gebhart/patrepeval huggingface dataset:
Active Conformation of the Erythropoietin Receptor (2006)

In the absence of erythropoietin (Epo) cell surface Epo receptors (EpoR) are dimeric; dimerization is mediated mainly by the transmembrane domain. Binding of Epo changes the orientation of the two receptor subunits. This conformational change is transmitted through the juxtamembrane and transmembrane domains, leading to activation of JAK2 kinase and induction of proliferation and survival signals. To define the active EpoR conformation(s) we screened libraries of EpoRs with random mutations in the transmembrane domain and identified several point mutations that activate the EpoR in the absence of ligand, including changes of either of the first two transmembrane domain residues (Leu(226) and Ile(227)) to cysteine. Following this discovery, we performed cysteine-scanning mutagenesis in the EpoR juxtamembrane and transmembrane domains. Many mutants formed disulfide-linked receptor dimers, but only EpoR dimers linked by cysteines at positions 223, 226, or 227 activated EpoR signal transduction pathways and supported proliferation of Ba/F3 cells in the absence of cytokines. These data suggest that activation of dimeric EpoR by Epo binding is achieved by reorienting the EpoR transmembrane and the connected cytosolic domains and that certain disulfide-bonded dimers represent the activated dimeric conformation of the EpoR, constitutively activating downstream signaling. Based on our data and the previously determined structure of Epo bound to a dimer of the EpoR extracellular domain, we present a model of the active and inactive conformations of the Epo receptor.
Low Titer Group O Whole Blood in Emergency Situations (2014)

In past and ongoing military conflicts, the use of whole blood (WB) as a resuscitative product to treat trauma-induced shock and coagulopathy has been widely accepted as an alternative when availability of a balanced component-based transfusion strategy is restricted or lacking. In previous military conflicts, ABO group O blood from donors with low titers of anti-A/B blood group antibodies was favored. Now, several policies demand the exclusive use of ABO group-specific WB. In this short review, we argue that the overall risks, dangers, and consequences of "the ABO group-specific approach," in emergencies, make the use of universal group O WB from donors with low titers of anti-A/B safer. Generally, risks with ABO group-specific transfusions are associated with in vivo destruction of the red blood cells transfused. The risk with group O WB is from the plasma transfused to ABO-incompatible patients. In the civilian setting, the risk of clinical hemolytic transfusion reactions (HTRs) due to ABO group-specific red blood cell transfusions is relatively low (approximately 1:80,000), but the consequences are frequently severe. Civilian risk of HTRs due to plasma incompatible transfusions, using titered donors, is approximately 1:120,000 but usually of mild to moderate severity. Emergency settings are often chaotic and resource limited, factors well known to increase the potential for human errors. Using ABO group-specific WB in emergencies may delay treatment because of needed ABO typing, increase the risk of clinical HTRs, and increase the severity of these reactions as well as increase the danger of underresuscitation due to lack of some ABO groups. When the clinical decision has been made to transfuse WB in patients with life-threatening hemorrhagic shock, we recommend the use of group O WB from donors with low anti-A/B titers when logistical constraints preclude the rapid availability of ABO group-specific WB and reliable group matching between donor and recipient is not feasible.
Prediction of Organic Reaction Outcomes Using Machine Learning (2017)

Computer assistance in synthesis design has existed for over 40 years, yet retrosynthesis planning software has struggled to achieve widespread adoption. One critical challenge in developing high-quality pathway suggestions is that proposed reaction steps often fail when attempted in the laboratory, despite initially seeming viable. The true measure of success for any synthesis program is whether the predicted outcome matches what is observed experimentally. We report a model framework for anticipating reaction outcomes that combines the traditional use of reaction templates with the flexibility in pattern recognition afforded by neural networks. Using 15 000 experimental reaction records from granted United States patents, a model is trained to select the major (recorded) product by ranking a self-generated list of candidates where one candidate is known to be the major product. Candidate reactions are represented using a unique edit-based representation that emphasizes the fundamental transformation from reactants to products, rather than the constituent molecules' overall structures. In a 5-fold cross-validation, the trained model assigns the major product rank 1 in 71.8% of cases, rank ≤3 in 86.7% of cases, and rank ≤5 in 90.8% of cases.
In vivo transfer of gene and oligodeoxynucleotides into skin of fetal rats by incubation in amniotic fluid. (1996)

One of the tools to test an in vitro hypothesis in vivo is transgenic/gene targeting technology. Transgenic technology provides many advantages such as: (1) the study of specific gene function as systemic and developmental effects; and (2) testing of specific gene function chronically. nevertheless, one disadvantage of this technology is the difficulty in tissue-specific targeting of the transgenic expression. Another useful tool is the in vivo gene transfer approach. Therefore, we tested a potential novel model for the study of transgene expression and knock-out using antisense technology. Here, we have demonstrated that incubation of hemagglutinating virus of Japan (HVJ)-liposome complex containing FITC-labeled oligonucleotides in the amniotic fluid of fetal rats resulted in the nuclear localization of fluorescence in the skin (epidermis and dermis). Similarly, transfection of beta-galactosidase gene resulted in positive staining in several surface layers of the skin. Thus, local gene or antisense oligonucleotide transfer approach into the skin may be useful for studying the role of autocrine/paracrine mediators and treating diseases.
Topological Photonic Systems (2018)

Opportunities are growing for the design of photonic systems that are &#8220;topologically protected&#8221; from defects and disorders&#8212;and in which light can be made to propagate in a single preferred direction.
Trial of Calcium to Prevent Preeclampsia (1997)

Calcium supplementation during pregnancy did not prevent preeclampsia, pregnancy-associated hypertension, or adverse perinatal outcomes in healthy nulliparous women.
A novel synthesis of 4-aryl- and 4-heteroarylpyridines via diethyl(4-pyridyl)borane. (1985)

A convenient method for the preparation of 4-aryl- and 4-heteroarylpyridines by the palladium-catalyzed cross-coupling reaction of diethyl (4-pyridyl) borane with aryl and heteroaryl halides is described.
An autumn tale: geriatric rheumatoid arthritis (2017)

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by erosive arthritis and systemic organ involvement. The disease may affect all ages and both sexes; usually it is seen in young women aged 25-45. Recent studies have shown that RA is among the most common inflammatory disease in older age groups. While elderly-onset rheumatoid arthritis (EORA) is still discussed in the literature, it is generally accepted as a disease beginning after 65 years of age. Compared with young-onset rheumatoid arthritis (YORA), it was found that EORA had different characteristics. EORA is characterized by more equal gender distribution, higher frequency of acute onset with constitutional symptoms, more frequent involvement of large joints, and lower frequency of rheumatoid factor (RF) positivity. Earlier diagnosis, less erosive disease and less disease-modifying antirheumatic drug usage were reported as distinguishing EORA from YORA patients. These various clinical presentations may cause difficulties in diagnosis and differential diagnosis of EORA. However, different clinical and treatment approaches may be needed in these patients. In this article, the clinical and laboratory characteristics, prognosis and treatment principles of EORA will be discussed in light of recent literature data.
Molecular-Level Functional Magnetic Resonance Imaging of Dopaminergic Signaling (2014)

We demonstrate a technique for mapping brain activity that combines molecular specificity and spatial coverage using a neurotransmitter sensor detectable by magnetic resonance imaging (MRI). This molecular functional MRI (fMRI) method yielded time-resolved volumetric measurements of dopamine release evoked by reward-related lateral hypothalamic brain stimulation of rats injected with the neurotransmitter sensor. Peak dopamine concentrations and release rates were observed in the anterior nucleus accumbens core. Substantial dopamine transients were also present in more caudal areas. Dopamine-release amplitudes correlated with the rostrocaudal stimulation coordinate, suggesting participation of hypothalamic circuitry in modulating dopamine responses. This work provides a foundation for development and application of quantitative molecular fMRI techniques targeted toward numerous components of neural physiology.
Intraluteal Prostaglandin Biosynthesis and Signaling Are Selectively Directed Towards PGF2alpha During Luteolysis but Towards PGE2 During the Establishment of Pregnancy in Sheep1 (2012)

In ruminants, endometrial prostalgandin (PG) F(2alpha) causes functional luteolysis, whereas luteal synthesis of PGF(2alpha) is required for structural luteolysis. PGE(2) is considered to be a luteoprotective mediator. Molecular aspects of luteal PGF(2alpha) and PGE(2) biosynthesis and signaling during the estrous cycle and establishment of pregnancy are largely unknown. The objectives of the present study were 1) to determine the regulation of proteins involved in PGF(2alpha) and PGE(2) biosynthesis, catabolism, transport and signaling in the corpus luteum (CL); 2) to investigate the transport of interferon tau (IFNT), PGF(2alpha), and PGE(2) from the uterus to the ovary through the vascular utero-ovarian plexus (UOP); and 3) to compare the intraluteal production of PGF(2alpha) and PGE(2) on Days 12, 14, and 16 of the estrous cycle and pregnancy in sheep. Our results indicate that luteal PG biosynthesis is selectively directed towards PGF(2alpha) at the time of luteolysis and towards PGE(2) during the establishment of pregnancy. Moreover, the ability of the CL of early pregnancy to resist luteolysis is due to increased intraluteal biosynthesis of PGE(2) and PGE(2) receptor (PTGER) 2 (also known as EP2)- and PTGER4 (also known as EP4)-mediated signaling. We also found that IFNT protein is not transported through the UOP from the uterus to the ovary; in contrast, a large proportion of endometrial PGE(2) is transported from the uterus to the ovary through the UOP. These results indicate that endometrial PGE(2) stimulated by pregnancy is transported locally to the ovary, which increases luteal PGE(2) biosynthesis and hence activates luteal PTGER2 and PTGER4 signaling, thus protecting the CL during the establishment of pregnancy in sheep.
Inhibition of Tyrosine Phosphorylation Prevents Delayed Neuronal Death following Cerebral Ischemia (1993)

Protein tyrosine phosphorylation plays an important role in the regulation of neuronal function. We examined the effects of inhibition of tyrosine phosphorylation on ischemic neuronal damage in the CA 1 region of the hippocampus. In the gerbil hippocampus, genistein and lavendustin A, tyrosine kinase inhibitors, were administered 30 min before initiation of 5-min ischemia and reperfusion. Both genistein and lavendustin A blocked tyrosine phosphorylation and prevented delayed neuronal death (DND). However, genistin, an inactive analogue of genistein, did not block DND. Genistein was dose-dependent in the inhibition of DND after ischemia and reperfusion. Administration of genistein 5 to 10 min after ischemia and reperfusion was ineffective in blocking DND in the CA 1 region of the hippocampus. The tyrosine kinase inhibitors selectively blocked the phosphorylation of microtubule-associated protein (MAP)-2 kinase following ischemia and reperfusion injury. These results suggest that tyrosine phosphorylation in the ischemic brain is important for neuronal injury and that MAP-2 kinase may play a role in the onset of delayed neuronal death.
Enhanced revascularization of the ischemic limb by angiogenic therapy. (1993)

The data clearly indicate that an angiogenic growth factor, endothelial cell growth factor, promotes revascularization in this experimental ischemic hindlimb model, raising the possibility that in the future such agents might be of value in humans.
Content based file type detection algorithms (2003)

Identifying the true type of a computer file can be a difficult problem. Previous methods of file type recognition include fixed file extensions, fixed "magic numbers" stored with the files, and proprietary descriptive file wrappers. All of these methods have significant limitations. This paper proposes algorithms for automatically generating "fingerprints" of file types based on a set of known input files, then using the fingerprints to recognize the true type of unknown files based on their content, rather than metadata associated with them. Recognition is performed by three different algorithms based on: byte frequency analysis, byte frequency cross-correlation analysis, and file header/trailer analysis. Tests were run to measure the accuracy of these algorithms. The accuracy varied from 23% to 96% depending upon which algorithm was used. These algorithms could be used by virus scanning packages, firewalls, intrusion detection systems, forensic analyses of computer hard drives, Web browsers, or any other program that needs to identify the types of files for proper operation. File type detection is also important to the operating systems for correct identification and handling of files regardless of file extension.
Mining Critical Metals and Elements from Seawater: Opportunities and Challenges (2015)

The availability and sustainable supply of technology metals and valuable elements is critical to the global economy. There is a growing realization that the development and deployment of the clean energy technologies and sustainable products and manufacturing industries of the 21st century will require large amounts of critical metals and valuable elements including rare-earth elements (REEs), platinum group metals (PGMs), lithium, copper, cobalt, silver, and gold. Advances in industrial ecology, water purification, and resource recovery have established that seawater is an important and largely untapped source of technology metals and valuable elements. This feature article discusses the opportunities and challenges of mining critical metals and elements from seawater. We highlight recent advances and provide an outlook of the future of metal mining and resource recovery from seawater.
Laminin and its neurite outgrowth‐promoting domain in the brain in Alzheimer's disease and Down's syndrome patients (1992)

Immunocytochemistry, radioimmunoassay, immunoblotting, Northern analysis, and polymerase chain reaction (PCR) technique were applied to investigate the distribution of laminin and its neurite outgrowth domain in brains of neuropathologically verified cases of Alzheimer's disease and Down's syndrome. New antibodies against a neurite outgrowth domain of laminin were characterized and were used in localization of this peptide antigen in the human brain. Laminin was found as large punctate deposits in all plaques in the affected brains. Laminin synthesis was increased as assessed by RNA blotting and immunoblotting, and glial cells were heavily immunoreactive with antibodies for a neurite outgrowth-promoting peptide antigen of the B2 chain of laminin. This peptide antigen not only was produced by glial cells but also was deposited in the brain tissue. As this peptide antigen promotes neurite outgrowth at low concentrations, and is specifically neurotoxic at high concentrations, it may play a synergistic role with other molecules in inducing the sprouting and neurodegeneration occurring in brains of patients with either Alzheimer's disease or Down's syndrome.
Temperature Influence on the Secondary Structure of Avidin and Avidin−Biotin Complex:  A Vibrational Circular Dichroism Study (2001)

Vibrational absorption and vibrational circular dichroism spectra of avidin with and without d-biotin in phosphate buffer were recorded in the amide I‘ (1800−1600 cm-1) region as a function of temperature. The differences in the unfolding pathway of avidin in the presence and absence of biotin were examined using the curve-fitting results of absorption spectra, and the variable-temperature absorption and VCD spectra. This study reveals, contrary to previous spectroscopic studies, but in agreement with X-ray structural studies, that avidin contains β-sheet structures with turns and bends, but does not contain α-helical structure. Also a cooperative structural transition leading to formation of aggregated antiparallel β-strands, with increasing temperature, has been inferred. In avidin−biotin complex, however, some reversible unfolding of β-sheet structure is noted but a cooperative structural transition has not been noted with increase in temperature. Two-dimensional (2D)-VCD correlation spectroscopy has also been used to analyze the sequence of events in structural unfolding of avidin.
Compression of View on Anonymous Networks—Folded View— (2011)

View is a labeled directed graph containing all information about the network that a party can learn by exchanging messages with its neighbors. View can be used to solve distributed problems on an anonymous network (i.e., a network that does not guarantee that every party has a unique identifier). This paper presents an algorithm that constructs views in a compressed form on an anonymous n-party network of any topology in at most 2n rounds with O(n <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> \log n) bit complexity, where the time complexity (i.e., the number of local computation steps per party) is O(n <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> \log n). This is the first view-construction algorithm that runs in O(n) rounds with polynomial bits complexity. The paper also gives an algorithm that counts the number of nonisomorphic views in the network in O(n <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> \log n) time complexity if a view is given in the compressed form. These algorithms imply that some well-studied problems, including the leader election problem, can deterministically be solved in O(n) rounds with polynomial bit and time complexity on an anonymous n-party network of any topology.
Rapid plasmid DNA sequencing with multiple octamer primers. (1994)

Oligonucleotide walking is an important technique for generating new DNA sequence information. We have developed an efficient sequencing method based on the use of octamer primers, which can potentially simplify and reduce the cost of sequencing. In this procedure the plasmid DNA is thoroughly denatured in the presence of heat and NaOH. Following cooling, the mixture is aliquoted into tubes containing the different octamer primers and neutralized by the addition of HCl. The mixture is then sequenced by a modified Sequenase protocol that involves performing the initial labeling reactions at low temperature (on ice) and the termination reactions at high temperatures (43 degrees C). Analysis of sequencing gels revealed octamer sequencing to be as effective as sequencing with 17-mer primers.
The myeloic related protein MRP8/14 (27E10 antigen)— usefulness as a potential marker for disease activity in ulcerative colitis and putative biological function (1995)

MRP8, MRP14 and their heterodimer MRP8/14 (27E10 antigen) are myeloic related proteins which have been shown to have a major role in inflammatory and immunological responses. In the present study monospecific antibodies against MRPs were used to investigate immunohistochemically the distribution of these proteins in routinely processed bowel tissues from 23 patients with ulcerative colitis (UC). MRP8, MRP14 and their heterocomplex MRP8/14 were demonstrated in the majority of granulocytes and macrophages in tissues of patients with active UC. Furthermore by employing the ELISA technique we measured MRP8/14 serum levels in 62 patients with UC and the results were compared with those for healthy controls. Disease activities were determined by established clinical activity indices. Serum MRP8/14 concentrations were significantly (P < 0.0001) increased in patients with active ulcerative colitis. No enhancement of serum levels were found for MRP14 and MRP8 alone, respectively. The follow-up of individual patients with initially active disease showed a decrease of MRP8/14 serum levels in parallel with clinical improvement following the start of therapy. It is thus concluded that MRP8/14 accurately reflects the degree of disease activity in UC. Further, possible biological function of MRPs seems to be associated with the heterodimeric form (27E10 antigen) rather than with individual proteins. Our morphological results confirm the finding of enhanced MRP8/14 serum levels in patients with active UC.
Advances in High Content Screening for Drug Discovery (2003)

Cell-based target validation, secondary screening, lead optimization, and structure-activity relationships have been recast with the advent of HCS. Prior to HCS, a computational approach to the characterization of the functions of specific target proteins and other cellular constituents, along with whole-cell functions employing fluorescence cell-based assays and microscopy, required extensive interaction among the researcher, instrumentation, and software tools. Early HCS platforms were instrument-centric and addressed the need to interface fully automated fluorescence microscopy, plate-handling automation, and seamless image analysis. HCS has since evolved into an integrated solution for accelerated drug discovery by encompassing the workflow components of assay and reagent design, robust instrumentation for automated fixed-end-point and live cell kinetic analysis, generalized and specific BioApplication software (Cellomics, Pittsburgh, PA) modules that produce information on drug responses from cell image data, and informatics/bioinformatics solutions that build knowledge from this information while providing a means to globalize HCS throughout an entire organization. This review communicates how these recent advances are incorporated into the drug discovery workflow by presenting a real-world use case.