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Macroautophagy/autophagy plays a dual role in many physiological processes of multicellular eukaryotes. In plants, autophagy can be used by both host and pathogen for a beneficiary infection outcome. Plants employ a two-tier innate immune system to defend against invading pathogens. Cell surface localized pattern recognition receptors recognize conserved pathogen-associated molecular patterns (PAMPs) and launch pattern-triggered immunity (PTI) to provide broad-spectrum resistance. Pathogens inject a battery of effector proteins into their hosts to counter PTI and compromise the primary immune response. Hosts induce a second layer of defense called effector-triggered immunity (ETI) to counter the effects of these effectors. In addition to ETI and PTI, autophagy is emerging as a central cellular process modulated by both host and pathogens toward their respective advantage. Pathogens lacking the ability to inject effectors are compromised in virulence. However, molecular targets and biochemical characterization of most of these effector proteins remain elusive. In a recent paper we presented a systematic analysis of interaction between autophagy proteins of Arabidopsis thaliana with effectors from bacterial, fungal, oomycete and nematode pathogens. Abbreviations: ATG, autophagy related; BiFC, bimolecular fluorescence complementation; ETI, effector-triggered immunity; PAMPs, pathogen-associated molecular patterns; PTI, pattern-triggered immunity.

We study the charge and spin dependent scattering in a set of CoFeB thin films whose crystalline order is systematically enhanced and controlled by annealing at increasingly higher temperatures. Terahertz conductivity measurements reveal that charge transport closely follows the development of the crystalline phase, with the increasing structural order leading to higher conductivity. The terahertz-induced ultrafast demagnetization, driven by spin-flip scattering mediated by the spin–orbit interaction, is measurable in the pristine amorphous sam- ple and much reduced in the sample with the highest crystalline order. Surprisingly, the largest demagnetization is observed at intermediate annealing temperatures, where the enhancement in spin-flip probability is not associated with an increased charge scattering. We are able to correlate the demagnetization amplitude with the magnitude of the in-plane magnetic anisotropy, which we characterize independently, sug- gesting a magnetoresistance-like description of the phenomenon.

We present the science case for the proposed Daksha high energy transients mission. Daksha will comprise of two satellites covering the entire sky from 1~keV to $>1$~MeV. The primary objectives of the mission are to discover and characterize electromagnetic counterparts to gravitational wave source; and to study Gamma Ray Bursts (GRBs). Daksha is a versatile all-sky monitor that can address a wide variety of science cases. With its broadband spectral response, high sensitivity, and continuous all-sky coverage, it will discover fainter and rarer sources than any other existing or proposed mission. Daksha can make key strides in GRB research with polarization studies, prompt soft spectroscopy, and fine time-resolved spectral studies. Daksha will provide continuous monitoring of X-ray pulsars. It will detect magnetar outbursts and high energy counterparts to Fast Radio Bursts. Using Earth occultation to measure source fluxes, the two satellites together will obtain daily flux measurements of bright hard X-ray sources including active galactic nuclei, X-ray binaries, and slow transients like Novae. Correlation studies between the two satellites can be used to probe primordial black holes through lensing. Daksha will have a set of detectors continuously pointing towards the Sun, providing excellent hard X-ray monitoring data. Closer to home, the high sensitivity and time resolution of Daksha can be leveraged for the characterization of Terrestrial Gamma-ray Flashes., Comment: 19 pages, 7 figures. Accepted in Experimental Astronomy. More details about the mission at https://www.dakshasat.in

We present Daksha, a proposed high energy transients mission for the study of electromagnetic counterparts of gravitational wave sources, and gamma ray bursts. Daksha will comprise of two satellites in low earth equatorial orbits, on opposite sides of earth. Each satellite will carry three types of detectors to cover the entire sky in an energy range from 1 keV to >1 MeV. Any transients detected on-board will be announced publicly within minutes of discovery. All photon data will be downloaded in ground station passes to obtain source positions, spectra, and light curves. In addition, Daksha will address a wide range of science cases including monitoring X-ray pulsars, studies of magnetars, solar flares, searches for fast radio burst counterparts, routine monitoring of bright persistent high energy sources, terrestrial gamma-ray flashes, and probing primordial black hole abundances through lensing. In this paper, we discuss the technical capabilities of Daksha, while the detailed science case is discussed in a separate paper., Comment: 9 pages, 3 figures, 1 table. Accepted in Experimental Astronomy. Additional information about the mission is available at https://www.dakshasat.in

The rising trend of gastrointestinal (GI) cancer has become a global burden due to its aggressive nature and poor prognosis. Long noncoding RNAs (lncRNAs) have recently been reported to be overexpressed in different GI cancers and may contribute to cancer progression and chemoresistance. ,ey are featured with more than 200 nucleotides, commonly polyadenylated, and lacking an open reading frame. LncRNAs, particularly urothelial carcinoma-associated 1 (UCA1), are oncogenes involved in regulating cancer progression, such as cell proliferation, invasion, migration, and chemoresistance, particularly in GI cancer. ,is review was aimed to present an updated focus on the molecular regulatory roles and patterns of lncRNA UCA1 in progression and chemoresistance of different GI cancers, as well as deciphering the underlying mechanisms and its interactions with key molecules involved, together with a brief presentation on its diagnostic and prognostic values. ,e regulatory roles of lncRNA UCA1 are implicated in esophageal cancer, gastric cancer, pancreatic cancer, hepatobiliary cancer, and colorectal cancer, where they shared similar molecular mechanisms in regulating cancer phenotypes and chemoresistance. Comparatively, gastric cancer is the most intensively studied type in GI cancer. LncRNA UCA1 is implicated in biological roles of different GI cancers via interactions with various molecules, particularly microRNAs, and signaling pathways. In conclusion, lncRNA UCA1 is a potential molecular target for GI cancer, which may lead to the development of a novel chemotherapeutic agent. Hence, it also acts as a potential diagnostic and prognostic marker for GI cancer patients.

The rising trend of gastrointestinal (GI) cancer has become a global burden due to its aggressive nature and poor prognosis. Long noncoding RNAs (lncRNAs) have recently been reported to be overexpressed in different GI cancers and may contribute to cancer progression and chemoresistance. ,ey are featured with more than 200 nucleotides, commonly polyadenylated, and lacking an open reading frame. LncRNAs, particularly urothelial carcinoma-associated 1 (UCA1), are oncogenes involved in regulating cancer progression, such as cell proliferation, invasion, migration, and chemoresistance, particularly in GI cancer. ,is review was aimed to present an updated focus on the molecular regulatory roles and patterns of lncRNA UCA1 in progression and chemoresistance of different GI cancers, as well as deciphering the underlying mechanisms and its interactions with key molecules involved, together with a brief presentation on its diagnostic and prognostic values. ,e regulatory roles of lncRNA UCA1 are implicated in esophageal cancer, gastric cancer, pancreatic cancer, hepatobiliary cancer, and colorectal cancer, where they shared similar molecular mechanisms in regulating cancer phenotypes and chemoresistance. Comparatively, gastric cancer is the most intensively studied type in GI cancer. LncRNA UCA1 is implicated in biological roles of different GI cancers via interactions with various molecules, particularly microRNAs, and signaling pathways. In conclusion, lncRNA UCA1 is a potential molecular target for GI cancer, which may lead to the development of a novel chemotherapeutic agent. Hence, it also acts as a potential diagnostic and prognostic marker for GI cancer patients.

Multilayer X-ray mirrors consist of a coating of a large number of alternate layers of high Z and low Z materials with a typical thickness of 10-100 Angstrom, on a suitable substrate. Such coatings play an important role in enhancing the reflectivity of X-ray mirrors by allowing reflections at angles much larger than the critical angle of X-ray reflection for the given materials. Coating with an equal thickness of each bilayer enhances the reflectivity at discrete energies, satisfying Bragg condition. However, by systematically varying the bilayer thickness in the multilayer stack, it is possible to design X-ray mirrors having enhanced reflectivity over a broad energy range. One of the most important applications of such a depth graded multilayer mirror is to realize hard X-ray telescopes for astronomical purposes. Design of such multilayer X-ray mirrors and their characterization with X-ray reflectivity measurements require appropriate software tools. We have initiated the development of hard X-ray optics for future Indian X-ray astronomical missions, and in this context, we have developed a program, DarpanX, to calculate X-ray reflectivity for single and multilayer mirrors. It can be used as a stand-alone tool for designing multilayer mirrors with required characteristics. But more importantly, it has been implemented as a local model for the popular X-ray spectral fitting program, XSPEC, and thus can be used for accurate fitting of the experimentally measured X-ray reflectivity data. DarpanX is implemented as a Python 3 module, and an API is provided to access the underlying algorithms. Here we present details of DarpanX implementation and its validation for different type multilayer structures. We also demonstrate the model fitting capability of DarpanX for experimental X-ray reflectivity measurements of single and multilayer samples., Comment: Accepted for publication in Astronomy and Computing, 13 pages, 9 figures

Plants employ cell-surface pattern recognition receptors (PRRs) to detect pathogens. Although phytohormones produced during PRR signaling play an essential role in innate immunity, a direct link between PRR activation and hormone regulation is unknown. EFR is a PRR that recognizes bacterial EF-Tu and activates immune signaling. Here we report that EFR regulates the phytohormone jasmonic acid (JA) through direct phosphorylation of a receptor-like cytoplasmic kinase, BIK1. The BIK1 structure revealed that the EFR-phosphorylated sites reside on a uniquely extended loop away from the BIK1 kinase core domain. Phosphomimetic mutations of these sites resulted in increased phytohormones and enhanced resistance to bacterial infections. In addition to its documented plasma membrane localization, BIK1 also localizes to the nucleus and interacts directly with WRKY transcription factors involved in the JA and salicylic acid (SA) regulation. These findings demonstrate the mechanistic basis of signal transduction from PRR to phytohormones, mediated through a PRR-BIK1-WRKY axis.

Production of reactive oxygen species (ROS) is critical for successful activation of immune responses against pathogen infection. The plant NADPH oxidase RBOHD is a primary player in ROS production during innate immunity. However, how RBOHD is negatively regulated remains elusive. Here we show that RBOHD is regulated by C-terminal phosphorylation and ubiquitination. Genetic and biochemical analyses reveal that the PBL13 receptor-like cytoplasmic kinase phosphorylates RBOHD's C-terminus and two phosphorylated residues (S862 and T912) affect RBOHD activity and stability, respectively. Using protein array technology, we identified an E3 ubiquitin ligase PIRE (PBL13 interacting RING domain E3 ligase) that interacts with both PBL13 and RBOHD. Mimicking phosphorylation of RBOHD (T912D) results in enhanced ubiquitination and decreased protein abundance. PIRE and PBL13 mutants display higher RBOHD protein accumulation, increased ROS production, and are more resistant to bacterial infection. Thus, our study reveals an intricate post-translational network that negatively regulates the abundance of a conserved NADPH oxidase.

Production of reactive oxygen species (ROS) is critical for successful activation of immune responses against pathogen infection. The plant NADPH oxidase RBOHD is a primary player in ROS production during innate immunity. However, how RBOHD is negatively regulated remains elusive. Here we show that RBOHD is regulated by C-terminal phosphorylation and ubiquitination. Genetic and biochemical analyses reveal that the PBL13 receptor-like cytoplasmic kinase phosphorylates RBOHD's C-terminus and two phosphorylated residues (S862 and T912) affect RBOHD activity and stability, respectively. Using protein array technology, we identified an E3 ubiquitin ligase PIRE (PBL13 interacting RING domain E3 ligase) that interacts with both PBL13 and RBOHD. Mimicking phosphorylation of RBOHD (T912D) results in enhanced ubiquitination and decreased protein abundance. PIRE and PBL13 mutants display higher RBOHD protein accumulation, increased ROS production, and are more resistant to bacterial infection. Thus, our study reveals an intricate post-translational network that negatively regulates the abundance of a conserved NADPH oxidase.

Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, has resulted thus far in greater than 933,000 deaths worldwide; yet disease pathogenesis remains unclear. Clinical and immunological features of patients with COVID-19 have highlighted a potential role for changes in immune activity in regulating disease severity. However, little is known about the responses in human lung tissue, the primary site of infection. Here we show that pathways related to neutrophil activation and pulmonary fibrosis are among the major up-regulated transcriptional signatures in lung tissue obtained from patients who died of COVID-19 in Wuhan, China. Strikingly, the viral burden was low in all samples, which suggests that the patient deaths may be related to the host response rather than an active fulminant infection. Examination of the colonic transcriptome of these patients suggested that SARS-CoV-2 impacted host responses even at a site with no obvious pathogenesis. Further proteomics analysis validated our transcriptome findings and identified several key proteins, such as the SARS-CoV-2 entry-associated protease cathepsins B and L and the inflammatory response modulator S100A8/A9, that are highly expressed in fatal cases, revealing potential drug targets for COVID-19.

Nucleotide-binding leucine-rich repeat (NLR) immune receptors play a critical role in defence against pathogens in plants and animals. However, we know very little about NLR-interacting proteins and the mechanisms that regulate NLR levels. Here, we used proximity labeling (PL) to identify the proteome proximal to N, which is an NLR that confers resistance to Tobacco mosaic virus (TMV). Evaluation of different PL methods indicated that TurboID-based PL provides more efficient levels of biotinylation than BioID and BioID2 in plants. TurboID-based PL of N followed by quantitative proteomic analysis and genetic screening revealed multiple regulators of N-mediated immunity. Interestingly, a putative E3 ubiquitin ligase, UBR7, directly interacts with the TIR domain of N. UBR7 downregulation leads to an increased amount of N protein and enhanced TMV resistance. TMV-p50 effector disrupts the N-UBR7 interaction and relieves negative regulation of N. These findings demonstrate the utility of TurboID-based PL in plants and the N-interacting proteins we identified enhance our understanding of the mechanisms underlying NLR regulation.

Alpha Particle X-ray Spectrometer (APXS) is one of the two scientific experiments on Chandrayaan-2 rover named as Pragyan. The primary scientific objective of APXS is to determine the elemental composition of the lunar surface in the surrounding regions of the landing site. This will be achieved by employing the technique of X-ray fluorescence spectroscopy using in-situ excitation source Cm-244 emitting both X-rays and alpha particles. These radiations excite characteristic X-rays of the elements by the processes of particle induced X-ray emission (PIXE) and X-ray fluorescence (XRF). The characteristic X-rays are detected by the state-of-the-art X-ray detector known as Silicon Drift Detector (SDD), which provides high energy resolution as well as high efficiency in the energy range of 1 to 25 keV. This enables APXS to detect all major rock forming elements such as, Na, Mg, Al, Si, Ca, Ti and Fe. The Flight Model (FM) of the APXS payload has been completed and tested for various instrument parameters. The APXS provides energy resolution of 135 eV at 5.9 keV for the detector operating temperature of about -35 deg C. The design details and the performance measurement of APXS are presented in this paper.

Solar X-ray Monitor (XSM) is one of the scientific instruments on-board Chandrayaan-2 orbiter. The XSM along with instrument CLASS (Chandras Large Area Soft x-ray Spectrometer) comprise the remote X-ray fluorescence spectroscopy experiment of Chandrayaan-2 mission with an objective to determine the elemental composition of the lunar surface on a global scale. XSM instrument will measure the solar X-rays in the energy range of 1-15 keV using state-of-the-art Silicon Drift Detector (SDD). The Flight Model (FM) of the XSM payload has been designed, realized and characterized for various operating parameters. XSM provides energy resolution of 180 eV at 5.9 keV with high time cadence of one second. The X-ray spectra of the Sun observed with XSM will also contribute to the study of solar corona. The detailed description and the performance characteristics of the XSM instrument are presented in this paper.

Nucleotide-binding leucine-rich repeat (NLR) immune receptors play a critical role in defence against pathogens in plants and animals. However, we know very little about NLR-interacting proteins and the mechanisms that regulate NLR levels. Here, we used proximity labeling (PL) to identify the proteome proximal to N, which is an NLR that confers resistance to Tobacco mosaic virus (TMV). Evaluation of different PL methods indicated that TurboID-based PL provides more efficient levels of biotinylation than BioID and BioID2 in plants. TurboID-based PL of N followed by quantitative proteomic analysis and genetic screening revealed multiple regulators of N-mediated immunity. Interestingly, a putative E3 ubiquitin ligase, UBR7, directly interacts with the TIR domain of N. UBR7 downregulation leads to an increased amount of N protein and enhanced TMV resistance. TMV-p50 effector disrupts the N-UBR7 interaction and relieves negative regulation of N. These findings demonstrate the utility of TurboID-based PL in plants and the N-interacting proteins we identified enhance our understanding of the mechanisms underlying NLR regulation.

Multigram drug depot systems for extended drug release could transform our capacity to effectively treat patients across a myriad of diseases. For example, tuberculosis (TB) requires multimonth courses of daily multigram doses for treatment. To address the challenge of prolonged dosing for regimens requiring multigram drug dosing, we developed a gastric resident system delivered through the nasogastric route that was capable of safely encapsulating and releasing grams of antibiotics over a period of weeks. Initial preclinical safety and drug release were demonstrated in a swine model with a panel of TB antibiotics. We anticipate multiple applications in the field of infectious diseases, as well as for other indications where multigram depots could impart meaningful benefits to patients, helping maximize adherence to their medication., QC 20190509

Alpha Particle X-ray Spectrometer (APXS) is one of the two scientific experiments on Chandrayaan-2 rover named as Pragyan. The primary scientific objective of APXS is to determine the elemental composition of the lunar surface in the surrounding regions of the landing site. This will be achieved by employing the technique of X-ray fluorescence spectroscopy using in-situ excitation source Cm-244 emitting both X-rays and alpha particles. These radiations excite characteristic X-rays of the elements by the processes of particle induced X-ray emission (PIXE) and X-ray fluorescence (XRF). The characteristic X-rays are detected by the state-of-the-art X-ray detector known as Silicon Drift Detector (SDD), which provides high energy resolution as well as high efficiency in the energy range of 1 to 25 keV. This enables APXS to detect all major rock forming elements such as, Na, Mg, Al, Si, Ca, Ti and Fe. The Flight Model (FM) of the APXS payload has been completed and tested for various instrument parameters. The APXS provides energy resolution of 135 eV at 5.9 keV for the detector operating temperature of about -35 deg C. The design details and the performance measurement of APXS are presented in this paper.

Solar X-ray Monitor (XSM) is one of the scientific instruments on-board Chandrayaan-2 orbiter. The XSM along with instrument CLASS (Chandras Large Area Soft x-ray Spectrometer) comprise the remote X-ray fluorescence spectroscopy experiment of Chandrayaan-2 mission with an objective to determine the elemental composition of the lunar surface on a global scale. XSM instrument will measure the solar X-rays in the energy range of 1-15 keV using state-of-the-art Silicon Drift Detector (SDD). The Flight Model (FM) of the XSM payload has been designed, realized and characterized for various operating parameters. XSM provides energy resolution of 180 eV at 5.9 keV with high time cadence of one second. The X-ray spectra of the Sun observed with XSM will also contribute to the study of solar corona. The detailed description and the performance characteristics of the XSM instrument are presented in this paper.

Receptor-like cytoplasmic kinases (RLCKs) in Arabidopsis play a central role in the integration of signaling input from various growth and immune signaling pathways. BOTRYTIS-INDUCED KINASE 1 (BIK1), belonging to the RLCK family, is an important player in defense against bacterial and fungal pathogens and in ethylene and brassinosteroid hormone signaling. In this study, the purification and crystallization of a first member of the class VI family of RLCK proteins, BIK1, are reported. BIK1 was crystallized using the microbatch-under-oil method. X-ray diffraction data were collected to 2.35 Å resolution. The crystals belonged to the monoclinic space group C2, with two monomers per asymmetric unit.

Receptor-like cytoplasmic kinases (RLCKs) in Arabidopsis play a central role in the integration of signaling input from various growth and immune signaling pathways. BOTRYTIS-INDUCED KINASE 1 (BIK1), belonging to the RLCK family, is an important player in defense against bacterial and fungal pathogens and in ethylene and brassinosteroid hormone signaling. In this study, the purification and crystallization of a first member of the class VI family of RLCK proteins, BIK1, are reported. BIK1 was crystallized using the microbatch-under-oil method. X-ray diffraction data were collected to 2.35 Å resolution. The crystals belonged to the monoclinic space group C2, with two monomers per asymmetric unit.

The National Cancer Policy Forum of the National Academies of Sciences, Engineering and Medicine sponsored a workshop on July 24 and 25, 2017 on Long-Term Survivorship after Cancer Treatment. The workshop brought together diverse stakeholders (patients, advocates, academicians, clinicians, research funders, and policymakers) to review progress and ongoing challenges since the Institute of Medicine (IOM)'s seminal report on the subject of adult cancer survivors published in 2006. This commentary profiles the content of the meeting sessions and concludes with recommendations that stem from the workshop discussions. Although there has been progress over the past decade, many of the recommendations from the 2006 report have not been fully implemented. Obstacles related to the routine delivery of standardized physical and psychosocial care services to cancer survivors are substantial, with important gaps in care for patients and caregivers. Innovative care models for cancer survivors have emerged, and changes in accreditation requirements such as the Commission on Cancer's (CoC) requirement for survivorship care planning have put cancer survivorship on the radar. The Center for Medicare & Medicaid Innovation's Oncology Care Model (OCM), which requires psychosocial services and the creation of survivorship care plans for its beneficiary participants, has placed increased emphasis on this service. The OCM, in conjunction with the CoC requirement, is encouraging electronic health record vendors to incorporate survivorship care planning functionality into updated versions of their products. As new models of care emerge, coordination and communication among survivors and their clinicians will be required to implement patient- and community-centered strategies.

Microbial patterns are recognized by cell-surface receptors to initiate pattern-triggered immunity (PTI) in plants. Receptor-like cytoplasmic kinases (RLCKs), such as BIK1, and calcium-dependent protein kinases (CPKs) are engaged during PTI to activate the NADPH oxidase RBOHD for reactive oxygen species (ROS) production. It is unknown whether protein kinases besides CPKs and RLCKs participate in RBOHD regulation. We screened mutants in all ten Arabidopsis MAP4 kinases (MAP4Ks) and identified the conserved MAP4K SIK1 as a positive regulator of PTI. sik1 mutants were compromised in their ability to elicit the ROS burst in response to microbial features and exhibited compromised PTI to bacterial infection. SIK1 directly interacts with, phosphorylates, and stabilizes BIK1 in a kinase activity-dependent manner. Furthermore, SIK1 directly interacts with and phosphorylates RBOHD upon flagellin perception. Thus, SIK1 positively regulates immunity by stabilizing BIK1 and activating RBOHD to promote the extracellular ROS burst.

In the present study, out of 1156 neonatal goat kids, 238 showing clinical diarrhea were used for detection of toxinotypes of Clostridium perfringens, Enteropathogenic E. coli (EPEC), Group A rotavirus (GARV) and Bovine coronavirus (BCV). Isolation and toxinotyping of isolates were done by multiplex Polymerase chain reaction (PCR) using primers for cpa, cpb, cpb2, etx and iap genes. For EPEC, isolation and identification were done using bfpA gene and SYBR green based real time PCR (qPCR). GARV and BCV were detected, by one-step RT-PCR (osRT-PCR). The incidence of C. perfringens was 15.13% with 75% isolates toxinotype A, 25% type D and 61.11% of isolates carrying the β2-toxin gene. The incidence of EPEC was 68.07% based on qPCR, whereas 21.85% were positive for GARV and 15.97% for BCV by osRT-PCR. There was mixed infection of C. perfringens and EPEC in 11.76% and 3.78% for C. perfringens and GARV and 2.1% of C. perfringens and BCV. EPEC and GARV was 19.74% and EPEC plus BCV positivity was 11.34%. GARV and BCV was 5.88%, and 4.20% had mixed infection of EPEC, GARV and BCV. Of the total diarrheic kids sampled, 0.84% had mixed infection of C. perfringens, GARV, BCV and EPEC. On the basis of the above findings, it may be concluded that isolation, multiplex PCR and real time PCR facilitated the characterization of circulating C. perfringens toxinotypes and EPEC in goats reared under semi-arid conditions. The importance of enteritis caused by GARV and BCV and their role in mixed infection in goats requires extensive screening and pathogenicity studies to associate the symptoms with disease., U populaciji od 1156 neonatalnih jarića 238 je pokazivalo kliničke znakove proljeva. Od njih su uzeti uzorci izmeta za dokazivanje toksinskih tipova bakterije Clostridium perfringens, enteropatogenih sojeva bakterije E. coli (engl. enteropathogenic E. coli, EPEC), rotavirusa skupine A (engl. group A rotavirus, GARV) i goveđeg koronavirusa (engl. bovine coronavirus, BCV). Izdvajanje i toksinska tipizacija izolata provedeni su višestrukom lančanom reakcijom polimerazom (PCR) upotrebom početnica za gene cpa, cpb, cpb2, etx i iap. Izdvajanje i identifikacija EPEC-a provedeni su pretragom na gen bfpA i PCR-om u stvarnom vremenu, uz upotrebu SYBR zelenila (qPCR). Za dokaz rotavirusa skupine A i goveđeg koronavirusa upotrijebljena je RT-PCR (osRT-PCR). Incidencija bakterije C. perfringens iznosila je 15,13 %. Od toga je 75 % izolata pripadalo toksinskom tipu A, 25 % tipu D, dok je 61,11 % izolata imalo gen za toksin β2. Incidencija EPEC-a iznosila je 68,07 %, a 21,85 % pretraženih uzoraka bilo je pozitivno na GARV te 15,97 % na BCV. Mješovita infekcija bakterijom C. perfringens i EPEC-om utvrđena je u 11,76 % uzoraka, C. perfringens i GARV u 3,78 % te C. perfringens i BCV u 2,1 % pretraženih uzoraka. Mješovita infekcija EPEC-om i GARV-om utvrđena je u 19,74 %, a EPEC-om i BCV-om u 11,34 %. Mješovita infekcija rotavirusom i koronavirusom bila je ustanovljena u 5,88 %, a mješovita infekcija EPEC-om, GARV-om i BCV-om u 4,20 % uzoraka. Od ukupnog broja pretražene jaradi s proljevom u njih 0,84 % dokazana je mješovita infekcija bakterijom C. perfringens, rotavirusom skupine A, goveđim koronavirusom i EPEC-om. Na osnovi prikazanih rezultata može se zaključiti da izdvajanje, višestruki PCR te PCR u stvarnom vremenu omogućuju karakterizaciju i praćenje kolanja toksinskih tipova bakterija C. perfringens i EPEC-a u koza uzgajanih u sušnim uvjetima. Važnost enteritisa uzrokovanog rotavirusom skupine A i goveđim koronavirusom te njihova uloga kod mješovitih infekcija u koza zahtijevaj

The National Cancer Policy Forum of the National Academies of Sciences, Engineering and Medicine sponsored a workshop on July 24 and 25, 2017 on Long-Term Survivorship after Cancer Treatment. The workshop brought together diverse stakeholders (patients, advocates, academicians, clinicians, research funders, and policymakers) to review progress and ongoing challenges since the Institute of Medicine (IOM)'s seminal report on the subject of adult cancer survivors published in 2006. This commentary profiles the content of the meeting sessions and concludes with recommendations that stem from the workshop discussions. Although there has been progress over the past decade, many of the recommendations from the 2006 report have not been fully implemented. Obstacles related to the routine delivery of standardized physical and psychosocial care services to cancer survivors are substantial, with important gaps in care for patients and caregivers. Innovative care models for cancer survivors have emerged, and changes in accreditation requirements such as the Commission on Cancer's (CoC) requirement for survivorship care planning have put cancer survivorship on the radar. The Center for Medicare & Medicaid Innovation's Oncology Care Model (OCM), which requires psychosocial services and the creation of survivorship care plans for its beneficiary participants, has placed increased emphasis on this service. The OCM, in conjunction with the CoC requirement, is encouraging electronic health record vendors to incorporate survivorship care planning functionality into updated versions of their products. As new models of care emerge, coordination and communication among survivors and their clinicians will be required to implement patient- and community-centered strategies.

Microbial patterns are recognized by cell-surface receptors to initiate pattern-triggered immunity (PTI) in plants. Receptor-like cytoplasmic kinases (RLCKs), such as BIK1, and calcium-dependent protein kinases (CPKs) are engaged during PTI to activate the NADPH oxidase RBOHD for reactive oxygen species (ROS) production. It is unknown whether protein kinases besides CPKs and RLCKs participate in RBOHD regulation. We screened mutants in all ten Arabidopsis MAP4 kinases (MAP4Ks) and identified the conserved MAP4K SIK1 as a positive regulator of PTI. sik1 mutants were compromised in their ability to elicit the ROS burst in response to microbial features and exhibited compromised PTI to bacterial infection. SIK1 directly interacts with, phosphorylates, and stabilizes BIK1 in a kinase activity-dependent manner. Furthermore, SIK1 directly interacts with and phosphorylates RBOHD upon flagellin perception. Thus, SIK1 positively regulates immunity by stabilizing BIK1 and activating RBOHD to promote the extracellular ROS burst.

Microbial patterns are recognized by cell-surface receptors to initiate pattern-triggered immunity (PTI) in plants. Receptor-like cytoplasmic kinases (RLCKs), such as BIK1, and calcium-dependent protein kinases (CPKs) are engaged during PTI to activate the NADPH oxidase RBOHD for reactive oxygen species (ROS) production. It is unknown whether protein kinases besides CPKs and RLCKs participate in RBOHD regulation. We screened mutants in all ten Arabidopsis MAP4 kinases (MAP4Ks) and identified the conserved MAP4K SIK1 as a positive regulator of PTI. sik1 mutants were compromised in their ability to elicit the ROS burst in response to microbial features and exhibited compromised PTI to bacterial infection. SIK1 directly interacts with, phosphorylates, and stabilizes BIK1 in a kinase activity-dependent manner. Furthermore, SIK1 directly interacts with and phosphorylates RBOHD upon flagellin perception. Thus, SIK1 positively regulates immunity by stabilizing BIK1 and activating RBOHD to promote the extracellular ROS burst.

PurposeAsians report worse experiences with care than Whites. This could be due to true differences in care received, expectations about care, or survey response styles. We examined responses to the Consumer Assessment of Healthcare Providers and Systems (CAHPS®) Medicare survey items by Whites and Asians, controlling for underlying level on the CAHPS constructs.MethodsWe conducted multiple group analyses to evaluate measurement equivalence of CAHPS Medicare survey data between White and Asian Medicare beneficiaries for CAHPS reporting composites (communication with personal doctor, access to care, plan customer service) and global ratings of care using pooled data from 2007 to 2011. Responses were obtained from 1,326,410 non-Hispanic Whites and 40,672 non-Hispanic Asians (hereafter referred to as Whites and Asians). The median age for Whites was 70, with 24 % 80 or older, and 70 for Asians, with 23 % 80 or older. Fifty-eight percent of Whites and 56 % of Asians were female.ResultsA model without group-specific estimates fit the data as well as a model that included 12 group-specific estimates (7 factor loadings, 3 measured variable errors, and 2 item intercepts): Comparative Fit Index = 0.947 and 0.948; root-mean-square error of approximation = 0.052 and 0.052, respectively). Differences in latent CAHPS score means between Whites and Hispanics estimated from the two models were similar, differing by 0.053 SD or less.ConclusionsThis study provides support for measurement equivalence of the CAHPS Medicare survey composites (communication, access, customer service) and global ratings between White and Asian respondents, supporting comparisons of care experiences between the two groups.

There is growing interest in high-energy astrophysics community for the development of sensitive instruments in the hard X-ray energy extending to few hundred keV. This requires position sensitive detector modules with high efficiency in the hard X-ray energy range. Here, we present development of a detector module, which consists of 25 mm x 25 mm CeBr3 scintillation detector, read out by a custom designed two dimensional array of Silicon Photo-Multipliers (SiPM). Readout of common cathode of SiPMs provides the spectral measurement whereas the readout of individual SiPM anodes provides measurement of interaction position in the crystal. Preliminary results for spectral and position measurements with the detector module are presented here., Comment: Published in SPIE Proceedings Vol. 10392

Chickpea (Cicer arietinum L.) is the one of the most important pulse crops in the world and its production is limited by terminal drought. Unlike conventional breeding for yield, it is more challenging and requires to be measured in terms of its manifestation towards changing performance of a genotype under stress. An evaluation of a panel developed for drought and breeding studies has clearly identified the presence of large variability for drought tolerance. A large number of traits have been screened and it has been inferred that drought susceptibility index is the best way to identify genotypes that have resilience to terminal drought. However, different genotypes possessed various physiological mechanisms to cope with the effects of drought and, hence, provide ample opportunities to breeders to combine them to develop drought-tolerant genotypes. The chickpea genotypes L550, PG112 and ICC92944 have shown higher mean values for yield traits under stress and have desirable terminal drought-tolerant mechanisms for yield and other associated characters such as lower DSI, higher HI, higher BY and higher grain yield. They have, thus, emerged as stable genotypes for yield under stress situations. Though MABC for root traits has been identified, rapid screening techniques using CTD and identification of markers for MSI and RWC to be used for screening segregating generations appears to be promising in north Indian conditions. This is because unlike in south India, drought in the north India develops abruptly after a cold period, giving little time for the root system to respond. Thus, breeding for terminal drought tolerance would require concentrating on these traits too.

PurposeAsians report worse experiences with care than Whites. This could be due to true differences in care received, expectations about care, or survey response styles. We examined responses to the Consumer Assessment of Healthcare Providers and Systems (CAHPS®) Medicare survey items by Whites and Asians, controlling for underlying level on the CAHPS constructs.MethodsWe conducted multiple group analyses to evaluate measurement equivalence of CAHPS Medicare survey data between White and Asian Medicare beneficiaries for CAHPS reporting composites (communication with personal doctor, access to care, plan customer service) and global ratings of care using pooled data from 2007 to 2011. Responses were obtained from 1,326,410 non-Hispanic Whites and 40,672 non-Hispanic Asians (hereafter referred to as Whites and Asians). The median age for Whites was 70, with 24 % 80 or older, and 70 for Asians, with 23 % 80 or older. Fifty-eight percent of Whites and 56 % of Asians were female.ResultsA model without group-specific estimates fit the data as well as a model that included 12 group-specific estimates (7 factor loadings, 3 measured variable errors, and 2 item intercepts): Comparative Fit Index = 0.947 and 0.948; root-mean-square error of approximation = 0.052 and 0.052, respectively). Differences in latent CAHPS score means between Whites and Hispanics estimated from the two models were similar, differing by 0.053 SD or less.ConclusionsThis study provides support for measurement equivalence of the CAHPS Medicare survey composites (communication, access, customer service) and global ratings between White and Asian respondents, supporting comparisons of care experiences between the two groups.

There is growing interest in high-energy astrophysics community for the development of sensitive instruments in the hard X-ray energy extending to few hundred keV. This requires position sensitive detector modules with high efficiency in the hard X-ray energy range. Here, we present development of a detector module, which consists of 25 mm x 25 mm CeBr3 scintillation detector, read out by a custom designed two dimensional array of Silicon Photo-Multipliers (SiPM). Readout of common cathode of SiPMs provides the spectral measurement whereas the readout of individual SiPM anodes provides measurement of interaction position in the crystal. Preliminary results for spectral and position measurements with the detector module are presented here., Comment: Published in SPIE Proceedings Vol. 10392

259 Background: Asians report worse experiences with care than Whites. This could be due to true differences in care received, expectations about care, or survey response styles. To examine measurement equivalence of the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Medicare survey items between Whites and Asians. Methods: We conducted multiple group confirmatory factor analyses to evaluate measurement equivalence of CAHPS Medicare survey data between White and Asian Medicare beneficiaries for three CAHPS reporting composites (communication with personal doctor, access to care, plan customer service) and global ratings of care using pooled CAHPS data from 2007-2011. Responses were obtained from non-Hispanic whites (n = 1,326,410) and Asians (n = 40,672). The median age for whites was 70, with 24% 80 or older, and 70 for Asians, with 23% 80 or older. Fifty-eight percent of the whites and 56% of the Asians were female. Results: A model without group-specific estimates fit the data as well as a model that included 12 group-specific estimates suggested by Lagrange multiplier tests (Comparative Fit Index = 0.922, Root Mean Square Error of Approximation = 0.064). Three of the 12 group-specific estimates consisted of 7 factor loadings, 3 measured variable errors, and 2 item intercepts. Six of the factor loadings were larger for Asians than for whites. Conclusions: This study provides general support for measurement equivalence in response to the CAHPS Medicare survey composites (communication, access, customer service) and global ratings between White and Asian respondents, supporting comparison of care experiences for the two groups.

259 Background: Asians report worse experiences with care than Whites. This could be due to true differences in care received, expectations about care, or survey response styles. To examine measurement equivalence of the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Medicare survey items between Whites and Asians. Methods: We conducted multiple group confirmatory factor analyses to evaluate measurement equivalence of CAHPS Medicare survey data between White and Asian Medicare beneficiaries for three CAHPS reporting composites (communication with personal doctor, access to care, plan customer service) and global ratings of care using pooled CAHPS data from 2007-2011. Responses were obtained from non-Hispanic whites (n = 1,326,410) and Asians (n = 40,672). The median age for whites was 70, with 24% 80 or older, and 70 for Asians, with 23% 80 or older. Fifty-eight percent of the whites and 56% of the Asians were female. Results: A model without group-specific estimates fit the data as well as a model that included 12 group-specific estimates suggested by Lagrange multiplier tests (Comparative Fit Index = 0.922, Root Mean Square Error of Approximation = 0.064). Three of the 12 group-specific estimates consisted of 7 factor loadings, 3 measured variable errors, and 2 item intercepts. Six of the factor loadings were larger for Asians than for whites. Conclusions: This study provides general support for measurement equivalence in response to the CAHPS Medicare survey composites (communication, access, customer service) and global ratings between White and Asian respondents, supporting comparison of care experiences for the two groups.

PurposeLittle is known about factors associated with unmet needs for symptom management in patients with cancer.MethodsPatients with a new diagnosis of lung and colorectal cancer from the diverse nationally representative Cancer Care Outcomes Research and Surveillance cohort completed a survey approximately 5 months after diagnosis (N = 5,422). We estimated the prevalence of unmet need for symptom management, defined as patients who report that they wanted help for at least one common symptom (pain, fatigue, depression, nausea/vomiting, cough, dyspnea, diarrhea) during the 4 weeks before the survey but did not receive it. We identified patient factors associated with unmet need by using logistic regression with random effects to account for clustering within study sites.ResultsOverall, 15% (791 of 5,422) of patients had at least one unmet need for symptom management. Adjusting for sociodemographic and clinical factors, African American race, being uninsured or poor, having early-stage lung cancer, and the presence of moderate to severe symptoms were associated with unmet need (all P < .05). Furthermore, patients who rated their physician's communication score < 80 (on a 0 to 100 scale) had adjusted rates of an unmet need for symptom management that were more than twice as high as patients who rated their physicians with a perfect communication score (23.1% v 10.0%; P < .001).ConclusionA significant minority of patients with newly diagnosed lung and colorectal cancer report unmet needs for symptom management. Interventions to improve symptom management should consider the importance of physician communication to the patient's experience of disease.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address s, Funding Agencies|Terry Fox Foundation Grant [TF-13-20]; UAEU Program for Advanced Research (UPAR) [31S118]; NIH [AR47901, R21CA188818, R15 CA137499-01, F32CA177139, P20RR016477, P20GM103434, R01CA170378, U54CA149145, U54CA143907, R01-HL107652, R01CA166348, R01GM071725, R01 CA109335-04A1, 109511R01CA151304CA168997 A11106131R03CA1711326 1P01AT003961RO1 CA100816P01AG034906 R01AG020642P01AG034906-01A1R01HL108006]; NIH NRSA Grant [F31CA154080]; NIH (NIAID) R01: Combination therapies for chronic HBV, liver disease, and cancer [AI076535]; Sky Foundation Inc. Michigan; University of Glasgow; Beatson Oncology Centre Fund; Spanish Ministry of Economy and Competitivity, ISCIII [PI12/00137, RTICC: RD12/0036/0028]; FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion [CTS-6844, CTS-1848]; Consejeria de Salud of the Junta de Andalucia [PI-0135-2010, PI-0306-2012]; ISCIII [PIE13/0004]; FEDER funds; United Soybean Board; NIH NCCAM Grant [K01AT007324]; NIH NCI Grant [R33 CA161873-02]; Michael Cuccione Childhood Cancer Foundation Graduate Studentship; Ovarian and Prostate Cancer Research Trust, UK; West Virginia Higher Education Policy Commission/Division of Science Research; National Institutes of Health; Italian Association for Cancer Research (AIRC) [IG10636, 15403]; GRACE Charity, UK; Breast Cancer Campaign, UK; Michael Cuccione Childhood Cancer Foundation Postdoctoral Fellowship; Connecticut State University; Swedish Research Council; Swedish Research Society; University of Texas Health Science Centre at Tyler, Elsa U. Pardee Foundation; CPRIT; Cancer Prevention and Research Institute of Texas; NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIH National Institute on Alcohol Abuse and Alcoholism (NIAAA); Gilead and Shire Pharmaceuticals; NIH/NCI [1R01CA20009, 5R01CAl27258-05, R21CA184788, NIH P30 CA22453, NCI RO1 28704]; Scottish Governments Rural and Environment Science and Analytical Services Divis

BackgroundSince 1990, the National Cancer Institute (NCI) and Centers for Medicare and Medicaid Services (CMS) have collaborated to create linked data resources to improve our understanding of patterns of care, health care costs, and trends in utilization. However, existing data linkages have not included measures of patient experiences with care.ObjectiveTo describe a new resource for quality of care research based on a linkage between the Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS®) patient surveys and the NCI's Surveillance, Epidemiology and End Results (SEER) data.DesignThis is an observational study of CAHPS respondents and includes both fee-for-service and Medicare Advantage beneficiaries with and without cancer. The data linkage includes: CAHPS survey data collected between 1998 and 2010 to assess patient reports on multiple aspects of their care, such as access to needed and timely care, doctor communication, as well as patients' global ratings of their personal doctor, specialists, overall health care, and their health plan; SEER registry data (1973-2007) on cancer site, stage, treatment, death information, and patient demographics; and longitudinal Medicare claims data (2002-2011) for fee-for-service beneficiaries on utilization and costs of care.ParticipantsIn total, 150,750 respondents were in the cancer cohort and 571,318 were in the non-cancer cohort.Main measuresThe data linkage includes SEER data on cancer site, stage, treatment, death information, and patient demographics, in addition to longitudinal data from Medicare claims and information on patient experiences from CAHPS surveys.Key resultsSizable proportions of cases from common cancers (e.g., breast, colorectal, prostate) and short-term survival cancers (e.g., pancreas) by time since diagnosis enable comparisons across the cancer care trajectory by MA vs. FFS coverage.ConclusionsSEER-CAHPS is a valuable resource for information about Medicare beneficiaries' experie

BackgroundSince 1990, the National Cancer Institute (NCI) and Centers for Medicare and Medicaid Services (CMS) have collaborated to create linked data resources to improve our understanding of patterns of care, health care costs, and trends in utilization. However, existing data linkages have not included measures of patient experiences with care.ObjectiveTo describe a new resource for quality of care research based on a linkage between the Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS®) patient surveys and the NCI's Surveillance, Epidemiology and End Results (SEER) data.DesignThis is an observational study of CAHPS respondents and includes both fee-for-service and Medicare Advantage beneficiaries with and without cancer. The data linkage includes: CAHPS survey data collected between 1998 and 2010 to assess patient reports on multiple aspects of their care, such as access to needed and timely care, doctor communication, as well as patients' global ratings of their personal doctor, specialists, overall health care, and their health plan; SEER registry data (1973-2007) on cancer site, stage, treatment, death information, and patient demographics; and longitudinal Medicare claims data (2002-2011) for fee-for-service beneficiaries on utilization and costs of care.ParticipantsIn total, 150,750 respondents were in the cancer cohort and 571,318 were in the non-cancer cohort.Main measuresThe data linkage includes SEER data on cancer site, stage, treatment, death information, and patient demographics, in addition to longitudinal data from Medicare claims and information on patient experiences from CAHPS surveys.Key resultsSizable proportions of cases from common cancers (e.g., breast, colorectal, prostate) and short-term survival cancers (e.g., pancreas) by time since diagnosis enable comparisons across the cancer care trajectory by MA vs. FFS coverage.ConclusionsSEER-CAHPS is a valuable resource for information about Medicare beneficiaries' experie

ImportanceShared decision making is associated with improved patient-reported outcomes of cancer treatment, but not all patients prefer to participate in medical decisions. Results from studies of the effect of matching between actual and preferred medical decision roles on patients' perceptions of care quality have been conflicting.ObjectivesTo determine whether shared decision making was associated with patient ratings of care quality and physician communication and whether patients' preferred decision roles modified those associations.Design, setting, and participantsWe performed a population- and health system-based survey of participants in the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) study diagnosed with lung and/or colorectal cancer between 2003 and 2005 (56% with colorectal cancer, 40% with non-small-cell lung cancer, and 5% with small-cell lung cancer). The CanCORS study included 9737 patients (cooperation rate among patients contacted, 59.9%) treated in integrated care delivery systems, academic institutions, private offices, and Veterans Affairs hospitals. The medical records were abstracted between October 11, 2005, and April 30, 2009; all analyses were conducted between 2013 and 2014.InterventionsWe surveyed patients specifically about their preferred roles in cancer treatment decisions and their actual roles in decisions about surgery, chemotherapy, and radiation therapy. We analyzed the responses of 5315 patients who completed baseline surveys and reported decision roles for a total of 10 817 treatment decisions and assessed associations of patients' decision roles with patient-reported quality of care and physician communication.Main outcomes and measuresThe outcomes (identified before data collection) included patient-reported excellent quality of care and top ratings (highest score) on a physician communication scale.ResultsAfter adjustment, patients describing physician-controlled (vs shared) decisions were less likely t

ContextRelatively few data are available about symptoms among cancer patients.ObjectivesTo describe the prevalence and severity of symptoms among a large, representative cohort of newly diagnosed cancer patients.MethodsWe collected survey data about symptoms (pain, fatigue, depression, nausea/vomiting, cough, dyspnea, and diarrhea) from 5422 patients with incident lung and colorectal cancer from the diverse, nationally representative Cancer Care Outcomes Research and Surveillance Consortium cohort. We described the prevalence of any symptoms and moderate/severe symptoms approximately four to six months after diagnosis. We used logistic regression to identify patient and clinical characteristics associated with symptoms, and calculated adjusted proportions of patients with symptoms.ResultsIn total, 5067 (93.5%) patients reported at least one symptom in the four weeks before their survey, with 51% reporting at least one moderate/severe symptom. Lung cancer patients reported more symptoms than colorectal cancer patients. Patients who received treatment or had more comorbidities were more likely to report symptoms. For example, after adjustment, patients who received chemotherapy during the six weeks before the survey were more likely than others to report at least one symptom (97.3% vs. 90.8%, P<0.001), and at least one moderate/severe symptom (56.8% vs. 46.2%, P<0.001). After adjustment, early- vs. late-stage patients did not differ in reports of at least one symptom (93.6% vs. 93.4%, P=0.853) and differed only slightly in reports of at least one moderate/severe symptom (53.3% vs. 49.6%, P=0.009).ConclusionMost recently diagnosed lung and colorectal cancer patients have cancer-related symptoms regardless of stage, and more than half have at least one moderate/severe symptom.