gebhart/patrepeval huggingface dataset:
Improved in vivo anti-tumor effects of IgA-Her2 antibodies through half-life extension and serum exposure enhancement by FcRn targeting (2015)

Antibody therapy is a validated treatment approach for several malignancies. All currently clinically applied therapeutic antibodies (Abs) are of the IgG isotype. However, not all patients respond to this therapy and relapses can occur. IgA represents an alternative isotype for antibody therapy that engages FcαRI expressing myeloid effector cells, such as neutrophils and monocytes. IgA Abs have been shown to effectively kill tumor cells both in vitro and in vivo. However, due to the short half-life of IgA Abs in mice, daily injections are required to reach an effect comparable to IgG Abs. The relatively long half-life of IgG Abs and serum albumin arises from their capability of interacting with the neonatal Fc receptor (FcRn). As IgA Abs lack a binding site for FcRn, we generated IgA Abs with the variable regions of the Her2-specific Ab trastuzumab and attached an albumin-binding domain (ABD) to the heavy or light chain (HCABD/LCABD) to extend their serum half-life. These modified Abs were able to bind albumin from different species in vitro. Furthermore, tumor cell lysis of IgA-Her2-LCABD Abs in vitro was similar to unmodified IgA-Her2 Abs. Pharmacokinetic studies in mice revealed that the serum exposure and half-life of the modified IgA-Her2 Abs was extended. In a xenograft mouse model, the modified IgA1 Abs exhibited a slightly, but significantly, improved anti-tumor response compared to the unmodified Ab. In conclusion, empowering IgA Abs with albumin-binding capacity results in in vitro and in vivo functional Abs with an enhanced exposure and prolonged half-life.
Pathologic Alterations in the Diabetic Neuropathies of Humans (1996)

Pathologic study of nerve tissue is especially useful for the recognition of interstitial events such as inflammation or vascular alterations that cannot be inferred from clinical or electrophysiologic findings and may provide insight into an underlying mechanism or cause. Considerable variation in the natural history and pathologic alterations among diabetic neuropathies suggests that they are heterogeneous. For diabetic polyneuropathy, two mechanisms need to be considered. The first assumes that hyperglycemia induces metabolic derangements that directly affect Schwann cells (or myelin), nodes of Ranvier, or axons. The second assumes that hyperglycemia and metabolic derangement affect the structure and function of endoneurial microvessels, which then induce fiber changes by altering the blood-nerve barrier, inducing hypoxia or ischemia, or by unknown mechanisms. In proximal diabetic neuropathy, there is increasing evidence that the characteristic lesion is an inflammatory (immune) vasculitis that induces ischemic nerve fiber degeneration. Truncal radiculopathy may be due to an inflammatory polyganglionopathy. In cranial nerve III neuropathy, the monophasic course and the pathologic alterations of ischemia suggest that localized vasculitis should be excluded in future cases. Many upper limb mononeuropathies in diabetes mellitus are from carpal tunnel syndrome. Repetitive shear forces, anatomic factors, and excessive stiffness of connective tissues may cause these mononeuropathies.
C5-Epimerase and 2-O-Sulfotransferase Associate in Vitro to Generate Contiguous Epimerized and 2-O-Sulfated Heparan Sulfate Domains (2015)

Heparan sulfate (HS), a complex polysaccharide of the cell surface, is endowed with the remarkable ability to bind numerous proteins and, as such, regulates a large variety of biological processes. Protein binding depends on HS structure; however, in the absence of a template driving its biosynthesis, the mechanism by which protein binding sequences are assembled remains poorly known. Here, we developed a chemically defined 13C-labeled substrate and NMR based experiments to simultaneously follow in real time the activity of HS biosynthetic enzymes and characterize the reaction products. Using this new approach, we report that the association of C5-epimerase and 2-O-sulfotransferase, which catalyze the production of iduronic acid and its 2-O-sulfation, respectively, is necessary to processively generate extended sequences of contiguous IdoA2S-containing disaccharides, whereas modifications are randomly introduced when the enzymes are uncoupled. These data shed light on the mechanisms by which HS motifs are generated during biosynthesis. They support the view that HS structure assembly is controlled not only by the availability of the biosynthetic enzymes but also by their physical association, which in the case of the C5-epimerase and 2-O-sulfotransferase was characterized by an affinity of 80 nM as demonstrated by surface plasmon resonance experiments.
Circulating Tumor Cells in Patients with Breast Cancer Dormancy (2004)

The CTCs that are dying must be replenished every few hours by replicating tumor cells somewhere in the tissues. Hence, there appears to be a balance between tumor replication and cell death for as long as 22 years in dormancy candidates. We conclude that this is one mechanism underlying tumor dormancy.
Transgenerational Epigenetic Effects (2008)

Transgenerational epigenetic effects include all processes that have evolved to achieve the nongenetic determination of phenotype. There has been a long-standing interest in this area from evolutionary biologists, who refer to it as non-Mendelian inheritance. Transgenerational epigenetic effects include both the physiological and behavioral (intellectual) transfer of information across generations. Although in most cases the underlying molecular mechanisms are not understood, modifications of the chromosomes that pass to the next generation through gametes are sometimes involved, which is called transgenerational epigenetic inheritance. There is a trend for those outside the field of molecular biology to assume that most cases of transgenerational epigenetic effects are the result of transgenerational epigenetic inheritance, in part because of a misunderstanding of the terms. Unfortunately, this is likely to be far from the truth.
Mass spectrometry imaging for plant biology: a review (2015)

Mass spectrometry imaging (MSI) is a developing technique to measure the spatio-temporal distribution of many biomolecules in tissues. Over the preceding decade, MSI has been adopted by plant biologists and applied in a broad range of areas, including primary metabolism, natural products, plant defense, plant responses to abiotic and biotic stress, plant lipids and the developing field of spatial metabolomics. This review covers recent advances in plant-based MSI, general aspects of instrumentation, analytical approaches, sample preparation and the current trends in respective plant research.
Electric Hybrid Drive Systems for Passenger Cars and Taxis (1991)

&lt;div class="htmlview paragraph"&gt;Various hybrid drive configurations are described and their advantages and disadvantages for application in passenger cars are discussed; specifically, these are the series hybrid, the parallel hybrid, hybrid drives with added torque and speed, single and two-shaft hybrids.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The Volkswagen and AUDI group has developed different vehicles with hybrid drive for various applications. These vehicles are described and test results are presented on their energy consumption, emissions and driving performance. In conclusion, some considerations are pursued concerning their chances on the market in different scenarios.&lt;/div&gt;
Subcellular localization of low-abundance human immunodeficiency virus nucleic acid sequences visualized by fluorescence in situ hybridization. (1990)

Detection and subcellular localization of human immunodeficiency virus (HIV) were investigated using sensitive high-resolution in situ hybridization methodology. Lymphocytes infected with HIV in vitro or in vivo were detected by fluorescence after hybridization with either biotin or digoxigenin-labeled probes. At 12 hr after infection in vitro, a single intense signal appeared in the nuclei of individual cells. Later in infection, when cytoplasmic fluorescence became intense, multiple nuclear foci frequently appeared. The nuclear focus consisted of newly synthesized HIV RNA as shown by hybridization in the absence of denaturation and by susceptibility to RNase and actinomycin D. Virus was detected in patient lymphocytes and it was shown that a singular nuclear focus also characterizes cells infected in vivo. The cell line 8E5/LAV containing one defective integrated provirus revealed a similar focus of nuclear RNA, and the single integrated HIV genome was unequivocally visualized on a D-group chromosome. This demonstrates an extremely sensitive single-cell assay for the presence of a single site of HIV transcription in vitro and in vivo and suggests that it derives from one (or very few) viral genomes per cell. In contrast, productive Epstein-Barr virus infection exhibited many foci of nuclear RNA per cell.
J wave and hypothermia. (2005)

Hypothermia can result from exposure to a cold environment (e.g., accidental drowning) or it can be induced and used as a brain protection strategy (e.g., therapeutic hypothermia). One common ECG presentation with hypothermia is the J wave, which is related to the altered cellular activities during hypothermia. A case study is used in this article to illustrate the presentation of a J wave with a patient experiencing hypothermia.
Exosomes from acellular Wharton’s jelly of the human umbilical cord promotes skin wound healing (2018)

Exosomes are being enriched in the native niche of the umbilical cord and can enhance wound healing in vivo through their cargo. Exosomes from the acellular gelatinous Wharton's jelly and the cargo protein alpha-2-macroglobulin have tremendous potential as a noncellular, off-the-shelf therapeutic modality for wound healing.
Gene Discovery Provides Clues to Cause of Age-Related Macular Degeneration (2005)

A trio of studies has identified a gene variant that may be responsible for about half of the 15 million age-related macular degeneration (AMD) cases in the United States. The finding also suggests that inflammation plays an important role in the etiology of the disease.
Biomechanical time‐tolerance of fresh cadaveric human spine specimens (1985)

Changes in the biomechanical properties of fresh cadaveric spinal specimens due to long-term freeze storage and long test periods have been investigated. Fresh cadaveric specimens were divided into three groups: Group A specimens were tested fresh on the 1st day and 13 subsequent days; Group B specimens were tested on the 1st day, frozen in sealed bags at -18 degrees C for 21 days, and tested for 13 consecutive days after thawing; and Group C specimens were frozen for up to 232 days and tested for 14 consecutive days after thawing. We could not find any significant differences between the behavior of the three test groups. This implies that freezing and storage, even for long periods, do not significantly alter the physical properties of cadaveric spinal specimens. Concerning the differences observed on a daily basis, the mean value of the maximum displacement for the 1st day did not differ significantly from the corresponding mean value for the 13 consecutive days. This was true for all three groups, although there was some indication that the fresh group specimens showed greater variation than the two frozen groups.
Serum ferritin in hematologic malignancies (1980)

Serum ferritin was measured in a variety of hematologic malignancies at presentation, in remission following therapy, and in relapse. Ferritin was strikingly increased in all acute leukemias at presentation and in relapse, in the blastic crisis of CML, and in smouldering leukemia. Remission in both ALL and ANLL was associated with a reduction of serum ferritin, and this normalization was a function of remission duration. In the malignant lymphomas serum ferritin was related to tumor histology. Highest levels were found in Hodgkin disease and histiocytic lymphoma, normal levels in lymphocytic lymphoma, and intermediate levels in mixed histiocytic-lymphocytic lymphoma. In all cases, remission was associated with normalization of serum ferritin. These correlations suggest that serum ferritin measurements may be of clinical usefulness in the initial evaluation and in the assessment of response to therapy in patients with acute leukemia and malignant lymphoma.
Novel Drug-Delivery Stent (2001)

The first human experience with the new drug-delivery stent showed a minimal amount of neointimal proliferation in the stented segment. Late lumen loss at the reference sites adjacent to the stent was acceptable and predominantly due to plaque proliferation.
Intravascular ultrasound imaging of coronary arteries. Is three layers the norm? (1992)

The intracoronary ultrasound image appearance of young, morphologically normal coronary artery walls is homogeneous without layering. A three-layered appearance suggests the presence of at least 178 microns of intimal thickening and is seen more frequently with advancing age.
Development of the first well-defined tungsten oxo alkyl derivatives supported on silica by SOMC: towards a model of WO3/SiO2 olefin metathesiscatalyst (2010)

A well-defined, silica-supported tungsten oxo alkyl species prepared by the surface organometallic chemistry approach displays high and sustained activity in propene metathesis. Remarkably, its catalytic performances outpace those of the parent imido derivative, underlining the importance of the oxo ligand in the design of robust catalysts.
Polymeric Materials for Microelectronic Applications (1995)

Photophysics, photochemistry, and optical phenomena of polymers for microelectronics are closely related to one another. By using polyimides as typical examples, it is discussed how photophysics such as charge transfer process affects photochemistry such as photosensitivity of polyimides. Photochemistry such as photoisomerization induces the change in refractive indices providing the phase modulation in optical devices. Microstructure of a polymer liquid crystal is also elucidated by fluorescence spectroscopy.
Serum‐free media for cultures of primitive and mature hematopoietic cells (1994)

The in vitro culture of human hematopoietic cells has many research and therapeutic applications. Traditionally, human hematopoietic cultures have been conducted using serum-containing media. The disadvantages inherent in the use of serum could be eliminated by the use of serum-free media. In this review, we summarize and discuss the current status of serum-free media for both mature and immature human hematopoietic cells. The mature hematopoietic cells discussed are of lymphoid (e.g., lymphokine activated killer cells and tumor infiltrating lymphocytes) and myeloid origin (e.g., monocytes/macrophages). The cultures of immature hematopoietic cells discussed are clonogenic and long-term cultures. In addition, we briefly review the types of human hematopoietic cells, their clinical applications, and the basic strategies and components used to formulate serum-free media, Finally, we outline future requirements and directions in the development of serum-free media for primitive hematopoietic cells.
Allergenic cross-reactivities in flea-reactive canine serum samples. (1996)

It is possible that dogs may become sensitized to fleas via exposure to other insects, and flea allergenic dogs may have signs of pruritus, in the absence of fleas, if exposed to cross-reactive insects.
The Carboxy-Terminal Domain of Hsc70 Provides Binding Sites for a Distinct Set of Chaperone Cofactors (1998)

The modulation of the chaperone activity of the heat shock cognate Hsc70 protein in mammalian cells involves cooperation with chaperone cofactors, such as Hsp40; BAG-1; the Hsc70-interacting protein, Hip; and the Hsc70-Hsp90-organizing protein, Hop. By employing the yeast two-hybrid system and in vitro interaction assays, we have provided insight into the structural basis that underlies Hsc70's cooperation with different cofactors. The carboxy-terminal domain of Hsc70, previously shown to form a lid over the peptide binding pocket of the chaperone protein, mediates the interaction of Hsc70 with Hsp40 and Hop. Remarkably, the two cofactors bind to the carboxy terminus of Hsc70 in a noncompetitive manner, revealing the existence of distinct binding sites for Hsp40 and Hop within this domain. In contrast, Hip interacts exclusively with the amino-terminal ATPase domain of Hsc70. Hence, Hsc70 possesses separate nonoverlapping binding sites for Hsp40, Hip, and Hop. This appears to enable the chaperone protein to cooperate simultaneously with multiple cofactors. On the other hand, BAG-1 and Hip have recently been shown to compete in binding to the ATPase domain. Our data thus establish the existence of a network of cooperating and competing cofactors regulating the chaperone activity of Hsc70 in the mammalian cell.
Design and testing of high sensitivity microreceiver coil apparatus for nuclear magnetic resonance and imaging (2001)

We report the design and testing of a nuclear magnetic resonance (NMR) microcoil receiver apparatus, employing solenoidal microreceiver coils of dimensions of tens to hundreds of microns, using applied field of 9 T (proton resonance frequency 383 MHz). For the smallest receiver coils we attain sensitivity sufficient to observe proton NMR with signal to noise (S/N) one in a single scan applied to a ∼10 μm3 (10 fl) water sample, containing 7×1011 total proton spins. We also test the dependence of the S/N on important coil parameters, including coil composition and resistivity, turn spacing, and lead lengths.
Pathologies of temporal difference methods in approximate dynamic programming (2010)

Approximate policy iteration methods based on temporal differences are popular in practice, and have been tested extensively, dating to the early nineties, but the associated convergence behavior is complex, and not well understood at present. An important question is whether the policy iteration process is seriously hampered by oscillations between poor policies, roughly similar to the attraction of gradient methods to poor local minima. There has been little apparent concern in the approximate DP/reinforcement learning literature about this possibility, even though it has been documented with several simple examples. Recent computational experimentation with the game of tetris, a popular testbed for approximate DP algorithms over a 15-year period, has brought the issue to sharp focus. In particular, using a standard set of 22 features and temporal difference methods, an average score of a few thousands was achieved. Using the same features and a random search method, an overwhelmingly better average score was achieved (600,000-900,000). The paper explains the likely mechanism of this phenomenon, and derives conditions under which it will not occur.
Interface Magnetism and Spin Wave Scattering in Ferromagnet-Insulator-Ferromagnet Tunnel Junctions (1998)

Careful tunneling studies in high quality $\mathrm{Co}/{\mathrm{Al}}_{2}{\mathrm{O}}_{3}/{\mathrm{Ni}}_{80}{\mathrm{Fe}}_{20}$ junctions show a junction magnetoresistance (JMR) of 20.2% and 27.1% at 295 and 77 K, respectively, where the latter is in agreement with Julliere's model. The temperature dependence of the JMR can be explained by the temperature dependence of surface magnetization. The decrease of the JMR with increasing dc bias is intrinsic to ferromagnetic junctions. The strong disagreement with recent theories in the low dc bias region can be attributed to magnetic excitations in these junctions, as seen in inelastic tunneling measurements.
A rapid method of cloning functional variable-region antibody genes in Escherichia coli as single-chain immunotoxins. (1990)

We have devised a strategy based on polymerase chain reaction (PCR) for the rapid cloning of functional antibody genes as single-chain immunotoxins. RNA from a hybridoma producing an antibody (OVB3) that reacts with ovarian cancer cells was used as a template to make the first strand of a cDNA. Then a second strand was synthesized and amplified by using two sets of DNA primers that (i) hybridized to the ends of the light- and heavy-chain variable regions, (ii) encoded a linker peptide, and (iii) contained appropriate restriction enzyme sites for cloning. After 30 cycles of PCR, the DNA fragments containing sequences encoding the light- and heavy-chain variable regions were cloned into an Escherichia coli expression vector containing a portion of the Pseudomonas exotoxin gene. Clones encoding recombinant single-chain immunotoxins were expressed in E. coli and the protein product was assessed for its ability to bind to or kill cells bearing the OVB3 antigen. By using this approach it should be possible to rapidly clone the functional variable region sequences of many different antibodies from hybridoma RNA.
Tahara (2006)

Lisa M. Halpern lives in Hartford, CT. The deceased woman described in this article is a fictional composite of some of the women Halpern has encountered while participating in the tahara. Contact author: [email protected]. Reflections is coordinated by Veneta Masson, MA, RN: [email protected].
Melanocortin Receptor 4 Deficiency Affects Body Weight Regulation, Grooming Behavior, and Substrate Preference in the Rat (2011)

Obesity is caused by an imbalance between energy intake and expenditure and has become a major health-care problem in western society. The central melanocortin system plays a crucial role in the regulation of feeding and energy expenditure, and functional loss of melanocortin receptor 4 (MC4R) is the most common genetic cause of human obesity. In this study, we present the first functional Mc4r knockout model in the rat, resulting from an N-ethyl-N-nitrosourea mutagenesis-induced point mutation. In vitro observations revealed impaired membrane-binding and subsequent nonfunctionality of the receptor, whereas in vivo observations showed that functional loss of MC4R increased body weight, food intake, white adipose mass, and changed substrate preference. In addition, intracerebroventricular (ICV) administration of Agouti-Related Protein(79-129) (AgRP(79-129)), an MC4R inverse agonist, or Melanotan-II (MTII), an MC4R agonist, did affect feeding behavior in wild-type rats but not in homozygous mutant rats, confirming complete loss of MC4R function in vivo. Finally, ICV administration of MTII induced excessive grooming behavior in wild-type rats, whereas this effect was absent in homozygous mutant rats, indicating that MTII-induced grooming behavior is exclusively regulated via MC4R pathways. Taken together, we expect that the MC4R rat model described here will be a valuable tool for studying monogenic obesity in humans. More specifically, the relative big size and increased cognitive capacity of rats as compared to mice will facilitate complex behavioral studies and detailed mechanistic studies regarding central function of MC4R, both of which ultimately may help to further understand the specific mechanisms that induce obesity during loss of MC4R function.