gebhart/patrepeval huggingface dataset:
Functional gene expression domains: defining the functional unit of eukaryotic gene regulation (2000)

The term functional domain is often used to describe the region containing the cis acting sequences that regulate a gene locus. "Strong" domain models propose that the domain is a spatially isolated entity consisting of a region of extended accessible chromatin bordered by insulators that have evolved to act as functional boundaries. However, the observation that independently regulated loci can overlap partially or completely raises questions about functional requirements for physically isolated domain structures. An alternative model, the "weak" domain model, proposes that domain structure is determined by the distribution of binding sites for positively acting factors, without a requirement for functional boundaries. The domain would effectively be the region that contains these factor-binding sites. Specificity of promoter-enhancer interactions would play a major role in maintaining the functional autonomy of adjacent genes. Sequences that interfere with these interactions (frequently characterised as insulators) would be selected against if they occurred within the domain but not at the edges, or in the interdomain regions. As a result, insulators would often be found near the borders of domains without necessarily being selected to act as boundaries.
Pharmacokinetics, Safety, and Efficacy of Trastuzumab Administered Every Three Weeks in Combination With Paclitaxel (2003)

Additional investigation of trastuzumab administered every 3 weeks is warranted. In combination with paclitaxel, it is generally well tolerated. Plasma trastuzumab trough levels and clinical response rates compare favorably with those achieved with the standard weekly trastuzumab regimen plus chemotherapy. The presence of trastuzumab does not alter exposure to paclitaxel.
Three-Dimensional Molecular Theory of Solvation Coupled with Molecular Dynamics in Amber (2010)

We present the three-dimensional molecular theory of solvation (also known as 3D-RISM) coupled with molecular dynamics (MD) simulation by contracting solvent degrees of freedom, accelerated by extrapolating solvent-induced forces and applying them in large multi-time steps (up to 20 fs) to enable simulation of large biomolecules. The method has been implemented in the Amber molecular modeling package, and is illustrated here on alanine dipeptide and protein G.
Characterization of Nucleic Acids by Nanopore Analysis (2002)

Single-stranded DNA and RNA molecules in solution can be driven through a nanoscopic pore by an applied electric field. As each molecule occupies the pore, a characteristic blockade of ionic current is produced. Information about length, composition, structure, and dynamic motion of the molecule can be deduced from modulations of the current blockade.
Imaging of layer by layer growth processes during molecular beam epitaxy of GaAs on (111)A substrates by scanning electron microscopy (1998)

When we use a scanning electron microscope-molecular beam epitaxy system with a GaAs (111)A substrate that dramatically improves the flatness of the growing surface, it makes possible detailed observations of the near-equilibrium growth processes of island nucleation, coalescence, and step motion. These observations allow the quantitative analysis of the growth processes based on the standard model of crystal growth. As an example, the Ga adatom surface diffusion length is directly determined from the dependence of measured step velocity on the Ga arrival rate.
The Inflammatory Cascade in Acute Ischemic Renal Failure (2002)

The pathogenesis of human acute ischemic renal failure is complex. Studies in animals have revealed a number of factors that could contribute to the injury associated with acute ischemic renal failure. Despite these discoveries, we have yet to devise a therapeutic regimen that will ameliorate or prevent acute renal failure in humans. Nevertheless we have made great strides in understanding mechanisms that contribute to acute ischemic renal failure. An important component is the contribution of the inflammatory cascade brought about by tissue reperfusion following an ischemic period. This review summarizes recent studies that implicate the inflammatory cells in the development of renal injury associated with acute ischemic renal failure. Because of the complex overlapping pathways involved in the inflammatory cascade, blocking single molecules is unlikely to be successful in reducing renal injury. Rather broadly abrogating the inflammatory cascade is likely to yield the greatest success in the treatment and prevention of acute ischemic renal failure.
A rapid and highly efficient method for preparation of competentEscherichia colicells (1990)

Journal Article A rapid and highly efficient method for preparation of competent Escherichia coli cells Get access A. Nishimura, A. Nishimura * *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Morita, M. Morita 1Kansai Medical University18–89 Uyama-higashi, Hirakata Osaka, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Y. Nishimura, Y. Nishimura Search for other works by this author on: Oxford Academic PubMed Google Scholar Y. Sugino Y. Sugino 1Kansai Medical University18–89 Uyama-higashi, Hirakata Osaka, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 20, 25 October 1990, Page 6169, https://doi.org/10.1093/nar/18.20.6169 Published: 25 October 1990 Article history Received: 02 July 1990 Published: 25 October 1990
Alterations of Rb Pathway Components Are Frequent Events in Patients with Oral Epithelial Dysplasia and Predict Clinical Outcome in Patients with Squamous Cell Carcinoma (2005)

Deregulation of the p16/pRb/cyclin D1 pathway is an early event in acquisition of dysplasia, but deregulation of both pRb and p53 pathways is associated with malignant transformation and adverse prognosis in oral tumorigenesis.
Apelin is a positive regulator of ACE2 in failing hearts (2013)

Angiotensin converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system (RAS), catalyzing the conversion of Angiotensin II to Angiotensin 1-7. Apelin is a second catalytic substrate for ACE2 and functions as an inotropic and cardioprotective peptide. While an antagonistic relationship between the RAS and apelin has been proposed, such functional interplay remains elusive. Here we found that ACE2 was downregulated in apelin-deficient mice. Pharmacological or genetic inhibition of angiotensin II type 1 receptor (AT1R) rescued the impaired contractility and hypertrophy of apelin mutant mice, which was accompanied by restored ACE2 levels. Importantly, treatment with angiotensin 1-7 rescued hypertrophy and heart dysfunctions of apelin-knockout mice. Moreover, apelin, via activation of its receptor, APJ, increased ACE2 promoter activity in vitro and upregulated ACE2 expression in failing hearts in vivo. Apelin treatment also increased cardiac contractility and ACE2 levels in AT1R-deficient mice. These data demonstrate that ACE2 couples the RAS to the apelin system, adding a conceptual framework for the apelin-ACE2-angiotensin 1-7 axis as a therapeutic target for cardiovascular diseases.
Gradient Flow in Recurrent Nets: the Difficulty of Learning Long-Term Dependencies (2001)

Introduction Recurrent networks (crossreference Chapter 12) can, in principle, use their feedback connections to store representations of recent input events in the form of activations. The most widely used algorithms for learning what to put in short-term memory, however, take too much time to be feasible or do not work well at all, especially when minimal time lags between inputs and corresponding teacher signals are long. Although theoretically fascinating, they do not provide clear practical advantages over, say, backprop in feedforward networks with limited time windows (see crossreference Chapters 11 and 12). With conventional &amp;quot;algorithms based on the computation of the complete gradient&amp;quot;, such as &amp;quot;Back-Propagation Through Time&amp;quot; (BPTT, e.g., [22, 27, 26]) or &amp;quot;Real-Time Recurrent Learning&amp;quot; (RTRL, e.g., [21]) error signals &amp;quot;flowing backwards in time&amp;quot; tend to either (1) blow up or (2) vanish: the temporal evolution of the backpropagated error exponentially depends on the size of th
Simulation modeling and optimization using ProModel (1999)

The ProModel Optimization Suite is a powerful yet easyto-use simulation tool for modeling all types of manufacturing systems ranging from small job shops and machining cells to large mass production, flexible manufacturing systems, and supply chain systems. ProModel is a Windows based system with an intuitive graphical interface and object-oriented modeling constructs that eliminate the need for programming. It combines the flexibility of a general-purpose simulation language with the convenience of a data-driven simulator. In addition, ProModel utilizes an optimization tool called SimRunner that performs sophisticated " what-if" analysis by running automatic factorial design of experiments on the model, providing the best answer possible. This paper provides an overview of the ProModel Optimization Suite and presents its modeling, analysis, and optimization capabilities.
The dissociation of NO from nitrosylhemoglobin. (1978)

The reaction between nitrosylhemoglobin and an excess of deoxymyoglobin has been used to study the kinetics of ligand dissociation from Hb4(NO)4 and Hb4(no)1 species. The kinetics of the dissociation of the first NO molecule from Hb4(no)4 was studied by the ligand replacement method. The results indicate that: (a) the ligand dissociation reaction in Hb4(NO)4 is a cooperative process. This is consistent with the results of Moore and Gibson (Moore, E.G., and Gibson, Q.H. (1977) J. Biol. Chem. 251, 2788-2794). (b) alpha and beta chains in the T state formed by adding IHP to Hb4(NO)4 show kinetic heterogeneity. (c) A similar kinetic heterogeneity is shown by alpha and beta chains in the species Hb4NO in the absence of IHP.(d) The value for the NO dissociation rate constant calculated from the slow phases observed in (b) and (c) is similar to that estimated for the R state. These results suggest that the R to T transition brought about with or without inositol hexaphosphate changes the ligand affinity of one type of the chains much more than of the other. On the basis of IR and EPR studies, it is suggested that alpha chains undergo larger functional changes in R to T transition (or vice versa) in nitrosylhemoglobin. The kinetic parameters for HbNO are compared with those of HbO2 and HbCO and the implications of the results for the reaction mechanism are discussed.
Private genome analysis through homomorphic encryption (2015)

The performance numbers for BGV are better than YASHE when homomorphically evaluating deep circuits (like the Hamming distance algorithm or approximate Edit distance algorithm). On the other hand, it is more efficient to use the YASHE scheme for a low-degree computation, such as minor allele frequencies or χ2 test statistic in a case-control study.
Comparison of Surface Markers between Human and Rabbit Mesenchymal Stem Cells (2014)

This study investigated whether there are marked differences in surface markers between rabbit and human mesenchymal stem cells (MSCs). Murine and rabbit MSCs have been reported to be CD90-negative. Rat MSCs have been reported to be CD71-negative. Our previous study also shows that rabbit MSCs are CD29-negative. However, human MSCs are generally considered to be CD29-, CD71-, and CD90-positive. Therefore, the surface markers of human MSCs might differ from those of other species. Rabbit bone marrow MSCs were obtained that had a multi-differentiation potential. The phenotype of these cells was studied using flow cytometry antibodies for 25 rabbit surface markers, namely, CD13, CD14, CD29, CD31, CD34, CD44, CD45, CD49d, CD49f, CD51, CD54, CD59, CD71, CD73, CD90, CD105, CD106, CD133, CD166, MHC I, MHC II, α-smooth muscle actin (α-SMA), cytokeratin, desmin, and vimentin. The phenotype of commercially available human MSCs was similarly studied using antibodies for human surface markers. CD14, CD31, CD34, CD45, CD49d, CD49f, CD51, CD54, CD71, CD106, CD133, MHC II, and cytokeratin were absent from both rabbit and human MSCs, while CD44, α-SMA, and vimentin were present on both cell lines. CD13, CD29, CD59, CD73, CD90, CD105, CD166, and MHC I were present on human MSCs, but not on rabbit MSCs. However, desmin was present on rabbit MSCs, but not on human MSCs. In total, the surface expression of nine markers differed between human and rabbit MSCs, whereas the surface expression of 16 markers was the same in the two cell lines.
Platelets Support Extracellular Sialylation by Supplying the Sugar Donor Substrate (2014)

Sizable pools of freely circulating glycosyltransferases are in blood, but understanding their physiologic contributions has been hampered because functional sources of sugar donor substrates needed to drive extracellular glycosylation have not been identified. The blood-borne ST6Gal-1 produced and secreted by the liver is the most noted among the circulatory glycosyltransferases, and decorates marrow hematopoietic progenitor cells with α2,6-linked sialic acids and restricts blood cell production. Platelets, upon activation, secrete a plethora of bioactive molecules including pro- and anti-inflammatory mediators. Cargos of sugar donor substrates for glycosyltransferase activity have also been reported in platelets. Here, we implemented a cell-based system to interrogate platelets for their ability to deliver effectively the sugar donor substrate for extracellular ST6Gal-1 to function. We report that thrombin-activated platelets, at physiologic concentration and pH, can efficiently and effectively substitute for CMP-sialic acid in extracellular ST6Gal-1-mediated sialylation of target cell surfaces. Activated platelets can also supply the sialic acid donor to sialylate the synthetic acceptor, Gal(β1,4)GlcNAcα-o-benzyl, with the product Sia(α2,6)Gal(β1,4)GlcNAcα-o-benzyl structurally confirmed by LC/MS. Platelet-secreted donor substrate was recovered in the 100,000 × g sediment, strongly suggesting the association of this otherwise soluble substrate, putatively CMP-sialic acid, within platelet microparticles. Sequestration within microparticles may facilitate delivery of glycosylation substrate at effective dosages to sites of extracellular glycosylation while minimizing excessive dilution.
Math1 : An Essential Gene for the Generation of Inner Ear Hair Cells (1999)

The mammalian inner ear contains the cochlea and vestibular organs, which are responsible for hearing and balance, respectively. The epithelia of these sensory organs contain hair cells that function as mechanoreceptors to transduce sound and head motion. The molecular mechanisms underlying hair cell development and differentiation are poorly understood. Math1, a mouse homolog of the Drosophila proneural gene atonal, is expressed in inner ear sensory epithelia. Embryonic Math1-null mice failed to generate cochlear and vestibular hair cells. This gene is thus required for the genesis of hair cells.
Activation of adenovirus-coded protease and processing of preterminal protein (1994)

Adenoviruses code for a protease that is essential for infectivity and is activated by a disulfide-linked peptide, derived from the C terminus of the virus structural protein pVI (pVI-CT). The protease was synthesized at relatively high levels late in infection and was detected in both cytoplasmic and nuclear fractions of adenovirus-infected cells. DNA was not found to be a cofactor of the protease, as previously proposed (W. F. Mangel, W. J. McGrath, D. Toledo, and C. W. Anderson, Nature [London] 361:274-275, 1993), but a role for DNA in facilitating the activation of the protease by pVI-CT in vivo cannot be ruled out. Adenovirus preterminal protein is a substrate for the virus-coded protease, with digestion to the mature terminal protein proceeding via the formation of two intermediates. Each of the three cleavage sites in the preterminal protein was identified by N-terminal sequencing and shown to conform to the substrate specificity of adenovirus protease, (M,L,I)XGX-X. Functional studies revealed that preterminal protein and intermediates but not mature terminal protein associated with adenovirus polymerase, while only the intact preterminal protein and none of its digestion products bound to DNA. These results suggest that the virus-coded protease may influence viral DNA replication by cleavage of both genome-bound and freely soluble preterminal protein, with consequent alterations to their functional properties.
Thia Zip Reaction for Synthesis of Large Cyclic Peptides:  Mechanisms and Applications (1999)

This paper describes the mechanism and application of an efficient thia zip cyclization that involves a series of intramolecular rearrangements in a cysteine-rich peptide for the synthesis of large end-to-end cyclic peptides. Key functional groups required in this reaction include an Nα-cysteine, a thioester, and at least one internal free thiol in a peptide. The zip reaction is initiated by intramolecular transthioesterification through an internal thiol with the thioester. A thiolactone is formed under ring−chain tautomeric equilibrium that favors ring formation in aqueous buffered solution at pH > 7. Successive ring expansions through thiol−thiolactone exchanges in the direction of the amino terminus lead finally to a large Nα-amino thiolactone which then undergoes a spontaneous and irreversible ring contraction through a sequence-independent S to N acyl isomerization to form an end-to-end lactam. The reversible thiolactone exchanges are sequence-dependent, and the rate-determining steps are shown by rate studies on model peptides. The assistance of internal thiols in reducing the ring sizes and hence the entropy of the thiolactone exchanges correlates well with cyclization rates. Zip-assisted end-to-end cyclizations forming 93- and 99-atom rings through a series of small thiolactone intermediates were 60−200-fold faster under strongly denaturing conditions such as 8 M urea than the corresponding unassisted lactamization. The thia zip reaction has been applied successfully to the synthesis of a 31-amino acid cyclic peptide, the naturally occurring cyclopsychotride that shows the antimicrobial activity. In addition, the thia zip reaction also enables the synthesis of an engineered cyclic 33-amino acid animal defensin by replacing the end-to-end disulfide with a lactam, which retains the antimicrobial activities of the native open-chain form.
Molecular Cloning and Identification of -Acyl-D-glucosamine 2-Epimerase from Porcine Kidney as a Renin-binding Protein (1996)

N-Acetylneuraminic acid (NeuAc) is an important molecule in biological recognition systems. NeuAc is known to be biosynthesized either from UDP-N-acetyl-D-glucosamine by an action of UDP-N-acetyl-D-glucosamine 2-epimerase or from N-acetyl-D-glucosamine by N-acyl-D-glucosamine 2-epimerase (GlcNAc 2-epimerase). However, the physiological function of the GlcNAc 2-epimerase in NeuAc biosynthesis has not been fully evaluated. To clarify the role of GlcNAc 2-epimerase in NeuAc biosynthesis, the enzyme and its gene were isolated from porcine kidney cortex. Escherichia coli cells transformed with the gene expressed the GlcNAc 2-epimerase having the same properties as those of the GlcNAc 2-epimerase from porcine kidney. Sequence analysis indicated that the gene was capable of synthesizing a 46.5-kDa protein (402 amino acids) with a conserved leucine zipper motif. Homology search for the cloned gene revealed that the GlcNAc 2-epimerase was identical with renin-binding protein (RnBP) in porcine kidney (Inoue, H., Fukui, K., Takahashi, S., and Miyake, Y.(1990) J. Biol. Chem. 265, 6556-6561) (identity: 99.6% in nucleotide sequence, 99.0% in amino acid sequence). That GlcNAc 2-epimerase is a RnBP was confirmed by its ability to bind porcine kidney renin and mask its protease activity. These findings provide unequivocal evidence that the enzyme GlcNAc 2-epimerase is a RnBP.
Isotopic analysis of Cu in blood serum by multi-collector ICP-mass spectrometry: a new approach for the diagnosis and prognosis of liver cirrhosis? (2015)

The isotopic composition of blood serum Cu has been investigated as a potential parameter for the diagnosis and prognosis of liver cirrhosis. Serum samples from supposedly healthy women (reference population) and from a group of female patients suffering from liver cirrhosis of different etiologies were analysed. The procedure for isolation of serum Cu and the measurement protocol for its isotopic analysis by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) were evaluated. Significant differences in the isotopic composition of Cu were observed between the reference population and the patients. A wide spread in δ(65)Cu was observed within the cirrhosis population and δ(65)Cu seems to be linked to the severity of the disease. Patients with end-stage liver disease showed a significantly lighter serum Cu isotopic composition. Many clinical parameters used for the diagnosis and monitoring of liver diseases, i.e. the levels of aspartate aminotransferase, De Ritis ratio, prothrombin and international normalized ratio, albumin, bilirubin, Na and C-reactive protein, correlate well with the δ(65)Cu values, as did the ceruloplasmin level and the ceruloplasmin/Cu concentration ratio. The isotopic composition of serum Cu appears to reveal the synthetic and hepatocellular function of the liver synergistically with inflammation and fluid retention in the cohort studied. A relevant relationship was also observed between δ(65)Cu and scores of mortality risk, such as the Model for End-stage Liver Disease (MELD) and MELD-Na. Thus, the isotopic composition of serum Cu shows potential as a new approach for the prognosis of liver disease, and although further investigation is required, for evaluation of the mortality risk in end-stage liver disease and prioritization of liver transplants.
A Potential Anti‐Pregnancy Vaccine Built by Conjugation of the β‐Subunit of Human Chorionic Gonadotropin to Adjuvant‐Active Muramyl Peptide (1987)

The beta-subunit of human chorionic gonadotropin (hCG) conjugated to tetanus toxoid is being investigated as a vaccine for human fertility control. Initial clinical trials indicated that the level of antibody response induced by such an immunogen was not always sufficient to prevent pregnancy. Therefore, efforts are being made to evaluate new carriers for the beta-subunit and to select adjuvants to yield a more efficient vaccine. In the present report, we demonstrate that conjugates of the beta-subunit of hCG with muramyl dipeptide (MDP), or its nonpyrogenic derivative murabutide, may have potential as an effective antipregnancy vaccine. The copolymer of beta hCG and MDP administered with Al(OH)3 to mice induced a high anti-beta hCG response, better than that induced by the conjugate of beta hCG to tetanus toxoid given with Al(OH)3. Moreover, the antibodies induced by such an immunogen were competent for neutralizing the biological activity of hCG in vivo. Even more interesting, a copolymer of beta hCG and of murabutide induced high levels of biologically active antibodies. This immunogen may represent a promising candidate for the development of an efficient vaccine for human fertility control.