Ancient and traditional cultures have claimed another realm exists beyond everyday experience that can be accessed by shamanic and divination methods. Modern science views such claims with suspicion. ...Evidence is presented that this may be changing. Carl Jung proposed a conscious realm and an unconscious realm-the unconscious realm included the personal unconscious and the collective unconscious. Later, with his theory of synchronicity, he proposed a material realm and a psychic realm arising from a unitary realm. This essay follows Jung's colleague, Marie-Louise von Franz, and her efforts to identify ideas in science similar to Jung's. Von Franz found two French scientists with two realms similar to what Jung proposed: Olivier Costa de Beauregard and Albert Lautman. At the time von Franz published Divination and Synchronicity, quantum physicist David Bohm likewise proposed two realms: an implicit order and an explicit order. Recently, English physicist and Anglican priest Sir John Polkinghorne published his version of two realms. Contemporary physics claims there is an everyday world modeled by causal mechanistic science and a different quantum realm. This leads a contemporary physicist to sound like a shaman or diviner. The examples just considered are theoretical. In contrast, two examples from experimental physics-the hydrogen spectrum and Shaw's dripping faucet-embody a realm of time and a timeless pattern. The evidence considered supports Polkinghorne's suggestion that changes are underway, transforming science in ways similar to Jung's and von Franz's dual realms.
The purpose of this analysis was to assess the long-term impact of adding bevacizumab to adjuvant chemotherapy for early triple-negative breast cancer (TNBC).
Patients eligible for the open-label ...randomized phase III BEATRICE trial had centrally confirmed triple-negative operable primary invasive breast cancer (pT1a–pT3). Investigators selected anthracycline- and/or taxane-based chemotherapy for each patient. After definitive surgery, patients were randomized 1:1 to receive ≥4 cycles of chemotherapy alone or with 1 year of bevacizumab (5 mg/kg/week equivalent). Stratification factors were nodal status, selected chemotherapy, hormone receptor status, and type of surgery. The primary end point was invasive disease-free survival (IDFS; previously reported). Secondary outcome measures included overall survival (OS) and safety.
After 56 months’ median follow-up, 293 of 2591 randomized patients had died. There was no statistically significant difference in OS between treatment arms in either the total population (hazard ratio 0.93, 95% confidence interval CI 0.74–1.17; P = 0.52) or pre-specified subgroups. The 5-year OS rate was 88% (95% CI 86–90%) in both treatment arms. Updated IDFS results were consistent with the primary IDFS analysis. Five-year IDFS rates were 77% (95% CI 75–79%) with chemotherapy alone versus 80% (95% CI 77–82%) with bevacizumab. From 18 months after first study dose to study end, new grade ≥3 adverse events occurred in 4.6% and 4.5% of patients in the two arms, respectively.
Final OS results showed no significant benefit from bevacizumab therapy for early TNBC. Late-onset toxicities were rare in both groups. Five-year OS and IDFS rates suggest that the prognosis for patients with TNBC is better than previously thought.
NCT00528567
Persistent cold temperatures, a paucity of nutrients, freeze-thaw cycles, and the strongly seasonal light regime make Antarctica one of Earth’s least hospitable surface environments for complex life. ...Cyanobacteria, however, are well-adapted to such conditions and are often the dominant primary producers in Antarctic inland water environments. In particular, the network of meltwater ponds on the ‘dirty ice’ of the McMurdo Ice Shelf is an ecosystem with extensive cyanobacteria-dominated microbial mat accumulations. This study investigated intact polar lipids (IPLs), heterocyte glycolipids (HGs), and bacteriohopanepolyols (BHPs) in combination with 16S and 18S rRNA gene diversity in microbial mats of twelve ponds in this unique polar ecosystem. To constrain the effects of nutrient availability, temperature and freeze-thaw cycles on the lipid membrane composition, lipids were compared to stromatolite-forming cyanobacterial mats from ice-covered lakes in the McMurdo Dry Valleys as well as from (sub)tropical regions and hot springs. The 16S rRNA gene compositions of the McMurdo Ice Shelf mats confirm the dominance of Cyanobacteria and Proteobacteria while the 18S rRNA gene composition indicates the presence of Ochrophyta, Chlorophyta, Ciliophora, and other microfauna. IPL analyses revealed a predominantly bacterial community in the meltwater ponds, with archaeal lipids being barely detectable. IPLs are dominated by glycolipids and phospholipids, followed by aminolipids. The high abundance of sugar-bound lipids accords with a predominance of cyanobacterial primary producers. The phosphate-limited samples from the (sub)tropical, hot spring, and Lake Vanda sites revealed a higher abundance of aminolipids compared to those of the nitrogen-limited meltwater ponds, affirming the direct affects that N and P availability have on IPL compositions. The high abundance of polyunsaturated IPLs in the Antarctic microbial mats suggests that these lipids provide an important mechanism to maintain membrane fluidity in cold environments. High abundances of HG keto-ols and HG keto-diols, produced by heterocytous cyanobacteria, further support these findings and reveal a unique distribution compared to those from warmer climates.
Cyanobacteria in polar environments face environmental challenges, including cold temperatures and extreme light seasonality with small diurnal variation, which has implications for polar circadian ...clocks. However, polar cyanobacteria remain underrepresented in available genomic data, and there are limited opportunities to study their genetic adaptations to these challenges. This paper presents four new Antarctic cyanobacteria metagenome-assembled genomes (MAGs) from microbial mats in Lake Vanda in the McMurdo Dry Valleys in Antarctica. The four MAGs were classified as
sp. BulkMat.35,
MP8IB2.15,
sp. MP8IB2.171, and
MP9P1.79. The MAGs contain 2.76 Mbp - 6.07 Mbp, and the bin completion ranges from 74.2-92.57%. Furthermore, the four cyanobacteria MAGs have average nucleotide identities (ANIs) under 90% with each other and under 77% with six existing polar cyanobacteria MAGs and genomes. This suggests that they are novel cyanobacteria and demonstrates that polar cyanobacteria genomes are underrepresented in reference databases and there is continued need for genome sequencing of polar cyanobacteria. Analyses of the four novel and six existing polar cyanobacteria MAGs and genomes demonstrate they have genes coding for various cold tolerance mechanisms and most standard circadian rhythm genes with the
sp. BulkMat.35 and
MP9P1.79 contained
, a divergent homolog of
.
The optimal regimen for adjuvant breast cancer chemotherapy is undefined. We compared sequential to concurrent combination of doxorubicin and cyclophosphamide with docetaxel chemotherapy in women ...with node-positive non-metastatic breast cancer. We report the final, 10-year analysis of disease-free survival (DFS), overall survival (OS), and long-term safety.
A total of 3298 women with HER2 nonamplified breast cancer were randomized to doxorubicin and cyclophosphamide every 3 weeks for four cycles followed by docetaxel (AC → T) every 3 weeks for four cycles or docetaxel, doxorubicin, and cyclophosphamide (TAC) every 3 weeks for six cycles. The patients received standard radiotherapy and endocrine therapy and were followed up for 10 years with annual clinical evaluation and mammography.
The 10-year DFS rates were 66.5% in the AC → T arm and 66.3% in the TAC arm (P = 0.749). OS was 79.9% in the AC → T arm and 78.9% in the TAC arm (P = 0.506). TAC was associated with higher rates of febrile neutropenia, although G-CSF primary prophylaxis greatly reduced this risk. AC → T was associated with a higher rate of myalgia, hand-foot syndrome, fluid retention, and sensory neuropathy.
This 10-year analysis of the BCIRG-005 trial confirmed that the efficacy of TAC was not superior to AC → T in women with node-positive early breast cancer. The toxicity profiles differ between arms and were consistent with previous reports. The TAC regimen with G-CSF support provides shorter adjuvant treatment duration with less toxicity.
ClinicalTrials.gov Identifier NCT00312208.
In this Letter, we explore the hypothesis that the smooth appearance of bow shocks around some red supergiants (RSGs) might be caused by the ionization of their winds by external sources of ...radiation. Our numerical simulations of the bow shock generated by IRC −10414 (the first-ever RSG with an optically detected bow shock) show that the ionization of the wind results in its acceleration by a factor of 2, which reduces the difference between the wind and space velocities of the star and makes the contact discontinuity of the bow shock stable for a range of stellar space velocities and mass-loss rates. Our best-fitting model reproduces the overall shape and surface brightness of the observed bow shock and suggests that the space velocity and mass-loss rate of IRC −10414 are 50 km s−1 and 10−6 M yr−1, respectively, and that the number density of the local interstellar medium is 3 cm−3. It also shows that the bow shock emission comes mainly from the shocked stellar wind. This naturally explains the enhanced nitrogen abundance in the line-emitting material, derived from the spectroscopy of the bow shock. We found that photoionized bow shocks are 15-50 times brighter in optical line emission than their neutral counterparts, from which we conclude that the bow shock of IRC −10414 must be photoionized.
Precambrian marine carbonate strata are commonly assumed to have formed in warm‐water carbonate factories due to the temperature dependence of non‐skeletal carbonate precipitation rates. However, ...some climate models and geological observations suggest that global climate was cool for tens of millions of years prior to the onset of Snowball Earth glaciation at ∼717 Ma, in conflict with common interpretations of pre‐glacial carbonates as warm‐water carbonate factories. We report the occurrence of guttulatic microfabric—a petrographic fingerprint of ikaite, a carbonate mineral that only forms in cold sedimentary environments—in the Beck Spring Dolomite, a carbonate succession deposited in a low‐latitude shallow marine environment between ∼780 and 730 Ma. This interpretation of pre‐glacial carbonate factories aligns cold conditions with vase‐shaped microfossils, possible algal fossils, and molecular clock dates for crown‐group metazoans. Our observations indicate that these marine ecosystems were able to thrive in cold low‐latitude environments millions of years before the Snowball glaciations.
Plain Language Summary
Between 717 and 635 million years ago, Earth experienced two dramatic global glacial events, known as “Snowball Earth” glaciations, during which ice covered the oceans all the way to the equator. Geoscientists are still seeking to fully understand what caused these extreme climate events and how life on Earth survived them. Although geochemists have a variety of tools to reconstruct the temperature of ancient oceans, these methods are difficult to apply in rocks this old because primary signals have been too altered. Instead, we looked for a key microscopic fingerprint (“guttulatic microfabric”) of a type of calcium carbonate mineral (“ikaite”) that only forms in cold‐water environments. Previous work had proposed that we might expect to find evidence of this cold‐water carbonate mineral associated with a specific type of sediment called “giant ooids.” We found abundant evidence of guttulatic microfabric in sedimentary rocks containing giant ooids that formed in a low‐latitude shallow marine environment millions of years before the onset of global glaciation. Our observations suggest that Earth’s climate was cold before the onset of global glaciation, which could mean that marine organisms were accustomed to cold conditions well before the Snowball glaciations.
Key Points
Guttulatic microfabric is a characteristic fingerprint of ikaite, a mineral that forms only in cold‐water depositional environments
We report guttulatic microfabrics in grains and cements associated with giant ooids in the Tonian Beck Spring Dolomite
Our findings demonstrate that global climate was cold millions of years before the onset of the Sturtian glaciation
Dissolved iron and manganese and total dissolvable iron were measured in water column samples collected from the polynya region of the southern Ross Sea during cruises in November–December 1994 ...(spring 1994) and December 1995 to January 1996 (summer 1995). Iron and manganese addition bottle incubation experiments were also performed during these cruises in order to assess the nutritional sufficiency of ambient iron and manganese concentrations for growth of the phytoplankton community. Generally high dissolved iron concentrations (>0.5 nM) and relatively complex iron and manganese vertical profiles were obtained during the spring 1994 cruise, compared with the summer 1995 data. Dissolved iron concentrations in the upper water column averaged 1.0 nM during spring 1994 and 0.23 nM in summer 1995, excluding two stations where concentrations exceeding 1 nM are attributed to inputs from melting sea ice. The observed differences in the distribution of iron and manganese between spring 1994 and summer 1995 are attributed to seasonal decreases in the up welling of bottom waters and melting of sea ice, which supply these metals into the upper water column, combined with the cumulative removal of iron and manganese from the water column throughout the spring and summer, due to biological uptake, vertical export and scavenging by suspended and sinking particles. Results of the metal addition bottle incubation experiments indicate that ambient dissolved iron concentrations are adequate for phytoplankton growth requirements during the spring and early summer, when algal production is highest and Phaeocystis antarctica dominates the algal community, whereas low dissolved iron concentrations limit algal community growth later in the summer, except in the stratified, iron‐enriched waters near melting sea ice, where diatoms are able to bloom. Our observations and the inferred seasonal distributions of P. antarctica and diatoms in these waters suggest that iron availability and vertical mixing (i.e., irradiance) exert the primary controls on phytoplankton growth and community structure in the southern Ross Sea during the spring and summer.
The transcriptome of Toxoplasma gondii Radke, Jay R; Behnke, Michael S; Mackey, Aaron J ...
BMC biology,
12/2005, Letnik:
3, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Toxoplasma gondii gives rise to toxoplasmosis, among the most prevalent parasitic diseases of animals and man. Transformation of the tachzyoite stage into the latent bradyzoite-cyst form underlies ...chronic disease and leads to a lifetime risk of recrudescence in individuals whose immune system becomes compromised. Given the importance of tissue cyst formation, there has been intensive focus on the development of methods to study bradyzoite differentiation, although the molecular basis for the developmental switch is still largely unknown.
We have used serial analysis of gene expression (SAGE) to define the Toxoplasma gondii transcriptome of the intermediate-host life cycle that leads to the formation of the bradyzoite/tissue cyst. A broad view of gene expression is provided by >4-fold coverage from nine distinct libraries (approximately 300,000 SAGE tags) representing key developmental transitions in primary parasite populations and in laboratory strains representing the three canonical genotypes. SAGE tags, and their corresponding mRNAs, were analyzed with respect to abundance, uniqueness, and antisense/sense polarity and chromosome distribution and developmental specificity.
This study demonstrates that phenotypic transitions during parasite development were marked by unique stage-specific mRNAs that accounted for 18% of the total SAGE tags and varied from 1-5% of the tags in each developmental stage. We have also found that Toxoplasma mRNA pools have a unique parasite-specific composition with 1 in 5 transcripts encoding Apicomplexa-specific genes functioning in parasite invasion and transmission. Developmentally co-regulated genes were dispersed across all Toxoplasma chromosomes, as were tags representing each abundance class, and a variety of biochemical pathways indicating that trans-acting mechanisms likely control gene expression in this parasite. We observed distinct similarities in the specificity and expression levels of mRNAs in primary populations (Day-6 post-sporozoite infection) that occur prior to the onset of bradyzoite development that were uniquely shared with the virulent Type I-RH laboratory strain suggesting that development of RH may be arrested. By contrast, strains from Type II-Me49B7 and Type III-VEGmsj contain SAGE tags corresponding to bradyzoite genes, which suggests that priming of developmental expression likely plays a role in the greater capacity of these strains to complete bradyzoite development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As mass incarceration and supervision decline in the U.S., subtler forms of “invisible punishment” continue to affect individuals with a history of legal system involvement. Increasingly, the state ...recedes from direct involvement in invisible punishment, instead devolving responsibility—and potentially controlling at a distance—community-based organizations. In the process, punishment in the community is shaped by both the state and various segments of civil society. The present ethnography examines how staffers at a community-based reentry organization are subject to and resistant to state influence, and how this resistance generates new forms of invisible punishment. While state influence directs staffers to provide services focused on altering clients’ internal dispositions, staffers resist state influence by encouraging members to be their own advocates against the penal system. This agonistic process of resistance generates a hybridized form of invisible punishment, commingling the organizational goals and routines of penal state authorities with those of reentry staffers who see advocating against structures of punishment as a core mission. The final, hybridized form of this mode of penalty requires the client not only to look inward to effect dispositional changes, but also to look outward to be an active agent advocating against the exclusionary penal structures affecting them.
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