gebhart/patrepeval huggingface dataset:
Miniature 3-Axis Distal Force Sensor for Minimally Invasive Surgical Palpation (2011)

Minimally invasive surgery (MIS) is a surgical technique that offers distinct advantages in reducing pain and patients' recovery time. However, the drawback due to the lack of force and tactile feedback presents a great deal of limitations in MIS procedures. Tissue palpation, which is easily conducted during traditional open surgery to examine tissue properties and abnormalities, is not possible when performing surgery in a minimally invasive manner. This paper proposes a specially designed miniature 3-axis distal force sensor that can be used to perform tissue palpation, measuring tissue interaction forces at the tip of a surgical instrument. Relying on an optical sensing scheme, the sensor can measure forces within measurement ranges of ±3 N in axial direction and ±1.5 N in radial direction. The resolution is 0.02 N. It is compatible with laparoscopic operations and can be used to localize tissue lesions or relatively hard nodules buried under an organ's surface, which are not detectable by visual means.
Haemodynamic responses to stimulation of the splanchnic and cardiac sympathetic nerves in the anaesthetized cat. (1986)

The changes in cardiac output and mean right atrial pressure (R.A.P.) evoked at different circulating blood volumes by stimulation of the splanchnic sympathetic nerves were investigated in adrenalectomized cats under chloralose anaesthesia, with unopened chests and spontaneous respiration and with active vascular reflexes. The cardiac autonomic nerves were cut or blocked pharmacologically. Stimulation of the distal ends of the splanchnic nerves at 4 Hz caused aortic pressure and R.A.P. to rise to maximum values at 2 min before declining slowly. Cardiac output rose more slowly to a steady state at 3 min; at higher circulating volumes it fell initially. Although the output increments were slower in development they were better sustained than those in total peripheral resistance. The proportionate output increments were largest and the R.A.P. increments least at low circulating volumes whereas at high volumes the R.A.P. increments were large but the output changes were small or negative; the pattern of changes resembled that resulting from infusion of blood. Stimulation of the cardiac sympathetic nerves evoked a rise in output and a fall in R.A.P. related in magnitude to the initial value of R.A.P. On simultaneous stimulation of the splanchnic and cardiac sympathetic nerves the changes in output combined whereas the R.A.P. changes cancelled, to give output increments of 25‐50% with little change in R.A.P. at all circulating volumes. At high circulating volumes infusion of blood did not usually alter output or aortic pressure, but splanchnic nerve stimulation increased peripheral resistance and aortic pressure and commonly evoked a rise in left ventricular stroke work which could not be accounted for by known adrenergic mechanisms or by elevation of left ventricular end‐diastolic pressure. Portal venous pressure was consistently elevated by splanchnic nerve stimulation; it rose more slowly than did aortic pressure or R.A.P. and was independent of a changing central venous pressure provided this did not exceed +5 mmHg. The cardiac output increments were not related to changes in the ratio between the input and output resistances of the portal vein and it is concluded that displacement blood from the peripheral to the central vasculature was induced by contraction capacitance vessels.
Production of Polyclonal Antisera (2003)

All immunochemical procedures require a suitable antiserum or monoclonal antibody raised against the antigen of interest Polyclonal antibodies are raised by injecting an immunogen into an animal and, after an appropriate time, collecting the blood fraction containing the antibodies of interest. In producing antibodies, several parameters must be considered with respect to the final use to which the antibody will be put. These include (1) the specificity of the antibody, i.e., the ability to distinguish between different antigens, (2) the avidity of the antibody, i.e., the strength of binding, and (3) the titer of the antibody, which determines the optimal dilution of the antibody in the assay system. A highly specific antibody with high avidity may be suitable for immunohistochemistry, where it is essential that the antibody remains attached during the extensive washing procedures, but may be less useful for immunoaffinity chromatography, as it may prove impossible to elute the antigen from the column without extensive denaturation.
Characterization of zebrafish Rad52 and replication protein A for oligonucleotide-mediated mutagenesis (2005)

Zebrafish has become a favorite model organism not only in genetics and developmental biology, but also for the study of cancer, neuroscience and metabolism. However, strategies for reverse genetics in zebrafish are mostly limited to the use of antisense oligonucleotides, and therefore the development of other targeting methods is highly desirable. Here, we report an approach to gene targeting in this system in which single-stranded oligonucleotides and zebrafish Rad52 protein are employed. It has been proposed that a single-stranded oligonucleotide containing a mutation can be incorporated into the genome by annealing to the single-stranded region of the lagging strand of the replication fork. Rad52 is expected to accelerate the annealing step. In vitro experiments using purified truncated Rad52 proteins and replication protein A (RPA) showed that annealing of oligonucleotides is accelerated by Rad52 in the presence of RPA. We developed a simple and sensitive PCR-based method to detect point mutations in the genome. In exploratory experiments, we found that microinjection of single-stranded oligonucleotide targeted to a specific gene together with truncated Rad52 into zebrafish embryos resulted in a low level of recombinant copies in 3 of the 80 embryos tested under these conditions.
Food and Drug Administration Studies of High-Temperature Food Packaging (1991)

Food/package interactions that result from the use of microwave susceptors and dual ovenable trays have been extensively studied by FDA's Indirect Additives Laboratory. Temperatures in excess of 212°F are common for such packaging. Susceptors are typically constructed of plastic such as polyethylene terephthalate (PET), adhesives, and paper. Dual ovenable packaging may be constructed of crystallized PET or PET-laminated paperboard and may or may not include adhesive. At elevated temperatures, both volatile and nonvolatile chemicals from these materials can migrate into foods. An analytical procedure based on headspace gas chromatography and mass selective detection is used to determine volatiles, whereas high-performance liquid chromatography with UV detection is quite suitable for determining PET oligomers and adhesive plasticizers. A general scheme for conducting high temperature cooking simulations and migration studies is described and a summary of typical migration data is presented.
Substitution of valine-865 by methionine or leucine in the human androgen receptor causes complete or partial androgen insensitivity, respectively with distinct androgen receptor phenotypes. (1993)

We have identified two different single nucleotide missense substitutions at valine-865 in exon 7 of the human androgen receptor (AR) gene in two families with androgen resistance. Val-->methionine is associated with the complete syndrome; Val-->leucine is associated with the partial form. In genital skin fibroblasts, both alterations yield a normal maximum binding capacity, but an increased apparent equilibrium dissociation constant for all androgens tested. In genital skin fibroblasts, Val865-Met A-R complexes have increased rate constants of dissociation with 5 alpha-dihydrotestosterone, and the nonmetabolized ligands methyltrienolone or mibolerone (MB); their Val865-Leu counterparts have increased rates with methyltrienolone and MB, but not with 5 alpha-dihydrotestosterone. In transiently transfected COS-1 or PC-3 cells, Met865 AR is more severely impaired than Leu865 AR in transactivating two different androgen-responsive reporter constructs, thereby correlating with clinical phenotype. In COS-1 cells exposed to MB for 74 h, this relative impairment correlates with the relative instability of the MB-binding activity of each mutant AR, suggesting that their respective intrinsic transcriptional regulatory competence is normal. Notably, these mutant ARs lose significantly more MB-binding activity than immunoreactivity, suggesting that prolonged MB exposure induces them to adopt a nonbinding state. The position homologous to Val865 in the AR is occupied by Leu or Met in the three steroid receptors closely related to the AR. This indicates the structural subtlety that underlies the steroid-binding activity of different steroid receptors.
Transitions to and from the CD4-Bound Conformation Are Modulated by a Single-Residue Change in the Human Immunodeficiency Virus Type 1 gp120 Inner Domain (2009)

Binding to the primary receptor CD4 induces conformational changes in the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein that allow binding to the coreceptor (CCR5 or CXCR4) and ultimately trigger viral membrane-cell membrane fusion mediated by the gp41 transmembrane envelope glycoprotein. Here we report the derivation of an HIV-1 gp120 variant, H66N, that confers envelope glycoprotein resistance to temperature extremes. The H66N change decreases the spontaneous sampling of the CD4-bound conformation by the HIV-1 envelope glycoproteins, thus diminishing CD4-independent infection. The H66N change also stabilizes the HIV-1 envelope glycoprotein complex once the CD4-bound state is achieved, decreasing the probability of CD4-induced inactivation and revealing the enhancing effects of soluble CD4 binding on HIV-1 infection. In the CD4-bound conformation, the highly conserved histidine 66 is located between the receptor-binding and gp41-interactive surfaces of gp120. Thus, a single amino acid change in this strategically positioned gp120 inner domain residue influences the propensity of the HIV-1 envelope glycoproteins to negotiate conformational transitions to and from the CD4-bound state.
Brain glucose sensing and body energy homeostasis: role in obesity and diabetes (1999)

The brain has evolved mechanisms for sensing and regulating glucose metabolism. It receives neural inputs from glucosensors in the periphery but also contains neurons that directly sense changes in glucose levels by using glucose as a signal to alter their firing rate. Glucose-responsive (GR) neurons increase and glucose-sensitive (GS) decrease their firing rate when brain glucose levels rise. GR neurons use an ATP-sensitive K+ channel to regulate their firing. The mechanism regulating GS firing is less certain. Both GR and GS neurons respond to, and participate in, the changes in food intake, sympathoadrenal activity, and energy expenditure produced by extremes of hyper- and hypoglycemia. It is less certain that they respond to the small swings in plasma glucose required for the more physiological regulation of energy homeostasis. Both obesity and diabetes are associated with several alterations in brain glucose sensing. In rats with diet-induced obesity and hyperinsulinemia, GR neurons are hyporesponsive to glucose. Insulin-dependent diabetic rats also have abnormalities of GR neurons and neurotransmitter systems potentially involved in glucose sensing. Thus the challenge for the future is to define the role of brain glucose sensing in the physiological regulation of energy balance and in the pathophysiology of obesity and diabetes.
Human monoclonal antibody with dual GM2/GD2 specificity derived from an immunized melanoma patient. (1990)

GM2 ganglioside is a common cell surface constituent of human melanoma and other tumors of neuroectodermal origin, and vaccination with GM2 ganglioside results in high levels of anti-GM2 antibodies in patients with melanoma. Lymphocytes from a GM2-vaccinated patient (VS) were transformed by Epstein-Barr virus and tested for production of antibodies with reactivity for GM2-positive tumor cells. A high percentage of antibody-producing B cells was detected, but antibody reactivity was generally lost during culture expansion. Two cultures, however, remained stable for antibody productivity and one was used to develop a stable hybrid line with mouse myeloma. The monoclonal antibody (designated 3-207) derived from patient VS has dual specificity for GM2 and GD2, despite the fact that only GM2 antibody could be detected in the patient's serum. Monoclonal antibody 3-207 shows high-titered reactivity with a range of melanoma, astrocytoma, neuroblastoma, and leukemia cell lines, cells with prominent cell surface expression of GM2 and GD2. The cell surface reactivity of monoclonal antibody 3-207 was not abolished by treatment of target cells with neuraminidase, as the enzyme converted GD2 to GM2, which was still detected by monoclonal antibody 3-207.
Detection of a glycosylated subunit in human serum ferritin (1981)

Ferritin was purified from the serum of two patients with idiopathic haemochromatosis. The protein contained three types of subunit--the H and L subunits of tissue ferritins (although only a trace of H could be detected) and a third subunit, 'G', with the highest apparent molecular weight. Only the 'G' subunit band stained for carbohydrate, indicating that a proportion of the subunits of human serum ferritin are glycosylated. Although serum was obtained from patients with idiopathic haemochromatosis, it is probable that the 'G' subunit is a component of normal serum ferritin.
Computer modelling of the receptor-binding domains of VEGF and PIGF (1997)

Models of the platelet-derived growth factor (PDGF)-like domains of vascular endothelial growth factor (VEGF) and placenta growth factor (PIGF) were built based on their homology to PDGF. These domains contain most of the determinants for receptor binding. The sequences of these proteins exhibit limited but significant homology to that of platelet-derived growth factor (PDGF), a member of the cystine knot growth factor family. The eight cysteine residues that are involved in intra- and interchain disulphide bonds are conserved. Two high affinity receptors for VEGF have been identified, only one of which binds PIGF. The models presented here are consistent with results that show that VEGF receptor binding is mediated by charged residues in the loops. A comparison of the models suggests that the difference in receptor-binding specificity between VEGF and PIGF may be due to differences in the distribution of positively charged residues and the exposure of hydrophobic residues in the loops.
The oral DPP‐4 inhibitor linagliptin significantly lowers HbA1c after 4 weeks of treatment in patients with type 2 diabetes mellitus (2011)

Linagliptin administration led to attenuation of postprandial glucose excursions and, despite a low HbA1c at baseline, statistically significant reductions in HbA1c after only 4 weeks of treatment. Linagliptin had a safety and tolerability profile similar to placebo in T2DM patients.
A Probiotic Adjuvant Lactobacillus rhamnosus Enhances Specific Immune Responses after Ocular Mucosal Immunization with Chlamydial Polymorphic Membrane Protein C (2016)

Recent advances in the development of chlamydia vaccines, using live-attenuated or ultraviolet light-inactivated chlamydia, are paving the way for new possibilities to oppose the societal challenges posed by chlamydia-related diseases, such as blinding trachoma. An effective subunit vaccine would mitigate the risks associated with the use of a whole-cell vaccine. Our rationale for the design of an efficient subunit vaccine against Chlamydia trachomatis (Ct) is based on the membrane proteins involved in the initial Ct-host cell contact and on the route of immunization that mimics the natural infection process (i.e., via the ocular mucosa). The first aim of our study was to characterize the specific conjunctival and vaginal immune responses following eye drop immunization in BALB/c mice, using the N-terminal portion of the Ct serovar E polymorphic membrane protein C (N-PmpC) as the subunit vaccine antigen. Second, we aimed to examine the adjuvant properties of the probiotic Lactobacillus rhamnosus (LB) when formulated with N-PmpC. N-PmpC applied alone stimulated the production of N-PmpC- and Ct serovar B-specific antibodies in serum, tears and vaginal washes, whereas the combination with LB significantly enhanced these responses. The N-PmpC/LB combination initiated a T cell response characterized by an elevated percentage of CD25+ T cells and CD8+ effector T cells, enhanced CD4+ T-helper 1 skewing, and increased regulatory T cell responses. Together, these results show that eye drop vaccination with combined use of N-PmpC and a live probiotic LB stimulates specific cellular and humoral immune responses, not only locally in the conjunctiva but also in the vaginal mucosa, which could be a promising approach in Ct vaccine development.
Single-body lensed-fiber scanning probe actuated by magnetic force for optical imaging (2009)

We propose a fiber-based hand-held scanning probe suitable for the sample arm of an optical imaging system including optical coherence tomography. To achieve compactness, a single-body lensed-fiber and a solenoid actuator were utilized. The focusing lens of the probe was directly formed onto the distal end of a fiber, which eliminated the need for additional optical components and optical alignment. A ferromagnetic iron bead was glued onto the middle of the fiber to enable actuation by magnetic force, which allowed easy fabrication and good practicality. The fiber piece having the built-in fiber lens was forced to oscillate in its resonant frequency. With the implemented probe, optical coherence tomography images of a human fingertip and a pearl were obtained at an imaging speed of 30 frames/s over a scanning range of 4 mm.
HEMCAM, an adhesion molecule expressed by c-kit+ hemopoietic progenitors. (1996)

We have characterized the adhesion molecule HEMCAM, which is expressed by hemopoietic progenitors of embryonic bone marrow. HEMCAM belongs to the immunoglobulin superfamily and consists of the V-V-C2-C2-C2 Ig domains. There are three mRNA splice variants. One has a short cytoplasmic tail; another has a long tail; while the third seems to lack transmembrane and cytoplasmic regions. Except for the NH2-terminal sequence, HEMCAM is identical to gicerin, a molecular involved in neurite outgrowth and Wilm's kidney tumor progression in the chicken and it is significantly homologous with MUC18 a molecule involved in melanoma progression and metastasis in human beings. In the bone marrow the HEMCAM+ cell population contains c-kit+ subsets. HEMCAM+ cells coexpressing the receptor tyrosine kinase c-kit give rise to T cells at a frequency of 0.17 when injected intrathymically in congenic animals. As HEMCAM+, c-kit+ cells differentiate into myeloid and erythroid CFU's the double-positive cell population seems to contain precursors for multiple lineages. HEMCAM promotes cell-cell adhesion of transfected cells. Cross-linking of murine HEMCAM leads to cell spreading of T-lymphocyte progenitors adhering to the vascular adhesion molecules, PECAM-1 and VCAM-1. Thus, HEMCAM is likely to be involved in cellular adhesion and homing processes.
Channel routing in Manhattan-diagonal model (2002)

This paper presents a new technique of channel routing based on the Manhattan-Diagonal (MD) model. The layout grid is assumed to consist of two layers with tracks in horizontal, vertical and /spl plusmn/45/spl deg/ directions. First, we consider the non-overlap model and present a simple O(l,d) time algorithm that routes an arbitrary channel with no cyclic vertical constraints in w tracks, where l is the length of the channel, d is the channel density, and d/spl les/w/spl les/(d+1). Next, we describe an output-sensitive algorithm that can route general channels with cyclic vertical constraints using w tracks, in O(l,w) time allowing overlapping of wiring segments in two layers. The router outputs an 18-track solution for the Deutsch's difficult example, a 2-track solution for Burstein's difficult channel, and a 15-track solution for cycle.tough without inserting any extra row or column. Apart from quick termination, the proposed algorithms provide solutions with significantly low via count and reduced wire length. The study thus reveals the superiority of MD-routing strategy to classical techniques.
Retrovirally Transduced Mouse Dendritic Cells Require CD4+ T Cell Help to Elicit Antitumor Immunity: Implications for the Clinical Use of Dendritic Cells (2000)

Presentation of MHC class I-restricted peptides by dendritic cells (DCs) can elicit vigorous antigen-specific CTL responses in vivo. It is well established, however, that T cell help can augment CTL function, raising the question of how best to present tumor-associated MHC class I epitopes to induce effective tumor immunity. To this end, we have examined the role of MHC class II peptide-complexes present on the immunizing DCs in a murine melanoma model. To present MHC class I- and II-restricted Ags reliably on the same cell, we retrovirally transduced bone marrow-derived DCs with the model Ag OVA encoding well-defined class I- and II-restricted epitopes. The importance of CD4+ T cells activated by the immunizing DCs in this model is demonstrated by the following findings: 1) transduced DCs presenting class I and class II epitopes are more efficient than class I peptide-pulsed DCs; 2) MHC class II-deficient DCs fail to induce tumor protection; 3) CD4+ T cell depletion abolishes induction of tumor protection; and 4) DCs presenting bovine serum Ags are more effective in establishing tumor immunity than DCs cultured in syngeneic serum. When MHC class II-deficient DCs were directly activated via their CD40 receptor, we indeed observed a moderate elevation of OVA-specific CTL activity. However, this increase in CTL activity was not sufficient to induce in vivo tumor rejection. Thus, our results demonstrate the potency of genetically modified DCs that express both MHC class I and II epitopes, but caution against the use of DCs presenting only the former.
Polyanhydride microspheres. IV. Morphology and characterization of systems made by spray drying (1992)

Abstract The morphology of bioerodible polyanhydride microspheres produced by spray drying is described. Microspheres prepared from a variety of homo‐ and copolymers were studied and characterized using X‐ray powder diffraction, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Crystalline polymers, such as poly(sebacic anhydride) (P(SA)) and poly(fumaric acid) (P(FA)), yielded microspheres with a crenelated and porous surface, as judged by SEM. Polymers, with lower crystallinity, such as copolymers of carboxyphenoxypropane and sebacic acid P(CPP‐SA), yielded microspheres with a smooth external surface. Polymer crystallinity decreased after spray drying, for both blank and drug loaded microspheres.