutations published to date in LMNA encoding lamin A/C.
Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway (2006)

Keap1-Nrf2-ARE signaling plays a significant role in protecting cells from endogenous and exogenous stresses. The development of Nrf2 knockout mice has provided key insights into the toxicological importance of this pathway. These mice are more sensitive to the hepatic, pulmonary, ovarian, and neurotoxic consequences of acute exposures to environmental agents and drugs, inflammatory stresses, as well as chronic exposures to cigarette smoke and other carcinogens. Under quiescent conditions, the transcription factor Nrf2 interacts with the actin-anchored protein Keap1, largely localized in the cytoplasm. This quenching interaction maintains low basal expression of Nrf2-regulated genes. However, upon recognition of chemical signals imparted by oxidative and electrophilic molecules, Nrf2 is released from Keap1, escapes proteasomal degradation, translocates to the nucleus, and transactivates the expression of several dozen cytoprotective genes that enhance cell survival. This review highlights the key elements in this adaptive response to protection against acute and chronic cell injury provoked by environmental stresses.
The 3'-flanking sequence of the bovine growth hormone gene contains novel elements required for efficient and accurate polyadenylation. (1992)

In addition to the conserved AAUAAA hexanucleotide, GU- and U-rich sequences in the 3'-flanking region are thought to be critical for efficient polyadenylation. The 3'-flanking sequence requirements for efficient and accurate polyadenylation of the bovine growth hormone (bGH) gene were determined by quantitative S1 nuclease analysis of transcripts derived from various bGH 3' deletions and block mutations transiently transfected into COS-1 cells. Though the bGH 3'-flanking sequence contains a portion of the putative GU efficiency element, we find that mutation of this element leads to a marginal decrease in efficiency similar to that from mutation of other sequences that do not contain recognizable GU- or U-rich motifs. The data are consistent with a diffuse efficiency element in the bGH polyadenylation signal rather than a discrete element as is thought to exist in other mammalian signals. We have also determined that a region from 18 to 27 nucleotides downstream of the cleavage site contains sequences required for correctly positioning the cleavage site.
Register connection (1993)

Code optimization and scheduling for superscalar and superpipelined processors often increase the register requirement of programs. For existing instruction sets with a small to moderate number of registers, this increased register requirement can be a factor that limits the effectivess of the compiler. In this paper, we introduce a new architectural method for adding a set of extended registers into an architecture. Using a novel concept of connection, this method allows the data stored in the extended registers to be accessed by instructions that apparently reference core registers. Furthermore, we address the technical issues involved in applying the new method to an architecture: instruction set extension, procedure call convention, context switching considerations, upward compatibility, efficient implementation, compiler support, and performance. Experimental results based on a prototype compiler and execution driven simulation show that the proposed method can significantly improve the performance of superscalar processors with a small or moderate number of registers.
Nonreciprocal exchanges of information between DNA duplexes coinjected into mammalian cell nuclei. (1985)

We have examined the mechanism of homologous recombination between plasmid molecules coinjected into cultured mammalian cells. Cell lines containing recombinant DNA molecules were obtained by selecting for the reconstruction of a functional Neor gene from two plasmids that bear different amber mutations in the Neor gene. In addition, these plasmids contain restriction-length polymorphisms within and near the Neor gene. These polymorphisms did not confer a selectable phenotype but were used to identify and categorize selected and nonselected recombinant DNA molecules. The striking conclusion from this analysis is that the predominant mechanism for the exchange of information between coinjected plasmid molecules over short distances (i.e., less than 1 kilobase) proceeds via nonreciprocal homologous recombination. The frequency of homologous recombination between coinjected plasmid molecules in cultured mammalian cells is extremely high, approaching unity. We demonstrate that this high frequency requires neither a high input of plasmid molecules per cell nor a localized high concentration of plasmid DNA within the nucleus. Thus, it appears that plasmid molecules, once introduced into the nucleus, have no difficulty seeking each other out and participating in homologous recombination even in the presence of a vast excess of host DNA sequences. Finally, we show that most of the homologous recombination events occur within a 1-h interval after the introduction of plasmid DNA into the cell nucleus.
CENP-E is an essential kinetochore motor in maturing oocytes and is masked during Mos-dependent, cell cycle arrest at metaphase II (1997)

CENP-E, a kinesin-like protein that is known to associate with kinetochores during all phases of mitotic chromosome movement, is shown here to be a component of meiotic kinetochores as well. CENP-E is detected at kinetochores during metaphase I in both mice and frogs, and, as in mitosis, is relocalized to the midbody during telophase. CENP-E function is essential for meiosis I because injection of an antibody to CENP-E into mouse oocytes in prophase completely prevented progression of those oocytes past metaphase I. Beyond this, CENP-E is modified or masked during the natural, Mos-dependent, cell cycle arrest that occurs at metaphase II, although it is readily detectable at the kinetochores in metaphase II oocytes derived from mos-deficient (MOS-/-) mice that fail to arrest at metaphase II. This must reflect a masking of some CENP-E epitopes, not the absence of CENP-E, in meiosis II because a different polyclonal antibody raised to the tail of CENP-E detects CENP-E at kinetochores of metaphase II-arrested eggs and because CENP-E reappears in telophase of mouse oocytes activated in the absence of protein synthesis.
OaSiS: integrating safety reasoning for decision support in oncology (2002)

Oncologists manage the treatment of cancer patients under a variety of protocol-based clinical trials. Each trial requires data to be collected for monitoring efficacy and toxicity. The life-threatening nature of cancer and the toxicity of therapy emphasise the safety-critical nature of oncology. OaSiS provides decision support for protocol-based treatment of cancer and contributes to better data management and safer, more consistent application of protocols. It offers a highly graphical interface, employs logic-based problem-solving and is implemented in PROLOG.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer (2012)

This work strongly suggests that genes associated with EMT may play a significant role in cisplatin resistance in ovarian cancer, therefore potentially leading to the development of predictive biomarkers of drug response or novel therapeutic strategies for overcoming drug resistance.
Proteolytic processing of foot-and-mouth disease virus polyproteins expressed in a cell-free system from clone-derived transcripts (1987)

All picornaviral genes are expressed as a single, large polyprotein, which is proteolytically processed into the system produces functional proteins, including viral protease 3C, which plays a major role in processing the precursor proteins. To study the function of the two putative proteases 3C and leader (L) in processing, we constructed several cDNA plasmids encoding various regions of the FMDV type A12 genome. These plasmids, containing FMDV cDNA segments under the control of the T7 promoter, were transcribed in vitro by using T7 RNA polymerase and then translated in rabbit reticulocyte lysates. The expressed FMDV gene products were identified by immunoprecipitation with specific antisera and analyzed by gel electrophoresis. The results demonstrate the following: (i) the leader protein, L, is processed from the structural protein precursor, P1, in the absence of any P2 or P3 region proteins; (ii) protein 2A remains associated with the structural protein precursor, P1, rather than the precursor, P2; (iii) the processing of the P1-2A/P2 junction is not catalyzed by 3C or L; (iv) the proteolytic processing of polyproteins from the structural P1 region (except VP4/VP2) and the nonstructural P2 and P3 region is catalyzed by 3C.
Nonlinear magneto-optical rotation with frequency-modulated light in the geophysical field range (2006)

Recent work investigating resonant nonlinear magneto-optical rotation (NMOR) related to long-lived $({\ensuremath{\tau}}_{\mathrm{rel}}\ensuremath{\sim}1\mathrm{s})$ ground-state atomic coherences has demonstrated potential magnetometric sensitivities exceeding ${10}^{\ensuremath{-}11}\phantom{\rule{0.3em}{0ex}}\mathrm{G}∕\sqrt{\mathrm{Hz}}$ for small $(\ensuremath{\lesssim}1\phantom{\rule{0.3em}{0ex}}\mathrm{\ensuremath{\mu}}\mathrm{G}$) magnetic fields. In the present work, NMOR using frequency-modulated light (FM NMOR) is studied in the regime where the longitudinal magnetic field is in the geophysical range$(\ensuremath{\sim}500\mathrm{mG})$, of particular interest for many applications. In this regime a splitting of the FM NMOR resonance due to the nonlinear Zeeman effect is observed. At sufficiently high light intensities, there is also a splitting of the FM NMOR resonances due to ac Stark shifts induced by the optical field, as well as evidence of alignment-to-orientation conversion type processes. The consequences of these effects for FM-NMOR-based atomic magnetometry in the geophysical field range are considered.
Targeting of Tumor-Associated Macrophages Made Possible by PEG-Sheddable, Mannose-Modified Nanoparticles (2013)

It is increasingly evident that tumor-associated macrophages (TAMs) play an important role in tumor invasion, proliferation, and metastasis. While delivery of drugs, imaging agents, and vaccines to TAMs was achieved by exploiting membrane receptors on TAMs, the uptake by normal macrophages remains an issue. In this communication, we report a PEG-sheddable, mannose-modified nanoparticle platform that can efficiently target TAMs via mannose-mannose receptor recognition after acid-sensitive PEG shedding in the acidic tumor microenvironment, while their uptake by normal macrophages in the mononuclear phagocyte system (MPS) organs was significantly reduced due to effective PEG shielding at neutral pH. These nanoparticles have the potential to target drugs of interest to TAMs, with decreased uptake by normal macrophages.
Diagnostic Impact and Cost-effectiveness of Whole-Exome Sequencing for Ambulant Children With Suspected Monogenic Conditions (2017)

Singleton WES in children with suspected monogenic conditions has high diagnostic yield, and cost-effectiveness is maximized by early application in the diagnostic pathway. Pediatricians should consider early referral of children with undiagnosed syndromes to clinical geneticists.
Improved Theoretical Ground-State Energy of the Hydrogen Molecule (1968)

The potential-energy curve for the electronic ground state of the hydrogen molecule has been calculated for 1 ≤ R ≤ 3.2 a.u. in double precision and using a 100-term expansion for the electronic wavefunction. Accuracy of the previously computed diagonal corrections for nuclear motion has been tested. The vibrational equation has been solved for all isotopes of the hydrogen molecule and for the rotational quantum number J ≤ 10. The calculated adiabatic dissociation energy of H2, corrected for relativistic and radiative effects, is by 3.8 cm−1 larger than the experimental value, hence the theoretical total energy is by the same amount lower than the experimental value. The calculated vibrational quanta for H2 are by 0.5–0.9 cm−1 larger than the experimental ones.
[A high aged case of herpes simplex viral encephalitis associated with progressive cerebral white matter lesion]. (2001)

An 80-year-old male without abnormal past medical history presented with coma, general seizures, and fever subsequent to abnormal behavior. The pressure of the cerebrospinal fluid(CSF) elevated(13.5-20.5 cm H2O), and CSF examination revealed pleocytosis with predominant mononuclear cells(80-879/mm3) and elevated protein level(32-130 mg/dl). DNAs of herpes simplex virus(HSV) type 1 and 2 in CSF were not confirmed by polymerase chain reaction method in the acute phase. The HSV(type 1) antibody(HSV-1 Ab) ratio of serum to CSF(= [serum HSV-1 Ab]/[CSF HSV-1 Ab]) was 0.98 and HSV-1 Ab index(= [CSF HSV-1 Ab]/[serum HSV-1 Ab] divided by [CSF albumin]/[serum albumin]) was 62.4. Initial fluid attenuated inversion recovery(FLAIR) (TR/TE/TI = 6,882/110/1,700 msec) axial magnetic resonance(MR) imaging showed hyperintensity in the subfrontal area, inferomedial portions of the temporal lobes, cingulate gyri, and insular cortices bilaterally. Meningoencephalitis caused by HSV-1 was diagnosed based on the values of HSV-1 Ab ratio of serum to CSF(less than 20), of HSV-1 Ab index(larger than 1.91), and the findings of MR imaging. Diffuse white matter lesions manifesting hyperintensity on FLAIR imaging in the bilateral frontal and temporal lobes close to the affected cortices developed approximately six weeks after the onset despite administration of antiviral agent and steroid. The lesion extensively involved the white matter of the bilateral frontal and temporal lobes finally. The initial value of myelin basic protein(MBP) in CSF was 0.9 ng/ml (normal value: less than 4 ng/ml). Subsequent measurement of MBP in CSF about two, six weeks, two, three, and six months after the onset showed a marked increase of 233.9 ng/ml followed by a gradual decrease of 25.4 ng/ml, 18.4 ng/ml, 7.4 ng/ml and 4.3 ng/ml, respectively. Therefore, demyelination of the lesion in the cerebral white matter was suggested by the chronological change in FLAIR imaging and MBP in CSF.
A Location-Based Vertical Handover Algorithm for Limitation of the Ping-Pong Effect (2008)

In this paper a location-based algorithm is proposed for managing soft mobile-controlled vertical handover between wireless systems. The case of a dual-mode terminal equipped with UMTS and IEEE 802.11 network interface cards is analysed in detail, and an novel approach for optimizing goodput and limit the so-called ping-pong effect is defined. The novel algorithm is based on a preliminary handover initiation phase triggered on the basis of mobile node location. Handover is then carried out by following a goodput estimation phase allowed by a transient of by casting during soft handovers. Experimental results provide an assessment on the use of location information to drive handover decisions.
Kinetic characterization of intramolecular and intermolecular hammerhead RNAs with stem II deletions. (1994)

A method is described to obtain intramolecular cleavage rates for the hammerhead ribozyme during in vitro transcription. By avoiding RNA purification and renaturation, the potential for formation of inactive conformations of the RNA is minimized. By showing that an intramolecular hammerhead and a closely related intermolecular hammerhead cleave at the same rate under a given set of conditions, we confirm that both reactions probably have the same rate-limiting step. An in vitro selection strategy was used to isolate active hammerheads from a library of molecules where six randomized nucleotides replaced stem-loop II. The sequence and number of nucleotides which replace stem-loop II have large effects on hammerhead cleavage activity. The relative activities of three sequences selected from the intramolecular library are the same when the sequences are transferred into an intermolecular hammerhead background.
Effects of maternal antenatal glucocorticoid treatment on apoptosis in the ovine fetal cerebral cortex (2008)

We examined the effects of single and multiple maternal glucocorticoid courses on apoptosis in the cerebral cortices of ovine fetuses (CC). Ewes received single dexamethasone or placebo courses at 104-106 or 133-135 days or multiple courses between 76-78 and 104-106 days gestation. In the single-course groups, ewes received four 6 mg dexamethasone or placebo injections every 12 hr for 48 hr. Multiple-course groups received the same treatment once per week for 5 weeks. Neuronal and nonneuronal apoptotic cell numbers per square millimeter were determined with TUNEL and NeuN staining and with caspase-3 enzyme activity on CC tissues harvested at 106-108 (70%) or 135-137 (90%) days of gestation. Apoptotic cell numbers and caspase-3 activity were 50% lower (P < 0.02) after single placebo courses at 90% than 70% gestation; 90% of apoptotic cells were (P < 0.01) nonneuronal at both ages. Nonneuronal apoptotic cells and caspase-3 activity were 40% and 20% lower (P < 0.02) after single dexamethasone than placebo courses at 70%, but not 90%, gestation. Caspase-3 activity was 20% lower (P < 0.01) after multiple dexamethasone than placebo courses, but apoptotic cell number did not differ. We conclude that nonneuronal apoptosis represents the major form of apoptosis in the CC at both 70% and 90% of gestation. Apoptosis in nonneuronal cells decreases with maturity and after a single course of dexamethasone at 70%, but not at 90%, gestation and not after multiple courses at 70% gestation. We speculate that a single course of glucocorticoids exerts maturational changes on the rate of apoptosis in the cerebral cortex of preterm ovine fetuses.
Field Experiments in Lincolnshire on the Chemical Treatment of Soil infected with Heterodera schachtii (1937)

This communication is concerned with the field trials of substances which in previous small-scale experiments had shown promise of controlling “potatò-sickness” when they were mixed with infected soil.
Involvement of Cyclic GMP and Protein Kinase G in the Regulation of Apoptosis and Survival in Neural Cells (2002)

Our current understanding of nitric oxide (NO), cyclic GMP (cGMP) and protein kinase G (PKG) signaling pathways in the nervous systems has its origins in the early studies conducted on vascular tissues during the late 1970s and early to mid-1980s. The pioneering research into the NO/cGMP/PKG pathway in blood vessels conducted by the laboratories of Drs. Ferid Murad, Louis Ignarro and Robert Furchgott ultimately led to the awarding of the 1998 Nobel Prize in Physiology or Medicine to these three scientists. On the basis of further pioneering studies by Drs. John Garthwaite, Solomon Snyder, Steven Vincent and many other neuroscientists during the late 1980s and throughout the 1990s, it became recognized that NO serves as a neurotransmitter/neuromodulator in the central and peripheral nervous systems and that certain neural cells possess a cGMP signaling pathway similar to that in vascular smooth muscle cells. Although NO (at high concentrations) is toxic and thought to participate in neuronal cell death during stroke and neurodegenerative diseases (e.g. amyotrophic lateral sclerosis, Alzheimer's disease, HIV dementia and Parkinson's disease), recent evidence suggests that NO at low physiological concentrations can act as an antiapoptotic/prosurvival factor in certain neural cells (e.g. PC12 cells, motor neurons and neurons of dorsal root ganglia, hippocampus and sympathetic nerves). The antiapoptotic effects of NO are mediated, in part, by cGMP and a downstream target protein, PKG. Other cGMP-elevating factors (e.g. atrial and brain natriuretic peptides) and direct PKG activator (e.g. 8-bromo-cGMP) also have antiapoptotic effects which have been quantified by the new capillary electrophoresis with laser-induced fluorescence detector technology. Inhibition of soluble guanylyl cyclase and lowering of basal cGMP levels cause apoptosis in unstressed neural cells (NG108-15 and N1E-115 cells). The cGMP/PKG pathway appears to play an essential role in preventing activation of a proapoptotic pathway, thus promoting neural cell survival.
Ligand-induced conformational changes observed in single RNA molecules (1999)

We present the first demonstration that fluorescence resonance energy transfer can be used to track the motion of a single molecule undergoing conformational changes. As a model system, the conformational changes of individual three-helix junction RNA molecules induced by the binding of ribosomal protein S15 or Mg(2+) ions were studied by changes in single-molecule fluorescence. The transition from an open to a folded configuration was monitored by the change of fluorescence resonance energy transfer between two different dye molecules attached to the ends of two helices in the RNA junction. Averaged behavior of RNA molecules closely resembles that of unlabeled molecules in solution determined by other bulk assays, proving that this approach is viable and suggesting new opportunities for studying protein-nucleic acids interactions. Surprisingly, we observed an anomalously broad distribution of RNA conformations at intermediate ion concentrations that may be attributed to foldability differences among RNA molecules. In addition, an experimental scheme was developed where the real-time response of single molecules can be followed under changing environments. As a demonstration, we repeatedly changed Mg(2+) concentration in the buffer while monitoring single RNA molecules and showed that individual RNA molecules can measure the instantaneous Mg(2+) concentration with 20-ms time resolution, making it the world's smallest Mg(2+) meter.
Regression of non-irradiated metastases after extracranial stereotactic radiotherapy in metastatic renal cell carcinoma (2006)

To the EditorThe treatment options in renal cancer are few and the response rates are low. It is also a cancer form that has a diverse biology-the vast majority of cases progress rapidly but in a s...