gebhart/patrepeval huggingface dataset:
Colorectal cancer (CRC) cohort analysis of patients treated with buparlisib in a distinctive tissue-agnostic trial model for molecularly preselected tumors. (2015)

644 Background: This is a CRC cohort analysis from the novel Novartis “Signature” program of tissue-agnostic, genetic alteration specific signal-finding protocols. Potential patients are identified via standard-of-care profiling; we bring the ‘Protocol to the Patient’, with rapid start-up process. Buparlisib (BKM120) is an oral pan-PI3K inhibitor evaluated in this program. Methods: Patients had progressive/relapsed CRC harboring PI3K pathway activated tumors, measurable disease, ECOG PS ≤1, and adequate organ function. A local CLIA-certified test is sufficient for eligibility. Central post hoc broad tumor molecular profiling of genetic alteration is performed. BKM120 was given orally (100 mg) qd. The primary objective is to assess clinical benefit (SD or better at 16 weeks). Statistical design adaptively clusters patients into cohorts for independent analysis for early futility or efficacy. Results: 18 CRC patients were dosed: 10 females, 15 Caucasian, median age 58 years (40-80), all had ECOG PS ≤1. Median prior therapies: 4 (1-13). Actionable alterations present at baseline (local): 10 (55.6%) PIK3CA mutation, 4 (22.2%) PTEN loss (IHC), 3 (16.7%) each PTEN mutated and PIK3R1 mutated. Median time on study was 5.1 weeks (1-16). Frequently observed AEs: nausea (67%), fatigue (39%), vomiting (33%), diarrhea (33%), anxiety (28%) and decreased appetite (28%). Three patients discontinued due to AEs. At week 16: 13 patients did not meet clinical benefit criteria and 5 patients were non-evaluable. Two patients had SD at week 8. Central genomic profiling: DNA from 14 patients was assessed covering a panel of 288 cancer genes. All patients had a mutation in APC, 10 (71%) also had KRAS mutations and 11 (79%) had mutations in TP53. Three patients with the lowest PFS exhibited mutations in ERBB2 and ERBB4. Concordance between local and central lab results was 73%. Conclusions: This program facilitated the enrollment of molecularly profiled CRC patients with PI3K pathway alterations. In this cohort, BKM120 had a manageable safety profile with negligible activity as single agent. Further evaluation can determine the effect of BKM120 in combination with other agents. NCT01833169 Clinical trial information: NCT01833169.
Structure−Property Model for Membrane Partitioning of Oligopeptides (1999)

The aim of this study was to develop a structure-property model for membrane partitioning of oligopeptides using statistical design methods and multivariate data analysis. A set of 20 tetrapeptides with optional N-methylations at residues 2 and 4 was designed by a D-optimal design procedure. After synthesis and purification, the membrane partitioning abilities of the peptides were tested in two chromatographic systems with phospholipids as the stationary phase: immobilized artificial membrane chromatography (IAM) and immobilized liposome chromatography (ILC). The relationship between these measures and three different sets of calculated descriptors was analyzed by partial least-squares projection to latent structures (PLS). The descriptors used were the molecular surface area, Molsurf parameters, and Volsurf parameters. All three models were of good statistical quality and supported that a large hydrogen-bonding potential and the presence of a negative charge impair membrane partitioning, whereas hydrophobic parameters promote partitioning. The findings are in accordance with what has been found for absorption of known drugs and have implications for the design of peptide-like drugs with good oral bioavailability.
Psychromonas heitensis sp. nov., a psychrotolerant bacterium isolated from seawater in Japan (2008)

Four bacterial strains, 04HE-4-40, A4I-9, A4I-21 and AK15-027(T), were isolated from Heita Bay off Kamaishi in Japan. Based on 16S rRNA gene sequence analysis, the isolates were placed as a new lineage within the genus Psychromonas. The 16S rRNA gene sequence similarity values between the isolates and type strains of recognized Psychromonas species were less than 97 %. The DNA G+C contents of the isolates were about 38 mol%. The major respiratory quinone was Q-8, and the predominant cellular fatty acids were 16 : 1omega7c and 16 : 0. The isolates were able to grow at 30 degrees C, unlike other Psychromonas species. Based on the results of the phylogenetic analysis and phenotypic characteristics and DNA-DNA hybridization data, the isolates represent a novel species, for which the name Psychromonas heitensis sp. nov. is proposed. The type strain is AK15-027(T) (=MBIC 06898(T)=NCIMB 14416(T)).
The Ternary Systems BaO–TiO 2 –SnO 2 and BaO‐TiO 2 ‐ZrO 2 (1958)

An investigation of the ternary systems BaO‐TiO 2 ‐SnO 2 and BaO‐TiO 2 ‐ZrO 2 led to the discovery of two new compounds belonging to the system BaO‐TiO 2 . These compounds, Ba 2 Ti 9 ‐O 20 and Ba 2 Ti 9 O 20 , are stabilized by minute additions of SnO 2 or ZrO 2 . The known compound BaTi 2 O 5 can be obtained only from the molten phase and decomposes below 1300°C. into Ba 2 Ti 5 O 12 and BaTiO 2 . In these systems no ternary compounds are found. The ternary phase diagrams can be divided into regions with high and low dielectric losses, which are in accordance with the phase relations. Tables with crystallographic data of the new compounds are included.
ChemInform Abstract: Vinylidene Transition‐Metal Complexes. Part 13. Reactivity of (IrH5(PiPr3)2) and (IrH2Cl(PiPr3)2) Toward Alk‐1‐ynes: Synthesis of Four‐, Five‐ and Six‐Coordinate Iridium Complexes Containing Alkynyl, Vinyl and Vinylidene Ligands. (1991)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Parkin and PINK1 mutations in early-onset Parkinson’s disease: comprehensive screening in publicly available cases and control (2009)

Our data support a trend towards a higher frequency of heterozygosity for pathogenic parkin or PINK1 mutations in patients compared with normal controls, but this effect was small and did not reach significance in our cohort of 250 cases and 276 controls.
2, Pulse-mode expansions and refractive indices in plane-wave propagation (1987)

This memo presents basic background theory for treating simultaneous propagation of electromagnetic pulses of various colors, directed along a common ray, through a molecular vapor. The memo discusses some techniques for expanding the positive frequency part of the transverse electric field into pulse modes, characterized by carrier frequencies within a modulated envelope. We discuss, in the approximation of plane waves with slowly varying envelopes, a set of uncoupled envelope equations in which a polarization mode-envelope acts as a source for an electric-field envelope. These equations, when taken with a prescription for the polarization field, are the basic equations of plane-wave pulse propagation through a molecular medium. We discuss two ways of treating dispersive media, one based upon expansions in the frequency domain and the other based in the time domain. In both cases we find envelope equations that involve group velocities. This memo represents a portion of a more extensive treatment of propagation to be presented separately. Many of the equations presented here have been described in various books and articles. They are collected and described here as a summary and review of contemporary theory.
In Vitro Definition of the Yeast RNA Polymerase I Enhancer (1993)

In vitro conditions are reported under which an EcoRI-HpaI fragment of the Saccharomyces cerevisiae ribosomal gene spacer will enhance transcription from an adjacent RNA polymerase I promoter. Enhancement is largely independent of orientation and distance and is proportional to copy number. Mapping experiments reveal that two separate regions of the EcoRI-HpaI fragment are independently capable of promoter stimulation. These regions appear to correspond to elements which have been shown by previous workers to cause enhancement in vivo. Using the detergent Sarkosyl to limit the number of rounds of transcription from each promoter, we found that the degree of enhancement is similar whether one or many rounds of transcription occur. This finding supports a model in which the enhancer increases the number of stable promoter complexes but does not alter the loading of polymerase on an active promoter. Once the stable promoter complex is formed, the enhancer can be physically severed from the promoter with no loss of enhancement. Likewise, the upstream activation region of the promoter can be severed from the core promoter domain once the stable complex has been formed. These results are interpreted to mean that the enhancer functions only to assist stable complex formation and, once that is accomplished, the enhancer is dispensable.
Abstract TP56: Angiographic Flow Index on DSA Correlates with Cerebral Flow Measured by Quantitative MRA (2017)

Introduction: Digital subtraction angiography (DSA) has traditionally been used to provide high-resolution anatomical imaging but is not readily used to assess cerebral hemodynamics. Here we examine the relationship between time density transit time (TT) on DSA, vessel cross-sectional area and flow obtained from QMRA of the same artery. Methods: Patients seen at our institution between 2009 and 2015 who had concomitant DSA and Quantitative MRA prior to any treatment for a vascular lesion were retrospectively reviewed. Transit time (TT) on DSA was defined as time needed for contrast to change image intensity from 25%-25%. Flow volume rate (mL/min) and vessel cross-sectional area were measured using QMRA. Angio flow index (FI) = [Cross sectional area/TT 25-25%] was calculated and analyzed relative to flow. Results: 48 patients (mean age was 51 years) were included. There was a significant correlation (Spearman’s) between the MCA and ACA flows and the angio flow index ( P &lt;0.001, rho=0.66). The same positive correlation was present for the individual MCA flows ( P &lt;0.001, rho=0.81) and ACA flows ( P &lt;0.001, rho=0.52) and the angio flow index. Conclusion: Angio flow index correlated significantly with intracranial flows measured by QMRA, and so angio flow index may be used as an indirect tool for assessment of cerebral flow during interventional procedures.
Novel Benzofuran and Benzothiophene Biphenyls as Inhibitors of Protein Tyrosine Phosphatase 1B with Antihyperglycemic Properties (2000)

Insulin resistance in the liver and peripheral tissues, together with a pancreatic cell defect, are the common causes of Type 2 diabetes. It is now appreciated that insulin resistance can result from a defect in the insulin receptor signaling system, at a site post binding of insulin to its receptor. Protein tyrosine phosphatases (PTPases) have been shown to be negative regulators of the insulin receptor. Inhibition of PTPases may be an effective method in the treatment of Type 2 diabetes. We have identified two novel series of benzofuran/benzothiophene biphenyl oxo-acetic acids and sulfonyl-salicylic acids as potent inhibitors of PTP1B with good oral antihyperglycemic activity. To assist in the design of these inhibitors, crystallographic studies have attempted to identify enzyme inhibitor interactions. Resolution of crystal complexes has suggested that the inhibitors bind to the enzyme active site and are held in place through hydrogen bonding and van der Waals interactions formed within two hydrophobic pockets. In the oxo-acetic acid series, hydrophobic substitutents at position-2 of the benzofuran/benzothiophene biphenyl framework interacted with Phe182 of the catalytic site and were very critical to the intrinsic activity of the molecule. The hydrophobic region of the catalytic-site pocket was exploited and taken advantage by hydrophobic substituents at either the alpha-carbon or the ortho aromatic positions of the oxo-acetic acid moiety. Similar ortho aromatic substitutions on the salicylic acid-type inhibitors had no effect, primarily due to the different orientation of these inhibitors in the catalytic site. The most active inhibitors of both series inhibited recombinant human PTP1B with phosphotyrosyl dodecapeptide TRDI(P)YETD(P)Y(P)YRK as the source of the substrate with IC(50) values in the range of 20-50 nM. Compound 68 was one of the most active compounds in vivo, normalizing plasma glucose levels at the 25 mg/kg dose (po) and the 1 mg/kg dose (ip). Compound 68 was also selective against several other PTPases.
Franck - Condon shift and temperature dependence of the zero-phonon binding energy of the deep selenium centre in silicon (1996)

Using the steady-state photocurrent technique spectral distributions of the photoionization cross section for holes of the deep selenium centre in silicon have been measured at 11 temperatures within the temperature range . A novel analytical model is proposed which properly accounts for the competing ionization processes into the light- and heavy-hole valence bands. Curve fittings based on detailed numerical calculations of convolution integrals result in a Franck - Condon shift of about meV together with an effective phonon energy of about meV. The partial shrinkage coefficient quantifying the shrinkage of the zero-phonon binding energy for holes, , with respect to that of the bandgap was found to be about , indicating an approximate pinning of the deep single substitutional selenium level to the conduction band edge. A hole binding energy of meV at T = 0 was obtained from an extrapolation of the fitted curve.
Compact low coupling dual -antennas for MIMO applications in handheld devices (2009)

A dual-port slot strip antenna array for MIMO handheld devices is presented. This antenna array uses a T-shaped slot with changed widths to improve isolation between the two ports. The antenna has the combination of omni-directional radiation, high efficiency and compact size in an easy to fabricate structure. The experimental and simulated results validate the proposed design.
Spirangien A and B, Highly Cytotoxic and Antifungal Spiroketals from the Myxobacterium Sorangium cellulosum: Isolation, Structure Elucidation and Chemical Modifications (2005)

Abstract Two novel highly cytotoxic metabolites, spirangien A ( 1 ) and B ( 2 ), were isolated from the myxobacterium Sorangium cellulosum (strain So ce90). The structures were elucidated by detailed NMR spectroscopic analysis. The previously unknown molecular framework common to spirangien A and B includes a highly functionalized spiroketal core structure, a side chain bearing a pentaene chromophore and a terminal carboxyl group, and a total of thirteen stereocenters. The absolute configuration at C‐3 was determined by degradation and subsequent fragment analysis by GC. The relative stereochemistry of the spiroketal structure was proposed on the basis of vicinal proton couplings and ROESY data for hydroperoxide derivative 4 , obtained by ozonolysis of spirangien A, and for 1,3‐diene 5 , obtained by cross‐metathesis with ethylene. X‐ray crystal structure analysis of 5 confirmed its structure and unambiguously provided the complete relative stereochemistry of all twelve stereocenters. The 1,3‐diene derivative 5 still shows strong cytotoxic activity. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)
NiV-M budding is enhanced by NiV-C in an ESCRT-dependent manner. (2016)

&lt;p&gt;&lt;b&gt;(A)&lt;/b&gt; A schematic of the NiV genome is shown, with the NiV genes arrayed between the genomic termini, the 3’ leader (3’le) and 5’ trailer (5’tr). NiV-V and -W are produced by the stochastic inclusion of additional G nucleotides in the P mRNA via polymerase stuttering (as indicated in the schematic), thus creating a frameshift at that juncture, while NiV-C is produced off an alternate reading frame. &lt;b&gt;(B)&lt;/b&gt; NiV-M was co-transfected with vector only or with HA-tagged NiV-derived gene products into 293T cells, and relative virus-like particle budding was determined as described in Materials and Methods. COX IV is shown as the cell lysate loading control. Error bars represent standard deviations for 3 independent experiments. Only NiV-C had a significant effect on M budding relative to the vector control. ***, p&lt;0.001, one-way ANOVA followed by Bonferroni posttests. &lt;b&gt;(C)&lt;/b&gt; CCL-81 Vero cells were infected with Gluc-expressing WT or NiV-C knockout NiV at MOI 2. Virus titers were determined from supernatant collected at 24 hpi. Error bars represent standard deviations for 3 replicates. **, p&lt;0.01, 2-tailed Student’s t-test. &lt;b&gt;(D)&lt;/b&gt; At 24 hpi, cell lysates (CL) were collected, and virions were ultracentrifuged through 20% sucrose and resuspended in Laemmli SDS sample buffer for Western analysis. Normalized relative budding values are shown below the blot. &lt;b&gt;(E)&lt;/b&gt; Knockout of NiV-C did not affect Gluc production, indicating unimpaired protein production. ns, not significant, two-way ANOVA followed by Bonferroni posttests. &lt;b&gt;(F)&lt;/b&gt; Vps4A-inducible 293 cells were transfected with NiV-M and with or without NiV-C-HA as indicated. At 4 hours post-transfection, media was changed with or without doxycycline. Error bars represent standard deviations for 3 independent experiments. **, p&lt;0.01, one-way ANOVA followed by Bonferroni posttests. Only NiV-C enhancement of NiV-M-mediated VLP budding was significantly affected by induction of DN Vps4A.&lt;/p&gt;
Learning Deep Representations of Objects and Materials for Material Recognition (2016)

We study the problem of recognizing the material of an object from its single image. We are interested in how representations learned by convolutional neural networks (CNNs) for object recognition can be transferred for material recognition.We first propose a procedure for transfer learning using a 16-layer CNN model. First, it is trained for object recognition using a dataset of object images (ImageNet). Then, the model is fine-tuned for material recognition using a material dataset created in the authors' lab, which is an extended version of FMD dataset (Sharan et al., IJCV, 2013). The dataset (named EFMD) consists of 10,000 images belonging to the same 10 classes as FMD. Finally, while fixing from 1st to 9th layers, only 10th to 16th layers of the model are further fine-tuned using a training subset of FMD. The model obtained by this procedure achieves prediction accuracy 83%±0.99 on FMD, which is close to the reported human performance 84.9%. In addition, we analyze the effect of representations of local and non-local surface properties on performance by employing models on deformed images of FMD. First, we use two datasets, namely t15 and t30, consisting of images that are deformed "locally" using synthesized texture forms with 15x15 and 30x30 patches, respectively. Then, we use two datasets of images deformed to emphasize non-local properties of surfaces using bilateral and high-pass filters, called bf and hf, respectively. The proposed procedure provides 65.3%±1.13, 69.8%±0.82, 69.2%±1.00, and 64.7%±1.90, while the human performance is reported as 38.7%, 46.9%, 64.8%, and 65.3% on t15, t30, hf, and bf, respectively. This result can be attributed to the locality of representations learned in CNNs implied by the local convolutions. Overall, our results suggest that object representations can be transferred for learning material representations in CNNs to model local surface properties and recognize materials. Meeting abstract presented at VSS 2016
[Mitral valve replacement with concomitant coronary bypass for the papillary muscle rupture after acute myocardial infarction in situs inversus]. (1992)

A 53-year-old man, who was known to have situs inversus totalis all of his life, had acute myocardial infarction complicated by partial rupture of the posterior papillary muscle causing mitral regurgitation and pulmonary edema. The patient underwent mitral valve replacement (Omnicarbon 27 mm) with concomitant aortocoronary saphenous vein bypass, and he is now doing well 9 months following the operation. To our knowledge, this is the first case of the successful mitral valve replacement and concomitant aortocoronary saphenous vein bypass on a patient with situs inversus totalis (mirror-image dextrocardia) in Japan.
Hair’s the Question: White/Gray Hair (2018)

1. Sara Wasserbauer, MD, FISHRS (drwasserbauer{at}californiahairsurgeon.com) 1. Walnut Creek, California, USA </br>![][1]</img> The questions presented by the author are not taken from the ABHRS item pool and accordingly will not be found on the ABHRS Certifying Examination. A set of
A nitroxyl-responsive near-infrared fluorescent chemosensor for visualizing H2S/NO crosstalk in biological systems (2019)

We present a near-infrared (NIR) fluorescent probe, NR-HNO, which was successfully applied to visualizing H2S/NO "crosstalk" by the fluorescence detection of nitroxyl with a fast response time (5 min) and a large Stokes shift (131 nm) in living cells and tissue; it was also used to image nitroxyl in live mice.
Molecular Basis for the Relative Substrate Specificity of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Proteases (2001)

We have used a random hexamer phage library to delineate similarities and differences between the substrate specificities of human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV) proteases (PRs). Peptide sequences were identified that were specifically cleaved by each protease, as well as sequences cleaved equally well by both enzymes. Based on amino acid distinctions within the P3-P3' region of substrates that appeared to correlate with these cleavage specificities, we prepared a series of synthetic peptides within the framework of a peptide sequence cleaved with essentially the same efficiency by both HIV-1 and FIV PRs, Ac-KSGVF/VVNGLVK-NH(2) (arrow denotes cleavage site). We used the resultant peptide set to assess the influence of specific amino acid substitutions on the cleavage characteristics of the two proteases. The findings show that when Asn is substituted for Val at the P2 position, HIV-1 PR cleaves the substrate at a much greater rate than does FIV PR. Likewise, Glu or Gln substituted for Val at the P2' position also yields peptides specifically susceptible to HIV-1 PR. In contrast, when Ser is substituted for Val at P1', FIV PR cleaves the substrate at a much higher rate than does HIV-1 PR. In addition, Asn or Gln at the P1 position, in combination with an appropriate P3 amino acid, Arg, also strongly favors cleavage by FIV PR over HIV PR. Structural analysis identified several protease residues likely to dictate the observed specificity differences. Interestingly, HIV PR Asp30 (Ile-35 in FIV PR), which influences specificity at the S2 and S2' subsites, and HIV-1 PR Pro-81 and Val-82 (Ile-98 and Gln-99 in FIV PR), which influence specificity at the S1 and S1' subsites, are residues which are often involved in development of drug resistance in HIV-1 protease. The peptide substrate KSGVF/VVNGK, cleaved by both PRs, was used as a template for the design of a reduced amide inhibitor, Ac-GSGVF Psi(CH(2)NH)VVNGL-NH(2.) This compound inhibited both FIV and HIV-1 PRs with approximately equal efficiency. These findings establish a molecular basis for distinctions in substrate specificity between human and feline lentivirus PRs and offer a framework for development of efficient broad-based inhibitors.