gebhart/patrepeval huggingface dataset:
Phase I study of enzastaurin (ENZ) and bevacizumab (BV) in patients with advanced cancer (2008)

3529 Background: ENZ is an oral kinase inhibitor that suppresses tumor growth through PKC and PI-3 kinase/AKT. BV is a monoclonal antibody that binds VEGF and inhibits angiogenesis. Since ENZ and BV complement each other in inhibiting angiogenesis, we conducted a Phase I study of ENZ and BV in advanced cancer patients (pts). Methods: Eligible pts had advanced cancer, adequate organ function and no co-morbidities suggesting increased risk of drug-related toxicities. Six pts were enrolled per cohort; if ≤ 1 DLT occured the next cohort opened. A treatment cycle consisted of 28 days (Dose Levels [DL] 1, 2 and 2a) or 21 days (DL 3 and 3a). A loading dose of ENZ 1125mg was given on Day 1, Cycle 1 for each cohort. DL 1 consisted of ENZ 500mg po daily and BV 5mg/kg IV on Days 1 and 15 of each cycle. Pts were then alternately assigned to DL 2 (BV 10mg/kg IV on Days 1 and 15) or DL 3 (BV 15mg/kg IV on Day 1 every 21 days). The ENZ dose remained 500mg daily. Additional pts were then alternately assigned to DL 2a (ENZ 250mg bid and BV 10mg/kg IV on Days 1 and 15) or DL 3a (ENZ 250mg bid and BV 15mg/kg IV on Day 1 every 21 days). DLT was defined as any of the following occurring in Cycle 1: Grade (G) 4 neutropenia ≥ 7 days, febrile neutropenia, G 3 thrombocytopenia with bleeding or G 4 thrombocytopenia, G 3 non-hematological toxicities, and toxicities associated with BV. Results: 24 pts (13 with ovarian cancer) are evaluable for toxicity through at least one cycle (6 each at DL 1, 2, 3 and 3 each at DL 2a and 3a). Fifteen are evaluable for response. One DLT (G 3 transaminitis) occurred after the first cycle at DL 2. This resolved after decreasing ENZ for 1 cycle, and the pt continues on study at full doses. No apparent increase in ENZ or BV toxicity was seen. One SAE (deep venous thrombosis) occurred at DL 3 after 3 cycles. Common toxicities included fatigue, chromaturia, dry/sore mouth, nausea and diarrhea. Eight pts (53%) had partial response (PR) or stable disease (SD) as best response. Seven of these pts remain on study with a range of duration of PR or SD of 8–24 weeks. Conclusions: The addition of ENZ to BV in any of the currently approved BV dosing schedules is well tolerated and clinically active in advanced cancer pts. The combination of ENZ and BV may be appropriate for further study in pts with NSCLC, colon or ovarian cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Genentech Eli Lilly
Evaluation of border gateway protocol (BGP) version 4 (V4) in the tactical environment (2002)

The Army Technical Architecture (ATA) mandated the use of BGP V4 as the exterior gateway dynamic routing protocol for use across communications systems that employ Internet Protocol (IP). This paper provides an analysis of the behavior of BGP under certain network states that exists in the tactical environment, such as network re-initialization, steady state, topology change, and task re-organization. Based on the analysis, BGP parameters are selected to minimize the bandwidth utilization for the above-mentioned network states.
Hypovitaminosis D in Medical Inpatients (1998)

Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily allowance and those without apparent risk factors for vitamin D deficiency.
Excel 2007: The Missing Manual (2006)

Microsoft Excel continues to grow in power, sophistication, and capability, but one thing that has changed very little since the early '90s is its user interface. The once-simple toolbar has been packed with so many features over the years that few users know where to find them all. Microsoft has addressed this problem in Excel 2007 by radically redesigning the user interface with a tabbed toolbar that makes every feature easy to locate and use. Unfortunately, Microsoft's documentation is as scant as ever, so even if users can find advanced features, they probably won't know what to do with them. Excel 2007: The Missing Manual covers the entire gamut of how to build spreadsheets, add and format information, print reports, create charts and graphics, and use basic formulas and functions. Like its siblings in the Missing Manual series, this book crackles with a fine sense of humor and refreshing objectivity about its subject, guiding readers through the new Excel with clear explanations, step-by-step instructions, lots of illustrations, and friendly, time-saving advice. It's a perfect primer for small businesses with no techie to turn to, as well as those who want to organize household and office information.
Flame Aerosol Synthesized Cr Incorporated TiO2 for Visible Light Photodegradation of Gas Phase Acetonitrile (2013)

A series of Cr–TiO2 nanoparticles with different atomic ratios of Ti to Cr have been synthesized by adopting a one-step flame aerosol synthesis technique. The photocatalytic activity of flame aerosol made TiO2 loaded with various amounts of Cr was studied as a catalyst for gas phase photodegradation of acetonitrile (ACN) under visible light (400–800 nm). It was found that the optimal concentrations of Cr and TiO2 exist (Ti/Cr atomic ratio = 40) for the efficient oxidation of ACN in the gas phase. XRD patterns showed a decrease in the anatase phase with increase in the amount of Cr loading. Our H2–temperature programmed reduction (TPR) results indicate a strong interaction (Cr–O–Ti) between support and dopant in the Cr modified TiO2 as-synthesized catalysts. Our XPS results illustrated that the relative atomic percentage value of Ti3+/Ti4+ characterized by XPS was significantly high for the Cr/TiO2 nanoparticles with Ti/Cr = 40 atomic ratio (Ti3+/Ti4+ = 1.14, 42.1%), whereas other samples demonstrated low atomic percentage value of Ti3+/Ti4+ (Ti3+/Ti4+ = 0.18–1.05). Moreover, Cr interacts with the TiO2 nanostructure in the interface of flame-made nanoparticles, bulk Cr oxide exists over the surface of TiO2 nanostructure. The photodegradation ability of TiO2/Cr catalyst with Ti/Cr atomic ratio of 40 was highly related to the existence of Cr6+ species which strongly interacted with TiO2. The reduction peaks in Cr-doped TiO2 shifted to much lower temperatures, due to the increase in the reduction potential of titania and chromium species. The strong interaction (formation of Cr–O–Ti bonds) is the main reason that Cr/TiO2 is an active photocatalyst in visible light. Among all of the catalysts tested, the system with Ti/Cr atomic ratio 40 demonstrated a superior catalytic performance with the rate constant of 0.812 m3 g–1 mol–1 under visible light irradiation. The proposed route of the catalytic activity of the above material in visible light involves the reaction of dopant level electrons with surface Cr, which makes available valence band holes to perform oxidation reactions.
Control of sebaceous gland function in the rat by alpha-melanocyte-stimulating hormone. (1975)

The effect of alpha-MSH on sebum secretion and preputial gland weight was examined in intact, castrated and hypophysectomized male rats and in hypophysectomized rats receiving treatment with either testosterone propionate (TP) or progesterone. After treatment with alpha-MSH for 2 weeks, increases in sebum secretion occurred in intact, castrated and hypophysectomized rats, but larger responses were found in the hypophysectomized rats that had received treatment with either TP or progesterone, suggesting that alpha-MSH acts synergistically with TP and progesterone to stimulate sebum secretion. Alpha-Melanocyte-stimulating hormone also increased preputial gland weight in intact rats, but there was no response after castration and only a small response after hypophysectomy. However, when the hypophysectomized rats received simultaneous treatment with either TP or progesterone, alpha-MSH increased preputial gland weight. It is suggested that alpha-MSH acts directly on the sebaceous glands to stimulate lipogenesis and, together with steroid hormones, may have an important role in controlling sebaceous glandd function in the rat and other hairy mammals. With the evolution of hair, certain of the MSH peptides may have lost their significance as pigmentary hormones and have developed a sebotrophic function. For this reason, it might be more appropriate to refer to these peptides as the 'sebotrophins'.
Transforming growth factor‐β1 (TGF‐β1) up‐regulation of collagen type II in primary cultures of rabbit articular chondrocytes (RAC) involves increased mRNA levels without affecting mRNA stability and procollagen processing (1992)

The effect of transforming growth factor-beta 1 (TGF-beta 1) on collagen biosynthesis was investigated in confluent primary monolayer cultures of rabbit articular chondrocytes (RAC). Exposure to TGF-beta (0.1, 1, and 10 ng/ml) in serum-free medium caused a dose- and time-dependent stimulation of collagen biosynthesis associated with an increase of steady-state levels of procollagen type II mRNA. Elevation of the mRNA steady-state did not result from a stabilization of the transcript, as shown by measure of the mRNA half-life. Electrophoresis (SDS-PAGE) showed that TGF-beta stimulates the synthesis of most collagen isotypes, including type II, without qualitative change in their distribution. Moreover, pulse-chase experiments revealed that TGF-beta did not affect the processing rate of type II procollagen. TGF-beta slightly stimulated the production of prostaglandin E2 (PGE2), which could in turn exert an inhibition on collagen synthesis. However, addition of indomethacin to block prostaglandin synthesis did not further enhance the TGF-beta-induced stimulation of collagen production, suggesting that this mediator was not implicated in the effect. Moreover, TGF-beta increased steady-state levels of procollagen type II, I, and III mRNAs even in the presence of indomethacin. Despite these increased mRNA levels, only the production of type II collagen was significantly augmented, suggesting that type I procollagen mRNA was not fully translated. In addition, the TGF-beta-induced stimulation of collagen synthesis was observed whenever ascorbic acid is added or not in the culture medium. In conclusion, TGF-beta, which is present in great amount in bone and cartilage, can increase the collagen production of cultured RAC and might therefore play a role in the early events of cartilage repair, such as those observed in osteoarthritis.
Topology Dissemination Based on Reverse-Path Forwarding (TBRPF) (2004)

Topology Dissemination Based on Reverse-Path Forwarding (TBRPF) is a proactive, link-state routing protocol designed for mobile ad-hoc networks, which provides hop-by-hop routing along shortest paths to each destination. Each node running TBRPF computes a source tree (providing paths to all reachable nodes) based on partial topology information stored in its topology table, using a modification of Dijkstra's algorithm. To minimize overhead, each node reports only *part* of its source tree to neighbors. TBRPF uses a combination of periodic and updates to keep all neighbors informed of the reported part of its source tree. Each node also has the option to report additional topology information (up to the full topology), to provide improved robustness in highly mobile networks. TBRPF performs neighbor discovery using differential HELLO messages which report only *changes* in the status of neighbors. This results in HELLO messages that are much smaller than those of other link-state routing protocols such as OSPF.
The effect of preweaning and postweaning housing on the behaviour of the laboratory mouse (Mus musculus) (2007)

Standard housing for laboratory mice severely restricts natural behaviour and the control that the animal has over its environment. Providing the cage with objects is a method that has been used to both increase environmental complexity, promote the performance of natural behaviour and provide greater controllability for the animal. This method of furnishing cages has mostly been studied in adult animals, and little is known about the influence that the preweaning environment has on the behaviour of mice as adults. This study aimed to investigate the effects on mice behaviour of preweaning and postweaning housing environment. In this experiment, 64 pairs of animals of the strain C57BL/6J were used. Half of the animals were born and reared until weaning in standard cages and the other half in cages twice the size of the standard and furnished with nesting material, a cardboard tube, a PVC nest box and a wooden chewblock. After weaning, half the animals in each group were changed to the other type of cage, whereas the other half remained in the same environment; in both cases they were kept in single-sex pairs of littermates. Behaviour during the dark, active period was studied through video recordings. We found no main effects of preweaning environment on behaviour; however, mice moved from furnished to standard cages at weaning showed a decrease in inactive behaviour at four weeks of age. Mice housed after weaning in standard cages spent less time inactive, and more time engaging in activities like feeding and drinking, self-grooming and allogrooming. A sex difference was also found, in that females showed a greater performance of exploratory behaviour as well as a greater prevalence of stereotypies. The use of different objects and locations within the furnished cage was also analysed at both ages. Results show that at eight weeks of age mice spent more time at the top of the cage, and that the use of the nest box (although not for resting) increased between four and eight weeks. Mice were found to use the nest box as a nesting site/sleeping place only at age four weeks, whereas they always used the nesting material for sleeping.
Assessment of the Integrin α5β1 Antagonist JSM6427 in Proliferative Vitreoretinopathy Using In Vitro Assays and a Rabbit Model of Retinal Detachment (2010)

JSM6427 is a promising treatment for PVR, with data suggesting that inhibition of alpha5beta1-fibronectin interactions addresses multiple pathways involving retinal pigment epithelial, glial, and inflammatory cells.
FDA Approval: Idelalisib Monotherapy for the Treatment of Patients with Follicular Lymphoma and Small Lymphocytic Lymphoma (2015)

On July 23, 2014, the FDA granted accelerated approval to idelalisib (Zydelig tablets; Gilead Sciences, Inc.) for the treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma or relapsed small lymphocytic lymphoma (SLL) who have received at least two prior systemic therapies. In a multicenter, single-arm trial, 123 patients with relapsed indolent non-Hodgkin lymphomas received idelalisib, 150 mg orally twice daily. In patients with follicular lymphoma, the overall response rate (ORR) was 54%, and the median duration of response (DOR) was not evaluable; median follow-up was 8.1 months. In patients with SLL, the ORR was 58% and the median DOR was 11.9 months. One-half of patients experienced a serious adverse reaction of pneumonia, pyrexia, sepsis, febrile neutropenia, diarrhea, or pneumonitis. Other common adverse reactions were abdominal pain, nausea, fatigue, cough, dyspnea, and rash. Common treatment-emergent laboratory abnormalities were elevations in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, absolute lymphocytes, and triglycerides. Continued approval may be contingent upon verification of clinical benefit in confirmatory trials.
Repression of Translation of Human Estrogen Receptor α by G-Quadruplex Formation (2009)

Tissue-specific expression of the human estrogen receptor alpha gene (ESR1) is achieved through multiple promoter sequences resulting in various mRNA transcripts encoding a common protein but differing in their 5'-untranslated region (5'-UTR). Many cancers are estrogen-sensitive with neoplastic growth stimulated through the estrogen receptor, a transcription factor that regulates developmental genes. We demonstrate that the human ESR1 gene is rich in potential quadruplex-forming sequences with 3 of 20 identified within exonic regions. In particular, we show using CD, UV, and NMR spectroscopy that a stable DNA G-quadruplex motif is formed within the exon C gene sequence. This motif, which PCR shows is transcribed in normal and neoplastic endometrium and in MCF-7 cells, forms a stable RNA quadruplex demonstrable by CD and UV analysis. Cloning the exon C G-quadruplex sequence upstream of a luciferase reporter gene caused a 6-fold reduction of enzymatic activity compared to a mutant sequence. We conclude that the exon C G-quadruplex motif is present in the 5'-UTR of the mRNA transcript, where it modulates the efficiency of translation.
Endovascular Treatment of Experimental Aneurysms with Liquid Polymers: The Protective Potential of Stents (1996)

Liquid polymers have previously been used to treat experimental and human aneurysms. However, the delivery of a liquid embolic material into the cerebral circulation involves a high risk of irreversible vessel occlusion and stroke. To evaluate methods for the safe and effective treatment of experimental aneurysms with liquid polymer injection, we tested four different techniques to deliver cellulose acetate polymer (CAP) or N-hexyl-cyanoacrylate into canine side-wall carotid artery aneurysms. The animals were observed for 1 to 10 weeks after treatment. Two aneurysms were treated without protection of the distal circulation, one with CAP and another with N-hexyl-cyanoacrylate. In four cases, an angioplasty balloon was inflated within the parent artery during endosaccular injection of CAP. In two of these cases, the balloon was placed adjacent to the aneurysm orifice, resulting in simultaneous occlusion of both the aneurysm and the parent artery, and in the other two cases, the balloon was positioned proximal to the aneurysm, resulting in temporary flow arrest. Three aneurysms were treated with either CAP or N-hexyl-cyanoacrylate after implantation of a balloon-expandable tantalum stent within the parent artery across the aneurysm orifice. Complete angiographic obliteration was achieved in all but one case. One aneurysm ruptured. Another partially occluded aneurysm reopened 10 weeks after treatment. In all cases treated without stents, distal migration of the polymer resulted in either stenosis or occlusion of the parent arteries. The combination of stent implantation and polymer injection resulted in permanent aneurysm occlusion without detectable polymer migration. An intravascular stent deployed within the parent artery across the aneurysm orifice acted as a safety net during endosaccular polymer injection by allowing blood to flow from the aneurysm cavity while preventing distal migration of liquid polymer.
Spatial and temporal regulation of a foreign gene by a prestalk-specific promoter in transformed Dictyostelium discoideum. (1986)

We analyzed a developmentally regulated prestalk-specific gene from Dictyostelium discoideum encoding a cathepsin-like protease. A hybrid gene was constructed by fusing 2.5 kilobases of 5' flanking sequences and part of the coding region of the gene in-frame to the Escherichia coli beta-glucuronidase gene and was transformed into D. discoideum cells. In cells transformed with this vector, the gene fusion showed the same temporal regulation as the endogenous gene during multicellular development and, like endogenous prestalk genes, was highly inducible by cyclic AMP in in vitro cell cultures. Moreover, immunofluorescence studies showed that the fusion protein had the same spatial distribution within the migrating pseudoplasmodium as the endogenous gene. The results indicate that the regions of the D. discoideum prestalk-specific cathepsin gene contain all the necessary information for proper temporal, spatial, and cyclic AMP regulation of a prestalk cell-type gene in D. discoideum transformants and leads the way for experiments to identify the cell-type-specific regulatory elements.
The gene for the β subunit of porcine FSH: absence of consensus oestrogen-responsive element and presence of retroposons (1990)

To elucidate the structure and control of expression of the porcine FSH-beta subunit gene, two genomic clones were isolated and the entire gene structure was determined to the extent of 10 kb, consisting of 6 kb of the 5'-flanking region and 4 kb of the transcriptional unit. The porcine FSH-beta gene consisted of three exons the same as the human and bovine genes, but the positions of both splicing sites of porcine intron-1 were unique. It is known that the synthesis of FSH is regulated by gonadal steroids, gonadotrophin-releasing hormone (GnRH) and inhibin. However, the consensus steroid-responsive element was unexpectedly absent in the 5'-flanking region of 6 kb. On the other hand, the potential binding sites for activator protein-1 (AP1) and AP2, which might be stimulated by the GnRH-protein kinase C cascade, were present at seven and five positions respectively. An imperfect cyclic AMP-responsive element was also present. Southern blot analyses, using the cDNA and genomic fragments as probes, gave smear patterns suggesting the presence of repetitive sequences in the porcine FSH-beta gene. A survey of homology with the repetitive sequences revealed that short interspersed repeated sequences (SINES)-type non-viral retroposons were present with about 250 bp length repeats twice in the 5'-flanking region and once each in intron-1 and the 3'-flanking region. Other SINES-like sequences were also found in intron-1, exon-2 and exon-3. In comparison with the 5'-flanking sequences of the porcine alpha and LH-beta genes, there were no significantly conserved regions, implying a lack of common modulation of the three subunit genes.
Competitive bidding in electricity supply (1993)

As significant additional capacity comes on line in the United Kingdom in the next few years [1, 2], a genuine commercially competitive electricity supply market will gradually replace the prevailing somewhat artificial ‘market’ conditions. In genuinely competitive conditions, several producers compete to win a share of the market and bid against each other to supply the grid. The prices bid by suppliers for blocks of generation offered to the grid would reflect what portions of the load curve a supplier hopes to win for each type of plant in its possession. This, in turn, depends on production cost estimates, temporal considerations of system demand variation, unit commitment costs, and commercial considerations such as profit or economic utility maximisation and expectations of competitor behaviour. This is a wholly new situation, and has not been theorised or modelled to any significant extent. The paper develops conceptual models and mathematical tools for a fuller understanding of these issues.
Adenovirus-Associated Virus Multiplication (1971)

The two complementary strand species of 5-bromodeoxyuridine-substituted, adenovirus-associated virus type 2 (AAV-2) deoxyribonucleic acid were preparatively separated in CsCl density gradients and further purified by sedimentation through 5 to 20% sucrose. The base composition of each strand species was determined, and it was found that the species banding at a greater density in CsCl (heavy strands) had an expected higher thymidine content (26.5%) than that 21.7%) of the less dense species (light strands). Furthermore, the base composition of in vivo-synthesized, AAV-specific ribonucleic acid was similar to that of light-strand deoxyribonucleic acid, and this ribonucleic acid apparently hybridized only with heavy strands. These observations indicate that the heavy-strand species alone serves as the transcriptional template in vivo. This study represents the first instance in which the base composition and specificity of in vivo transcription have been determined for each of the complementary strands of an animal virus deoxyribonucleic acid.