*2.1. Occurrence, General Appearance, Physical Properties and Optical Data*

Krasnoshteinite was found in the core of the borehole #2001, with a depth of 247.6–248 m, drilled in the Romanovskiy area (30 km south of the city of Berezniki) of the Verkhnekamskoe potassium salt deposit, Perm Krai, Western Urals, Russia. The general data on this well-known. Huge deposits are given in monographs [5,6]. Krasnoshteinite occurs in halite-carnallite rock and is associated with dritsite (Li2Al4(OH)12Cl2·3H2O) [7], dolomite, magnesite, quartz, Sr-bearing baryte, kaolinite, potassic feldspar, congolite, members of the goyazite SrAl3(PO4)(PO3OH)(OH)6–woodhouseite CaAl3(PO4)(SO4)(OH)6 series, fluorite, hematite, and anatase. The new mineral was probably formed as a result of diagenetic or post-diagenetic processes in halite-carnallite evaporitic rock of the Layer E of the Verkhnekamskoe deposit.

Krasnoshteinite occurs as separate tabular to lamellar crystals of up to 0.06 × 0.25 × 0.3 mm (Figure 1a,b) and their parallel intergrowths (Figure 1c) embedded in carnallite and halite. In some cases, tiny crystals of krasnoshteinite overgrow its larger crystal in random orientations to form a crystal cluster (Figure 1d). Samples shown in Figure 1 were separated after dissolution of a host halite-carnallite rock in water.

Crystals of krasnoshteinite are flattened on the *ab* plane. The pedions {010} and {0-10} and the pinacoid {100} are major lateral faces of the tabular crystals. The surface of the most developed "face" of a crystal is typically complicated, rough, and demonstrating coarse or/and fine striation along {100} (Figure 1); it is usually composed by several poorly formed faces belonging to the 0*kl* zone.

Krasnoshteinite is a transparent colorless mineral with a white streak and vitreous luster. It is brittle, with a Mohs hardness is ca. of 3. Krasnoshteinite demonstrates perfect cleavage on {010} and an imperfect cleavage on {100}. A fracture is stepped (observed under the microscope). The mineral is non-fluorescent in the ultraviolet light. The density measured by flotation in heavy liquids (bromoform + dimethylformamide) is 2.11 (1) g/cm3, and the density calculated using the empirical formula and the unit-cell parameters determined from single-crystal X-ray diffraction data is 2.115 g/cm3.

In plane polarized light, krasnoshteinite is colorless and non-pleochroic. It is optically biaxial (+), α = 1.563 (2), β = 1.565 (2), γ = 1.574 (2) (589 nm). 2*V* (meas.) = 50 (10)◦ and 2*V* (calc.) = 51◦. Dispersion of optical axes is distinct, *r* > *v*. Optical orientation is: *Y* = *b*, and *X* = *a*.

**Figure 1.** Separate crystals (**a**,**b**) and crystal clusters ((**c**,**d**): small crystals overgrow large crystal) of krasnoshteinite. Blocky crystals of dolomite and distorted quartz crystal are observed in (**b**).


*2.2. H-1PV + Histone Deacetylase Inhibitors (Valproic Acid)*

Preclinical proof-of-concept was also obtained for another treatment combining H-1PV with the histone deacetylase (HDAC) inhibitor (HDACi) valproic acid (VPA) [33]. HDACis hold significant promise in cancer therapy, due to their ability to cause malignant cell growth inhibition, re-differentiation and death [34]. Most interestingly, HDAC inhibition was also found to potentiate the oncotoxicity of various OVs, including vesicular stomatitis [35], herpes- [36], adeno- [37] and parvo [33]-viruses (for a review, see Reference [38]). The synergism between HDACi and H-1PV was first demonstrated by Li et al., who conducted preclinical testing of this combination in cervical carcinoma and PDAC models [33]. VPA proved to synergize with H-1PV in inducing DNA damage, oxidative stress and death in PDAC-derived cell lines. This cooperation was traced back, at least in part, to the ability of VPA to stimulate the acetylation and, in consequence, the oncotoxic activity of the viral protein NS1. Interestingly, VPA-induced hyperacetylation of NS1 was also associated with enhanced H-1PV DNA replication and viral gene transcription, ultimately boosting virus multiplication in tumor cells. The VPA-dependent increase in both H-1PV intrinsic oncotoxicity and multiplication was reflected in the potentiation of tumor suppression in animal models. In order to establish a clinically relevant animal model of PDAC, patient-derived material was xeno-transplanted in non-obese diabetic/severe combined immunodeficiency disease (NOD/SCID) mice. Alternatively, the human AsPC-1 cell line was implanted into nude rats. Tumors were subjected to mono versus combinatorial treatment and tumor growth parameters were comparatively evaluated. In line with the in vitro observations, H-1PV + VPA administration resulted in enhanced NS1 and H-1PV intra-tumoral accumulation, correlating with an increase in oxidative stress and subsequent apoptosis in co-treated tumors. The combination achieved complete AsPC-1 tumor eradication. Patient-derived xenografts were also responsive, yet to a somewhat

lesser extent, probably due to the characteristic PDAC intra-tumoral heterogeneity and prominent presence of stroma. tent, probably due to the characteristic PDAC intra-tumoral heterogeneity and prominent presence of stroma.

in vitro observations, H-1PV + VPA administration resulted in enhanced NS1 and H-1PV intra-tumoral accumulation, correlating with an increase in oxidative stress and subsequent apoptosis in co-treated tumors. The combination achieved complete AsPC-1 tumor eradication. Patient-derived xenografts were also responsive, yet to a somewhat lesser ex-

*Cancers* **2021**, *13*, x 6 of 15

It is noteworthy that besides its effects on tumor cell growth and OV oncotoxicity, VPA was reported to modulate the immune system, providing an additional possible interface for cooperation with OVs at the level of their intrinsic immuno-stimulating activity. VPA was indeed shown to: It is noteworthy that besides its effects on tumor cell growth and OV oncotoxicity, VPA was reported to modulate the immune system, providing an additional possible interface for cooperation with OVs at the level of their intrinsic immuno-stimulating activity. VPA was indeed shown to:

As a whole, the above data speak for the high translational relevance of VPA to the future development of PV-based combinatorial (immuno) therapies. As a whole, the above data speak for the high translational relevance of VPA to the future development of PV-based combinatorial (immuno) therapies.

In conclusion, two drugs that are available on the pharmaceutical market, i.e., gemcitabine (cytostatic) and VPA (antiepileptic), proved to be efficient in synergizing with H-1PV to suppress pancreatic cancer (Figure 2). In conclusion, two drugs that are available on the pharmaceutical market, i.e., gemcitabine (cytostatic) and VPA (antiepileptic), proved to be efficient in synergizing with H-1PV to suppress pancreatic cancer (Figure 2).

**Figure 2.** Parvovirus-based viro-immunotherapeutic combinations under development against pancreatic ducatl adenocarcinoma (PDAC). H-1PV-induced tumor cell lysis cooperates with gemcitabine-triggered programmed tumor cell death, valproic acid (VPA)-dependent epigenetic transcription regulation or interferon (IFN)-γ-induced immuno-stimulation to suppress PDAC. Preclinical data suggest that the immune system mediates, at least in part, this cooperation. H-1PV infection of tumor cells leads to the release of PAMPs/DAMPs, such as high-mobility group box 1 protein (HMGB1), which in turn alert the immune system to danger and mobilize an inflammatory antitumor immune response. Various aspects of H-1PV-, gemcitabine-, VPA- and IFN-γ-exerted immunomodulation may converge and synergize upon exposure of the host immune system to the respective combinations. The underlying mechanisms remain to be elucidated in detail by gathering extensive clinical experience. For details and references, see main text. **Figure 2.** Parvovirus-based viro-immunotherapeutic combinations under development against pancreatic ducatl adenocarcinoma (PDAC). H-1PV-induced tumor cell lysis cooperates with gemcitabine-triggered programmed tumor cell death, valproic acid (VPA)-dependent epigenetic transcription regulation or interferon (IFN)-γ-induced immuno-stimulation to suppress PDAC. Preclinical data suggest that the immune system mediates, at least in part, this cooperation. H-1PV infection of tumor cells leads to the release of PAMPs/DAMPs, such as high-mobility group box 1 protein (HMGB1), which in turn alert the immune system to danger and mobilize an inflammatory antitumor immune response. Various aspects of H-1PV-, gemcitabine-, VPA- and IFN-γ-exerted immunomodulation may converge and synergize upon exposure of the host immune system to the respective combinations. The underlying mechanisms remain to be elucidated in detail by gathering extensive clinical experience. For details and references, see main text.

#### Another combination with substantial potential for clinical development relies on the *2.3. H-1PV + Proinflammatory Cytokines (Interferon-Gamma)*

*2.3. H-1PV + Proinflammatory Cytokines (Interferon-Gamma)*

mutual complementation of H-1PV- and IFN-γ-mediated immune stimulation. It was Another combination with substantial potential for clinical development relies on the mutual complementation of H-1PV- and IFN-γ-mediated immune stimulation. It was shown that IFN-γ improves the vaccination potential of the virus and diminishes the development of peritoneal carcinomatosis in preclinical PDAC models. Concomitant intraperitoneal administration of both H-1PV and IFN-γ in these models led to extended animal survival correlating with enhanced peritoneal macrophage and splenocyte responses against tumor cells [42].


**3. Endfire mm-wave array for mobile phone**

Endfire array antenna is the array with the direction of maximum radiation, which lies along the line of the array. As shown in **Figure 7**, the endfire array is achieved with array element along the *y*-axis and maximum radiation direction in the *x*-axis. Compared with the broadside array, for the mobile phone with desired beam directions 1, 2, 3, and 4 in **Figure 1**, endfire array can be directly integrated into the PCB and save the thickness of the mobile phone. So, for mobile phones with a specific geometry of thin thickness, endfire array is preferable. However, due to the thin thickness of the mobile phone and thus the thin thickness of the endfire array, how to achieve the endfire array with the superior performance of thin thickness, small clearance, wide bandwidth, multiple polarization, and wide beam coverage is challenging. This section summarizes the typical design methods of horizontal-polarized endfire mm-wave array first. Then, the typical design methods of vertical-polarized endfire mm-wave array are summarized. Finally, the dual-polarized endfire mm-wave arrays are summarized.

### **3.1 Horizontal-polarized endfire mm-wave array**

To better summarize the horizontal polarization endfire mm-wave array for mobile phones, **Figure 8** shows the conceptual diagram of some typical horizontal polarization endfire mm-wave arrays. As shown in **Figure 9(b)**, the simplest method to achieve the endfire radiation is to deploy the mm-wave array vertical to the system ground. As the radiation element is horizontal polarization, horizontal polarization endfire mm-wave array is achieved. A similar idea can be found in [33] where the broadband magnetoelectric dipole antenna is applied as the element where 109.5% relative bandwidth is achieved. However, the critical drawback of this method is that the width of the mm-wave array should be enough to achieve proper performance. Thus, the thickness of the mobile phone is affected by the mm-wave array. A dipole antenna closing to the system ground, as shown in **Figure 9(c)**, has endfire radiation with horizontal polarization. The system ground can redirect the radiation to achieve a high gain. The parallel double line [34] or the slot line with balun [35] can be applied to feed

**Figure 7.** *Conceptual diagram of the antenna array with endfire radiation pattern.*

#### **Figure 8.**

*Typical design schematics of dual-polarized endfire mm-wave array. (a) Vertical deployment of dual-polarized element. (b) Horizontal-polarized dipole with vertical-polarized dipole. (c) Horizontal-polarized dipole with vertical-polarized horn. (d) Horizontal-polarized slot with vertical-polarized horn. (e) Two SIW horns with a polarizer. (f) Dual-polarized slot antennas.*

#### **Figure 9.**

*Conceptual diagram of the typical horizontal polarization endfire mm-wave array. (a) Mm-wave array on the mobile phone. (b) Vertical deployment for endfire radiation. (c) Dipole element for endfire radiation. (d) Monopole element for endfire radiation. (e) Open slot element for endfire radiation.*

the dipole. To achieve the wide bandwidth, the distance between the dipole antenna ground should be large. In [36], the arm length of the dipole antenna is tuned to different values to widen the bandwidth. Similar to the Yagi antenna, several directors are applied in [37–39] to further enhance the array gain and bandwidth. The monopole antenna of half-wavelength mode can also be placed near the system ground to achieve

the horizontal polarization endfire radiation, as shown in **Figure 9(d)**. This structure has been studied in [40], working at 60 GHz with a bandwidth of 6 GHz. Also, the open-ended slot antenna can radiate the horizontal polarization endfire pattern, as shown in **Figure 9(e)**. This structure has been studied in [41] working at 28 GHz with a bandwidth of 5 GHz. To achieve good performance with wide bandwidth, the space of the monopole antenna and slot antenna in **Figure 8** should be large.

### **3.2 Vertical-polarized endfire mm-wave array**

To better summary the vertical polarization endfire mm-wave array for mobile phone, **Figure 10** shows the conceptual diagram of some typical vertical polarization endfire mm-wave arrays. As shown in **Figure 10(b)**, the simplest method to achieve the endfire radiation is to deploy the mm-wave array vertically to the system ground. As the radiation element is vertical polarization, vertical polarization endfire mm-wave array is achieved. A similar idea can be found in [42, 43] where the slot, dielectric, and cavity resonators are applied simultaneously to achieve a wideband width of 47.1% [42] and 94.1 [43]. However, the critical drawback of this method is also that the width of the mm-wave array should be enough to achieve proper performance. Thus, the thickness of the mobile phone is affected by the mm-wave array. As shown in **Figure 10(c)**, the cavity slot element can be applied to radiate the vertical polarization pattern. Although the cavity slot element can achieve a low profile, the key technical difficulty is to achieve wide bandwidth. In [44], a substrate-integrated waveguide (SIW) endfire antenna array with zero clearance is designed. Three arbitrary pad-loading metallic vias are investigated to match the impedance within a relative bandwidth of 60%. Also, the slot on the SIW [45], taper slot [46], and the metasurface structure [47] can be applied to achieve a wide bandwidth of the SIW slot antenna. For the dipole element in **Figure 10(d)** and the monopole element in **Figure 10(e)**, vertical polarization with endfire radiation can be achieved. In [30], the monopole element with the parasitic element is applied to achieve the endfire radiation with steering beams. In [48], the compact vertically polarized endfire monopole-based Yagi antenna-in-package is proposed with a relative bandwidth of 16%. For the dipole or monopole element, the height should be large for a large bandwidth. By combing the cavity slot element and dipole/monopole element, the endfire magnetoelectric antenna with stable performance within a wide bandwidth can be achieved. For example, the SIW cavity slot antenna and dipole antenna in [49, 50]

#### **Figure 10.**

*Conceptual diagram of the typical vertical-polarized endfire mm-wave array. (a) mm-wave array on the mobile phone. (b) Vertical deployment for endfire radiation. (c) Cavity slot element for endfire radiation. (d) Dipole element for endfire radiation. (e) Monopole element for endfire radiation.*

**Figure 11.**

*Typical design schematics of integrating the mm-wave array in the mobile phone. (a) Using a window to reduce the blockage from metal-bezel. (b) Using the metal-bezel to design the mm-wave array antenna.*

and the SIW cavity slot antenna and monopole antenna in [51] are combined to achieve the wideband endfire magnetoelectric antenna. Also, to achieve good performance with wide bandwidth, the profile of the dipole element or the monopole element in **Figure 11** should be large.

#### **3.3 Dual-polarized endfire mm-wave array**

With the horizontal-polarized endfire mm-wave array and vertical-polarized endfire mm-wave array, the dual-polarized endfire mm-wave array can be easily achieved. For example, if the mm-wave array vertical to the system ground in **Figure 9(b)** and **Figure 10(b)** can radiate dual-polarized patterns, dual-polarized endfire mm-wave array can be easily achieved. This idea can be found in [52], where a dual-polarized slot antenna is vertically deployed on a mobile phone, as shown in **Figure 8(a)**. Thus, a dual-polarized endfire mm-wave array with a − 10 dB impedance bandwidth from 23.2 to 29.7 GHz is achieved in [52]. This method also has the drawback of being high profile. Also, if the horizontal dipole element in **Figure 8(c)** and vertical dipole element in **Figure 10(d)** can be designed in the near space, dual-polarized mm-wave dipole array can also be achieved. In [40, 53], the dual-polarized endfire mm-wave dipole array is achieved by combing the vertical dipole and horizontal dipole as shown in **Figure 8(b)**. The dual-polarized endfire mm-wave array antenna should have a large profile to achieve the good performance. To reduce the profile, the horizontal-polarized dipole element in **Figure 9(c)** and the vertical-polarized horn element in **Figure 10(c)** can be combined to achieve the low-profile dual-polarized endfire mm-wave array. In [54], the low-profile dual-polarized endfire mm-wave array is realized by co-designing a horizontal-polarized yagi-uda antenna and a vertical-polarized SIW horn antenna, as shown in **Figure 8(c)**. Also, the horizontal-polarized dipole antenna with balun feeding can replace the yagi-uda antenna to achieve a wide bandwidth [55]. In addition, the clearance of the combination of horizontal-polarized dipole element and vertically polarized horn element can be further reduced by using the transition plates [56, 57] or the overlapped apertures [58]. The dual-polarized endfire mm-wave array antenna with horizontal-polarized dipole element and vertically polarized horn element usually has a large clearance to achieve a good performance. To reduce the clearance, the horizontal-polarized open slot element in **Figure 9(e)** and vertical-polarized horn element in **Figure 10(c)** can be applied. In [59], the dual-polarized endfire mm-wave array with a small clearance is realized by co-designing a horizontal-polarized open

*Recent Advances in the mm-Wave Array for Mobile Phones DOI: http://dx.doi.org/10.5772/intechopen.112043*

slot antenna and a vertical-polarized horn element, as shown in **Figure 8(d)**. The horizontal-polarized open slot antenna consists of two metal blocks with a slot, and the vertical-polarized horn element is a SIW horn antenna. In [60, 61], the horizontalpolarized open slot antenna is realized by using two SIW structures. In [41, 62], the horizontal-polarized open slot antenna and the vertical-polarized horn are integrated into a single SIW structure. Besides, two SIW horns with a polarizer can be applied to achieve the dual linearly polarized endfire antenna [63, 64] or 45° dual linearly polarized endfire antenna [65], as shown in **Figure 8(e)**. Also, in [66], the orthogonal slot can be excited simultaneously to achieve the dual-polarized mm-wave endfire chainslot antenna, as shown in **Figure 8(f)**.