gebhart/patrepeval huggingface dataset:
The effect of α2‐δ and other accessory subunits on expression and properties of the calcium channel α1G (1999)

1. The effect has been examined of the accessory alpha2-delta and beta subunits on the properties of alpha1G currents expressed in monkey COS-7 cells and Xenopus oocytes. 2. In immunocytochemical experiments, the co-expression of alpha2-delta increased plasma membrane localization of expressed alpha1G and conversely, the heterologous expression of alpha1G increased immunostaining for endogenous alpha2-delta, suggesting an interaction between the two subunits. 3. Heterologous expression of alpha2-delta together with alpha1G in COS-7 cells increased the amplitude of expressed alpha1G currents by about 2-fold. This finding was confirmed in the Xenopus oocyte expression system. The truncated delta construct did not increase alpha1G current amplitude, or increase its plasma membrane expression. This indicates that it is the exofacial alpha2 domain that is involved in the enhancement by alpha2-delta. 4. Beta1b also produced an increase of functional expression of alpha1G, either in the absence or the presence of heterologously expressed alpha2-delta, whereas the other beta subunits had much smaller effects. 5. None of the accessory subunits had any marked influence on the voltage dependence or kinetics of the expressed alpha1G currents. These results therefore suggest that alpha2-delta and beta1b interact with alpha1G to increase trafficking of, or stabilize, functional alpha1G channels expressed at the plasma membrane.
Dynamical regimes and hydrodynamic lift of viscous vesicles under shear (2009)

The dynamics of two-dimensional viscous vesicles in shear flow, with different fluid viscosities etain and etaout inside and outside, respectively, is studied using mesoscale simulation techniques. Besides the well-known tank-treading and tumbling motions, an oscillatory swinging motion is observed in the simulations for large shear rate. The existence of this swinging motion requires the excitation of higher-order undulation modes (beyond elliptical deformations) in two dimensions. Keller-Skalak theory is extended to deformable two-dimensional vesicles, such that a dynamical phase diagram can be predicted for the reduced shear rate and the viscosity contrast etain/etaout. The simulation results are found to be in good agreement with the theoretical predictions, when thermal fluctuations are incorporated in the theory. Moreover, the hydrodynamic lift force, acting on vesicles under shear close to a wall, is determined from simulations for various viscosity contrasts. For comparison, the lift force is calculated numerically in the absence of thermal fluctuations using the boundary-integral method for equal inside and outside viscosities. Both methods show that the dependence of the lift force on the distance ycm of the vesicle center of mass from the wall is well described by an effective power law ycm(-2) for intermediate distances 0.8Rp< approximately ycm< approximately 3Rp with vesicle radius Rp. The boundary-integral calculation indicates that the lift force decays asymptotically as 1/[ycm ln(ycm)] far from the wall.
The dental hygienist in research: progress over 100 years. (2013)

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In 1966, an article was published in the Journal of the American Dental Hygienists' Association titled, “The Role of the Dental Hygienist in Dental Research.”[1][2] The paper was authored by two dental hygienists with master's degrees and a dentist, all from the School of
Enzymatic Kinetic Resolution of [4](1,2)Ferrocenophane Derivatives (1992)

Abstract The enol acetate of (±)-[4](1,2)ferrocenophan-1-one was enantioselectively hydrolyzed by using lipase PS to afford (+)-(R)-[4](1,2)ferrocenophan-1-one and (+)-(S)-1-acetoxy[4](1,2)ferrocenophan-1-ene. By using lipase PS or lipozyme, (±)-1-acetoxy[4](1,2)ferrocenophane was resolved into the (+)-(1R)-alcohol and the (−)-(1S)-acetate. The lipase-mediated transesterification and esterification of (±)-1-hydroxy[4](1,2)ferrocenophane led to the formation of the (+)-(1R)-ester and the (−)-(1S)-alcohol.
FGF2 regulates proliferation of neural crest cells, with subsequent neuronal differentiation regulated by LIF or related factors (1994)

Two of the key early events in the development of the peripheral nervous system are the proliferation of neural crest precursor cells and their subsequent differentiation into different neural cell types. We present evidence that members of the fibroblast growth factor family, (FGF1 or FGF2) act directly on the neural crest cells in vitro to stimulate proliferation in the presence of serum. These findings correlate with in situ hybridisation analysis, which shows FGF2 mRNA is expressed in cells both in the neural tube and within newly formed sensory ganglia (dorsal root ganglia, DRG) at embryonic day 10 in the mouse, when neural crest precursors are proliferating within the DRG. This data infers an autocrine/paracrine loop for FGF regulation of proliferation. Evidence supporting this notion is provided by the finding that part of the endogenous proliferative activity in the NC cultures is related to FGF. It was also found, in early neural crest cultures, that exogenous FGF completely inhibited neuronal differentiation, probably as a direct consequence of its mitogenic activity. In order to stimulate neuronal differentiation significantly, it was necessary to remove the FGF and replace it with leukemia inhibitory factor (LIF) or related factors. Under these conditions, 50% of the cells differentiated into neurons, which developed a sensory neuron morphology and were immunoreactive for the sensory markers CGRP and substance P. These data support a model of neural crest development, whereby multipotential neural crest precursor cells are stimulated to divide by FGF and subsequent development into sensory neurons is regulated by LIF or other cytokines with a similar signalling mechanism.
Overexpression of thermoalkalophilic lipase from Bacillus stearothermophilus L1 in Saccharomyces cerevisiae (2003)

An expression vector system was developed for the secretory production of recombinant Bacillus stearothermophilus L1 lipase in Saccharomyces cerevisiae. The mature L1 lipase gene was fused to α-amylase signal sequence from Aspergillus oryzae for the effective secretion into the culture broth and the expression was controlled under GAL10 (the gene coding UDP-galactose epimerase of S. cerevisiae) promoter. S. cerevisiae harboring the resulting plasmid successfully secreted L1 lipase into the culture broth. To examine an optimum condition for L1 lipase expression in the fed-batch culture, L1 lipase expression was induced at three different growth phases (early, mid, and late-exponential growth phases). Maximum production of L1 lipase (1,254,000 U/l, corresponding to 0.65/l) was found when the culture was induced at an early growth phase. Secreted recombinant L1 lipase was purified only through CM-Sepharose chromatography, and the purified enzyme showed 1,963 U/mg of specific activity and thermoalkalophilic properties similar to those reported for the enzyme expressed in Escherichia coli.
A human ubiquitin-conjugating enzyme homologous to yeast UBC8. (1994)

Ubiquitin-conjugating enzymes catalyze the covalent attachment of ubiquitin to cellular substrates. Here we describe the isolation of a novel ubiquitin-conjugating enzyme from human placenta and the cloning of the corresponding cDNA. DNA sequencing revealed that this gene, UbcH2, encodes a protein with significant sequence similarity to yeast UBC8. In contrast to a previous report (Qin, S., Nakajima, B., Nomura, M., and Arfin, S. M. (1991) J. Biol. Chem. 266, 15549-15554), we discovered that UBC8 is interrupted by a single intron bearing an unusual branch point sequence. The revised amino acid sequence of yeast UBC8 exhibits 54% amino acid sequence identity to human UbcH2. Moreover, full-length UbcH2 and UBC8 enzymes expressed from their cDNAs show similar enzymatic activities in vitro by catalyzing the ubiquitination of histones, suggesting that the two enzymes may fulfill similar functions in vivo. Interestingly, comparison of the enzymatic activities of a truncated UBC8 (Qin, S., Nakajima, B., Nomura, M. and Arfin, S. M. (1991) J. Biol. Chem. 266, 15549-15554) and of the full-length enzyme (this report) suggests, that the first 12 amino-terminal residues of UBC8 are required for ubiquitination of histones in vitro but not for thiolester formation with ubiquitin. This suggests that the NH2 terminus of UBC8 may be necessary either for substrate recognition or for the transfer of ubiquitin onto substrates. The UbcH2 gene is located on chromosome 7 and shows a complex expression pattern with at least five different mRNAs.
Long-term efficacy, safety and durability of Juv&eacute;derm&reg; XC (2013)

Abstract: Over the last decade, there has been increasing interest in minimally invasive cosmetic treatments, especially for facial rejuvenation. Next to botulinum toxin injection, the injection of soft tissue fillers is the second most frequent minimally invasive procedure performed in the USA. Hyaluronic acid (HA) is the most commonly used dermal filler. One of patients’ main concerns about filler injections pertains to pain and discomfort. Topical anesthetics, nerve blocks, and/or the incorporation of lidocaine to the filler have been applied in order to reduce distress and pain. Despite nerve blocks being an effective form of anesthesia, they may distort the area to be treated, as well as lengthen and complicate the procedure. Studies have shown that the incorporation of lidocaine to HA fillers significantly reduces pain and discomfort. Yet, one of the dilemmas about the addition of lidocaine solution to HA fillers is the possible alteration of the physical characteristics of the product by negatively impacting the efficacy and/or duration of the filler. The concern is that the addition of lidocaine could dilute the product, creating less correction per mL, changing the product's viscosity and consequently the “lifting” ability. Also, this dilution could reduce the product's duration. There may be a difference between a physician adding an aqueous solution into a lidocaine-free version of HA and the pre-incorporated lidocaine version of HA. An aqueous solution might dilute the product, while the pre-incorporated powder lidocaine appears to avoid this problem. Juvéderm ® XC is manufactured with powder lidocaine 0.3%; it is associated with significantly less injection pain than Juvéderm ® and other lidocaine-free versions of HA. Studies have shown that lidocaine enhances treatment comfort and optimizes the injection experience while maintaining a similar safety and effectiveness profile. Regarding the longevity, further study is necessary to determine if there is any difference in durability. Keywords: dermal filler, hyaluronic acid, Juvéderm XC, lidocaine, Juvéderm, dermatologic procedures
The SSRI discontinuation syndrome (1998)

A characteristic selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome appears to exist. It is usually mild, commences within 1 week of stopping treatment, resolves spontaneously within 3 weeks, and consists of diverse physical and psychological symptoms, the commonest being dizziness, nausea, lethargy and headache. SSRI reinstatement leads to resolution within 48 h. A transient stage of serotonin dysregulation appears central to causation with pharmacokinetic and pharmacodynamic differences accounting for the variation in incidence between the SSRIs. Discontinuation reactions are clinically relevant due to the associated morbidity, the potential for misdiagnosis and inappropriate treatment and because they may impair future antidepressant compliance. To minimize incidence, SSRIs, like other antidepressants, should be withdrawn gradually. Provisional diagnostic criteria for the SSRI discontinuation syndrome are proposed. Prospective studies are required to investigate the syndrome, particularly its effects on patient care.
Retargeting of Human T Cells to Tumor-Associated MUC1: The Evolution of a Chimeric Antigen Receptor (2008)

MUC1 is a highly attractive immunotherapeutic target owing to increased expression, altered glycosylation, and loss of polarity in >80% of human cancers. To exploit this, we have constructed a panel of chimeric Ag receptors (CAR) that bind selectively to tumor-associated MUC1. Two parameters proved crucial in optimizing the CAR ectodomain. First, we observed that the binding of CAR-grafted T cells to anchored MUC1 is subject to steric hindrance, independent of glycosylation status. This was overcome by insertion of the flexible and elongated hinge found in immunoglobulins of the IgD isotype. Second, CAR function was highly dependent upon strong binding capacity across a broad range of tumor-associated MUC1 glycoforms. This was realized by using an Ab-derived single-chain variable fragment (scFv) cloned from the HMFG2 hybridoma. To optimize CAR signaling, tripartite endodomains were constructed. Ultimately, this iterative design process yielded a potent receptor termed HOX that contains a fused CD28/OX40/CD3zeta endodomain. HOX-expressing T cells proliferate vigorously upon repeated encounter with soluble or membrane-associated MUC1, mediate production of proinflammatory cytokines (IFN-gamma and IL-17), and elicit brisk killing of MUC1(+) tumor cells. To test function in vivo, a tumor xenograft model was derived using MDA-MB-435 cells engineered to coexpress MUC1 and luciferase. Mice bearing an established tumor were treated i.p. with a single dose of engineered T cells. Compared with control mice, this treatment resulted in a significant delay in tumor growth as measured by serial bioluminescence imaging. Together, these data demonstrate for the first time that the near-ubiquitous MUC1 tumor Ag can be targeted using CAR-grafted T cells.
Induction of Multiple Follicular Development by a Single Dose of Long-Acting Recombinant Follicle-Stimulating Hormone (FSH-CTP, Corifollitropin Alfa) for Controlled Ovarian Stimulation beforein VitroFertilization (2004)

In a first feasibility study, the efficacy and safety of a single dose of recombinant long-acting FSH (FSH-CTP) were investigated in in vitro fertilization (IVF) patients undergoing controlled ovarian stimulation with a flexible GnRH antagonist protocol. Eligible subjects were randomized to receive a single dose of 120 micro g (n = 25), 180 microg (n = 24), or 240 microg (n = 25) corifollitropin alfa (FSH-CTP) or to start daily fixed doses of 150 IU recombinant FSH (rFSH) (n = 24, reference). Subjects who received a single dose of FSH-CTP continued 1 wk after injection (treatment d 8) with fixed daily doses of 150 IU rFSH (Puregon/Follistim) until the day of triggering final oocyte maturation. The terminal half-life of FSH-CTP was, on average, 65 h and dose independent. Cycle cancellation before human chorionic gonadotropin (hCG) administration occurred in only three subjects treated with FSH-CTP. The median duration of stimulation was 10.0 d in each FSH-CTP group and 9.0 d in the daily rFSH group. The total number of follicles at least 11 mm at stimulation d 8 and at the day of hCG administration tended to increase with dose of FSH-CTP, although a significant dose-response relationship was revealed only for the number of follicles at least 15 mm on the day of hCG (P = 0.03). Serum estradiol levels and inhibin-B levels were not significantly different between the four groups on d 8 and on the day of hCG. In total, 12 subjects (17.6%) in the FSH-CTP groups and two subjects (8.3%) in the rFSH group experienced a premature LH rise (defined as LH >or= 10 IU/liter) before the start of the GnRH antagonist (P value not significant between groups). This relatively high incidence of women demonstrating an early LH rise in the FSH-CTP groups may be related to the higher initial rises of serum estradiol and the use of a flexible GnRH antagonist protocol. The mean number of oocytes recovered per started cycle was higher in FSH-CTP-treated subjects compared with rFSH-treated subjects (significant at P = 0.03 for the 240- microg FSH-CTP group), but no difference could be noted between the number of good quality embryos (range of means, 3.8-4.8 per attempt), and equal numbers of embryos were available for embryo transfer. In summary, FSH-CTP appeared to be a potent inducer of multiple follicular growth; additional research will be needed to select the optimal FSH-CTP dose and treatment time interval.
Cancer vaccines: progress reveals new complexities (2002)

The future of vaccine designA decade ago, it seemed clear that our burgeoning knowledge of the molecular identities of tumor-associated antigens and a deeper understanding of basic immunology would point the way to an effective therapeutic cancer vaccine.Significant progress has been made and objective regressions after immune-based treatments are observed in some patients -even in those with bulky, metastatic disease.Notwithstanding this progress, we do not yet have a cancer vaccine in hand that can reliably increase patient survival or induce tumor destruction.The creation of therapeutic cancer vaccines has proven to be an enormous challenge, and many of the strategies learned in the development of highly successful vaccines against infectious agents simply do not apply to cancer vaccines.Issues of antigenic change and immune escape are present in both antitumor and antiviral situations.However, one big difference between antiviral and antitumor vaccines is that the former are preventative whereas the latter are generally expected to be therapeutic.Another problem with the targeting of tumor antigens relates to their poor immunogenicity.Tumor antigens appear to be relatively well tolerated in the host, perhaps because many of these antigens are also expressed in normal tissues.In this context, a successful cancer vaccine raises the specter of autoimmune attack if the vaccines are ultimately powerful enough to eliminate cancer cells.In this review, we highlight new challenges that have been revealed by recent progress in the field of tumor immunology.We then attempt to outline a future plan for cancer immunotherapy.
MIMO performance of enhanced UMTS four-antenna structures for mobile phones in the presence of the user’s head (2007)

In this paper, we have presented the reverberation chambers (RC) evaluation of the multiple-input-multiple-output (MIMO) system performance of several UMTS four-antenna systems with low and high planar inverted-F antennas (PIFAs) isolation. It has been measured that the neutralization technique is always improving the performances even with the presence of the user's head, due to the high isolation obtained between the antennas and their high total efficiencies.
KRAS Mutation Testing in Colorectal Cancer (2009)

In the US, colorectal cancer is the third leading cause of cancer-related death. Approximately 20% of patients present with metastatic disease, and an additional 30% to 40% develop metastasis during the course of their disease. Patients with metastatic colon cancer have a 5-year survival rate of only 11%. Although surgery is the mainstay of treatment for early stage colon cancer, adjuvant treatment is usually used in patients advanced stage disease. In particular, epidermal growth factor receptor (EGFR) inhibitor therapies have emerged as effective treatments in a subset of patients with metastatic colorectal carcinoma. Two anti-EGFR biologics, cetuximab and panitumumab, have been approved by the Food and Drug Administrations for the treatment of refractory metastatic colorectal carcinoma. Mounting evidence has shown that these therapies are ineffective in tumors with mutations of codons 12 and 13 of exon 2 of the KRAS gene. Because of this compelling data, the National Comprehensive Cancer Network and the American Society of Clinical Oncology have recommended determination of KRAS mutation status in all patients with metastatic colorectal cancer who are candidates for anti-EGFR therapy. Anatomic pathologists play an integral role in coordinating the testing for KRAS mutations, as this assay is performed on tissue samples selected by the pathologist. Herein, the authors present an up-to-date review of the biologic, clinical, and laboratory aspects of KRAS mutation testing in colorectal cancer.
Overview of the relationship between ischemia and congestive heart failure (2000)

Ischemic heart disease is the principal etiology of heart failure in the Western world. Myocardial ischemia is important in cardiac remodeling, a process that leads to a progressive change in the shape and size of the heart and significantly worsens the prognosis of patients with heart failure. Preventing ischemic events, therefore, is an important goal in the management of patients with coronary artery disease. Statins have been shown to reduce the number of ischemic events in these patients, whereas the benefit of beta-blocker and aldosterone antagonist therapy on ischemic causes of heart failure remains unclear. Several large trials involving patients with asymptomatic left ventricular dysfunction after myocardial infarction or heart failure have shown that angiotensin-converting enzyme (ACE) inhibitors reduce the incidence of progressive heart failure, death, and ischemic events, thus establishing ACE inhibitors as first-line therapy for these patients. Other lines of evidence have suggested that ACE inhibitor therapy may also benefit patients with preserved left ventricular function, a hypothesis that is being evaluated in three large, controlled, randomized trials. One of these trials, the Heart Outcomes Prevention Evaluation (HOPE) study, was terminated prematurely because it demonstrated the significant positive effects of the ACE inhibitor ramipril on cardiovascular outcomes in patients with coronary artery disease and preserved left ventricular function. A growing body of data confirms the relationship between ischemia and heart failure and the benefits of ACE inhibitor treatment in a broad range of high-risk patients.
A sequence motif responsible for ER export and surface expression of Kir2.0 inward rectifier K+ channels (2001)

Integral membrane proteins are sorted via the secretory pathway. It was proposed that this pathway is non-selective provided that the cargo protein is properly assembled and lacks an endoplasmic reticulum (ER) retention signal. However, recent experimental evidence suggests that efficient export of proteins from the ER to the Golgi complex is not simply a default pathway. Here we demonstrate a novel sequence motif (FxYENEV) in the cytoplasmic C-terminus of mammalian inward rectifier potassium (Kir) channels which determines ER export. This motif is found to be both necessary and sufficient for efficient export from the ER that eventually leads to efficient surface expression of Kir2.1 channels.
Xeno-Free Defined Conditions for Culture of Human Embryonic Stem Cells, Neural Stem Cells and Dopaminergic Neurons Derived from Them (2009)

hESCs and NSCs can be maintained in xeno-free defined media for a prolonged period of time while retaining their ability to differentiate into authentic dopaminergic neurons. Our defined medium system provides a path to a scalable GMP-applicable process of generation of dopaminergic neurons from hESCs for therapeutic applications, and a ready source of large numbers of neurons for potential screening applications.