gebhart/patrepeval huggingface dataset:
Homozygous WNT10b mutation and complex inheritance in Split-Hand/Foot Malformation (2008)

Split-Hand/Foot Malformation (SHFM) is a complex limb malformation affecting the central rays of the autopod. We studied a large consanguineous kindred afflicted with autosomal recessive SHFM. Twelve affected members had central feet reductions with or without hand involvement while the remaining one had the mildest phenotype and atypical SHFM. We identified by homozygosity mapping a novel SHFM locus at 12q13.11-q13 with a maximum multipoint lod score of 5.47 and by subsequent candidate gene approach a homozygous missense WNT10b mutation (p.R332W) in all affected individuals but the atypical case plus in an asymptomatic female. We propose that either a second locus contributes to the manifestation of SHFM phenotype or a suppressor locus prevented trait manifestation in the non-penetrant female. We also investigated linkage to the five known SHFM loci. Four of the loci were excluded, while in TP63 [tumor protein p63 (SHFM4)], the only known gene responsible for SHFM, we detected in most affected subjects a rare insertion variant (rs34201045) at the alternate promoter used for transcription of the N-terminal-truncated p63 isotype. This is the first reported WNT10b mutation on the pathogenesis of limb development and recessive mutation in SHFM.
Software persistent memory (2012)

Persistence of in-memory data is necessary for many classes of application and systems software. We pro-pose Software Persistent Memory (SoftPM), a new mem-ory abstraction which allows malloc style allocations to be selectively made persistent with relative ease. Particularly, SoftPM’s persistent containers implement automatic, orthogonal persistence for all in-memory data reachable from a developer-defined root structure. Writing new applications or adapting existing applica-tions to use SoftPM only requires identifying such root structures within the code. We evaluated the correct-ness, ease of use, and performance of SoftPM using a suite of microbenchmarks and real world applica-tions including a distributed MPI application, SQLite (an in-memory database), and memcachedb (a distributed memory cache). In all cases, SoftPM was incorporated with minimal developer effort, was able to store and re-cover data successfully, and provide significant perfor-mance speedup (e.g., up to 10X for memcachedb and 83 % for SQLite). 1
The Cost of Trading Transparency: What We Know, What We Don’t Know, and How We Will Know (2008)

Results from several major studies of index composition changes indicate that trading transparency accounts for more than half the market impact cost of composition changes in the two most popular U.S. indices. The growth of transparent custom index exchange-traded funds (ETFs) and the introduction of actively managed ETFs with relatively transparent trading will increase investor exposure to trading transparency costs. Fortunately, researchers can quantify the performance penalty that trading transparency imposes on investors. <b>TOPICS:</b>Exchange-traded funds and applications, exchanges/markets/clearinghouses, mutual fund performance
Course of Migraine During Pregnancy and Postpartum: A Prospective Study (2003)

The aim of this study was to investigate prospectively the course of migraine during pregnancy and postpartum. Of all the pregnant women consecutively attending an obstetrics and gynaecology department for a routine first-trimester antenatal check-up, 49 migraine sufferers--two were affected by migraine with aura (MA) and 47 by migraine without aura (MO)--who had experienced at least one attack during the 3 months preceding pregnancy were identified, enrolled in the study and given a headache diary. Subsequent examinations were performed at the end of the second and third trimesters and 1 month after delivery. Migraine was seen to improve in 46.8% of the 47 MO sufferers during the first trimester, in 83.0% during the second and in 87.2% during the third, while complete remission was attained by 10.6%, 53.2%, and 78.7% of the women, respectively. Migraine recurred during the first week after childbirth in 34.0% of the women and during the first month in 55.3%. Certain risk factors for lack of improvement of migraine during pregnancy were identified: the presence of menstrually related migraine before pregnancy was associated with a lack of headache improvement in the first and third trimesters, while second-trimester hyperemesis, and a pathological pregnancy course were associated with a lack of headache improvement in the second trimester. Breast feeding seemed to protect from migraine recurrence during postpartum.
Bifidobacterium infantis 35624: a novel probiotic for the treatment of irritable bowel syndrome. (2009)

Irritable bowel syndrome (IBS) is a common disorder with widespread prevalence. Due to its heterogeneous pathogenesis, efficacious treatments are lacking. The few medications that are effective for treating global IBS symptoms have either been withdrawn or restricted due to detrimental side effects; thus, safe and effective alternatives are urgently needed. Increasing data have revealed that inflammatory changes may play a role in the development of IBS, and probiotics, commensal organisms with inherent health benefits, may alter that milieu. Although their exact mechanisms of action remain elusive, it is clear that the beneficial properties inherent to each probiotic species are strain specific. Bifidobacterium infantis 35624 ( B infantis 35624; Bifantis, The Procter & Gamble Company, Cincinnati, OH), is a probiotic with unique abilities to reduce intestinal inflammation. Two randomized, controlled trials have validated its efficacy for treating both individual and global IBS symptoms without evidence to suggest an increase in adverse events. B. infantis 35624 appears safe and effective for the treatment of IBS.
Poly(N‐vinylcarbazole) chemically modified graphene oxide (2010)

Abstract A new soluble donor‐acceptor type poly( N ‐vinylcarbazole)‐covalently functionalized graphene oxide (GO‐PVK) has been synthesized by reaction of DDAT ( S ‐1‐dodecyl‐S′‐(α,α′‐dimethyl‐α″‐aceticacid)trithiocarbonate)‐PVK with GO‐toluene‐2,4‐diisocynate. The incorporation of sufficient amount of PVK chains makes the modified GO nanosheets readily dispersible in organic solvents. The resulting material exhibits an enhanced solubility of 10 mg/mL in organic solvents. Covalent grafting of PVK onto the edge and surface of GO nanosheets did not change the carbazole absorption in the ultraviolet region, but substantially reduced the absorption intensity of GO in the visible region. The intensity of the emission band of GO‐PVK at 437 nm was a little bit quenched when compared with that of DDAT‐PVK, suggesting intramolecular quenching from PVK to GO. Such intramolecular quenching process may involve energy or electron transfer between the excited singlet states of the PVK moiety and the GO moiety. The HOMO/LUMO values and the energy bandgap of GO‐PVK experimentally estimated by the onset of the redox potentials are −5.60, −3.58, and 2.02 eV, respectively. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2642–2649, 2010
The Elaboration Likelihood Model as a Theory of Attitude Formation: A Mathematical Analysis (1993)

The Elaboration Likelihood Model as a Theory of Attitude Formation: A Mathematical Analysis Mark A. Hamilton, Mark A. Hamilton 1Associate professor of communication sciences at the University of Connecticut. John E. Hunter is a professor of psychology at Michigan State University. Franklin J. Boster is an associate professor of communication at Michigan State University. Portions of this essay were presented at meetings of the lnternational Communication Association, Sun Francisco, CA, May, 1989, and the Speech Communication Association, Chicago, lL, November, 1 990. Address correspondence to: Mark Hamilton, Department of Communication Sciences, University of Connecticut, Storrs, CT 06269-1 085 Search for other works by this author on: Oxford Academic Google Scholar John E. Hunter, John E. Hunter 1Associate professor of communication sciences at the University of Connecticut. John E. Hunter is a professor of psychology at Michigan State University. Franklin J. Boster is an associate professor of communication at Michigan State University. Portions of this essay were presented at meetings of the lnternational Communication Association, Sun Francisco, CA, May, 1989, and the Speech Communication Association, Chicago, lL, November, 1 990. Address correspondence to: Mark Hamilton, Department of Communication Sciences, University of Connecticut, Storrs, CT 06269-1 085 Search for other works by this author on: Oxford Academic Google Scholar Franklin J. Boster Franklin J. Boster 1Associate professor of communication sciences at the University of Connecticut. John E. Hunter is a professor of psychology at Michigan State University. Franklin J. Boster is an associate professor of communication at Michigan State University. Portions of this essay were presented at meetings of the lnternational Communication Association, Sun Francisco, CA, May, 1989, and the Speech Communication Association, Chicago, lL, November, 1 990. Address correspondence to: Mark Hamilton, Department of Communication Sciences, University of Connecticut, Storrs, CT 06269-1 085 Search for other works by this author on: Oxford Academic Google Scholar Communication Theory, Volume 3, Issue 1, February 1993, Pages 50–65, https://doi.org/10.1111/j.1468-2885.1993.tb00056_3_1.x Published: 08 July 2009
Nicotine Inhibits Cytokine Production by Placenta Cells via NFκB: Potential Role in Pregnancy-Induced Hypertension (2007)

Pregnancy-induced hypertension (PIH), also known as preeclampsia, is one of the major causes of maternal and fetal death. While the precise cause of PIH is not known, aberrant cytokine production and placenta participation are considered to be important factors. Gestational cigarette smoking, which is widely accepted to be harmful to both the mother and fetus, is protective against PIH. Based on the antiinflammatory activity of nicotine, the major component of cigarettes, we examined the effect of nicotine and other cholinergic agonists on placental inflammatory responses ex vivo. We observed that nicotine and other cholinergic agonists significantly suppress placenta cytokine production following stimulation. Placenta cells express the alpha7 nicotinic acetylcholine receptor (alpha7nAChR), and using cholinergic antagonists, we demonstrated that the antiinflammatory effect of nicotine and other cholinergic agonists is, in part, mediated through the nAChR pathway. By contrast, cholinergic stimulation had no effect on the expression of soluble fms-like tyrosine kinase (sFlt), an antiangiogenic substance implicated in maternal vascular dysfunction during PIH. Mechanistic studies reveal that cholinergic agonists exert their antiinflammatory effects through the NFkappaB pathway. Taken together, our results suggest that cholinergic agonists, including nicotine, may reduce cytokine production by placenta cells via NFkappaB to protect against PIH.
Bringing bioelectricity to light: all-optical electrophysiology using microbial rhodopsins (2014)

My work has focused on the development and application of fluorescent voltage-sensitive proteins based on microbial rhodopsins. These probes led to the discovery of electrical activity in the bacterium Escherichia coli, the first robust optical recordings of action potentials (APs) in mammalian neurons using a genetically encoded voltage reporter, and the development of a genetically targetable all-optical electrophysiology system.\nI first introduce an engineered fluorescent voltage sensor based on green-absorbing proteorhodopsin. Expression of the proteorhodopsin optical proton sensor (PROPS) in E. coli revealed electrical spiking at up to 1 hertz. Spiking was sensitive to chemical and physical perturbations and coincided with rapid efflux of a small-molecule fluorophore, suggesting that bacterial efflux machinery may be electrically regulated.\nI then present another microbial rhodopsin, Archaerhodopsin 3 (Arch), whose endogenous fluorescence exhibited a twofold increase in brightness between -150 mV and +150 mV and a sub-millisecond response time. In rat hippocampal neurons, Arch detected single electrically triggered APs with an optical signal-to-noise ratio &gt; 10. A mutant, Arch(D95N), lacked endogenous proton pumping and had 50% greater sensitivity than the wild type but had a slower response (41 ms). Nonetheless, Arch(D95N) also resolved individual APs.\nFinally, I introduce evolved archaerhodopsin-based voltage indicators and a spectrally orthogonal channelrhodopsin actuator, which together enabled all-optical electrophysiology. A directed evolution screen yielded two mutants, QuasAr1 and QuasAr2, that showed improved brightness and voltage sensitivity relative to previous archaerhodopsin-based sensors, and microsecond response times. An engineered channelrhodopsin actuator, CheRiff, showed high light sensitivity and rapid kinetics. A coexpression vector, Optopatch, enabled cross-talk-free genetically targeted all-optical electrophysiology. In cultured neurons, the Optopatch system probed membrane voltage across temporal and spatial scales, from the sub-cellular and sub-millisecond dynamics of AP propagation, to the simultaneous measurement of firing patterns of many neurons in a circuit. In brain slices, Optopatch induced and reported APs and subthreshold events with high signal-to-noise ratios. In human stem cell-derived neurons, Optopatch measurements revealed homeostatic tuning of intrinsic excitability, a subtle form of plasticity that had yet to be observed in human neurons.\nThe suite of tools and techniques presented here enable high-throughput, genetically targeted, and spatially resolved electrophysiology without the use of conventional electrodes.
Brain metastases from non-central nervous system tumors: evaluation with PET. (1993)

Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) was performed in 19 patients with brain metastases from non-central nervous system (CNS) neoplasms and one patient with a primary CNS lymphoma. Various histopathologic types were represented by the primary neoplasms in the patients with metastases. Only 21 of the 31 lesions (68%) were detected with FDG PET as discrete, metabolically active foci (relative to surrounding structures). Six of the nondetected lesions may have been nondiscernible owing to their small size and/or isointensity relative to closely apposed normal gray matter. However, four lesions of at least 1.2 cm in diameter showed frankly decreased FDG accumulation relative to normal brain. These findings suggest that studies of FDG accumulation by a variety of non-CNS neoplasms and their CNS metastases are in order and that extrapolation of the successes of FDG PET in imaging of primary glial tumors to imaging of brain metastases should proceed with caution.
Why are there not more herbicide‐tolerant crops? (2005)

Herbicide-tolerant (HT) varieties of corn, soybean, canola (oilseed rape) and cotton have been grown since the mid-1990s, and have been widely adopted by farmers in several countries. HT genes have been inserted into or selected for in many other species, including almost all major crop species in the world and many minor crops and ornamental species. In some cases this has been done specifically to introduce the HT trait, whereas in others the HT gene has been used as a selectable marker (eg the bar gene, conferring glufosinate-ammonium tolerance). However, in very few cases have the HT crops generated been commercialized, despite the weed-control advantages that many such crops would offer. There are several reasons for this, including the high research and development costs associated with developing the new HT crop cultivars, the high cost of obtaining regulatory clearance for the HT crops or products derived from them, international trade issues relating to genetically modified crops, and issues surrounding the expanded herbicide registration for the new use and the potential impact of this on the existing registration status of the herbicide. New HT crops are unlikely to be developed unless they offer a sufficiently large advantage to farmers and a substantial assured market to justify the associated development and regulatory costs.
Freeze-drying and quality evaluation of protein drugs. (1992)

Gamma interferon from genetic recombination (IFN) has been found to have an optimal pH at about 7. An increase in IFN concentration may cause a decrease in solution clarity. A proper selection of isotonizing agent, as well as the addition of sugars, is effective in improving the clarity. The amount of IFN adsorbed on filter membranes varies with the membrane materials: cellulose acetate adsorbs much IFN, 2-fluorovinylidene is the next, followed by polysulfon, and polycarbonate adsorbs it least of all materials tested. Stainless steel adsorbs little IFN, and the level can be lowered even more by electropolishing. Silicone coating can decrease the amount adsorbed to about 1 microgram per vial of 10 ml. The effect of pressure given to the IFN solution during filtration is negligible. Transfer of IFN solution through pipings of conventional shape may result in partial deactivation by bubbling. At around pH 7, a lower pH of IFN solution causes a higher moisture level of the freeze-dried product. Moisture levels up to 3% have no effect on IFN stability. Upon reconstitution of freeze-dried IFN by vigorous shaking with distilled water, filtration of the solution may become difficult because polymers might have been formed during vigorous shaking. The addition of L-cysteine, maltose, and human serum albumin, has been found to be as effective in preventing such unfavorable reactions. Fatty acids in human serum albumin, which is effective in stabilizing IFN, has been found to participate in preventing denaturation of human serum albumin upon freezing and freeze-drying; however, the denaturation prevention mechanisms are not clear yet.
Mammalian gene targeting with designed zinc finger nucleases (2005)

Gene targeting by homologous recombination is a powerful method to manipulate the genome precisely and could be exploited to correct genetic defects. Zinc finger nucleases are designed proteins that fuse a zinc finger DNA binding domain to the nuclease domain from the FokI restriction endonuclease. Zinc finger nucleases were generated that stimulated gene targeting from half-site sequences from the human beta-globin gene and the human common gamma-chain gene. Zinc finger nucleases were also generated that stimulated gene targeting at full sites from the green fluorescent protein gene and the human CD8alpha gene. This work built on the prior zinc finger design work of others and in targeting these four genes had a 100% success rate at designing nucleases to the consensus half-site 5'-GNNGNNGNN-3' and the consensus full site 5'-NNCNNCNNCNNNNNNGNNGNNGNN-3', suggesting that zinc finger nucleases can be empirically designed to stimulate gene targeting in a large portion of the mammalian genome.
IL-12: monoclonal antibodies specific for the 40-kDa subunit block receptor binding and biologic activity on activated human lymphoblasts (1991)

IL-12, formerly known as cytotoxic lymphocyte maturation factor, is a cytokine that stimulates proliferation of PHA-activated human peripheral blood lymphoblasts and synergizes with low concentrations of IL-2 in the induction of lymphokine-activated killer cells. IL-12 is a 75-kDa heterodimer composed of disulfide-bonded 40-kDa and 35-kDa subunits. mAb prepared against a partially purified preparation of natural IL-12 have been characterized by 1) immunoprecipitation of 125I-labeled IL-12, 2) immunodepletion of IL-12 bioactivity, 3) Western blotting of IL-12, 4) inhibition of [125I]IL-12 binding to its cellular receptor, and 5) neutralization of IL-12 bioactivity. Twenty antibodies immunoprecipitate 125I-labeled IL-12 and immunodeplete IL-12 bioactivity as assessed in the T cell proliferation and lymphokine-activated killer cell induction assays. Western blot analysis demonstrated that each antibody binds to the 75-kDa heterodimer and to the 40-kDa subunit. An IL-12R-binding assay identified 12 individual antibodies that inhibited the binding of [125I]IL-12 to its cellular receptor. Two inhibitory antibodies, 4A1 and 7B2, were tested in the neutralization assay and found to block IL-12 bioactivity whereas one noninhibitory antibody, 8E3, was shown not to neutralize IL-12 bioactivity. Antibodies 4A1 and 8E3 can simultaneously bind to the 75-kDa heterodimer demonstrating that inhibitory and noninhibitory epitopes are spatially distinct on the 40-kDa protein. The ability of antibodies specific for the 40-kDa subunit of IL-12 to block receptor binding of [125I]IL-12 and to neutralize IL-12 bioactivity suggests that localized determinants on the 40-kDa subunit may be necessary for binding to the IL-12 cellular receptor.
Activity of a single-chain immunotoxin that selectively kills lymphoma and other B-lineage cells expressing the CD40 antigen. (1995)

We have constructed anti-CD40 immunotoxins consisting of the single chain Fv (sFv) region of the anti-human CD40 mAb G28-5 fused to a truncated form of Pseudomonas exotoxin, PE40. CD40 is an integral membrane glycoprotein found on the surface of B-lineage cells, including lymphomas and leukemias, as well as certain carcinomas. Two forms of the immunotoxin were constructed, one with the light chain variable (VL) region of the sFv preceding the heavy chain variable region (VH) [G28-5 sFv(VL-VH)-PE40] and the second with the sFv in the opposite orientation [G28-5 sFv(VH-VL)-PE40]. Although both forms of G28-5 sFv-PE40 specifically bound to CD40 in ELISAs, the binding of G28-5 sFv(VL-VH)-PE40 was > 10-fold higher. A number of malignant B- and T-cell lines were screened for CD40 expression and susceptibility to G28-5 sFv(VL-VH)-PE40. All of the B-lineage cells tested were CD40 positive and sensitive to the anti-CD40 immunotoxin, with EC50s ranging from 2.5-70 ng/ml, whereas none of the T cell leukemias or lymphomas were antigen positive or were affected by the immunotoxins. Consistent with the antigen-binding results, the VL-VH immunotoxin was > 10-fold more cytotoxic than the VH-VL immunotoxin. The anti-CD40 single-chain immunotoxin fusion protein G28-5 sFv(VL-VH)-PE40 represents a potent and specific cytotoxic agent for the elimination of normal and transformed B-lineage cells expressing CD40.
Recent Advances in Peptides for Enhancing Transdermal Macromolecular Drug Delivery (2016)

Transdermal delivery of drugs, a compelling route of systemic drug delivery, provides painless, reliable, targeted, efficient and cost effective therapeutic regimen for patients. However, its use is limited by skin barrier especially the stratum corneum barrier. Moreover, transdermal delivery of macromolecules remains a challenge. Naturally, varieties of physical methods, chemical enhancers and drug carriers have been used to counteract this limitation. Recently, transdermal peptides discovered as safer, more efficient and more specific enhancers could promote the delivery of macromolecules across the skin. Herein, the underlying transdermal peptides are included. Subsequently, we have discussed typical applications and the possible mechanism of two groups of biologically inspired transdermal peptide enhancers, namely cell penetration peptides and transdermal enhanced peptides.