gebhart/patrepeval huggingface dataset:
Transplantation of ex vivo expanded cord blood (2002)

Umbilical cord blood (CB) from unrelated donors is increasingly used to restore hematopoiesis after myeloablative therapy. CB transplants are associated with higher rates of delayed and failed engraftment than are bone marrow transplants, particularly for adult patients. We studied the ex vivo expansion of CB in an attempt to improve time to engraftment and reduce the graft failure rate in the recipients. In this feasibility study, 37 patients (25 adults, 12 children) with hematologic malignancies (n = 34) or breast cancer (n = 3) received high-dose therapy followed by unrelated allogeneic CB transplantation. A fraction of each patient's CB allograft was CD34-selected and cultured ex vivo for 10 days prior to transplantation in defined media with stem cell factor, granulocyte colony-stimulating factor, and megakaryocyte growth and differentiation factor. The remainder of the CB graft was infused without further manipulation. Two sequential cohorts of patients were accrued to the study. The first cohort had 40% and the second cohort had 60% of their CB graft expanded. Patients received a median of 0.99 x 10(7) total nucleated cells (expanded plus unexpanded) per kilogram. The median time to engraftment of neutrophils was 28 days (range, 15-49 days) and of platelets was 106 days (range, 38-345 days). All evaluable patients who were followed for 28 days or longer achieved engraftment of neutrophils. Grade III/IV acute GVHD was documented in 40% and extensive chronic GVHD in 63% of patients. At a median follow-up of 30 months, 13 (35%) of 37 of patients survived. This study demonstrates that the CD34 selection and ex vivo expansion of CB prior to transplantation of CB is feasible. Additional accrual will be required to assess the clinical efficacy of expanded CB progenitors.
Complete Regression of Metastatic Cervical Cancer After Treatment With Human Papillomavirus–Targeted Tumor-Infiltrating T Cells (2015)

Durable, complete regression of metastatic cervical cancer can occur after a single infusion of HPV-TILs. Exploratory studies suggest a correlation between HPV reactivity of the infusion product and clinical response. Continued investigation of this therapy is warranted.
Characterization of a novel receptor that maps near the natural killer gene complex: demonstration of carbohydrate binding and expression in hematopoietic cells. (1999)

A novel type II integral membrane protein has been identified in the course of screening for genes overexpressed in a mouse model of chronic myelogenous leukemia blast crisis. This new protein, designated NKCL, consists of a 210-amino acid polypeptide with a short, NH2-terminal cytoplasmic tail of 17 amino acids preceding a transmembrane domain and a COOH-terminal extracellular region. The COOH-terminal 132 amino acids bear typical features of the C-type animal lectin carbohydrate-recognition domain. The Nkcl gene is unique in that it maps just proximal to the region of the genome that encodes group V members of the C-type animal lectin family near the natural killer gene complex on mouse chromosome 6, but its protein product also has features of several group II C-type animal lectins. Most notably, it has a complete Ca2+-binding site 2, which forms part of the sugar-binding site in other members of the family, and binds mannose in a Ca2+-dependent manner. Moreover, its expression is not restricted to natural killer cells, as reported for the majority of group V lectins. Nkcl is expressed in pluripotent myeloid precursors, precursor and mature macrophages, and neutrophils.
Experimental Certification of Random Numbers via Quantum Contextuality (2013)

The intrinsic unpredictability of measurements in quantum mechanics can be used to produce genuine randomness. Here, we demonstrate a random number generator where the randomness is certified by quantum contextuality in connection with the Kochen-Specker theorem. In particular, we generate random numbers from measurements on a single trapped ion with three internal levels, and certify the generated randomness by showing a bound on the minimum entropy through observation of violation of the Klyachko-Can-Binicioglu-Shumovsky (KCBS) inequality. Concerning the test of the KCBS inequality, we close the detection efficiency loophole for the first time and make it relatively immune to the compatibility loophole. In our experiment, we generate 1 × 10(5) random numbers that are guaranteed to have 5.2 × 10(4) bits of minimum entropy with a 99% confidence level.
Bacterial Biofilm Formation, Encrustation, and Antibiotic Adsorption to Ureteral Stents Indwelling in Humans (1998)

Encrustation and urinary tract infection are problematic complications of ureteral stent usage. The objective of our first study was to use surface science techniques to examine three ureteral stent types for encrustation, biofilm formation, and antibiotic adsorption after use in patients. Black Beauty (N = 16), LSe (N = 16), and SofFlex (N = 32) ureteral stents were recovered from patients who had received trimethoprim or ciprofloxacin while the stent was indwelling. These stents were examined with X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy/energy-dispersive X-ray analysis (SEM/EDX) for the presence and composition of encrustation or biofilm. Conditioning films and encrustations were found on all stents. Encrustation elements (Ca, Mg, P) were identified on 11 of 16 Black Beauty (69%), 7 of 16 LSe (44%), and 12 of 32 SofFlex (38%) stents. The stent type, duration of insertion, and age or sex of the patient did not correlate significantly with the amount of encrustation. Bacterial biofilms were found on 1 of 7 Black Beauty stents (14%) and 7 of 32 SofFlex stents (22%). In a second study, an additional 28 patients with SofFlex stents were treated with ciprofloxacin (N = 16) or ofloxacin (N = 12). Their stents were subjected to high-performance liquid chromatography to determine if oral antibiotic therapy can lead to drug adsorption to the stent. Analysis showed that both ciprofloxacin and ofloxacin adsorbed to the stent surfaces. The mean concentrations of the two antibiotics within the conditioning film of the stents were 0.99 microg/mL and 0.34 microg/mL, respectively. These surface science techniques provide a comprehensive method of evaluating ureteral stents and other prosthetic devices in vivo.
Gene Silencing Nucleic Acids Designed by Scanning Arrays: Anti-EGFR Activity of siRNA, Ribozyme and DNA Enzymes Targeting a Single Hybridization-accessible Region using the Same Delivery System (2003)

Gene silencing nucleic acids such as ribozymes, DNA enzymes (DNAzymes), antisense oligonucleotides (ODNs), and small interfering (si)RNA rely on hybridization to accessible sites within target mRNA for activity. However, the accurate prediction of hybridization accessible sites within mRNAs for design of effective gene silencing reagents has been problematic. Here we have evaluated the use of scanning arrays for the effective design of ribozymes, DNAzymes and siRNA sequences targeting the epidermal growth factor receptor (EGFR) mRNA. All three gene silencing nucleic acids designed to be complementary to the same array-defined hybridization accessible-site within EGFR mRNA were effective in inhibiting the growth of EGFR over-expressing A431 cancer cells in a dose dependent manner when delivered using the cationic lipid (Lipofectin) delivery system. Effects on cell growth were correlated in all cases with concomitant dose-dependent reduction in EGFR protein expression. The control sequences did not markedly alter cell growth or EGFR expression. The ribozyme and DNAzyme exhibited similar potency in inhibiting cell growth with IC50 values of around 750 nM. In contrast, siRNA was significantly more potent with an IC50 of about 100 nM when delivered with Lipofectin. The potency of siRNA was further enhanced when Oligofectamine was used to further improve both the cellular uptake and subcellular distribution of fluorescently labelled siRNA. Our studies show that active siRNAs can be designed using hybridization accessibility profiles on scanning arrays and that siRNAs targeting the same array-designed hybridization accessible site in EGFR mRNA and delivered using the same delivery system are more potent than ribozymes and DNAzymes in inhibiting EGFR expression in A431 cells.
Neisseria gonorrhoeae PLD directly interacts with Akt kinase upon infection of primary, human, cervical epithelial cells (2006)

Neisseria gonorrhoeae secrets a phospholipase D (NgPLD), which augments complement receptor 3 (CR3)-mediated invasion of cervical epithelial cells. To elucidate the signalling pathways triggered with gonococcus CR3-engagement and the putative function of NgPLD in these events, we analysed the contribution of the phosphoinositide-Akt pathway to cervical infection. Our data indicated that Akt plays a critical role in cervical infection. Inhibition of myosin light chain kinase, PtdIns(4,5)P2, and Akt functions resulted in decreased gonococcus invasion of primary, human, cervical epithelial cells as well as Akt kinase activity. Akt activity was similarly impaired when cervical cells were challenged with NgPLD-mutant gonococci. Conversely, the PI3-kinase inhibitor, LY294002, enhanced gonococcal invasion of, and Akt activity within, primary cervical cells. We demonstrated that NgPLD directly binds to the Akt PH domain and can compete with a natural Akt ligand, PtdIns(3,4,5)P3, for Akt binding. Collectively, our data suggested that NgPLD augments gonococcus invasion of cervical epithelia by interacting with Akt kinase in a PI3-kinase-independent manner, which results in subversion of normal cervical cell signalling.
Expression of TDP-43 C-terminal Fragments in Vitro Recapitulates Pathological Features of TDP-43 Proteinopathies (2009)

The disease protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS) was identified recently as the TDP-43 (TAR DNA-binding protein 43), thereby providing a molecular link between these two disorders. In FTLD-U and ALS, TDP-43 is redistributed from its normal nuclear localization to form cytoplasmic insoluble aggregates. Moreover, pathological TDP-43 is abnormally ubiquitinated, hyperphosphorylated, and N-terminally cleaved to generate C-terminal fragments (CTFs). However, the specific cleavage site(s) and the biochemical properties as well as the functional consequences of pathological TDP-43 CTFs remained unknown. Here we have identified the specific cleavage site, Arg(208), of a pathological TDP-43 CTF purified from FTLD-U brains and show that the expression of this and other TDP-43 CTFs in cultured cells recapitulates key features of TDP-43 proteinopathy. These include the formation of cytoplasmic aggregates that are ubiquitinated and abnormally phosphorylated at sites found in FTLD-U and ALS brain and spinal cord samples. Furthermore, we observed splicing abnormalities in a cell culture system expressing TDP-43 CTFs, and this is significant because the regulation of exon splicing is a known function of TDP-43. Thus, our results show that TDP-43 CTF expression recapitulates key biochemical features of pathological TDP-43 and support the hypothesis that the generation of TDP-43 CTFs is an important step in the pathogenesis of FTLD-U and ALS.
Adenovirus Vector Designed for Expression of Toxic Proteins (2001)

To construct recombinant adenoviruses expressing biologically active proteins may be impossible, or result in a significant reduction in virus yield, if the protein expressed has an inhibitory effect on virus replication or cellular growth. To overcome this problem, we previously designed adenovirus vectors expressing foreign proteins from inducible promoters. However, during our work with a replication-deficient virus expressing the ASF/SF2 splicing factor from a progesterone antagonist-inducible gene cassette, we discovered that ASF/SF2 was expressed at a significant level in the 293 producer cell line, even in the absence of inducer. 293 cells code for adenovirus E1A and E1B proteins and thus support the growth of E1-deficient adenoviruses. Here we show that this background ASF/SF2 expression results from a low level of E1A-mediated transactivation of the basal promoter driving transgene expression. To overcome the problem of leaky expression, we reconstructed a novel gene cassette that combines an inducible promoter and a Lac repressor protein-based block to reduce transcriptional elongation. We show that this novel vector system dramatically reduced background transgene expression and therefore should be useful for the rescue and propagation of high-titer stocks of recombinant adenoviruses expressing toxic proteins.
Integrin-linked Protein Kinase Regulates Fibronectin Matrix Assembly, E-cadherin Expression, and Tumorigenicity (1998)

Fibronectin (Fn) matrix plays important roles in many biological processes including morphogenesis and tumorigenesis. Recent studies have demonstrated a critical role of integrin cytoplasmic domains in regulating Fn matrix assembly, implying that intracellular integrin-binding proteins may be involved in controlling extracellular Fn matrix assembly. We report here that overexpression of integrin-linked kinase (ILK), a newly identified serine/threonine kinase that binds to the integrin beta1 cytoplasmic domain, dramatically stimulated Fn matrix assembly in epithelial cells. The integrin-linked kinase activity is involved in transducing signals leading to the up-regulation of Fn matrix assembly, as overexpression of a kinase-inactive ILK mutant failed to enhance the matrix assembly. Moreover, the increase in Fn matrix assembly induced by ILK overexpression was accompanied by a substantial reduction in the cellular E-cadherin. Finally, we show that ILK-overexpressing epithelial cells readily formed tumors in nude mice, despite forming an extensive Fn matrix. These results identify ILK as an important regulator of pericellular Fn matrix assembly, and suggest a novel critical role of this integrin-linked kinase in cell growth, cell survival, and tumorigenesis.
Mobile Augmented Reality: Applications and Human Factors Evaluations (2006)

Recent trends in military operations (quick-reaction forces, putting fewer warfighters at risk, and increasing the use of unmanned vehicles) have increased the difficulty in acquiring and maintaining situation awareness (SA). Augmented reality (AR) has the potential to meet some of these new challenges. AR systems integrate computer-generated graphics (or annotations) with the user's view of the real world. These annotations can be cues to establish and maintain SA, or they can provide virtual opposing forces (OPFOR) for training scenarios. However, the design of the user interface of a mobile AR system presents a unique set of technical challenges. The interface must be capable of automatically deciding what annotations need to be shown. Furthermore, it must select the characteristics of those annotations (including appearance, size, and drawing style) to ensure the display is intuitive and unambiguous. In the training applications, the virtual OPFOR must appear and behave realistically. We discuss the development of our augmented reality system and the human factors testing we have performed. We apply the system to two military needs: situation awareness during operations and training.
Effects of anabaseine‐related analogs on rat brain nicotinic receptor binding and on avoidance behaviors (1994)

Abstract Several novel anabaseine‐derived compounds were investigated with respect to their ability to displace high affinity [ 3 H]cytisine binding in rat brain membranes, as well as their ability to improve passive and active avoidance behaviors in nucleus basalis‐lesioned rats. The relative potencies for displacement of 1 nM [ 3 H]cytisine binding IC50 in parentheses: anabaseine (70 nM) &gt; DMAB (140 nM) = DMXB (150 nM) &gt; anabasine (270 nM) &gt; DMAC (420 nM). Passive avoidance behavior in bilaterally nucleus basalis‐lesioned rats was improved by each of these drugs to an extent comparable to that observed with (–)‐nicotine. The relative potencies of these compounds for improving this behavior exhibited a pattern very similar to their affinities for displacing [ 3 H]cytisine binding (nicotine &gt; anabaseine &gt; DMXB &gt; DMAB = DMAC &gt; anabasine). Acquisition of active avoidance behavior was slower in unilaterally and bilaterally nucleus basalis‐lesioned rats than unlesioned controls; (−)‐nicotine improved acquisition behavior only in the former group. At doses that improved passive avoidance behavior, DMXB also improved acquisition of active avoidance behavior in unilaterally lesioned rats, while DMAB and DMAC did not. (−)Nicotine and DMXB had no effect on escape behavior in the active avoidance task at doses that improved retention of avoidance behavior itself. These results suggest that anabaseine and several of its analogs bind to brain α4β2 nicotinic receptors and mimic non‐spatial, memory‐related behaviors in a nicotine‐like manner. © 1994 Wiley‐Liss, Inc.
Vulnerability of the Recurrent Laryngeal Nerve in the Anterior Approach to the Lower Cervical Spine (1997)

The recurrent laryngeal nerve on the right side is highly vulnerable to injury if ligature of the inferior thyroid vessels is not performed as laterally as possible or if retraction of the midline structures along with the recurrent laryngeal nerve is not performed intermittently. Avoiding injury to the recurrent laryngeal nerve, especially on the right side, is a major consideration during an anterior approach to lower cervical spine.
Protective efficacy of IgM monoclonal antibodies in experimental group B streptococcal infection is a function of antibody avidity. (1988)

We have produced and characterized six mAb directed against group B streptococci (GBS). All antibodies are IgM. We have previously shown that some of these antibodies are highly protective in the treatment of experimental infections in neonatal rats, whereas others do not appear to have any protective efficacy. Using an ELISA, we demonstrate the specificity of both protective and nonprotective antibodies. Two antibodies, binding different epitopes, are directed against antigenic structures present on all GBS; two are specific for type III carbohydrate determinants; one binds to a protein Ag present on all type I and II GBS; and one appears to bind to type Ia GBS only. Quantitative absorption assays provide evidence that the difference between protective antibodies and nonprotective antibodies is the avidity that the antibody demonstrates for the epitope recognized on the surface of the bacteria; 10 to 15 times as much protective antibody binds to GBS as does nonprotective antibody. Direct binding experiments with radiolabeled antibody confirm this conclusion.
The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception (2015)

PR homology domain-containing member 12 (PRDM12) belongs to a family of conserved transcription factors implicated in cell fate decisions. Here we show that PRDM12 is a key regulator of sensory neuronal specification in Xenopus. Modeling of human PRDM12 mutations that cause hereditary sensory and autonomic neuropathy (HSAN) revealed remarkable conservation of the mutated residues in evolution. Expression of wild-type human PRDM12 in Xenopus induced the expression of sensory neuronal markers, which was reduced using various human PRDM12 mutants. In Drosophila, we identified Hamlet as the functional PRDM12 homolog that controls nociceptive behavior in sensory neurons. Furthermore, expression analysis of human patient fibroblasts with PRDM12 mutations uncovered possible downstream target genes. Knockdown of several of these target genes including thyrotropin-releasing hormone degrading enzyme (TRHDE) in Drosophila sensory neurons resulted in altered cellular morphology and impaired nociception. These data show that PRDM12 and its functional fly homolog Hamlet are evolutionary conserved master regulators of sensory neuronal specification and play a critical role in pain perception. Our data also uncover novel pathways in multiple species that regulate evolutionary conserved nociception.
Yersinia pestis Evades TLR4-dependent Induction of IL-12(p40)2 by Dendritic Cells and Subsequent Cell Migration (2008)

At the temperature of its flea vector (approximately 20-30 degrees C), the causative agent of plague, Yersinia pestis, expresses a profile of genes distinct from those expressed in a mammalian host (37 degrees C). When dendritic cells (DC) are exposed to Y. pestis grown at 26 degrees C (Y. pestis-26 degrees), they secrete copious amounts of IL-12p40 homodimer (IL-12(p40)(2)). In contrast, when DCs are exposed to Y. pestis grown at 37 degrees C (Y. pestis-37 degrees), they transcribe very little IL-12p40, which is secreted as IL-12p40 monomer (IL-12p40). Y. pestis-26 degrees also induces migration of DCs to the homeostatic chemokine CCL19, whereas Y. pestis-37 degrees does not; migratory DCs are positive for IL-12p40 transcription and secrete mostly IL-12(p40)(2); DCs lacking IL-12p40 do not migrate. Expression of acyltransferase LpxL from Escherichia coli in Y. pestis-37 degrees results in the production of a hexa-acylated lipid A, also seen in Y. pestis-26 degrees, rather than tetra-acylated lipid A normally seen in Y. pestis-37 degrees. The LpxL-expressing Y. pestis-37 degrees promotes DC IL-12(p40)(2) production and induction of DC migration. In addition, absence of TLR4 ablates production of IL-12(p40)(2) in DC exposed to Y. pestis-26 degrees. The data demonstrate the molecular pathway by which Y. pestis evades induction of early DC activation as measured by migration and IL-12(p40)(2) production.
Laser tissue welding: A comprehensive review of current and future (1995)

Laser techniques for joining tissue, in combination with other surgical technologies, will be a hallmark of surgery in the next century. At present, there are many clinical applications of tissue welding and soldering which are beginning to achieve wide spread acceptance. These exciting clinical developments are the result of many advances which have been made in the past few years in our understanding of the mechanism of laser tissue welding. Also contributing to this progress are many important technical refinements such as tissue solders and feedback control of the laser device. In this article, we describe in depth the history and development of laser tissue welding including key theoretical concepts as well as crucial experiments which have added to our insight into this phenomenon. We also review the evolving concepts of its clinical application and indicate clinical applications which are likely to become more important in the future.
Human malignant melanoma cell line (HMV-II) for isolation of influenza C and parainfluenza viruses (1990)

HMV-II, a human malignant melanoma cell line, was compared with other cell lines (MDCK, Vero, and LLC-MK2) and primary cultures of monkey kidney (PMK) cells for the isolation and quantification of influenza and parainfluenza viruses. HMV-II cells were superior to MDCK and LLC-MK2 cells in quantification of the influenza C virus and were used successfully in the isolation of the virus from clinical specimens. The HMV-II cell line was also more sensitive for isolating parainfluenza viruses from clinical specimens than were Vero and PMK cells; there was, however, no significant difference in the quantification of the viruses among these cultures. As far as influenza A and B viruses were concerned, the HMV-II cell line was significantly less sensitive than MDCK cells, and no virus was isolated from clinical specimens with HMV-II cells. Thus, HMV-II cells are useful for the isolation of influenza C and parainfluenza viruses as an alternative to embryonated hen's eggs and PMK cells.