gebhart/patrepeval huggingface dataset:
Homophilic Interactions Mediated by Receptor Tyrosine Phosphatases μ and κ. A CRITICAL ROLE FOR THE NOVEL EXTRACELLULAR MAM DOMAIN (1995)

The receptor-like protein tyrosine phosphatases (RPTP) mu and RPTP kappa have a modular ectodomain consisting of four fibronectin type III-like repeats, a single Ig-like domain, and a newly identified N-terminal MAM domain. The function of the latter module, which comprises about 160 amino acids and is found in diverse transmembrane proteins, is not known. We previously reported that both RPTP mu and RPTP kappa can mediate homophilic cell interactions when expressed in insect cells. Here we show that despite their striking structural similarity, RPTP mu and RPTP kappa fail to interact in a heterophilic manner. To examine the role of the MAM domain in homophilic binding, we expressed a mutant RPTP mu lacking the MAM domain in insect Sf9 cells. Truncated RPTP mu is properly expressed at the cell surface but fails to promote cell-cell adhesion. Homophilic cell adhesion is fully restored in a chimeric RPTP mu molecule containing the MAM domain of RPTP kappa. However, this chimeric RPTP mu does not interact with either RPTP mu or RPTP kappa. These results indicate that the MAM domain of RPTP mu and RPTP kappa is essential for homophilic cell-cell interaction and helps determine the specificity of these interactions.
Duly diligent utilities (2005)

Increasingly, utilities need to think of their operations as businesses and as such, they are not only in the business of providing raw and drinking water, sewage services and stormwater services, they also need to acquit those operations in a manner consistent and compliant with the jurisdiction in which they operate. In this paper, we discuss the legal frameworks with which utilities should be familiar and show how having comprehensive and defensible risk management systems in place can demonstrate that a utility is conducting its business in a duly diligent fashion.
Interactions between insulin resistance and insulin secretion in the development of glucose intolerance (2000)

Subjects who develop type 2 diabetes have a complex phenotype with defects in insulin secretion, increased hepatic glucose production, and resistance to the action of insulin, all of which contribute to the development of overt hyperglycemia. Although the precise mechanisms whereby these three factors interact to produce glucose intolerance and diabetes are uncertain, it has been suggested that the final common pathway responsible for the development of type 2 diabetes is the failure of the pancreatic β cell to compensate for insulin resistance (1). Here, we review evidence for this model from both human and animal studies, and we consider the effects of specific drug treatments and of heightened FFA levels on insulin sensitivity and insulin secretion in individuals at risk for type 2 diabetes.

Coleman and coworkers (2), drawing on their work with the ob/ob mouse, first proposed that a failure of β-cell compensation for insulin resistance is responsible for the development of type 2 diabetes. When insulin-resistant ob/ob mice, which provide a genetic model of obesity, were bred with mice of different strains, the phenotypes of the progeny differed depending on their genetic background. Mice carrying the ob mutation in the C57BL/6 background had relatively normal blood glucose levels, whereas in the C57Ks background the animals developed overt hyperglycemia. The major difference between these two mouse strains lay in their β-cell responses. The nondiabetic C57BL/6 mice underwent a marked expansion of β-cell mass, whereas C57Ks animals showed histologic evidence of islet degeneration, degranulation, and progressive atrophy. The C57Ks animals accordingly had insulin levels about one-tenth those of the C57BL/6 animals, and these levels declined progressively with age. These data indicated that the genetic background on which insulin resistance develops influences the adequacy of pancreatic β-cell compensation for insulin resistance, and hence the predisposition to diabetes.
Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome (2014)

Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-American-British (FAB) classification and 62 (17.1%) of the 362 patients based on the World Health Organization (WHO) classification. ASXL1 mutation was closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2, SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1-mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1 mutation was an independent poor prognostic factor for survival. Sequential studies showed that the original ASXL1 mutation remained unchanged at disease progression in all 32 ASXL1-mutated patients but were frequently accompanied with acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1, SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild patients, only one acquired ASXL1 mutation at leukemia transformation. In conclusion, ASXL1 mutations in association with other genetic alterations may have a role in the development of MDS but contribute little to disease progression.
Global Identification of Human Transcribed Sequences with Genome Tiling Arrays (2004)

Elucidating the transcribed regions of the genome constitutes a fundamental aspect of human biology, yet this remains an outstanding problem. To comprehensively identify coding sequences, we constructed a series of high-density oligonucleotide tiling arrays representing sense and antisense strands of the entire nonrepetitive sequence of the human genome. Transcribed sequences were located across the genome via hybridization to complementary DNA samples, reverse-transcribed from polyadenylated RNA obtained from human liver tissue. In addition to identifying many known and predicted genes, we found 10,595 transcribed sequences not detected by other methods. A large fraction of these are located in intergenic regions distal from previously annotated genes and exhibit significant homology to other mammalian proteins.
Feedback 360º. ¿Qué piensan de su empresa los clientes, proveedores y empleados? Lo que hay que saber (1998)

An analysis of the results of complex radiation treatment of 153 cases of cancer of the corpus uteri was performed. The five-year survival rate was 65.1%. Stage, histologic pattern of tumor, patient's age and intracavitary radiation technique appeared to be factors of treatment efficacy. Application of 60Co spherical radioactivity sources was followed by a significantly higher 5-year survival than that of linear ones.
Dynamic behavior of hepatitis C virus quasispecies in patients undergoing orthotopic liver transplantation (1994)

We have studied the distribution of viral sequences from the 5' noncoding region and from a fragment of the E2/NS2 region of the hepatitis C virus (HCV) genome in samples obtained before and after liver transplantation in two patients with HCV cirrhosis. The population of viral sequences in both regions were established by sequencing cloned PCR products. In both cases, the complexity of the viral quasispecies decreased after transplantation, although the consensus nucleotide and amino acid sequences remained unchanged. It is suggested that both positive and negative selection and random sampling events contribute substantially in shaping the genetic composition of HCV quasispecies and that recurrence of HCV infection may occur under equilibrium conditions.
Structure and Sequence of the Centromeric DNA of Chromosome 4 in Saccharomyces cerevisiae (1986)

The CEN4 sequences from chromosome 4 that impart mitotic stability to autonomously replicating (ARS) plasmids in yeast cells have been localized to a 1,755-base-pair (bp) fragment. This fragment could be cut in half to give two adjacent, nonoverlapping fragments, that each contained some mitotic stabilization sequences. One of the half-fragments worked as efficiently as the larger fragment from which it was derived, while the other half provided a much poorer degree of mitotic stabilization. Sequencing of 2,095 bp of DNA including this region revealed the presence of a centromere consensus sequence, elements I, II, and III (M. Fitzgerald-Hayes, L. Clarke, and J. Carbon, Cell 29:235-244, 1982), in the half-fragment providing high levels of mitotic stability. The poorly stabilizing half-fragment did not contain any obvious sequence homologies to other centromere sequences. Deletion analysis of the 1,755-bp fragment indicated that removal of the 14-bp element I plus 16 of the 82 bp of element II impaired mitotic stability. Removal of elements I and II eliminated the mitotic stability provided by the consensus sequence.
On The Generalization of Error-Correcting WOM Codes (2007)

WOM (write once memory) codes are codes for efficiently storing and updating data in a memory whose state transition is irreversible. Storage media that can be classified as WOM includes flash memories, optical disks and punch cards. Error-correcting WOM codes can correct errors besides its regular data updating capability. They are increasingly important for electronic memories using MLCs (multi-level cells), where the stored data are prone to errors. In this paper, we study error-correcting WOM codes that generalize the classic models. In particular, we study codes for jointly storing and updating multiple variables - instead of one variable - in WOMs with multi-level cells. The error-correcting codes we study here are also a natural extension of the recently proposed floating codes. We analyze the performance of the generalized error- correcting WOM codes and present several bounds. The number of valid states for a code is an important measure of its complexity. We present three optimal codes for storing two binary variables in n q-ary cells, where n = 1,2,3, respectively. We prove that among all the codes with the minimum number of valid states, the three codes maximize the total number of times the variables can be updated.
Adventure tourists on water: linking expectations, affect, achievement and enjoyment to the adventure (2000)

This exploratory study examined a range of factors that surround participants' experiences in adventure tourism activities. Participants (n=73) engaged in two water-based adventure tourism activities (white-water rafting and sea-kayaking) were categorised into either a low challenge or a high challenge group based on the discrepancy between ratings of post-adventure risk and competence. Significant differences were found between these challenge groups on their expectation of the likelihood of injury in both activities. Further differences were found between the rafting challenge groups on measures of affect (tense and threatened) and the sea-kayaking challenge group on sources of enjoyment (arousal and challenge). Based on these differences, and in consideration of the duration of each activity, adventure tourists are categorised into one of four categories: fearless thrill-seekers, daring thrill-seekers, ecotourists, and competence-testers.
Emergence of α5β1 fibronectin‐ and αvβ3 vitronectin‐receptor expression in melanocytic tumour progression (1994)

Cell adhesion is crucial in the process of tumour progression. As integrins are important receptor molecules involved in cell adhesion, we studied the distribution of the alpha 1-6, alpha v, alpha IIb, beta 1, beta 3, and beta 4 integrin subunits in tissue sections of common naevocellular naevi (n = 22), dysplastic naevi (16), thin (24) and thick primary cutaneous melanomas (28), and melanoma metastases (25). We found correlated expression of alpha 1/alpha 2, of alpha 4/alpha 5/beta 3, and of alpha 6/beta 4. Decrease of alpha 6 and beta 4, and increase of alpha 4 and alpha v were found to be correlated with melanoma progression. Furthermore, expression of alpha 5 and beta 3 was detected only in primary melanoma and melanoma metastasis. Our findings indicate that during melanoma progression alterations in integrin expression occur, the most striking being emergence of alpha 5 beta 1 fibronectin and alpha v beta 3 vitonectin receptor.
Dry powder inhalers for pulmonary drug delivery (2004)

The pulmonary route is an interesting route for drug administration, both for effective local therapy (asthma, chronic obstructive pulmonary disease or cystic fibrosis) and for the systemic administration of drugs (e.g., peptides and proteins). Well-designed dry powder inhalers are highly efficient systems for pulmonary drug delivery. However, they are also complicated systems, the the performance of which relies on many aspects, including the design of the inhaler (e.g., resistance to air flow and the used de-agglomeration principle to generate the inhalation aerosol), the powder formulation and the air flow generated by the patient. The technical background of these aspects, and how they may be tuned in order to obtain desired performance profiles, is reviewed. In light of the technical background, new developments and possibilities for further improvements are discussed.
Transcription by RNA polymerase II: initiator‐directed formation of transcription‐competent complexes 1 (1992)

Studies of transcription by RNA polymerase II have revealed two promoter elements, the TATA motif and the initiator (Inr), capable of directing specific transcription initiation. Although binding to the TATA motif by one of the components of the transcription machinery has been shown to be the initial recognition step in transcription complex formation, many promoters that lack a traditional TATA motif have recently been described. In such TATA-less promoters, the Inr element is critical in positioning RNA polymerase II. Various Inr elements have been described and classified according to sequence homology. These Inr elements are recognized specifically by Inr-binding proteins. Interaction between these Inr-binding proteins and components of the basal transcription machinery provides a means through which a transcription competent complex can be formed.
Inhibiting transcription of chromosomal DNA using antigene RNAs (2005)

Transcription start sites are critical switches for converting recognition of chromosomal DNA into synthesis of RNA. We report that antigene peptide nucleic acid (agPNA) oligomers or antigene RNA (agRNA) duplexes can target transcription start sites and block gene expression. Our data suggest that chromosomal DNA within cells is readily accessible to recognition by synthetic agents. agPNAs and agRNAs will be useful tools for silencing gene expression and will provide insights into natural mechanisms for controlling transcription.
Antitumor effect of a transducible fusogenic peptide releasing multiple proapoptotic peptides by caspase-3 (2008)

We have designed a novel peptide, TK3, composed of three functional domains, a protein transduction domain, a TAT followed by three tandem repeats of a proapoptotic peptide, and a caspase-3 cleavage site, (KLAKLAK)(2)-DEVD. TK3 was able to transduce into cells and then activate caspase-3, which in turn cleaved TK3 to release additional (KLAKLAK)(2) peptides. (KLAKLAK)(2) was well transduced by TAT into tumor cells and was able to induce apoptosis in vitro and in vivo. TK3 also induced apoptosis and inhibited angiogenesis in endothelial cells. Further, direct injection of TK3 into established B16F10 melanoma tumors in C57BL/6 mice resulted in almost complete inhibition of the tumor growth. These results suggest that TK3 could be beneficial for the treatment of accessible tumors and used as an adjuvant for cancer therapy.
Cooling rate dependence of the glass transition temperature of polymer melts: Molecular dynamics study (2002)

A coarse-grained bead spring model of short polymer chains is studied by constant pressure molecular dynamics (MD) simulations. Due to two competing length scales for the length of effective bonds and the energetically preferred distance between nonbonded beads, one observes a glass transition when dense melts are cooled down (as shown in previous work, at a pressure p=1 the mode coupling critical temperature is at Tc≈0.45 and the Vogel–Fulcher temperature is T0≈0.33, in Lennard-Jones units). The present work extends these studies, estimating a cooling-rate-dependent glass transition temperature Tg(Γ) by cooling the model system from T=0.6 down to T=0.3, applying cooling rates from Γ≈10−3 to Γ≈10−6 (in MD time units), and attempting to identify Tg(Γ) from a kink in the volume versus temperature or potential energy versus temperature curves. It is found that Tg(Γ) lies in the range 0.43⩽Tg(Γ)⩽0.47, for the cooling rates quoted, and the variation of Tg(Γ) for Γ is compatible with the expected logarithmic variations. We will show why a detailed distinction between competing theories on these cooling rate effects would need an excessive amount of computer time. To estimate also the melting transition temperature Tm of this model, the sytem was prepared in a crystalline configuration as an initial state and heated up. The onset of diffusion, accompanied by an isotropization of the pressure tensor was observed for Tm≈0.77. This implies that the model is suitable for studying deeply supercooled melts.
Sequence of an intestinal cDNA encoding human gastric inhibitory polypeptide precursor. (1987)

Gastric inhibitory polypeptide (GIP) is a 42-amino acid hormone that stimulates insulin secretion in the presence of glucose. Complementary DNA clones encoding human GIP were isolated from a library prepared with RNA from duodenum. The predicted amino acid sequence indicates that GIP is derived by proteolytic processing of a 153-residue precursor, preproGIP. The GIP moiety is flanked by polypeptide segments of 51 and 60 amino acids at its NH2 and COOH termini, respectively. The former includes a signal peptide of about 21 residues and an NH2-terminal propeptide of 30 amino acids. GIP is released from the precursor by processing at single arginine residues. There is a region of nine amino acids in the COOH-terminal propeptide of the GIP precursor that has partial homology with a portion of chromogranin A as well as pancreastatin.
Post-translational processing of the epidermal growth factor receptor. Glycosylation-dependent acquisition of ligand-binding capacity. (1985)

The post-translational processing of the epidermal growth factor receptor in human A431 epidermoid carcinoma cells has been investigated.By employing the affinity matrix epidermal growth factor Affi-Gel in conjunction with immunoprecipitation, it has been demonstrated that core oligosaccharide addition is essential for the acquisition of epidermal growth factorbinding activity.Furthermore, the initial 160-kDa translation product was observed to undergo a processing step by which ligand-binding activity was acquired with a half-time of approximately 30 min while exhibiting no apparent change in mobility on sodium dodecyl sulfate-polyacrylamide gels.This was shown not to involve the conversion of high-mannose chains to complex chains which have been capped with fucose and sialic acid.Possible explanations for this activation in terms of translocation of intermediates and/or formation of disulfide bonds are discussed.Epidermal growth factor is a peptide hormone which is a potent mitogen for a wide variety of cultured cells.Its biological effects, which are mediated by binding to specific cell-
BMP and activin receptor expression in lens development. (2004)

These results indicate that multiple members of the TGFbeta family have the potential to signal during lens fiber differentiation and suggest there may be cross-talk between different signaling pathways.
Effects of behavioral changes and mixing patterns in mathematical models for smallpox epidemics (2005)

First, we study the effects of behavioral changes in a smallpox attack model. Response strategies to a smallpox bioterrorist attack have focused on interventions such as isolation, contact tracing, quarantine, ring vaccination, and mass vaccination. We formulate and analyze a mathematical model in which some individuals lower their daily contact activity rates once an epidemic has been identified in a community. We use computer simulations to analyze the effects of behavior change alone and in combination with other control measures. We demonstrate that the spread of the disease is highly sensitive to how rapidly people reduce their contact activity. 
Next, we study mixing patterns between age groups using social networks. The course of an epidemic through a population is determined by the interactions among individuals. To capture these elements of reality; we use the contact network simulations for the city of Portland, Oregon that were developed as part of the TRANSIMS/EpiSims project to study and identify mixing patterns. We analyze contact patterns between different age groups and identify those groups who are at higher risk of infection. We describe a new method for estimating transmission matrices that describe the mixing and the probability of transmission between the age groups. Our results show that the mixing structure within the population is divided into two main groups, adults and children. 
Finally, we study the effects of mixing patterns in the presence of population heterogeneity. We investigate the impact that different mixing assumptions have on the spread of a disease in an age-structured differential equation model. We use a realistic mixing population and investigate the impact that this mixing pattern has on epidemic outcomes when compared to a randomly mixing population. Furthermore, we investigate the impact on a smallpox epidemic of population heterogeneity such as differences in susceptibility and infectivity within the population for a smallpox epidemic outbreak. We find that different mixing assumptions lead to differences in disease prevalence and final epidemic size. We also demonstrate that a smallpox epidemic is greatly reduced by the level of residual immunity in the population.
Enzymatic cyclization reactions of geraniol, farnesol and geranylgeraniol, and those of truncated squalene analogs having C20and C25by recombinant squalene cyclase (2004)

The substrate specificity of squalene-hopene cyclase was investigated using the C10-C25 analogs including naturally occurring substances, e.g. geraniol (C10), farnesol (C15) and geranylgeraniol (C20). No cyclization occurred for geraniol, but a significantly high conversion ratio (64%) was observed for farnesol, yielding the cyclic sesquiterpenes consisting of 6/6-fused bicyclic ring systems. Among them, an attractive compound having C30 was produced, in the structure of which acyclic the farnesol unit is linked to the bicyclic skeleton through ether linkage. Conversion of geranylgeraniol was low (ca. 12%). The squalene analogs having C20 and C25 also were cyclized in yields of ca. 33-36%, but the analogs having the methyl group at C7 and/or at C11 underwent no cyclization; the large steric bulk size of C7-Me and/or C11-Me, which is arranged in [small alpha]-disposition for all the pre-chair conformation, would have interacted repulsively with the cyclase recognition site near to the C7 and/or C11, resulting in no construction of the all-chair conformation inside the reaction cavity. A relatively low yield of geranylgeraniol indicated that a less bulky hydrogen atom must be located at C14 for the efficient polycyclization reaction. The squalene cyclase shows remarkably broad substrate specificity to accept the truncated analogs having carbon-chain lengths of C(15)-C25 in addition to C30.