gebhart/patrepeval huggingface dataset:
Long targeting arms do not increase the efficiency of homologous recombination in the β-globin locus of murine embryonic stem cells (2003)

The correction of mutant beta-globin genes has long been a therapeutic goal for patients with beta-thalassemia or hemoglobinopathies. The use of homologous recombination (HR) to achieve this goal is an attractive approach because it eliminates the need to include regulatory sequences in the therapeutic construct, and it eliminates mutagenesis induced by random integration. However, HR is a very inefficient process for gene correction, and its efficiency is probably locus dependent. The length of targeting arms is thought to be a determinant of targeting efficiency, so we compared the ability of standard (8-kb) versus very long (16-, 24-, and 110-kb) regions of homology to correct a mutant murine beta-globin gene in embryonic stem cells. Increasing the length of the targeting sequences did not increase the efficiency of HR in this locus, suggesting that alternative approaches will be required to improve the efficiency of this approach for globin gene correction.
Diauxic Cell Behavior Enables Detoxification of CHO Cell Culture Medium During Fed Batch Cultivation (2006)

For aims of process optimisation an increased cell and product concentration could not be achieved by simple glucose and glutamine feeding due to the growth inhibiting tension of their waste products lactate and several organic acids. The experiments pointed out that any significant accumulation of lactate has to be avoided. By applying an intelligent feeding technique we could induce a so far not oftenseen remetabolisation of the toxic waste product lactate for biosynthesis purposes and therefore denote this phase as gluconeogenesis. The induction of the gluconeogenitic phase was achieved by a continuous feeding of TCA-cycle anaplerotic amino acids glutamine and asparagine. The utilisation of waste products diminishes the growth inhibiting effect. As a consequence of the removement of lactate a prolongation of cell growth was achieved, because of the occurrence of a second exponential phase when the cells grow on lactate as a carbon source. Although in this phase the growth rate was decreased the overall number of cells was improved. Increased biomass correlates with an increase of product titre.
Pharmacological Basis of CD101 Efficacy: Exposure Shape Matters (2017)

CD101 is a novel echinocandin with concentration-dependent fungicidal activity <i>in vitro</i> and a long half-life (∼133 h in humans, ∼70 to 80 h in mice). Given these characteristics, it is likely that the shape of the CD101 exposure (i.e., the time course of CD101 concentrations) influences efficacy. To test this hypothesis, doses which produce the same total area under the concentration-time curve (AUC) were administered to groups of neutropenic ICR mice infected with <i>Candida albicans</i> R303 using three different schedules. A total CD101 dose of 2 mg/kg was administered as a single intravenous (i.v.) dose or in equal divided doses of either 1 mg/kg twice weekly or 0.29 mg/kg/day over 7 days. The studies were performed using a murine disseminated candidiasis model. Animals were euthanized at 168 h following the start of treatment. Fungi grew well in the no-treatment control group and showed variable changes in fungal density in the treatment groups. When the CD101 AUC from 0 to 168 h (AUC<sub>0-168</sub>) was administered as a single dose, a >2 log<sub>10</sub> CFU reduction from the baseline at 168 h was observed. When twice-weekly and daily regimens with similar AUC values were administered, net fungal stasis and a >1 log<sub>10</sub> CFU increase from the baseline were observed, respectively. These data support the hypothesis that the shape of the CD101 AUC influences efficacy. Thus, CD101 administered once per week demonstrated a greater degree of fungal killing than the same dose divided into twice-weekly or daily regimens.
Disruption of the novel plant protein NEF1 affects lipid accumulation in the plastids of the tapetum and exine formation of pollen, resulting in male sterility in Arabidopsis thaliana (2004)

A novel male-sterile mutant of Arabidopsis thaliana was isolated by means of T-DNA tagging. Pollen abortion of the mutant was evident after microspore release, and pollen grains were completely absent at anthesis. Transmission electron microscope analysis revealed that primexine was coarsely developed, and that although sporopollenin was produced, it was not deposited onto the microspore plasma membrane. The sporopollenin that failed to be deposited aggregated and accumulated within the locule and on the locule wall. Finally, as no exine formation was observed, the mutant was named nef1. The plastoglobuli within the plastids of the tapetum were reduced, and lipid accumulation was considerably decreased. The mutant had a significantly altered leaf chloroplast ultrastructure and showed various growth defects. Lipid analysis revealed that the total lipid content in nef1 was lower than that in the wild type, which indicated that Nef1 was involved in lipid metabolism. Cloning of the full-length Nef1 indicated that the gene encodes a novel plant protein of 1123 amino acids with limited sequence similarities to membrane proteins or transporter-like proteins, and the NEF1 is predicted to be a plastid integral membrane protein. Motif analysis revealed that NEF1 contains prokaryotic membrane lipoprotein lipid attachment sites that are involved in maintaining cell envelope integrity. It is predicted that the Nef1 encodes a membrane protein that maintains the envelope integrity in the plastids.
Detection of parvovirus B19 in donated blood: a model system for screening by polymerase chain reaction (1993)

A highly sensitive and rapid method for routinely screening large numbers of donated blood units for parvovirus B19 by the polymerase chain reaction (PCR) was developed. Over a 3-month trial period in Edinburgh, B19 DNA was detected in 6 of 20,000 consecutive units of blood (0.03%), in concentrations ranging from 2.4 x 10(4) to 5 x 10(10) copies of viral DNA per ml. Seroconversion for B19-specific immunoglobulin M and immunoglobulin G and disappearance of circulating B19 DNA occurred in the interval between donation and recall in four of the five implicated donors who could be recalled. B19 DNA was detected in 18 of 27 separate batches of non-heat-treated factor VIII and IX concentrate manufactured from donated plasma unscreened for B19 DNA. Dry-heat treatment at 80 degrees C for 72 h reduced but did not always eliminate detectable B19 from factor VIII concentrates, consistent with recent observations that current methods for virus inactivation during blood product manufacture are insufficient to entirely eliminate B19 infectivity. The methods developed in this study for PCR screening could be applied routinely to prevent transfusion of B19 in blood and blood products and could play an important role in the prevention of iatrogenic transmission of infection. PCR screening could also be used for detection and exclusion of a range of other transmission-associated viruses for which current serological detection methods are only partially effective.
Potential roles of decidual prolactin in early pregnancy (2001)

Successful establishment of pregnancy is dependent on uterine receptivity at the time of trophoblast invasion and implantation. The endometrium undergoes morphological and functional differentiation during the mid- to late secretory phase of the menstrual cycle in preparation for such an event. These changes are orchestrated by ovarian steroid hormones. However, local autocrine-paracrine signalling at the deciduo-placental interface is crucial for successful establishment of pregnancy. One key cytokine that may regulate many functions in implantation is prolactin. Prolactin is secreted by the decidualized endometrium at the time of predicted conception and, in the event of pregnancy, local expression and secretion of prolactin persists until term. Prolactin mediates its effect on target cells through interaction with single-pass transmembrane receptors. Localization of the sites of expression of the prolactin receptor indicates that the cytokine may regulate an array of functions in the pregnant uterus that are crucial in im-plantation and early pregnancy.
Medical robotics in computer-integrated surgery (2003)

This paper provides a broad overview of medical robot systems used in surgery. After introducing basic concepts of computer-integrated surgery, surgical CAD/CAM, and surgical assistants, it discusses some of the major design issues particular to medical robots. It then illustrates these issues and the broader themes introduced earlier with examples of current surgical CAD/CAM and surgical assistant systems. Finally, it provides a brief synopsis of current research challenges and closes with a few thoughts on the research/industry/clinician teamwork that is essential for progress in the field.
A case-based learning approach to grouping cases with multiple malformations. (1995)

A case-based classification system can provide assistance to specialists in dysmorphology. This article describes a case-based model designed to assist in identification and retrospective analysis of rare types of syndromes that have proved difficult to diagnose. The primary task of diagnosis is complemented by a learning, or grouping, task. Using data sets of diagnosed cases in related categories of syndromes, we demonstrate how a case-based learning algorithm can extend the retrieval and indexing mechanisms of standard databases to provide a focus for analysis of syndrome classifications.
Losslessness, feedback equivalence, and the global stabilization of discrete-time nonlinear systems (1994)

In this paper a necessary and sufficient condition for a nonlinear system of the form /spl Sigma/, given by x(k+1)=f(x(k))+g(x(k))u(k), y(k)=h(x(k))+J(x(k))u(k), to be lossless is given, and it is shown that a lossless system can be globally asymptotically stabilized by output feedback if and only if the system is zero-state observable. Then, we investigate conditions under which /spl Sigma/ can be rendered lossless via smooth state feedback. In particular, we show that this is possible if and only if the system in question has relative degree /spl lcub/0,...,0/spl rcub/ and has lossless zero dynamics. Under suitable controllability-like rank conditions, we prove that nonlinear systems having relative degree /spl lcub/0,...,0/spl rcub/ and lossless zero dynamics can be globally stabilized by smooth state feedback. As a consequence, we obtain sufficient conditions for a class of cascaded systems to be globally stabilizable. The global stabilization problem of the nonlinear system /spl Sigma/ without output is also investigated in this paper by means of feedback equivalence. Some of the results are parallel to analogous ones in continuous-time, but in many respects the theory is substantially different and many new phenomena appear.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis of Functionalized Dialkyl Ketones from Carboxylic Acid Derivatives and Alkyl Halides (2012)

Unsymmetrical dialkyl ketones can be directly prepared by the nickel-catalyzed reductive coupling of carboxylic acid chlorides or (2-pyridyl)thioesters with alkyl iodides or benzylic chlorides. A wide variety of functional groups are tolerated by this process, including common nitrogen protecting groups and C-B bonds. Even hindered ketones flanked by tertiary and secondary centers can be formed. The mechanism is proposed to involve the reaction of a (L)Ni(alkyl)(2) intermediate with the carboxylic acid derivative.
Nanobiotechnology and Cell Biology: Micro- and Nanofabricated Surfaces to Investigate Receptor-Mediated Signaling (2008)

Advances in microfabrication and nanofabrication are opening new opportunities to investigate complicated questions of cell biology in ways not before possible. In particular, the spatial regulation of cellular processes can be examined by engineering the chemical and physical environment to which the cell responds. Lithographic methods and selective chemical modification schemes can provide biocompatible surfaces that control cellular interactions on the micron and submicron scales on which cells are organized. Combined with fluorescence microscopy and other approaches of cell biology, a widely expanded toolbox is becoming available. This review illustrates the potential of these integrated engineering tools, with an emphasis on patterned surfaces, for investigating fundamental mechanisms of receptor-mediated signaling in cells. We highlight progress made with immune cells and in particular with the IgE receptor system, which has been valuable for developing technology to gain new information about spatial regulation in signaling events.
p53 mutations are associated with histologic transformation of follicular lymphoma (1993)

The majority of low-grade non-Hodgkin's lymphomas (NHL) undergo clinical progression toward intermediate- and high-grade lymphomas. This progression is often associated with histologic transformation from follicular to diffuse-type NHL. The pathogenetic mechanisms underlying this evolution are presently unknown. In this study, we have analyzed the role in NHL progression of relevant genetic lesions affecting proto-oncogenes and tumor suppressor genes. Sequential biopsies from 21 patients with clinical progression with (5 cases) or without (16 cases) evidence of histologic transformation were analyzed for karyotypic changes, c-myc rearrangements and deletions affecting 6q27 by Southern blot analysis, and p53 mutations by single-strand conformation polymorphism (SSCP) analysis coupled with direct sequencing of polymerase chain reaction-amplified products. No novel cytogenetic aberration was detected in association with progression, and all samples analyzed displayed a normal c-myc gene. Mutations of the p53 gene were detected in 4 of 5 cases displaying histologic transformation from follicular to diffuse-type NHL and in none of the 16 cases displaying clinical progression in the absence of histologic transformation. In 1 of these positive cases, the same mutation was also present in the pretransformation biopsy, correlating with the presence of diffuse-type areas within a predominant follicular pattern. In 1 of these cases, a deletion of 6q27 was also detected in the posttransformation biopsy along with a p53 mutation. These findings indicate that p53 mutations are associated with and may be responsible for histologic transformation of follicular lymphoma.
Nanowire-Based Biosensors (2006)

ADVERTISEMENT RETURN TO ISSUEPREVFEATURESNEXTNanowire-Based BiosensorsFernando Patolsky, Gengfeng Zheng, and Charles M. LieberCite this: Anal. Chem. 2006, 78, 13, 4260–4269Publication Date (Web):July 1, 2006Publication History Published online1 July 2006Published inissue 1 July 2006https://pubs.acs.org/doi/10.1021/ac069419jhttps://doi.org/10.1021/ac069419jnewsACS Publications. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views8434Altmetric-Citations623LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (432 KB) Get e-Alertsclose SUBJECTS:Biotechnology,Sensors Get e-Alerts
Evidence in Support of Collateral Sprouting After Sensory Nerve Resection (1996)

The extent and time course of sensory recovery has been investigated in 13 patients who had resection of a cutaneous nerve. Seven patients were studied within 8 weeks of denervation; 6 others were studied more than 6 months after denervation. Touch sensation was evaluated using a computer-assisted measuring device that recorded the pressure thresholds for static and moving touch, and static and moving two-point discrimination within a continual range from 0.1 to 100 gm per square millimeter. Recovery of sensation within the autonomous zone of the resected nerve could be documented as early as 3 weeks after denervation. After 6 months, two-point discrimination had recovered in the previously denervated areas. Thresholds for all test modalities were found to be elevated within the sensory distribution of adjacent nerves, which suggests that these areas have been the donor source for reinnervation of the chronically denervated territory. Anesthetic block of these adjacent donor nerves resulted in loss of the recovered sensation.
EXTENDED RELEASE QUETIAPINE FUMARATE IN MAJOR DEPRESSIVE DISORDER: ANALYSIS IN PATIENTS WITH ANXIOUS DEPRESSION (2012)

Quetiapine XR monotherapy improved symptoms of depression in patients with higher and lower levels of anxiety.
Programmed cell death in bacteria: proteic plasmid stabilization systems (1995)

Bacterial plasmids are stabilized by a number of different mechanisms. Here we describe the molecular aspects of a group of plasmid-encoded gene systems called the proteic killer gene systems. These systems mediate plasmid maintenance by selectively killing plasmid-free cells (post-segregational killing or plasmid addiction). The group includes ccd of F, parD/pem of R1/R100, parDE of RP4/RK2, and phd/doc of P1. All of these systems encode a stable toxin and an unstable antidote. The antidotes prevent the lethal action of their cognate toxins by forming tight complexes with them. The antidotes are degraded by cellular proteases. Thus, the different decay rates of the toxins and antidotes seem to be the molecular basis of toxin activation in plasmid-free cells. The operons encoding the toxins and antidotes are autoregulated at the level of transcription either by a complex formed by the toxins and the cognate antidotes or by the antidote alone. The cellular targets of the killer proteins have been determined to be DNA gyrase in the case of ccd of F and DnaB in the case of parD of R1. Surprisingly, the Escherichia coli chromosome encodes at least two of these peculiar gene systems.
Cochlear implants: Current designs and future possibilities (2008)

The cochlear implant is the most successful of all neural prostheses developed to date. It is the most effective prosthesis in terms of restoration of function, and the people who have received a cochlear implant outnumber the recipients of other types of neural prostheses by orders of magnitude. The primary purpose of this article is to provide an overview of contemporary cochlear implants from the perspective of two designers of implant systems. That perspective includes the anatomical situation presented by the deaf cochlea and how the different parts of an implant system (including the user's brain) must work together to produce the best results. In particular, we present the design considerations just mentioned and then describe in detail how the current levels of performance have been achieved. We also describe two recent advances in implant design and performance. In concluding sections, we first present strengths and limitations of present systems and then offer some possibilities for further improvements in this technology. In all, remarkable progress has been made in the development of cochlear implants but much room still remains for improvements, especially for patients presently at the low end of the performance spectrum.
High-molecular-weight glycoproteins of human teratocarcinoma defined by monoclonal antibodies to carbohydrate determinants. (1985)

Three mouse monoclonal antibodies to distinct cell surface antigens were derived from immunizations with cells of Tera-1, a human teratocarcinoma cell line, and a membrane preparation of placental tissue. The distribution of the antigens on 165 cultured lines of various human tumors and normal cells was determined by mixed hemadsorption assays and on fresh tissues by immunofluorescence staining. K4 antigen is expressed on cell lines derived from teratocarcinomas but not on any other cultured cell tested. Normal adult colonic epithelium, some fetal tissues, and specimens of testicular teratocarcinoma were also K4 positive. K21 antigen was detected on teratocarcinoma cell lines and, at more than 100-fold lower levels, on cultures of normal and malignant kidney epithelium but not on other cultured cells. K21 expression in normal tissues is restricted to the epithelium of fetal intestine and bronchus. Other fetal tissues and all adult normal tissues tested lacked K21. A subset of teratocarcinoma specimens (5 of 8) was reactive with antibody K21. P12 antigen is represented on a wide range of cell lines and tissues, including a subset of teratocarcinomas. AbK4, AbK21, and AbP12 react with carbohydrate sequences present on high-molecular-weight glycoproteins. AbK21 and AbP12 recognize the lacto-N-tetraose and lacto-N-fucopentaose III (X-hapten) structures, respectively, whereas AbK4 reacts with a neuraminidase-sensitive determinant.
Effective partial redundancy elimination (1994)

Partial redundancy elimination is a code optimization with a long history of literature and implementation. In practice, its effectiveness depends on issues of naming and code shape. This paper shows that a combination of global reassociation and global value numbering can increase the effectiveness of partial redundancy elimination. By imposing a discipline on the choice of names and the shape of expressions, we are able to expose more redundancies.
Identification of Multiple Antigens Recognized by Tumor-Infiltrating Lymphocytes From a Single Patient: Tumor Escape by Antigen Loss and Loss of MHC Expression (2004)

The authors describe a patient who experienced recurrence of metastatic melanoma after an initial dramatic response to immunotherapy using peptides derived from gp100, MART-1, and tyrosinase emulsified in incomplete Freund's adjuvant, and present data to support the hypothesis that the progression of disease in this patient was due to in vivo immunoselection for immunoresistant tumor variants. The authors previously demonstrated the existence of T-cell clones in this patient's peripheral blood and tumor-infiltrating lymphocytes (TILs) reactive against multiple antigens, including gp100, the tyrosinase-related protein (TRP)-2, a novel TRP-2 isoform-TRP-2-6b, SOX10, and the melanoma antigen NY-ESO-1. In addition to the multiple HLA-A2 restricted T-cell clones, the authors have now identified additional HLA-B/C-restricted as well as class II (HLA-DP)-restricted anti-melanoma antigen T-cell clones from this patient's TIL. One recurrent tumor showed loss of expression of multiple tumor antigens but retention of HLA class I expression. The other recurrent lesion showed total loss of HLA class I expression even though the tumor cells still expressed many melanoma antigens. This paper thus provides evidence for both the effectiveness of the immune destruction of cancer as well as problems associated with antigen-loss tumor escape mechanisms.
Irreversible Electroporation Near the Heart: Ventricular Arrhythmias Can Be Prevented With ECG Synchronization (2011)

Unsynchronized irreversible electroporation close to the heart can cause fatal ventricular arrhythmias. Synchronizing irreversible electroporation pulse delivery with absolute refractory period avoids significant cardiac arrhythmias.